Severe fatigue in the first year following SARS-CoV-2 infection: A prospective cohort study 5 139 experienced for symptomatic patients or SARS-CoV-2 diagnosis date for asymptomatic patients. Acute COVID-19 symptoms were those reported <14 days since illness onset. Clinical severity groups were defined based on WHO COVID-19 severity criteria [22]: mild disease as having a RR<20/min and SpO2>94% on room air at both D0 and D7; moderate disease as having a RR 20-30/min and/or SpO2 90-94% or receiving oxygen therapy at D0 or D7; severe disease as having a RR>30/min and/or SpO2<90% or receiving oxygen therapy at D0 or D7; critical disease as ICU admission due to COVID-19 at any point. Highrisk comorbidities were those associated with severe COVID-19 [22]. BMI was coded in kg/m2 as: <25, underweight or normal weight; 25-30, overweight; >30, obese. Migration background was categorised as Dutch and non-Dutch based on the country of birth of the participant and their parents [23, 24]; those of non-Dutch background were further classified as originating from a high-income (HIC) or low-/middle-income country (LMIC) [25]. Highest educational level was categorised as: none; primary/secondary school; vocational training; university-level. The highest reported anxiety and sadness scores at D0 and D7 (baseline) were categorised as hardly any anxiety/sadness (0 or 1), low (2-5) and high (6-10). Statistical analyses Socio-demographic and clinical characteristics of participants were compared between clinical severity groups. Proportions of participants with severe fatigue and corresponding 95% confidence intervals (CIs) were calculated among survey-responders at months 1, 3, 6, 9 and 12, overall and by clinical severity. The proportion of participants in paid employment on prolonged leave due to COVID-19 at month 12 were compared between those severely fatigued or not using Pearson’s χ2 test. Fatigue severity over time was modelled using linear mixed-effects regression, including a random intercept to account for between-patient variation at baseline. Months since illness onset , age and sex were included as fixed covariates, regardless of statistical significance. Three multivariable models were constructed: model 1 added sociodemographic and clinical characteristics; model 2 added COVID-19 clinical severity; model 3 added symptoms reported during acute infection (i.e., baseline anxiety and sadness, acute fatigue, myalgia, headache, cough, dyspnoea, and fever). Variables with a Wald χ2 test p-value<0.20 in the multivariable model with age, sex, and months since illness onset were included in further multivariable analyses. Each multivariable model was then generated using a backwards selection approach. Adjusted beta-coefficients (aβ) and their 95% CIs are presented, showing the mean difference in fatigue severity
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