The Prevalence, Severity, and Impact of Post-COVID Persistent Fatigue, Post-Exertional Malaise, and Chronic Fatigue Syndrome

Abstract

Fatigue is common after viral infections, including SARS-CoV-2. Our purpose was to report the prevalence and impact of persistent fatigue 6 months after SARS-CoV-2 infection, considering post-exertional malaise and criteria for chronic fatigue syndrome. Since March 2020, individuals tested for SARS-CoV-2 at the Geneva University Hospitals outpatient testing center benefit from remote ambulatory follow-up (COVICARE). This study included all individuals tested between March 2020 and December 2020 and whose follow-up was at 6 months or more after their test date. Follow-up included questions about the prevalence of symptoms (yes/no) and their severity using a Likert scale (mild, moderate, or severe). Fatigue was assessed using the Eastern Cooperative Oncology Group (ECOG) scale and the Chalder fatigue scale. The Chalder fatigue scale was scored using the 4-item Likert and the bimodal scoring schemes. A score of ≥ 4 on bimodal scoring indicated severe fatigue. The DePaul brief questionnaire was used to identify post-exertional malaise and criteria for chronic fatigue syndrome. The Sheehan Disability Scale was used to assess functional impairment. Reduced work capacity was defined as missing days off work or having a reduced productivity on the Sheehan disability scale. Comorbidities were considered present if pre-existing prior to SARS-CoV-2 infection. Statistical analysis included descriptive comparisons of percentages using chi-square tests and Student’s t test. Overall, 5515 individuals participated in this study (response rate 70.7%), with 5406 participants at 6 months or more after their test date. A total of 1497 (27.7%) participants had a documented positive SARS-CoV-2 test and were ultimately included in the study. The median time for follow-up was 225 days (interquartile range 207–398). Respectively, fatigue was reported by 17.2%, post-exertional malaise by 8.2%, and the presence of criteria for chronic fatigue syndrome by 1.1% of SARS-CoV-2-positive individuals, compared to 8.9%, 3.5%, and 0.5% of SARS-CoV-2-negative individuals. Characteristics are presented in Table 1 . Out of SARS-CoV-2-positive participants with fatigue ( n = 258), 35.3% had moderate to severe limitations on the ECOG scale, and 83.0% had a score ≥ 4 on the Chalder fatigue scale. The Chalder fatigue scale revealed a mean score of 19 out of 33, SD 5.4, and a mean score of 6.7 out of 11, SD 3.3 using bimodal scoring. After adjusting for age and sex, 47.7% of SARS-CoV-2-positive individuals with fatigue at 6 months or more had the frequency and severity criteria for post-exertional malaise, and 6.2% had criteria for chronic fatigue syndrome. Individuals had a higher prevalence of insomnia, cognitive impairment, headaches, generalized pain, functional impairment, reduced work capacity, and decreased physical activity, after SARS-CoV-2 infection. The prevalence of these sequelae was adjusted for age and sex and was increasingly higher with severe fatigue, with post-exertional malaise, or when criteria for chronic fatigue syndrome were present (Fig. 1 ). The prevalence of newly developed insomnia, cognitive impairment, headache, generalized pain, and functional and physical impairment stratified by fatigue severity including post-exertional malaise and criteria for chronic fatigue syndrome in SARS-CoV-2-positive individuals at 6 months or more after their infection ( n = 1497)*. Prevalence is adjusted for age and sex. Only newly reported symptoms and sequelae after SARS-CoV-2 infection were included in this analysis. Severe fatigue is defined as a Chalder fatigue scale score ≥ 4. The DePaul brief questionnaire evaluated the frequency and severity of symptoms characterizing post-exertional malaise including heaviness or drowsiness after exercise, pain, fatigue, and exhaustion after minimal effort, as well as the time required for recovery. Using a Likert scale, a score of 2 or more on the frequency (5 questions) and severity (5 questions) of symptoms indicated post-exertional malaise. If recovery required more than 14 h after minimal physical or mental activity, the questionnaire was positive for chronic fatigue syndrome.

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