Long COVID: Where Are We in 2023?

• Published in: Missouri medicine 2023-03, Vol.120 (2), p.102-105
• Main Authors: Regunath, Hariharan, Goldstein, Nir M, Guntur, Vamsi P
• Format: Article
• Language: English
• Subjects: Chronic fatigue syndrome; Coronaviruses; COVID-19; Disease control; Humans; Post-Acute COVID-19 Syndrome
• ISSN: 0026-6620

The term "COVID Long-Hauler" or "LongHaul COVID" was first created by patients within few months of the onset of the pandemic.1, 2 The first publication of persistent symptoms following acute COVID-19 was from Italy in July 2020, where-in, 143 hospitalized patients with acute COVID-19 between April and May 2020, who eventually tested negative by polymerase chain reaction (PCR), were followed for two months as out-patient and 87.4% had at least one persistent symptom.3 The database study from the United States (U.S.) Department of Veterans Affairs (VA) was the first largest study to show that beyond a month of illness, there existed a higher risk for death and healthcare utilization because of a variety of incident respiratory, cardiovascular, neurological, musculoskeletal, gastrointestinal and metabolic disorders.4 Subsequently, multiple other observational studies have been published.5-10 The systematic reviews that followed, were limited by the low quality of such studies, lack of standardized definition and representative biologic markers for the different organ systems involved as a part of this syndrome. To date, "long COVID" remains loosely defined by the Centers for Disease Control and Prevention (CDC) as new-onset, persistent or evolving symptoms that linger beyond four weeks following recovery from a documented acute COVID illness or diagnosis, and characterized by persistent physical or mental health issues.11 The World Health Organization (WHO) uses a longer interval of 12 weeks in the absence of an alternative explanation or diagnosis.12, 13 Consensus continues to be lacking for a unified definition due to wide variations in study criteria, measures, and quality.14 Long COVID, post-COVID conditions, post-acute sequelae of SARS CoV-2 (PASC), chronic COVID-19, ongoing symptomatic COVID-19, postCOVD-19 persistent symptoms, and post COVID-19 syndrome are all merely different terms for a set of continued symptoms that linger after recovery from acute illness. An elusive variety of direct (viral) and indirect pathophysiological hypotheses for long COVID, included viral persistence/reservoir in different tissues, mitochondrial dysfunction, immune dysregulation as a continuation from the initial infection, persistent vascular endothelial or other organ injury, triggering or exacerbation of auto-immunity, gut dysbiosis and certain co-morbidities that increase the risk for long COVID.20-24 The most interesting of these mechanisms is evidence for persiste