Safety of monovalent and bivalent BNT162b2 mRNA COVID-19 vaccine boosters in at-risk populations in Israel: a large-scale, retrospective, self-controlled case series study.

BACKGROUND: COVID-19 continues to be a major health threat, particularly among at-risk groups, including individuals aged 60 years or older and people with particular medical conditions. Nevertheless, the absence of sufficient vaccine safety information is one of the key contributors to vaccine refusal. We aimed to assess the short-term safety profile of the BNT162b2 mRNA COVID-19 vaccine booster doses. METHODS: In this self-controlled case series study, we used a database of members of the largest health-care organisation in Israel. We analysed the medical records of individuals at risk of COVID-19 complications who had received two doses of the monovalent BNT162b2 mRNA COVID-19 vaccine (tozinameran, Pfizer-BioNTech) as their primary course of vaccination and then also received BNT162b2 mRNA COVID-19 vaccine boosters between July 30, 2021, and Nov 28, 2022, as a monovalent first or second booster, or as a bivalent first, second, or third booster, or a combination of these. We included individuals who had active membership of the health-care organisation and who were alive (excluding COVID-19 deaths) throughout the entire study period. We excluded individuals who, during the study period, were either not active Clalit Health Services members or died of non-COVID-19 causes, and those who were infected with COVID-19 during the 7-day period after vaccination. Individuals' at-risk status was assessed on the day before the baseline period started. The primary outcome was non-COVID-19 hospitalisation for 29 adverse events that might be associated with vaccination. For each adverse event, we compared the risk difference of hospitalisation during a 28-day pre-vaccination baseline period versus during a 28-day post-vaccination period, using a non-parametric percentile bootstrap method. FINDINGS: Of the 3 574 243 members of the health-care organisation, 1 073 110 received a first monovalent booster, 394 251 received a second monovalent booster, and 123 084 received a bivalent first, second, or third booster. Overall, we found no indication of an elevated risk of non-COVID-19 hospitalisation following administration of any of the booster vaccines (risk difference in events per 100 000 individuals: first monovalent booster -37·1 [95% CI -49·8 to -24·2]; second monovalent booster -37·8 [-62·2 to -13·2]; and bivalent booster -18·7 [-53·6 to 15·4]). Except for extremely rare elevated risks after the first monovalent booster-of myocarditis (risk difference 0·7 events per 100 000 individuals [95% CI 0·3-1·3]), seizures (2·2 [0·4-4·1]), and thrombocytopenia (2·6 [0·7-4·7])-we found no safety signals in other adverse events, including ischaemic stroke. INTERPRETATION: This study provides the necessary vaccine safety assurances for at-risk populations to receive timed roll-out booster vaccinations. These assurances could reduce vaccine hesitancy and increase the number of at-risk individuals who opt to become vaccinated, and thereby prevent the severe outcomes associated with COVID-19. FUNDING: Israel Science Foundation and Israel Precision Medicine Partnership programme.

Risk assessment of human mpox infections: retrospective cohort study.

OBJECTIVES: The global supply of vaccines against mpox (previously called monkeypox virus infection) was significantly lower than the demand. Therefore, evidence-based vaccine prioritization criteria, based on risk assessment were needed. Our objective was therefore to identify the characteristics of individuals at the highest risk for mpox. METHODS: This population-based cohort study included all Clalit Health Services (CHS) subjects assumed to be at risk for mpox. The eligibility criteria for inclusion were determined based on known characteristics of people with infection worldwide and insights of lesbian, gay, bisexual, transgender, queer+ (LGBTQ+) -specialized CHS clinicians. Cox hazards models were used to identify the risk factors for mpox within the study cohort. The study commenced on 6 June 2022, the date of the first known mpox in CHS members, until 31 July 2022, when the mpox vaccination campaign started. RESULTS: A total of 8088 individuals of 4.7 million CHS members (0.18%) were identified according to the study inclusion criteria. Of those, 69 (0.85%) developed infection during the study period. Risk factors for mpox were birth in 1980 or later (hazard ratio, 5.04; 95% CI, 2.11-12.02), history of syphilis (2.62; 1.58-4.35), registration to primary healthcare clinics in the Tel Aviv district (2.82; 1.44-5.54), HIV-pre-exposure prophylaxis medication use (3.96; 2.14-7.31), PDE5 inhibitors use (2.92; 1.77-4.84), and recent sexually transmitted infections (STIs) within the last 18 months (2.27; 1.35-3.82). No infections were observed in individuals with none of the factors. Individuals with three or more risk factors had a 20.30-fold (10.39-39.69) higher risk for mpox compared with those with 0-2, with 85.5% (75.0-92.8%) sensitivity and 77.8% (76.9-78.7%) specificity. DISCUSSION: Weighting individuals' risk levels based on validated risk factors against vaccine availability can assist health systems in the equitable prioritization of vaccine allocation in various future outbreaks, given supply-demand gaps.

Effectiveness of a bivalent mRNA vaccine booster dose to prevent severe COVID-19 outcomes: a retrospective cohort study.

BACKGROUND: In late 2022, the SARS-CoV-2 omicron (B.1.1.529) BA.5 sublineage accounted for most of the sequenced viral genomes worldwide. Bivalent mRNA vaccines contain an ancestral SARS-CoV-2 strain component plus an updated component of the omicron BA.4 and BA.5 sublineages. Since September, 2022, a single bivalent mRNA vaccine booster dose has been recommended for adults who have completed a primary SARS-CoV-2 vaccination series and are at high risk of severe COVID-19. We aimed to evaluate the effectiveness of a bivalent mRNA vaccine booster dose to reduce hospitalisations and deaths due to COVID-19. METHODS: We did a retrospective, population-based, cohort study in Israel, using data from electronic medical records in Clalit Health Services (CHS). We included all members of CHS who were aged 65 years or older and eligible for a bivalent mRNA COVID-19 booster vaccination. We used hospital records to identify COVID-19-related hospitalisations and deaths. The primary endpoint was hospitalisation due to COVID-19, which we compared between participants who received a bivalent mRNA booster vaccination and those who did not. A Cox proportional hazards regression model with time-dependent covariates was used to estimate the association between the bivalent vaccine and hospitalisation due to COVID-19 while adjusting for demographic factors and coexisting illnesses. FINDINGS: Between Sept 27, 2022, and Jan 25, 2023, 569 519 eligible participants were identified. Of those, 134 215 (24%) participants received a bivalent mRNA booster vaccination during the study period. Hospitalisation due to COVID-19 occurred in 32 participants who received a bivalent mRNA booster vaccination and 541 who did not receive a bivalent booster vaccination (adjusted hazard ratio 0·28, 95% CI 0·19-0·40). The absolute risk reduction for hospitalisations due to COVID-19 in bivalent mRNA booster recipients versus non-recipients was 0·089% (95% CI 0·075-0·101), and the number needed to vaccinate to prevent one hospitalisation due to COVID-19 was 1118 people (95% CI 993-1341). INTERPRETATION: Participants who received a bivalent mRNA booster vaccine dose had lower rates of hospitalisation due to COVID-19 than participants who did not receive a bivalent booster vaccination, for up to 120 days after vaccination. These findings highlight the importance of bivalent mRNA booster vaccination in populations at high risk of severe COVID-19. Further studies with longer observation times are warranted. FUNDING: None.

Effectiveness of a second BNT162b2 booster vaccine against hospitalization and death from COVID-19 in adults aged over 60 years.

The rapid emergence of the B.1.1.529 (Omicron) variant of SARS-CoV-2 led to a global resurgence of coronavirus disease 2019 (COVID-19). Israeli authorities approved a fourth COVID-19 vaccine dose (second booster) for individuals aged 60 years and over who had received a first booster dose 4 or more months earlier. Evidence for the effectiveness of a second booster dose in reducing hospitalizations and mortality due to COVID-19 is warranted. This retrospective cohort study included all members of Clalit Health Services who were aged 60-100 years and who were eligible for the second booster on 3 January 2022. Hospitalizations and mortality due to COVID-19 in participants who received the second booster were compared with those for participants who received one booster dose. Cox proportional hazards regression models with time-dependent covariates were used to estimate the association between the second booster and hospitalization 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. Hospitalization due to COVID-19 occurred in 270 of the second-booster recipients and in 550 participants who received one booster dose (adjusted hazard ratio, 0.36; 95% confidence interval (CI): 0.31-0.43). 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% CI: 0.17-0.28). This study demonstrates a substantial reduction in hospitalizations and deaths due to COVID-19 conferred by a second booster in Israeli adults aged 60 years and over.

Effectiveness of the BNT162b2 Vaccine after Recovery from Covid-19.

BACKGROUND: The risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) decreases substantially among patients who have recovered from coronavirus disease 2019 (Covid-19). However, it is unknown how long protective immunity lasts. Current guidelines recommend vaccination of recovered patients even though data regarding vaccine effectiveness in such cases are still limited. METHODS: In this retrospective cohort study, we reviewed electronic medical records from a large health care organization in Israel to assess reinfection rates in patients who had recovered from SARS-CoV-2 infection before any vaccination against Covid-19. We compared reinfection rates among patients who had subsequently received the BNT162b2 vaccine (Pfizer-BioNTech) and those who had not been vaccinated between March 1 and November 26, 2021. We used a Cox proportional-hazards regression model with time-dependent covariates to estimate the association between vaccination and reinfection after adjustment for demographic factors and coexisting illnesses. Vaccine effectiveness was estimated as 1 minus the hazard ratio. In a secondary analysis, we evaluated the vaccine effectiveness of one dose as compared with two doses. RESULTS: A total of 149,032 patients who had recovered from SARS-CoV-2 infection met the eligibility criteria. Of these patients, 83,356 (56%) received subsequent vaccination during the 270-day study period. Reinfection occurred in 354 of the vaccinated patients (2.46 cases per 100,000 persons per day) and in 2168 of 65,676 unvaccinated patients (10.21 cases per 100,000 persons per day). Vaccine effectiveness was estimated at 82% (95% confidence interval [CI], 80 to 84) among patients who were 16 to 64 years of age and 60% (95% CI, 36 to 76) among those 65 years of age or older. No significant difference in vaccine effectiveness was found for one dose as compared with two doses. CONCLUSIONS: Among patients who had recovered from Covid-19, the receipt of at least one dose of the BNT162b2 vaccine was associated with a significantly lower risk of recurrent infection.