Long COVID and Post-infective Fatigue Syndrome: A Review

Abstract

Fatigue is a dominant feature of both acute and convalescent coronavirus disease 2019 (COVID-19) (sometimes termed "long-COVID"), with up to 46% of patients reporting fatigue that lasts from weeks to months. The investigators of the international Collaborative on Fatigue Following Infection (COFFI) conducted a systematic review of post-COVID fatigue and a narrative review on fatigue after other infections, and made recommendations for clinical and research approaches to assessing fatigue after COVID-19. In the majority of COVID-19 cohort studies, persistent fatigue was reported by a significant minority of patients, ranging from 13% to 33% at 16-20 weeks post-symptom onset. Data from the prospective cohort studies in COFFI and others indicate that fatigue is also a prevalent outcome from many acute systemic infections, notably infectious mononucleosis, with a case rate for clinically significant Post-infective fatigue after exclusion of recognized medical and psychiatric causes, ranging from 10%-35% at 6 months. To better characterize post-COVID fatigue, the COFFI investigators recommend the following: application of validated screening questionnaires for case detection; standardized interviews encompassing fatigue, mood, and other symptoms; and investigative approaches to identify end-organ damage and mental health conditions.

Keywords: COVID-19; assessment; cohorts; fatigue; post-viral.

Figure 1.

Prevalence of fatigue in COVID-19 from prospective studies. Black symbols refer to the original rate reported by each study. Gray symbols refer to rate recalculated with all eligible individuals included in the denominator.

Figure 2.

Prevalence of fatigue in COVID-19 from cross-sectional studies. The box extends from the 25th to 75th percentiles, the line represents the median, and the whiskers show the minimum and maximum. Week 28 is represented by a single study. (A) shows the original rates reported by the included studies. The proportion of patients reporting fatigue were as follows: 10%–73% at 4–7 weeks [17, 23, 24, 28], 22%–69% at 8–11 weeks [13, 15, 21, 22, 26], 39%–52% at 12–15 weeks [12, 18, 19], 16%–59% at 16–20 weeks [14, 16, 20, 25, 27], and 34% at 28 weeks from symptom onset [29]. (B) shows these rates recalculated with all eligible individuals included in the denominator: 8%–24% at 4–7 weeks [17, 23, 24, 28], 10%–55% at 8–11 weeks [13, 15, 21, 22, 26], 14%–26% at 12–15 weeks [12, 18, 19], 13%–33% between weeks 16 and 20 [14, 16, 20, 25, 27], and 32% at 28 weeks from symptom onset [29].