Vaccinated Individuals with Lower Level of Antibodies Face Higher Risk of COVID-19 Breakthrough Infections, Finds New Research

Vaccinated individuals with lower level of antibodies are more exposed to COVID-19 breakthrough infections, according to a new study. This could help decide who should be chosen first for the third shot of the COVID-19 vaccine.

New groundbreaking research by the Sheba Medical Center (Tel Aviv, Israel) has shown that some individuals who have received the COVID-19 vaccine have lesser antibodies than other inoculated individuals, placing them at a higher risk of becoming infected by the SARS-CoV-2 virus.


Despite the high efficacy of the BNT162b2 messenger RNA vaccine against SARS-CoV-2, rare breakthrough infections have been reported, including infections among health care workers. In their study, the researchers characterized all COVID-19 breakthrough infections among 39 fully vaccinated health care workers during the four-month period after the second vaccine dose and compared the peri-infection humoral response in these workers with the response in matched controls. They found a low rate of breakthrough infection (0.4%). Among the 39 workers who tested positive for COVID-19, most had few symptoms, yet 19% had long COVID-19 symptoms (>6 weeks).

Most of the infected health care workers had N gene Ct values that suggested they had been infectious at some point. Most importantly, the researchers found that low titers of neutralizing antibody and S-specific IgG antibody may serve as markers of breakthrough infection. In this study, the correlation between levels of neutralizing antibodies and breakthrough infections was stronger than that for IgG antibodies. The researchers found that the difference in the peak titers of neutralizing and IgG antibodies between cases and controls was more strongly associated with the risk of infection than the difference in the peri-infection titers. This finding was consistent with the hypothesis that the neutralizing antibody titer after vaccination is a marker of overall immune response and suggested a possible role for the IgG titer. Thus, a decrease in the titer of either of these antibodies (rather than in the peak titer) may not accurately predict a decrease in protection.

Moreover, the team found that the peri-infection neutralizing antibody titers correlated with the viral load and thus with the infectivity of breakthrough cases. This result may eventually be even more important, since vaccine-induced immunity has been shown to be greatly protective against clinical disease but somewhat less protective against both infection and infectivity. Identifying immune correlates of protection (or lack thereof) from SARS-CoV-2 is critical to predicting how the expected antibody decay will affect clinical outcomes, if and when a booster dose will be needed, and whether vaccinated persons are protected. Such capacity for prediction is particularly important for new vaccine development.

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Sheba Medical Center