Redox imbalance links COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome

• Published in: Proceedings of the National Academy of Sciences - PNAS 2021-08, Vol.118 (34), p.1-10
• Main Authors: Paul, Bindu D., Lemle, Marian D., Komaroff, Anthony L., Snyder, Solomon H.
• Format: Article
• Language: English
• Subjects: Abnormalities; Adenosine triphosphate; Animals; ATP; Bacterial diseases; Biological Sciences; Chronic fatigue syndrome; Cognitive ability; Complications; Coronaviruses; COVID-19; COVID-19 - complications; COVID-19 - etiology; COVID-19 - immunology; COVID-19 - metabolism; Drug development; Encephalomyelitis; Encephalomyelitis - immunology; Encephalomyelitis - metabolism; Fatigue; Fatigue Syndrome, Chronic - immunology; Fatigue Syndrome, Chronic - metabolism; Humans; Inflammation; Intolerance; Neurological diseases; Orthostatic tolerance; Oxidation-Reduction; PERSPECTIVE; Post-Acute COVID-19 Syndrome; Respiratory diseases; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Signs and symptoms; Subgroups; Viral diseases
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.2024358118

Although most patients recover from acute COVID-19, some experience postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC). One subgroup of PASC is a syndrome called “long COVID-19,” reminiscent of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS is a debilitating condition, often triggered by viral and bacterial infections, leading to years-long debilitating symptoms including profound fatigue, postexertional malaise, unrefreshing sleep, cognitive deficits, and orthostatic intolerance. Some are skeptical that either ME/CFS or long COVID-19 involves underlying biological abnormalities. However, in this review, we summarize the evidence that people with acute COVID-19 and with ME/CFS have biological abnormalities including redox imbalance, systemic inflammation and neuroinflammation, an impaired ability to generate adenosine triphosphate, and a general hypometabolic state. These phenomena have not yet been well studied in people with long COVID-19, and each of them has been reported in other diseases as well, particularly neurological diseases. We also examine the bidirectional relationship between redox imbalance, inflammation, energy metabolic deficits, and a hypometabolic state. We speculate as to what may be causing these abnormalities. Thus, understanding the molecular underpinnings of both PASC and ME/CFS may lead to the development of novel therapeutics.