Downregulating Angiotensin Converting Enzyme2 (ACE2) expression may be a shared mechanism for RNA viruses. Evaluate the expressions of ACE2 effectors: the long non-coding RNA 'MALAT-1', the micro-RNA 'miR-200c-3p' and the histone deacetylase 'SIRT1' in SARS-COV-2 patients and correlate to disease severity. Sera samples from 98 SARS-COV-2 patients and 30 healthy control participants were collected. qRT-PCR was used for MALAT-1 and miR-200c-3p expression. SIRT1 was measured using ELISA. In sera of COVID-19 patients, gene expression of miR-200c-3p is increased while MALAT-1 is decreased. SIRT1 protein level is decreased (P value < 0.001). Findings are accentuated with increased disease severity. Serum MALAT-1, miR-200c-3p and SIRT1 could be used as diagnostic markers at cut off values of 0.04 (95.9 % sensitivity), 5.59 (94.9 % sensitivity, 99 % specificity), and 7.4 (98 % sensitivity) respectively. A novel MALAT-1-miR-200c-3p-SIRT1 pathway may be involved in the regulation of SARS-COV-2 severity.