Hospitalized Patients With Severe Coronavirus Disease 2019 During the Omicron Wave in Israel: Benefits of a Fourth Vaccine Dose

Background: Waning immunity and an increased incidence of coronavirus disease 2019 (COVID-19) during the Omicron outbreak led the Israeli Ministry of Health to recommend a fourth vaccine dose for high-risk individuals. In this study, we assessed its effect for hospitalized patients with severe breakthrough COVID-19. Methods: In this multicenter cohort study of hospitalized adults with severe COVID-19 in Israel, from 15 to 31 January 2022, cases were divided according to the number of vaccinations received. Poor outcome was defined as mechanical ventilation or in-hospital death and was compared between 3- and 4-dose vaccinees using logistic regression. Results: Included were 1049 patients, median age 80 years. Among them, 394 were unvaccinated, 386 and 88 had received 3 or 4 doses, respectively. The 3-dose group was older, included more males, and immunosuppressed patients but with similar outcomes, 49% vs 51% compared with unvaccinated patients (P =. 72). Patients who received 4 doses were similarly older and immunosuppressed but had better outcomes compared with unvaccinated patients, 34% vs 51% (P <. 01). We examined independent predictors for poor outcome in patients who received either 3 or 4 doses a median of 161 days or 14 days before diagnosis, respectively. Receipt of the fourth dose was associated with protection (odds ratio, 0.51; 95% confidence interval,. 3-.87), as was remdesivir. Male sex, chronic renal failure, and dementia were associated with poor outcomes. Conclusions: Among hospitalized patients with severe breakthrough COVID-19, a recent fourth dose was associated with significant protection against mechanical ventilation or death compared with 3 doses.