MicroRNAs and cytokines as potential predictive biomarkers for COVID-19 disease progression

Host microRNAs can influence the cytokine storm associated SARS-CoV-2 infection and proposed as biomarkers for COVID-19 disease. In the present study, serum MiRNA-106a and miRNA-20a were quantified by real time-PCR in 50 COVID-19 patients hospitalized at Minia university hospital and 30 healthy volunteers. Profiles of serum inflammatory cytokines (TNF-alpha, IFN-gamma, and IL-10) and TLR4 were analyzed by Eliza in patients and controls. A highly significant decrease (P value=0.0001) in the expressions of miRNA-106a and miRNA-20a was reported in COVID-19 patients compared to controls. A significant decrease in the levels of miRNA-20a was also reported in patients with lymphopenia, patients having chest CT severity score (CSS)>19 and in patients having O-2 saturation less than 90%. Significantly higher levels of TNF-alpha, IFN-gamma, IL-10 and TLR4 were reported in patients compared to controls. IL-10 and TLR4 levels were significantly higher in patients having lymphopenia. TLR-4 level was higher in patients with CSS>19 and in patients with hypoxia. Using univariate logistic regression analysis, miRNA-106a, miRNA-20a, TNF-alpha, IFN-gamma, IL-10 and TLR4 were identified as good predictors of disease. Receiver operating curve showed that the downregulation of miRNA-20a in patients having lymphopenia, patients with CSS>19 and patients with hypoxia could be a potential biomarker with AUC=0.68 +/- 0.08, AUC=0.73 +/- 0.07 and AUC=0.68 +/- 0.07 respectively. Also, ROC curve showed accurate association between the increase of serum IL-10 and TLR-4 and lymphopenia among COVID-19 patients with AUC=0.66 +/- 0.08 and AUC=0.73 +/- 0.07 respectively. ROC curve showed also that serum TLR-4 could be a potential marker for high CSS with AUC=0.78 +/- 0.06. A negative correlation was detected between miRNA-20a with TLR-4 (r=-0.30, P value=0.03). We concluded that, miR-20a, is a potential biomarker of COVID-19 severity and blockade of IL-10 and TLR4 may constitute a novel therapy for COVID-19 patients.