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Q&A #68 with Dr. Rhonda Patrick (3/1/25)

Posted on March 14th 2025 (4 months)

Dr. Rhonda Patrick discusses saturated fats and LDL, luteolin's benefits, glyphosate risks, natural vs. artificial flavors, and black cumin seed effects.

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Q&A #63 with Dr. Rhonda Patrick (10/12/24)

Posted on October 21st 2024 (8 months)

Dr. Rhonda Patrick discusses her supplement stack, avoiding microplastics, creatine for brain health, and mRNA vaccine autoimmunity risks.

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Are children, infants, and unborn infants susceptible to COVID-19? | Rhonda Patrick

Posted on April 3rd 2022 (about 3 years)

In this clip, Dr. Rhonda Patrick reviews the recently published data on children's susceptibility to COVID-19.

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News & Publications

  • A new study reveals low serotonin levels as the key driver of 'long COVID' symptoms. healthnews.com
    Serotonin Virus COVID-19

    Most people recover from COVID-19 within a few weeks of symptom onset. However, some experience long-term complications that last several weeks or months, a phenomenon previously referred to as “long COVID” and now known as “post-acute sequelae after SARS-CoV-2 infection,” or PASC, characterized by chronic fatigue, brain fog, and other neurocognitive symptoms.

    Scientists don’t fully understand what causes PASC, but viral persistence, chronic inflammation, hypercoagulability, and autonomic dysfunction likely play roles. A recent study links these drivers to a single cause: low serotonin levels.

    Researchers analyzed the blood of participants enrolled in a long-term study of COVID-19 and PASC. They found that the participants had low serotonin levels post-infection, and those levels predicted whether a person recovered fully or developed PASC.

    Then, using a mouse model of COVID-19, they demonstrated that viral inflammation altered genetic pathways regulating serotonin absorption in the gut – the primary source of the body’s serotonin. They also showed that serotonin depletion impairs vagal nerve activity, in turn reducing hippocampal activity and driving neurocognitive dysfunction. Giving the mice a selective serotonin reuptake inhibitor (SSRI, a drug that promotes serotonin uptake in the gut) improved their cognitive function.

    These findings suggest that low serotonin levels drive the symptoms associated with PASC and highlight the potential for SSRI treatment following COVID-19 illness. Learn about the symptoms of PASC (“long-haul COVID”) in this clip featuring Dr. Roger Seheult.

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  • Higher omega-3 status may confer protection against COVID-19, according to a new study. www.ncbi.nlm.nih.gov
    Omega-3 Inflammation Immune System COVID-19

    Omega-3 fatty acids may protect against COVID-19, a new study shows. People with higher levels of omega-3s in their red blood cells were less likely to contract COVID-19 or require hospitalization if infected.

    Researchers calculated the concentrations of docosahexaenoic acid (DHA), a type of omega-3 derived from fatty fish, in the blood of more than 110,000 people enrolled in the UK Biobank study. They also calculated the participants' Omega-3 Index – a measure of total omega-3 fatty acid concentrations in red blood cells. They reviewed the participants' medical records to determine if they had ever contracted COVID-19 and, if so, the severity and outcome of their disease.

    They found that people with the highest Omega-3 Indices (8 percent) were less likely to contract COVID-19 or have a severe outcome than those with the lowest Indices (3.5 percent). Those with the highest DHA levels were 21 percent less likely to test positive for COVID-19 and 26 percent less likely to be hospitalized due to COVID-19 infection.

    In silico (computer modeling) experiments demonstrate that one of the mechanisms driving omega-3s' protective effects in the setting of COVID-19 may be related to their capacity to prevent the spike protein, the primary antigenic component of SARS-CoV-2, from binding to cellular receptors that allow the virus to enter cells. Other evidence points to the anti-inflammatory properties of omega-3s, which may reduce host inflammatory response and disease severity.

    These findings suggest that omega-3s confer protection against COVID-19. Listen to former FMF guest and omega-3 expert Dr. Bill Harris elaborate on this study.

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  • Vitamin C and arginine may reduce symptoms of fatigue for people with long COVID. www.mdpi.com
    Vitamin C COVID-19 Supplements

    Supplemental vitamin C and arginine reduce symptoms associated with long COVID, a new study shows. People who took the combined supplements experienced less fatigue and performed better during exercise.

    Researchers gave people with long COVID either a combination of liposomal vitamin C and arginine or a placebo for four weeks. They measured their walking speed, strength, and endothelial function before and after the intervention.

    They found that those who took the vitamin C/arginine combination improved on measures of speed, strength, and endothelial function compared to those who took the placebo. They were also less likely to report experiencing fatigue.

    Vitamin C is an essential nutrient that exerts robust antioxidant properties. Evidence suggests that liposomal formulations of vitamin C are more bioavailable than conventional forms. Learn more about vitamin C in our overview article. Arginine is an amino acid that plays roles in vasodilation. Evidence suggests that arginine metabolism is altered in the setting of COVID-19.

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  • For men, low testosterone may mean high risk of severe COVID-19, study suggests. (2021) www.sciencedaily.com
    Hormones Testosterone COVID-19

    From the article:

    The researchers measured several hormones in blood samples from 90 men and 62 women who came to Barnes-Jewish Hospital with symptoms of COVID-19 and who had confirmed cases of the illness. For the 143 patients who were admitted to the hospital, the researchers measured hormone levels again at days 3, 7, 14 and 28, as long as the patients remained hospitalized over these time frames. In addition to testosterone, the investigators measured levels of estradiol, a form of estrogen produced by the body, and IGF-1, an important growth hormone that is similar to insulin and plays a role in maintaining muscle mass.

    Among women, the researchers found no correlation between levels of any hormone and disease severity. Among men, only testosterone levels were linked to COVID-19 severity. A blood testosterone level of 250 nanograms per deciliter or less is considered low testosterone in adult men. At hospital admission, men with severe COVID-19 had average testosterone levels of 53 nanograms per deciliter; men with less severe disease had average levels of 151 nanograms per deciliter. By day three, the average testosterone level of the most severely ill men was only 19 nanograms per deciliter.

    The lower the levels of testosterone, the more severe the disease. For example, those with the lowest levels of testosterone in the blood were at highest risk of going on a ventilator, needing intensive care or dying. Thirty-seven patients – 25 of whom were men – died over the course of the study.

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  • COVID-19 may deplete testosterone, helping to explain male patients' poorer prognosis. (2020) www.sciencedaily.com
    Hormones Immune System Testosterone COVID-19

    From the article:

    “Testosterone is associated with the immune system of respiratory organs, and low levels of testosterone might increase the risk of respiratory infections. Low testosterone is also associated with infection-related hospitalisation and all-cause mortality in male in ICU patients, so testosterone treatment may also have benefits beyond improving outcomes for COVID-19,” Professor Çayan explains.

    “In our study, the mean total testosterone decreased, as the severity of the COVID-19 increased. The mean total testosterone level was significantly lower in the ICU group than in the asymptomatic group. In addition, the mean total testosterone level was significantly lower in the ICU group than in the Intermediate Care Unit group. The mean serum follicle stimulating hormone level was significantly higher in the ICU group than in the asymptomatic group.

    “We found, Hypogonadism – a condition in which the body doesn’t produce enough testosterone -in 113 (51.1%) of the male patients.

    “The patients who died, had significantly lower mean total testosterone than the patients who were alive.

    “However, even 65.2% of the 46 male patients who were asymptomatic had a loss of loss of libido.”

    […]

    In the patients who had pre-COVID-19 serum gonadal hormones test (n: 24), serum total testosterone level significantly decreased from pre-COVID-19 level of 458±198 ng/dl to 315±12 ng/dl at the time of COVID-19 in the patients (p=0.003).

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  • Low testosterone may increase risk of COVID-19 hospitalization by 2.4-fold in men. (2022) www.sciencedaily.com
    Hormones Testosterone COVID-19

    From the article:

    The team analyzed the cases of 723 men who tested positive for COVID-19, mostly in 2020 before vaccines were available. The data indicate that low testosterone is an independent risk factor for COVID-19 hospitalization, similar to diabetes, heart disease and chronic lung disease.

    They found that men with low testosterone who developed COVID-19 were 2.4 times more likely to require hospitalization than men with hormone levels in the normal range. Further, men who were once diagnosed with low testosterone but successfully treated with hormone replacement therapy were no more likely to be hospitalized for COVID-19 than men whose testosterone levels had always tested in the normal range.

    […]

    “Low testosterone turned out to be a risk factor for hospitalization from COVID, and treatment of low testosterone helped to negate that risk,” Dhindsa said. “The risk really takes off below a level of 200 nanograms per deciliter, with the normal range being 300 to 1,000 nanograms per deciliter. This is independent of all other risk factors that we looked at: age, obesity or other health conditions. But those people who were on therapy, their risk was normal.”

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  • Female reproductive steroids provide anti-inflammatory and antibody production suggesting COVID-19 symptom protection. (2020) www.sciencedaily.com
    Pregnancy Estrogen COVID-19 Polyphenol Pregnenolone

    From the article

    Female reproductive steroids, estrogen and progesterone and its physiologically active metabolite, allopregnanolone, provide anti-inflammatory functions, reshape competence of immune cells, stimulate antibody production and promote respiratory epithelial cell repair, and inhibit the ACE2 receptor, the door of access for the novel coronavirus (SARS-CoV-2) to infect the organism, suggesting they may protect against COVID-19 symptoms, according to Pinna’s report. The paper is published in Trends in Endocrinology and Metabolism.

    Pinna became interested in the role of reproductive steroids in COVID-19 pathology in March when early case reports showed COVID-19 positive pregnant women who had no COVID-19 symptoms, had escalated symptoms – severe enough to require intensive care – immediately after giving birth. The severity of symptoms coincided with a rapid drop of estradiol, progesterone, and allopregnanolone.

    “Hormones that help sustain the pregnancy – like progesterone – are 100 times more concentrated in a pregnancy’s third trimester. Estradiol, allopregnanolone, and progesterone all have important anti-inflammatory functions and are involved in resetting the immune system. This suggests that pregnant women became symptomatic, and some were even admitted to the ICU, after delivering their babies because of the rapid drop in these hormones,” said Pinna. “The correlation was really striking.”

    According to recent CDC data, in the United States, 38,071 women who were pregnant contracted COVID-19, with 51 deaths – 0.13%. For non-pregnant women, the death toll is 2%.

    “Pregnant women are 15 times less likely to die from COVID than other women,” said Pinna.

    Additionally, nutrition may also play a role when diets are enriched with phytoestrogens – plant-produced ‘estrogen’ – (in foods such as soybeans, lentils, oats). Phytoestrogens have the ability to bind directly to human estrogen receptors, or can be converted to estradiol by the microbiome.

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  • Vitamin C Deficiency in Blood Samples of COVID-19 Patients www.mdpi.com
    Vitamin C COVID-19

    People with COVID-19 have lower levels of vitamin C.

    Micronutrients – vitamins and minerals – facilitate the body’s immune responses to viral infections. Poor micronutrient status diminishes these responses and may contribute to the emergence of more virulent strains of viruses. Findings from a recent study suggest that people with COVID-19 have poor vitamin C status.

    Vitamin C is a water-soluble vitamin that plays important roles in immune function. For example, immune cells release large quantities of reactive oxygen species, often incurring damage. To protect themselves from this damage, immune cells accumulate large quantities of vitamin C, which serves as an antioxidant within the cells. Immune cells also release interferons, a class of proteins that participate in antiviral activity. Some evidence indicates that vitamin C promotes interferon production.

    The investigators collected 82 blood samples from patients with COVID-19 and healthy people. They categorized the patients according to the severity of their disease (mild, severe, critical, fatal) and measured the concentrations of various micronutrients (vitamins A, C, D, and E) in their blood samples.

    They found that the patients with COVID-19 had markedly lower vitamin C concentrations than the healthy people. Patients with the lowest concentrations tended to have longer hospital stays and were more likely to die than those with higher concentrations. The investigators did not observe similar trends for any of the other micronutrients measured. However, other research has shown that poor vitamin D status increases the risk of COVID-19 infection and severe outcomes.

    These findings demonstrate that people with COVID-19 have poor vitamin C status, which may influence the severity of their disease. Learn more about the health benefits of vitamin C in our overview article.

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  • Spike proteins that extrude from SARS-CoV-2 promote inflammatory responses on the endothelial cells that form the blood-brain barrier. www.sciencedaily.com
    Brain Inflammation Immune System COVID-19 Blood-Brain Barrier

    SARS-CoV-2, the virus that causes COVID-19, disrupts the blood-brain barrier.

    COVID-19 is widely regarded as a respiratory illness, but evidence suggests it affects multiple organ systems, including the central nervous system. For example, some people with COVID-19 experience headaches, nausea, vomiting, or “brain fog” – indicators of neurological involvement. Evidence from a 2020 study suggests that SARS-CoV-2, the virus that causes COVID-19, disrupts the blood-brain barrier.

    SARS-CoV-2 enters cells via the angiotensin-converting enzyme 2 (ACE2), a protein that is widespread among the body’s tissues and plays important roles in blood pressure control. Once inside the cell, SARS-CoV-2 replicates, triggering a robust immune response and eliciting widespread inflammation.

    The blood-brain barrier, a semi-permeable barrier that separates the blood from the brain’s extracellular fluid, prevents the entry of neurotoxic substances into the brain. Disruption of the blood-brain barrier has been implicated in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis, among others.

    The investigators first examined postmortem brain tissue from healthy people as well as people who had been diagnosed with hypertension (high blood pressure) or dementia to identify the presence of ACE2 in the brain blood vessels. They found that not only was ACE2 present in the blood vessels, but it was particularly abundant in people with hypertension or dementia. Then, using an in vitro model of the blood-brain barrier, they assessed the effects of exposure to the SARS-CoV-2 spike protein, the primary infectious particle on the virus. They found that exposure to the spike protein impaired blood-brain barrier function and integrity. Finally, using a tissue model that mimics the movement of fluid in the barrier, they found that the spike protein increased barrier permeability.

    These findings suggest that SARS-CoV-2 binds to ACE2 receptors in the brain and impairs blood-brain barrier function and integrity. These effects may be exacerbated in people with co-existing illnesses such as hypertension or dementia.

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  • Sulforaphane exhibits antiviral activity against pandemic SARS-CoV-2 and seasonal HCoV-OC43 coronaviruses in vitro and in mice www.nature.com
    Sulforaphane COVID-19

    Sulforaphane may be beneficial for the prevention and treatment of coronavirus infections.

    Sulforaphane is a bioactive compound derived from certain cruciferous vegetables, including broccoli (especially broccoli sprouts) and red kale. Robust evidence from epidemiological, clinical, rodent, and in vitro studies indicates that sulforaphane exhibits antioxidant, anti-inflammatory, and antiviral properties. Findings from a recent study suggest that sulforaphane is beneficial for the prevention and treatment of coronavirus infections.

    Coronaviruses are a group of related viruses that cause illness in birds and mammals, including humans. Members of this group include SARS-CoV-1 (which causes severe acute respiratory syndrome, or SARS), MERS-CoV (which causes Middle East respiratory syndrome, or MERS), SARS-CoV-2 (which causes COVID-19), and HCoV-OC43 (which causes the common cold), as well as others.

    The investigators conducted a two-part study involving cultured cells and mice. First, they exposed the cells to sulforaphane for one to two hours and then infected them with SARS-CoV-2 and HCoV-OC43. They also assessed the effects of sulforaphane on previously infected cells. They found that sulforaphane roughly halved the replication of the two viruses in both scenarios. Then they repeated the experiment, but they added remdesivir, an antiviral medication commonly used to treat COVID-19, to the sulforaphane and found that the compounds worked in a synergistic fashion to potently reduce viral replication.

    Next, they gave mice sulforaphane prior to infecting them with SARS-CoV-2 and gauged the compound’s effects. They found that sulforaphane decreased viral replication in the animals' lungs by 1.5 orders of magnitude – a 30-fold reduction – compared to infected mice that didn’t receive sulforaphane. The mice that received sulforaphane also exhibited less lung inflammation, one of the hallmarks of COVID-19 and a driver of poor disease outcomes.

    These findings demonstrate that sulforaphane may be beneficial for preventing or treating COVID-19 while modulating inflammation that typically accompanies the illness. Learn about other strategies that reduce the risk of COVID-19 infection in this episode featuring Dr. Roger Seheult.

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  • More evidence having poor vitamin D status before infection increases COVID-19 severity and death risk. www.eurekalert.org
    Vitamin D COVID-19

    Vitamin D is a fat-soluble vitamin that plays key roles in several physiological processes, including immune function. Robust evidence demonstrates links between poor vitamin D status and severe outcomes following infection with SARS-CoV-2, the virus that causes COVID-19. Now, findings from a recent study suggest that poor vitamin D status prior to infection with SARS-CoV-2 increases the risk of severe disease and/or death from COVID-19.

    During an infection, vitamin D deficiency can lead to over-expression of renin (an enzyme produced in the kidneys) and subsequent activation of the renin-angiotensin-system, a critical regulator of blood pressure, inflammation, and body fluid homeostasis. Disturbances in this system can drive poor outcomes, such as acute respiratory distress syndrome and death in COVID-19. Research suggests that supplemental vitamin D during hospitalization with COVID-19 improves outcomes. Vitamin D levels may drop during a viral infection, however, so measuring pre-infection status provides a more accurate assessment of the vitamin’s protective effects.

    The authors of the study reviewed the medical records of 253 patients whose vitamin D levels had been measured two weeks to two years prior to testing positive for COVID-19. They categorized the patients according to disease severity (critical, severe, moderate, or mild). They classified the patients' vitamin D status as deficient, below 20 nanograms per milliliter (ng/ml); insufficient, 20 to 29.9 ng/ml; adequate, 30-39.9 ng/ml; or high-normal, above 40 ng/mL.

    They found that patients categorized as having critical or severe COVID-19 disease were 14 times more likely to have pre-infection vitamin D deficiency than patients with moderate or mild disease. Patients with vitamin D deficiency were more likely to have coexisting illnesses, such as diabetes, high blood pressure, and chronic obstructive pulmonary disease and were 11 times more likely to die from COVID-19, compared with those who had vitamin D sufficiency.

    These findings suggest that pre-infection vitamin D deficiency markedly increases the risk of critical or severe disease and death in patients with COVID-19. Learn more about the importance of vitamin D in COVID-19 in this episode featuring frontline physician Dr. Roger Seheult.

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  • SARS-CoV-2 infection may cause autoimmune disease, especially in men. www.sciencedaily.com
    COVID-19 Autoimmunity

    SARS-CoV-2, the virus that causes COVID-19, elicits a wide range of effects on the human body, many of which are sex-specific. For example, males and females are equally likely to become infected with SARS-CoV-2, but men are more likely to experience worse outcomes and death, regardless of age. Findings from a recent study suggest that men are more likely than women to develop autoimmune activation after SARS-CoV-2 infection.

    Autoimmune activation occurs when the body launches an immune response to its own tissue, driving autoimmune disease. Scientists don’t fully understand the causes of autoimmune activation, but evidence suggests that interactions between genetic and environmental factors play critical roles. Autoimmune diseases affect approximately 7 percent of people in the United States and are more common in women than in men. Examples include type 1 diabetes, Hashimoto’s thyroiditis, lupus, and multiple sclerosis.

    The authors of the study recruited male and female health care workers who had been infected with SARS-CoV-2 and were either symptomatic or asymptomatic for COVID-19. They tested the participants' blood to identify the presence of autoantibodies – antibodies that are directed against the body’s own tissues. Then they measured the autoantibodies' reactivity to proteins linked to several common autoimmune disorders.

    They found that males and females who had been infected with SARS-CoV-2 had autoantibodies in their blood that persisted up to six months post infection, regardless of disease severity. However, men were more likely to exhibit greater autoantibody reactivity, especially if they had experienced at least a mild infection.

    These findings suggest that SARS-CoV-2 infection elicits an autoimmune response that may persist several months, potentially contributing to the phenomenon known as “long COVID.” Males appear to be more vulnerable to this autoimmune response than females. Learn more about the long-term complications associated with COVID-19 in this episode featuring Dr. Roger Seheult.

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  • SARS-CoV-2 protein drives alpha synuclein aggregation, a hallmark of Parkinson's disease. medicalxpress.com
    Parkinson's COVID-19

    Scientists have identified an emerging pattern of associations between SARS-CoV-2 (the virus that causes COVID-19) and Parkinson’s disease. For example, the loss of smell is one of the most common symptoms reported in SARS-CoV-2 infection, but it is also an early symptom of Parkinson’s disease, often preceding diagnosis by many years. In addition, some recent case reports describe patients who presented with probable Parkinson’s disease after recovering from severe SARS-CoV-2 infection. Now, evidence from a recent study suggests that the SARS-CoV-2 nucleocapsid protein drives aggregation of alpha synuclein, a hallmark of Parkinson’s disease.

    SARS-CoV-2 nucleocapsid proteins are helical structures that are housed within the viral membrane. They encapsulate SARS-CoV-2’s genome, protecting it from the host cellular environment. The virus produces large quantities of nucleocapsid proteins once inside an infected cell because they play critical roles in virion assembly and viral replication.

    Alpha synuclein is a type of neuronal protein that regulates synaptic vesicle movements and neurotransmitter release. Its aggregation, a progressive process that spreads from cell to cell, impairing brain function, is a dominant feature in the pathophysiology of Parkinson’s disease.

    The authors of the report assessed alpha synuclein aggregation in both the absence and presence of the SARS-CoV-2 spike protein (the virus’s primary infectious particle) and the nucleocapsid protein. They found that in the absence of any SARS-CoV-2 proteins, aggregation naturally occurred after about 10 days. The spike protein had no effect on aggregation time, but following exposure to the nucleocapsid protein, aggregation occurred in less than one day – more than 10 times faster than normal.

    Then they studied the effects of the nucleocapsid protein in a cell model of Parkinson’s disease. They injected some of the cells with nucleocapsid protein (about the amount one would expect during SARS-CoV-2 infection) and alpha synuclein and injected some with alpha synuclein alone. They found that twice as many cells injected with both proteins died compared to those injected with alpha synuclein alone.

    These findings suggest that the SARS-CoV-2 nucleocapsid protein drives aggregation of alpha synuclein and promotes cells death in a model of Parkinson’s disease. Learn more about Parkinson’s disease in this episode featuring Dr. Gizelle Petzinger.

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  • WHO issues warning about Omicron variant. www.npr.org
    COVID-19

    The World Health Organization (WHO) recently issued warnings about Omicron, a newly emerged variant of SARS-CoV-2, the virus that causes COVID-19. Omicron is driving a substantial uptick in the number of COVID-19 cases in South Africa and other nations. The first U.S. case was recently detected in a fully-vaccinated person living in California, and several other states are now reporting Omicron cases.

    The WHO has classified Omicron as a variant of concern. To be considered a variant, a virus must have sufficient mutations to change a portion of its genetic code. Variants of concern further exhibit a wide range of characteristics that differ from the parent strain, including changes in transmissibility, disease severity, clinical presentation, immune response, or response to treatments and vaccines.

    Several SARS-CoV-2 variants have been identified, including Delta, a variant of concern that first emerged in India in December 2020 and has at least 13 mutations. Delta is currently the dominant form of the virus in the U.S. By contrast, the Omicron variant has approximately 50 mutations, roughly 30 of which are present in the spike protein, the major surface protein that SARS-CoV-2 uses to enter cells, where it can replicate.

    Scientists do not yet know the consequences of these mutations, which have the potential to increase transmissibility or reduce vaccine effectiveness. Early reports from Israeli health officials suggest that Omicron is highly transmissible but elicits only mild symptoms in fully vaccinated people.

    Although the WHO and governing bodies worldwide have responded quickly to the news of Omicron’s emergence, determining the full extent of the variant’s effects on human health may take several weeks. Public health containment strategies such as being vaccinated, wearing masks, washing hands, and physically distancing remain essential to reducing the spread of COVID-19.

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  • The SARS-CoV-2 virus infects adipose tissue, increasing inflammation during COVID-19 illness. www.biorxiv.org
    Obesity COVID-19

    The SARS-CoV-2 virus, which causes COVID-19, has infected over 255 million individuals worldwide. Obesity and related diseases such as type 2 diabetes and hypertension are strong independent risk factors for infection, severe disease, and death. Findings of a new report indicate that SARS-CoV-2 infiltrates adipose tissue, causing inflammation and worsening disease severity.

    Severe COVID-19 is characterized by immune hyperreactivity that creates systemic inflammation mediated by excessive production of pro-inflammatory proteins. Obesity is also characterized by excessive immune reactivity and inflammation, potentially putting people with obesity at greater risk of COVID-19 complications. However, further investigation is needed to understand the mechanisms by which obesity increases COVID-19 severity and whether these mechanisms are independent of type 2 diabetes, hypertension, and other obesity-related conditions.

    The investigators recruited adults with obesity who were patients of a bariatric surgery center and had not had a SARS-CoV-2 infection. They collected adipose tissue samples from multiple fat depots around the body such as subcutaneous fat (under the skin), visceral fat (wrapped around internal organs), and pericardial and epicardial fat (around the heart) on the day participants underwent bariatric surgery. The researchers also collected adipose tissue samples from adults who had died from COVID-19 illness. They isolated cells from the connective tissue, sorted them based on type (such as mature adipocyte, pre-adipocyte, and adipose tissue macrophage), and characterized their gene expression and surface receptor population. Then, they exposed the cells to the SARS-CoV-2 virus and observed changes.

    The authors found that the SARS-CoV-2 virus infects adipose tissue from multiple depots around the body, but that macrophages were the main cell type infected. They found low expression of the angiotensin converting enzyme (ACE)-2 receptor in these macrophages, indicating that the virus enters through a different route than the primary entry point in cells of the lungs and gut. Upon exposure to the SARS-CoV-2 virus, these cells increased production of pro-inflammatory cytokines. In adipose tissue samples from participants who had died of COVID-19, the investigators found SARS-CoV-2 infection in mature adipocytes in addition to macrophages.

    These results are the first to show that the SARS-CoV-2 virus can infect adipose tissue in vivo and that this tissue type may contribute to excess inflammation during COVID-19 illness, especially in older adults with a higher BMI.

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  • Patients with obesity and COVID-19 produce mostly autoimmune SARS-CoV-2 antibodies, not neutralizing. pubmed.ncbi.nlm.nih.gov
    Obesity Immune System COVID-19 Autoimmunity

    Obesity is a strong independent risk factor for COVID-19, the disease caused by the SARS-CoV-2 virus. Previous research has shown that people with obesity generate fewer antibodies in response to viral infection or vaccination; however, whether antibody quality is also affected by obesity is unknown. Findings published in a new report show that the majority of the antibodies found in people with obesity are autoimmune and not able to neutralize the SAR-CoV-2 virus, putting individuals with obesity at greater risk of severe COVID-19.

    Obesity increases the rate of inflammaging, the process of chronic low-grade inflammation that wears down the body’s tissues over time, putting people with obesity at greater risk of many diseases. Inflammaging increases the risk of autoimmunity by increasing the concentration of damaged cellular components in the blood, potentially triggering the immune system to generate antibodies against its own cells. Previous research has shown that many patients with severe COVID-19 generate autoimmune antibodies that increase the risk of long-term complications. Because people with obesity experience increased baseline inflammaging, they may be at greater risk of developing long-term autoimmune complications for COVID-19; however, no published studies have yet addressed this concern.

    The investigators collected blood from 15 participants with a lean BMI (less than 25) and 15 participants with an obese BMI (greater than 30) who tested positive for SARS-CoV-2. The investigators also collected blood from 30 participants who had not had a SARS-CoV-2 infection and were matched for age, sex, and BMI. The researchers measured the concentration of neutralizing antibodies (meaning antibodies that bind to the SARS-CoV-2 spike protein and prevent viral entry into cells), non-neutralizing antibodies, and autoimmune antibodies.

    Participants with obesity had fewer SARS-CoV-2 antibodies than participants with a lean BMI, confirming previous reports. While all 15 SARS-CoV-2-positive participants with a lean BMI had circulating neutralizing antibodies, only a few participants with obesity did. The researchers found that SARS-CoV-2 infection increased the concentration of autoimmune antibodies in all patients, but the concentration of autoimmune antibodies was always higher in participants with obesity. Finally, they found that participants with the highest concentration of autoimmune antibodies also had the highest levels of serum C-reactive protein, a marker of chronic inflammation, suggesting that inflammation is integral to developing autoimmunity.

    These data confirm previous reports that obesity reduces the effectiveness of the immune response in COVID-19 patients and increases the risk of autoimmunity.

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  • Older adults with a higher BMI spread more infectious SARS-CoV-2 aerosol particles. www.pnas.org
    Obesity Pollution COVID-19

    The SARS-CoV-2 virus is transmitted through aerosols that are generated when an infected person breathes, talks, sneezes, or coughs. The amount and size of aerosol droplets a person exhales can vary drastically between individuals and may be affected by diet and age. Findings of a recent study suggest that humans and non-human primates with greater age and body mass index (BMI) produce more aerosol droplets during COVID-19 infection.

    Aerosol droplets are produced when air passes over mucus-coated airways during breathing. This mucus determines the size of aerosol droplets produced. A healthy mucus layer forms large droplets, while a dysfunctional mucus layer produces droplets that aerosolize into many smaller infectious droplets. Mucus structure and composition are influenced by age, environment, disease, and the microbiota. A Western, obesity-promoting diet is often deficient in fiber, starving the beneficial bacteria in the gut that produce metabolites such as short chain fatty acids that regulate the lung mucus barrier. Older adults also experience degradation of the lung mucus layer, potentially influencing aerosol droplet size.

    The researchers recruited 194 participants from the United States. They asked participants to breathe into a particle detector to measure the quantity of exhaled particles in the size range of three to five micrometers. They characterized participants who exhaled 156 particles per liter of air or less during the breath test as low spreaders and participants above this level of superspreaders. The particle detector was connected to an air filter that collected the particles so the concentration of SARS-CoV-2 virus could be measured. The investigators also used a sample of eight non-human primates to better understand the effects of SARS-CoV-2 infection. The investigators exposed rhesus macaques and green monkeys to either the SARS-CoV-2 or tuberculosis virus and monitored them for up to 60 days. The non-human primates performed a similar breath test as the one used in the human participants.

    The authors found no relationship between sex and aerosol particle number; however, there were significant statistical relationships among age, BMI, and particle size. The strongest correlation was found between particle size and BMI-years, which is calculated as BMI multiplied by age. Participants in the bottom 50 percent for BMI-years exhaled significantly less aerosol than participants in the top 50 percent. In non-human primates, SARS-CoV-2 or tuberculosis infection increased the number of aerosol particles exhaled in proportion to the amount of viral RNA measured from mucus swabs.

    The authors concluded that age, BMI, and active infection decrease aerosol particle size and may contribute to viral spread. Future models of pandemic progression should take these factors into account.

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  • "Decoy" proteins in amniotic fluid and breast milk protect fetuses and infants from severe COVID-19. medicalxpress.com
    COVID-19 Breast Milk

    Most pregnant women who develop COVID-19 experience mild or asymptomatic illness and rarely transmit the disease to their infants in utero or postpartum. Findings from a new study suggest that specialized “decoy” proteins in amniotic fluid and breast milk protect fetuses and newborns from severe COVID-19.

    SARS-CoV-2, the virus that causes COVID-19, gains entry to cells via various receptor proteins, including angiotensin-converting enzyme 2 (ACE2), CD26, CD147, and neuropilin-1 (NRP-1), among others. These proteins are typically embedded in cellular membranes, but they can also be found in soluble form, existing freely in bodily fluids. Some evidence suggests that soluble forms of ACE2, in particular, serve as “viral traps,” or decoys, effectively preventing SARS-CoV-2 from interacting with membrane-bound forms.

    The authors of the study analyzed amniotic fluid (collected at 37 weeks' gestation) and breast milk (collected at two and six weeks postpartum) that had been stored prior to the COVID-19 pandemic. They centrifuged the samples and then measured the amount of soluble ACE2, CD26, CD147, and NRP-1 present.

    Their analysis revealed that all the samples contained an abundance of the soluble forms of the various proteins. Amniotic fluid contained more CD26 than breast milk, but breast milk contained higher amounts of ACE2 and NRP-1. In addition, the soluble proteins in amniotic fluid were of different isoforms (shorter) than those in breast milk. These findings suggest that soluble receptors in breast milk and amniotic fluid act as decoy receptors to reduce the risk of SARS-CoV-2 infection and/or severe COVID-19 outcomes in fetuses and infants.

    Interestingly, human milk oligosaccharides (HMOs) in breast milk serve as decoys to protect the infant from gut infections. In order for pathogenic bacteria to cause infection, they must first target and bind to specific carbohydrates found on the cells that line the gut. However, the overall structure and shape of HMOs mimics that of the carbohydrate targets. The pathogens bind to the HMOs, instead, foiling their ability to establish themselves in the gut. Learn more about HMOs and other immunomodulatory aspects of breast milk in our overview article.

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  • Antibodies generated by the poliovirus vaccine inhibit SARS-CoV-2 replication. www.news-medical.net
    COVID-19

    As of October 3, 2021, the SARS-CoV-2 virus, the virus that causes COVID-19, has infected more than 235 million people worldwide and claimed the lives of more than 4.8 million people. Despite the growing number of approved vaccines available, only 34 percent of the world population has been vaccinated for reasons including lack of availability and vaccine hesitancy. A new report finds that the antibodies produced following poliovirus vaccination offer protection against SARS-CoV-2 infection.

    During development of the earliest SARS-CoV-2 vaccines, researchers found exploratory data to support the use of existing vaccines developed against other viruses for use in preventing SARS-CoV-2 infection. The poliovirus vaccine was identified as possibly effective because it contains a protein called RNA-dependent RNA polymerase (RdRp), which directs viral replication in polioviruses and coronaviruses. However, no studies have been conducted to measure the efficacy of polio-induced immunity against the SARS-CoV-2 virus.

    The researchers collected data from more than 300 participants between the ages of 18 and 80 years with no history of COVID-19 or SARS-CoV-2 vaccination. They collected a blood sample from participants before inoculation with the poliovirus vaccine and four weeks after. The researchers measured the concentration of antibodies against the RdRp protein and the ability of those antibodies to inhibit the replication of the SARS-CoV-2 virus using immunoassays.

    During the four weeks between their baseline visit and follow-up visit, only five participants out of 298 reported testing positive for COVID-19; of these, all reported mild symptoms. No participants were hospitalized or died during the study and there were no serious reactions to the vaccine. Compared to their baseline blood sample, 85.2 percent of participants had an increase in anti-RdRp antibodies at four weeks post-vaccination. The researchers randomly selected 54 post-vaccine samples out of the 298 available. Among these samples, 94.4 percent exhibited efficacy in reducing replication of SARS-CoV-2 virus.

    These data demonstrate that antibodies generated by exposure to the poliovirus vaccine are effective in reducing SARS-CoV-2 replication, providing a safe, inexpensive, and widely-available alternative to SARS-CoV-2-specific vaccines.

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  • Monoclonal antibody treatment improves COVID-19 outcomes. www.nejm.org
    COVID-19

    Current approved treatment protocols for COVID-19 involve provision of supportive care, such as supplemental oxygen or mechanical ventilation, and administration of remdesivir, an antiviral drug. Results of a recent phase 3 clinical trial demonstrate that REGEN-COV, a combination of the monoclonal antibodies casirivimab and imdevimab, improves outcomes in people who have COVID-19.

    Monoclonal antibodies are proteins that mimic the body’s natural antibodies. They are mass-produced in a laboratory setting and help the body combat harmful pathogens such as viruses. In late 2020, the Food and Drug Administration granted emergency use authorization for REGEN-COV as a post-exposure treatment for patients meeting specific criteria based on robust data from phase 1 and phase 2 clinical trials. REGEN-COV has demonstrated activity against current variants of concern and those of interest, including the alpha, beta, delta, epsilon, gamma, and iota variants.

    The phase 3 trial involved three cohorts of non-hospitalized participants who had tested positive for COVID-19 less than 72 hours prior to entering the trial. Cohort 1 included participants who were 18 years of age or older (average age, 50 years); cohort 2 included participants who were younger than 18 years of age; and cohort 3 included participants who were pregnant. Investigators randomly assigned participants in cohort 1 to receive REGEN-COV at a dose of either 1,200 milligrams (600 milligrams of each antibody), 2,400 milligrams (1200 milligrams of each antibody), or a placebo, delivered via intravenous infusion. The investigators measured antibodies against SARS-CoV-2 in the participants' blood and categorized the participants as antibody-positive, antibody-negative, or other, if the test was inconclusive. They also measured the participants' viral load. Participants tracked their symptoms and reported them using a validated electronic diary.

    Because the trial for cohorts 2 and 3 is ongoing, this report included data for cohort 1 only. The trial demonstrated that 1.3 percent of participants who received the 2,400-milligram dose and 4.6 percent of participants who received a placebo required hospitalization or died; similarly, 1.0 percent of participants who received the 1,200-milligram dose and 3.4 percent of those who received a placebo required hospitalization or died. Participants with a high viral load were more likely to be hospitalized or die than participants with a low viral load. Symptom resolution among participants who received the monoclonal antibody treatment occurred four days earlier than those who received a placebo; similarly, viral load reduction was faster with monoclonal antibody treatment than with the placebo. Serious adverse events were rare and occurred more often among participants who received the placebo.

    These findings suggest that the combined monoclonal antibody treatment REGEN-COV demonstrates efficacy against COVID-19 and exhibits a strong safety profile. Learn more about COVID-19 treatments in this episode featuring Dr. Roger Seheult.

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  • Vitamin D reduces the risk of death from COVID-19. www.medrxiv.org
    COVID-19

    Since COVID-19’s emergence in late 2019, the disease has claimed the lives of nearly 5 million people worldwide. Scientists predict that SARS-CoV-2, the virus that causes COVID-19, will likely achieve endemic status in the coming years, so identification of strategies that bolster viral immunity and reduce negative outcomes is essential. Findings from a recent study suggest that optimal blood levels of vitamin D could markedly reduce the risk of death from COVID-19.

    Vitamin D regulates the expression of thousands of genes in the human body via its interaction with specialized cellular proteins called vitamin D receptors. Nearly all cell types involved in the body’s immune response (monocytes/macrophages, T cells, B cells, natural killer cells, and dendritic cells) possess vitamin D receptors. Consequently, vitamin D plays essential roles in the regulation of both innate and adaptive immune systems.

    The Endocrine Society defines optimal blood levels of vitamin D as 40 to 60 nanograms per milliliter (ng/mL). Unfortunately, approximately 40 percent of people living in the United States are vitamin D deficient, based on Endocrine Society standards. Deficiency is associated with poor bone health in adults and children as well as severe outcomes in COVID-19. Certain populations are at greater risk for deficiency, especially older adults, dark-skinned people (such as those of African or Hispanic descent), and people who have obesity, low education, or diabetes.

    The authors of the study analyzed data from one population-based study (which measured long-term vitamin D status in more than 400 million people worldwide) and seven clinical studies (which measured vitamin D levels post-infection). They used a machine learning model to compute the expected death rates among the patients based on characteristics such as the patients' age, sex, median vitamin D levels, and whether they had diabetes. The timeframe for the data collection preceded the advent of vaccines against COVID-19.

    The analysis revealed that people who had optimal vitamin D levels preceding SARS-CoV-2 infection were highly unlikely to die from their illness, suggesting that vitamin D reduces the risk of death from COVID-19. However, these findings were based on observational data, so interpretation of the findings must take into account the higher death rates associated with age and comorbidities (coexisting illnesses). Learn more about the role of vitamin D in COVID-19 in this episode featuring Dr. Roger Seheult.

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  • Delayed administration of Pfizer vaccine provides robust immunity. www.medrxiv.org
    COVID-19

    Early data indicated that the Pfizer BioNTech mRNA vaccine demonstrated 90 percent efficacy in preventing infection from the alpha variant of SARS-CoV-2, the virus that causes COVID-19. The vaccine is typically administered in two doses, delivered three to four weeks apart. However, in the setting of vaccine shortages in some areas of the United States, some public health agencies have opted to deliver the vaccines on an extended interval. Findings from a recent study suggest that the vaccine elicits robust humoral immunity even when doses are delivered 16 weeks apart.

    Humoral immunity, also known as antibody-mediated immunity, is an aspect of the immune response to specific antigens. It occurs when foreign material, such as a pathogen, is detected in the body. Lymphocytes are the primary drivers of humoral immunity.

    The authors of the study measured humoral responses to two doses of the Pfizer BioNTech vaccine, delivered 16 weeks apart. The study included 22 people who had never been infected with SARS-CoV-2 and 21 people who had been infected. Among those who had previously been infected, ten participants did not receive a second dose, leaving 11 recipients of two doses. The authors collected blood samples for testing prior to the first dose, three weeks after the first dose, three months after the first dose, and three weeks after the second dose.

    They found that providing a second dose to previously infected people did not significantly improve humoral responses. However, humoral responses in people who had never been infected increased markedly after the delayed second dose, achieving levels comparable to those observed in previously infected people.

    These findings suggest that delaying the second dose of the Pfizer BioNTech vaccine as much as 16 weeks provides robust humoral immunity against SARS-CoV-2 infection. Learn more about COVID-19 vaccines in this episode featuring Dr. Roger Seheult and Dr. Rhonda Patrick.

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  • Antibodies to the ACE2 receptor may drive "long COVID" symptoms. news.uams.edu
    COVID-19

    SARS-CoV-2, the virus that causes COVID-19, binds to a receptor on a cellular receptor called angiotensin-converting enzyme 2 (ACE2) to enter the cell and replicate. This process markedly impairs ACE2 receptor function. Findings from a recent study suggest that antibodies for the ACE2 receptor develop after COVID-19 illness, driving long-term complications.

    Most people recover from COVID-19 illness within a few weeks of symptom onset. Some, however, experience long-term complications that last several weeks or months, a phenomenon previously referred to as “long COVID” and now known as “Post-Acute Sequelae after SARS-CoV-2 infection,” or PASC.

    Many of the acute symptoms of COVID-19 arise from overactivation of the body’s immune system following loss of ACE2 function. A key player in this overactivation is the renin-angiotensin-system, an important regulator of blood pressure, inflammation, and body fluid homeostasis. Disturbances in this system in the setting of SARS-CoV-2 infection can drive poor outcomes, such as acute respiratory distress syndrome and death in COVID-19.

    The authors of the study analyzed blood samples for the presence of ACE2 antibodies in 67 people who had a history of previous SARS-CoV-2 infection and 13 people with no history of infection. They also measured ACE2 levels and activity in the participants' blood.

    Whereas 81 percent of the participants with previous infection had antibodies against ACE2, none of the participants who had never been infected had antibodies. Even though ACE2 levels were comparable in both infected and non-infected participants, ACE2 activity was lower among participants with antibodies compared to those without antibodies.

    These findings suggest that following SARS-CoV-2 infection, antibodies against the ACE2 receptor can be detected in the blood. These antibodies, which likely form early in the disease process, impair ACE2 function, providing a potential mechanism for PASC. One limitation of this study is that the blood samples were de-identified, meaning that they carried no identifiers or information about whether the samples were from people who experienced long-term complications of COVID-19.

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  • Many people infected with SARS-CoV-2 do not develop antibodies to the virus. www.forbes.com
    COVID-19

    Current vaccines against COVID-19 provide powerful protection against the disease. Some evidence suggests that when people who have been infected with the original strain of SARS-CoV-2 (the virus that causes COVID-19) are vaccinated against the disease, they develop unusually robust immunity, a phenomenon known as “hybrid immunity.” However, a recent report describes findings that suggest many people infected with SARS-CoV-2 do not develop antibodies to the virus.

    The study involved 72 people who had tested positive for COVID-19 but were symptom-free for at least three weeks. The authors of the study tested the participants' blood for the presence of antibodies to the spike protein (the primary infectious particle of the SARS-CoV-2 virus) as well as other viral particles at the time of enrollment and at subsequent follow-up visits. They gathered information regarding the participants' demographics, viral load, and symptom severity.

    Two of the participants (3 percent) reported no symptoms, 13 (18 percent) reported mild symptoms, 48 (67 percent) reported moderate symptoms, and 9 (12 percent) reported severe symptoms. The authors' analysis revealed that 36 percent of the participants failed to develop detectable antibody levels against the SARS-CoV-2 spike protein or other infectious particles. Those who did not develop antibodies were on average 10 years younger and had lower viral loads than those who developed higher antibody levels.

    These findings indicate that the antibody response to SARS-CoV-2 infection is variable and subject to a variety of factors. Vaccines against COVID-19, on the other hand, provide predictable antibody responses. It is important to note that although antibodies are important components of the body’s immune response, cellular immunity plays a critical role, too. Learn more about COVID-19 vaccines in this clip featuring Dr. Roger Seheult.

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  • Vaccination against COVID-19 cuts risk of long-term complications following breakthrough infection by half. www.nytimes.com
    COVID-19

    The delta variant of SARS-CoV-2, the virus that causes COVID-19, exhibits greater resistance to antibodies and higher transmissibility than other variants, raising concerns that people who have been vaccinated might be vulnerable to breakthrough infections and subsequent complications. Findings from a recent study indicate that people are vaccinated against COVID-19 are less likely to develop long-term complications following breakthrough infections.

    COVID-19 is an acute illness caused by infection with the SARS-CoV-2 virus. Although most people recover from COVID-19 within a few weeks of presenting with symptoms, some experience long-term complications that affect multiple organs, including the heart, lung, kidney, skin, and brain.

    The prospective, case-control study drew on self-reported data from more than 1 million United Kingdom-based adult users of the COVID Symptom Study mobile phone app. Participants had received at least one dose of the two-dose AstraZeneca, Moderna, or Pfizer vaccines during an eight-month period between December 2020 and July 2021. The authors of the study matched vaccinated persons who tested positive for COVID-19 (cases) with vaccinated persons who tested negative for COVID-19 (controls). They also included data from unvaccinated persons.

    Of the 1.2 million people who had received only one dose, approximately 0.5 percent reported a breakthrough infection. Of the nearly 1 million people who had received both doses, approximately 0.2 percent reported a breakthrough infection. Those who experienced breakthrough infections were 49 percent less likely to experience long-term complications, were less likely to be hospitalized, and were more likely to have few or no symptoms than unvaccinated persons. People who lived in low-income areas or had obesity were more likely to experience breakthrough infections after receiving only one dose.

    These findings suggest that vaccination against COVID-19 reduces the risk of long-term complications following breakthrough infections by half. They underscore the importance of continued efforts to vaccinate eligible persons, especially those who are more likely to experience long-term complications, such as those who live in low-income areas or who have obesity. Learn more about the long-term complications of COVID-19 in this clip featuring Dr. Roger Seheult.

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  • mRNA vaccines provide long-lasting immunity and protection from SARS-CoV-2 variants. www.bloomberg.com
    Immune System Vaccine COVID-19

    SARS-CoV-2 mRNA vaccines (e.g., Moderna and Pfizer-N-BioTech) are effective in preventing infection and have even greater efficacy in preventing severe COVID-19 illness and hospitalization. However, many people in the United States received their vaccine early in 2021, more than six months before the time of this writing. Whether the protection afforded by vaccination lasts as time passes and more SARS-CoV-2 variants emerge is unclear. Findings of a report published in August provide insights into long-term immunity following vaccination or SARS-CoV-2 infection, concerns about emerging variants, and implications for vaccination boosters.

    During infection with a virus, the innate immune system immediately produces inflammation to fight the infection. Within days or weeks, the adaptive immune system produces antibodies that are specific to the virus. These antibodies bind to a small piece of the viral particle, called an antigen. White blood cells such as macrophages and neutrophils participate in the innate response, while B and T cells facilitate the adaptive response. Plasma B cells are responsible for producing antibodies; however, these cells steadily decrease in number over time. Memory B cells store the genetic information needed to produce virus-specific antibodies upon reinfection. Memory T cells are also responsible for “remembering” viruses in this way. Memory CD4+ T cells rapidly respond to reinfection to support inflammation and antibody production. Memory CD8+ T cells, also called cytotoxic T cells, bind to virus-infected host cells and order them to undergo apoptosis (i.e., programmed cell death).

    The authors of the report analyzed a set of 342 blood samples collected from 61 participants at one, three, and six months following vaccination. This group of participants included SARS-CoV-2 naive individuals (i.e., those who were never infected with the virus) and SARS-CoV-2 recovered individuals. The investigators measured the concentration of circulating antibodies that bind to the SARS-CoV-2 receptor binding domain protein and spike protein. They also measured the concentration of memory B cells and T cells and characterized these cells’ response when challenged with SARS-CoV-2 antigens.

    The concentration of serum antibodies declined over time, but was still detectable at six months post-vaccination. mRNA vaccination produced memory B cells that respond to the receptor binding domain protein of the Alpha, Beta, and Delta variants, called cross-binding memory. These memory B cells had significantly more hypermutation, the process by which B cells rearrange their DNA in order to produce antibodies to new antigens, and increased in concentration between three and six months post-vaccination. Cross-binding B cells were more common in SARS-CoV-2 recovered patients than naive patients. mRNA vaccination also increased memory CD4+ and CD8+ T cells.

    The immune response to mRNA vaccination and infection with the SARS-CoV-2 virus evolves over time, which may have implications for the future use of booster vaccines. These results should be considered with caution as this research has yet to be peer-reviewed.

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  • COVID-19 may increase a person's risk for neurodegenerative disease. www.sciencedirect.com
    COVID-19 Neurodegeneration

    COVID-19 is an acute illness caused by infection with the SARS-CoV-2 virus. Although most people recover from COVID-19 within a few weeks of presenting with symptoms, some experience long-term complications that affect multiple organs, including the heart, lung, kidney, skin, and brain. Findings from a recent study suggest that SARS-CoV-2 infection may promote neurodegenerative disease.

    Neurodegenerative diseases are chronic disorders of the central nervous system that are characterized by chronic progressive loss of neuronal structure and function. They often emerge in mid-to-late adult life and are increasingly common, affecting roughly 37 million people worldwide – a number expected to increase as human lifespan increases. Although scientists don’t fully understand the underlying causes of most neurodegenerative diseases, protein aggregation in the brain is a widely accepted contributing factor. Previous research has shown that the SARS-CoV-2 spike protein binds to heparin (a protein involved in blood clotting) and heparin binding proteins, accelerating the aggregation of proteins involved in neurodegeneration.

    Since many of the biological functions of a protein depend upon its affinity to bind with other proteins, the authors of the study used a web-based algorithm called HDOCK to gauge the binding affinity between the receptor binding domain of the SARS-CoV-2 spike protein between heparin and several aggregation-prone heparin-binding proteins implicated in neurodegenerative diseases, including amyloid-beta, alpha-synuclein, tau, and TAR DNA binding protein.

    They found that SARS-CoV-2 spike protein exhibited differing binding affinities for the various proteins. Heparin showed the highest affinity, with the others exhibiting affinity in decreasing order: prion, amyloid-beta, tau, TAR DNA binding protein, and alpha-synuclein.

    These findings suggest that the heparin-binding site on the spike protein facilitates the subsequent binding to amyloid proteins, potentially leading to neurodegeneration in the brain. Learn more about risk factors that drive Alzheimer’s disease, a type of neurodegenerative disease, in this episode featuring Dr. Dale Bredesen.

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  • COVID-19 may increase diabetes risk. www.cell.com
    COVID-19

    SARS-CoV-2, the virus that causes COVID-19, elicits both acute and chronic damage to the lungs and heart. Other parts of the body may be affected, too, including the kidneys, brain, skin, and olfactory tissues. Evidence from a recent study indicates that SARS-CoV-2 infects pancreatic beta cells, increasing the risk of developing diabetes.

    Pancreatic beta cells are endocrine cells that produce, store, and release insulin. Beta cell failure and death are hallmarks of type 1 and type 2 diabetes. Multiple factors can promote beta cell death, including viral infection and hyperglycemia (high blood glucose), among others. Cases of new-onset diabetes, hyperglycemia, and diabetic ketoacidosis (a life-threatening condition that can accompany hyperglycemia) in people who have had COVID-19 are on the rise.

    The SARS-CoV-2 virus exploits the ACE2 receptor to gain entry into cells and replicate. The ACE2 receptor is widely distributed in the body’s tissues, including pancreatic tissues. Other cellular factors involved in SARS-CoV-2 entry include transmembrane serine protease 2, transferrin receptor, and neuropilin 1. Neuropilin 1 participates in pain sensing and angiogenesis (the development of new blood vessels) and is a receptor for vascular endothelial growth factor-A.

    The authors of the study collected pancreatic islet cells from healthy organ donors and from patients who had died from COVID-19 (collected during autopsy). They infected the cells with SARS-CoV-2 and performed various assays to determine the presence of cellular factors that contribute to infection. They measured insulin levels and glucose-stimulated insulin secretion, a measure of beta cell insulin release, in the infected cells.

    They determined that SARS-CoV-2 infects beta cells, and this infection promotes beta cell death and decreases insulin release. They also found that beta cells express ACE2, transmembrane serine protease 2, transferrin receptor, and neuropilin 1. They posited that neuropilin 1, and possibly transferrin receptor, provide the stimulus for SARS-CoV-2 entry into beta cells.

    These findings demonstrate that SARS-CoV-2 promotes beta cell death and may increase the risk of developing diabetes associated with COVID-19 illness. Learn about some of the other complications associated with COVID-19 in this episode featuring Dr. Roger Seheult.

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  • COVID-19 illness is linked with impaired cognitive function even months after recovery. www.sciencedaily.com
    Brain Memory COVID-19

    Researchers and clinicians are growing increasingly concerned about the possibility of COVID-19 having a persistent impact on health that extends far beyond recovery from acute illness. In particular, anecdotal reports of former patients experiencing depression, “brain fog,” and difficulty finding the right words in conversation even months later appear to point to a potential long-term impact on cognition. A recent large-scale study offers evidence that COVID-19 promotes long-term cognitive deficits, even among those who experience the mildest form of the disease.

    The study recruited a representative cohort of 81,337 UK participants (average age, 46 years) to take part in a citizen science project known as the Great British Intelligence Test, a widely promoted free opportunity for people to identify their cognitive strengths. Participants performed a series of clinically validated online tasks assessing their emotional processing abilities, as well as cognitive skills such as attention, problem solving, and working memory. Scores from this latter group of tests were pooled to extract a composite score of global cognitive ability for each participant.

    After completing the cognitive tasks, participants were asked to provide some details about their experiences with COVID-19 – information that the researchers went on to use to build a predictive model of their global cognitive and emotional processing abilities.

    Their analysis revealed that clinically confirmed cases of COVID-19 infection were associated with significant cognitive deficits even nine months following infection (the longest period recorded in the study). This was particularly evident in complex tasks that required participants to reason, plan ahead, and solve problems using analogies, although the researchers also observed a general slowing of reaction times across all tasks.

    The scale of this cognitive impairment depended on the severity of respiratory symptoms. People who had severe cases of COVID-19 that required hospitalization and ventilation exhibited the greatest cognitive decline, surpassing the average decline observed in former stroke victims, as well as the mean cognitive difference between groups that differed by 10 years of age.

    Perhaps most surprisingly, the researchers found a significant degree of cognitive decline even in mild cases of COVID-19 who remained at home for the duration of their illness. These individuals performed below what would have been expected if they had not contracted the infection, roughly equivalent to 3.5 IQ points in a classic intelligence test.

    This study offers evidence that COVID-19 infection might have long-term health implications far beyond respiratory symptoms and that recovery may be associated with tangible impairments in certain aspects of higher cognitive function. It remains to be explored whether these deficits remain in the longer term.

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  • Low antibody levels in vaccinated people predict risk of breakthrough infection. www.nature.com
    Vaccine COVID-19

    Messenger RNA (mRNA) vaccines, such as the Pfizer and Moderna vaccines, have significantly reduced SARS-CoV-2 infection and COVID-19 disease rates in areas with vaccine availability. However, a small number of people who have received both doses of an mRNA vaccine have reported breakthrough cases with mild COVID-19 symptoms. New findings suggest people with breakthrough SARS-CoV-2 infection have lower than normal antibody levels preceding infection.

    Recent research has reported breakthrough cases of COVID-19 in just four percent of nursing home residents and staff in Chicago, while a report from Kentucky found breakthrough infections in 25 percent of fully vaccinated residents and seven percent of fully vaccinated staff. A study of healthcare workers who had received an mRNA vaccine in India found breakthrough infections in 13 percent of participants. In all studies, symptoms experienced by those with a breakthrough infection were significantly milder and were less likely to require hospitalization than in unvaccinated people. So far, no predictor of breakthrough infection has been identified.

    The investigators performed their research at Israel’s largest medical center where 91 percent of staff received two doses of a SARS-CoV-2 mRNA vaccine in January 2021. Workers underwent testing for infection using an RT-PCR assay, which measures the amount of viral RNA in a sample. During the same month, Israel experienced a surge in COVID-19 cases, providing good conditions for detecting nearly all breakthrough infections in this population. A breakthrough infection was defined as the detection of SARS-CoV-2 using an RT-PCR assay performed 11 or more days after the second dose of vaccine if no direct exposure or symptoms were reported during the first six days following the second vaccine dose. For each participant who had a breakthrough infection, the researchers found four to five uninfected staff members and compared antibody levels among them.

    Among the nearly 1,500 participants who had available RT-PCR data, only 39 participants (three percent) experienced a breakthrough case. Participants with breakthrough infections had lower antibody levels in the week preceding the onset of symptoms than uninfected vaccinated participants. As the concentration of neutralizing antibodies increased, the risk of breakthrough infection decreased. Most breakthrough cases resulted in mild symptoms such as upper respiratory congestion, muscle aches, fever, and loss of taste and smell. While most symptoms resolved after six weeks, 19 percent of breakthrough cases were “long COVID-19” cases with prolonged symptoms. In all breakthrough cases, contact with an unvaccinated person was the suspected exposure.

    This research suggests that testing of antibody levels following vaccination may identify individuals susceptible to breakthrough infection. Previous infection with the SARS-CoV-2 virus provides additional protection, called hybrid immunity. A report covered in this edition of the Science Digest found that people with hybrid immunity are more protected from reinfection with variant strains.

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  • COVID-19 vaccines are less effective against the delta variant, especially the Pfizer-BioNTech vaccine. www.axios.com
    Vaccine COVID-19

    As the COVID-19 pandemic continues into its second year, a number of variants have emerged, such as the delta variant, which is a highly contagious SARS-CoV-2 variant first identified in India in December 2020. The increase in transmissibility - the ability of a disease to be passed from one individual to another - is due to mutations of the viral spike protein, which allows entry into human cells. Findings of a report released this week show that vaccines that were effective against the original SARS-CoV-2 strain are less effective against the delta variant.

    Viruses are small particles containing genetic material (RNA in the case of SARS-CoV-2) and a lipid capsule with protein structures on the surface. They do not contain the cellular machinery to create new viruses and depend on host cells for replication. Messenger RNA (mRNA) vaccines, such as the Pfizer-BioNTech and Moderna vaccines, work by delivering modified viral RNA encapsulated in a lipid membrane to human cells. These lipid droplets fuse with the lipid membranes of human cells in the respiratory tract and elsewhere and deliver mRNA to the inside of the cell. Once inside the cell, the vaccine mRNA directs the cell to produce more of the modified viral protein. This tricks the immune system into thinking these cells are infected and the body mounts an immune response that ultimately results in the production of antibodies that bind to the SARS-CoV-2 spike protein, preventing subsequent infection.

    Reports published before the emergence of the delta variant demonstrate an efficacy of 95 percent for the Pfizer-BioNTech vaccine and 93 percent for the Moderna vaccine against the original Wuhan Hu-1 strain. Because the delta variant has a modified spike protein, it is unclear if vaccines designed for the original SARS-CoV-2 spike protein will be effective against current and future variants.

    The authors analyzed data from patients of the Mayo Clinical Health System in Minnesota, Wisconsin, Arizona, Florida, and Iowa starting in January 2021, when the original SARS-CoV-2 strain was most prevalent, and ending in July 2021, when the delta variant was most prevalent. The study included more than 25,000 vaccinated participants and 25,000 unvaccinated participants matched for age, sex, race, ethnicity, state of residence, and history of prior SARS-CoV-2 testing.

    The delta variant prevalence in Minnesota increased from less than one percent in May 2021 to over 70 percent in July 2021; whereas the original strain prevalence decreased from 85 percent to 13 over the same period. The researchers found that the Moderna vaccine was between 81 and 91 percent effective and the Pfizer-BioNTech vaccine was between 69 and 81 percent effective against infection with the original SARS-CoV-2 virus prior to May 2021. These vaccines were also highly effective in preventing hospitalization from infection with the original virus with the Moderna vaccine showing 81 to 97 percent efficacy and the Pfizer-BioNTech vaccine showing 73 to 93 percent efficacy. By July, the total effectiveness in preventing infection decreased to 76 percent for the Moderna vaccine and 42 percent for the Pfizer-BioNTech vaccine, indicating a loss of efficacy over time as variants became more common.

    Next, the authors compared vaccine effectiveness across multiple states over the entire study period. In most states, the Moderna vaccine was twice as effective in preventing breakthrough infections than the Pfizer-BioNTech vaccine. This difference in effectiveness against breakthrough infections between the vaccines was highest in July, when the delta variant was most prevalent. This was especially true in Florida, where the risk of breakthrough infection was 60 percent lower after vaccination with the Moderna vaccine compared to the Pfizer-BioNTech vaccine. Across all dates, the Moderna vaccine was twice as effective in preventing COVID-19 associated hospitalization compared to the Pfizer-BioNTech vaccine.

    While both vaccines demonstrate effectiveness in preventing infection and hospitalization, their effectiveness has declined over time as the prevalence of SARS-CoV-2 variants increased. The authors suggested additional studies in large and diverse populations are needed to guide public health policy. This manuscript has yet to be peer-reviewed.

    Previous infection with the original strain of the SARS-CoV-2 along with vaccination creates what is known as “hybrid immunity.” People who have hybrid immunity have a broader and more robust antibody response, as observed in this trial, which is covered in this edition of the Science Digest.

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  • Previous infection with SARS-CoV-2 plus vaccination protects against variants. www.nature.com
    Vaccine COVID-19

    The delta variant of SARS-CoV-2, the virus that causes COVID-19, is one of multiple variants to exhibit increased resistance to antibodies as well as higher transmissibility. It is unclear if vaccination or prior infection with the original Wuhan Hu-1 strain is effective against these emerging variants. But now, a new report suggests individuals who have recovered from infection with the original SARS-CoV-2 strain are protected from variants such as delta, especially following vaccination.

    A virus strain is considered the “parent” form of a virus. For example, SARS-CoV-1 and SARS-CoV-2 are strains of the broader SARS-CoV line of viruses. To be considered a variant, a virus must have sufficient mutations to change a portion of its genetic code. In the case of the delta variant, increased transmissibility is the result of genetic changes to the receptor binding domain, a portion of the viral spike protein. This protein enables viruses to enter cells and is the main target of SARS-CoV-2 vaccines. Its genetic change in the delta variant has scientists concerned that individuals who have recovered from the original virus or an early variant may not be protected against later variants with altered spike proteins.

    During infection with a virus, the innate immune system immediately produces inflammation to fight the infection. Within days or weeks, the adaptive immune system produces antibodies that are specific to the virus. These antibodies bind to a small piece of the viral particle, called an antigen. Plasma B cells are the white blood cells responsible for producing antibodies; however, these cells steadily decrease in number over time and do not protect against reinfection with the same virus. Memory B cells store the genetic information needed to produce virus-specific antibodies upon reinfection.

    The authors of the novel report recruited 63 participants between the ages of 26 and 73 years old who were convalescent, meaning they had recovered from SARS-CoV-2 infection. Some participants had received a vaccine (only mRNA vaccines were included) and others had not. The researchers collected blood samples from their participants at about six weeks, six months, and one year following infection in order to characterize their immune responses specifically to the receptor binding domain of the SARS-CoV-2 spike protein. Immunity measures included specificity (the number of antigens to which an antibody will bind), reactivity (the strength to which an antibody binds its antigen), and neutralizing activity (the antibodies' ability to block infection).

    Their analysis revealed that convalescent participants who had not been vaccinated maintained their plasma antibody levels 12 months following infection, providing protection from reinfection. Notably, convalescent participants who had received an mRNA vaccine had 30 times more antibodies and 50 times greater neutralizing activity against the original SARS-CoV-2 strain 12 months following infection than unvaccinated convalescent participants. Neutralizing activity against the alpha, beta, iota, and gamma variants was also ten times greater at 12 months compared to vaccinated individuals who have never had the virus. This means the immune system will react strongly if a vaccinated convalescent individual catches one of the viral variants.

    Antibody-producing B cells evolved over time in both vaccinated and unvaccinated convalescent participants; however, receiving an mRNA vaccine increased receptor binding domain antibodies eightfold. Without vaccination, convalescent participants lost a significant portion of antibodies that were specific for the receptor binding domain of the spike protein at six months post-infection, putting them at greater risk for reinfection. The authors showed that memory B cells continually mutate their antibody structures to increase reactivity and specificity over time, providing stronger immunity against a wider array of strains.

    The authors concluded that immunity in convalescent individuals is long lasting. Vaccination provides additional protection against SARS-CoV-2 variants in convalescent individuals. However, an article covered in this edition of the Science Digest suggests current mRNA vaccines may be less effective against the delta variant in vaccinated people who have never had a SARS-CoV-2 infection.

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  • The Pfizer-BioNTech and AstraZeneca COVID-19 vaccines are highly effective against the delta variant. www.nejm.org
    COVID-19

    The delta variant of SARS-CoV-2, the virus that causes COVID-19, first emerged in India and has since become a global concern. To be considered a variant, a virus must have sufficient mutations to change a portion of its genetic code. The delta variant carries seven mutations. A recent report describes the effectiveness of the Pfizer-BioNTech and AstraZeneca vaccines against the delta variant.

    The Pfizer-BioNTech vaccine is mRNA-based. It contains the genetic instructions for synthesis of a single viral protein that stimulates the immune system to make antibodies against the SARS-CoV-2 spike protein. mRNA vaccine technology allows rapid scaling of vaccine production and facilitates modification if the virus mutates significantly. The AstraZeneca vaccine is adenoviral vector-based. It uses a modified version of the chimpanzee adenovirus (ChAdOx1) to deliver the genetic information that codes for the SARS CoV-2 spike protein. Adenovirus vector vaccines are currently being tested for numerous infectious agents, ranging from malaria to HIV. Both the Pfizer-BioNTech and AstraZeneca vaccines require two doses for optimal immunity.

    The authors of the report took two approaches to gauge vaccine effectiveness against the delta variant versus the alpha variant (the first SARS-CoV-2 form). First, they compared vaccination status in people who had symptomatic COVID-19 with vaccination status in people who reported symptoms but had a negative test. Next, they estimated the proportion of people with cases caused by the delta variant relative to those caused by the alpha variant, based on vaccination status. Nearly 80,000 people were included in the analysis.

    The authors found that the effectiveness of both vaccines was lower against the delta variant than against the alpha variant, but the Pfizer-BioNTech vaccine was at least 88 percent effective against delta after two doses, and the AstraZeneca vaccine was 67 percent effective after two doses. Notably, both vaccines were only 30 percent effective against the delta variant after only one dose.

    These findings indicate that the Pfizer-BioNTech and AstraZeneca vaccines against COVID-19 are highly effective against the delta variant and underscore the importance of obtaining both doses for optimal immunity. Learn more about COVID-19 vaccines in this clip featuring Dr. Roger Seheult.

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  • Heart rate irregularities are common after recovering from COVID-19. www.upi.com
    COVID-19

    Although most people who have COVID-19 recover within a few weeks of becoming ill, many continue to experience symptoms for several weeks or even months after recovering. The most common long-term effects are fatigue, “brain fog,” and loss of smell or taste. A recent study using data from wearable devices found that people who have COVID-19 often experience resting heart rate irregularities long after recovery.

    Wearable health monitoring devices – often simply called “wearables” – are electronic instruments that patients or consumers can wear to monitor their health, fitness, activity, or sleep. Wearables can transmit information to a physician or to the user in real time, allowing the wearer to actively participate in monitoring and maintaining their own health. Examples of wearables include smartwatches, activity trackers, and sleep monitors. Data from wearable devices may help identify people who have COVID-19.

    The study investigators drew on data collected from DETECT, an app-based study of people who routinely use a smartwatch or other wearable device. The goal of DETECT is to ascertain whether changes in heart rate, activity levels (measured via step count), and sleep can identify early signs of viral illnesses, including COVID-19. They reviewed data from 875 people who developed symptoms of an acute respiratory illness and were tested for COVID-19. Of these, 234 tested positive, and 641 tested negative. They calculated deviations in the participants' baseline heart rate by subtracting their average baseline heart rate from their daily heart rate. They grouped participants based on how many beats per minute that their heart rate deviated from baseline (less than one, one to five, or more than five beats) over a period of 28 to 56 days after developing symptoms.

    The data revealed that participants who tested positive for COVID-19 took longer to return to their baseline resting heart rate, activity levels, and sleep quantity than those who did not. They tended to experience a brief period early in the course of their illness during which their heart rate was slower than normal (bradycardia), followed by a heart rate that was faster than normal (tachycardia). Their tachycardia did not resolve until approximately 79 days after initially developing symptoms. About 13 percent of the COVID-19-positive participants experienced an increase in heart rate of more than five beats per minute that persisted more than 133 days. These participants were more likely to have reported cough, body aches, and shortness of breath than those who experienced lesser deviations (less than one beat per minute) from their baseline resting heart rate. Participants' sleep quantity returned to baseline levels about 24 days after developing symptoms, and their activity levels returned to baseline levels after about 32 days.

    These findings indicate that COVID-19 elicits a wide range of long-term health effects. The authors of the study posited that these effects reflect autonomic nervous system dysfunction or ongoing inflammation, but further study in larger groups is necessary to fully understand the effects of COVID-19 illness. Learn more about how scientists are using wearable devices to diagnose COVID-19 in this episode featuring Dr. Michael Snyder.

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  • mRNA vaccines elicit long-term immunity against COVID-19. medicine.wustl.edu
    COVID-19

    Evidence indicates that immunity following infection with SARS-CoV-2, the virus that causes COVID-19, lasts as long as 11 months. Questions remain, however, regarding the duration of immunity elicited by mRNA vaccines against the virus. Findings from a recent study indicate that mRNA vaccines elicit long-term immunity due to the presence of germinal centers in the lymph tissue.

    Germinal centers are small, transient structures that form in the lymph nodes, gut, and spleen in response to an acute infection or vaccination. They produce plasma cells and memory B cells – long-lasting immune cells that secrete antibodies that provide protection against future reinfection. Germinal centers are important components of the body’s adaptive immune response.

    The authors of the study conducted a two-part experiment. The first experiment involved 14 healthy adults who had received the Pfizer BioNTech COVID-19 vaccine and had never been infected with SARS-CoV-2. The authors of the study sampled cells taken from the lymph nodes of the participants three, four, five, and seven weeks after they received the first dose of the two-dose vaccine. They sampled lymph tissue from 10 of the participants 15 weeks after their first dose.

    Analysis of the lymph tissue indicated that germinal centers were generating antibody-producing B cells three weeks after the initial dose. Germinal center activity remained high through successive weeks, and at 15 weeks after the first dose 80 percent of participants still demonstrated germinal center activity.

    The second experiment involved 41 healthy adults who received the Pfizer BioNTech vaccine, including eight who had previously been infected with SARS-CoV-2. The authors collected blood samples from each of the participants before the first dose and again at four, five, seven, and 15 weeks afterward.

    The blood samples revealed that antibody levels increased slowly among participants who had never been exposed to the virus, peaking about one week after the second dose. In contrast, antibody levels among those who had previously been infected with SARS-CoV-2 were high before the first dose. These levels increased rapidly upon vaccination and peaked higher than those who had never been infected.

    These findings suggest that the immune response to mRNA vaccines is robust and long-lasting. They also underscore the value of vaccination even after having been infected with SARS-CoV-2.

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  • A ketogenic diet improves immunity and reduces excessive inflammation. elifesciences.org
    Ketosis COVID-19 Ketogenic Diet

    A Western dietary pattern, characterized by a low intake of fruits and vegetables and a high intake of red and processed meats and added sugars, promotes chronic diseases, including obesity. It also increases low-grade inflammation by directly reprogramming immune cells to become pro-inflammatory. Authors of a recent report investigated the impact of a ketogenic diet on immunity.

    Glucose is the primary energy source for most cells in the body. However, when a person fasts or restricts carbohydrate intake, the body produces ketones from dietary and body fat for energy. One such ketone is beta-hydroxybutyrate, which has been shown to ameliorate low-grade inflammation and related diseases in mice. Whether consuming a very low carbohydrate diet alters immunity in humans is unclear.

    The investigators recruited 44 healthy adults to complete a three-week ketogenic diet that provided less than 30 grams of carbohydrates per day (the amount in about two slices of sandwich bread). Participants gave blood samples before and after the diet period for measurement of immune cells, including antibody-producing T cells. The researchers exposed white blood cells from the pre-diet and post-diet timepoints to varying concentrations of beta-hydroxybutyrate for 48 hours, stimulated them to produce an immune response, and measured the effect.

    When exposed to beta-hydroxybutyrate, pre-diet white blood cells associated with the innate immune system (the driver of chronic low-grade inflammation) did not alter their behavior; however, antibody-producing white blood cells associated with the adaptive immune system became more active. CD4+ and CD8+ T cells exposed to the highest concentration of beta-hydroxybutyrate (10 millimolar), comparable to the maximum circulating level in humans, produced more cytokines used to fight infection. Regulatory T cells, which prevent autoimmunity and excessive inflammation, also increased their activity, including the mitochondrial metabolism of ketones. Participants lost a significant amount of weight over the three-week ketogenic diet period, and their post-diet T cells showed the same metabolic and immunological responses as those in the in vitro experiment.

    The authors concluded that a very low carbohydrate diet or ketogenic diet is a clinical tool for improving T cell-mediated immunity. They suggested that nutrition and dietary interventions should be used more in modern medicine.

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  • COVID-19 causes gray matter losses in areas of the brain involved in taste, smell, and memory. www.news-medical.net
    COVID-19

    At the time of this publication, more than 182,000,000 cases of COVID-19 have been diagnosed worldwide. Although most cases are mild to moderate in severity, lasting only a few weeks, the long-term effects of the disease are unknown. Findings from a recent study suggest that COVID-19 causes long-term gray matter losses in areas of the brain involved in taste, smell, and memory.

    COVID-19 affects multiple organ systems and elicits a wide range of flu-like symptoms, including cough and fatigue. Many infected persons experience loss of taste or smell, with one study finding that 96 percent of people with active COVID-19 had some loss of smell. Approximately one-third of these had altered smell six to eight weeks after initial diagnosis. Some researchers have hypothesized that SARS-CoV-2, the virus that causes COVID-19, crosses the olfactory mucosa and progresses to the olfactory bulb in the brain, thus gaining access to the nervous system.

    The current study involved 782 adults who had undergone initial brain imaging as part of the UK Biobank study. Approximately half of the participants developed COVID-19 after their initial scan (15 of whom were hospitalized), while the remainder (matched for age, sex, and ethnicity) did not. All participants underwent a second scan, and the two scans were compared.

    The comparison revealed substantive COVID-19-related damage and gray matter losses in the areas of the brain responsible for taste and smell, especially in the left parahippocampal gyrus, the left superior insula, the left lateral orbitofrontal cortex, the left anterior cingulate cortex, the left supramarginal gyrus, and the right temporal pole. Those who were hospitalized showed losses in smell- and memory-related brain regions, especially in the areas around the left cingulate cortex, the right hippocampus, and the amygdala.

    Although these findings have not been peer-reviewed, they suggest that COVID-19 affects the brain in ways that are not fully understood and underscore the need for continued monitoring of COVID-19 patients. The proximity of these losses to areas of the brain responsible for memory raise concerns that people who have had COVID-19 might be at greater risk for developing Alzheimer’s disease or other forms of dementia. A newly formed international consortium is investigating this possibility.

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  • Previous infection with the common cold protects against SARS-CoV-2 infection and COVID-19 illness. www.inverse.com
    COVID-19

    The SARS-CoV-2 virus and the associated COVID-19 disease remain significant global health threats. Since the emergence of SARS-CoV-2 at the end of 2019, much has been learned about its infection course, including transmission, replication, and immune reactivity. Findings of a new report demonstrate the effects of previous infection with the common cold virus on the course of SARS-CoV-2 infection.

    The SARS-CoV-2 virus first enters the upper respiratory tract (i.e., the nasopharynx) via the angiotensin-converting enzyme (ACE) 2 receptor and replicates in epithelial tissue, peaking in concentration within one week of infection. The amount of viral replication in the early stages of infection determines transmissibility and predicts the severity of COVID-19 illness. As the number of viral particles increases, the immune system enhances the expression of interferon-stimulated genes, which are necessary for the antiviral response. People who have had a recent viral infection, such as the common cold, may have greater interferon-stimulated gene expression at the time of SARS-CoV-2 infection, limiting viral replication.

    The researchers used nasopharyngeal swabs from 170 patients with a confirmed SARS-CoV-2 infection and eight healthcare workers who did not have an infection. The researchers used swabs from multiple time points to monitor infection progression, including viral replication and immune response. They obtained information regarding previous viral infections, health history, and COVID-19 status from medical records. In a second experiment, the researchers exposed in vitro human bronchial epithelial cells to rhinovirus, which causes the common cold, before exposure to the SARS-CoV-2 virus to determine the effects of previous infection on immunity.

    The authors found that the SARS-CoV-2 virus elicits increased expression of interferon-stimulated genes after four days of replication similar to other viral infections. Participants with the highest concentration of the protein CXCL10 (a proxy for interferon-stimulated gene expression) were less likely to require hospitalization but had a higher concentration of viral particles in their nasopharynx. The authors posited that patients in the hospital had likely been sick for a longer period of time and had passed the point of infection when viral replication and interferon-stimulated gene expression are highest. In vitro cells that had been previously infected with rhinovirus increased their expression of interferon-stimulated genes, including the short version of the ACE2 receptor. Unlike the long version, SARS-CoV-2 cannot enter through the short ACE2 receptor, meaning that previous rhinovirus infection prevents SARS-CoV-2 entry and dampens viral replication.

    These findings demonstrate that previous infection with rhinovirus decreases the risk of contracting the SARS-CoV-2 virus and may decrease the severity of COVID-19 disease.

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  • Bone marrow cells produce long-lasting immunity against reinfection by the SARS-CoV-2 virus. www.sciencedaily.com
    COVID-19

    COVID-19 is caused by infection from SARS-CoV-2, a type of coronavirus. Following SARS-CoV-2 infection, the immune system produces antibodies specific for the SARS-CoV-2 spike protein that prevent reinfection. However, research from early in the COVID-19 pandemic reported a rapid loss of these antibodies a few months after infection. Findings of more recent research suggest SARS-CoV-2 immunity may last longer than previously thought.

    B cells are white blood cells that originate in the bone marrow. During an infection, mature B cells enter the bloodstream as plasma cells, where they are activated to produce antibodies specific for the active pathogen. When the infection has resolved, B cells called long-lived bone marrow plasma cells return to the bone marrow where they lie dormant until exposure to the same pathogen reoccurs, providing long-lasting immunity.

    The researchers collected blood from 77 patients who had recovered from mild SARS-CoV-2 infection approximately one month following the onset of symptoms and then every three months. They also collected bone marrow samples from 18 participants seven to eight months after infection and from 11 healthy volunteers with no history of SARS-CoV-2 infection or vaccination. Finally, they collected a second bone marrow sample from six participants 11 months after infection.

    In the first four months following infection, the concentration of plasma spike antibodies decreased by almost 10 percent; however, this rate slowed over time so that only seven percent of antibodies were lost between four and 11 months. At seven months post-infection, bone marrow samples from most recovered patients contained bone marrow plasma cells specific for SARS-CoV-2, and the concentration of these cells remained stable at 11 months post-infection. Participants had no spike antigen-producing cells in their blood at the time of bone marrow sampling, meaning all antibody-producing cells were located in bone marrow only at 7 and 11 months post-infection.

    These findings demonstrate that infection with the SARS-CoV-2 virus results in long-term immunity from long-lived bone marrow plasma cells, even though concentrations of antigen in the bloodstream decrease over time.

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  • Vitamin D treatment reduces the risk of severe outcomes, including death, in patients with COVID-19 www.mdpi.com
    Vitamin D COVID-19

    Vitamin D deficiency in the setting of COVID-19 can lead to over-expression of renin (an enzyme produced in the kidneys) and subsequent activation of the renin-angiotensin-system, a critical regulator of blood pressure, inflammation, and body fluid homeostasis. Disturbances in this system can drive poor outcomes, such as acute respiratory distress syndrome (ARDS) and death in COVID-19. Findings from a recent study suggest that supplementation with calcifediol, an intermediate molecule in the production of the active form of vitamin D, reduces the risk of death due to COVID-19.

    Unlike other vitamins – trace nutrients that must be consumed in the diet – vitamin D is a steroid hormone that is produced in the body. Its synthesis occurs in a stepwise manner that begins in the skin following exposure to ultraviolet light and ends in the kidneys with the production of 1α,25-dihydroxyvitamin D, or 1,25(OH)2D, the active steroid hormone.

    The retrospective cohort study involved 537 patients living in Spain who were hospitalized with COVID-19 during a three-month period in early 2020. Of these patients, 79 received vitamin D treatment providing 532 micrograms (~21,000 IU) of calcifediol on the first day of their hospital stay, and 266 micrograms of calcifediol (~9,300 IU) on days 3, 7, 14, 21, and 28. The primary outcome measure was death during the first 30 days of hospitalization.

    During the study period, 20 percent of patients who did not receive vitamin D treatment died. More of the patients in the untreated group had chronic kidney disease, but fewer had diabetes, cancer, high blood pressure, or other cardiovascular diseases, compared to the treated group. They also had low oxygen saturation levels and were more likely to have elevated inflammatory markers. Twenty-five percent of this group developed ARDS. Only 5 percent of those who received vitamin D treatment died, and only 10 percent of these developed ARDS, even though the patients in this group were more likely to have comorbidities (coexisting health conditions) compared to the untreated group.

    These findings suggest that vitamin D reduces the risk of severe outcomes, including death, in patients with COVID-19. The authors of the study noted that this small study was observational in design, possibly limiting the interpretation of these findings. They also noted that although none of the patients in this cohort were assessed for vitamin D deficiency, most of the people who live in southern Spain tend to be deficient during the time of year when the study was conducted.

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  • COVID-19 vaccines effective against emerging variants. www.the-scientist.com
    COVID-19

    In recent months, several variants of SARS-CoV-2, the virus that causes COVID-19, have emerged. The most notable of these are B.1.1.7, first identified in the United Kingdom; B.1.351, first identified in South Africa; and P.1, first identified in Brazil. To be considered a variant, a virus must have sufficient mutations to change a portion of its genetic code. The B.1.1.7 variant has 17 mutations, the B.1.351 variant has 10 mutations, and the P.1 variant has three mutations. Findings from three recent studies indicate that vaccines and boosters using mRNA technology or recombinant technology are effective against the variants.

    mRNA-based vaccines contain the genetic instructions for synthesis of a single viral protein that, when injected into the body, stimulates the immune system to make antibodies against a spike protein located on the SARS-CoV-2 surface. The use of mRNA vaccine technology allows rapid scaling of vaccine production and facilitates modification if the virus mutates significantly. Two mRNA vaccines (Pfizer-BioNTech and Moderna) are currently authorized for use in the United States.

    Recombinant vaccine technology inserts the genetic information for the spike protein into insect cells, which are then harvested, purified, and housed in nanoparticles. The Novavax recombinant vaccine has been tested in trials in the United States, United Kingdom, Mexico, and South Africa.

    The first of the studies assessed effectiveness of the Pfizer-BioNTech vaccine against the B.1.1.7 variant. The study was conducted in Israel, where 95 percent of all COVID-19 cases were caused by the B.1.1.7 variant. The authors of the study found that two doses of Pfizer-BioNTech vaccine were 97 percent effective against COVID-19 (including those caused by the B.1.1.7 variant) in vaccine recipients aged 16 to 85 years.

    The second study was a phase 2 trial that assessed three candidate mRNA vaccines from Moderna: a booster against B.1.351; a combination booster containing a 50-50 mix of the original vaccine and the B.1.351 vaccine; and a booster containing a lower dose of the original vaccine. Vaccination with the B.1.351 booster or the 50-50 mix of the B.1.351 vaccine and the original vaccine increased antibody titers against both the B.1.351 and P.1 variants.

    A third study looked at the effectiveness of the Novavax vaccine against the B.1.351 variant among people living in South Africa, where the variant first emerged. The vaccine was tested among HIV-negative and HIV-positive participants. It was 60 percent effective against mild, moderate, and severe COVID-19 illness in HIV-negative participants and 50 percent effective in HIV-positive participants.

    These findings indicate that three commonly used vaccines are highly effective against emerging SARS-CoV-2 variants in adults. Ongoing and future trials will assess their efficacy and safety in other populations.

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  • Regular exercise reduces COVID-19 risk. www.sandiegouniontribune.com
    COVID-19

    Regular physical activity promotes physical and mental well-being and reduces the risk of developing chronic diseases such as cardiovascular disease and cancer. Findings from a new study suggest that regular physical activity also reduces the risk of developing COVID-19.

    Most international public health organizations recommend that adults of all ages engage in at least 150 minutes of moderate intensity aerobic physical exercise or at least 75 minutes of vigorous intensity aerobic physical exercise each week, or an equivalent combination of both. Most adults fall far short of these recommendations, however.

    The retrospective observational study involved more than 48,000 patients who had been diagnosed with COVID-19 between January and October 2020. The study investigators obtained data regarding the patients' physical activity levels in the two-year period between March 2018 and March 2020 via their electronic health records. They categorized the patients as “consistently inactive” (zero to 10 minutes per week), having “some activity” (11 to 149 minutes per week), or “consistently meeting guidelines” (150+ minutes per week).

    Statistical analysis revealed that COVID-19 patients who were consistently inactive were 2.26 times more likely to be hospitalized; 1.73 times more likely to be admitted to the intensive care unit (ICU), and 2.49 times more likely to die due to COVID-19 than patients who were consistently meeting guidelines. Engaging in some activity mitigated risk slightly: Consistently inactive patients were 1.2 times more likely to be hospitalized, 1.1 times more likely to be admitted to the ICU, and 1.32 times more likely to die from COVID-19 than patients who were doing some physical activity.

    These findings suggest that physical activity decreases the risk of developing COVID-19 and underscore public health messaging to promote regular physical activity. For people who are unable to regularly engage in exercise due to physical limitations or injury, sauna use may be an alternative. Heat exposure during sauna use mimics many of the physiological responses to exercise, including immune-boosting effects. Learn more about sauna use in our overview article.

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  • Omega-3 fatty acids improve clinical outcomes in severe COVID-19. translational-medicine.biomedcentral.com
    Omega-3 COVID-19

    Nutritional status plays critical roles in fighting infections, influencing not only how well the body’s immune system works but also how pathogens behave in the body. Findings from a new study suggest that omega-3 fatty acids improve clinical outcomes in critically ill patients with COVID-19.

    Omega-3 fatty acids, such as eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and alpha-linoleic acid (ALA) are essential nutrients. They participate in a wide range of physiological functions, including immune responses. Evidence suggests that omega-3 fatty acids stabilize cell membranes, regulate immune function, impair hyper-inflammatory reactions, and reduce severe outcomes associated with infections, such as systemic inflammatory response syndrome and multiple organ dysfunction syndrome.

    The double-blind, randomized clinical trial involved 101 critically ill hospitalized patients (average age, 65 years) diagnosed with COVID-19. Twenty-eight of the patients received 1,000 milligrams of supplemental omega-3 fatty acids via enteral feeding daily for two weeks, commencing 24 hours after admission to the intensive care unit. The supplement provided 400 milligrams of EPA and 200 milligrams of DHA. The remainder of the participants received enteral feeding without supplemental omega-3 fatty acids. The study investigators collected the participants' anthropometric data, medical histories, dietary records, and biochemical measures of respiratory and renal function.

    The one-month survival rate was 21 percent among the patients who received the supplemental omega-3 fatty acids, versus 3 percent among those who did not receive the supplement. The supplemented group also had improved markers of respiratory and renal function, including higher arterial pH, bicarbonate, and urinary output levels and lower blood urea-nitrogen, creatinine, and potassium levels.

    These findings suggest that supplemental omega-3 fatty acids improve respiratory and renal function in critically ill patients with COVID-19. Although the study was sufficiently powered, the sample size was small, necessitating future studies with larger groups.

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  • Previous COVID-19 infection or vaccination confers long-term protection against future severe disease outcomes. www.forbes.com
    COVID-19

    Following infection with the SARS-CoV-2 infection, the adaptive immune system produces neutralizing antibodies that attack the virus and prevent further illness in those who recover. Vaccination provides another means of developing long-lasting immunity. However, neutralizing antibody concentrations decline with time following vaccination or previous infection. Authors of a recent report created a model for predicting the decline of neutralizing antibody concentrations over time and what is needed to maintain long-term immunity.

    Those who recover from SARS-CoV-2 infection have an estimated 89 percent protection from reinfection, while vaccine protection estimates range from 50 percent to 95 percent. There is concern that new variants may bypass immune protection in vaccinated and previously infected people. Predictive models of immunity may guide the distribution of vaccines and vaccine boosters as the pandemic progresses.

    The researchers combined and standardized data from trials studying the neutralizing antibody response to seven different vaccines and data from a group of recovered participants. They created a model based on previous research of the influenza virus to estimate the concentration of antibodies needed to provide 50 percent protection against SARS-CoV-2 infection. Lastly, they used their model to predict the efficacy of a new vaccine released in March 2021.

    The authors reported that the antibody concentration needed to provide 50 percent protection is just 20 percent of the average concentration in recovered people three to four months following infection. The concentration needed to prevent severe COVID-19 disease is only 3 percent of convalescent levels. Using their model, the investigators predicted a significant decline in antibody concentration over 250 days following vaccination; however, the predicted concentration is still high enough to prevent severe disease. The model was also highly effective in predicting the efficacy of a new vaccine (79 percent estimated efficacy, 81 percent reported efficacy).

    The authors noted that methods for measuring neutralizing antibody activity and recovery status varied widely among the studies they used to create the model, which may decrease its efficacy; however, early use of the model provided accurate results.

    Link to full text.

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  • Sunlight is more effective at inactivating the SARS-CoV-2 virus than predicted. www.sciencealert.com
    COVID-19

    As the global COVID-19 pandemic continues, new ways of battling SARS-CoV-2, the virus that causes the disease, are needed, especially in areas where vaccine distribution is low. Sunlight is an inexpensive and widely-available tool for disinfection, but may require too much time to be effective. Researchers have discovered a discrepancy between the expected and actual rates of ultraviolet (UV) sterilization for the SARS-CoV-2 virus, although the reason for this discrepancy is unknown.

    Sunlight contains a spectrum of wavelengths of UV radiation including UVA and UVB light, which directly damage viral RNA and inactivate viruses. The time it takes for sunlight to sterilize a given virus depends on the size of the viral genome and the wavelength of light. In a 2005 report from the US Army, researchers created an equation for calculating the sunlight sterilization times for various viruses in a variety of geographic locations.

    The same group of researchers used their model to estimate the expected time to 90 percent sterilization of the SARS-CoV-2 virus for various locations within and outside the US during different seasons. A second group of researchers from the National Biodefense Institute conducted an experimental study in which they measured the [90 percent sterilization time] of the SARS-CoV-2 virus (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313905/) suspended in simulated saliva or laboratory media and dried on stainless steel using artificial UVB light.

    When compared to the estimates produced by the first group of researchers, actual time to sterilization for SARS-CoV-2 virus in simulated saliva was eight times faster than expected. When exposed to UV light at a level one would expect at a latitude of 40 degrees north at noontime during the summer, the 90 percent sterilization time was 6.8 minutes. Sterilization time for the virus in laboratory media was three times faster than expected at 14.3 minutes.

    Both groups of researchers concluded that sunlight could be an important tool in fighting the spread of the SARS-CoV-2 virus, but factors like latitude, season, and weather all affect the time required for sterilization. They cautioned that low sunlight exposure in many northern cities during the winter months may lengthen the 90 percent sterilization time. Further research is needed to understand why sunlight sterilization is more effective against the SARS-CoV-2 virus than originally estimated.

    Link to full study.

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  • A measles-based vector vaccine may be effective against COVID-19. news.osu.edu
    COVID-19

    More than 200 vaccine candidates for COVID-19 are currently in development, employing a wide range of vaccine technologies. Findings from a new study demonstrate that a measles-based vector vaccine may be effective against COVID-19.

    Measles is a highly contagious disease caused by the measles virus. The current measles vaccine, which was developed in the early 1960s, is based on an attenuated, live virus. It has been one of the safest and most successful vaccines ever used in children and is often delivered as part of a triple vaccine against measles, mumps, and rubella, commonly referred to as the MMR vaccine.

    Vector vaccines use an altered version of a virus to deliver instructions, in the form of genetic material, to induce antibody production against a different virus. Vector vaccines have been used safely against a variety of viral illnesses, including influenza, hepatitis, and others.

    COVID-19 is caused by the SARS-CoV-2 virus. The primary antigenic component – the part of the virus that provokes an immune response – is a spiky protein on the surface of the vaccine (aptly named a spike protein) that attaches to receptors on mammalian cells. Prior to its attachment, it is referred to as the prefusion spike protein.

    The authors of the study developed several measles virus vector vaccines carrying genetic material for different forms of the SARS-CoV-2 and tested them in several rodent models. They found that vaccines carrying genetic information for the prefusion spike protein induced neutralizing antibody levels higher than those present in convalescent plasma of patients recovered from COVID-19, as well as a robust T cell immune response, even among animals previously vaccinated against measles. In fact, the prefusion spike protein vector vaccine provided complete protection against SARS-CoV-2 challenge and associated respiratory illness – in a single immunization.

    These findings suggest that the measles vaccine is an excellent vehicle for delivering protection against the SARS-CoV-2 virus. The authors posited that their vector-based prefusion spike protein vaccine could be incorporated into the current MMR vaccine as a quadruple protection against multiple pathogens.

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  • More than half of hospitalized COVID-19 patients with elevated troponin levels have heart damage. www.sciencedaily.com
    COVID-19

    Emerging evidence suggests that COVID-19, the disease caused by SARS-CoV-2, elicits a wide range of cardiovascular-related complications, including myocarditis (inflammation of the heart muscle), ventricular failure, myocardial infarction (heart attack), and others. Findings from a recent study indicate that more than half of hospitalized patients who have severe COVID-19 and elevated troponin levels have heart damage.

    Troponin is a group of three proteins that regulate heart and skeletal muscle contractions. Elevated levels of cardiac-specific troponin are indicators of heart muscle damage. Many people who are hospitalized with COVID-19 have elevated troponin levels.

    The study involved 148 patients (average age, 64 years) who had recovered from severe COVID-19 illness. Of these, 48 required ventilator support. The authors used a form of magnetic resonance imaging called multi-parametric cardiovascular magnetic resonance imaging to assess heart muscle damage in the patients.

    The imaging revealed that more than half (54 percent) of the patients exhibited signs of heart damage, including infarction (tissue death) and/or ischemia (poor blood supply), or both; some showed signs of myocarditis-like scarring. A quarter of the patients had ischemia; of these, two-thirds had no prior history of coronary disease. The majority of patients (88 percent) exhibited limited extent myocarditis-like injury, and nearly one-third (30 percent) of these had active myocarditis.

    These findings suggest that COVID-19 exerts deleterious effects on multiple organ systems, including the cardiovascular system, and underscores the need for monitoring COVID-19 patients well after recovery.

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  • SARS-CoV-2 virus targets and damages the muscle cells of the heart in the setting of COVID-19. medicine.wustl.edu
    COVID-19

    COVID-19 elicits a wide range of cardiovascular-related complications. Whether these problems are due to viral presence in the heart tissue, or they’re driven by the body’s systemic inflammatory response to the virus has remained unknown. Findings from a new study demonstrate that the SARS-CoV-2 virus targets the cardiomyocytes of the heart in the setting of COVID-19, causing myocarditis.

    SARS-CoV-2, the virus that causes COVID-19, exploits the ACE2 receptor to gain entry into cells. A specific region of the virus called a spike protein binds to a cell’s ACE2 receptor, and the virus injects its genetic material – RNA – into the cytosol. Once inside, the virus hijacks the body’s natural replicating processes to promote viral reproduction.

    Myocarditis is a condition characterized by inflammation of the heart muscle (myocardium). It typically manifests as chest pain, heart failure, or sudden death. Myocarditis commonly occurs after a viral infection.

    Using stem cells, the authors of the study developed an engineered heart tissue system that mimicked many aspects of SARS-CoV-2-induced inflammation of the heart muscle. Their model demonstrated that SARS-CoV-2 infects the heart’s muscle cells, driving many deleterious effects, including reduced expression of genes related to metabolism and contraction, and promoting inflammation and cell death. The model confirmed that SARS-CoV-2 entered the cells via ACE2 and quickly replicated, produced viral particles, and activated the interferon response – classic features of viral infection.

    These findings demonstrate that myocarditis in the setting of COVID-19 occurs due to SARS-CoV-2 infection of heart muscle cells and provide a unique model by which to study the disease. Learn more about COVID-19 in this new episode featuring Dr. Roger Seheult.

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  • A single dose of two currently available vaccines reduces COVID-19-related hospitalizations. www.the-scientist.com
    COVID-19

    Global vaccination programs have administered more than 218 million COVID-19 vaccine doses across 99 countries, at roughly 6.15 million doses per day. A recent study shows that a single dose of two currently available vaccines reduces COVID-19-related hospitalizations.

    The authors of the prospective cohort study drew on data from the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 database, a compendium of information that links vaccination, primary care, testing, hospitalization, and death records for 5.4 million people living in Scotland. They conducted a statistical analysis to estimate effectiveness of a single dose of the Pfizer and Oxford-AstraZeneca vaccines against COVID-19-related hospitalization.

    The analysis revealed that a single dose of the Pfizer vaccine reduced the risk of COVID-19-related hospitalization by 85 percent at 28 to 34 days post-vaccination. A single dose of the Oxford-AstraZeneca vaccine reduced risk by 94 percent at the same time frame post-vaccination. The results were similar (81 percent reduced risk) when the authors limited the analysis to vaccine recipients over the age of 80 years.

    These findings suggest that a single dose of two currently available COVID-19 vaccines effectively reduces the risk of hospitalization due to the disease and underscore the importance of expediting vaccinations globally. This study is in pre-print and has not undergone peer-review.

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  • Children are less likely to develop and spread COVID-19. www.eurekalert.org
    COVID-19

    The incidence, clinical characteristics, and severity of outcomes of COVID-19 in children differ from those seen in adults. Questions remain regarding whether these differences are due to decreased susceptibility or testing and whether infected children can infect others. Findings from a recent study suggest that children are less likely to develop and spread COVID-19.

    The authors of the study collected data from 637 households in which all members (3,353 total) had been tested for COVID-19 using polymerase chain reaction (PCR), a type of diagnostic test. A subset of 714 household members underwent serological testing for the presence of antibodies to the SARS-CoV-2 virus, the virus that causes COVID-19. They analyzed the data using mathematical modeling.

    The PCR data indicated that nearly half (1,510) of the household members tested positive for COVID-19, but children (defined as 20 years and younger) were half as likely to test positive compared to adults. Interestingly, the serological data revealed that PCR testing under-detected infections in children. The mathematical modeling data indicated that children were 43 percent less likely than adults to be infected with SARS-CoV-2. If infected, they were 63 percent less likely than adults to spread the infection.

    These findings suggest that low susceptibility and under-detection of positive cases in children contribute to the low number of COVID-19 cases in children. The authors of the study posited that their model could have application in other settings, such as nursing homes and schools, to help understand disease transmission and guide public health policy.

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  • Humidity inside face masks contributes to reduced severity of COVID-19 outcomes. www.eurekalert.org
    COVID-19

    Public health experts recommend wearing masks to reduce the risk of developing COVID-19. Evidence indicates that the masks serve as simple barriers to prevent viral transmission during high-risk scenarios. Findings from a new study suggest that the humidity inside masks contributes to reduced severity of COVID-19 outcomes.

    Viral respiratory infections such as colds and influenza exhibit seasonal characteristics and commonly occur during colder weather, when indoor air humidity is often low. Studies in mice have shown that susceptibility to influenza increased in low humidity.

    The current study measured the humidity of the respired air inside four types of commonly worn masks – an N95 mask, a disposable surgical mask, a two-layer cotton-polyester mask, and a heavy cotton mask. Volunteers breathed into a sealed steel box in which the humidity was measured. Air temperatures during the experiment ranged from 46° to 98° F.

    The authors of the study found that all four mask types increased the humidity of the volunteers' respired air, especially at lower temperatures. Humidity inside the thick cotton mask was highest compared to the others, regardless of temperature.

    These findings demonstrate that the protective effects of wearing a mask may be due the increase in humidity in the inspired air of the user. They also underscore the importance of wearing masks indoors where relative humidity may be low.

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  • High-dose vitamin D booster therapy reduces the risk of death among COVID-19 patients. www.mdpi.com
    Vitamin D COVID-19

    A growing body of evidence suggests that vitamin D plays a critical role in preventing and treating COVID-19. Observational data demonstrate that people who take vitamin D regularly are 34 percent less likely to develop COVID-19. Findings from a recent study show that high-dose vitamin D booster therapy reduces the risk of death among COVID-19 patients.

    The retrospective, cross-sectional observational study involved 986 COVID-19 patients admitted to two hospitals in the United Kingdom (Royal Preston Hospital and University Hospitals of Leicester) over a period of approximately seven months in 2020. The authors of the study categorized the patients according to their vitamin D status: replete (> 50 nmol/L), insufficient (25 to 50 nmol/L), or deficient (< 25 nmol/L), and whether they received high-dose vitamin D booster therapy or not.

    The average age of the participants at Royal Preston Hospital was 76 years, and their average vitamin D levels were 45 nmol/L (insufficient). The average age of the participants at University Hospitals of Leicester was 70 years, and their average vitamin D levels were 43 nmol/L (insufficient). A total of 151 of the patients received vitamin D booster therapy; 66 percent of these received 40,000 IU weekly, and 32 percent received 20,000 IU weekly.

    The data from this observational study indicated that those who received vitamin D therapy were 87 percent less likely to die from COVID-19, regardless of their baseline vitamin D levels. Clinical trials using varying vitamin D doses and frequencies are critical to determining whether vitamin D is indeed causal in the fight against COVID-19. Some randomized controlled trials have shown that weekly and daily vitamin D doses are protective against respiratory infections but single monthly doses are not. Furthermore, inter-individual variation in response to vitamin D supplementation is fairly common. In a sample of 35 healthy young people given 8,000 IU of vitamin D, 14 were high responders, 11 were mid responders, and 10 were low responders

    The time and circumstances surrounding administration are important, too. For example, one recent study involving just 208 COVID-19 patients found no benefit when seriously ill patients received vitamin D roughly 10 days after symptom onset in conjunction with other treatments, including dexamethasone. The FMF team has identified several flaws in this study’s design and implementation.

    First, the patients who received vitamin D had more pre-existing conditions (obesity, high blood pressure, and diabetes) than the patients who received the placebo at baseline, so one would expect these patients to have worse outcomes, regardless of supplementation. In addition, there is considerable discordance between the primary endpoints: More of the patients who received vitamin D died, but fewer were admitted to the ICU or were ventilated, an anomaly that suggests the caregivers were not blinded and were biased to undertreat the vitamin D group.

    Perhaps the greatest flaw is how underpowered the study is. With a sample size of only 208 participants, the authors of the study would have 80 percent power to detect a 50 percent difference in hospital length-of-stay. Setting the bar such that hospitalization stays need to be cut in half for vitamin D to be deemed successful is unrealistic. Even if vitamin D supplementation did cut hospitalization in half, there is still a 20 percent chance the study would not show it. (For comparison, millions of people are prescribed low dose “baby” aspirin to prevent a major coronary event despite the fact that 265 people would have to be treated in order for just one person to actually benefit from it.)

    Finally, title of the article is incorrect. As explained in this article in Nature, studies never prove the null hypothesis, they only reject or fail to reject it. In this study, the null hypothesis is that there is no difference in outcome between vitamin D and a placebo. Because the findings in this study did not reach statistical significance, it failed to prove there is a difference but did not prove that there was no difference.

    A randomized controlled trial to investigate the prophylactic use of vitamin D for reducing COVID-19-associated hospitalization and mortality (VIVID Trial) is currently underway and is still recruiting participants. This type of trial may be the best hope for proving the clinical benefit of vitamin D in COVID-19 since people would take vitamin D before illness occurs. Hospital-based treatment trials are challenging because patients are already very sick, and it may be too late for vitamin D to be protective.

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  • Regular use of supplemental vitamin D reduces the risk of developing COVID-19. academic.oup.com
    Vitamin D COVID-19

    Vitamin D is a fat-soluble vitamin that plays key roles in several physiological processes, including immune function. Research indicates that people who take supplemental vitamin D are less likely to have acute respiratory tract infections. Findings from a new study suggest that regular use of supplemental vitamin D reduces the risk of developing COVID-19.

    Vitamin D deficiency in the setting of COVID-19 can lead to over-expression of renin (an enzyme produced in the kidneys) and subsequent activation of the renin-angiotensin-system, a critical regulator of blood pressure, inflammation, and body fluid homeostasis. Disturbances in this system can drive poor outcomes in COVID-19.

    The study involved nearly 8,300 adults enrolled in the UK Biobank study who had been tested for COVID-19. The investigators collected information about the participants' demographics and health status, use of vitamin D supplements (as well as other vitamins), and circulating vitamin D levels.

    The authors found that people who took vitamin D regularly (daily or weekly) tended to be older, have better overall health, and to take other supplements. They also had higher levels of circulating vitamin D. Notably, they were 34 percent less likely to develop COVID-19 compared to people who did not take vitamin D.

    Although this was an observational study and causation cannot be established, these findings suggest that regular vitamin D supplementation is beneficial in reducing the risk of developing COVID-19. The authors posited that the protective effects of vitamin D are attributable to the vitamin’s capacity to maintain cell junctions to reduce the risk of infection; enhance cellular innate immunity; or modulate the renin-angiotensin-system.

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  • Angiotensin receptor blockers (ARBs) as a COVID-19 treatment? encycla.com
    Blood Pressure COVID-19

    Almost a year ago, I remember seeing this post here about how ACE inhibitors and ARBs may increase the risk of severe COVID-19:

    https://www.foundmyfitness.com/news/s/kyzlip/ace_inhibitors_and_angiotensin_receptor_blockers_may_increase_the_risk_of_severe_covid-19

    It turns out, after many large observational studies, including metanalysis of these studies, that these drugs do not increase risk and decrease risk in some circumstances:

    https://www.medrxiv.org/content/10.1101/2020.05.03.20089375v1

    Two randomized controlled trials that suspended ACEi/ARBs in COVID-19 positive hospitalized patients such as BRACE Corona (https://pubmed.ncbi.nlm.nih.gov/33464336/) showed again no delirious impact of RAS inhibitors in the context of COVID-19 hospitalization.

    Mounting in vitro and in vivo data supports the theory that these drugs may, if dosed appropriately, help in the context of COVID-19 - e.g. ARBs may be a viable treatment.

    For instance, this animal study establishes a causal link between the renin-angiotensin system and COVID-19:

    https://www.researchsquare.com/article/rs-124634/v1

    In the above animal study, it’s shown that the ACE2 enzyme activity itself (not as a receptor) modulates the severity of lung damage. While ARBs do not directly affect the ACE2 receptor, they likely work to stop this lung damage in a similar way (see https://www.nature.com/articles/nm1267 - for SARS, where losartan performs as well as soluble ACE2 in attenuating lung injury).

    I’ve already typed too much (!) but the page above is a good catalog of these trials (de novo invitation of ARBs / renin-angiotensin modulating drugs in the context fo COVID-19)

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  • Moderna COVID-19 vaccine effective against emerging variants of SARS-CoV-2 virus. investors.modernatx.com
    COVID-19

    On December 18, 2020, the Food and Drug Administration granted emergency use authorization for the Moderna mRNA vaccine against SARS-CoV-2, the virus that causes COVID-19. In recent weeks, however, variants of the SARS-CoV-2 virus have emerged, raising questions about the vaccine’s efficacy. A recent report from Moderna summarizes their findings regarding the two variants.

    To be considered a variant, a virus must have sufficient mutations to change a portion of its genetic code. Several variants of the SARS-CoV-2 virus have emerged, but the most notable of these, B.1.1.7, first identified in the United Kingdom, and B.1.351, identified in South Africa, appear to be more virulent than previous variants. The B.1.1.7 variant has 17 mutations, eight of which are located in the spike protein, the major surface protein that the virus uses to gain access into cells. The B.1.351 variant has 10 mutations located in the spike protein.

    The Moderna group tested their vaccine’s capacity to produce neutralizing antibodies against the new variants. They determined that the two-dose vaccine was equally effective against the B.1.1.7 variant in terms of inducing neutralizing antibodies. The level of neutralizing antibodies was sixfold lower against the B.1.351 variant, but this level is still considered sufficient to provide protection against infection. Moderna is investigating whether a third dose (a “booster”) will provide even better immunity against the variants.

    The findings presented in this report have not been subjected to peer-review.

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  • Neurological effects of COVID-19 still evident six months after recovery. www.scientificamerican.com
    Brain COVID-19

    COVID-19 primarily manifests as a respiratory illness, but cardiovascular, gastrointestinal, and neurological symptoms have been reported in some cases. Although most of these symptoms are acute and resolve within a few weeks, many people experience long-term complications of the illness, a phenomenon referred to as “post-COVID-19 syndrome. A recent report describes the long-term neurological effects of COVID-19.

    Mounting evidence indicates that COVID-19 affects the neurological system. A previous report found that the range of acute neurological symptoms associated with COVID-19 included psychoses, delirium, encephalitis, strokes, and Guillain-Barré syndrome. Other evidence suggests that COVID-19 affects speech. A case report describes a woman who manifested stuttering and word-finding difficulties during her COVID-19 illness. A recent lay article described the occurrence of stutter several weeks after recovering from COVID-19. Neuroscientists posit that the inflammatory response that accompanies COVID-19 perturbs the brain neurocircuitry that controls speech.

    The most recent study investigating neurological phenomena associated with COVID-19 involved 165 people (average age, 65 years) who had been hospitalized for the illness and had recovered. Six months after discharge from the hospital, the patients were assessed for long-term neurological symptoms.

    The assessments revealed that more than one-third of the patients experienced long-term neurological abnormalities after COVID-19 illness. The most common complaints were fatigue, memory and attention problems, sleep disorders, and muscle pains. Others included depression, anxiety, visual disturbances, impaired sense of smell, and tingling or numbness. The patients who reported having cognitive deficits were more likely to have experienced worse respiratory symptoms and required longer hospitalization than those without cognitive problems.

    These findings suggest that COVID-19 is associated with a wide range of neurological disorders and many of these disorders manifest long after the original infection. The authors noted that since their study excluded patients with pre-existing neurological disorders, their findings might underestimate the full burden of neurological symptoms associated with COVID-19.

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  • SARS-CoV-2: Transitioning from pandemic to endemic. www.eurekalert.org
    COVID-19

    On March 11, 2020, the World Health Organization declared the global outbreak of SARS-CoV-2 infection, known as COVID-19, a pandemic. A recent report identifies the immunological characteristics of SARS-CoV-2 that will govern its transition from pandemic to endemic status.

    The epidemiological view of endemic disease is one that is continuously, predictably present in the human population. An endemic disease is in a steady state in which the infection does not die out and the number of infected people does not increase exponentially.

    The SARS-CoV-2 virus, the cause of COVID19, is one of seven coronaviruses known to infect humans. Four of these human coronaviruses are globally endemic and elicit mild symptoms, while the remaining two, SARS-CoV (which causes severe acute respiratory syndrome, or SARS) and MERS-CoV (which causes Middle East respiratory syndrome, or MERS), are associated with more severe disease outcomes and death.

    The authors of the report developed an epidemiological model based on key aspects of immunity, all of which centered on reinfection. These aspects included how susceptible a population is to reinfection, whether the disease weakens after reinfection, and how quickly the virus spreads after reinfection.

    The authors' analysis suggested that once SARS-CoV-2 becomes endemic, the disease profile will look considerably different than it does now, affecting primarily children, eliciting mild symptoms, and providing immunity against severe outcomes with future reinfection. In this scenario, vaccination might not be required. However, the current vaccines against SARS-CoV-2 will play a role in how fast the virus becomes endemic, especially if they induce short-lived immunity but reduce the severity of disease upon reinfection. The authors posited that as milder reinfections become more common, reliance on symptoms as a surveillance tool to curb the virus’s spread will become more difficult.

    These findings suggest that in the coming years SARS-CoV-2 infection will become endemic, but until then, public health containment strategies such as wearing masks and social distancing remain essential.

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  • Low incidence of anaphylactic shock with Pfizer-BioNTech coronavirus vaccine. www.cdc.gov
    COVID-19

    Anaphylaxis, sometimes referred to as anaphylactic shock, is a severe, potentially life-threatening reaction to an allergen. It affects the entire body, and its symptoms include skin rash, shortness of breath, nausea, vomiting, and anxiety, among others. A recent report describes the incidence of anaphylactic shock following immunization with the Pfizer-BioNTech coronavirus vaccine.

    The Pfizer-BioNTech vaccine, also known by its generic name tozinameran or its brand name Comirnaty, induces an immune response against SARS-CoV-2, the virus responsible for COVID-19. A clinical trial involving more than 43,000 people demonstrated that the vaccine has an efficacy rate of 95 percent in preventing the disease. The most common reactions to the vaccine were injection site reactions, fatigue, headache, muscle pain, chills, joint pain, and fever.

    The Centers for Disease Control and Prevention (CDC) report that some severe reactions have occurred. As of December 23, 2020, nearly 1.9 million people in the United States had received their first dose of Pfizer-BioNTech vaccine. Of these, 21 experienced anaphylaxis (a rate of 11.1 people per one million doses), including 17 in people with a documented history of allergies or allergic reactions, seven of whom had a history of anaphylaxis. The onset of anaphylactic symptoms in most of the people was 13 minutes (with a range of two to 150 minutes). The CDC reported that of the 20 people for whom follow-up information was available, all had recovered.

    The findings presented in this report suggest that the Pfizer-BioNTech vaccine has an excellent safety profile and is safe for most people. However, the CDC recommends that vaccination locations should take the following precautions: ensure that necessary supplies are available to manage anaphylaxis; screen potential vaccine recipients to identify those who require extra precautions; establish post-vaccine observation periods (15 to 30 minutes, depending on patient history); ensure that healthcare providers can recognize the signs and symptoms of anaphylaxis early; and immediately treat suspected anaphylaxis with epinephrine.

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  • Omega-3 supplementation protected against loss of smell in patients with benign brain tumors (randomized controlled trial). academic.oup.com
    Omega-3 COVID-19

    Omega-3 fatty acids ameliorate olfactory losses.

    The sellar and parasellar regions of the brain comprise a complex anatomical area located near the pituitary gland. Tumors in these regions often require resection using endoscopic nasal procedures, which are often associated with concomitant olfactory function losses. In some patients these losses persist long after the procedure and are sometimes permanent. Findings from a new study suggest that omega-3 fatty acids ameliorate olfactory losses associated with endoscopic nasal procedures.

    Omega-3 fatty acids are polyunsaturated fats that play essential roles in human health. They influence cell membrane integrity, affect the function of membrane-bound cellular receptors, and participate in a vast array of physiological functions. Omega-3 fatty acids are present in flaxseed, soybeans, canola oil, fish, and other seafood. They are also widely available as dietary supplements.

    The prospective, randomized controlled trial involved 87 patients with sellar or parasellar tumors who were undergoing endoscopic nasal resection. Roughly half of the patients received nasal saline irrigations (standard treatment) or nasal saline irrigations plus 2,000 milligrams of supplemental omega-3 fatty acids daily. The participants underwent a smell test before and at six weeks, three months, and six months after the procedure.

    At the six-week point, 25 percent of the patients in both groups had experienced a clinically significant loss in olfactory function. However, at three and six months post-procedure, the patients who took omega-3 fatty acids had less olfactory loss than patients without supplementation.

    The authors of the study suggested that the improvements they observed in the patients' olfactory function were due to omega-3 fatty acids' neuroprotective effects as well as their capacity to promote synaptic plasticity and neurotransmitter function. Interestingly, many people report olfactory losses with viral infections, including COVID-19. A new clinical trial is investigating whether omega-3 fatty acids can protect and even restore lost sense of smell in patients with COVID-19.

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  • Moderate fever may protect against acute respiratory distress syndrome in COVID-19. www.frontiersin.org
    Inflammation COVID-19

    The primary cause of death from COVID-19 is acute respiratory distress syndrome (ARDS), a severe form of acute lung injury characterized by rapid breathing, shortness of breath, and a low blood oxygen level. The authors of recent review posit that moderate fever protects against ARDS in COVID-19.

    The body’s fever response is a hallmark of infection and inflammation. An increase in core body temperature of a few degrees (no higher than ~102°F) is generally recognized as safe and improves survival from and resolution of many infections. For example, evidence indicates that people who take medications to reduce fever associated with influenza are 5 percent more likely to die. Conversely, extremely high fever in the setting of systemic inflammation is harmful. Notably, the fever response is diminished in older adults.

    Fundamental to the fever response is a short-term accumulation of heat shock proteins (HSP), a class of proteins that play important roles in providing protection from lung injury. HSPs increase markedly with fever but require a “cool-down” period to maintain their effectiveness. In COVID-19 illness, the increase in HSPs is transient, lasting only about two hours after the onset of fever.

    The authors of the review hypothesized that allowing patients with COVID-19 to experience brief (two hour) periods of fever, followed by administration of medications to reduce fever would maintain the highest levels of protective HSPs. They cautioned that their hypothesis must be tested in large, randomized clinical trials, however.

    The authors also suggested that strategies that promote HSP activation may provide protection against COVID-19. Sauna use, in particular, induces long-term activation of HSPs and is associated with reduced risk of developing certain chronic or acute respiratory illnesses, such as pneumonia. Findings from large epidemiological studies indicate that men who used the sauna four to seven times per week were 41 percent less likely to develop pneumonia than men who used the sauna less often or not at all. Read more about sauna use in our overview article.

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  • Mild or asymptomatic cases of COVID-19 provide immunity against future reinfection. www.iflscience.com
    COVID-19

    COVID-19 is a respiratory disease with a clinical spectrum that ranges from no or few symptoms to acute respiratory failure, sepsis, and multiple organ dysfunction syndrome. More than 82 million cases of the illness have been reported worldwide. Most healthy people who contract COVID-19 are not hospitalized, however, making it difficult to determine the extent to which infection confers future immunity. A recent report indicates that even mild or asymptomatic cases of COVID-19 provide immunity against future reinfection.

    The authors of the report conducted a cross-sectional case-control study to assess T cell and neutralizing antibody immunity approximately four months after the United Kingdom lockdown commenced in March 2019. They drew on a subset of data from the UK COVIDsortium, a longitudinal study of a London-based cohort of hospital healthcare workers. The study involved 76 healthcare workers who tested positive for the presence of SARS-CoV-2 (the virus that causes COVID-19) and 60 healthcare workers (of similar age, gender, and ethnicity) who tested negative. Those who tested positive completed self-reported health questionnaires to identify mild or asymptomatic infections around the time of onset. The investigators measured immune response via serial blood sampling.

    They found that 89 percent of the healthcare workers who had tested positive had neutralizing antibodies against SARS-CoV-2, regardless of disease severity. The antibody responses did not always match T cell responses, which tended to be lower after asymptomatic infection than in symptomatic infection. The healthcare workers that lacked neutralizing antibodies and had undetectable T cell responses to the SARS-CoV-2 spike protein (the primary viral antigen) did have T cells that reacted with other SARS-CoV-2 antigens.

    These findings suggest that most people who have mild or asymptomatic SARS-CoV-2 infection carry immunity against future reinfection at four months post-infection. Other research indicates that immunity may last as long as six months.

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  • Biological sex differences in COVID-19 risk explained. www.eurekalert.org
    COVID-19

    Biological sex differences play critical roles in health, a circumstance observed in the higher rates of severe outcomes or death among men diagnosed with COVID-19, despite nearly equal infection rates among both sexes. Authors of a recent review suggest that these anomalies may be due to sex-based differences in the number of two proteins: the angiotensin-converting enzyme 2 receptor and the toll-like receptor 7.

    The angiotensin-converting enzyme 2 (ACE2) receptor is widely distributed among the body’s tissues. It plays key roles in the maintenance of blood pressure. SARS-CoV-2, the virus that causes COVID-19, exploits ACE2 to gain entry into cells by binding to a cell’s ACE2 receptor and injecting its genetic material into the cytosol, where it can replicate. Normal ACE2 function is markedly impaired in COVID-19 illness. The authors of the review report that women express twice the number of ACE2 receptors as men, providing a sort of “backup” population of receptors to carry out their normal function.

    Toll-like receptor 7 (TLR-7) is an element of the body’s immune response. It facilitates pathogen recognition and activates innate immune function. Women express twice the number of TLR-7s than men. The authors report that this translates to a more robust immune response among women than among men.

    The authors also pointed out that hormonal differences (such as higher estrogen levels in women) and sociocultural factors influence the differential COVID-19 risk profiles among men and women. They posited that repurposing drugs that affect ACE2, such as ACE2 inhibitors and ACE2 receptor blockers may be useful in treating COVID-19.

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  • SARS-CoV-2 virus-like particles remain infectious longer in cooler temperatures. www.eurekalert.org
    COVID-19

    Many viral infections show seasonality, with surges often occurring in cooler months. This phenomenon has been observed with SARS-CoV-2, the virus responsible for COVID-19, as the number of cases in the northern hemisphere has surged as outside temperatures have plunged. Findings from a new study indicate that SARS-CoV-2 particles remain infectious longer in cooler temperatures.

    SARS-CoV-2 is a type of human coronavirus. At least seven coronaviruses are known to infect humans, including SARS-CoV-1 (which causes severe acute respiratory syndrome, or SARS) and MERS-CoV (which causes Middle East respiratory syndrome, or MERS). SARS-CoV-2 is highly virulent and requires novel strategies for its study, such as virus-like particles – multiprotein structures that mimic the parent virus but lack the viral genome.

    The authors of the study used atomic force microscopy to observe how well the virus-like particles withstood environmental changes. They applied the virus-like particles to a glass surface and then exposed them to different temperatures (ranging from 71° F to 93° F) in humid and dry conditions.

    They found that exposure to warm temperatures (93° F) for as little as 30 minutes caused the outer structure of the virus-like particles to break down. However, the particles' integrity was not affected at cooler temperatures (71° F). The effects of warm temperatures were greater in dry conditions than in humid ones.

    These findings suggest that SARS-CoV-2 remains infectious longer in cooler, drier environments, such as those encountered outside during winter months or indoors and underscore the importance of adherence to public health guidelines for washing hands, wearing masks, and distancing whenever possible.

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  • Possible link between COVID-19 and acute appendicitis in children. www.news-medical.net
    COVID-19

    COVID-19 is caused by the SARS-CoV-2 virus. In adults, COVID-19 primarily manifests as a respiratory illness, but cardiovascular, neurological, and gastrointestinal symptoms have been reported. In children, the primary manifestations of the disease are fever and mild respiratory or gastrointestinal symptoms. A recent report suggests that acute appendicitis is associated with SARS-CoV-2 infection in children.

    The report summarizes the case histories of four children who had acute appendicitis. The children ranged in age from 11 to 17 years and were either Hispanic (three) or white (one). Two of the children had obesity, and one of them had a serious underlying health condition (aplastic anemia). The children had concurrent or previous SARS-CoV-2 infection. All four children required surgical intervention, and all recovered.

    The authors of the report proposed three reasons for the possible connection between SARS-CoV-2 infection and acute appendicitis: gastrointestinal symptoms of COVID-19 are fairly common in children; the SARS-CoV-2 virus tends to linger in the gut long after the initial infection; and the ACE-2 receptor (the means by which SARS-CoV-2 gains entry into cells) is present throughout the gut, including in the appendix.

    They also noted that appendicitis is fairly common, especially among adolescents, so the link to COVID-19 may be coincidental. However, 31 percent of the children who presented with acute appendicitis during the study period were SARS-CoV-2 positive, whereas the positive rate among the general pediatric population was only 8 percent.

    These case reports point to a possible link between SARS-CoV-2 viral infection and acute appendicitis in children and underscore the need for testing for the virus in children who present with severe gastrointestinal symptoms.

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  • Immunity to the SARS-CoV-2 virus lasts at least six months after infection. www.the-scientist.com
    COVID-19

    As the COVID-19 global pandemic enters its second year, scientists now have data on some of the long-term effects of the infection, which is caused by the SARS-CoV-2 virus. A new report details the efficacy of the immune response months after beating the active infection. The paper also reports possible chronic complications from COVID-19.

    The immune system utilizes both rapid-acting and long-term defenses against infection. Plasma B cells produce antibodies to fight active infections, while memory B cells circulate throughout the body for months or years after an infection has ended, ready to attack if re-infection occurs. However, because viruses evolve and change their genome quickly, antibodies may be less effective over time.

    The investigators assessed 87 participants for approximately one to six months after infection. They collected blood from participants to assess memory B cell quantity, antibody quantity, and the ability of antibodies to neutralize the virus after infection. Participants reported symptoms using common surveys.

    The number of antibodies specific for the SARS-CoV-2 spike antigen decreased significantly from 1.3 to 6.2 months after infection, and the ability of these antibodies to neutralize the virus decreased fivefold. However, memory B cell concentrations were slightly increased, leading to the authors to conclude that immunity was intact 6.2 months after infection. Additionally, the authors reported that participants who experienced the most severe cases of COVID-19 were more likely to report chronic symptoms of shortness of breath, fatigue, unexplained fever, neurological abnormalities, and others.

    These findings suggest that immunity to the SARS-CoV-2 virus lasts at least six months after infection. It is important to note that this article is in pre-print and has not yet been peer-reviewed.

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  • Melatonin use associated with lower risk for COVID-19. www.sciencedaily.com
    Melatonin COVID-19

    SARS-CoV-2 is the virus responsible for COVID-19. As SARS-CoV-2 infection rates climb, scientists continue to search for drugs that could be repurposed for COVID-19 treatment. Authors of a new multiomics study report that melatonin use dramatically reduced the likelihood of SARS-CoV-2 infection, especially for African Americans.

    Multiomics is an approach to data analysis that incorporates multiple levels of cellular biology, including the genome (DNA), transcriptome (RNA), and proteome (protein). The network of interactions between these multiple “omes” and a virus and its host is referred to as the interactome.

    The authors built multiomic data sets from several previous studies in humans, animals, and cell lines to investigate the SARS-CoV-2-host interactome. Based on these data sets, the authors identified 34 drugs that could be repurposed for COVID-19. Next, they reviewed the medical records of more than 18,000 participants for use of those drugs and presence of SARS-CoV-2 infection.

    They found that melatonin usage was associated with a 28 percent reduced likelihood of having a positive SARS-CoV-2 PCR test for the general population and 52 percent reduced likelihood for African Americans. The authors also reported similarities between the disease progression of COVID-19 and inflammatory bowel disease as well as inflammatory profiles of COVID-19 and asthma.

    This study used state-of-the-art data analysis to find associations between SARS-CoV-2 infection and a number of biological factors; however, clinical trials are needed to confirm the efficacy of melatonin supplementation in preventing or treating infection. This study has not yet completed peer-review.

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  • Ordinary healthcare products reduce viral load of coronaviruses. www.sciencedaily.com
    COVID-19

    Coronaviruses comprise a group of related viruses that cause illness in birds and mammals, including humans. While some coronaviruses cause fairly benign illness (such as the common cold), others can cause serious, even life-threatening disease (such as SARS-CoV-2, which causes COVID-19). As the number of COVID-19 cases continues to increase globally, identifying strategies to reduce or prevent its spread is essential. Findings from a recent study indicate that ordinary healthcare products may be useful in reducing viral load of coronaviruses.

    Viral load refers to the quantity of virus particles present in an organism following exposure. With most viruses, higher viral loads are associated with worse outcomes.

    The authors of the study assessed the merits of several healthcare products, including a saline nasal rinse, a 1 percent solution of baby shampoo, peroxide oral rinses, and mouthwashes in reducing viral load. They tested the products against human coronavirus 229e, a human respiratory pathogen with a structure similar to that of SARS-CoV2, by incubating the virus in the presence of the solutions for 30 seconds, one minute, and two minutes at room temperature.

    They found that the baby shampoo solution inactivated more than 99.9 percent of the virus after two minutes. The mouthwashes and oral rinses were similarly effective, with some products inactivating more than 99.9 percent of virus after 30 seconds and some inactivating 99.99 percent of the virus after 30 seconds. They found no benefit from using the saline nasal rinse.

    These findings suggest that ordinary household healthcare products are useful in preventing viral load of a coronavirus similar to SARS-CoV-2. Such products may be beneficial in reducing or preventing transmission of COVID-19.

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  • High dose vitamin C reduces COVID-19 severity and death. journals.sagepub.com
    Vitamin C COVID-19

    Currently selected for this coming member’s digest by team member Melisa B.

    SARS-CoV-2, the virus that causes COVID-19, stimulates the innate immune system, causing systemic inflammation that damages the lungs. Evidence suggests that those with the most severe cases of COVID are made sicker not by increased viral replication, but by unregulated inflammation. New evidence suggests that high dose intravenous vitamin C decreases inflammation, symptom severity, and death due to COVID-19.

    Vitamin C is essential for proper immune regulation. White blood cells produce harmful chemicals to attack pathogens and carry large amounts of vitamin C to neutralize the free radicals these attacks generate. Without enough vitamin C in the body, inflammation can cause severe damage to host tissues or even death.

    The authors of the study enrolled 56 ICU patients with confirmed SARS-CoV-2 infection and severe pneumonia. They assigned participants to receive either high-dose intravenous vitamin C (24 grams per day for seven days) or a placebo (water). The authors of the study monitored the participants for inflammation, disease severity, and death.

    Participants in the high-dose intravenous vitamin C group experienced a statistically significant improvement in lung function, as measured by blood oxygen content, over seven days. They also exhibited a statistically significant decrease in blood concentrations of the proinflammatory cytokine interleukin-6. Participants with multiple organ dysfunction were less likely to die.

    High dose intravenous vitamin C therapy was found to be safe in this small pilot study, but the authors advised that further research is needed to confirm its benefits for COVID-19. These results have been shared in a preprint report, meaning they haven’t been peer reviewed yet. It is also important to note that intravenous vitamin C can result in blood concentrations that are 30 to 70 times higher than the same oral dose, so these results cannot be used to support the use of oral vitamin C supplements for SARS-CoV-2 or any other infection.

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  • SARS-CoV-2, the virus that causes COVID-19, blocks pain receptors. www.sciencedaily.com
    COVID-19

    People who are infected with a virus commonly report having aches and pains. Most people who are infected with SARS-CoV-2, the virus that causes COVID-19, exhibit symptoms such as fever, cough, and difficulty breathing, but not pain. Findings from a new study demonstrate that SARS-CoV-2 blocks pain receptors.

    Robust evidence suggests that SARS-CoV-2 exploits the ACE2 receptor to gain entry into cells. A specific region of the virus called a spike protein binds to a cell’s ACE2 receptor, and the virus injects its genetic material – RNA – into the cytosol. Once inside, the virus hijacks the body’s natural replicating processes to promote viral reproduction.

    Other evidence points to the possibility that ACE2 is not the sole means of entry, however, and that other proteins, such as the neuropilin-1 receptor (NRP-1), may be involved. NRP-1 participates in pain sensing and angiogenesis (the development of new blood vessels) and is a receptor for vascular endothelial growth factor-A (VEGF-A). When VEGF-A binds to NRP-1, it elicits neuronal hyperexcitability, producing pain.

    The authors of the study wanted to see if the spike protein would interfere with VEGF-A/NRP-1 signaling in a rodent model of nerve pain. They used VEGF-A as a trigger to induce pain, and then they administered the SARS-CoV-2 spike protein.

    They found that the spike protein interfered with pain signaling and effectively blocked the VEGF-A-induced pain. They saw this effect regardless of how much spike protein was present.

    These findings suggest that SARS-CoV-2 blocks pain, which may have relevance for disease spread via asymptomatic people. Learn more about COVID-19 in these Q&As featuring Dr. Rhonda Patrick, released April 14 and June 10.

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  • Zinc improves outcomes of COVID-19. www.theladders.com
    Zinc COVID-19

    Zinc is an essential nutrient that plays key roles in immune function. Sources of zinc include red meat, poultry, nuts, beans, and seafood. Findings presented at the recent European Society of Clinical Microbiology and Infectious Disease Conference on Coronavirus Disease suggest that zinc provides protection against COVID-19.

    The study involved 249 adults (average age, 63 years) who had been hospitalized in early 2020 for COVID-19-related treatment. The authors of the study analyzed blood samples from the patients to determine their serum zinc levels and inflammatory status, as measured by interleukin-6 (IL-6).

    The analyses revealed that 21 of the patients died from complications associated with COVID-19. The average zinc level among the patients 61 micrograms per deciliter (mcg/dL). (Normal serum zinc concentrations range between 70 and 100 mcg/dL.) Poor zinc status was linked with worse outcomes. Zinc levels among patients who survived averaged 63 mcg/dL, but among those died, levels averaged 43 mcg/dL, suggesting that zinc plays an important role in improving outcomes of COVID-19. Lower zinc levels also correlated with higher levels of IL-6, indicative of systemic inflammation.

    It’s noteworthy that zinc exists as a divalent cation (a positively charged ion) and cannot enter cells without a transporter. Uptake of zinc requires an ionophore, a molecule that can transport ions across a lipid membrane. Quercetin, a bioactive compound present in a variety of fruits and vegetables, especially apples and onions, is a zinc ionophore. Consuming zinc-rich foods along with quercetin-rich foods may boost zinc’s effectiveness. You can read more about quercetin in our overview article.

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  • A calcium-rich nasal spray reduces the number of small respiratory droplets exhaled among people at high risk for COVID-19. www.eurekalert.org
    COVID-19

    Robust evidence indicates that SARS-CoV-2, the virus that causes COVID-19, spreads primarily via respiratory droplets in the exhaled air of infected persons. Although the wearing of face masks is a critical component of global public health strategies to prevent spread of the disease, small respiratory droplets that are less than 1 micron in diameter can pass through the masks. A recent study demonstrates that administration of a calcium-rich nasal spray may reduce the number of small respiratory droplets exhaled among people at high risk.

    Components of the upper respiratory system – the nose, trachea, and bronchi – play critical roles in protecting the body from infection by capturing inhaled pathogens in mucus, which can then be swallowed and destroyed in the gut. If pathogens are not cleared in a timely manner, they can be transported deeper into the lungs or spread to others via exhaled air in droplets. Calcium binds with mucin (a sticky component of mucus), increasing the surface elasticity of the mucus-airway surface and helping to prevent the formation of small droplets.

    The study involved three distinct high-risk groups of people: students, essential workers (food processing employees), and people in quarantine with an infected family member. In all, 92 people participated in the study. Each of the participants received a dose of nasal spray composed of calcium chloride and sodium chloride in distilled water (with a salt content similar to seawater), administered via a hand-held mister for one to two minutes. The authors of the study measured the participants' exhaled airborne particles before and after receiving the spray using a particle detector.

    They found that the number of small exhaled particles decreased by an average of 75 percent across the three different groups, markedly outperforming surgical masks. These findings suggest administration of a calcium-rich nasal spray can play an important role in reducing the spread of COVID-19. The authors posited that the spray could be used in both personal and public health settings with minimal or no contact.

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  • Exposure to common cold viruses may provide protection against COVID-19. www.eurekalert.org
    COVID-19

    SARS-CoV-2, the virus that causes COVID-19, is one of the coronaviruses, a large family of viruses that typically causes mild to moderate upper-respiratory tract illnesses, like the common cold. Findings from a new study demonstrate that exposure to common cold coronaviruses may provide immunity to SARS-CoV-2.

    The average person has one or two episodes of the common cold every year. The immune system responds to cold-causing viruses by producing B cells. These cells make antibodies, which in turn neutralize the viruses, rendering them harmless. Some B cells become memory B cells, which can remain in the body for a long time, even after the virus is cleared, to efficiently recognize and destroy returning viruses.

    The authors of the study analyzed blood serum and peripheral blood mononuclear cells (a type of immune cell) from 21 healthy people who had never been exposed to SARS-CoV-2 (sampled before the emergence of the virus) and 26 people who were recovering from COVID-19 (sampled four to nine weeks after showing symptoms). In particular, they looked for reactivity against two proteins – the S and N proteins – of SARS-CoV-2 and the S proteins of two coronaviruses that cause colds in people. The S, or spike, proteins are shared characteristics of all coronaviruses.

    They found that the memory B cells that formed following common cold exposure did not differentiate between the different coronaviruses, but instead showed cross-reactivity to the S protein on the SARS-CoV-2 virus to elicit immunity. These findings indicate that having a common cold might provide some degree of protection against SARS-CoV-2, but they do not demonstrate the extent or duration of protection conferred.

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  • Extensive neurological system involvement reported in COVID-19 illness. www.the-scientist.com
    COVID-19

    SARS-CoV-2, the virus responsible for COVID-19 illness, is a respiratory pathogen that elicits notable properties of multisystem involvement and copious, often longstanding, complications. A recent study describes the effects of SARS-CoV-2 infection on the nervous system.

    Hints that COVID-19 was affecting the nervous system came early in the pandemic, when some infected patients reported smell and taste dysfunction30293-0/fulltext), visual disturbances, or memory impairment. These phenomena point to a neurological source.

    The retrospective study summarized the neurological symptoms manifested among 43 patients between the ages of 16 and 85 years with either suspected or confirmed COVID-19 illness admitted to a hospital in London, England. The range of symptoms affected both central and peripheral nervous systems and included psychoses, delirium, encephalitis, strokes, and Guillain-Barré syndrome. The authors of the study noted a marked uptick in the number of cases of acute disseminated encephalomyelitis, a potentially fatal condition that more commonly occurs in children after a viral infection. Despite the extensive neurological involvement seen in these patients, many of them had minor respiratory symptoms.

    These findings point to the multifaceted aspects of COVID-19 illness and underscore the need for providers to assess patients for neurological symptoms to improve outcomes.

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  • Antibody component demonstrates effectiveness against COVID-19. www.upmc.com
    COVID-19

    Antibodies defend cells from bacteria and viruses by neutralizing pathogens' biological effects. Antibodies that neutralize SARS-CoV-2, the virus that causes COVID-19, are important tools in treating or even preventing the disease. Researchers have identified a tiny component of an antibody that neutralizes SARS-CoV-2 by blocking its capacity to bind to the angiotensin converting enzyme 2 (ACE2) receptor.

    SARS-CoV-2 exploits the ACE2 receptor to gain entry into cells. A specific region of the virus called a spike protein binds to a cell’s ACE2 receptor, and the virus injects its genetic material – RNA – into the cytosol. Once inside, the virus hijacks the body’s natural replicating processes to promote viral reproduction.

    The researchers identified the component, called Ab8, from a library of 100 billion potential candidates. They conducted in vitro and animal studies to confirm its effectiveness and used electron microscopy to determine how Ab8 worked.

    They found that Ab8 completely neutralized SARS-CoV-2 in vitro and in mice and hamsters. The authors of the study speculated that Ab8’s small size might facilitate its delivery as an inhaled or intradermal drug. These findings demonstrate that Ab8 shows promise as a therapeutic and preventive drug against COVID-19.

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  • Possible mechanisms associated with severe respiratory complications in patients with COVID-19 identified. www.the-scientist.com
    COVID-19

    Bradykinin is a proinflammatory protein that participates in the homeostatic control of blood pressure. It induces hypotension (low blood pressure) and vasodilation. Hyaluronic acid is a molecule with a high capacity for retaining water. Findings from a new study suggest that bradykinin and hyaluronic acid work in a synergistic fashion to impair gas exchange in the lungs of people with severe cases of COVID-19.

    COVID-19, the disease caused by SAR-CoV-2, can cause severe lung complications, including pneumonia. As COVID-19 pneumonia progresses, the lungs' air sacs fill with fluid. Shortness of breath typically ensues, eventually leading to acute respiratory distress syndrome, a form of lung failure.

    The authors of the study analyzed gene expression data from cells in bronchoalveolar lavage fluid samples taken from nine COVID-19-positive patients. They compared the data to those obtained from healthy people.

    They noted a critical imbalance in the renin-angiotensin-system, a critical regulator of blood pressure, inflammation, and body fluid homeostasis. This imbalance promoted alterations in the expression of the key components of the system, chiefly an increase in bradykinin receptors. The authors also observed that genes that drive hyaluronic acid synthesis and breakdown were altered in the COVID-19 bronchoalveolar lavage fluid samples from the COVID-19 patients. The likely outcome of these changes would be increased bradykinin levels, vascular dilation, vascular permeability, and the formation of a viscous jelly-like substance that would negatively impact gas exchange in the lungs.

    These findings point to molecular mechanisms underlying the complications associated with COVID-19 and provides therapeutic intervention possibilities for already-approved pharmaceuticals.

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  • Emerging data suggest that COVID-19 is a vascular illness. elemental.medium.com
    COVID-19

    COVID-19 is a respiratory illness caused by the novel coronavirus SARS-CoV-2. Symptoms of COVID-19 range from mild upper airway distress to progressive life-threatening viral pneumonia. At the time of this writing, more than 22 million people have been infected with the virus and more than 782,000 people have died. A recent article summarizes emerging data suggesting that COVID-19 is also a vascular illness that elicits deleterious effects on the cardiovascular system.

    SARS-CoV-2 virus enters human cells via the ACE2 receptor. Viral particles bind to the ACE2 receptor and together they travel into the cell. These viral particles can bind to a large number of ACE2 molecules, sequestering them from the cell surface and decreasing ACE2. The accompanying loss of ACE2 function can cause serious health consequences due to ACE2’s participation in key physiological processes. Blood vessels are rich in ACE2 receptors.

    Although symptoms of COVID-19 are primarily related to its effects on the respiratory system, cardiovascular-related symptoms have been reported as well, including cardiac inflammation, blood clots, stroke, and “COVID toes” – blister-like lesions that appear on the digits of some infected people.

    Several peer-reviewed articles have been published documenting cardiovascular-related symptoms in COVID-19 illness. One publication describes how SARS-CoV-2 infects the endothelial cells that line blood vessels to elicit endothelial cell dysfunction and subsequent cardiovascular complications. Another publication reports how widespread evidence of blood clots and endothelial cell infection in the lungs of people who died from COVID-19. One researcher suggested that the best therapy for COVID-19 might not be antiviral therapy; rather, drugs that stabilize the vascular endothelial tissue might be more effective.

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  • Severe vitamin D deficiency in people with COVID-19 associated with greater risk of death than those with normal levels. pubmed.ncbi.nlm.nih.gov
    Vitamin D COVID-19

    Severe vitamin D deficiency in people with COVID-19 associated with greater risk of death than those with normal levels.

    Vitamin D is a fat-soluble vitamin that is stored in the liver and fatty tissues of the body. Perhaps best known for its role in maintaining calcium balance and bone health, vitamin D plays critical roles in immune function. Recent evidence suggests that vitamin D deficiency is associated with poor outcomes in COVID-19. Findings from a new study suggest that poor vitamin D status increases the risk of death from COVID-19.

    The authors of the retrospective, observational study analyzed data collected from 42 patients with acute respiratory failure due to COVID-19 who were treated in Bari, Italy, during a six-week period during the spring of 2020. The authors of the study classified the patients according to their vitamin D status: normal, insufficient, moderate deficiency, or severe deficiency. According to the Endocrine Society, vitamin D concentrations less than 20 ng/mL (50 nmol/L) define “deficiency,” and concentrations ranging from 52.5 to 72.5 nmol/L (21 to 29 ng/mL) define “insufficiency.”

    They found that 81 percent of the patients had low vitamin D status. After ten days of of hospitalization, patients with severe vitamin D deficiency were 50 percent more likely to die, while those with vitamin D levels greater than or equal to 10 ng/mL had a 5 percent chance of death.

    These findings indicate that severe vitamin D deficiency may predict poor prognosis in patients with poor vitamin D status, suggesting that adjunctive treatment that involves vitamin D repletion might improve disease outcomes. Learn more about the role of vitamin D in COVID-19 in this clip featuring Dr. Rhonda Patrick.

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  • T lymphocytes may bridge the gap in COVID-19 immunity. www.sciencedaily.com
    Immune System COVID-19

    Immunity and susceptibility to COVID-19 is an area of ongoing research. Findings from a recent study indicate that T cells that react to the SARS-CoV-2 spike protein are present in both COVID-19 patients and healthy people unexposed to the virus.

    T lymphocytes, also known as T cells, are part of the body’s adaptive immune response. T cells are produced when the body encounters a viral, bacterial, or fungal pathogen. T cells come in a variety of forms, including helper T cells, cytotoxic T cells and memory T cells.

    Previous research has demonstrated the presence of SARS-CoV-2-reactive T cells circulating in the blood of unexposed people. The current study characterized T cell reactivity against the SARS-CoV-2 spike protein in COVID-19 patients and unexposed people.

    The authors of the study combined isolated immune cells from both COVID-19 patients and unexposed people to synthetic segments of the SARS-CoV-2 spike protein. They found reactive memory T-helper cells in 83 percent of people with COVID-19 and 35 percent of people who had not been exposed to the virus. The T cells of COVID-19 patients reacted to both the N- and the C-terminal ends of the SARS-CoV-2 spike protein. However, the T cells of unexposed individuals reacted primarily to the C-terminal end of the spike protein — a region that shares similarity with “common cold” coronaviruses.

    These findings suggest that there is some pre-existing immunity in the general population against SARS-CoV-2, possibly due to exposure to the common cold coronaviruses. Larger studies are needed to determine if cross-immunity will affect the clinical outcomes of COVID-19 patients.

    Learn more about COVID-19 in these Q&As featuring Dr. Rhonda Patrick, posted April 14 and June 10.

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  • Evidence mounts that exposure to "common cold" coronaviruses may yield some protection against SARS-CoV-2. www.sciencedaily.com
    Immune System COVID-19

    Scientists are learning more about how people respond to SARS-CoV-2, the new coronavirus responsible for the ongoing COVID-19 pandemic. Findings from a recent study suggest that prior exposure to “common cold” coronaviruses may generate the production of SARS-CoV-2 specific T cells.

    SARS-CoV-2 belongs to the Coronaviridae family of RNA viruses. There are four coronaviruses known to circulate among the world’s population and transmit the “common cold.”

    A healthy person’s response to a viral infection involves a coordinated effort between the innate and adaptive immune systems. Whereas the innate immune system — the first line of defense — involves barrier functions, such as those provided by the skin, the adaptive immune system includes distinct cell types that work together to neutralize the virus. T cells kill virus-infected cells and present viral fragments to B cells, which in turn produce antibodies against the virus. Some T cells, known as memory T cells, are long-lived and persist in the body to defend against future attacks by the same virus or related viruses.

    Previous research on other viral infections has demonstrated that cross-reactive T cells circulating in a person’s blood may protect them from developing severe disease. The current study investigated the T cell response to the SARS-CoV-2 virus and explored the features of cross-reactive immunity.

    The authors of the study examined blood collected from healthy people prior to the emergence of the SARS-CoV-2 virus. They detected CD4+ T cells in the blood of approximately half of the people unexposed to the SARS-CoV-2 virus. The authors speculate that these observations indicate the existence of cross-reactive immunity between SARS-CoV-2 and the coronaviruses that cause the “common cold.” They submit that this cross-reactivity may be a hopeful sign. However, it may also complicate COVID-19 vaccine trials if some subjects have pre-existing immunity.

    These findings suggest that prior exposure to a related coronavirus stimulates the production of SARS-CoV-2 reactive T cells that persist in the body. Whether these T cells help an individual clear COVID-19 remains to be seen.

    Learn more about COVID-19 in these Q&As featuring Dr. Rhonda Patrick, posted April 14 and June 10.

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  • T cells may be key to providing long-lasting immunity to SARS-CoV-2. www.sciencedaily.com
    Immune System Virus COVID-19

    Much remains unknown about SARS-CoV-2, the new coronavirus responsible for the on-going COVID-19 pandemic. Two important questions revolve around why some people become severely ill while others experience no symptoms, and the associated implications for long-term immunity. Findings from a recent study suggest that prior exposure to related coronaviruses may affect the production of T cells that affect disease severity and immunity.

    SARS-CoV-2 belongs to the Coronaviridae family of RNA viruses. There are six coronaviruses known to infect humans, having effects that range from severe pneumonia (SARS-CoV-1 and MERS-CoV) to the “common cold”.

    A healthy person infected with a virus mounts a coordinated immune response involving distinct cell types that work together to neutralize the invading pathogen. The adaptive immune system includes T cells that kill virus-infected cells and display antigens (viral fragments) to B cells, which in turn produce antibodies against the virus. Research demonstrates that T cells persist in the body longer than antibodies. For example, 11 years after recovering from SARS-CoV-1 infection, memory T cells were still present, while antibodies were undetectable two to three years after the disease resolved.

    Proteins are highly conserved among related coronaviruses. The current study investigated whether the blood of people who had recovered from SARS-CoV-1 or SARS-CoV-2 contained immune factors that would react to isolated SARS-CoV-2 viral proteins.

    The authors of the study identified SARS-CoV-2 virus-specific memory T cells in the blood of people who had recovered from COVID-19. The authors then analyzed the blood of 15 SARS-CoV-1 resolvers, 17 years after infection. They observed that all individuals possessed viral-specific T cells that responded not only to SARS-CoV-1 viral proteins but also to SARS-CoV-2 proteins. These results suggest that T cells provide long-lasting protection and offer some cross-protection between SARS-CoV-1 and SARS-CoV-2. The researchers even detected SARS-CoV-2 specific T cells in 19 out of 37 people unexposed to either SARS-CoV-1 or SARS-CoV-2, suggesting they had encountered a related coronavirus, possibly one responsible for the “common cold”.

    These findings suggest that T cells produced against SARS-CoV-2 will provide long-term immunity. This research also supports the idea that prior infection with a related coronavirus affords some immunity against SARS-CoV-2 infection, and might explain the variations observed in infection rates and disease severity.

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  • A potential role for zinc in COVID-19 prevention and treatment. www.eurekalert.org
    COVID-19

    COVID-19, the disease caused by the novel coronavirus SARS-CoV-2, has infected more than 13 million people worldwide. Identifying strategies to prevent or treat the disease is a priority for disease specialists. Findings from a new study indicate that zinc might be beneficial against COVID-19.

    Zinc is a mineral, first recognized for its influence on growth and development and now widely understood to play critical roles in immune function, protein synthesis, wound healing, DNA synthesis, and cell division. Deficiency of this essential nutrient can cause growth and cognitive defects, poor immune function, and impaired wound healing. A recent review describes the benefits and mechanisms of action associated with zinc in COVID-19 prevention and treatment.

    The authors of the review presented data regarding zinc’s role in COVID-19, respiratory viruses, pneumonia, pediatric respiratory infections, and lung inflammation. They describe robust data demonstrating that zinc adequacy supports immune function. Conversely, they point out that zinc deficiency impairs the body’s immune response and may increase a person’s risk of developing respiratory tract infections.

    Zinc exerts potent anti-inflammatory, antiviral, and antibacterial qualities. In light of these qualities, the authors of the review suggested that zinc repletion via supplementation may be a viable means of combating pneumonia and other respiratory illnesses, including COVID-19, via zinc’s capacity to reduce lung inflammation, improve airway clearance, and prevent ventilator-induced lung injury.

    Interestingly, zinc concentrations drop during sepsis, a life-threatening inflammatory condition that can arise due to the body’s response to a bacterial or viral infection, including SARS-CoV-2. This drop may be a result of nutritional immunity – a biological phenomenon wherein a host organism sequesters minerals such as zinc or iron in an effort to reduce a pathogen’s virulence. Some researchers have suggested that zinc supplementation during sepsis could render a potentially harmless dose of zinc into a toxic one. Read more about zinc and its role in immunity and protection against respiratory infections in our comprehensive overview article.](https://www.foundmyfitness.com/topics/zinc).

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  • Cardiac abnormalities are present in roughly half of all COVID-19 patients. www.newsweek.com
    COVID-19

    Emerging evidence suggests that COVID-19, the disease caused by SARS-CoV-2, elicits a wide range of cardiovascular-related complications, including myocarditis (inflammation of the heart muscle), ventricular failure, myocardial infarction (heart attack), and others. In addition, SARS-CoV-2 virus particles have been found in the myocardium and vascular endothelium of some COVID-19 patients. Findings from a recent study suggest that cardiac abnormalities are present in roughly half of all COVID-19 patients.

    The authors of the study conducted an online survey of sonographers and clinicians performing echocardiography (an ultrasound of the heart) on more than 1,200 patients with either confirmed or a high probability of COVID-19 in 69 countries. The sonographers and clinicians responded to a series of questions about the patients' demographics, the reason for and results of the echocardiogram, and whether the results influenced subsequent treatment of the patient.

    The authors found that the patients were between the ages of 52 and 71 years, and the majority (70 percent) were male. Patients with an abnormal echocardiogram were more likely to have ischemic heart disease, heart failure, or valvular heart disease, but were equally likely to have hypertension or diabetes mellitus, compared to patients with a normal echocardiogram. The surveys revealed that left or right ventricular abnormalities were observed in more than half (55 percent) of all patients. These abnormalities were severe in 14 percent of the patients. A change in treatment occurred for roughly one-third of patients subsequent to their echocardiogram.

    These findings suggest that cardiovascular complications commonly occur during COVID-19 illness, and imaging studies can influence treatment. These findings suggest that cardiovascular complications commonly occur during COVID-19 illness, and imaging studies can influence treatment. Learn more about COVID-19 in these Q&As featuring Dr. Rhonda Patrick, posted April 14 and June 10.

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  • Majority of patients who received COVID-19 convalescent plasma recovered. www.eurekalert.org
    COVID-19

    Evidence supporting the use of convalescent plasma to treat disease dates back to the early 1900s when physicians transfused blood products from recovered influenza patients to treat the sick. Findings from a recent study indicate that convalescent plasma is a viable treatment for patients with severe or life-threatening COVID-19.

    The study, which was conducted in early 2020, involved 25 patients admitted to hospitals in Houston, Texas, who were diagnosed with severe and/or life-threatening COVID-19. Symptoms of severe disease include shortness of breath, rapid breathing, and low blood oxygen saturation. Symptoms of life-threatening disease include respiratory failure, sepsis, and/or multiple organ dysfunction or failure. The patients were between the ages of 19 and 77 years, and the majority had at least one underlying health problem, such as diabetes, high blood pressure, abnormal cholesterol levels, or other conditions.

    Each of the patients received plasma donated from people who had recovered from COVID-19 and had been asymptomatic for two weeks. The recipients were evaluated on the day of their transfusion and again at one week and two weeks afterward. They were rated on a six-point scale reflecting their clinical status.

    One week after receiving the transfusion, nine of the patients improved by at least one point on the clinical status scale, and seven of these were discharged. Two weeks after the transfusion, 19 of the patients improved by at least one point, and 11 of these had been discharged. None of the patients experienced any adverse events related to the transfusion, but one patient died from an unrelated condition.

    These findings suggest that convalescent plasma is a safe treatment option for patients with severe and/or life-threatening COVID-19 disease. However, the authors of the study acknowledged that co-administration of other therapies could have confounded their results, with some treatments either improving or worsening outcomes.

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  • Strokes in COVID-19 are rare but are more severe, occur in younger patients, and have higher mortality rate. www.eurekalert.org
    Heart Disease Mortality COVID-19

    During the study period of March 15 through April 19, 2020, out of 3,556 hospitalized patients with diagnosis of COVID-19 infection, 32 patients (0.9%) had imaging-proven ischemic stroke. They compared those 32 patients admitted with stroke and COVID-19 to those admitted only with stroke (46 patients) and found that the patients with COVID-19:

    tended to be younger, average age of 63 years vs. 70 years for non-COVID stroke patients; had more severe strokes, average score of 19 vs. 8 on the National Institutes of Health Stroke Scale; had higher D-dimer levels, 10,000 vs. 525, which can indicate significant blood clotting; were more likely to be treated with blood thinners, 75% vs. 23.9%; were more likely to have a cryptogenic stroke in which the cause is unknown, 65.6% vs. 30.4%; and were more likely to be dead at hospital discharge, 63.6% vs. 9.3%. Conversely, COVID-19 stroke patients were less likely than those stroke patients without the novel coronavirus to have high blood pressure (56.3% vs. 76.1%) or to have a prior history of stroke (3.1% vs. 13%).

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  • Recovered COVID-19 patients carry T-cells that might promote long-term immunity. www.sciencemag.org
    Immune System Virus COVID-19

    Critical elements of the body’s immune system are T-cells, a class of lymphocytes that promote an appropriate immune response and actively engage in the destruction of pathogens. Findings from two new studies suggest that people who are infected with SARS-CoV-2, the virus that causes COVID-19, have T-cells that target the virus.

    The first of the two studies analyzed blood samples collected 20 to 35 days after the onset of symptoms in 20 non-hospitalized COVID-19 patients who were no longer symptomatic. All of the COVID-19 patients that were tested carried SARS-CoV-2 specific helper T-cells and nearly three-quarters carried natural killer T-cells.

    The authors of the study also investigated whether people who haven’t been infected with SARS-CoV-2 might have immunity to the virus by analyzing blood samples from 2015 to 2018, well before the pandemic began. They found that roughly half of the samples had helper T-cells that recognized SARS-CoV-2.

    Similar results were found in the second study, which analyzed blood samples from 18 people with COVID-19. Their findings demonstrated that 83 percent of COVID-19 patients carried helper T-cells and 35 percent of uninfected people carried helper T-cells. The authors of both studies suggested that this cross-reactivity likely stems from a previous infection with coronaviruses that cause colds.

    These findings suggest that a subset of the population might be better equipped to fight of infection from SARS-CoV-2 due to previous exposure to other coronaviruses.

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  • Treatment with interferon-α2b speeds up recovery of COVID-19 patients in exploratory study www.eurekalert.org
    COVID-19 IL-6

    From the article:

    “Interferons are our first line of defence against any and all viruses - but viruses such as corona-viruses have co-evolved to very specifically block an interferon response … Treatment with interferon will override the inhibitory effects of the virus.”

    Fish says that the research team considered IFN-α therapy for COVID-19 after they demonstrated interferons had therapeutic benefits during the SARS outbreak of 2002 and 2003.

    In this study, the authors examined the course of disease in a cohort of 77 individuals with confirmed COVID-19 admitted to Union Hospital, Tongii Medical College, Wuhan, China, between January 16th and February 20th 2020. The individuals evaluated in this study consisted of only moderate cases of COVID-19, as none of the patients required intensive care or oxygen supple-mentation or intubation. The researchers demonstrated a significantly different rate of viral clearance for each treatment group and notably, IFN-α2b treatment accelerated viral clearance by approximately 7 days. Treatment with IFN-α2b, whether alone or in combination with ARB, accelerated viral clearance when compared to ARB treatment alone. IFN treatment was also demonstrated to significantly reduce circulating levels of IL-6 and CRP, whether alone or in combination with ARB.

    Despite the study’s limitations of a small, non-randomised cohort, the work provides several important and novel insights into COVID-19 disease, notably that treatment with IFN-α2b accelerated viral clearance from the upper respiratory tract and also reduced circulating inflammatory biomarkers, hinting at functional connections between viral infection and host end-organ damage by limiting the subsequent inflammatory response in the lungs of patients.

    As an uncontrolled, exploratory study, Fish says a randomized clinical trial is a crucial next step: “A clinical trial with a larger cohort of infected patients that are randomized to treatment with interferon-alpha or to a placebo would further this research”.

    In the meantime, the findings from this study are the first to suggest therapeutic efficacy of IFN-α2b as an available antiviral intervention for COVID-19, which may also benefit public health measures by shortening the duration of viral clearance and therefore slowing the tide of the pandemic."

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  • Majority of COVID-19 patients found to be vitamin D deficient. www.medrxiv.org
    Vitamin D COVID-19

    Several factors increase the risk of death due to COVID-19, including hypertension, obesity, male sex, advanced age, living at a northern latitude, and coagulopathy. Interestingly, poor vitamin D status is associated with all of these factors. Findings from a small, retrospective study revealed that vitamin D deficiency was a common feature among the majority of COVID-19 patients with severe outcomes.

    The study involved COVID-19 patients treated in the intensive care unit (ICU) at a tertiary care academic medical center in the United States. Of 20 COVID-19 patients for whom vitamin D levels were available, 13 were treated in the ICU. Of those, 11 (nearly 85 percent) were vitamin D deficient. All of the ICU patients under the age of 75 were vitamin D deficient.

    The authors of the study noted that COVID-19-related death and vitamin D deficiency are more common among African Americans. They also suggested that vitamin D deficiency contributes to the severity of COVID-19 outcomes via impairment of the immune system and prothrombotic effects.

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  • Gut bacteria use flavonoids to prime the body's immune response and protect against influenza. Press release: https://www.sciencedaily.com/releases/2017/08/170803141048.htm
    Gut Microbiome Virus COVID-19

    Gut bacteria process bioactive plant-based dietary compounds and, in turn, produce metabolites not synthesized by their human hosts. Many of these metabolites influence human health by regulating physiological processes such as nutritional homeostasis, energy expenditure, and immunity. A 2017 study demonstrated that microbial metabolites produced from flavonoids modulate the body’s response to influenza infection.

    Flavonoids are bioactive compounds present in a variety of fruits and vegetables. More than 4,000 flavonoids have been identified in the human diet. When gut bacteria called Clostridium orbiscindens break down flavonoids, they produce a metabolite known as desaminotyrosine (DAT). DAT helps the body produce interferon, a signaling molecule that activates the immune system.

    The authors of the rodent study gave mice DAT for seven days and then infected them with influenza. The mice continued to receive DAT for 14 days post-infection. A control group of mice received no DAT.

    The mice that received the DAT exhibited lower levels of viral RNA and less epithelial damage and apoptosis in their lungs. They also experienced less weight loss and were less likely to die from their infection than control mice. Interestingly, if mice were given DAT two days post-infection, they had worse outcomes than the mice who received DAT before infection, suggesting that DAT primed the immune system for an appropriate response to an immune challenge.

    These findings suggest that dietary compounds can boost immune function and highlight the importance of regular consumption of these protective compounds to prime the immune system.

    Press release: https://www.sciencedaily.com/releases/2017/08/170803141048.htm

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  • Vitamin D can suppress cytokine storms in COVID-19 patients reducing mortality. news.northwestern.edu
    Vitamin D COVID-19

    A cytokine storm is an excessive release of pro-inflammatory molecules that occurs during severe COVID-19 and is a common cause of death. A new study suggests that vitamin D could reduce the risk of developing a cytokine storm and decrease COVID-19 mortality.

    Vitamin D is a fat-soluble vitamin that plays essential roles in numerous physiological processes including the regulation of blood pressure, calcium homeostasis, and immune function. Previous work on other coronaviruses demonstrates that vitamin D can counteract a cytokine storm by strengthening the innate immune response and inhibiting the adaptive immune system from over-responding to a viral infection. COVID-19 mortality varies across countries and age groups, with the elderly being particularly susceptible.

    Previous research has suggested a connection between vitamin D deficiency and C-reactive protein (CRP), a protein that increases in the blood in response to inflammation and infection. Furthermore, elevated blood levels of CRP are indicative of severe COVID-19. The current study used large-scale data to investigate whether there is an association between vitamin D deficiency and the severity of COVID-19.

    The authors of the study examined COVID-19 data from patients in ten countries, together with vitamin D and CRP data from previous studies. They estimated that patients with normal vitamin D levels had a 15.6 percent reduced risk of severe COVID-19 compared to patients with severe vitamin D deficiency.

    These findings suggest that vitamin D could suppress the cytokine storm in COVID-19 patients and reduce disease severity. More research is needed to determine if these findings hold true when vitamin D levels are measured directly.

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  • Delayed clearance of SARS-CoV2 in males likely due to high ACE2 expression in testes, which serve as viral reservoirs. www.medrxiv.org
    COVID-19

    Infection with SARS-CoV2, the virus that causes COVID-19, disproportionally affects men more than women in terms of both incidence and severity. Some evidence indicates that men are more than twice as likely to die from COVID-19 than women. Findings from a new study suggest that the testes serve as reservoirs for the virus due to increased expression of the ACE2 receptor.

    The ACE2 receptor is widely distributed among the body’s tissues. SARS-CoV2 exploits ACE2 to gain entry into cells by binding to a cell’s ACE2 receptor and injecting its genetic material into the cytosol, where it can replicate.

    The study involved 68 patients (48 males, 20 females) who had been diagnosed with COVID-19. The patients, who were between the ages of 3 and 57 years, underwent daily testing via oropharyngeal/nasopharyngeal swab to assess their viral load. The testing revealed that females cleared the virus roughly two days earlier than males.

    The authors of the study then examined tissue expression patterns of ACE2 as reported in RNA expression databases. They found that testicular tissue is one of the highest sites of ACE2 expression. Ovarian tissue has very low ACE2 expression. These findings suggest that males have delayed viral clearance of SARS-CoV2 due to high expression of ACE2 receptors in testicular tissue, which serves as a reservoir for the virus.

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  • Blood glucose control among people with type 2 diabetes influences COVID-19-related mortality. www.sciencedaily.com
    Diabetes COVID-19

    Type 2 diabetes is a metabolic disorder characterized by high blood glucose and insulin resistance. Poor blood glucose control is associated with many diabetes-related complications and death. Findings from a new study indicate that blood glucose control influences outcomes in COVID-19.

    The most common symptoms of infection from SARS-CoV2, the virus responsible for COVID-19, include fever, cough, shortness of breath, and other respiratory system involvement. Recent evidence suggests that SARS-CoV2 can attack other organ systems, as well. People with preexisting health conditions such as diabetes are at higher risk of severe illness and even death with COVID-19.

    The retrospective, multi-centered study reviewed 7,337 cases of COVID-19 patients in Hubei Province, China. Of these cases, 952 patients had type 2 diabetes.

    The review indicated that patients with type 2 diabetes were more likely to have preexisting hypertension, coronary heart disease, cerebrovascular disease, and kidney dysfunction than patients without diabetes. They were also more likely to report having fatigue and difficulty breathing associated with COVID-19.

    In addition, COVID-19 patients with type 2 diabetes required more intensive care than patients without diabetes. For example, they had a higher need for antibiotics and other drugs and often required respiratory interventions such as oxygen and various types of ventilation. The mortality rate among COVID-19 patients was considerably higher among people with type 2 diabetes. In particular, 7.8 percent of patients with type 2 diabetes died compared to 2.7 percent of patients without diabetes.

    The authors of the study identified blood glucose control as a primary risk factor for severe illness and death among type 2 diabetes patients. Well-controlled blood glucose was associated with considerably lower mortality during hospitalization.

    These findings shed light on the association between type 2 diabetes and COVID-19 severity and death and underscore the need for educating high-risk patients, especially those with type 2 diabetes, on the importance of maintaining blood glucose control.

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  • Current options for addressing cardiovascular complications of COVID-19. www.frontiersin.org
    COVID-19 Cardiovascular

    Current options for addressing cardiovascular complications of COVID-19. Although COVID-19 commonly presents as a respiratory infection, the illness targets multiple organ systems, including the cardiovascular system. In one study, patients with cardiac injury accounted for nearly one-fourth of severe cases of COVID-19. A recent article describes the inflammatory aspects of COVID-19, identifies current therapies used in regard to cardiac injury, and suggests guidelines for clinical practice.

    The authors of the article identify three primary drivers of cardiac injury in COVID-19: direct viral infection to cardiac tissues, cytokine storm, and aggravation of preexisting cardiovascular disease. They posited that direct infection of cardiac tissue might be related to increased expression of angiotensin-converting enzymes-2 (ACE2) receptors in the heart. SARS-CoV-2, the virus that causes COVID-19, exploits ACE2 to gain entry into cells. Cytokine storm can occur in COVID-19 when SARS-CoV-2 infection provokes an excessive immune response that, in turn, induces multiple organ dysfunction. COVID-19 infection severely burdens the cardiovascular system, aggravating preexisting cardiovascular morbidities and triggering grave events, such as exacerbation of heart failure or acute coronary syndromes.

    The authors also suggest that targeting inflammation – the underlying cause of the aforementioned drivers of cardiac injury – is critical to preserving cardiac health in COVID-19. They identify various drugs currently in use that target the central pathways associated with inflammation; balance the body’s immune responses; and reduce inflammation.

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  • People with COVID-19 are at higher risk of complications associated with thrombotic events. www.sciencedaily.com
    Omega-3 COVID-19

    Known complications of COVID-19 illness include acute respiratory failure, pneumonia, and acute kidney failure, among others. Recent findings now indicate that people with COVID-19 are at higher risk of complications associated with thrombotic events.

    Thrombotic events can occur when the procoagulant (clotting) forces and anticoagulant and fibrinolytic forces are disrupted. These events can affect multiple organ systems. Common manifestations of thrombotic dysfunction include deep venous thrombosis (blood clots in the legs) or pulmonary embolism (blood clots in the lungs), or disseminated intravascular coagulation (a systemic, life-threatening blood clotting disorder).

    Reports from two hospitals in France indicate that pulmonary embolism occurred in 23 to 30 percent of critically ill COVID-19 patients – considerably higher than is commonly observed in critically ill patients without COVID-19. A single case report described thrombotic events that affected a patient’s lungs, brain, and kidneys. These findings suggest that early monitoring via imaging tests and treatment with anti-clotting factors is critical for COVID-19 patients.

    Interestingly, omega-3 fatty acids might be useful as prophylactic measures against thrombotic events. Previous research indicates that omega-3 fatty acid intake of 4.7 grams or more per week from either fish or supplements reduced lower venous thromboembolism risk 22 to 26 percent and reduced pulmonary embolism risk 39 to 60 percent.

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  • Poor vitamin D status prevalent among patients with acute respiratory distress syndrome. www.atsjournals.org
    Vitamin D COVID-19

    Vitamin D is a fat-soluble vitamin that plays critical roles in several physiological processes, including blood pressure regulation, calcium homeostasis, and immune function. Approximately 70 percent of people living in the United States have low vitamin D levels. Findings of a study presented at a 2016 scientific conference suggested that vitamin D insufficiency is associated with increased risk for developing acute respiratory distress syndrome (ARDS).

    ARDS is a severe form of acute lung injury characterized by rapid breathing, shortness of breath, and a low blood oxygen level and can lead to respiratory failure and death. It commonly occurs with viral illnesses, including influenza and COVID-19.

    The retrospective study, which drew on data collected as part of a multicenter randomized controlled trial, involved 476 patients diagnosed with ARDS. The patients' vitamin D status was assessed upon admission to the hospital. Vitamin D levels less than 20 ng/ml were considered “low.”

    The assessments indicated that approximately 90 percent of the patients had low vitamin D levels, even when the data were adjusted for age and severity of illness. The patients with low vitamin D levels spent an average of six days longer on mechanical ventilation compared to patients with higher levels. These findings suggest that poor vitamin D status contributes to increased risk for developing ARDS and influences disease outcomes associated with ventilator needs.

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  • The betacoronaviruses can induce immune responses against one another, generating neutralizing antibodies and/or cross-reactive antibodies. www.ncbi.nlm.nih.gov
    Immune System COVID-19

    Betacoronaviruses are a subfamily of the coronaviruses – a group of related viruses that cause illness in birds and mammals, including humans. Members of this subfamily include SARS-CoV-1 (which causes severe acute respiratory syndrome, or SARS), MERS-CoV (which causes Middle East respiratory syndrome, or MERS), SARS-CoV-2 (which causes COVID-19), and HCoV-OC43 (which causes the common cold). A 2013 study found that betacoronaviruses generate cross-reactive antibodies against SARS-CoV in serological testing.

    Serological tests detect antibodies present in the blood following a response to a specific infection, such as SARS or COVID-19. Previous studies have found that SARS-CoV-1 can generate antibodies against HCoV-OC43 (which could offer cross-immunity). Similarly, HCoV-OC43 can generate cross-reactive antibodies against SARS-CoV-1 (which could generate false positives on serological antibody tests).

    The seroprevalence study involved 94 game-food animal handlers, 28 SARS patients, and 152 healthy blood donors in Southern China. The authors of the study used indirect immunofluorescence and neutralizing antibody tests to screen for antibodies.

    They found that two of the animal handlers had antibodies against HCoV-EMC and SARS-CoV-1, with low levels of neutralizing antibodies. However, 17 of the SARS patients had neutralizing antibodies against HCoV-OC43. None of the healthy blood donors had any antibodies against either virus.

    These findings suggest that betacoronaviruses can induce immune responses against one another, generating neutralizing antibodies and/or cross-reactive antibodies against each other. This could confound serological surveillance studies investigating the prevalence of SARS-CoV-2 infection, while also raising the possibility for cross-immunity. No data currently exist demonstrating that betacoronaviruses generate cross-reactive and/or neutralizing antibodies against SARS-CoV-2. Both scenarios are probable.

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  • Chloroquine or hydroxychloroquine, when used in combination with metformin, increased risk of death in mice blogs.sciencemag.org
    Metabolic Syndrome COVID-19 Metformin

    Chloroquine and hydroxychloroquine are antimalarial drugs currently being used under Emergency Use Authorization as treatments for COVID-19. Recently published data from a mouse study suggest that these drugs carry a significant risk of death when either is given in combination with metformin.

    Metformin is a drug commonly used to treat type 2 diabetes. It is the fourth most commonly prescribed medication in the United States, with more than 80 million prescriptions for the drug written yearly.

    Previous research has demonstrated that chloroquine and metformin, when used independently, exert anti-cancer effects. The current study investigated whether the two drugs, when used in combination, would have a synergistic effect against cancer.

    The authors of the study injected mice with saline, chloroquine, hydroxychloroquine, and/or metformin for four weeks. They found that the combination of chloroquine and metformin killed 40 percent of the mice. The combination of hydroxychloroquine and metformin killed 30 to 40 percent of the mice. All the treated mice exhibited high levels of lactate dehydrogenase and creatine kinase – indicators of tissue damage. Some of the mice treated with hydroxychloroquine and metformin exhibited signs of increased autophagy in their hearts, livers, and kidneys.

    These findings suggest that when chloroquine or hydroxychloroquine are given in combination with metformin, they can increase the risk of death in mice. Further clinical trials are needed to determine if these findings translate to humans.

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  • Exercise might protect against deadly COVID-19 complication. www.eurekalert.org
    Exercise COVID-19

    Acute respiratory distress syndrome (ARDS) is a severe form of acute lung injury, characterized by rapid breathing, shortness of breath, and a low blood oxygen level. It occurs in as many as 17 percent of all COVID-19 cases and can lead to respiratory failure and death. Findings presented in a recent review suggest that extracellular superoxide dismutase (EcSOD), a potent antioxidant enzyme produced by the muscles during exercise, can reduce the risk of developing ARDS.

    A critical feature of the pathogenesis of ARDS is an excessive immune response that leads to increased production of reactive oxygen species and pro-inflammatory mediators in the lungs. Evidence indicates that EcSOD is highly expressed in lung tissues, where it inhibits many of the pathological features of ARDS and acts as a scavenger of superoxide. Loss of EcSOD activity in mice markedly increases risk of death due to ARDS, however.

    An abundance of evidence demonstrates that even a single session of exercise can boost EcSOD production in muscles. Taken together, these findings suggest that exercise could provide protection against ARDS by upregulating EcSOD production.

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  • Cardiac injury commonly occurs in patients with COVID-19 and markedly increases risk of death among patients with preexisting cardiovascular disease. jamanetwork.com
    Heart Disease COVID-19

    People who have cardiovascular diseases such as coronary artery disease, atherosclerosis, or heart failure often have poor outcomes during acute illness. Cardiac injury commonly occurs with COVID-19 illness, exacerbating preexisting cardiovascular disease. A recent editorial summarizes the available data regarding adverse outcomes associated with cardiovascular disease and COVID-19.

    The authors of the editorial describe the findings from two recent studies conducted at a teaching hospital in Wuhan, China. One study compared the outcomes of hospitalized COVID-19 patients who had myocardial damage versus COVID-19 patients without myocardial damage. More than half (51 percent) of those with myocardial damage died while in the hospital, but only 4.5 percent of those without myocardial damage died in the hospital. Another study had similar findings, with higher death rates (59.6 percent) among patients with preexisting cardiovascular disease and elevated troponin (a marker of cardiac injury) compared to those with normal troponin levels (8.9 percent).

    The findings from these two studies suggest that cardiac injury commonly occurs in patients with COVID-19 and markedly increases risk of death among patients with preexisting cardiovascular disease. These patients might require more aggressive care than other patients.

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  • Expert opinion: ACE2 increases risk of infection but decreases severity of disease. jamanetwork.com
    COVID-19

    From the article:

    “In summary, older individuals, especially those with hypertension and diabetes, have reduced ACE2 expression and upregulation of angiotensin II proinflammatory signaling; the increase in ACE2 levels with ACEI/ARB treatment is more likely to be corrective to these changes. We hypothesize that with superimposed COVID-19 disease, SARS-CoV-2 binding to ACE2 acutely exaggerates this proinflammatory background, predisposing these subpopulations to greater COVID-19 disease severity and mortality. This hypothesis is in line with the evidence of a protective role of angiotensin II antagonism against sepsis-associated acute lung injury and supports continuing therapy with ACEIs/ARBs and, more so, urgently calls for expanding ongoing trials treating patients with severe COVID-19 with RAS interventions to examine the role of these interventions in preventing lethal lung complications of COVID-19 as cases surge around the world.”

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  • Successful MERS vaccine in mice may hold promise for COVID-19 vaccine www.eurekalert.org
    Vaccine COVID-19

    From the article:

    “The vaccine is an innocuous parainfluenza virus (PIV5) carrying the "spike” protein that MERS uses to infect cells. All the vaccinated mice survived a lethal dose of the MERS coronavirus. […] The researchers note several factors that make PIV5 expressing a coronavirus spike protein an appealing platform for vaccine development against emerging coronaviruses. First, PIV5 can infect many different mammals, including humans, without causing disease. PIV5 is also being investigated as a vaccine for other respiratory diseases including respiratory syncytial virus (RSV) and influenza. Second, the fact that a low dose of the vaccine was sufficient to protect the mice might be beneficial for creating enough vaccine for mass immunization. And finally, the vaccine in the current study was the most effective MERS vaccine to date in animal models of the disease."

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  • Experimental antiviral drug effective against COVID-19 in mice. www.eurekalert.org
    COVID-19

    Infection from SARS-CoV-2, the virus responsible for COVID-19, can cause extensive damage to the respiratory system, especially the lungs. No treatments for COVID-19 currently exist, however. Findings from a recent study in human airway cells and in mice suggest that EIDD-2801, an experimental antiviral drug, might be useful in preventing or treating the lung damage associated with COVID-19.

    EIDD-2801 is a ribonucleoside analog, a compound that mimics natural ribonucleosides as a means to block viral replication. Previous work demonstrates that EIDD-2801 is effective against several unrelated viruses including influenza, Ebola, and coronaviruses. A key advantage to EIDD-2801 is that it is available in an easy-to-take pill form.

    The authors of the study explored the effects of EIDD-2801 on viral replication of SARS-CoV-2 in human epithelial airway cells. They found that the drug inhibited viral replication in a dose-dependent manner. Then they gauged the drug’s effectiveness as a prophylactic. They found that when mice received the drug shortly after being infected, they lost less weight and experienced less lung damage compared to mice that didn’t receive the drug. The degree of protection was dependent upon the timing of drug administration during the course of the disease, with earlier being better.

    These findings suggest that EIDD-2801 is effective against COVID-19 respiratory symptoms in mice. Further study in humans is warranted.

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  • Recombinant form of ACE2 reduced SARS-CoV-2 infection in cultured cells. www.eurekalert.org
    COVID-19

    SARS-CoV-2 exploits a receptor on angiotensin-converting enzyme 2, or ACE2, to gain entry into cells. The virus binds to a cell’s ACE2 receptor and injects its genetic material into the cytosol so the virus can replicate. A recent study suggests that an experimental antiviral drug called APN01 might inhibit SARS-CoV-2’s capacity to bind with ACE2.

    APN01, also known as human recombinant soluble angiotensin-converting enzyme 2, or hrsACE2, is a genetically engineered drug. A previous clinical trial demonstrated hrsACE2’s efficacy against acute respiratory distress syndrome, a common complication of SARS-CoV-2 infection.

    The authors of the current study isolated SARS-CoV-2 from nasopharyngeal (roof of the mouth) samples taken from a patient in Sweden who tested positive for COVID-19. Then they infected cultured cells with the isolated virus with or without the presence of hrsACE2. Fifteen hours after infection, they found that hrsACE2 inhibited viral entry by a factor of 1,000-5,000 by impairing SARS-CoV-2’s ability to bind to the ACE2 receptor.

    These findings demonstrate that hrsACE2 shows promise as a therapeutic against COVID-19. Future clinical trials will further elucidate the drug’s efficacy in humans.

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  • SARS-CoV-2 replicates in the throat, making it more contagious than other coronaviruses. www.eurekalert.org
    Virus COVID-19

    COVID-19 is highly contagious, spreading rapidly from person to person, primarily through respiratory droplets produced when an infected person coughs or sneezes. A recent study indicates that SARS-CoV-2, the virus responsible for COVID-19, replicates in the throat, increasing its transmissibility.

    The authors of the study followed nine patients who presented with symptoms of COVID-19. They collected nose and throat swabs and sputum samples from the patients to test for the presence of SARS-CoV-2 throughout the course of their illness and up to four weeks after the onset of symptoms. They found that the swabs and sputum samples showed high levels of infectious viral particles – an indication that, unlike related coronaviruses, SARS-CoV-2 didn’t need to travel to the lungs to replicate. Instead, it rapidly replicated in the throat in the early days of infection, producing a high viral load. These findings suggest that people with SARS-CoV-2 infection can transmit the virus before they are aware that they are infected.

    The authors noted that sputum samples with fewer than 100,000 copies of viral RNA didn’t contain any infectious viral particles, suggesting that patients who achieve this benchmark by day 10 of their illness can be discharged to isolation at home. This is critical information for overburdened hospitals and healthcare providers trying to determine when to discharge patients.

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  • Subgroups of children may be at greater risk of COVID-19 including those who are younger, have respiratory problems, or are immunocompromised. www.sciencedaily.com
    COVID-19

    Children are largely unaffected by COVID-19 infection, remaining disease-free or manifesting few or mild clinical signs and symptoms. Understanding how the infection affects children is critical to preventing the further spread of the disease. A recent study explored the characteristics and transmission patterns of COVID-19 among children in China.

    The study involved more than 2,000 children (average age, 7 years) living in mainland China who had been diagnosed with COVID-19. Children were classified as asymptomatic, mild, moderate, severe, or critical cases, based on diagnostic criteria that included fever, upper or lower respiratory involvement, diarrhea, and other symptoms.

    Approximately 4 percent of the children with COVID-19 were asymptomatic, and 51 percent and 38 percent were mild or moderate cases, respectively. Among children manifesting symptoms of the disease, only 5 percent had shortness of breath and fewer than 1 percent progressed to acute respiratory distress syndrome (ARDS) or multiorgan system dysfunction (MODS). These figures are in stark contrast to those observed in adults, where shortness of breath, ARDS, and MODS are far more common, especially in older adults.

    The data also indicated that children younger than one year old were at greatest risk of COVID-19 complications. A commentary on the study’s findings suggested that children who had pre-existing respiratory problems or were immunocompromised were also at greater risk. These findings underscore the need for further research into how COVID-19 manifests in younger patients to improve treatment and prevent disease spread.

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  • Some COVID-19 patients report loss of smell and taste, potentially signaling SARS-CoV2 infiltration of the central nervous system. www.the-scientist.com
    COVID-19

    The most common symptoms of infection from SARS-CoV2, the virus responsible for COVID-19, include fever, cough, shortness of breath, and indications of widespread respiratory system involvement. Recent evidence suggests that SARS-CoV2 can attack other organ systems, as well. In fact, some infected patients report loss of smell and taste, potentially signaling SARS-CoV2 infiltration of the central nervous system.

    SARS-CoV2 exploits the angiotensin-converting enzyme 2 (ACE2) receptor to gain entry into cells. One group of scientists described the expression of ACE2 in neurological tissue and assessed the possible contribution of neurological tissue damage to the death and disease associated with COVID-19. Previous research indicates that related coronaviruses infect the olfactory bulb in mice to promote neuronal death. In addition, viral presence and accompanying damage have been observed in human brain tissue following coronavirus infection.

    The authors of the current study noted that long before the neuronal damages occur, the endothelial tissues in cerebral capillaries rupture and bleed into the surrounding tissue, which is often fatal. They suggested that early signs of impaired smell or taste in an otherwise uncomplicated early-stage COVID-19 patient should be investigated thoroughly for central nervous system involvement. They concluded that although widespread homeostatic dysfunction is the primary cause of death among COVID-19 patients, cerebral edema due to neurological damage might expedite death before the onset of homeostatic failure. These findings can influence the triaging of patients with COVID-19.

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  • Covid-19 was transmitted to 3 out of 33 newborns during delivery with 0% mortality rate. jamanetwork.com
    Pregnancy COVID-19

    From the article: “Consistent with previous studies, the clinical symptoms from 33 neonates with or at risk of COVID-19 were mild and outcomes were favorable. Of the 3 neonates with symptomatic COVID-19, the most seriously ill neonate may have been symptomatic from prematurity, asphyxia, and sepsis, rather than SARS-CoV-2 infection.

    In this cohort, 3 of 33 infants (9%) presented with early-onset SARS-CoV-2 infection. Because strict infection control and prevention procedures were implemented during the delivery, it is likely that the sources of SARS-CoV-2 in the neonates’ upper respiratory tracts or anuses were maternal in origin. Although 2 recent studies have shown that there were no clinical findings or investigations suggestive of COVID-19 in neonates born to affected mothers, and all samples, including amniotic fluid, cord blood, and breast milk, were negative for SARS-CoV-2, the vertical maternal-fetal transmission cannot be ruled out in the current cohort. Therefore, it is crucial to screen pregnant women and implement strict infection control measures, quarantine of infected mothers, and close monitoring of neonates at risk of COVID-19."

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  • An open-label pilot trial found that the antimalarial drug hydroxychloroquine may be useful in the treatment of COVID-19. mediterranee-infection.com
    Virus Iron Arthritis Dairy COVID-19

    A number of randomized controlled trials are currently underway investigating various antiviral therapies for the treatment of COVID-19. Findings from a very small open-label study recently published in the Journal of Antimicrobial Agents found that hydroxychloroquine decreased viral nasopharyngeal levels of SARS-CoV-2 virus in COVID-19 patients in only three to six days in most patients.

    Hydroxychloroquine is a common antimalarial drug that is also used to treat rheumatoid arthritis and lupus. In 2017, it was the 128th most prescribed medication in the United States with more than five million prescriptions. It is relatively safe with a few side effects. This Wikipedia article provides an overview of hydroxychloroquine.

    In vitro studies in 2004 and 2005 showed that hydroxychloroquine is a potent inhibitor of SARS-CoV, the virus that causes severe acute respiratory syndrome, or SARS. A later study found that hydroxychloroquine improved survival rates in newborn mice infected with a related coronavirus.

    The current study involved 32 confirmed COVID-19 patients who were administered 600 milligrams of hydroxychloroquine daily for six days. Some patients also received the antibiotic azithromycin. Nasopharyngeal samples taken on day six of treatment indicated that 70 percent of the hydroxychloroquine-treated patients had cleared the virus compared with 12.5 percent in the group receiving standard of care. All of the patients who received both the antibiotic azithromycin and the hydroxychloroquine cleared the virus from nasopharyngeal samples.

    Azithromycin is an antibiotic that has been shown to have antiviral activity against some viruses like Ebola in animal studies. The safety profile of taking both hydroxychloroquine and azithromycin needs to be determined.

    In addition, randomized-controlled trials need to confirm whether these therapeutics are effective for the treatment of COVID-19. Large randomized-controlled trials are underway in China and the US. You can read more about those trials here.

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  • NIH clinical trial of investigational vaccine for COVID-19 begins. www.nih.gov
    Virus Protein COVID-19

    At the time of this writing, the worldwide death toll from COVID-19 has exceeded 10,000 people. As spread of the disease escalates, a phase 1 clinical trial of an investigational vaccine using an RNA vaccine has begun in Seattle, Washington.

    Conventional vaccines typically employ antigens – inactivated disease-promoting organisms or proteins produced by a virus or bacterium. Antigens mimic the infectious agent to provoke an immune response and provide immunity from future exposures.

    RNA vaccines, on the other hand, utilize a messenger RNA (mRNA) strand that codes for a disease-specific antigen. The vaccine delivers the mRNA strand to the body’s cells, where the genetic information is used to produce the antigen. Similar to the conventional vaccine-derived antigen, these cell-derived antigens drive an immune response.

    The phase 1 clinical trial involves approximately 45 healthy men and women between the ages of 18 and 55 years. The study participants will be enrolled into one of three cohorts to receive either a 25 microgram (mcg), 100 mcg, or 250 mcg dose, via intramuscular injection in their upper arm. A repeat dose will be given four weeks later. The patients will be monitored via follow-up visits after the vaccinations to gauge the vaccine’s safety and effectiveness.

    The mRNA vaccine used in this trial, known as mRNA-1273, has shown promise in animal studies, but this is the first trial to test it in humans. Enrollment has already begun for the trial. If you live in the Seattle area and would like to participate, read this information.

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  • Case report suggests that SARS-CoV-2 is not transmitted from pregnant mothers to their infants. www.eurekalert.org
    COVID-19

    Mother-to-child transmission of disease, also known as vertical transmission, can occur during pregnancy. Several viruses, including hepatitis B, herpes varicella-zoster (chickenpox), and human immunodeficiency virus (HIV), can be passed via vertical transmission. A recent report indicates that SARS-CoV-2, the virus that causes COVID-19, is not transmittable from pregnant mothers to their infants at birth.

    The report describes the clinical course of four live-born, full-term infants born to pregnant women who tested positive for COVID-19 in Wuhan, China. Three of the four infants did not test positive for the virus (the mother of the fourth infant did not provide consent for testing).

    None of the infants manifested clinical signs of COVID-19, such as respiratory or gastrointestinal problems, but two had mild rashes at birth. One of the infants developed breathing problems but responded to non-invasive mechanical ventilation.

    Although three of the four infants described in the report were born via Cesarean section, one was born vaginally and did not test positive for the virus. All the infants were isolated after birth and formula-fed.

    The authors of the report collected placenta, amniotic fluid, neonatal blood, gastric fluid, and anal swab samples from the infants for further study.

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  • More than 10 percent of people with COVID-19 are infected by someone who has the SARS-CoV-2 virus but is asymptomatic. www.eurekalert.org
    Virus COVID-19

    A critical factor in containing SARS-CoV-2, the virus that causes COVID-19, is understanding how quickly the virus spreads. Findings from a new study indicate that the SARS-CoV-2 spreads quickly due to its short serial interval, often before carriers are symptomatic.

    Serial interval refers to the amount of time between when a primary case (someone who is infected) develops symptoms and when a secondary case (the person they infect) develops symptoms. Some diseases, such as Ebola virus disease, have long serial intervals so containment is relatively easy despite the virulence of the virus. Other diseases, such as influenza, have short serial intervals, which contributes to their spread.

    The authors of the study reviewed 468 COVID-19 reports of disease transmission that occurred during a three-week period in mainland China, outside of Hubei Province. Each report provided information about when symptoms first appeared in both the primary and secondary cases, as well as where the transmission likely occurred.

    They found that the average serial interval for SARS-CoV-2 was approximately four days and more than 12 percent of disease transmissions occurred when the primary case was asymptomatic. These findings point to the importance of limiting exposure to the virus and can inform policymakers on which interventions might be more useful.

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  • US military scientists working to develop a therapeutic strategy against SARS-CoV-2. www.defenseone.com
    Immune System Protein COVID-19

    There are currently no vaccines to prevent infection with SARS-CoV-2, the virus that causes COVID-19. Although at least one clinical trial of an investigational vaccine is currently underway, the release of such a vaccine could take months or even years. Scientists at DARPA, the Defense Advanced Research Projects Agency, are working to develop a therapeutic strategy against SARS-CoV-2 using monoclonal antibodies.

    Antibodies are proteins that identify pathogens for destruction by the immune system. They arise from different cell lineages and bind to multiple epitopes – regions on viral proteins to which immune cells bind to drive a targeted immune response. Monoclonal antibodies, on the other hand, are made by identical immune cells cloned from a single, unique parent cell. They bind to a single, specific epitope.

    DARPA’s research is part of the Pandemic Prevention Program, or P3. Their goal is to determine which monoclonal antibodies the body produces when it encounters a particular virus, such as SARS-CoV-2, and then stimulate the body’s production of those antibodies. The process involves sequencing the RNA of B-cells taken from a person who has recovered from a particular pathogen and then producing antibodies against the pathogen. The antibodies can then be injected into a healthy person to promote immunity or injected into a sick person to facilitate recovery.

    This strategy can serve as a sort of stopgap measure until a vaccine is developed. Although identifying and producing these antibodies is a lengthy process, DARPA is working to facilitate discovery and accelerate capacity to produce the antibodies at scale.

    • Read this review of COVID-19 monoclonal antibody research for more information.
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  • Potential targets for immune responses to novel coronavirus have been identified, a crucial step in vaccine development. www.eurekalert.org
    Immune System Virus Protein COVID-19

    Coronaviruses, a genus of the Coronaviridae family, are enveloped viruses with a large positive-strand RNA genome. The recently identified SARS-CoV-2, the cause of the disease known as COVID19, is one of seven coronaviruses known to infect humans. Others include SARS-CoV (which causes severe acute respiratory syndrome, or SARS) and MERS-CoV (which causes Middle East respiratory syndrome, or MERS). A team of scientists recently identified several epitopes in the SARS-CoV-2 virus, a crucial step in vaccine development strategies.

    Epitopes are regions on viral proteins that immune cells bind to drive a targeted immune response. Most epitopes are approximately five or six amino acids in length. A typical full-length viral protein sequence may contain many different epitopes to which antibodies can bind.

    The authors of the study drew on data from the Immune Epitope Database as well as Virus Pathogen Resource, a compilation of information about known pathogenic viruses. The team compiled known epitopes from other coronaviruses, mapped the corresponding regions to SARS-CoV-2, and used the information to predict likely epitopes.

    They identified several specific regions in SARS-CoV-2 that have high homology to the SARS virus, indicating that SARS-CoV is the closest related virus to SARS-CoV-2. Specifically targeting these epitopes may generate immunity to related coronaviruses and promote resistance to viral evolution.

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