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Observational Study
. 2022 Nov 14;75(10):1688-1697.
doi: 10.1093/cid/ciac283.

Risk Factors and Multidimensional Assessment of Long Coronavirus Disease Fatigue: A Nested Case-Control Study

Ili Margalit  1   2   3 , Dana Yelin  2   3 , Moshe Sagi  4 , Maya Merav Rahat  5 , Liron Sheena  4 , Nadav Mizrahi  6 , Yael Gordin  7 , Hadar Agmon  6 , Nitzan Karny Epstein  6 , Alaa Atamna  1   2   3 , Ori Tishler  2   4 , Vered Daitch  5 , Tanya Babich  8 , Donna Abecasis  9 , Yoni Yarom  10 , Shirit Kazum  11 , Dorit Shitenberg  12 , Erik Baltaxe  12 , Odelia Elkana  13 , Irit Shapira-Lichter  3   9   14 , Leonard Leibovici  3   8 , Dafna Yahav  1   2
Affiliations
Observational Study

Risk Factors and Multidimensional Assessment of Long Coronavirus Disease Fatigue: A Nested Case-Control Study

Ili Margalit et al. Clin Infect Dis. .

Abstract

Background: Fatigue is the most prevalent and debilitating long-COVID (coronavirus disease) symptom; however, risk factors and pathophysiology of this condition remain unknown. We assessed risk factors for long-COVID fatigue and explored its possible pathophysiology.

Methods: This was a nested case-control study in a COVID recovery clinic. Individuals with (cases) and without (controls) significant fatigue were included. We performed a multidimensional assessment evaluating various parameters, including pulmonary function tests and cardiopulmonary exercise testing, and implemented multivariable logistic regression to assess risk factors for significant long-COVID fatigue.

Results: A total of 141 individuals were included. The mean age was 47 (SD: 13) years; 115 (82%) were recovering from mild coronavirus disease 2019 (COVID-19). Mean time for evaluation was 8 months following COVID-19. Sixty-six (47%) individuals were classified with significant long-COVID fatigue. They had a significantly higher number of children, lower proportion of hypothyroidism, higher proportion of sore throat during acute illness, higher proportions of long-COVID symptoms, and of physical limitation in daily activities. Individuals with long-COVID fatigue also had poorer sleep quality and higher degree of depression. They had significantly lower heart rate [153.52 (22.64) vs 163.52 (18.53); P = .038] and oxygen consumption per kilogram [27.69 (7.52) vs 30.71 (7.52); P = .036] at peak exercise. The 2 independent risk factors for fatigue identified in multivariable analysis were peak exercise heart rate (OR: .79 per 10 beats/minute; 95% CI: .65-.96; P = .019) and long-COVID memory impairment (OR: 3.76; 95% CI: 1.57-9.01; P = .003).

Conclusions: Long-COVID fatigue may be related to autonomic dysfunction, impaired cognition, and decreased mood. This may suggest a limbic-vagal pathophysiology.

Clinical trials registration: NCT04851561.

Keywords: post-COVID; post-viral fatigue.

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Conflict of interest statement

Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.

Figures

Figure 1.
Figure 1.
Participant flow diagram. Abbreviations: COVID, coronavirus disease; COVID-19, coronavirus disease 2019.
See this image and copyright information in PMC

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