Association of Receiving a Fourth Dose of the BNT162b Vaccine With SARS-CoV-2 Infection Among Health Care Workers in Israel.

Importance: Despite the high 3-dose vaccination rate among health care workers (HCWs) in Israel, a high rate of SARS-CoV-2 breakthrough infections in this group was observed during the Omicron wave. As a result, the Israeli Ministry of Health decided to recommend a fourth vaccine dose to medical staff. Objective: To evaluate the benefit of a fourth BNT162b2 vaccine dose on the breakthrough infection rate among HCWs. Design, Setting, and Participants: This multicenter cohort study was performed in January 2022, the first month of the 4-dose vaccination campaign, during a surge of the Omicron variant wave. All health care workers at 11 general hospitals in Israel who had been vaccinated with 3 doses up to September 30, 2021, and had not contracted COVID-19 before the vaccination campaign were included. Exposures: Vaccination with a fourth dose of the BNT162b2 vaccine during January 2022. Main Outcomes and Measures: Breakthrough COVID-19 infections in 4-dose recipients vs 3-dose recipients measured by a polymerase chain reaction test result positive for SARS-CoV-2. Health care workers were tested based on symptoms or exposure. Results: A total of 29 611 Israeli HCWs (19 381 [65%] female; mean [SD] age, 44 [12] years) had received 3 vaccine doses between August and September 2021; of these, 5331 (18%) received the fourth dose in January 2022 and were not infected by the first week after vaccination. Overall breakthrough infection rates were 368 of 5331 (7%) in the 4-dose group and 4802 of 24280 (20%) in the 3-dose group (relative risk, 0.35; 95% CI, 0.32-0.39). Similar reductions were found in a matched analysis by the exact day of receiving the third vaccine (relative risk, 0.61; 95% CI, 0.54-0.71) and in a time-dependent Cox proportional hazards regression model (adjusted hazard ratio, 0.56; 95% CI, 0.50-0.63). In both groups, no severe disease or death occurred. Conclusions and Relevance: In this cohort study, the fourth BNT162b2 vaccine dose resulted in a reduced breakthrough infection rate among hospital staff. This reduction was lower than that observed after the third dose; nevertheless, considering the high infectivity of the Omicron variant, which led to critical medical staff shortages, a fourth vaccine dose should be considered to mitigate the infection rate among HCWs.

Invasive fungal infections in critically ill COVID-19 patients in a large tertiary university hospital in Israel.

An increasing number of studies have tried to determine the incidence of invasive fungal infections (IFIs) in COVID-19 patients. Challenges in the diagnosis of pulmonary aspergillosis in these patients have led to new definitions of COVID-19-associated pulmonary aspergillosis (CAPA). The aim of this study was to determine the incidence and outcomes of and risk factors for IFIs in critically-ill COVID-19 patients, using the new definitions, in a tertiary center in Israel. METHODS: A case-controlled study (from 1 September 2020 to 31 March 2021) in which data from COVID-19 critically-ill patients with a diagnosis of IFI were collected and compared to a control group without IFI. RESULTS: The incidence of IFI amongst 311 COVID-19 critically-ill patients was 6.1%. 3.5% had CAPA and 3.5% had candidemia. In-hospital mortality was higher amongst patients with IFI compared to those without IFI (89.4% vs 60%, p < 0.03). The most significant predictors of IFI were cardiovascular co-morbidity and carbapenem use. CONCLUSIONS: The low incidence of CAPA in our group of COVID-19 critically-ill patients was consistent with recent reports, underscoring the importance of differentiating between true infection and colonization. Awareness and timely diagnosis of IFIs in COVID-19 critically-ill patients are imperative considering the associated high mortality.

The effect of a third BNT162b2 vaccine on breakthrough infections in health care workers: a cohort analysis.

OBJECTIVES: In August 2021, 6 months after mass vaccination of the Israeli population with the two-dose BNT162b2 mRNA vaccine, a surge of coronavirus disease 2019 infections, mostly from the delta variant, appeared also among the vaccinated. In response, the Israeli Ministry of Health initiated a booster (third dose) vaccination program. We assessed the protective effect of the third dose among health care workers (HCWs). METHODS: Infections with severe acute respiratory syndrome coronavirus 2 are monitored systematically among HCWs at the Hadassah tertiary care medical centre in Jerusalem, Israel. In this cohort, we included breakthrough infections, defined as those occurring >180 days since the second vaccine dose. The follow-up period lasted 120 days. We compared infection rates between HCWs who received the booster dose and those who received only the two-dose regimen. RESULTS: The rate of breakthrough infections among HCWs who received only the two-dose regimen was 21.4% (85 of 398). The rate in the boosted group was 0.7% (35/4973; relative risk 30, 95% CI 20-50). Those results were seen in all age groups. DISCUSSION: The significantly lower rate of breakthrough infections in boosted HCWs indicates substantial protection by a third vaccine dose.