• Moriah Bergwerk, Tal Gonen, Yaniv Lustig, Sharon Amit, Marc Lipsitch, Carmit Cohen, Michal Mandelboim, LevinEinav GalEGFrom the Infection Prevention and Control Unit (M.B., T.G., C.C., E.G.L., C.R., I.T., M.Z., G.R.-Y.), the Department of Clinical Microbiology (S.A.), General Management (Y.K.), and the Central Virology Laboratory, Public Health Authority, , Carmit Rubin, Victoria Indenbaum, Ilana Tal, Malka Zavitan, Neta Zuckerman, Adina Bar-Chaim, Yitshak Kreiss, and Gili Regev-Yochay.
• From the Infection Prevention and Control Unit (M.B., T.G., C.C., E.G.L., C.R., I.T., M.Z., G.R.-Y.), the Department of Clinical Microbiology (S.A.), General Management (Y.K.), and the Central Virology Laboratory, Public Health Authority, Ministry of Health (Y.L., M.M., V.I., N.Z.), Sheba Medical Center Tel Hashomer, Ramat Gan, Sackler School of Medicine, Tel Aviv University, Tel Aviv (T.G., Y.L., M.M., E.G.L., Y.K., G.R.-Y.), and the Laboratory Wing, Asaf Harofe Medical Center, Be'er Ya'akov (A.B.-C.) - all in Israel; St. George's School of Medicine of London and Faculty of Medicine, University of Nicosia, Nicosia, Cyprus (M.B.); and Harvard T.H. Chan School of Public Health, Boston (M.L.).
• N. Engl. J. Med. 2021 Oct 14; 385 (16): 147414841474-1484.

BackgroundDespite 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.MethodsAt 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.ResultsAmong 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.ConclusionsAmong 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.Copyright © 2021 Massachusetts Medical Society.

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