Second Booster Protects Against Breakthrough COVID-19 Variant Infections in Health Care Workers


Health care workers who got 4 total doses against COVID-19, 2 doses of which are boosters, experienced more than 10% lower breakthrough infection rate than those with only 3 total doses.

A new study from Israel demonstrated that health care workers (HCWs) with a fourth vaccine of BNT162b2 had a lower breakthrough infection rate against the Omicron variant of COVID-19, according to the authors of an article published in JAMA Network.

In December 2021, Omicron caused the fifth wave of COVID-19 to occur in Israel. More than 95% of HCWs had a booster shot, totaling 3 doses of BNT162b2 by September 2021. However, as the most infectious variant, Omicron caused many breakthrough infections among boosted HCWs and among the general population.

Based on the impact of the fifth wave of COVID-19 on the country, the Israeli Ministry of Health recommended 4 doses to adults who are either aged 60 years and older, are immunocompromised, or are HCWs. Followed this recommendation, investigators began in January 2022 to compare the breakthrough rates of infection in HCWs with 3 or 4 BNT162b2 doses.

HCWs from 11 hospitals--all were academic centers, 5 of which were tertiary care centers--received the Pfizer BNT162b2 messenger RNA vaccine as their fourth dose. Participants were limited to HCWs that had a third vaccine within 3 months of receiving the fourth.

Investigators performed weekly nasal swabs to test COVID-19 in participants with either 3 doses or 4 doses. Then they generated the rates of contraction among different subgroups, including age and sex. Investigators also performed matched analysis and regression modeling to establish the results.

The breakthrough infection rate was less for HCWs with a fourth BNT162b2 vaccine. Among the 5331 participants who received a fourth dose, there was a 7% breakthrough rate. Comparatively, participants who had 3 doses had a 20% breakthrough infection rate.

The fourth vaccine positively benefited all different subgroups, including sex, age, group, and profession. However, the fourth vaccine mitigated the infection rate of Omicron more than it did the Delta variant. Other multicenter studies also found that the fourth vaccine does not increase the antibody count as much as the third vaccine.

A separate Israeli study concluded that the data demonstrated that the fourth vaccine also benefitted the elderly population. The authors of that study also noted that older individuals aged 60 years and older and immunocompromised patients were also more willing to get this vaccine.

Even amongst the HCW population, older HCWs were more likely to get a second booster. Investigators believe it is because of their higher perceived risk of contracting COVID-19.

The authors of the study noted that this study was limited because HCWs were not routinely tested, and infections could have been missed. Additionally, receiving a fourth vaccine was voluntary and participants could be biased towards getting vaccinated in general. Finally, investigators only looked at breakthrough cases during January 2022, so one month might not be enough time to assess risk and breakthrough rate.

The authors additionally noted that it was important to look at HCWs and the role of the fourth vaccine because the need for isolation and quarantining among HCWs impacts the entire health care system. Though it was generally assumed that a fourth dose would not be valuable when HCWs were already boosted, this was not the case. Investigators noted that based on their results, the data demonstrate a fourth vaccine is advantageous for HCWs to protect against COVID-19 variants.


Cohen M, Oster Y, Moses A, et al. Association of Receiving a Fourth Dose of the BNT162b Vaccine With SARS-CoV-2 Infection Among Health Care Workers in Israel. JAMA Netw Open. 2022;5(8):e2224657. doi:10.1001/jamanetworkopen.2022.24657

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