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

Anouk Verveen; Elke Wynberg; Hugo D G van Willigen; Anders Boyd; Menno D de Jong; Godelieve de Bree; Udi Davidovich; Anja Lok; Eric P Moll van Charante; Hans Knoop; Maria Prins; Pythia Nieuwkerk; RECoVERED Study Group

doi:10.1093/ofid/ofac127

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

Open Forum Infect Dis. 2022 Apr 10;9(5):ofac127. doi: 10.1093/ofid/ofac127. eCollection 2022 May.

Authors

Anouk Verveen¹, Elke Wynberg^{2

3}, Hugo D G van Willigen^{3

4}, Anders Boyd^{2

5}, Menno D de Jong⁴, Godelieve de Bree³, Udi Davidovich^{2

6}, Anja Lok⁷, Eric P Moll van Charante^{8

9}, Hans Knoop¹, Maria Prins^{2

3}, Pythia Nieuwkerk¹; RECoVERED Study Group

Collaborators

RECoVERED Study Group:
Ivette Agard, Jane Ayal, Floor Cavdar, Marianne Craanen, Annemarieke Deuring, Annelies van Dijk, Ertan Ersan, Laura Del Grande, Joost Hartman, Nelleke Koedoot, Tjalling Leenstra, Romy Lebbink, Dominique Loomans, Agata Makowska, Tom du Maine, Ilja de Man, Amy Matser, Lizenka van der Meij, Marleen van Polanen, Maria Oud, Clark Reid, Leeann Storey, Marc van Wijk, Joost van den Aardweg, Joyce van Assem, Marijne van Beek, Thyra Blankert, Maartje Dijkstra, Orlane Figaroa, Leah Frenkel, Marit van Gils, Jelle van Haga, Xiaochuan Han, Agnes Harskamp-Holwerda, Mette Hazenberg, Soemeja Hidad, Nina de Jong, Neeltje Kootstra, Lara Kuijt, Colin Russell, Karlijn van der Straten, Annelou van der Veen, Bas Verkaik, Gerben-Rienk Visser

Affiliations

¹ Department of Medical Psychology, Amsterdam UMC, Amsterdam Public Health Research Institute, University of Amsterdam, Amsterdam, the Netherlands.
² Department of Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, the Netherlands.
³ Department of Infectious Diseases, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Amsterdam, the Netherlands.
⁴ Department of Medical Microbiology & Infection Prevention, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Amsterdam, the Netherlands.
⁵ Stichting HIV Monitoring, Amsterdam, the Netherlands.
⁶ Department of Social Psychology, University of Amsterdam, Amsterdam, the Netherlands.
⁷ Department of Psychiatry, Amsterdam UMC, location AMC, University of Amsterdam, Amsterdam, the Netherlands.
⁸ Department of Public & Occupational Health, Amsterdam UMC, Amsterdam Public Health Research Institute, University of Amsterdam, Amsterdam, the Netherlands.
⁹ Department of General Practice, Amsterdam UMC, Amsterdam Public Health Research Institute, University of Amsterdam, Amsterdam, the Netherlands.

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.