Nirmatrelvir Use and Severe Covid-19 Outcomes during the Omicron Surge.

BACKGROUND: The oral protease inhibitor nirmatrelvir has shown substantial efficacy in high-risk, unvaccinated patients infected with the B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data regarding the effectiveness of nirmatrelvir in preventing severe coronavirus disease 2019 (Covid-19) outcomes from the B.1.1.529 (omicron) variant are limited. METHODS: We obtained data for all members of Clalit Health Services who were 40 years of age or older at the start of the study period and were assessed as being eligible to receive nirmatrelvir therapy during the omicron surge. A Cox proportional-hazards regression model with time-dependent covariates was used to estimate the association of nirmatrelvir treatment with hospitalization and death due to Covid-19, with adjustment for sociodemographic factors, coexisting conditions, and previous SARS-CoV-2 immunity status. RESULTS: A total of 109,254 patients met the eligibility criteria, of whom 3902 (4%) received nirmatrelvir during the study period. Among patients 65 years of age or older, the rate of hospitalization due to Covid-19 was 14.7 cases per 100,000 person-days among treated patients as compared with 58.9 cases per 100,000 person-days among untreated patients (adjusted hazard ratio, 0.27; 95% confidence interval [CI], 0.15 to 0.49). The adjusted hazard ratio for death due to Covid-19 was 0.21 (95% CI, 0.05 to 0.82). Among patients 40 to 64 years of age, the rate of hospitalization due to Covid-19 was 15.2 cases per 100,000 person-days among treated patients and 15.8 cases per 100,000 person-days among untreated patients (adjusted hazard ratio, 0.74; 95% CI, 0.35 to 1.58). The adjusted hazard ratio for death due to Covid-19 was 1.32 (95% CI, 0.16 to 10.75). CONCLUSIONS: Among patients 65 years of age or older, the rates of hospitalization and death due to Covid-19 were significantly lower among those who received nirmatrelvir than among those who did not. No evidence of benefit was found in younger adults.

Comparing COVID-19-related hospitalization rates among individuals with infection-induced and vaccine-induced immunity in Israel.

With the COVID-19 pandemic ongoing, accurate assessment of population immunity and the effectiveness of booster and enhancer vaccine doses is critical. We compare COVID-19-related hospitalization incidence rates in 2,412,755 individuals across four exposure levels: non-recent vaccine immunity (two BNT162b2 COVID-19 vaccine doses five or more months prior), boosted vaccine immunity (three BNT162b2 doses), infection-induced immunity (previous COVID-19 without a subsequent BNT162b2 dose), and enhanced infection-induced immunity (previous COVID-19 with a subsequent BNT162b2 dose). Rates, adjusted for potential demographic, clinical and health-seeking-behavior confounders, were assessed from July-November 2021 when the Delta variant was predominant. Compared with non-recent vaccine immunity, COVID-19-related hospitalization incidence rates were reduced by 89% (87-91%) for boosted vaccine immunity, 66% (50-77%) for infection-induced immunity and 75% (61-83%) for enhanced infection-induced immunity. We demonstrate that infection-induced immunity (enhanced or not) provides more protection against COVID-19-related hospitalization than non-recent vaccine immunity, but less protection than booster vaccination. Additionally, our results suggest that vaccinating individuals with infection-induced immunity further enhances their protection.

Fourth Dose of BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting.

BACKGROUND: With large waves of infection driven by the B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), alongside evidence of waning immunity after the booster dose of coronavirus disease 2019 (Covid-19) vaccine, several countries have begun giving at-risk persons a fourth vaccine dose. METHODS: To evaluate the early effectiveness of a fourth dose of the BNT162b2 vaccine for the prevention of Covid-19-related outcomes, we analyzed data recorded by the largest health care organization in Israel from January 3 to February 18, 2022. We evaluated the relative effectiveness of a fourth vaccine dose as compared with that of a third dose given at least 4 months earlier among persons 60 years of age or older. We compared outcomes in persons who had received a fourth dose with those in persons who had not, individually matching persons from these two groups with respect to multiple sociodemographic and clinical variables. A sensitivity analysis was performed with the use of parametric Poisson regression. RESULTS: The primary analysis included 182,122 matched pairs. Relative vaccine effectiveness in days 7 to 30 after the fourth dose was estimated to be 45% (95% confidence interval [CI], 44 to 47) against polymerase-chain-reaction-confirmed SARS-CoV-2 infection, 55% (95% CI, 53 to 58) against symptomatic Covid-19, 68% (95% CI, 59 to 74) against Covid-19-related hospitalization, 62% (95% CI, 50 to 74) against severe Covid-19, and 74% (95% CI, 50 to 90) against Covid-19-related death. The corresponding estimates in days 14 to 30 after the fourth dose were 52% (95% CI, 49 to 54), 61% (95% CI, 58 to 64), 72% (95% CI, 63 to 79), 64% (95% CI, 48 to 77), and 76% (95% CI, 48 to 91). In days 7 to 30 after a fourth vaccine dose, the difference in the absolute risk (three doses vs. four doses) was 180.1 cases per 100,000 persons (95% CI, 142.8 to 211.9) for Covid-19-related hospitalization and 68.8 cases per 100,000 persons (95% CI, 48.5 to 91.9) for severe Covid-19. In sensitivity analyses, estimates of relative effectiveness against documented infection were similar to those in the primary analysis. CONCLUSIONS: A fourth dose of the BNT162b2 vaccine was effective in reducing the short-term risk of Covid-19-related outcomes among persons who had received a third dose at least 4 months earlier. (Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.).