In an Israeli single-institution prospective cohort study reported in The New England Journal of Medicine, Bergwerk et al identified breakthrough COVID-19 infections among 39 of 1,497 health-care workers fully vaccinated with the BNT162b2 (Pfizer-BioNTech) vaccine.
As stated by the investigators: “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. Data are needed to characterize these infections and define correlates of breakthrough and infectivity.”
The study was conducted at Sheba Medical Center in Tel Aviv, where 91% of 12,586 personnel received two doses of the BNT162b2 vaccine between December 19, 2020, and April 28, 2021. The largest COVID-19 pandemic surge in Israel had reached its peak on January 14, 2021. The study was initiated on January 20, 2021, 11 days after the first staff members had received a second dose of the BNT162b2 vaccine; data were collected for 14 weeks, through April 28, 2021.
The current analysis included 1,497 fully vaccinated workers with available repeat reverse-transcriptase polymerase chain reaction (RT-PCR) assay data. Workers were evaluated by RT-PCR, antigen-detecting rapid diagnostic testing (Ag-RDT), serologic assays, and genomic sequencing. Breakthrough infection was defined as detection of SARS–CoV-2 on RT-PCR assay performed 11 or more days after receipt of a second vaccine dose if no explicit exposure or symptoms had been reported during the first 6 days. In a matched case-control analysis, workers with breakthrough infection with antibody titers obtained within a week before SARS–CoV-2 detection (peri-infection period) were matched with four to five uninfected controls with prospectively collected serum samples. Infectivity was assessed via correlation between neutralizing antibody titers and N gene cycle threshold (Ct) values (viral RNA copy numbers).
Among 1,497 fully vaccinated workers with available RT-PCR data, 39 had documented breakthrough infections. Geometric mean titers of neutralizing antibodies during the peri-infection period were 192.8 among cases vs 533.7 among controls, yielding a case:control ratio of 0.361 (95% confidence interval [CI] = 0.165–0.787).
Peri-infection neutralizing antibody titers in breakthrough cases were associated with higher Ct values, indicating lower infectivity. Higher viral load (Ct value < 30) at some point during infection was observed in 29 breakthrough cases (74%); however, of these cases, 17 (59%) had positive results on concurrent Ag-RDT.
Of the 33 isolates from breakthrough cases tested, 28 (85%) were identified as the B.1.1.7 variant by either multiplex PCR assay or genomic sequencing.
Among all breakthrough cases, 26 (67%) had mild symptoms at some point during infection, with none requiring hospitalization, and 13 (33%) were asymptomatic throughout infection. Among all breakthrough cases, the most common symptoms included upper respiratory congestion (36%), myalgia (28%), loss of smell or taste (28%), and fever/rigors (21%). Residual symptoms 14 days after diagnosis were reported in 31% of cases. Long COVID-19 symptoms (> 6 weeks), including prolonged loss of smell, persistent cough, fatigue, weakness, dyspnea, or myalgia, were reported by 19%.
No cases of transmission from infected workers were documented.
The investigators concluded: “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.”
Disclosure: The study was supported by the Morris–Singer Foundation and by a cooperative agreement with the U.S. National Cancer Institute. For full disclosures of the study authors, visit nejm.org.