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The infection fatality risk (IFR) is the average number of deaths per infection by a pathogen and is key to characterizing the severity of infection across the population and for specific demographic groups. To date, there are few empirical estimates of IFR published due to challenges in measuring infection rates.1,2 Outside of closed, closely surveilled populations where infection rates can be monitored through viral surveillance, we must rely on indirect measures of infection, like specific antibodies. Representative seroprevalence studies provide an important avenue for estimating the number of infections in a community, and when combined with death counts can lead to robust estimates of the IFR. We estimated overall and age-specific IFR for the canton of Geneva, Switzerland using age-stratified daily case and death incidence reports combined with five weekly population-based seroprevalence estimates.3 From February 24th to June 2nd there were 5’039 confirmed cases and 286 reported deaths within Geneva (population of 506’765). We inferred age-stratified (5-9, 10-19, 20-49, 50-65 and 65+) IFRs by linking the observed number of deaths to the estimated number of infected individuals from each serosurvey. We account for the delays between infection and seroconversion as well as between infection and death.4 Inference is drawn in a Bayesian framework that incorporates uncertainty in seroprevalence estimates (supplement).Of the 286 reported deaths caused by SARS-CoV-2, the youngest person to die was 31 years old. Infected individuals younger than 50 years experienced statistically similar IFRs (range 0.00032-0.0016%), which increases to 0.14% (95% CrI 0.096-0.19) for those 50-64 years old to 5.6% (95% CrI 4.3-7.4) for those 65 years and older (supplement). After accounting for demography and age-specific seroprevalence, we estimate a population-wide IFR of 0.64% (95% CrI 0.38-0.98).Our results are subject to two notable limitations. Among the 65+ age group that died of COVID-19 within Geneva, 50% were reported among residents of assisted care facilities, where around 0.8% of the Geneva population resides. While the serosurvey protocol did not explicitly exclude these individuals, they are likely to have been under-represented. This would lead to an overestimation of the IFR in the 65+ age group if seroprevalence in this institutionalized population was higher than in the general population (supplement). Further, our IFR estimates are based on current evidence regarding post-infection antibody kinetics, which may differ between severe and mild infections. If mild infections have significantly lower and short-lived antibody responses, our estimates of IFR may be biased upwards.5Estimates of IFR are key for understanding the true pandemic burden and for weighing different risk reduction strategies. The IFR is not solely determined by host and pathogen biology, but also by the capacity of health systems to treat severe cases. Despite having among the highest per capita incidence in Switzerland, Geneva’s health system accommodated the influx of cases needing intensive care (peak of 80/110 ICU-beds including surge capacity) while maintaining care quality standards. As such, our IFR estimates can be seen as a best-case scenario with respect to health system capacity. Our results reveal that population-wide estimates of IFR mask great heterogeneity by age and point towards the importance of age-targeted interventions to reduce exposures among those at highest risk of death.

Introduction The COVID-19 pandemic has affected billions of people around the world both directly through the infection itself and indirectly through its economic, social and sanitary impact. Collecting data over time is essential for the understanding of the disease spread, the incidence of COVID-19-like symptoms, the level and dynamics of immunity, as well as the long-term impact of the pandemic. The objective of the study was to set up a longitudinal follow-up of adult participants of serosurveys carried out in the canton of Geneva, Switzerland, during the COVID-19 pandemic. This follow-up aims at monitoring COVID-19 related symptoms and SARS-CoV-2 seroconversion, as well as the overall impact of the pandemic on several dimensions of health and on socioeconomic factors over a period of at least 2 years., Methods and analysis Serosurvey participants were invited to create an account on the dedicated digital platform Specchio-COVID19 (https://www.specchio-covid19.ch/) . On registration, an initial questionnaire assessed sociodemographic and lifestyle characteristics (including housing conditions, physical activity, diet, alcohol and tobacco consumption), anthropometry, general health and experience related to COVID-19 (symptoms, COVID-19 test results, quarantines, hospitalisations). Weekly, participants were invited to fill in a short questionnaire with updates on self-reported COVID-19-compatible symptoms, SARS-CoV-2 infection testing and vaccination. A more detailed questionnaire about mental health, wellbeing, risk perception and changes in working conditions was proposed monthly. Supplementary questionnaires were proposed at regular intervals to assess more in depth the impact of the pandemic on physical and mental health, vaccination adherence, healthcare consumption and changes in health behaviours. At baseline, serology testing allowed to assess the spread of SARS-CoV-2 infection among the general population and subgroups of workers. Additionally, seropositive participants and a sample of randomly selected participants were invited for serologic testing at regular intervals in order to monitor both the seropersistance of anti-SARS-CoV-2 antibodies and the seroprevalence of anti-SARS-CoV-2 antibodies in the population of the canton of Geneva., Ethics and dissemination The study was approved by the Cantonal Research Ethics Commission of Geneva, Switzerland (CCER Project ID 2020-00881). Results will be disseminated in a variety of ways, via the SpecchioCOVID-19 platform, social media posts, press releases and through regular scientific dissemination methods (openaccess articles, conferences).