Covid-19 Breakthrough Infections in Vaccinated Health Care Workers

Abstract

Background Despite the high efficacy of the BNT162b2 messenger RNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rare breakthrough infections have been reported, including infections among health care workers. Data are needed to characterize these infections and define correlates of breakthrough and infectivity. Methods At the largest medical center in Israel, we identified breakthrough infections by performing extensive evaluations of health care workers who were symptomatic (including mild symptoms) or had known infection exposure. These evaluations included epidemiologic investigations, repeat reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assays, antigen-detecting rapid diagnostic testing (Ag-RDT), serologic assays, and genomic sequencing. Correlates of breakthrough infection were assessed in a case–control analysis. We matched patients with breakthrough infection who had antibody titers obtained within a week before SARS-CoV-2 detection (peri-infection period) with four to five uninfected controls and used generalized estimating equations to predict the geometric mean titers among cases and controls and the ratio between the titers in the two groups. We also assessed the correlation between neutralizing antibody titers and N gene cycle threshold (Ct) values with respect to infectivity. Results Among 1497 fully vaccinated health care workers for whom RT-PCR data were available, 39 SARS-CoV-2 breakthrough infections were documented. Neutralizing antibody titers in case patients during the peri-infection period were lower than those in matched uninfected controls (case-to-control ratio, 0.361; 95% confidence interval, 0.165 to 0.787). Higher peri-infection neutralizing antibody titers were associated with lower infectivity (higher Ct values). Most breakthrough cases were mild or asymptomatic, although 19% had persistent symptoms (>6 weeks). The B.1.1.7 (alpha) variant was found in 85% of samples tested. A total of 74% of case patients had a high viral load (Ct value, <30) at some point during their infection; however, of these patients, only 17 (59%) had a positive result on concurrent Ag-RDT. No secondary infections were documented. Conclusions Among fully vaccinated health care workers, the occurrence of breakthrough infections with SARS-CoV-2 was correlated with neutralizing antibody titers during the peri-infection period. Most breakthrough infections were mild or asymptomatic, although persistent symptoms did occur.

Occurrence of BNT162b2 Vaccine Adverse Reactions Is Associated with Enhanced SARS-CoV-2 IgG Antibody Response

“…Here, we demonstrate for the first time a clear correlation between adverse reactions and antibody levels. Recent studies showed that higher antibody levels are correlated with protection from symptomatic SARS-CoV-2 infection [11][12][13]. Therefore, our findings indicate that non-serious adverse reactions may be predictive of a favorable anti-COVID-19 protective effect.…”

Generation of a novel SARS-CoV-2 sub-genomic RNA due to the R203K/G204R variant in nucleocapsid: homologous recombination has potential to change SARS-CoV-2 at both protein and RNA level

“…At low levels of antibodies, the lungs appear to remain relatively protected against severe disease presumably by some combination of antibodies and amnestic responses restimulated by the time the lung is involved. In contrast, the early establishment of infection in the upper respiratory tract appears possible if antibody levels are low (47). We therefore postulate that variants that are more effective in interfering with Type 1 interferon responses would be more transmissible, but not necessarily cause severe disease in the context of waning immunity at an individual or population level.…”

Durability of antibody response to vaccination and surrogate neutralization of emerging variants based on SARS-CoV-2 exposure history

“…A large proportion of SARS-CoV-2 infections are asymptomatic 6 , and our results indicate that seropositivity alone is not sufficient to predict a robust antibody response to vaccination. Recent data suggest that lower responses to vaccination are associated with increased risk of breakthrough infection: Among vaccinated healthcare workers in Israel monitored from January to April 2021, neutralizing antibody and anti-spike IgG titers were significantly lower in workers with breakthrough infections in comparison with matched, uninfected controls 7 . The B.1.1.7 variant was detected in 85% of the breakthrough infections.…”