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ObjectivesThere are paucity of studies examining naturally acquired immunity against SARS-CoV-2 in children and adolescents, though they are generally the last group to be afforded the vaccine, and a significant portion of them are still unvaccinated. This study examined the duration of protection conferred by a previous SARS-CoV-2 infection amongst children and adolescents. DesignA retrospective study, applying two complementary approaches: a matched test-negative case control design and a retrospective cohort design. SettingNationally centralized database of Maccabi Healthcare Services, an Israeli national health fund that covers 2.5 million people. ParticipantsThe study population included between 293,743 and 458,959 individuals (depending on the model), 5-18 years of age, who were unvaccinated SARS-CoV-2 naive persons or unvaccinated convalescent patients. Main outcomes and measuresAnalyses focused on the period of July 1 to December 13, 2021, a Delta-dominant period in Israel. We evaluated three SARS-CoV-2-related outcomes: (1) documented PCR confirmed infection or reinfection, (2) COVID-19 and (3) severe COVID-19. ResultsOverall, children and adolescents who were previously infected acquired durable protection against reinfection (symptomatic or not) with SARS-CoV-2 for at least 18 months. Importantly, no COVID-19 related deaths were recorded in either the SARS-CoV-2 naive group or the previously infected group. Effectiveness of naturally-acquired immunity against a recurrent infection reached 89.2% (95% CI: 84.7%-92.4%) three to six months after first infection, mildly declining to 82.5% (95% CI, 79.1%-85.3%) nine months to one year after infection, then remaining rather steady for children and adolescents for up to 18 months, with a slight non-significant waning trend. Additionally, we found that ages 5-11 exhibited no significant waning of naturally acquired protection throughout the outcome period, whereas waning protection in the 12-18 age group was more prominent, but still mild. ConclusionsChildren and adolescents who were previously infected with SARS-CoV-2 remain protected against reinfection to a high degree for 18 months. Policy decision makers should consider when and if convalescent children and adolescents should be vaccinated. Nonetheless, further research is needed to examine naturally acquired immunity against emerging variants, including the Omicron.
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BackgroundReports of waning vaccine-induced immunity against COVID-19 have begun to surface. With that, the comparable long-term protection conferred by previous infection with SARS-CoV-2 remains unclear. MethodsWe conducted a retrospective observational study comparing three groups: (1)SARS-CoV-2-naive individuals who received a two-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 vaccine, (2)previously infected individuals who have not been vaccinated, and (3)previously infected and single dose vaccinated individuals. Three multivariate logistic regression models were applied. In all models we evaluated four outcomes: SARS-CoV-2 infection, symptomatic disease, COVID-19-related hospitalization and death. The follow-up period of June 1 to August 14, 2021, when the Delta variant was dominant in Israel. ResultsSARS-CoV-2-naive vaccinees had a 13.06-fold (95% CI, 8.08 to 21.11) increased risk for breakthrough infection with the Delta variant compared to those previously infected, when the first event (infection or vaccination) occurred during January and February of 2021. The increased risk was significant (P<0.001) for symptomatic disease as well. When allowing the infection to occur at any time before vaccination (from March 2020 to February 2021), evidence of waning natural immunity was demonstrated, though SARS-CoV-2 naive vaccinees had a 5.96-fold (95% CI, 4.85 to 7.33) increased risk for breakthrough infection and a 7.13-fold (95% CI, 5.51 to 9.21) increased risk for symptomatic disease. SARS-CoV-2-naive vaccinees were also at a greater risk for COVID-19-related-hospitalizations compared to those that were previously infected. ConclusionsThis study demonstrated that natural immunity confers longer lasting and stronger protection against infection, symptomatic disease and hospitalization caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 two-dose vaccine-induced immunity. Individuals who were both previously infected with SARS-CoV-2 and given a single dose of the vaccine gained additional protection against the Delta variant.
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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.
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Mass vaccination has the potential to curb the current COVID-19 pandemic by protecting vaccinees from the disease and possibly lowering the chance of transmission to unvaccinated individuals. The high effectiveness of the widely-administered BNT162b vaccine in preventing not only the disease but also infection suggests a potential for a population-level effect, critical for disease eradication. However, this putative effect is difficult to observe, especially in light of highly fluctuating spatio-temporal epidemic dynamics. Here, analyzing vaccination records and test results collected during a rapid vaccine rollout for a large population from 223 geographically defined communities, we find that the rates of vaccination in each community are highly correlated with a later decline in infections among a cohort of under 16 years old which are unvaccinated. These results provide observational evidence that vaccination not only protects individual vaccinees but also provides cross-protection to unvaccinated individuals in the community.
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Vaccinations are considered the major tool to curb the current SARS-CoV-2 pandemic. A randomized placebo-controlled trial of the BNT162b2 vaccine has demonstrated a 95% efficacy in preventing COVID-19 disease. These results are now corroborated with statistical analyses of real-world vaccination rollouts, but resolving vaccine effectiveness across demographic groups is challenging. Here, applying a multivariable logistic regression analysis approach to a large patient-level dataset, including SARS-CoV-2 tests, vaccine inoculations and personalized demographics, we model vaccine effectiveness at daily resolution and its interaction with sex, age and comorbidities. Vaccine effectiveness gradually increased post day 12 of inoculation, then plateaued, around 35 days, reaching 91.2% [CI 88.8%-93.1%] for all infections and 99.3% [CI 95.3%-99.9%] for symptomatic infections. Effectiveness was uniform for men and women yet declined mildly but significantly with age and for patients with specific chronic comorbidities, most notably type 2 diabetes. Quantifying real-world vaccine effectiveness, including both biological and behavioral effects, our analysis provides initial measurement of vaccine effectiveness across demographic groups.
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With more than 100 million confirmed COVID-19 cases as of March 2021, reinfection is still considered to be rare. In light of increasing reports of reinfected COVID-19 patients, the need to better understand the real risk for reinfection is critical, with potential effects on public health policies aimed at containing the spread of SARS-CoV-2. In this descriptive preliminary report, we conducted a large-scale assessment on the country level of the possible occurrence of COVID-19 reinfection within the members of a large healthcare provider in Israel. Out of 149,735 individuals with a documented positive PCR test between March 2020 and January 2021, 154 had two positive PCR tests at least 100 days apart, reflecting a reinfection proportion of 1 per 1000. Given our strict inclusion criteria, we believe these numbers represent true reinfection incidence in MHS and should be clinically regarded as such.
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Deployment of the BNT162b2 mRNA Covid-19 Vaccine in Israel began in December 2020. This is a retrospective analysis of serological data, describing SARS-CoV-2 anti-S IgG kinetics in 116 Israeli healthcare workers administrated the BNT162b2 vaccine. Seroconversion occurred by day 14 in all individuals, with IgG levels peaking approximately 30 days post inoculation. This study demonstrated the kinetics of the antibody response post vaccination with BNT162b2. The robustness of seroconversion was observed, alongside a statistically significant difference in IgG levels between employees over and younger 50 years of afge. Further research is required in order to examine the antibody kinetics overtime, as well as whether the age-dependent difference persists.
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Beyond their substantial protection of individual vaccinees, it is hoped that the COVID-19 vaccines would reduce viral load in breakthrough infections thereby further suppress onward transmission. Here, analyzing positive SARS-CoV-2 test results following inoculation with the BNT162b2 mRNA vaccine, we find that the viral load is reduced 4-fold for infections occurring 12-28 days after the first dose of vaccine. These reduced viral loads hint to lower infectiousness, further contributing to vaccine impact on virus spread.
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BackgroundBNT162b2 vaccines showed high efficacy against COVID-19 in a randomised controlled phase-III trial. A vaccine effectiveness evaluation in real life settings is urgently needed, especially given the global disease surge. Hence, we assessed the short-term effectiveness of the first dose of BNT162b2-vaccine against SARS-CoV-2 infection. Given the BNT162b2 Phase-III results, we hypothesized that the cumulative incidence of SARS-CoV-2 infection among vaccinees will decline after 12 days following immunization compared to the incidence during the preceding days. MethodsWe conducted a retrospective cohort study using data from 2{middle dot}6 million-member state-mandated health provider in Israel. Study population consisted of all members aged 16 or above years who were vaccinated with BNT162b2-vaccine between December/19/2020 and January/15/2021. We collected information regarding medical history and positive SARS-CoV-2 polymerase chain reaction test from days after first dose to January/17/2021. Daily and cumulative infection rates in days 13-24 were compared to days 1-12 after first dose using Kaplan-Meier survival analysis and generalized linear models. FindingsData of 503,875 individuals (mean age 59{middle dot}7 years SD=14{middle dot}7, 47{middle dot}8% males) were analysed, of whom 351,897 had 13-24 days of follow-up. The cumulative incidence of SARS-CoV-2 infection was 0{middle dot}57% (n=2484) during days 1-12 and 0{middle dot}27% (n=614) in days 13-24. A 51{middle dot}4% relative risk reduction (RRR) was calculated in weighted-average daily incidence of SARS-CoV-2 infection from 43{middle dot}41-per-100,000(SE=12{middle dot}07) in days 1-12 to 21{middle dot}08-per-100,000(SE=6{middle dot}16) in days 13-24 following immunization. The decrement in incidence was evident from day 18 after first dose. Similar RRRs were calculated in individuals aged 60 or above (44.5%), younger individuals (50.2%), females (50.0%) and males (52.1%). Findings were similar in sub-populations and patients with various comorbidities. ConclusionsWe demonstrated an effectiveness of 51% of BNT162b2 vaccine against SARS-CoV-2 infection 13-24 days after immunization with the first dose. Immunization with the second dose should be continued to attain the anticipated protection. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for follow-up studies regarding the effectiveness of BNT162b2 mRNA Covid-19 Vaccine without any language restrictions. The search terms were (BNT162b2 OR mRNA Covid-19 Vaccine) AND (effectiveness OR real-world OR phase IV) until Jan 15, 2021. We found no relevant observational studies among humans. We also assessed Phase II and Phase III clinical trials with BNT162b2 mRNA vaccine. Added value of this studyTo our knowledge, this is the first and largest phase IV study on the effectiveness of the BNT162b2 mRNA COVID-19 vaccine in real-world settings. Our findings showed that the first dose of the vaccine is associated with an approximately 51% reduction in the incidence of PCR-confirmed SARS-CoV-2 infections at 13 to 24 days after immunization compared to the rate during the first 12 days. Similar levels of effectiveness were found across age groups, sex, as well as among individuals residing in Arab or ultra-orthodox Jewish communities that display an increased COVID-19 risk. Implications of all the available evidenceThe study results indicate that in real life the first dose of the new BNT162b2 mRNA COVID-19 vaccine confers around 50% protection against overall SARS-CoV-2 infections (symptomatic or asymptomatic). Together our findings and the 95% efficacy shown in the phase III trial, suggest that the BNT162b2 vaccine should be administered in two doses to achieve maximum protection and impact in terms of disease burden reduction and possibly reducing SARS-CoV-2 transmission. COVID-19 vaccines should be urgently deployed globally.
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BackgroundRoutine testing for SARS-CoV-2 in the community is essential for guiding key epidemiological decisions from the quarantine of individual patients to enrolling regional and national preventive measures. Yet, the primary testing tool, the RT-qPCR based testing, is notoriously known for its low sensitivity, i.e. high risk of missed detection of carriers. Quantifying the false-negative rate (FNR) of the RT-qPCR test at the community settings and its dependence on patient demographic and disease progression is therefore key in designing and refining strategies for disease spread prevention. MethodsAnalyzing 843,917 test results of 521,696 patients, we identified false-negative (FN) and true-positive (TP) results as negative and positive results preceded by a COVID-19 diagnosis and followed by a later positive test. Regression analyses were used to determine associations of false-negative results with time of sampling after diagnosis, patient demographics and viral loads based on RT-qPCR Ct values of the next positive tests. FindingsThe overall FNR was 22.8%, which is consistent with previous studies. Yet, this rate was much lower at the first 5 days following diagnosis (10.7%) and only increased in later dates. Furthermore, the FNR was strongly associated with demographics, with odds ratio of 1.74 (95% CI: 1.58-1.90) for women over men and 1.36 (95% CI: 1.34-1.39) for 10 years younger patients. Finally, FNR was associated with viral loads (p-value 0.0005), with a difference of 1.50 (95% CI: 0.70-2.30) between the average Ct of the N gene in a positive test following a false-negative compared to a positive test following a true-positive. InterpretationOur results show that in the first few days following diagnosis, when results are critical for quarantine decisions, RT-qPCR testing is more reliable than previously reported. Yet the reliability of the test result is reduced in later days as well as for women and younger patients, where the viral loads are typically lower. FundingThis research was supported by the ISRAEL SCIENCE FOUNDATION (grant No. 3633/19) within the KillCorona - Curbing Coronavirus Research Program.