ABSTRACT
BackgroundData suggest that vaccine effectiveness against Covid-19-associated hospital admission and mortality is augmented with booster doses, but the benefit wanes within several months. However, the CDC recently concluded that second doses of bivalent vaccines this Spring were not warranted because existing data were insufficient to analyze the benefits of such a strategy. Therefore, our objective was to assess whether routinely boosting high-risk populations at least every 6 months may be warranted, depending on age and immune status. MethodsUtilizing a database of 3,574,243 members of Clalit Health Services (CHS), we analyzed the medical records of individuals who received none, or at least one dose of the BNT162b2 mRNA COVID-19 vaccine between January 1, 2021, and April 5, 2022. We examined the risk of moderate-to-severe Covid-19 hospitalization or death stratified by age group, immune status and time since receipt of the last vaccine dose during the early Omicron wave in Israel (December 20, 2021 to April 5, 2022). The number needed to vaccinate (NNV) was calculated as the inverse of the absolute risk reduction for various subgroups and Covid-19 waves. ResultsEligibility criteria were met by 3,381,480 CHS members. The absolute risk of Covid-19 moderate-to severe hospitalization or death during the Omicron wave increased with age, immunocompromised status, and time since receipt of the last vaccine dose. The NNVs varied greatly by age and immune status and were contingent on various disease prevalence scenarios. Among the severely immunocompromised, boosting at the start of the Omicron wave had an NNV ranging from 87 (95% CI 70-109) in persons ages [≥]80 to 1,037 (95% CI 999 -1,513) in persons ages 12-59. In the lower prevalence periods, the NNV for 6-month booster cadencing remained favorable for immunocompromised people in all age groups and immunocompetent people ages [≥]60. ConclusionsOur study provides evidence for the potential benefit of a routine 6-month cadence for Covid-19 boosters for the highest-risk groups, and possibly more frequently, even during relatively lower Covid-19 prevalence.
Subject(s)
COVID-19 , DeathABSTRACT
Background The oral antiviral molnupiravir is moderately effective in high-risk, unvaccinated non-hospitalized patients infected with early variants of SARS-CoV-2. Data regarding the effectiveness of molnupiravir against the B.1.1.529 (omicron) variant and in vaccinated populations are limited.Methods We obtained data for all members of Clalit Health Services, 40 years of age and older, eligible for molnupiravir therapy during the omicron surge. A Cox proportional-hazards regression model with time-dependent covariates was used to estimate the association between molnupiravir treatment and hospitalizations and deaths due to Covid-19, with adjustment for sociodemographic factors, coexisting conditions, and prior Covid-19 immunity status.Results A total of 19,868 participants met the eligibility criteria, of whom 1,069 (5%) received molnupiravir during the study period. In patients 65 years and above, the rate of hospitalizations related to Covid-19 in treated compared to untreated patients was 74.6 versus 127.6 per 100,000 person-days; adjusted hazard ratio (HR) 0.55 (95% CI, 0.34 to 0.88). The adjusted HR for death due to Covid-19 was 0.26 (95% CI, 0.10 to 0.73). Among patients aged 40 to 64, the hospitalizations rate in treated compared to untreated patients was 125.8 versus 49.1 per 100,000 person-days; adjusted HR 1.80 (95% CI, 0.86 to 3.77). The adjusted HR for death was 12.8 (95% CI, 3.41 to 48.2).Conclusions In a cohort of non-hospitalized, omicron-infected high-risk patients, molnupiravir therapy was associated with a significant reduction in hospitalizations and mortality due to Covid-19 in patients 65 years and above. However, no evidence of benefit was found in younger adults.
Subject(s)
COVID-19ABSTRACT
Background Nirmatrelvir, an inhibitor of the main protease of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has demonstrated a significant decrease in the risk of progression to severe disease in symptomatic high-risk patients infected with the B.1.617.2 (delta) variant of SARS-CoV-2. The effectiveness of nirmatrelvir against the B.1.1.529 variant (omicron) is unknown.Methods The study included all Clalit Health Services members, 40 years of age and older, with confirmed infection of SARS-CoV-2 during the omicron surge that were defined as high-risk for severe disease. A Cox proportional-hazards regression model with time-dependent covariates was used to estimate the association between nirmatrelvir treatment and hospitalizations and deaths due to Covid-19, with adjustment for individual sociodemographic factors, coexisting conditions, and prior Covid-19 immunity status.Results 109,213 participants were eligible for nirmatrelvir therapy during the two-month study period. Among the 42,819 eligible patients aged 65 years and above, 2,504 were treated with nirmatrelvir. Hospitalizations due to Covid-19 occurred in 14 out of the treated and 762 of the untreated patients: adjusted HR 0.33 (95% CI, 0.19 to 0.55). Death due to Covid-19 occurred in 2 treated and 151 untreated patients; adjusted HR: 0.19 (95% CI, 0.05 to 0.76). Among the 66,394 eligible patients 40 to 64 years of age, 1,435 were treated with nirmatrelvir. Hospitalizations due to Covid-19 occurred in 9 treated and 334 untreated patients: adjusted HR 0.78 (95% CI, 0.40 to 1.53). Death due to Covid-19 occurred in 1 treated and 13 untreated patients; adjusted HR: 1.64 (95% CI, 0.40 to 12.95).Conclusions Nirmatrelvir therapy was associated with a 67% reduction in Covid-19 hospitalizations and an 81% reduction in Covid-19 mortality in patients 65 years and above. However, no significant benefit in avoidance of severe Covid-19 outcomes was shown in younger adults.
Subject(s)
COVID-19ABSTRACT
The rapid emergence of the B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus-2 led to a global resurgence of coronavirus disease 2019 (Covid-19). Israeli authorities approved a 4th Covid-19 vaccine dose (second-booster) for individuals aged 60 and above who received a first booster dose four or more months earlier. Evidence regarding the effectiveness of a second-booster dose in reducing mortality due to Covid-19 is warranted. This retrospective cohort study included all members of Clalit Health Services, aged 60 to 100, eligible for the second-booster. Mortality due to Covid-19 among participants who received the second-booster was compared with participants who received one booster dose. A Cox proportional-hazards regression model with time-dependent covariates was used to estimate the association between the second-booster and death due to Covid-19 while adjusting for demographic factors and coexisting illnesses. A total of 563,465 participants met the eligibility criteria. Of those, 328,597 (58%) received a second-booster dose during the 40-day study period. Death due to Covid-19 occurred in 92 second-booster recipients and in 232 participants who received one booster dose (adjusted hazard ratio 0.22; 95% confidence interval 0.17 to 0.28). This study demonstrates a substantial reduction in Covid-19 mortality by the second-booster in eligible subjects.
Subject(s)
COVID-19ABSTRACT
Background: In December 2020, Israel began a mass vaccination program with the rapid rollout of the Pfizer-BioNTech COVID-19 BNT162b2 vaccine for adults in Israel. The campaign vaccinated fewer people than necessary for herd immunity. However, at the same time, government stringency measures in terms of closing public life were decreased. Real-world observational data were used to examine the effect of mass vaccination on Covid-19 mortality. Methods: The study period to examine the effect of vaccination on mortality was chosen to capture when at least 90% of the population over age 70 were vaccinated for less than seven months. Projected deaths as expected from vaccine efficacy and actual mortality data were compared for the study population with examination of potential confounding effects of government stringency. Average government stringency (Oxford Stringency Index) was calculated in the study period and the preceding period of the pandemic. Potential confounding effects of an age shift in the distribution of deaths were examined by analyzing the distributions of deaths and cases before and after the study period. Results: Confirmed deaths from COVID-19 in the population over 70 after mass vaccination were recorded as 370, versus 408 expected from applying person-days of vaccine efficacy, and 5,120 estimated without vaccinations. Conclusions: Vaccines against COVID-19 saved more lives than expected by simply applying individual vaccine efficacy to the vaccinated population in Israel, despite a loosening of government stringency.
Subject(s)
COVID-19ABSTRACT
Background In 2021 a new variant of SARS-CoV-2, which came to be called the alpha variant, spread around the world. There were conflicting reports on this COVID-19 variant strain’s potentially increased lethality. In Israel, this strain became predominant in a very short time period. Methods COVID-19 mortality and case fatality rates were examined in Israel in terms of weekly and cumulative numbers. Results COVID-19 case fatality rates in Israel rose quickly at the beginning of the pandemic and peaked in May 2020. The highest crude mortality came later in the second and third waves, but case the case fatality rates did not rise in 2021 with the increasing dominance of the alpha variant. Conclusions Based on the results of examining case-fatality and mortality rates, we concluded that while the alpha variant of the virus raised mortality, in line with the fact that it is more infectious than wild-type, once this strain was caught by patients in Israel, it was not more likely to kill them than the original strain