Evolution of Coronavirus Disease 2019 (COVID-19) Symptoms during the First 12 Months after Illness Onset

Abstract

Background: Few robust longitudinal data on long-Term coronavirus disease 2019 (COVID-19) symptoms are available. We evaluated symptom onset, severity and recovery across the full spectrum of disease severity, up to one year after illness onset. Methods: The RECoVERED Study is a prospective cohort study based in Amsterdam, the Netherlands. Participants aged≥18 years were enrolled following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis via the local public health service and from hospitals. Standardized symptom questionnaires were completed at enrollment, 1 week and month later, and monthly thereafter. Clinical severity was defined according to World Health Organization (WHO) criteria. Kaplan-Meier methods were used to compare time from illness onset to symptom recovery, by clinical severity. We examined determinants of time to recovery using multivariable Cox proportional hazards models. Results: Between 11 May 2020 and 1 May 2021, 342 COVID-19 patients (192 [56%] male) were enrolled, of whom 99/342 (29%) had mild, 145/342 (42%) moderate, 56/342 (16%) severe, and 42/342 (12%) critical disease. The proportion of participants who reported at least 1 persistent symptom at 12 weeks after illness onset was greater in those with severe/critical disease (86.7% [95% confidence interval {CI}=76.5-92.7%]) compared to those with mild or moderate disease (30.7% [95% CI=21.1-40.9%] and 63.8% [95% CI=54.8-71.5%], respectively). At 12 months after illness onset, two-fifths of participants (40.7% [95% CI=34.2-7.1]) continued to report≥1 symptom. Recovery was slower in female compared to male participants (adjusted hazard ratio [aHR] 0.65 [95% CI=.47-.92]) and those with a body mass index [BMI] ≥30kg/m2 compared to BMI<25kg/m2 (hazard ratio [HR] 0.62 [95% CI=.39-.97]). Conclusions: COVID-19 symptoms persisted for one year after illness onset, even in some individuals with mild disease. Female sex and obesity were the most important determinants of speed of recovery from symptoms.