Prevalence and severity of symptoms 3 months after infection with SARS-CoV-2 compared to test-negative and population controls in the Netherlands

Background: More information is needed on prevalence of long-term symptoms after SARS-CoV-2-infection. This prospective study assesses symptoms three months after SARS-CoV-2-infection compared to test-negative and population controls, and the effect of vaccination prior to infection. Methods: Participants enrolled after a positive (cases) or negative (test-negative controls) SARS-CoV-2-test, or after invitation from the general population (population controls). After three months, participants indicated presence of 41 symptoms, and severity of four symptoms. Permutation tests were used to select symptoms significantly elevated in cases compared to controls and to compare symptoms between cases that were vaccinated or unvaccinated prior to infection. Findings: Between May 19th and December 13th 2021 9166 cases, 1698 symptomatic but test-negative controls, and 3708 population controls enrolled. At three months, 13 symptoms, and severity of fatigue, cognitive impairment and dyspnoea, were significantly elevated between cases and controls. Of cases, 48.5% reported [≥]1 significantly elevated symptom, compared to 29.8% of test-negative controls and 26.0% of population controls. Effect of vaccination could only be determined for cases <65yrs, and was found to be significantly protective for loss of smell and taste but not for other symptoms. Interpretation: Three months after SARS-CoV-2 infection, almost half of the cases still report symptoms, which is higher than the background prevalence and prevalence in test-negative controls. Vaccination prior to infection was protective against loss of smell and taste as assessed in cases aged <65.