ABSTRACT: The exact role of epigenetics in the pathogenesis of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is unclear. Herein we have hypothesized that viral micro RNAs (miRNAs) may modulate host cellular and immune responses which may lead to varied clinical presentations. Using bioinformatics tools, we have first predicted putative miRNAs in the genotype of the SARS-CoV-2 and their potential gene targets. Thereafter, quantification of mRNA of key genes regulating inflammation, coagulation, neuropsychiatric functions, fibrosis and glucose metabolism was evaluated in the peripheral blood mononuclear cells and bone marrow of patients suffering from different severities of SARS-CoV-2 infection. Key genes regulating innate immunity, lymphopoiesis, T-cell and B-cell development, cytokine storm, coagulation pathways, fibrosis, neuropsychiatric manifestations, glucose metabolism, and olfaction were significantly downregulated in severe infection when compared with mild infection. Downregulated genes mRNA recovered to normal/near normal levels on recovery from infection. SARS-CoV-2 miRNAs appear promising players in the pathogenesis of COVID-19. Strategies silencing these miRNAs may be explored further as potential therapeutic targets. Patients with severe illness were defined as: respiratory rate ≥30 per min or SpO2 <90% in ambient air, or acute respiratory distress syndrome or septic shock and those with mild illness as: patients with any of the symptoms like fever, cough, sore throat, malaise, headache, muscle pain, nausea, vomiting, diarrhea, loss of taste and smell, but no dyspnea, or abnormal chest imaging. There were 4 severe SARS CoV-2 patients, Median age 57.5 years (Range 50-72 years), all males, median disease duration 7.5 days, duration of hospital stay 38 days with outcome as 3 deaths and one Post covid lung fibrosis. All 4 mild cases had median age 55.5 years (range 42-0 years), 3 males and one female, mean disease duration 2.8 days, mean duration of hospitalization 14.5 days and all recovered. Median age of all 4 recovered cases was 59 years (range 43-77 years), 3 males and one female, mean disease duration of 6 days, mean disease duration of 22 days and all recovered. There were 4 healthy subjects with median age 50 years (range 42-54 years) and there were 3 males and one female. All 3 patients who underwent bone marrow examination had severe Covid-19 and were different then the ones whose peripheral blood was analyed by qRT-PCR. Amongst Disease control subjects (n=3) who underwent bone marrow examination, two had adult onset immune thrombocytopenia and one had a suspicion of myelodysplastic syndrome which was reported to be normal.
