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COVID-19 breakthrough infections in vaccinated healthcare workers – Israel cohort study

Among Pfizer–BioNTech fully vaccinated healthcare workers, most breakthrough infections were mild or asymptomatic, although persistent symptoms did occur, found an Israeli study.

Since its rollout in late 2020 in Israel, the BNT162b2 messenger RNA vaccine (Pfizer–BioNTech) has been highly effective in preventing clinically significant coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The vaccine has also been shown to reduce the incidence of asymptomatic infection and the associated infectivity.

However, breakthrough infections have emerged in a small percentage of vaccine recipients, a phenomenon that has been described in other countries and health care institutions. To date, no correlate of protection from breakthrough infection has been reported.

At the Sheba Medical Center in Ramat Gan, Israel, we conducted a prospective cohort study to assess the effectiveness of the BNT162b2 vaccine among healthcare workers and to examine possible correlates of protection and infectivity in this population. Sheba Medical Centre is the largest medical centre in the country, staffed by 12,586 healthcare workers, including employees, students, and volunteers.

On January 20, 2021, we initiated the study at the centre, 11 days after the first employees had received a second dose of the BNT162b2 vaccine. Data were collected for 14 weeks, until April 28.

Concurrently, the third and largest COVID-19 pandemic surge emerged in Israel and reached its peak on 14, January 2021, with reports of an average of 8,424 daily cases.

From 19 December 2020, to 28 April 2021, a total of 91% of the centre personnel received two doses of the BNT162b2 vaccine. This period was followed by a rapid decrease in newly detected cases.

Simultaneously, efforts were extended to identify new cases with the use of daily health questionnaires, a telephone hotline, extensive epidemiologic investigations of exposure events, and contact tracing of infected patients and personnel.

Testing for the presence of SARS-CoV-2 by means of reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay remained readily available for fully vaccinated staff members who were symptomatic or had been exposed to an infected person, regardless of symptoms.

Antigen-detecting rapid diagnostic testing (Ag-RDT) was available as an initial screening tool in the personnel clinic in combination with RT-PCR testing. The study was approved by the institutional review board at Sheba Medical Center.

Study details

Covid-19 Breakthrough Infections in Vaccinated Health Care Workers

Moriah Bergwerk, Tal Gonen, Yaniv Lustig, Sharon Amit, Marc Lipsitch, Carmit Cohen, Michal Mandelboim, Einav Gal Levin, Carmit Rubin, Victoria Indenbaum, Ilana Tal, Malka Zavitan, Neta Zuckerman, Adina Bar-Chaim, Yitshak Kreiss, and Gili Regev-Yochay

Published in The New England Journal of Medicine 28 July 2021

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 healthcare workers. Data are needed to characterise these infections and define correlates of breakthrough and infectivity.

Methods
At the largest medical centre in Israel, we identified breakthrough infections by performing extensive evaluations of healthcare 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 generalised 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 neutralising antibody titers and N gene cycle threshold (Ct) values with respect to infectivity.

Results
Among 1497 fully vaccinated healthcare workers for whom RT-PCR data were available, 39 SARS-CoV-2 breakthrough infections were documented. Neutralising 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 neutralising 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 healthcare workers, the occurrence of breakthrough infections with SARS-CoV-2 was correlated with neutralising antibody titers during the peri-infection period. Most breakthrough infections were mild or asymptomatic, although persistent symptoms did occur.

 

The NEJM article – Covid-19 Breakthrough Infections in Vaccinated Health Care Workers (Open access)

 

See more from MedicalBrief archives:

 

Sisonke: Only 2% of breakthrough infections in J&J vaccinated health workers are severe

 

Risk of COVID very low in vaccinated medical workers — Large US study

 

99% strong immune response after Pfizer vaccination — UK's PITCH study

 

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