Fig. 2

The functions of host ncRNAs in the pathogenesis of COVID-19 and representative ncRNAs. a Possible COVID-19 disease course is depicted as differentially colored curves of disease severity over time.²¹⁶ b During the progression of this disease, viral invasion serves as the initial step. Following cleavage of the S protein into S1 and S2 subunits by furin in viral producer cells, the SARS-CoV-2 virus can effectively bind to the ACE2 receptor. Subsequent cleavage occurs either through TMPRSS2 or via endocytosis into the endolysosome. Upon entry into the cytoplasm, it undergoes replication to generate multiple copies for dissemination within the host organism. This is accompanied by translation of viral proteins or polypeptides, assembly, and eventual release into extracellular spaces. The released virus can undergo further reorganization, triggering release of inflammatory signaling molecules from infected cells and alveolar macrophages, while also recruiting T cells, monocytes, and neutrophils. Disease exacerbation leads to increased fluid accumulation in alveolar spaces and potentially cytokine storms that induce hyperinflammation. In late stages of illness, some patients may exhibit acute or persistent multiorgan deficits involving organs such as the brain, lungs, and heart. c In the context of COVID-19, several host miRNAs/lncRNAs/circRNAs have been identified through wet-lab experiments or bioinformatic analysis, elucidating their roles in various aspects of COVID-19 pathogenesis, encompassing viral invasion, replication, immune response modulation, multiorgan failure and long COVID. Biorender was used to generate this figure