Severe fatigue in the first year following SARS-CoV-2 infection: A prospective cohort study 5 137 INTRODUCTION Fatigue is among the most commonly reported symptoms of post-acute COVID-19 syndrome (PACS). PACS is defined by the World Health Organization (WHO) as the persistence of symptoms at 3 months after SARS-CoV-2 infection, lasting for at least 2 months [1]. Fatigue persisting beyond 6 months after infection is frequently reported among previously-hospitalised COVID-19 patients [2-5] and a growing body of evidence suggests that fatigue may also be long-lasting following mild COVID-19 [6, 7]. Persistent fatigue has been linked to other infectious diseases, including Epstein-Barr virus [8], Q-fever [9], influenza [10] and SARS-CoV-1 infection [11]. Estimates of the prevalence of fatigue following COVID-19 vary widely due to differences in the definition of fatigue, study design and study population [4, 7, 12, 13]. Few studies have measured fatigue using instruments with validated cut-offs for severe fatigue, nor have they explored risk factors for fatigue using prospectively-collected longitudinal data [14-16]. Insights into the occurrence, severity and risk factors of persistent fatigue post-COVID-19 are crucial to understanding and mitigating the long-term consequences of infection. In this prospective cohort study, we aimed to describe the presence of severe fatigue up to 12 months following illness onset across the full spectrum of COVID-19 severity, and identify risk factors associated with both severity of fatigue over time and persistent severe fatigue specifically. METHODS Study design and participants RECoVERED is a cohort study of individuals with SARS-CoV-2 infection in Amsterdam, the Netherlands. Enrolment began on 11 May 2020. Non-hospitalised participants were identified from notification data of laboratory-confirmed SARS-CoV-2 infection at the Public Health Service of Amsterdam and enrolled within 7 days of diagnosis [17]. Prospectively-enrolled hospitalised participants were identified from admissions to the COVID-19 wards of the Amsterdam University Medical Centres (AUMC) and enrolled within 7 days of admission. Up to 30 June 2020, a limited number of hospitalised patients were included retrospectively within 3 months following SARS-CoV-2 diagnosis. Eligibility criteria included laboratory confirmation of SARS-CoV-2 infection by reverse transcriptase polymerase chain reaction (RT-PCR), age 16-85 years, residing in the municipal region of Amsterdam, and adequate understanding of Dutch or English.
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