Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments

Infect Dis (Lond). 2021 Oct;53(10):737-754. doi: 10.1080/23744235.2021.1924397. Epub 2021 May 22.


Long COVID or post-COVID-19 syndrome first gained widespread recognition among social support groups and later in scientific and medical communities. This illness is poorly understood as it affects COVID-19 survivors at all levels of disease severity, even younger adults, children, and those not hospitalized. While the precise definition of long COVID may be lacking, the most common symptoms reported in many studies are fatigue and dyspnoea that last for months after acute COVID-19. Other persistent symptoms may include cognitive and mental impairments, chest and joint pains, palpitations, myalgia, smell and taste dysfunctions, cough, headache, and gastrointestinal and cardiac issues. Presently, there is limited literature discussing the possible pathophysiology, risk factors, and treatments in long COVID, which the current review aims to address. In brief, long COVID may be driven by long-term tissue damage (e.g. lung, brain, and heart) and pathological inflammation (e.g. from viral persistence, immune dysregulation, and autoimmunity). The associated risk factors may include female sex, more than five early symptoms, early dyspnoea, prior psychiatric disorders, and specific biomarkers (e.g. D-dimer, CRP, and lymphocyte count), although more research is required to substantiate such risk factors. While preliminary evidence suggests that personalized rehabilitation training may help certain long COVID cases, therapeutic drugs repurposed from other similar conditions, such as myalgic encephalomyelitis or chronic fatigue syndrome, postural orthostatic tachycardia syndrome, and mast cell activation syndrome, also hold potential. In sum, this review hopes to provide the current understanding of what is known about long COVID.

Keywords: Long-haul COVID-19; drug repurposing; long COVID; pathophysiology; post-COVID-19 syndrome; risk factors.

Publication types

  • Review

MeSH terms

  • COVID-19* / complications
  • Female
  • Humans
  • Mental Disorders*
  • Post-Acute COVID-19 Syndrome
  • Risk Factors
  • SARS-CoV-2

Grants and funding

No funding was received for this work.