Skeletal muscle alterations in patients with acute Covid‐19 and post‐acute sequelae of Covid‐19

Abstract

Skeletal muscle‐related symptoms are common in both acute coronavirus disease (Covid)‐19 and post‐acute sequelae of Covid‐19 (PASC). In this narrative review, we discuss cellular and molecular pathways that are affected and consider these in regard to skeletal muscle involvement in other conditions, such as acute respiratory distress syndrome, critical illness myopathy, and post‐viral fatigue syndrome. Patients with severe Covid‐19 and PASC suffer from skeletal muscle weakness and exercise intolerance. Histological sections present muscle fibre atrophy, metabolic alterations, and immune cell infiltration. Contributing factors to weakness and fatigue in patients with severe Covid‐19 include systemic inflammation, disuse, hypoxaemia, and malnutrition. These factors also contribute to post‐intensive care unit (ICU) syndrome and ICU‐acquired weakness and likely explain a substantial part of Covid‐19‐acquired weakness. The skeletal muscle weakness and exercise intolerance associated with PASC are more obscure. Direct severe acute respiratory syndrome coronavirus (SARS‐CoV)‐2 viral infiltration into skeletal muscle or an aberrant immune system likely contribute. Similarities between skeletal muscle alterations in PASC and chronic fatigue syndrome deserve further study. Both SARS‐CoV‐2‐specific factors and generic consequences of acute disease likely underlie the observed skeletal muscle alterations in both acute Covid‐19 and PASC.

A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications

“…These obviously include breathlessness due to low O 2 directly, and thrombotic events such as acute myocardial infarction [180,181], stroke [181][182][183], etc due to the microclots. The lack of O 2 transport to tissues explains straightforwardly how a nominally respiratory disease also leads to the dysfunction of organs such as the kidney [184,185], PoTS ( postural tachycardia syndrome [186]), myalgia in skeletal muscle [187,188], neurological disorders [189], and lactic acidosis [190,191] (the mass of lactate is too low to have been detected in our own COVID untargeted metabolomics experiments [192]), and potentially the benefits of hyperbaric O 2 therapy [193]. It is also worth stressing that amyloid structures themselves tend to be cytotoxic, often via membrane disruption [194][195][196][197][198].…”

Unheeded SARS-CoV-2 proteins? A deep look into negative-sense RNA

“…STRING analysis [ 38 ] of all proteins predicted to interact with nsORFs RNA revealed significant enrichment of several molecular and biological processes, such as alternative splicing, RNA processing, gene silencing and so on. ( Supplementary Table S2 ), which could potentially explain heterogenous and unexpectable symptoms of COVID-19 patients—from the muscle pain [ 39 ] to hepatobiliary and pancreatic injury [ 40 ]. All mentioned symptoms are frequently explained by a decrease of oxygen saturation or inflammatory factors, but, herein, we may have further demystified the complex mosaic of signaling behind such manifestations.…”

Skeletal Muscle in Hypoxia and Inflammation: Insights on the COVID-19 Pandemic

“…Indeed, after 10 days patients showed a 30% loss in rectus femoris cross-sectional area, a lower thickness (of almost 20%) of the quadriceps muscle (133) and weakness during knee-extensor and arm-flexor tests (135). The impairment in quadriceps strength and in general of muscle strength was significantly associated with a longer hospital stay (136). Low muscle mass is an independent risk factor for mortality (136).…”

“…The impairment in quadriceps strength and in general of muscle strength was significantly associated with a longer hospital stay (136). Low muscle mass is an independent risk factor for mortality (136). Not surprisingly, SARS-CoV-2 infected sarcopenic patients need a twice-long hospital stay and have an eight times higher mortality rate than non-sarcopenic subjects (137).…”