BNT162b2 Effectiveness Against Delta and Omicron Variants of Severe Acute Respiratory Syndrome Coronavirus 2 in Adolescents Aged 12-17 Years, by Dosing Interval and Duration.

BACKGROUND: Two- and 3-dose BNT162b2 vaccine effectiveness (VE) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, including Delta and Omicron variants, was assessed among adolescents in Canada, where first and second doses were spaced longer than the manufacturer-specified 3-week interval. METHODS: Test-negative design estimated VE against laboratory-confirmed SARS-CoV-2 infection ≥14 days after vaccination among 12-17-year-olds in Quebec and British Columbia, Canada, between 5 September 2021 and 30 April 2022 (epidemiological weeks 36-17). VE was explored by the interval between first and second doses, time since the second dose, and with a third dose. RESULTS: The VE against Delta was ≥90% until at least 5 months after the second dose. The VE against Omicron decreased from about 65%-75% at 2-3 weeks to ≤50% by the third month after vaccination, restored to approximately 65% by a third dose. Although confidence intervals overlapped, VE against Omicron was about 5%-7% higher (absolute) when first and second doses were spaced ≥8 versus 3-4 weeks apart. CONCLUSIONS: In adolescents, 2 BNT162b2 doses provided strong and sustained protection against Delta but reduced and rapidly waning VE against Omicron. A longer interval between first and second doses and a third dose marginally improved Omicron protection.

Addressing misclassification bias in vaccine effectiveness studies with an application to Covid-19.

Safe and effective vaccines are crucial for the control of Covid-19 and to protect individuals at higher risk of severe disease. The test-negative design is a popular option for evaluating the effectiveness of Covid-19 vaccines. However, the findings could be biased by several factors, including imperfect sensitivity and/or specificity of the test used for diagnosing the SARS-Cov-2 infection. We propose a simple Bayesian modeling approach for estimating vaccine effectiveness that is robust even when the diagnostic test is imperfect. We use simulation studies to demonstrate the robustness of our method to misclassification bias and illustrate the utility of our approach using real-world examples.

Observed negative vaccine effectiveness could be the canary in the coal mine for biases in observational COVID-19 studies.

Since the emergence of the SARS-CoV-2 Omicron variant, multiple observational studies have reported negative vaccine effectiveness (VE) against infection, symptomatic infection, and even severity (hospitalization), potentially leading to an interpretation that vaccines were facilitating infection and disease. However, current observations of negative VE likely stem from the presence of various biases (e.g., exposure differences, testing differences). Although negative VE is more likely to arise when true biological efficacy is generally low and biases are large, positive VE measurements can also be subject to the same mechanisms of bias. In this perspective, we first outline the different mechanisms of bias that could lead to false-negative VE measurements and then discuss their ability to potentially influence other protection measurements. We conclude by discussing the use of suspected false-negative VE measurements as a signal to interrogate the estimates (quantitative bias analysis) and to discuss potential biases when communicating real-world immunity research.

Current Challenges with the Use of Test-Negative Designs for Modeling COVID-19 Vaccination and Outcomes.

The widespread testing for SARS-CoV-2 infection has facilitated the use of test-negative designs (TND) for modeling COVID-19 vaccination and outcomes. Despite the comprehensive literature on TND, the use of TND in COVID-19 studies is relatively new and calls for robust design and analysis to adapt to a rapidly changing and dynamically evolving pandemic and to account for changes in testing and reporting practices. In this commentary, we aim to draw the attention of researchers to COVID-specific challenges in using TND as we are analyzing data amassed over more than two years of the pandemic. We first review when and why TND works, and general challenges in TND studies presented in the literature. We then discuss COVID-specific challenges which have not received adequate acknowledgment but may add to the risk of invalid conclusions in TND studies of COVID-19.

Effectiveness of COVID-19 vaccines against hospitalization and death in Canada: A multiprovincial test-negative design study.

BACKGROUND: A major goal of COVID-19 vaccination is to prevent severe outcomes (hospitalizations and deaths). We estimated the effectiveness of mRNA and ChAdOx1 COVID-19 vaccines against severe outcomes in four Canadian provinces between December 2020 and September 2021. METHODS: We conducted this multiprovincial retrospective test-negative study among community-dwelling adults aged ≥18 years in Ontario, Quebec, British Columbia, and Manitoba using linked provincial databases and a common study protocol. Multivariable logistic regression was used to estimate province-specific vaccine effectiveness against COVID-19 hospitalization and/or death. Estimates were pooled using random effects models. RESULTS: We included 2,508,296 tested subjects, with 31,776 COVID-19 hospitalizations and 5,842 deaths. Vaccine effectiveness was 83% after a first dose, and 98% after a second dose, against both hospitalization and death (separately). Against severe outcomes (hospitalization or death), effectiveness was 87% (95%CI: 71%-94%) ≥84 days after a first dose of mRNA vaccine, increasing to 98% (95%CI: 96%-99%) ≥112 days after a second dose. Vaccine effectiveness against severe outcomes for ChAdOx1 was 88% (95%CI: 75%-94%) ≥56 days after a first dose, increasing to 97% (95%CI: 91%-99%) ≥56 days after a second dose. Lower one-dose effectiveness was observed for adults aged ≥80 years and those with comorbidities, but effectiveness became comparable after a second dose. Two doses of vaccines provided very high protection for both homologous and heterologous schedules, and against Alpha, Gamma, and Delta variants. CONCLUSIONS: Two doses of mRNA or ChAdOx1 vaccines provide excellent protection against severe outcomes of hospitalization and death.

COVID-19 vaccine effectiveness against symptomatic SARS-CoV-2 infection during Delta-dominant and Omicron-dominant periods in Japan: a multi-center prospective case-control study (FASCINATE study).

BACKGROUND: Although several COVID-19 vaccines initially showed high efficacy, there have been concerns due to waning immunity and the emergence of variants with immune escape capacity. METHODS: A test-negative design case-control study was conducted in 16 healthcare facilities in Japan during the Delta-dominant period (August-September 2021) and the Omicron-dominant period (January-March 2022). Vaccine effectiveness (VE) against symptomatic SARS-CoV-2 infection was calculated for 2 doses for the Delta-dominant period and 2 or 3 doses for the Omicron-dominant period, compared to unvaccinated individuals. RESULTS: The analysis included 5795 individuals with 2595 (44.8%) cases. Among vaccinees, 2242 (55.8%) received BNT162b2 and 1624 (40.4%) received mRNA-1273 at manufacturer-recommended intervals. During the Delta-dominant period, VE was 88% (95% CI: 82-93) 14 days-3 months after dose 2 and 87% (95% CI: 38-97) 3-6 months after dose 2. During the Omicron-dominant period, VE was 56% (95% CI: 37-70) 14 days-3 months since dose 2, 52% (95% CI: 40-62) 3-6 months after dose 2, 49% (95% CI: 34-61) 6 + months after dose 2, and 74% (95% CI: 62-83) 14 + days after dose 3. Restricting to individuals at high risk of severe COVID-19 and additional adjustment for preventive measures (i.e. mask-wearing/high-risk behaviors) yielded similar estimates, respectively. CONCLUSIONS: In Japan where most are infection-naïve and strict prevention measures are maintained regardless of vaccination status, 2-dose mRNA vaccines provided high protection against symptomatic infection during the Delta-dominant period and moderate protection during the Omicron-dominant period. Among individuals who received an mRNA booster dose, VE recovered to a high level.

Effectiveness of vero cell inactivated vaccine against severe acute respiratory infections (SARI) in Sibu, Malaysia: A retrospective test-negative design.

The effectiveness of the vero cell inactivated vaccine (CoronaVac®) against severe acute respiratory infection ( SARI) caused by SARS-CoV-2 in the real world was assessed. A matched test-negative case-control design was employed using the web-based national information system, as well as the hospitalization dataset in Sibu Hospital. Vaccine effectiveness was measured by conditional logistic regression with adjustment for gender, underlying comorbidity, smoking status, and education level. Between 15 March and 30 September 2021, 838 eligible SARI patients were identified from the hospitalization records. Vaccine effectiveness was 42.4% (95% confidence interval [CI]: -28.3 to 74.1) for partial vaccination (after receiving the first dose to 14 days after receiving the second dose), and 76.5% (95% CI: 45.6 to 89.8) for complete vaccination (at 15 days or more after receiving the second dose). This analysis indicated that two doses of CoronaVac® vaccine provided efficacious protection against SARI caused by SARS-CoV-2 in the short term. However, the duration of protection, and performance against new variants need to be studied continuously.

Vaccine Effectiveness Against Influenza-Associated Urgent Care, Emergency Department, and Hospital Encounters During the 2021-2022 Season, VISION Network.

BACKGROUND: Following historically low influenza activity during the 2020-2021 season, the United States saw an increase in influenza circulating during the 2021-2022 season. Most viruses belonged to the influenza A(H3N2) 3C.2a1b 2a.2 subclade. METHODS: We conducted a test-negative case-control analysis among adults ≥18 years of age at 3 sites within the VISION Network. Encounters included emergency department/urgent care (ED/UC) visits or hospitalizations with ≥1 acute respiratory illness (ARI) discharge diagnosis codes and molecular testing for influenza. Vaccine effectiveness (VE) was calculated by comparing the odds of influenza vaccination ≥14 days before the encounter date between influenza-positive cases (type A) and influenza-negative and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative controls, applying inverse probability-to-be-vaccinated weights, and adjusting for confounders. RESULTS: In total, 86 732 ED/UC ARI-associated encounters (7696 [9%] cases) and 16 805 hospitalized ARI-associated encounters (649 [4%] cases) were included. VE against influenza-associated ED/UC encounters was 25% (95% confidence interval (CI), 20%-29%) and 25% (95% CI, 11%-37%) against influenza-associated hospitalizations. VE against ED/UC encounters was lower in adults ≥65 years of age (7%; 95% CI, -5% to 17%) or with immunocompromising conditions (4%; 95% CI, -45% to 36%). CONCLUSIONS: During an influenza A(H3N2)-predominant influenza season, modest VE was observed. These findings highlight the need for improved vaccines, particularly for A(H3N2) viruses that are historically associated with lower VE.

Effectiveness of Covid-19 vaccines against symptomatic and asymptomatic SARS-CoV-2 infections in an urgent care setting.

BACKGROUND: It is critical to monitor changes in vaccine effectiveness against COVID-19 outcomes for various vaccine products in different population subgroups. METHODS: We conducted a retrospective study in patients ≥12 years who underwent testing for SARS-CoV-2 virus from April 14 through October 25, 2021, at urgent care centers in the New York metropolitan area. Patients self-reported vaccination status at the time of testing. We used a test-negative design to estimate vaccine effectiveness (VE) by comparing odds of a positive test for SARS-CoV-2 infection among vaccinated (n = 474,805), partially vaccinated (n = 87,834), and unvaccinated (n = 369,333) patients, adjusted for demographic factors and calendar time. RESULTS: VE against symptomatic infection after 2 doses of mRNA vaccine was 96% (95% Confidence Interval: 95%, 97%) in the pre-delta period and reduced to 79% (95% CI: 77%, 81%) in the delta period. In the delta period, VE for 12-15-year-olds (85%; [95% CI: 81%, 88%]) was higher compared to older age groups (<65% for all other age groups). VE estimates did not differ by sex and race/ethnicity. VE against symptomatic infection was the highest for individuals with a prior infection followed by full vaccination. VE against symptomatic infection after the 2-dose mRNA-1273 vaccine (82% [95% CI: 80%, 84%]) was higher compared to the BNT162b2 vaccine (76% [95% CI: 74%, 78%]) in the delta period. VE after 1-dose of the Ad26.COV2.S vaccine was the lowest compared to other vaccines (19% [95% CI: 15%, 23%]) in the delta period. CONCLUSIONS: VE against infection after two doses of the mRNA vaccines was high initially, but significantly reduced against the delta variant for both FDA-approved vaccines.

Measuring the Effectiveness of COVID-19 Vaccines Used during a Surge of the Delta Variant of SARS-CoV-2 in Bangladesh: A Test-Negative Design Evaluation.

BACKGROUND: From May to December 2021, Bangladesh experienced a major surge in the Delta variant of SARS-CoV-2. The earlier rollout of several vaccines offered the opportunity to evaluate vaccine effectiveness against this variant. METHODS: A prospective, test-negative case-control study was conducted in five large hospitals in Dhaka between September and December 2021. The subjects were patients of at least 18 years of age who presented themselves for care, suffering COVID-like symptoms of less than 10 days' duration. The cases had PCR-confirmed infections with SARS-CoV-2, and up to 4 PCR test-negative controls were matched to each case, according to hospital, date of presentation, and age. Vaccine protection was assessed as being the association between the receipt of a complete course of vaccine and the occurrence of SARS-CoV-2 disease, with symptoms beginning at least 14 days after the final vaccine dose. RESULTS: In total, 313 cases were matched to 1196 controls. The genotyping of case isolates revealed 99.6% to be the Delta variant. Receipt of any vaccine was associated with 12% (95% CI: -21 to 37, p = 0.423) protection against all episodes of SARS-CoV-2. Among the three vaccines for which protection was evaluable (Moderna (mRNA-1273); Sinopharm (Vero Cell-Inactivated); Serum Institute of India (ChAdOx1 nCoV-19)), only the Moderna vaccine was associated with significant protection (64%; 95% CI: 10 to 86, p = 0.029). Protection by the receipt of any vaccine against severe disease was 85% (95% CI: 27 to 97, p = 0.019), with protection estimates of 75% to 100% for the three vaccines. CONCLUSIONS: Vaccine protection against COVID-19 disease of any severity caused by the Delta variant was modest in magnitude and significant for only one of the three evaluable vaccines. In contrast, protection against severe disease was high in magnitude and consistent for all three vaccines. Because our findings are not in complete accord with evaluations of the same vaccines in more affluent settings, our study underscores the need for country-level COVID-19 vaccine evaluations in developing countries.

Testing behaviour may bias observational studies of vaccine effectiveness.

BACKGROUND: Recent observational studies suggest that vaccines may have little effect in preventing infection with the Omicron variant of severe acute respiratory syndrome coronavirus 2. However, the observed effects may be confounded by patient factors, preventive behaviours, or differences in testing behaviour. To assess potential confounding, we examined differences in testing behaviour between unvaccinated and vaccinated populations. METHODS: We recruited 1,526 Australian adults for an online randomized study about coronavirus disease 2019 (COVID-19) testing in late 2021, collecting self-reported vaccination status and three measures of COVID-19 testing behaviour: testing in past month or ever and test intention if they woke with a sore throat. We examined the association between testing intentions and vaccination status in the trial's baseline data. RESULTS: Of the 1,526 participants (mean age 31 y), 22% had a COVID-19 test in the past month and 61% ever; 17% were unvaccinated, 11% were partially vaccinated (one dose), and 71% were fully vaccinated (two or more doses). Fully vaccinated participants were twice as likely as those who were unvaccinated (relative risk [RR] 2.2, 95% CI 1.8 to 2.8, p < 0.001) to report positive COVID testing intentions. Partially vaccinated participants had less positive intentions than fully vaccinated participants (RR 0.68, 95% CI 0.52 to 0.89, p < 0.001) but higher intentions than unvaccinated participants (RR 1.5, 95% CI 1.4 to 1.6, p = 0.002). DISCUSSION: Vaccination predicted greater COVID-19 testing intentions and would substantially bias observed vaccine effectiveness. To account for differential testing behaviours, test-negative designs are currently the preferred option, but their assumptions need more thorough examination.

HISTORIQUE: Selon de récentes études observationnelles, les vaccins peuvent avoir peu d'effet sur la prévention de l'infection par le variant Omicron du coronavirus 2 du syndrome respiratoire aigu sévère. Cependant, les effets observés peuvent être biaisés par des facteurs liés aux patients, des comportements préventifs ou des différences de comportements liés aux tests. Pour évaluer les facteurs confusionnels potentiels, les auteurs ont examiné les différences de comportements liés aux tests entre les populations non vaccinées et vaccinées. MÉTHODOLOGIE: Les auteurs ont recruté 1 526 adultes australiens en vue d'une étude randomisée en ligne sur les tests de la maladie à coronavirus 2019 (COVID-19) à la fin de 2021, afin de colliger l'état vaccinal autodéclaré et trois mesures sur les comportements liés aux tests de la COVID-19 : test au cours du mois précédent ou jamais auparavant et intention de se soumettre à un test en cas de mal de gorge. Ils ont examiné l'association entre les intentions de se soumettre à un test et l'état vaccinal dans les données de référence de l'étude. RÉSULTATS: Sur les 1 526 participants (d'un âge moyen de 31 ans), 22 % avaient subi un test de COVID-19 au cours du mois précédent et 61 % n'en avaient jamais subi; 17 % n'étaient pas vaccinés, 11 % l'étaient partiellement (une dose) et 71 % l'étaient pleinement (au moins deux doses). Les participants pleinement vaccinés étaient deux fois plus susceptibles que ceux qui ne l'étaient pas (risque relatif [RR] 2,2, IC à 95 % 1,8 à 2,8, p < 0,001) de déclarer des intentions de se faire tester contre la COVID-19. Les participants partiellement vaccinés avaient des intentions moins positives que les participants pleinement vaccinés (RR 0,68, IC à 95 % 0,52 à 0,89, p < 0,001), mais plus élevées que ceux qui ne l'étaient pas du tout (RR 1,5, IC à 95 % 1,4 à 1,6, p = 0,002). DISCUSSION: La vaccination était prédictive de plus grandes intentions de subir un test de COVID-19 et établissait un biais important à l'égard de l'efficacité réelle des vaccins. Pour tenir compte des comportements différentiels vis-à-vis des tests, les méthodologies de tests négatifs constituent actuellement la solution privilégiée, mais cette hypothèse doit être approfondie.

Influenza vaccine effectiveness against A(H3N2) during the delayed 2021/22 epidemic in Canada.

Influenza virus circulation virtually ceased in Canada during the COVID-19 pandemic, re-emerging with the relaxation of restrictions in spring 2022. Using a test-negative design, the Canadian Sentinel Practitioner Surveillance Network reports 2021/22 vaccine effectiveness of 36% (95% CI: -38 to 71) against late-season illness due to influenza A(H3N2) clade 3C.2a1b.2a.2 viruses, considered antigenically distinct from the 3C.2a1b.2a.1 vaccine strain. Findings reinforce the World Health Organization's decision to update the 2022/23 northern hemisphere vaccine to a more representative A(H3N2) clade 3C.2a1b.2a.2 strain.

Evaluating real-world COVID-19 vaccine effectiveness using a test-negative case-control design.

Aim: It is important to assess if clinical trial efficacy translates into real-world effectiveness for COVID-19 vaccines. Materials & methods: We conducted a modified test-negative design (TND) to evaluate the real-world effectiveness of three COVID-19 vaccines. We defined cases in two ways: self-reported COVID-19-positive tests, and self-reported positive tests with ≥1 moderate/severe COVID-19 symptom. Results: Any vaccination was associated with a 95% reduction in subsequently reporting a positive COVID-19 test, and a 71% reduction in reporting a positive test and ≥1 moderate/severe symptom. Conclusion: We observed high effectiveness across all three marketed vaccines, both for self-reported positive COVID-19 tests and moderate/severe COVID-19 symptoms. This innovative TND approach can be implemented in future COVID-19 vaccine and treatment real-world effectiveness studies. Clinicaltrials.gov identifier: NCT04368065.

COVID-19 vaccine effectiveness against hospitalization due to SARS-CoV-2: A test-negative design study based on Severe Acute Respiratory Infection (SARI) sentinel surveillance in Spain.

BACKGROUND: With the emergence of SARS-CoV-2, influenza surveillance systems in Spain were transformed into a new syndromic sentinel surveillance system. The Acute Respiratory Infection Surveillance System (SiVIRA in Spanish) is based on a sentinel network for acute respiratory infection (ARI) surveillance in primary care and a network of sentinel hospitals for severe ARI (SARI) surveillance in hospitals. METHODS: Using a test-negative design and data from SARI admissions notified to SiVIRA between January 1 and October 3, 2021, we estimated COVID-19 vaccine effectiveness (VE) against hospitalization, by age group, vaccine type, time since vaccination, and SARS-CoV-2 variant. RESULTS: VE was 89% (95% CI: 83-93) against COVID-19 hospitalization overall in persons aged 20 years and older. VE was higher for mRNA vaccines, and lower for those aged 80 years and older, with a decrease in protection beyond 3 months of completing vaccination, and a further decrease after 5 months. We found no differences between periods with circulation of Alpha or Delta SARS-CoV-2 variants, although variant-specific VE was slightly higher against Alpha. CONCLUSIONS: The SiVIRA sentinel hospital surveillance network in Spain was able to describe clinical and epidemiological characteristics of SARI hospitalizations and provide estimates of COVID-19 VE in the population under surveillance. Our estimates add to evidence of high effectiveness of mRNA vaccines against severe COVID-19 and waning of protection with time since vaccination in those aged 80 or older. No substantial differences were observed between SARS-CoV-2 variants (Alpha vs. Delta).

Two-Dose Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Effectiveness With Mixed Schedules and Extended Dosing Intervals: Test-Negative Design Studies From British Columbia and Quebec, Canada.

BACKGROUND: The Canadian coronavirus disease 2019 (COVID-19) immunization strategy deferred second doses and allowed mixed schedules. We compared 2-dose vaccine effectiveness (VE) by vaccine type (mRNA and/or ChAdOx1), interval between doses, and time since second dose in 2 of Canada's larger provinces. METHODS: Two-dose VE against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or hospitalization among adults ≥18 years, including due to Alpha, Gamma, and Delta variants of concern (VOCs), was assessed ≥14 days postvaccination by test-negative design studies separately conducted in British Columbia and Quebec, Canada, between 30 May and 27 November (epi-weeks 22-47) 2021. RESULTS: In both provinces, all homologous or heterologous mRNA and/or ChAdOx1 2-dose schedules were associated with ≥90% reduction in SARS-CoV-2 hospitalization risk for ≥7 months. With slight decline from a peak of >90%, VE against infection was ≥80% for ≥6 months following homologous mRNA vaccination, lower by ∼10% when both doses were ChAdOx1 but comparably high following heterologous ChAdOx1 + mRNA receipt. Findings were similar by age group, sex, and VOC. VE was significantly higher with longer 7-8-week versus manufacturer-specified 3-4-week intervals between mRNA doses. CONCLUSIONS: Two doses of any mRNA and/or ChAdOx1 combination gave substantial and sustained protection against SARS-CoV-2 hospitalization, spanning Delta-dominant circulation. ChAdOx1 VE against infection was improved by heterologous mRNA series completion. A 7-8-week interval between first and second doses improved mRNA VE and may be the optimal schedule outside periods of intense epidemic surge. Findings support interchangeability and extended intervals between SARS-CoV-2 vaccine doses, with potential global implications for low-coverage areas and, going forward, for children.

Effectiveness of complete primary vaccination against COVID-19 at primary care and community level during predominant Delta circulation in Europe: multicentre analysis, I-MOVE-COVID-19 and ECDC networks, July to August 2021.

IntroductionIn July and August 2021, the SARS-CoV-2 Delta variant dominated in Europe.AimUsing a multicentre test-negative study, we measured COVID-19 vaccine effectiveness (VE) against symptomatic infection.MethodsIndividuals with COVID-19 or acute respiratory symptoms at primary care/community level in 10 European countries were tested for SARS-CoV-2. We measured complete primary course overall VE by vaccine brand and by time since vaccination.ResultsOverall VE was 74% (95% CI: 69-79), 76% (95% CI: 71-80), 63% (95% CI: 48-75) and 63% (95% CI: 16-83) among those aged 30-44, 45-59, 60-74 and ≥ 75 years, respectively. VE among those aged 30-59 years was 78% (95% CI: 75-81), 66% (95% CI: 58-73), 91% (95% CI: 87-94) and 52% (95% CI: 40-61), for Comirnaty, Vaxzevria, Spikevax and COVID-19 Vaccine Janssen, respectively. VE among people 60 years and older was 67% (95% CI: 52-77), 65% (95% CI: 48-76) and 83% (95% CI: 64-92) for Comirnaty, Vaxzevria and Spikevax, respectively. Comirnaty VE among those aged 30-59 years was 87% (95% CI: 83-89) at 14-29 days and 65% (95% CI: 56-71%) at ≥ 90 days between vaccination and onset of symptoms.ConclusionsVE against symptomatic infection with the SARS-CoV-2 Delta variant varied among brands, ranging from 52% to 91%. While some waning of the vaccine effect may be present (sample size limited this analysis to only Comirnaty), protection was 65% at 90 days or more between vaccination and onset.

Vaccine effectiveness and duration of protection against symptomatic infections and severe Covid-19 outcomes in adults aged 50 years and over, France, January to mid-December 2021.

Background: SARS-CoV-2 continues to spread despite fast vaccine rollout, which could be attributed to waning immunity or to a reduced protection against some variants. A thorough characterization of vaccine protection and its duration in time is needed to inform vaccination policies and enhance public trust. Methods: We linked three national databases with exhaustive information on screening, vaccination and hospitalizations in France from January 1st to December 12, 2021. We performed a two-step analysis to estimate vaccine effectiveness against severe outcomes of Covid-19 (requiring hospitalization) in people aged 50 years or over, combining: (i) a test-negative case-control design to assess vaccine effectiveness against symptomatic infections; and (ii) a survival analysis to assess the additional protection against severe outcomes (hospitalizations, ICU admissions and inpatient deaths) in infected individuals. Findings: We found a high vaccine effectiveness in people aged 50 years or more, reaching 82% against symptomatic infections and 94% against hospitalizations, after a full vaccination scheme with the Covid-19 vaccines used in France.Vaccine effectiveness against symptomatic infections decreased over time, dropping to 53% after six months, but remained high against severe outcomes (90% after six months). The booster dose allowed restoring protection levels above 90% against symptomatic infections. Vaccine protection and its evolution in time, showed little difference against the variants that circulated prior to December 2021 in France, including the Delta variant. Interpretation: Though vaccine immunity decreases over time, vaccination remains crucial to provide individual protection against severe outcomes requiring hospitalization. This decline can be reversed by the receipt of a booster dose.