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Was there a benefit of vaccinating health care workers with a fourth dose of BNT162b2 vaccine during the Omicron outbreak?

In a recent study published in JAMA Network Open, researchers analyzed the effectiveness of the fourth dose of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BNT162b2 vaccination against the SARS-CoV-2 Omicron infection in medical professionals in Israel.

Study: Association of Receiving a Fourth Dose of the BNT162b Vaccine With SARS-CoV-2 Infection Among Health Care Workers in Israel. Image Credit: davide bonaldo/Shutterstock


The fifth wave of the coronavirus disease 2019 (COVID-19) pandemic, primarily driven by the SARS-CoV-2 Omicron variant and impacting both the vaccinated and unvaccinated populations, began in Israel in December 2021. Starting in August 2021, Israel became the first nation to give a third shot of the COVID-19 vaccine to the whole adult population.

In Israel, 90% of adults received the three doses of the SARS-CoV-2 BNT162b2 vaccine, including above 95% of health care workers (HCWs), till September 2021. In the Delta variant surge, the frequency of serious illness, breakthrough infections, and death were decreased significantly by this third dose or booster vaccination.

Despite the significant vaccination coverage, the highly contagious Omicron variant led to considerable breakthrough infections across the group that had received three vaccine doses. The Israeli Ministry of Health advised a voluntarily fourth dose of BNT162b2 vaccine to adults over the age of 60, people with compromised immune systems, and HCWs due to the safety and effectiveness of the third dose in averting infection and severe illness and probable diminishing immunity of the third vaccine dose.

About the study

The current multicenter cohort research assessed whether delivering a fourth dose of the COVID-19 BNT162b2 vaccination to HCWs during the SARS-CoV-2 Omicron variant outbreak was beneficial in Israel. The study aimed to determine the advantage of the fourth BNT162b2 vaccine dose on the breakthrough SARS-CoV-2 infection rate across HCWs.

The study was conducted during the peak of the Omicron variant wave in January 2022 in Israel, the first month of the fourth-dose vaccination program. The study included all HCWs from 11 Israelian general hospitals vaccinated with three BNT162b2 vaccine doses until 30 September 2021 and who had not acquired SARS-CoV-2 infection before the vaccination program, i.e., 2 January 2022. Besides, a fourth BNT162b2 vaccine dose was administered as part of the research protocol in January 2022.

Until 31 January 2022, the researchers gathered information on all participants' vaccination and breakthrough infection dates and anonymized demographic information on the personnel, including age, gender, and profession. They restricted the study and comparison of three-dose and four-dose recipients to the HCWs who were only vaccinated with the third shot between August and September 2021 since 99% of four-dose recipients received their third dose in these months.

The breakthrough SARS-CoV-2 infections in four-dose recipients compared to three-dose recipients, as determined by a COVID-19-positive polymerase chain reaction (PCR) test result, were the research's primary outcomes. HCWs were screened according to exposure to SARS-CoV-2 cases or symptoms. Additionally, the reporting guidelines the team followed was the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE).


According to the study results, 29611 Israeli HCWs, comprising 19381, i.e., 65%, women with an average age of 44 years, received three doses of the BNT162b2 vaccine between August and September 2021. Of these, 5331, i.e., 18%, received the fourth dose in January 2022, and none contracted the infection within the initial week of vaccination. 

In the four-dose group, the overall breakthrough infection rate was 7%, i.e., 368 of 5331, while in the three-dose group, it was 20%, i.e., 4802 of 24280. The fourth vaccination showed a substantial benefit at most enrolled hospitals and in subgroup assessments by age group, sex, and profession. A time-reliant Cox proportional hazards regression model and a matched evaluation by the specific day of getting the third vaccination revealed comparable decreases. There were no severe illnesses or fatalities in any group.

In addition, elder HCWs in the current cohort showed a greater vaccination rate. Furthermore, physicians had higher vaccination rates versus nurses and other occupations.

On the whole, the breakthrough COVID-19 rate among 29611 HCWs in Israel who received four doses of the BNT162b2 vaccination was 6.9%, compared to 19.8% among those who received three doses. These results imply that a fourth dose of the vaccine was valuable in avoiding SARS-CoV-2 breakthrough infections in HCWs, supporting the continued operation of the healthcare system throughout the pandemic.


Collectively, the study findings demonstrated that the fourth COVID-19 BNT162b2 vaccine dose caused a lower rate of breakthrough SARS-CoV-2 infection among hospital workers. This reduction was less pronounced than the one found following the third dose. However, the authors noted that the fourth dose of the SARS-CoV-2 vaccine should be considered to reduce the infection rate among HCWs in the upcoming COVID-19 waves to maintain the functionality of the healthcare system, given the high infectivity of the SARS-CoV-2 Omicron variant, which caused substantial medical staff shortages.

Journal reference:
  • Cohen, M. et al. (2022) "Association of Receiving a Fourth Dose of the BNT162b Vaccine With SARS-CoV-2 Infection Among Health Care Workers in Israel", JAMA Network Open, 5(8), p. e2224657. doi: 10.1001/jamanetworkopen.2022.24657.

Posted in: Medical Science News | Medical Research News | Disease/Infection News

Tags: Coronavirus, Coronavirus Disease COVID-19, covid-19, Epidemiology, Frequency, Health Care, Healthcare, Hospital, immunity, Omicron, Pandemic, Polymerase, Polymerase Chain Reaction, Research, Respiratory, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Syndrome, Vaccine

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Written by

Shanet Susan Alex

Shanet Susan Alex, a medical writer, based in Kerala, India, is a Doctor of Pharmacy graduate from Kerala University of Health Sciences. Her academic background is in clinical pharmacy and research, and she is passionate about medical writing. Shanet has published papers in the International Journal of Medical Science and Current Research (IJMSCR), the International Journal of Pharmacy (IJP), and the International Journal of Medical Science and Applied Research (IJMSAR). Apart from work, she enjoys listening to music and watching movies.

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