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The epigenetic features contribute to variations in host susceptibility to SARS-CoV-2 infection and severity of symptoms. This study aimed to evaluate the relationship between the relative expression of microRNAs (miRNAs) and the severity of the disease in COVID-19 patients. The miRNA profiles were monitored during the different stages of the disease course using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expression levels of the selected 11 miRNAs were measured in the blood samples collected from 73 patients (moderate, n = 37; severe, n = 25; critically ill, n = 11, a total of 219 longitudinal samples) on hospitalization day and days 7 and 21. Expression changes were expressed as "fold change" compared to healthy controls ( n = 10). Our study found that several miRNAs differed according to disease severity, with the miR-155-5p the most strongly upregulated ( p = 0.0001). A statistically significant negative correlation was observed between the expression of miR-155-5p and its target gene, the suppressor of cytokine signaling 1 ( SOCS1 ). The relative expression of miR-155-5p was significantly increased and SOCS1 was significantly decreased with the disease progression (r = -0.805 p = 0.0001, r = -0.940 p = 0.0001, r = -0.933 p = 0.0001 for admission, day 7, and day 21, respectively). The overexpression of miR-155-5p has significantly increased inflammatory cytokine production and promoted COVID-19 progression. We speculated that microRNA-155 facilitates immune inflammation via targeting SOCS1 , thus establishing its association with disease prognosis.