Insights from myalgic encephalomyelitis/chronic fatigue syndrome may help unravel the pathogenesis of postacute COVID-19 syndrome

Trends Mol Med. 2021 Sep;27(9):895-906. doi: 10.1016/j.molmed.2021.06.002. Epub 2021 Jun 7.


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause chronic and acute disease. Postacute sequelae of SARS-CoV-2 infection (PASC) include injury to the lungs, heart, kidneys, and brain that may produce a variety of symptoms. PASC also includes a post-coronavirus disease 2019 (COVID-19) syndrome ('long COVID') with features that can follow other acute infectious diseases and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Here we summarize what is known about the pathogenesis of ME/CFS and of 'acute' COVID-19, and we speculate that the pathogenesis of post-COVID-19 syndrome in some people may be similar to that of ME/CFS. We propose molecular mechanisms that might explain the fatigue and related symptoms in both illnesses, and we suggest a research agenda for both ME/CFS and post-COVID-19 syndrome.

Keywords: COVID-19; SARS-CoV-2; long COVID; myalgic encephalomyelitis/chronic fatigue syndrome; postacute sequelae of SARS-CoV-2; post–COVID-19 syndrome.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • COVID-19 / complications*
  • COVID-19 / etiology
  • COVID-19 / physiopathology
  • Energy Metabolism
  • Fatigue Syndrome, Chronic / etiology*
  • Fatigue Syndrome, Chronic / physiopathology
  • Gastrointestinal Microbiome
  • Humans
  • Nervous System / physiopathology
  • Post-Acute COVID-19 Syndrome