Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments
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Abstract
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.
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Long COVID syndrome and its mechanisms are still poorly understood, and it affects people regardless of COVID-19 severity, including younger adults, children, and non-hospitalised people.
“This syndrome and its underlying mechanisms are still poorly understood, as it affects people regardless of the severity of their COVID-19 infection, including younger adults, children, and those who were not hospitalised.”
From The Lancet Commission on lessons for the future from the COVID-19 pandemic (2022) · cites this paper as [339]
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- Authors
- Yong, S. J.
- Affiliations
- Sunway University (MY)
- Corresponding author
- Yong, Shin Jie
- ORCID
- Yong, Shin Jie
- Venue
- Infectious Diseases
- Publisher
- Informa UK Limited
- Published
- 2021-05-22
- Volume
- 53
- Issue
- 10
- Pages
- 737-754
- ISSN
- 0036-5548 (ISSN-L)
- 2374-4235
- 2374-4243
- PMC
- PMC8146298
- OpenAlex
- W3165449608
- Cited by
- 1,339
- References
- 201
- Citations by year
- 2026: 82 · 2025: 175 · 2024: 295 · 2023: 375 · 2022: 347 · 2021: 65
- FWCI
- 34.71
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by
- Locations
- Scandinavian Journal of Infectious Diseases (publishedVersion)
- Preprints.org (acceptedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Figshare (submittedVersion, cc-by)
- Figshare (cc-by)
- Topics
- Health Sciences › Medicine › Neurology › Long-Term Effects of COVID-19
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Dermatology › Dermatological and COVID-19 studies
- Keywords
- long COVID, pathophysiology, risk factors, treatment, fatigue, dyspnea, cognitive impairment, viral persistence, immune dysregulation, autoimmunity, D-dimer, C-reactive protein, lymphocyte count, rehabilitation, drug repurposing, chronic fatigue syndrome, postural orthostatic tachycardia syndrome, mast cell activation syndrome
- MeSH terms
- COVID-19, SARS-CoV-2, Post-Acute COVID-19 Syndrome, Mental Disorders, Female, Humans, Risk Factors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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