The Challenge of Long COVID-19 Management: From Disease Molecular Hallmarks to the Proposal of Exercise as Therapy

Abstract

Long coronavirus disease 19 (COVID-19) is the designation given to a novel syndrome that develops within a few months after infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and that is presenting with increasing incidence because of the numerous cases of infection. Long COVID-19 is characterized by a sequela of clinical symptoms that concern different organs and tissues, from nervous, respiratory, gastrointestinal, and renal systems to skeletal muscle and cardiovascular apparatus. The main common molecular cause for all long COVID-19 facets appears to be related to immune dysregulations, the persistence of inflammatory status, epigenetic modifications, and alterations of neurotrophin release. The prevention and management of long COVID-19 are still inappropriate because many aspects need further clarification. Exercise is known to exert a deep action on molecular dysfunctions elicited by long COVID-19 depending on training intensity, duration, and continuity. Evidence suggests that it could improve the quality of life of long COVID-19 patients. This review explores the main clinical features and the known molecular mechanisms underlying long COVID-19 in the perspective of considering exercise as a co-medication in long COVID-19 management.

Persistent SARS-CoV-2 Infection, EBV, HHV-6 and Other Factors May Contribute to Inflammation and Autoimmunity in Long COVID

“…For their part, Scurati et al found in their own review that exercise is known to exert a deep action on molecular dysfunctions elicited by long COVID-19. Of course, it depends on training, intensity, duration and continuity, but the information they presented bears the consideration of properly regulated exercise as part of the management protocol for long COVID [ 239 ]. For patients exhibiting the fatigue or post-exertional malaise characteristic of both long COVID and ME/CSF, a personalized, symptom-guided program for a phased return to activity is recommended [ 230 ].…”

Severe COVID-19 and its cardiopulmonary effects 6 and 18 months after hospital discharge

“…Regarding the management of symptoms, existing evidence is limited to exercise training rehabilitation, which improved dyspnea in Long COVID ( 42 ). Initial research mainly focused on symptom-centered treatments that included naltrexone against neuro-inflammation, beta blockers for postural tachycardia syndrome, antihistamines and/or intravenous immunoglobulins for immune dysfunction and cognitive pacing for cognitive dysfunction.…”

The pulmonary rehabilitation effect on long covid‐19 syndrome: A systematic review and meta‐analysis

“…The study population includes studies with adults (18 years or older) diagnosed with long COVID‐19, defined as the continuation or development of new symptoms 3 months after the initial SARS‐CoV‐2 infection (Scurati et al., 2022). Studies with acute or subacute populations were excluded.…”

“…Nevertheless, a consistent percentage of patients affected by COVID‐19 continue with symptoms after the acute phase. This new disease is known as Long COVID‐19 (LC) and was defined by the World Health Organization as “the continuation or development of new symptoms 3 months after the initial SARS‐CoV‐2 infection” (Scurati et al., 2022), and potentially affects from 10% to 50% of patients (Bouteleux et al., 2021). Due to multiorgan involvement in LC cases, breathlessness, fatigue, neuropsychological symptoms, cough, musculoskeletal pain, and alterations in smell and taste were the most commonly associated symptoms (Jimeno‐Almazán et al., 2021; Scurati et al., 2022).…”