Evaluation of Telephone Visits in Primary Care: Satisfaction of Pediatricians and Family Physicians and Their Perceptions of Quality of Care and Safety.

Telehealth has accelerated since the outbreak of the COVID-19 virus. As telephone visits become more common, it is important to examine the challenges involved in using this modality of care. In this study, we examined family physicians' and pediatricians' perceptions regarding three aspects of the use of telephone visits: quality of care, safety of care, and physicians' satisfaction. A total of 342 family physicians and pediatricians responded to an online survey. Respondents were asked to rate their degree of agreement with 17 statements inquiring about quality, safety, and satisfaction with telephone visits on a Likert scale ranging from 1 (strongly disagree) to 5 (strongly agree). This was followed by in-depth interviews between January and April 2023 with 26 physicians. Participants expressed satisfaction (3.66 ± 0.80) with the use of telephone visits and lower assessments of safety (3.03 ± 0.76) and quality (2.27 ± 0.76) of care using the telephone modality. Eighty percent of the respondents think combining a face-to-face visit with a telephone visit is recommended, and 51% noted that the inability to examine patients closely affects and impedes a physician's decision making. Most interviewees indicated that telephone visits are safe only with former patients they had already seen in the clinic. The findings shed light on the perceptions of family physicians and pediatricians regarding telephone visits. The lower assessments of quality and safety compared to the assessment of satisfaction underscore the need for careful use of telephone visits in healthcare. A proper and balanced selection of patients, implementing technological upgrades to the modality, and performing patient education practices are recommended.

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.

Examining the Patterns of Mpox Vaccine Uptake in a Vulnerable Population.

BACKGROUND: The current Mpox outbreak presents unique vaccination challenges in vulnerable populations. Understanding factors associated with vaccine uptake in vulnerable populations is required for a successful vaccination campaign. METHODS: This population-based cohort study was conducted in Clalit Health Services and included all individuals eligible for the Modified Vaccinia Ankara vaccine. Cox proportional hazards models were used to assess the characteristics associated with uptake of the first vaccine dose. RESULTS: Attendance to a primary healthcare clinic in the Tel Aviv district, repeated sexually transmitted infection screening, and the recent purchase of HIV-PrEP or PDE5 inhibitors were associated with higher vaccine adherence, whereas previous nonadherence with recommended vaccines, low sociodemographic status, and history of HIV were associated with lower adherence. CONCLUSIONS: These findings highlight the need for proactive patient and healthcare provider-oriented educational campaigns to curb vaccine hesitancy, and may help direct resources toward underserved populations, hence increasing equality in vaccine enrollment.

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.

Real-world effectiveness of a single dose of mpox vaccine in males.

The recent global outbreak of the monkeypox (mpox) virus in humans was declared a public health emergency by the World Health Organization in July 2022. The smallpox and mpox vaccine (JYNNEOS; Modified Vaccinia Ankara-Bavarian Nordic; MVA-BN), provided as a two-dose regimen, is currently the primary vaccine utilized against mpox. However, the efficacy of MVA-BN against mpox has never been demonstrated in clinical trials to date. Due to the limited supply of vaccines, the World Health Organization has recommended prioritizing the vaccination of high-risk groups. We evaluated the real-world effectiveness of a single, subcutaneous dose of MVA-BN in this observational, retrospective cohort study, which included the analysis of electronic health records of all members of Clalit Health Services eligible for the vaccine on 31 July 2022. We used a Cox proportional hazards regression model with time-dependent covariates to estimate the association between vaccination and mpox while adjusting for sociodemographic and clinical risk factors. In an analysis of 2,054 male individuals who met vaccine eligibility criteria, 1,037 (50%) were vaccinated during the study recruitment period and completed at least 90 d of follow-up. During the study period, 5 and 16 infections were confirmed in vaccinated and unvaccinated individuals, respectively. The adjusted vaccine effectiveness was estimated at 86% (95% confidence interval, 59-95%). Our results suggest that a single dose of subcutaneous MVA-BN in this high-risk cohort is associated with a significantly lower risk of MPXV infection.

Effectiveness of the BNT162b2 mRNA COVID-19 vaccine among adolescents with juvenile-onset inflammatory rheumatic diseases.

OBJECTIVES: The effectiveness of the BNT162b2 mRNA COVID-19 vaccine for adolescents with juvenile-onset inflammatory or immune rheumatic diseases (IRDs) is unknown. Several studies have suggested attenuated immunogenicity in patients with IRD. This study evaluated the effectiveness of the BNT162b2 mRNA COVID-19 vaccine in preventing COVID-19 infection in adolescents with juvenile-onset IRD compared with controls without immune rheumatic disease. METHODS: We used data from Clalit Health Services, the largest health-care organization in Israel, to conduct an observational cohort study from February to December 2021, involving 12-18 year-old adolescents diagnosed with IRD. Study outcomes included documented COVID-19 infection in relation to vaccination status and immunomodulatory therapy. We estimated vaccine effectiveness as one minus the risk ratio. Adolescents aged 12-18 years without immune rheumatic disease served as controls. RESULTS: A total of 1639 adolescents with IRD (juvenile idiopathic arthritis, SLE, or familial Mediterranean fever) were included and compared with 524 471 adolescents in the same age range without IRD. There was no difference in COVID-19 infection rates after the second dose of vaccine between those with IRD and controls (2.1% vs 2.1% respectively, P = 0.99). The estimated vaccine effectiveness for adolescents with IRD was 76.3% after the first dose, 94.8% after the second and 99.2% after the third dose. CONCLUSION: We found that the BNT162b2 mRNA vaccine was similarly effective against COVID-19 infection in adolescents with and without IRD. Immunomodulatory therapy did not affect its effectiveness. These results can encourage adolescents with IRD to get vaccinated against COVID-19.

Effectiveness of REGEN-COV antibody combination in preventing severe COVID-19 outcomes.

REGEN-COV, a combination of the monoclonal antibodies casirivimab and imdevimab, has been approved as a treatment for high-risk patients infected with SARS-CoV-2 within five days of their diagnosis. We performed a retrospective cohort study, and used data repositories of Israel's largest healthcare organization to determine the real-world effectiveness of REGEN-COV treatment against COVID-19-related hospitalization, severe disease, and death. We compared patients infected with Delta variant and treated with REGEN-COV (n = 289) to those infected but not-treated with REGEN-COV (n = 1,296). Demographic and clinical characteristics were used to match patients and for further adjustment as part of the C0x model. Estimated treatment effectiveness was defined as one minus the hazard ratio. Treatment effectiveness of REGEN-COV was 56.4% (95% CI: 23.7-75.1%) in preventing COVID-19 hospitalization, 59.2% (95% CI: 19.9-79.2%) in preventing severe COVID-19, and 93.5% (95% CI: 52.1-99.1%) in preventing COVID-19 death in the 28 days after treatment. In conclusion, REGEN-COV was effective in reducing the risk of severe sequelae in high-risk COVID-19 patients.

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.

BNT162b2 Vaccine Effectiveness against Omicron in Children 5 to 11 Years of Age.

BACKGROUND: Limited evidence is available on the real-world effectiveness of the BNT162b2 vaccine against coronavirus disease 2019 (Covid-19) and specifically against infection with the omicron variant among children 5 to 11 years of age. METHODS: Using data from the largest health care organization in Israel, we identified a cohort of children 5 to 11 years of age who were vaccinated on or after November 23, 2021, and matched them with unvaccinated controls to estimate the vaccine effectiveness of BNT162b2 among newly vaccinated children during the omicron wave. Vaccine effectiveness against documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and symptomatic Covid-19 was estimated after the first and second vaccine doses. The cumulative incidence of each outcome in the two study groups through January 7, 2022, was estimated with the use of the Kaplan-Meier estimator, and vaccine effectiveness was calculated as 1 minus the risk ratio. Vaccine effectiveness was also estimated in age subgroups. RESULTS: Among 136,127 eligible children who had been vaccinated during the study period, 94,728 were matched with unvaccinated controls. The estimated vaccine effectiveness against documented infection was 17% (95% confidence interval [CI], 7 to 25) at 14 to 27 days after the first dose and 51% (95% CI, 39 to 61) at 7 to 21 days after the second dose. The absolute risk difference between the study groups at days 7 to 21 after the second dose was 1905 events per 100,000 persons (95% CI, 1294 to 2440) for documented infection and 599 events per 100,000 persons (95% CI, 296 to 897) for symptomatic Covid-19. The estimated vaccine effectiveness against symptomatic Covid-19 was 18% (95% CI, -2 to 34) at 14 to 27 days after the first dose and 48% (95% CI, 29 to 63) at 7 to 21 days after the second dose. We observed a trend toward higher vaccine effectiveness in the youngest age group (5 or 6 years of age) than in the oldest age group (10 or 11 years of age). CONCLUSIONS: Our findings suggest that as omicron was becoming the dominant variant, two doses of the BNT162b2 messenger RNA vaccine provided moderate protection against documented SARS-CoV-2 infection and symptomatic Covid-19 in children 5 to 11 years of age. (Funded by the European Union through the VERDI project and others.).

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.

Shared trust of resident physicians in top-management and professional burnout: A cross-sectional study towards capacity for patient-focussed care, peer support and job expectations.

RATIONAL: Hospitals desire to achieve the strategy of patient-centred care but burnout inhibits its implementation. Management has a role in responding to needs of patients, junior professional staff, and the hospital, in the present and future. AIM: To test the association between shared organisational trust (OT) of resident physicians in top-management, a systemic organisational process, and professional burnout among residents. METHODS: Participants in this cross-sectional study, are 316 residents assigned to 31 internal medicine departments at eight out of 15 academic Israeli general public hospitals in various locations and sizes. All measures were published: Burnout, patient-focussed care, shared trust in top-management, and antecedents of organisational trust, which are: peer support, clinical autonomy, meeting expectations, and value congruence. Structural Equation Modelling was performed. RESULTS: The structural equation modelling model was recursive, explaining 14% of the variance in burnout. Shared trust in top-management was the strongest antecedent of burnout. The facilitation of patient-focussed care created shared trust in top-management which reduced burnout. DISCUSSION: To achieve patient-centred care, management is called upon to reduce burnout by aligning organisational processes with patient-focussed care. Shared trust in top-management may reduce burnout and enhance residents' sense of meaningfulness, engagement, and well-being.

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.

Community antibiotic prescriptions during COVID-19 era: a population-based cohort study among adults.

OBJECTIVES: This study investigated the association between the COVID-19 pandemic and antibiotic prescription ratios and the determinants of antibiotic prescription in the community. METHODS: The study was based on a retrospective population cohort of adults in a community setting. Antibiotic prescription ratios from March 1, 2020 to February 28, 2021 (COVID-19 period) were compared to similar months in previous years. Differences in visit type, infectious disease-related visit, and antibiotic prescription ratios during these visits were compared. A logistic regression model was used to identify independent determinants of antibiotic prescription during the study period. RESULTS: The cohort included almost 3 million individuals with more than 33 million community medical encounters per year. In the COVID-19 period, the antibiotic prescription ratio decreased 45% (from 34.2 prescriptions/100 patients to 19.1/100) compared to the previous year. Visits due to an infectious disease etiology decreased by 10% and prescriptions per visit decreased by 39% (from 1 034 425 prescriptions/3 764 235 infectious disease visits to 587 379/3 426 451 respectively). This decrease was observed in both sexes and all age groups. Telemedicine visits were characterized by a 10% lower prescription ratio compared to in-person visits. Thus, a threefold increase in telemedicine visits resulted in a further decrease in prescription ratios. The COVID-19 period was independently associated with a decrease in antibiotic prescription, with an OR of 0.852 (95% CI 0.848-0.857). DISCUSSION: We describe a significant decrease in antibiotic prescription ratios during the COVID-19 periods that was likely related to a decrease in the incidence of certain infectious diseases, the transfer to telemedicine, and a change in prescription practices among community-based physicians.

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.

BNT162b2 Vaccine Booster and Mortality Due to Covid-19.

BACKGROUND: The emergence of the B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 and the reduced effectiveness over time of the BNT162b2 vaccine (Pfizer-BioNTech) led to a resurgence of coronavirus disease 2019 (Covid-19) cases in populations that had been vaccinated early. On July 30, 2021, the Israeli Ministry of Health approved the use of a third dose of BNT162b2 (booster) to cope with this resurgence. Evidence regarding the effectiveness of the booster in lowering mortality due to Covid-19 is still needed. METHODS: We obtained data for all members of Clalit Health Services who were 50 years of age or older at the start of the study and had received two doses of BNT162b2 at least 5 months earlier. The mortality due to Covid-19 among participants who received the booster during the study period (booster group) was compared with that among participants who did not receive the booster (nonbooster group). A Cox proportional-hazards regression model with time-dependent covariates was used to estimate the association of booster status with death due to Covid-19, with adjustment for sociodemographic factors and coexisting conditions. RESULTS: A total of 843,208 participants met the eligibility criteria, of whom 758,118 (90%) received the booster during the 54-day study period. Death due to Covid-19 occurred in 65 participants in the booster group (0.16 per 100,000 persons per day) and in 137 participants in the nonbooster group (2.98 per 100,000 persons per day). The adjusted hazard ratio for death due to Covid-19 in the booster group, as compared with the nonbooster group, was 0.10 (95% confidence interval, 0.07 to 0.14; P<0.001). CONCLUSIONS: Participants who received a booster at least 5 months after a second dose of BNT162b2 had 90% lower mortality due to Covid-19 than participants who did not receive a booster.

Safety of the BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting.

BACKGROUND: Preapproval trials showed that messenger RNA (mRNA)-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had a good safety profile, yet these trials were subject to size and patient-mix limitations. An evaluation of the safety of the BNT162b2 mRNA vaccine with respect to a broad range of potential adverse events is needed. METHODS: We used data from the largest health care organization in Israel to evaluate the safety of the BNT162b2 mRNA vaccine. For each potential adverse event, in a population of persons with no previous diagnosis of that event, we individually matched vaccinated persons to unvaccinated persons according to sociodemographic and clinical variables. Risk ratios and risk differences at 42 days after vaccination were derived with the use of the Kaplan-Meier estimator. To place these results in context, we performed a similar analysis involving SARS-CoV-2-infected persons matched to uninfected persons. The same adverse events were studied in the vaccination and SARS-CoV-2 infection analyses. RESULTS: In the vaccination analysis, the vaccinated and control groups each included a mean of 884,828 persons. Vaccination was most strongly associated with an elevated risk of myocarditis (risk ratio, 3.24; 95% confidence interval [CI], 1.55 to 12.44; risk difference, 2.7 events per 100,000 persons; 95% CI, 1.0 to 4.6), lymphadenopathy (risk ratio, 2.43; 95% CI, 2.05 to 2.78; risk difference, 78.4 events per 100,000 persons; 95% CI, 64.1 to 89.3), appendicitis (risk ratio, 1.40; 95% CI, 1.02 to 2.01; risk difference, 5.0 events per 100,000 persons; 95% CI, 0.3 to 9.9), and herpes zoster infection (risk ratio, 1.43; 95% CI, 1.20 to 1.73; risk difference, 15.8 events per 100,000 persons; 95% CI, 8.2 to 24.2). SARS-CoV-2 infection was associated with a substantially increased risk of myocarditis (risk ratio, 18.28; 95% CI, 3.95 to 25.12; risk difference, 11.0 events per 100,000 persons; 95% CI, 5.6 to 15.8) and of additional serious adverse events, including pericarditis, arrhythmia, deep-vein thrombosis, pulmonary embolism, myocardial infarction, intracranial hemorrhage, and thrombocytopenia. CONCLUSIONS: In this study in a nationwide mass vaccination setting, the BNT162b2 vaccine was not associated with an elevated risk of most of the adverse events examined. The vaccine was associated with an excess risk of myocarditis (1 to 5 events per 100,000 persons). The risk of this potentially serious adverse event and of many other serious adverse events was substantially increased after SARS-CoV-2 infection. (Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.).

Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2-mRNA-vaccinated individuals.

The BNT162b2 mRNA vaccine is highly effective against SARS-CoV-2. However, apprehension exists that variants of concern (VOCs) may evade vaccine protection, due to evidence of reduced neutralization of the VOCs B.1.1.7 and B.1.351 by vaccine sera in laboratory assays. We performed a matched cohort study to examine the distribution of VOCs in infections of BNT162b2 mRNA vaccinees from Clalit Health Services (Israel) using viral genomic sequencing, and hypothesized that if vaccine effectiveness against a VOC is reduced, its proportion among breakthrough cases would be higher than in unvaccinated controls. Analyzing 813 viral genome sequences from nasopharyngeal swabs, we showed that vaccinees who tested positive at least 7 days after the second dose were disproportionally infected with B.1.351, compared with controls. Those who tested positive between 2 weeks after the first dose and 6 days after the second dose were disproportionally infected by B.1.1.7. These findings suggest reduced vaccine effectiveness against both VOCs within particular time windows. Our results emphasize the importance of rigorously tracking viral variants, and of increasing vaccination to prevent the spread of VOCs.