COVID-19 and post-infectious myalgic encephalomyelitis/chronic fatigue syndrome: a narrative review

Abstract

Coronavirus disease 2019 (COVID-19) is a viral infection which can cause a variety of respiratory, gastrointestinal, and vascular symptoms. The acute illness phase generally lasts no more than 2-3 weeks. However, there is increasing evidence that a proportion of COVID-19 patients experience a prolonged convalescence and continue to have symptoms lasting several months after the initial infection. A variety of chronic symptoms have been reported including fatigue, dyspnea, myalgia, exercise intolerance, sleep disturbances, difficulty concentrating, anxiety, fever, headache, malaise, and vertigo. These symptoms are similar to those seen in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a chronic multi-system illness characterized by profound fatigue, sleep disturbances, neurocognitive changes, orthostatic intolerance, and post-exertional malaise. ME/CFS symptoms are exacerbated by exercise or stress and occur in the absence of any significant clinical or laboratory findings. The pathology of ME/CFS is not known: it is thought to be multifactorial, resulting from the dysregulation of multiple systems in response to a particular trigger. Although not exclusively considered a post-infectious entity, ME/CFS has been associated with several infectious agents including Epstein-Barr Virus, Q fever, influenza, and other coronaviruses. There are important similarities between post-acute COVID-19 symptoms and ME/CFS. However, there is currently insufficient evidence to establish COVID-19 as an infectious trigger for ME/CFS. Further research is required to determine the natural history of this condition, as well as to define risk factors, prevalence, and possible interventional strategies.

Keywords: COVID-19; chronic fatigue syndrome; human coronavirus; myalgic encephalomyelitis; post-infectious fatigue; review.

Figure 1.

Summary of post-infectious ME/CFS mechanisms. Infective agents activate and alter immune system function leading to chronic inflammation, increased pro-inflammatory cytokine signaling, and abnormal function of multiple cell types including Th1, Th17, T-regulatory, and natural killer cells. Autoimmune mechanisms such as molecular mimicry and auto-reactive bystander cell activation can also be triggered during acute infection. Infective agents with neuro-invasive potential can cause inflammatory and ischemic damage to central nervous system cells and tissues, resulting in neuronal degeneration, demyelination, and subsequent functional impairment. Infective agents may also cause structural damage to mitochondria, leading to decreased energy production, altered metabolism, and reduced anti-oxidant function. These processes may underlie the symptoms reported in post-infectious ME/CFS.