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 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.

Post-acute symptoms, new onset diagnoses and health problems 6 to 12 months after SARS-CoV-2 infection: a nationwide questionnaire study in the adult Danish population

“…Increased frequency of post-acute symptoms in females compared to males and slower recovery in females have also been reported in other studies [11][12][13]15,16 , whereas the evidence regarding the influence of age is somewhat contradicting. In one study, an inverted-U formed association between age and worsening of health after infection was observed, similar to the present study, where the majority of symptoms were most frequently reported by the middle-aged (30-59 years) 14 , but reports of increased risk in older individuals 12,28 , young adults 17 , or no effect 11 also exist.…”

“…Parametric g-computation 10 on logistic regression was used to estimate RDs (with 95% confidence intervals) among the exposed with adjustment for completion time (6, 9 or 12 months), age, sex, obesity, comorbidities from the questionnaire, Charlson Comorbidity Index scores and healthcare occupation. Based on results of other studies [11][12][13][14][15][16][17] , these variables were considered potential confounders.…”

Long-Term Sequelae of COVID-19: A Systematic Review and Meta-Analysis of One-Year Follow-Up Studies on Post-COVID Symptoms

“…The current body of evidence suggested that female sex [20,25,32,35] and severe/critical acute infection [25,34,35] could be risk factors for experiencing long-term post-COVID symptoms. A cohort study with 342 COVID-19 patients [39] found that time to complete recovery (no ongoing symptoms) was significantly longer in those with moderate and severe/critical initial illness than mild cases, and at least one persistent symptom was reported by 16.4%, 49.5%, and 52.5% of participants in mild, moderate, and severe/critical groups at one year after infection, respectively. However, the pathophysiologic mechanisms of those long-lasting post-COVID symptoms remained unclear.…”

Self-reported symptoms as predictors of SARS-CoV-2 infection in the general population living in the Amsterdam region, the Netherlands

“…The finding that shortness of breath was not associated with a positive test was somewhat surprising, given that it is commonly reported in those with confirmed SARS-CoV-2 infection, with estimates of the prevalence ranging from 15% to 23% [7,8]. However, dyspnoea may occur relatively late in the course of the infection [37]. In those who tested positive in our sample, the median time between symptom onset and applying for a test (at which time the symptoms were assessed) was only 57 hours [IQR = 33-88] [38], which would be too soon for dyspnoea to occur in the majority of patients.…”