Evolution of COVID-19 symptoms during the first 12 months after illness onset

Wynberg, Elke; van Willigen, Hugo D G; Dijkstra, Maartje; Boyd, Anders; Kootstra, Neeltje A; van den Aardweg, Joost G; van Gils, Marit J; Matser, Amy; de Wit, Marije R; Leenstra, Tjalling; de Bree, Godelieve; de Jong, Menno D; Prins, Maria

BACKGROUND: Few robust longitudinal data on long-term 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 SARS-CoV-2 diagnosis via the local Public Health Service and from hospitals. Standardised symptom questionnaires were completed at enrolment, one week and month later, and monthly thereafter. Clinical severity was defined according to 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 one persistent symptom at 12 weeks after illness onset was greater in those with severe/critical disease (86.7%[95%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%]). At twelve months after illness onset, two-fifths of participants (40.7%[95%CI=34.2-47.1]) continued to report ≥1 symptom. Recovery was slower in female compared to male participants (aHR 0.65[95%CI=0.47-0.92]) and those with a BMI≥30kg/m 2 compared to BMI<25kg/m 2 (HR 0.62[95%CI=0.39-0.97]). 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.