Background: The long-term consequences of COVID-19 infection are becoming increasingly evident in recent studies. This repeated cross-sectional study aimed to explore the long-term health and cognitive effects of COVID-19, focusing on how virus variants, vaccination, illness severity, and time since infection impact post-COVID-19 outcomes. Methods: We examined three cohorts of university students (N = 584) and used non-parametric methods to assess correlations of various health and cognitive variables with SARS-CoV-2 infection, COVID-19 severity, vaccination status, time since infection, time since vaccination, and virus variants. Results: Our results suggest that some health and cognitive impairments may persist, with some even appearing to progressively worsen-particularly fatigue in women and memory in men-up to four years post-infection. The data further indicate that the ancestral SARS-CoV-2 variant may have the most significant long-term impact, while the Omicron variant appears to have the least. Interestingly, the severity of the acute illness was not correlated with the variant of SARS-CoV-2. The analysis also revealed that individuals who contracted COVID-19 after vaccination had better health and cognitive outcomes compared to those infected before vaccination. Conclusions: Overall, our results indicate that even in young individuals who predominantly experienced only mild forms of the infection, a gradual decline in health and fitness can occur over a span of four years post-infection. Notably, some negative trends-at least in men-only began to stabilize or even reverse during the fourth year, whereas in women, these trends showed no such improvement. These findings suggest that the long-term public health impacts of COVID-19 may be more severe and affect a much broader population than is commonly assumed.

Laboratory of Evolutionary Biology Department of Philosophy and History of Sciences Faculty of Science Charles University Viničná 7 128 00 Prague Czech Republic

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Persistent Health and Cognitive Impairments up to Four Years Post-COVID-19 in Young Students: The Impact of Virus Variants and Vaccination Timing