Skeletal Muscle and COVID-19: The Potential Involvement of Bioactive Sphingolipids.

SARS-CoV-2 virus infection is the cause of the coronavirus disease 2019 (COVID-19), which is still spreading over the world. The manifestation of this disease can range from mild to severe and can be limited in time (weeks) or persist for months in about 30-50% of patients. COVID-19 is considered a multiple organ dysfunction syndrome and the musculoskeletal system manifestations are beginning to be considered of absolute importance in both COVID-19 patients and in patients recovering from the SARS-CoV-2 infection. Musculoskeletal manifestations of COVID-19 and other coronavirus infections include loss of muscle mass, muscle weakness, fatigue or myalgia, and muscle injury. The molecular mechanisms by which SARS-CoV-2 can cause damage to skeletal muscle (SkM) cells are not yet well understood. Sphingolipids (SLs) represent an important class of eukaryotic lipids with structural functions as well as bioactive molecules able to modulate crucial processes, including inflammation and viral infection. In the last two decades, several reports have highlighted the role of SLs in modulating SkM cell differentiation, regeneration, aging, response to insulin, and contraction. This review summarizes the consequences of SARS-CoV-2 infection on SkM and the potential involvement of SLs in the tissue responses to virus infection. In particular, we highlight the role of sphingosine 1-phosphate signaling in order to aid the prediction of novel targets for preventing and/or treating acute and long-term musculoskeletal manifestations of virus infection in COVID-19.