Background:Systemic Inflammatory Response Syndrome (SIRS) is one of the acute complications of COVID-19 (Coronavirus infection). MicroRNA (miRNA) complement with 3’untranslated regions of messenger RNA (mRNA) and inhibits the translation of mRNA to proteins. Multiple studies revealed changes in the levels of circulating mi-RNAs in patients with SIRS. Hence analysis of miRNAs could serve as an effective biomarker in patient management by predicting the onset of SIRS in COVID-19 infection. Methods:In this comparative cross-sectional study, COVID-19 infected patients admitted in wards and Intensive Care Units (ICU) were enrolled. A total of 120 patients were distributed among two study groups with group A containing COVID-19 patients complicated with SIRS and group B containing COVID-19 patients without SIRS.COVID-19 infection was confirmed by RT-PCR (Reverse transcription-polymerase chain reaction). SIRS was diagnosed by validated clinical evaluation method. The quantification of miRNA was done using TB Green on the CFX96 Real-Time PCR detection system. Statistical analysis was performed using SPSS version 22.0 software. Results:The levels of miRNA-27b were significantly higher in group A compared to group B (28.364 ± 2.967 versus 25.519± 2.790, p26.91 for miRNA-27b gave 67.8% sensitivity and 75% specificity in predicting SIRS with an AUC (Area under curve) of 0.76. Similarly, for miRNA-627-5p, a cut-off of ≤31.1 gave a sensitivity of 61.4% and a specificity of 69.8% in predicting SIRS with an AUC of 0.68. Conclusion:Our study established an association between circulating levels of miRNA-27b and miRNA-627-5p in patients affected by COVID-19 infection complicated with SIRS.