Effectiveness of BNT162b2, mRNA-1273, and ChAdOx1-S vaccines against severe covid-19 outcomes in a nationwide mass vaccination setting: cohort study

Objective To estimate the effectiveness of the three covid-19 vaccines by Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273), and Oxford-AstraZeneca (ChAdOx1-S) in people after receiving two doses. Design Cohort study. Setting Nationwide, population based data in France, from the French National Health Data System (Système National des Données de Santé), between 27 December 2020 and 30 April 2021. Participants Adults aged ≥50 years receiving a first dose of BNT162b2, mRNA-1273, or ChAdOx1-S were randomly selected (1:1) and matched on the date of vaccination with one unvaccinated control. Individuals were matched on year of birth, sex, region of residence, and residence in a nursing home (for individuals aged ≥75 years). All individuals were followed up until 20 August 2021. Main outcome measures Primary outcome measure was vaccine effectiveness estimated at least 14 days after the second dose against covid-19 related hospital admission using Cox proportional hazards models adjusted for baseline characteristics and comorbidities. Vaccine effectiveness against covid-19 related death in hospital was also investigated. Results 11 256 832 vaccinated individuals were included in the study (63.6% (n=7 161 658) with the BNT162b2 vaccine, 7.6% (n=856 599) with the mRNA-1273 vaccine, and 28.8% (n=3 238 575) with the ChAdOx1-S vaccine), along with 11 256 832 matched unvaccinated controls. During follow-up (up to 20 August 2021), 43 158 covid-19 related hospital admissions and 7957 covid-19 related deaths in hospital were registered. Compared with unvaccinated controls, vaccine effectiveness of two doses against covid-19 related hospital admission was 91% (95% confidence interval 91% to 92%), 95% (93% to 96%), and 91% (89% to 94%) for the BNT162b2, mRNA-1273, and ChAdOx1-S vaccines, respectively. Similar results were observed for vaccine effectiveness of two doses against covid-19 related deaths in hospital (BNT162b2, 91% (90% to 93%);mRNA-1273, 96% (92% to 98%);and ChAdOx1 nCoV-19, 88% (68% to 95%)). At 5-6 months after receiving the second dose of vaccine, effectiveness remained high at 94% (92% to 95%) for the BNT162b2 vaccine and 98% (93% to 100%) for the mRNA-1273 vaccine. Vaccine effectiveness of ChAdOx1-S estimated at 3-4 months was 90% (63% to 97%). All three vaccines remained effective at the time of circulation of the delta variant of SARS-CoV-2 between 1 July and 20 August 2021 (effectiveness between 89% and 95%). Conclusions These findings provide evidence indicating that two doses of ChAdOx1-S is as effective as two doses of mRNA vaccines in France against the alpha and delta variants of SARS-CoV-2. The effectiveness of ChAdOx1-S should be further examined with a longer follow-up and in the light of the circulation of new SARS-CoV-2 variants of concern.

Risk for Myocardial Infarction, Stroke, and Pulmonary Embolism Following COVID-19 Vaccines in Adults Younger Than 75 Years in France.

BACKGROUND: The BNT162b2 (Pfizer-BioNTech) vaccine has been shown to be safe with regard to risk for severe cardiovascular events (such as myocardial infarction [MI], pulmonary embolism [PE], and stroke) in persons aged 75 years or older. Less is known about the safety of other COVID-19 vaccines or outcomes in younger populations. OBJECTIVE: To assess short-term risk for severe cardiovascular events (excluding myocarditis and pericarditis) after COVID-19 vaccination in France's 46.5 million adults younger than 75 years. DESIGN: Self-controlled case series method adapted to event-dependent exposure and high event-related mortality. SETTING: France, 27 December 2020 to 20 July 2021. PATIENTS: All adults younger than 75 years hospitalized for PE, acute MI, hemorrhagic stroke, or ischemic stroke (n = 73 325 total events). MEASUREMENTS: Linkage between the French National Health Data System and COVID-19 vaccine databases enabled identification of hospitalizations for cardiovascular events (MI, PE, or stroke) and receipt of a first or second dose of the Pfizer-BioNTech, mRNA-1273 (Moderna), Ad26.COV2.S (Janssen), or ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccine. The relative incidence (RI) of each cardiovascular event was estimated in the 3 weeks after vaccination compared with other periods, with adjustment for temporality (7-day periods). RESULTS: No association was found between the Pfizer-BioNTech or Moderna vaccine and severe cardiovascular events. The first dose of the Oxford-AstraZeneca vaccine was associated with acute MI and PE in the second week after vaccination (RI, 1.29 [95% CI, 1.11 to 1.51] and 1.41 [CI, 1.13 to 1.75], respectively). An association with MI in the second week after a single dose of the Janssen vaccine could not be ruled out (RI, 1.75 [CI, 1.16 to 2.62]). LIMITATIONS: It was not possible to ascertain the relative timing of injection and cardiovascular events on the day of vaccination. Outpatient deaths related to cardiovascular events were not included. CONCLUSION: In persons aged 18 to 74 years, adenoviral-based vaccines may be associated with increased incidence of MI and PE. No association between mRNA-based vaccines and the cardiovascular events studied was observed. PRIMARY FUNDING SOURCE: None.

Age and sex-specific risks of myocarditis and pericarditis following Covid-19 messenger RNA vaccines.

Cases of myocarditis and pericarditis have been reported following the receipt of Covid-19 mRNA vaccines. As vaccination campaigns are still to be extended, we aimed to provide a comprehensive assessment of the association, by vaccine and across sex and age groups. Using nationwide hospital discharge and vaccine data, we analysed all 1612 cases of myocarditis and 1613 cases of pericarditis that occurred in France in the period from May 12, 2021 to October 31, 2021. We perform matched case-control studies and find increased risks of myocarditis and pericarditis during the first week following vaccination, and particularly after the second dose, with adjusted odds ratios of myocarditis of 8.1 (95% confidence interval [CI], 6.7 to 9.9) for the BNT162b2 and 30 (95% CI, 21 to 43) for the mRNA-1273 vaccine. The largest associations are observed for myocarditis following mRNA-1273 vaccination in persons aged 18 to 24 years. Estimates of excess cases attributable to vaccination also reveal a substantial burden of both myocarditis and pericarditis across other age groups and in both males and females.

COVID-19 hotspots through clusters analysis in France (may-October 2020): where should we track the virus to mitigate the spread?

BACKGROUND: In France, the lifting of the lockdown implemented to control the COVID-19 first wave in 2020 was followed by a reinforced contact-tracing (CT) strategy for the early detection of cases and transmission chains. We developed a reporting system of clusters defined as at least three COVID-19 cases, within seven days and belonging to the same community or having participated in the same gathering, whether they know each other or not. The aim of this study was to describe the typology and criticality of clusters reported between the two lockdowns in France to guide future action prioritisation. METHODS: In this study we describe the typology and criticality of COVID-19 clusters between the two lockdowns implemented in France (between May and end of October 2020). Clusters were registered in a national database named "MONIC" (MONItoring des Clusters), established in May 2020. This surveillance system identified the most affected communities in a timely manner. A level of criticality was defined for each cluster to take into consideration the risk of spreading within and outside the community of occurrence, and the health impact within the community. We compared the level of criticality according to the type of community in which the cluster occurred using Pearson's chi-square tests. RESULTS: A total of 7236 clusters were reported over the study period, particularly in occupational environment (25.1%, n = 1813), elderly care structures (21.9%, n = 1586), and educational establishments (15.9%, n = 1154). We show a shift over time of the most affected communities in terms of number of clusters. Clusters reported in occupational environment and the personal sphere had increased during summer while clusters reported in educational environment increased after the start of the school year. This trend mirrors change of transmission pattern overtime according to social contacts. Among all reported clusters, 43.1% had a high level of criticality with significant differences between communities (p < 0.0001). A majority of clusters had a high level of criticality in elderly care structures (82.2%), in disability care centres (56.6%), and health care facilities (51.7%). CONCLUSION: These results highlight the importance of targeting public health action based on timely sustained investigations, testing capacity and targeted awareness campaigns. The emergence of new SARS-CoV-2 variants strengthen these public health recommendations and the need for rapid and prioritise vaccination campaigns.

Prevalence of SARS-CoV-2 antibodies in France: results from nationwide serological surveillance.

Assessment of the cumulative incidence of SARS-CoV-2 infections is critical for monitoring the course and extent of the COVID-19 epidemic. Here, we report estimated seroprevalence in the French population and the proportion of infected individuals who developed neutralising antibodies at three points throughout the first epidemic wave. Testing 11,000 residual specimens for anti-SARS-CoV-2 IgG and neutralising antibodies, we find nationwide seroprevalence of 0.41% (95% CI: 0.05-0.88) mid-March, 4.14% (95% CI: 3.31-4.99) mid-April and 4.93% (95% CI: 4.02-5.89) mid-May 2020. Approximately 70% of seropositive individuals have detectable neutralising antibodies. Infection fatality rate is 0.84% (95% CI: 0.70-1.03) and increases exponentially with age. These results confirm that the nationwide lockdown substantially curbed transmission and that the vast majority of the French population remained susceptible to SARS-CoV-2 in May 2020. Our study shows the progression of the first epidemic wave and provides a framework to inform the ongoing public health response as viral transmission continues globally.