The confirmed number of SARS-CoV-2 infections up to 18 October 2022 is 626 million worldwide, but information about factors affecting the probability of infection or a severe course of COVID-19 remains insufficient and often speculative. Only a small number of factors have been rigorously examined, mostly by retrospective or cross-sectional studies. We ran a preregistered study on 5164 Internet users who shared information with us about their exposure to 105 risk factors and reported being COVID-19 negative before the beginning of the fourth wave of COVID-19 in the Czech Republic. After the fourth wave, in which 709 (13.7%) of participants were infected, we used a partial Kendall test controlled for sex, age, and urbanization to compare the risk of infection and a severe course of the disease in subjects who initially did and did not report exposure to particular risk factors. After the correction for multiple tests, we identified 13 factors - including male sex, lower age, blood group B, and larger household size - that increased the risk of infection and 16 factors - including mask-wearing, borreliosis in the past, use of vitamin D supplements, or rooibos drinking - that decreased it. We also identified 23 factors that increased the risk of a severe course of COVID-19 and 12 factors that decreased the risk. This preregistered longitudinal study is of explorative nature. Therefore, although the observed effects were strong and remained highly significant even after correction for multiple tests, it will be necessary to confirm their existence in future independent studies.

Division of Biology Faculty of Science Charles University Prague 128 00 Czech Republic

Faculty of Electrical Engineering Czech Technical University Prague Prague 166 27 Czech Republic

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