Synergistic Effects of Multiple Factors Involved in COVID-19-dependent Muscle Loss

The COVID-19 pandemic caused by the novel SARS-CoV-2 coronavirus is an ongoing pandemic causing severe health crisis worldwide. Recovered COVID-19 patients go through several long-term side effects such as fatigue, headaches, dizziness, weight loss, and muscle loss among others. Our study sought to determine the molecular mechanisms behind muscle loss in COVID-19 patients. We hypothesized that multiple factors such as cytokine storm and therapeutic drugs (glucocorticoid and antiviral drugs) might be involved in muscle loss. Using the Gene Expression Omnibus database, we identified several studies that performed RNA sequencing on skeletal muscles with the treatment of cytokine, glucocorticoid, and antiviral drugs. Our study identified cytokines, such as IL-1b, and IL-6, associated with altered regulation of several genes involved in the myogenic processes, including Ttn, Cxxc5, Malat1, and Foxo1. We also observed that glucocorticoid altered the expression of Foxo1, Lcn2, Slc39a14, and Cdkn1a. Finally, we found out that the antiviral (RNA-dependent RNA polymerase inhibitor) drug regulates the expression of some of the muscle-related genes (Txnip, Ccnd1, Hdac9, and Fbxo32). Based on our findings, we hypothesize that the cytokine storm, glucocorticoids, and antiviral drugs might be synergistically involved in COVID-19-dependent muscle loss.