Long COVID and post-infective fatigue syndrome – a review


Senior Member
Carolina X Sandler, PhD, Vegard B B Wyller, PhD, Rona Moss-Morris, PhD, Dedra Buchwald, PhD, Esther Crawley, PhD, Jeannine Hautvast, PhD, Ben Z Katz, Hans Knoop, PhD, Paul Little, Renee Taylor, PhD, Knut-Arne Wensaas, PhD, Andrew R Lloyd, PhD, Long COVID and post-infective fatigue syndrome – a review, Open Forum Infectious Diseases, 2021;, ofab440, doi: 10.1093/ofid/ofab440

Fatigue is a dominant feature of both acute and convalescent COVID-19 (sometimes termed ‘long-COVID’), with up to 46% of patients reporting fatigue lasting weeks to months. The investigators of the international Collaborative on Fatigue Following Infection (COFFI) conducted a systematic review of post-COVID fatigue, a narrative review on fatigue after other infections and made recommendations for clinical and research approaches to assessment of fatigue following COVID-19.

In the majority of COVID-19 cohort studies, persistent fatigue was reported by a significant minority of patients, ranging from 13-33% 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, of 10-35% at 6 months.

To better characterize post-COVID fatigue, the COFFI investigators recommend: 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.

  • Fatigue after COVID-19 is common, but generally resolves over months, like other postinfective fatigue states
  • Post-COVID fatigue results from end-organ injury, mental health conditions, or idiopathic post-COVID fatigue
  • Post-COVID fatigue should be assessed with validated questionnaires, interviews, and protocolized investigations