Prospective cohort study of fatigue before and after SARS-CoV-2 infection in the Netherlands.

Fatigue is one of the most common persistent symptoms of SARS-CoV-2 infection. We aimed to assess fatigue during and after a SARS-CoV-2 infection by age, sex, presence of a medical risk condition, SARS-CoV-2 variant and vaccination status, accounting for pre-infection fatigue and compared with uninfected individuals. We used data from an ongoing prospective cohort study in the Netherlands (VASCO). We included 22,705 first infections reported between 12 July 2021 and 9 March 2024. Mean fatigue scores increased during infection, declined rapidly in the first 90 days post-infection, but remained elevated until at least 270 days for Delta and 120 days for Omicron infections. Prevalence of severe fatigue was 18.5% before first infection. It increased to 24.4% and 22.5% during acute infection and decreased to 21.2% and 18.9% at 90 days after Delta and Omicron infection, respectively. The prevalence among uninfected participants was lower than among matched Delta-infected participants during the acute phase of the infection and 90 days post-infection. For matched Omicron-infected individuals this was only observed during the acute phase. We observed no differences in mean post- vs pre-infection fatigue scores at 90-270 days post-infection by vaccination status. The impact of SARS-CoV-2 infection on the prevalence of severe fatigue was modest at population level, especially for Omicron.