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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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