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. Leveraging the centralized computerized database of Maccabi Healthcare Services (MHS), we assessed the correlation between time-from-vaccine and incidence of breakthrough infection between June 1 and July 27, the date of analysis. After controlling for potential confounders as age and comorbidities, we found a significant 1.51 fold (95% CI, 1.38-1.66) increased risk for infection for early vaccinees compared to those vaccinated later that was similar across all ages groups. The increased risk reached 2.26- fold (95% CI, 1.80-3.01) when comparing those who were vaccinated in January to those vaccinated in April. This preliminary finding of vaccine waning as a factor of time from vaccince should prompt further investigations into long-term protection against different strains.
The effectiveness of the coronavirus disease 2019 (COVID-19) BNT162b2 vaccine in preventing disease and reducing viral loads of breakthrough infections (BTIs) has been decreasing, concomitantly with ...the rise of the Delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, it is unclear whether the observed decreased effectiveness of the vaccine in reducing viral loads is inherent to the Delta variant or is dependent on time from immunization. By analyzing viral loads of over 16,000 infections during the current, Delta-variant-dominated pandemic wave in Israel, we found that BTIs in recently fully vaccinated individuals have lower viral loads than infections in unvaccinated individuals. However, this effect starts to decline 2 months after vaccination and ultimately vanishes 6 months or longer after vaccination. Notably, we found that the effect of BNT162b2 on reducing BTI viral loads is restored after a booster dose. These results suggest that BNT162b2 might decrease the infectiousness of BTIs even with the Delta variant, and that, although this protective effect declines with time, it can be restored, at least temporarily, with a third, booster, vaccine dose.
The duration of protection of the third (booster) dose of the BioNTech/Pfizer BNT162b2 mRNA Coronavirus Disease 2019 vaccine has been the subject of recent investigations, as global discussions ...around the necessity and effectiveness of a fourth dose are already underway. By conducting a retrospective study implementing a test-negative case-control design, analyzing 546,924 PCR tests performed throughout January 2022 by 389,265 persons who received at least two doses, we find that the effectiveness in each month-since-vaccination decreases significantly. Compared to those vaccinated five months prior to the outcome period, on August 2021, relative protection against infection waned from 53.4% a month after vaccination to 16.5% three months after vaccination. These results suggest that there is a significant waning of vaccine effectiveness against the Omicron variant of the third dose of the BNT162b2 vaccine within a few months after administration. Additional information could assist to comprehensively estimate the effectiveness of the three-dose-strategy.
Abstract
Background
Coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines were shown to be highly efficacious in preventing the disease in randomized controlled trials; nonetheless, ...evidence on the real-world effectiveness of this vaccine is limited. Study objective was to evaluate the effectiveness of BNT162b2 vaccine in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19-related hospitalization and mortality.
Methods
This historical cohort study included members of a large health provider in Israel that were vaccinated with at least 1 dose of BNT162b2. The primary outcome was incidence rate of a SARS-CoV-2 infection confirmed with real-time polymerase chain reaction (rt-PCR), between 7 and 27 days after second dose (protection-period), as compared to days 1–7 after the first dose, where no protection by the vaccine is assumed (reference-period).
Results
Data of 1 178 597 individuals vaccinated with BNT162b2 were analyzed (mean age 47.7 years SD = 18.1, 48.4% males) of whom 872 454 (74.0%) reached the protection period. Overall, 4514 infections occurred during the reference period compared to 728 during the protection period, yielding a weighted mean daily incidence of 54.8 per 100 000 (95% confidence interval CI: 26.1–115.0 per 100 000) and 5.4 per 100 000 (95% CI: 3.5–8.4 per 100 000), respectively. The vaccine effectiveness in preventing infection was 90% (95% CI: 79%–95%) and 94% (95% CI: 88%–97%) against COVID-19. Among immunosuppressed patients, vaccine effectiveness against infection was 71% (95% CI: 37%–87%). The adjusted hazard ratios for hospitalization in those infected were 0.82 (95% CI: .36–1.88), 0.45 (95% CI: .23–.90), and 0.56 (95% CI: .36–.89) in the age groups 16–44, 45–64. and ≥75 years, respectively.
Conclusions
The effectiveness of the BNT162b2 vaccine is comparable to the one reported in the phase III clinical trial.
We assessed the effectiveness of the BNT162b2 coronavirus disease 2019 (COVID-19) vaccine among 1.2 million vaccinees. We found a 90% reduction in all confirmed infections and 94% in symptomatic cases starting from 7 days after the second dose. A lower effectiveness was found in immunocompromised elderly.
Abstract
Background
Waning of protection against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) conferred by 2 doses of the BNT162b2 vaccine begins shortly after ...inoculation and becomes substantial within 4 months. With that, the impact of prior infection on incident SARS-CoV-2 reinfection is unclear. Therefore, we examined the long-term protection of naturally acquired immunity (protection conferred by previous infection) compared to vaccine-induced immunity.
Methods
A retrospective observational study of 124 500 persons, compared 2 groups: (1) SARS-CoV-2-naive individuals who received a 2-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 vaccine, and (2) previously infected individuals who have not been vaccinated. Two multivariate logistic regression models were applied, evaluating four SARS-CoV-2-related outcomes—infection, symptomatic disease (coronavirus disease 2019 COVID-19), hospitalization, and death—between 1 June and 14 August 2021, when the Delta variant was dominant in Israel.
Results
SARS-CoV-2-naive vaccinees had a 13.06-fold (95% confidence interval CI, 8.08–21.11) increased risk for breakthrough infection with the Delta variant compared to unvaccinated-previously-infected individuals, when the first event (infection or vaccination) occurred during January and February of 2021. The increased risk was significant for symptomatic disease as well. When allowing the infection to occur at any time between March 2020 and February 2021, evidence of waning naturally acquired immunity was demonstrated, although SARS-CoV-2 naive vaccinees still had a 5.96-fold (95% CI: 4.85–7.33) increased risk for breakthrough infection and a 7.13-fold (95% CI: 5.51–9.21) increased risk for symptomatic disease.
Conclusions
Naturally acquired immunity confers stronger protection against infection and symptomatic disease caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 2-dose vaccine-indued immunity.
The first real-world analysis of naturally acquired immunity versus vaccine induced immunity against SARS-CoV-2. Our findings illustrate that naturally acquired immunity confers stronger protection against infection and symptomatic disease caused by SARS-CoV-2, compared to the BNT162b2 two-dose vaccine-induced immunity.
The BNT162b2 COVID-19 vaccine has been shown to reduce viral load of breakthrough infections (BTIs), an important factor affecting infectiousness. This viral-load protective effect has been waning ...with time post the second vaccine and later restored with a booster shot. It is currently unclear though for how long this regained effectiveness lasts. Analyzing Ct values of SARS-CoV-2 qRT-PCR tests of over 22,000 infections during a Delta-variant-dominant period in Israel, we find that this viral-load reduction effectiveness significantly declines within months post the booster dose. Adjusting for age, sex and calendric date, Ct values of RdRp gene initially increases by 2.7 CI: 2.3-3.0 relative to unvaccinated in the first month post the booster dose, yet then decays to a difference of 1.3 CI: 0.7-1.9 in the second month and becomes small and insignificant in the third to fourth months. The rate and magnitude of this post-booster decline in viral-load reduction effectiveness mirror those observed post the second vaccine. These results suggest rapid waning of the booster's effectiveness in reducing infectiousness, possibly affecting community-level spread of the virus.
The clinical course of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is largely determined by host factors, with a wide range of ...outcomes. Despite an extensive vaccination campaign and high rates of infection worldwide, the pandemic persists, adapting to overcome antiviral immunity acquired through prior exposure. The source of many such major adaptations is variants of concern (VOCs), novel SARS-CoV-2 variants produced by extraordinary evolutionary leaps whose origins remain mostly unknown. In this study, we tested the influence of factors on the evolutionary course of SARS-CoV-2. Electronic health records of individuals infected with SARS-CoV-2 were paired to viral whole-genome sequences to assess the effects of host clinical parameters and immunity on the intra-host evolution of SARS-CoV-2. We found slight, albeit significant, differences in SARS-CoV-2 intra-host diversity, which depended on host parameters such as vaccination status and smoking. Only one viral genome had significant alterations as a result of host parameters; it was found in an immunocompromised, chronically infected woman in her 70s. We highlight the unusual viral genome obtained from this woman, which had an accelerated mutational rate and an excess of rare mutations, including near-complete truncating of the accessory protein ORF3a. Our findings suggest that the evolutionary capacity of SARS-CoV-2 during acute infection is limited and mostly unaffected by host characteristics. Significant viral evolution is seemingly exclusive to a small subset of COVID-19 cases, which typically prolong infections in immunocompromised patients. In these rare cases, SARS-CoV-2 genomes accumulate many impactful and potentially adaptive mutations; however, the transmissibility of such viruses remains unclear.
Despite extensive technological advances in recent years, objective and continuous assessment of physiologic measures after vaccination is rarely performed. We conducted a prospective observational ...study to evaluate short-term self-reported and physiologic reactions to the booster BNT162b2 mRNA (Pfizer-BioNTech, https://www.pfizer.com) vaccine dose. A total of 1,609 participants were equipped with smartwatches and completed daily questionnaires through a dedicated mobile application. The extent of systemic reactions reported after the booster dose was similar to that of the second dose and considerably greater than that of the first dose. Analyses of objective heart rate and heart rate variability measures recorded by smartwatches further supported this finding. Subjective and objective reactions after the booster dose were more apparent in younger participants and in participants who did not have underlying medical conditions. Our findings further support the safety of the booster dose from subjective and objective perspectives and underscore the need for integrating wearables in clinical trials.
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