ABSTRACT
BackgroundOn July 30, 2021, a third (booster) dose of the Pfizer BNT162b2 vaccine was approved in Israel for individuals 60 years or older who had been fully vaccinated (i.e., received two doses) at least five months previously. Here, we estimate the reduction in relative risk for confirmed infection and severe COVID-19 provided by the booster dose. Methods1,144,690 individuals aged 60y and older who were eligible for a booster dose were followed between July 30 and August 22, 2021. We defined dynamic cohorts where individuals initially belong to the non-booster cohort, leave it when receiving the booster dose and join the booster cohort 12 days later. Rates of infection and severe COVID-19 outcomes per person-days at risk were compared between the cohorts using Poisson regression, adjusting for possible confounding factors. ResultsTwelve days or more after the booster dose we found an 11.4-fold (95% CI: [10.0, 12.9]) decrease in the relative risk of confirmed infection, and a >10-fold decrease in the relative risk of severe illness. Under a conservative sensitivity analysis, we find {approx}5-fold protection against confirmed infection. ConclusionsIn conjunction with safety reports, this study demonstrates the effectiveness of a third vaccine dose in both reducing transmission and severe disease and indicates the great potential of curtailing the Delta variant resurgence by administering booster shots.
ABSTRACT
The short-term effectiveness of a two-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine was widely demonstrated. However, long term effectiveness is still unknown. A nationwide vaccination campaign was initiated early in Israel, allowing for a real-world evaluation of the interaction between protection and time-from-vaccine. The Delta (B.1.617.2) variant became the dominant strain in Israel in June 2021, as Israel is currently experiencing a new surge of cases. Leveraging the centralized computerized database of Maccabi Healthcare Services (MHS), we assessed the correlation between time-from-vaccine and incidence of breakthrough infection. We found that the risk for infection was significantly higher for early vaccinees compared to those vaccinated later. This preliminary finding should prompt further investigagions into long-term protection against different strains, and prospective clinical trials to examine the effect of a booster vaccine against breakthrough infection.
ABSTRACT
ImportanceWhile the mRNA BNT162b2 vaccine effectivness was demonstrated in general population, the question of effectiveness given confirmed exposure has yet been answered, though it has policy implications, as the need for self-quarantine when exposed and protective measures for vaccinated in high-risk areas. ObjectiveAssessing the BNT162b2 vaccine effectiveness in preventing SARS-CoV-2 infection given high-risk exposure, through analysis of household members of confirmed cases. DesignRetrospective cohort study. Data of household members of confirmed SARS-CoV-2 cases between 20/12/2020 and 17/03/2021 were collected. SettingNationally centralized database of Maccabi Healthcare Services (MHS), the second largest Healthcare Maintenance Organization in Israel. Participants2.5 million MHS members were considered, of which we included only households with two adult members, given possible lower transmission and susceptibility among children. Households with no prior confirmed infections and a confirmed index case during the study period were included. ExposureParticipants were classified into three vaccination groups in time of the index case (the confirmed exposure)-Unvaccinated; Fully Vaccinated(7 or more days post second dose) and a reference control group of Recently Vaccinated Once(0-7 days from the first dose, presumably still unprotected). Main Outcomes and MeasuresAssessing the probability of an additional SARS-CoV-2 infection in the household occurring within 10 days of an index case, calculated separately for the three vaccination groups. Main outcome was vaccine effectiveness given confirmed exposure. High testing rates among household members enabled us to estimate with a high degree of confidence effectiveness against asymptomatic SARS-CoV-2 infection as well. ResultsA total of 173,569 households were included, out of which 6,351 households had an index infection (mean [SD] age, 58.9 [13.5] years; 50% were women). Vaccine effectiveness of Fully Vaccinated compared to Unvaccinated participants was 80.0% [95% CI, 73.0-85.1] and 82.0% [95% CI, 75.5-86.7] compared to those Recently Vaccinated Once. Conclusion and RelevanceThe BNT162b2 vaccine is effective in a high-risk, real life, exposure scenario, but the protection rates afforded in these settings are lower than those previously described. Household members of COVID-19 patients and any individual with a confirmed exposure to COVID-19 are still at a considerable risk of being infected even if fully vaccinated.
ABSTRACT
ObjectiveData regarding the clinical characteristics of COVID-19 infection is rapidly accumulating. However, most studies thus far are based on hospitalized patients and lack longitudinal follow up. As the majority of COVID-19 cases are not hospitalized, prospective studies of symptoms in the population presenting to primary care are needed. Here, we assess the longitudinal dynamic of clinical symptoms in non-hospitalized individuals prior to and throughout the diagnosis of SARS-CoV-2 infection. DesignData on symptoms were extracted from electronic health records (EHR) consisting of both results of PCR tests and symptoms recorded by primary care physicians, and linked longitudinal self reported symptoms. SettingThe second largest Health Maintenance Organization in Israel, Maccabi Health Services ParticipantsFrom 1/3/2020 to 07/06/2020, information on symptoms from either surveys or primary care visits was available for 206,377 individuals, including 2,471 who tested positive for COVID-19. Main OutcomesLongitudinal prevalence of clinical symptoms in COVID-19 infection diagnosed by PCR testing for SARS-CoV-2 from nasopharyngeal swabs. ResultsIn adults, the most prevalent symptoms recorded in EHR were cough (11.6%), fever (10.3%), and myalgia (7.7%) and the most prevalent self-reported symptoms were cough (21%), fatigue (19%) and rhinorrhea and/or nasal congestion (17%). In children, the most prevalent symptoms recorded in the EHR were fever (7%), cough (5.5%) and abdominal pain (2.4%). Emotional disturbances were documented in 15.9% of the positive adults and 4.2% of the children. Loss of taste and smell, either self-reported or documented by a physician, 3 weeks prior to testing, were the most discriminative symptoms in adults (OR =11.18 and OR=5.47 respectively). Additional symptoms included self reported headache (OR = 2.03) and fatigue (OR = 1.73) and a documentation of syncope, rhinorrhea (OR = 2.09 for both) and fever (OR= 1.62) by a physician. Mean time to recovery was 23.5 {+/-} 9.9 days. Children had a significantly shorter disease duration (21.7 {+/-} 8.8 days, p-value=0.01). Several symptoms, including fatigue, myalgia, runny nose and shortness of breath were reported weeks after recovery. ConclusionsAs the COVID-19 pandemic progresses rapidly worldwide, obtaining accurate information on symptoms and their progression is of essence. Our study shed light on the full clinical spectrum of symptoms experienced by infected individuals in primary care, and may alert physicians for the possibility of COVID-19 infection.
ABSTRACT
Reliably identifying patients at increased risk for COVID-19 complications could guide clinical decisions, public health policies, and preparedness efforts. To date, the most globally accepted definitions of at-risk patients rely, primarily, on epidemiological characterization of hospitalized COVID-19 patients. However, such characterization overlooks, and fails to correct for, the prevalence of existing conditions in the wider SARS-CoV-2 positive population. Here, we analyze the complete medical records of all SARS-CoV-2 infected individuals (N=4,353) in a large Israeli health organization (representing a population of 2.3 million people), of whom 173 experienced moderate or severe symptoms of COVID-19, to identify the conditions that increase the risk of disease complications, in various age and sex strata. Our analysis suggests that cardiovascular and kidney diseases, obesity, and hypertension are significant risk factors for COVID-19 complications, as previously reported. Interestingly, it also indicates that depression (e.g., odds ratio, OR, for males 65 years or older: 2.94, 95% confidence intervals [1.55, 5.58]; P-value = 0.014) as well cognitive and neurological disorder (e.g., OR for individuals [≥] 65 year old: 2.65 [1.69, 4.17]; P-value < 0.001) are significant risk factors; and that smoking and background of respiratory diseases do not significantly increase the risk of complications. Adjusting existing risk definitions following these observations may improve their accuracy and impact the global pandemic containment efforts.
