Critical disease status and invasive mechanical ventilation (IMV) increase the risk of death in COVID-19. The miR-21-5p and miR-146a-5p are involved with molecules participating in severe forms of COVID-19. We aimed to find the relationship between miRNAs, the severity, IMV, and mortality in under 55 years hospitalized patients. Patients were stratified according to the severity of the IDSA/WHO criteria as severe and critical and subclassified into critical non-survivors and survivors. Ninety-seven severe/critical COVID-19 patients (median 43 years) were included. 81.3% of the deceased were male, and 18.8% were female. Higher expressions miR-21-5p levels were associated as follows: severe vs. critical disease (p=0.007, FC=0.498), PaO2/FiO2 index, mild vs. severe (p=0.027, FC=0.558), and survivors vs. non-survivors (p=0.03, FC=0.463). Also, we identified correlations with clinical variables: CRP (rho -0.54, p<0.001), D-Dimer (rho -0.47, p<0.05), related to damage in the kidney (rho=0.60, p<0.001), liver (rho=0.41, p<0.05), and lung (rho=0.54, p<0.001). Finally, miR-21-5p thresholds were calculated according to severity (8.191), IMV (8.191), and mortality (8.237); these values increased the risk of developing a critical disease (OR = 4.19), need for IMV (OR= 5.63), and death (OR= 6.00).

The increased expression levels of miR-21-5p are related to the worse outcome in COVID-19 patients hospitalized under 55 years. Also, it correlates with clinical variables that could lead to a more critical condition and raise the risk of higher severity and death.