BackgroundThe 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 COVID19-like symptoms, the level and dynamics of immunity, as well as the long-term impact of the pandemic. ObjectiveThe 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. MethodsSerosurvey participants were invited to create an account on the dedicated digital platform Specchio-COVID19 (https//www.specchio-covid19.ch/). Upon registration, an initial questionnaire assessed socio-demographic 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, hospitalizations). 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, well-being, 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, health care consumption and changes in health behaviors. 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 disseminationThe 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 Specchio-COVID19 platform, social media posts, press releases, and through regular scientific dissemination methods (open-access articles, conferences). Article summaryO_ST_ABSStrengths and limitationsC_ST_ABSO_LIThis is a large study with a diversified recruitment among the general population and mobilized workers. It will contribute to obtain a clearer picture of the impact of the COVID-19 pandemic, for both the general population and targeted subpopulations. C_LIO_LIA major strength of the study is the combined use of serological testing and questionnaires. While regular serological testing will help us to model evolution of the pandemic, self-reported data on socioeconomic characteristics, COVID-19-compatible symptoms, and general and mental health will allow us to monitor the progression of the COVID-19 pandemic as well as to thoroughly analyze its effects on several dimensions of health. C_LIO_LIThe longitudinal component of the study will provide insight into the extent and duration of immunity, as well as the long-term impact of the pandemic and the sanitary, social and economic measures associated with it. C_LIO_LIThe main limitation is that Specchio-COVID19 is based on self-reports with a risk of information bias. However, considering the pandemic context, participants are generally engaged to participate and to contribute to COVID-19 research. Further, at least half of the sample is based on random selection in the general population. C_LIO_LIThe study is primarily being conducted online, which may limit the generalizability of the findings, especially for the elderly and vulnerable populations, although internet access is extensive in Switzerland. Nonetheless, participants can use paper questionnaires to contribute to the major assessments. C_LI