Severe Fatigue in the First Year Following SARS-CoV-2 Infection: A Prospective Cohort Study

Abstract

Background: Severe fatigue can persist for months after coronavirus disease 2019 (COVID-19) onset. This longitudinal study describes fatigue severity and its determinants up to 12 months after illness onset across the full spectrum of COVID-19 severity.

Methods: RECoVERED, a prospective cohort study in Amsterdam, the Netherlands, enrolled participants aged ≥16 years after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis. Fatigue was measured using the validated Short Fatigue Questionnaire (SFQ; range 4-28) at months 1, 3, 6, 9, and 12 of follow-up. Fatigue severity was modeled over time using mixed-effects linear regression. Determinants of severe fatigue (SFQ ≥18) at 6 months since illness onset (ie, persistent fatigue) were identified using logistic regression.

Results: Between May 2020 and July 2021, 303 participants completed at least 1 fatigue questionnaire. Twelve months after illness onset, 17.4% (95% CI, 6.7% to 38.3%), 21.6% (95% CI, 11.2% to 37.7%), and 44.8% (95% CI, 28.0% to 62.9%) of participants with mild, moderate, and severe/critical COVID-19 (World Health Organization definition), respectively, experienced severe fatigue. When adjusting for age and sex, having ≥3 comorbidities (P = .007), severe/critical COVID-19 (P = .002), low mood (P < .001), and dyspnea in the first 2 weeks of illness (P = .001) were associated with more severe fatigue over time. Severe/critical COVID-19 (adjusted odds ratio [aOR], 3.37; 95% CI, 1.28 to 8.93) and low mood at enrollment (aOR, 2.43; 95% CI, 1.11 to 5.29) were associated with persistent fatigue. Recovery rarely occurred beyond 6 months after illness onset, regardless of COVID-19 severity.

Conclusions: The occurrence of severe fatigue in our cohort was high, especially among those with initially severe/critical COVID-19, with little recovery beyond 6 months after illness onset. Our findings highlight an urgent need for improved understanding of persistent severe fatigue following COVID-19 to help inform prevention and intervention.

Keywords: COVID-19; fatigue; infection; persistence; predictors.

Figure 1.

Central dot represents proportion with severe fatigue among those who completed each questionnaire; vertical bars are corresponding 95% CIs for that group. Total sample size differs per month due to varying survey response rates and lengths of follow-up time: Month 1: n = 212, Month 3: n = 258, Month 6: n = 208, Month 9: n = 148, Month 12: n = 89. Severe fatigue defined has a short fatigue questionnaire (SFQ) score ≥ 18.

Figure 2.

COVID-19 clinical severity defined as follows: mild disease as having a RR <20/min and SpO₂ >94% on room air at both D0 and D7 study visits; moderate disease as having a RR20–30/min and SpO₂ 90–94% or receiving oxygen therapy at D0 and/or D7 study visits; severe disease as having a RR >30/min and SpO2 <90% or receiving oxygen therapy at D0 and/or D7 study visits; critical disease as requiring ICU admission as a result of COVID-19 at any point. Highest baseline sadness score defined as the highest reported level of sadness at D0 or D7, subjectively reported on a scale from 0 to 10. Abbreviation: aOR, adjusted odds ratio.