Background Despite the high efficacy of the BNT162b2 messenger RNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rare breakthrough infections have been repo...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa2109072

Covid-19 Breakthrough Infections in Vaccinated Health Care Workers.

Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: a retrospective cohort study.

Background On July 30, 2021, the administration of a third (booster) dose of the BNT162b2 messenger RNA vaccine (Pfizer-BioNTech) was approved in Israel for persons who were 60 years of age or older and who had received a second dose of vaccine at least 5 months earlier. Data are needed regarding the effect of the booster dose on the rate of confirmed coronavirus 2019 disease (Covid-19) and the rate of severe illness. Methods We extracted data for the period from July 30 through August 31, 2021, from the Israeli Ministry of Health database regarding 1,137,804 persons who were 60 years of age or older and had been fully vaccinated (i.e., had received two doses of BNT162b2) at least 5 months earlier. In the primary analysis, we compared the rate of confirmed Covid-19 and the rate of severe illness between those who had received a booster injection at least 12 days earlier (booster group) and those who had not received a booster injection (nonbooster group). In a secondary analysis, we evaluated the rate of infection 4 to 6 days after the booster dose as compared with the rate at least 12 days after the booster. In all the analyses, we used Poisson regression after adjusting for possible confounding factors. Results At least 12 days after the booster dose, the rate of confirmed infection was lower in the booster group than in the nonbooster group by a factor of 11.3 (95% confidence interval [CI], 10.4 to 12.3); the rate of severe illness was lower by a factor of 19.5 (95% CI, 12.9 to 29.5). In a secondary analysis, the rate of confirmed infection at least 12 days after vaccination was lower than the rate after 4 to 6 days by a factor of 5.4 (95% CI, 4.8 to 6.1). Conclusions In this study involving participants who were 60 years of age or older and had received two doses of the BNT162b2 vaccine at least 5 months earlier, we found that the rates of confirmed Covid-19 and severe illness were substantially lower among those who received a booster (third) dose of the BNT162b2 vaccine.

https://www.nejm.org/doi/pdf/10.1056/NEJMoa2114255

Protection of BNT162b2 Vaccine Booster against Covid-19 in Israel.

The global supply of COVID-19 vaccines remains limited. An understanding of the immune response that is predictive of protection could facilitate rapid licensure of new vaccines. Data from a randomized efficacy trial of the ChAdOx1 nCoV-19 (AZD1222) vaccine in the United Kingdom was analyzed to determine the antibody levels associated with protection against SARS-CoV-2. Binding and neutralizing antibodies at 28 days after the second dose were measured in infected and noninfected vaccine recipients. Higher levels of all immune markers were correlated with a reduced risk of symptomatic infection. A vaccine efficacy of 80% against symptomatic infection with majority Alpha (B.1.1.7) variant of SARS-CoV-2 was achieved with 264 (95% CI: 108, 806) binding antibody units (BAU)/ml: and 506 (95% CI: 135, not computed (beyond data range) (NC)) BAU/ml for anti-spike and anti-RBD antibodies, and 26 (95% CI: NC, NC) international unit (IU)/ml and 247 (95% CI: 101, NC) normalized neutralization titers (NF50) for pseudovirus and live-virus neutralization, respectively. Immune markers were not correlated with asymptomatic infections at the 5% significance level. These data can be used to bridge to new populations using validated assays, and allow extrapolation of efficacy estimates to new COVID-19 vaccines.

/pdf/correlates-of-protection-against-symptomatic-and-5e2gy4ojz1.pdf

Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection.

The past several months have witnessed the emergence of SARS-CoV-2 variants with novel spike protein mutations that are influencing the epidemiological and clinical aspects of the COVID-19 pandemic. These variants can increase rates of virus transmission and/or increase the risk of reinfection and reduce the protection afforded by neutralizing monoclonal antibodies and vaccination. These variants can therefore enable SARS-CoV-2 to continue its spread in the face of rising population immunity while maintaining or increasing its replication fitness. The identification of four rapidly expanding virus lineages since December 2020, designated variants of concern, has ushered in a new stage of the pandemic. The four variants of concern, the Alpha variant (originally identified in the UK), the Beta variant (originally identified in South Africa), the Gamma variant (originally identified in Brazil) and the Delta variant (originally identified in India), share several mutations with one another as well as with an increasing number of other recently identified SARS-CoV-2 variants. Collectively, these SARS-CoV-2 variants complicate the COVID-19 research agenda and necessitate additional avenues of laboratory, epidemiological and clinical research.

/pdf/the-biological-and-clinical-significance-of-emerging-sars-4cwn3ih835.pdf

The biological and clinical significance of emerging SARS-CoV-2 variants.

Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data.

Summary Background On Dec 20, 2020, Israel initiated a nationwide COVID-19 vaccination campaign for people aged 16 years and older and exclusively used the Pfizer–BioNTech BNT162b2 mRNA COVID-19 vaccine (tozinameran). We provide estimates of the number of SARS-CoV-2 infections and COVID-19-related admissions to hospital (ie, hospitalisations) and deaths averted by the nationwide vaccination campaign. Methods In this retrospective surveillance study, we used national surveillance data routinely collected by the Israeli Ministry of Health from the first 112 days (Dec 20, 2020, up to our data cutoff of April 10, 2021) of Israel's vaccination campaign to estimate the averted burden of four outcomes: SARS-CoV-2 infections and COVID-19-related hospitalisations, severe or critical hospitalisations, and deaths. As part of the campaign, all individuals aged 16 years and older were eligible for inoculation with the BNT162b2 vaccine in a two-dose schedule 21 days apart. We estimated the direct effects of the immunisation programme for all susceptible individuals (ie, with no previous evidence of laboratory-confirmed SARS-CoV-2 infection) who were at least partly vaccinated (at least one dose and at least 14 days of follow-up after the first dose). We estimated the number of SARS-CoV-2 infection-related outcomes averted on the basis of cumulative daily, age-specific rate differences, comparing rates among unvaccinated individuals with those of at least partly vaccinated individuals for each of the four outcomes and the (age-specific) size of the susceptible population and proportion that was at least partly vaccinated. Findings We estimated that Israel's vaccination campaign averted 158 665 (95% CI 144 640–172 690) SARS-CoV-2 infections, 24 597 (18 942–30 252) hospitalisations, 17 432 (12 770–22 094) severe or critical hospitalisations, and 5532 (3085–7982) deaths. 16 213 (65·9%) of 24 597 hospitalisations and 5035 (91·0%) of 5532 of deaths averted were estimated to be among those aged 65 years and older. We estimated 116 000 (73·1%) SARS-CoV-2 infections, 19 467 (79·1%) COVID-19-related hospitalisations, and 4351 (79%) deaths averted were accounted for by the fully vaccinated population. Interpretation Without the national vaccination campaign, Israel probably would have had triple the number of hospitalisations and deaths compared with what actually occurred during its largest wave of the pandemic to date, and the health-care system might have become overwhelmed. Indirect effects and long-term benefits of the programme, which could be substantial, were not included in these estimates and warrant future research. Funding Israel Ministry of Health and Pfizer.

Infections, hospitalisations, and deaths averted via a nationwide vaccination campaign using the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine in Israel: a retrospective surveillance study.

Background: Israel recently initiated a rapid nationwide COVID-19 vaccination campaign to immunize persons ≥16 years of age and used exclusively Pfizer–BioNTech BNT162b2 mRNA COVID-19 vaccine according to schedule (two doses, 21 days apart). We provide the first estimates of the number of COVID-19 cases, hospitalizations, and deaths averted by a nationwide vaccination campaign. 

Methods: We used national surveillance data from the first 112 days (Dec 20, 2020 ‒ Apr 10, 2021) of Israel’s vaccination campaign to estimate averted burden of four outcomes: SARS-CoV-2 infections and COVID-19-related hospitalizations, severe or critical hospitalizations, and deaths. The direct effects of the immunization program were estimated for all susceptible individuals (i.e., no previous evidence of laboratory-confirmed SARS-CoV-2 infection) who were at least partially vaccinated (defined as receipt of at least one dose with ≥14 days after the first dose). Cases averted were estimated based on cumulative daily, age-specific rate differences comparing rates among unvaccinated to those who were at least partially vaccinated for each of the four outcomes and the (age-specific) size of the susceptible population and proportion that was at least partially vaccinated. 

Findings: Through Apr 10, 2021, we estimated that Israel’s vaccination campaign averted 158,665 (95% uncertainty range: 115,899‒201,431) SARS-CoV-2 infections, 24,597 (6,622‒42,571) hospitalizations, 17,432 (3,065‒31,799) severe and critical hospitalizations, and 5,533 (-1,146‒12,213) deaths. Of these, 66% of hospitalizations and 91% of deaths averted were among those ≥65 years of age. Seventy-three percent of SARS-CoV-2 infections and 79% of COVID-19-related hospitalizations and deaths averted stemmed from the protective effects in fully vaccinated persons. 

Interpretations: Without vaccination, Israel would have likely experienced triple the number of hospitalizations and deaths compared to what actually occurred during their largest wave of SARS-CoV-2 to date, which would have likely overwhelmed the healthcare system. Indirect effects and long-term benefits of the program, which could be substantial, were not included in these estimates and warrant future research. 

Funding: None.

Declaration of Interest: John McLaughlin, Frederick Angulo, Farid Khan, Gabriel Mircus, Kaijie Pan, Jo Southern, David Swerdlow, and Luis Jodar hold stock and stock options in Pfizer Inc. Marc Lipsitch has provided advice on COVID-19 free of charge to Janssen, Astra-Zeneca, Pfizer, and COVAXX (United Biomedical), as well as to the nonprofit One Day Sooner and has received consulting income or honoraria from Merck, Bristol Meyers Squibb, and Sanofi, and institutional research support from Pfizer. All other authors report no conflicts.

Infections, Hospitalizations, and Deaths Averted Via Direct Effects of the Pfizer-BioNTech BNT162b2 mRNA COVID-19 Vaccine in a Nationwide Vaccination Campaign, Israel

Meir Smaja

Papers

Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data.

Infections, hospitalisations, and deaths averted via a nationwide vaccination campaign using the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine in Israel: a retrospective surveillance study.

Infections, Hospitalizations, and Deaths Averted Via Direct Effects of the Pfizer-BioNTech BNT162b2 mRNA COVID-19 Vaccine in a Nationwide Vaccination Campaign, Israel