N-Acetylcysteine as A Potential Adjunctive Theraphy in Covid-19 Patients Associated Coagulopathy by Lowering Il-1????, D-dimer and Padua Scores Levels

Abstract

Introduction: Many unique pathologies, such as hyperinflammation and hypercoagulopathy, have been associated with Covid-19, resulting in critical illness and poor outcomes. N-Acetylcysteine (NAC), a precursor of the antioxidant glutathione, has a number of biological effects, including increasing antioxidant capacity, inhibiting viral replication, and suppressing the release of proinflammatory cytokines, such as IL-1????, which further reduces coagulopathy as measured by D-dimer and PADUA scores. The aim of this research is to analyze the effect of NAC as an adjunctive therapy on the level of IL-1????, D-dimer and PADUA scores among Covid-19 patients. Method: A quasi-experimental, non-equivalent group, single-center study included 91 hospitalized confirmed Covid-19 patients by RT-PCR, 75 patients received standard of care plus 5000 mg/72 hours of NAC and 16 patients received standard of care without NAC. On the first and eighth days of treatment, IL-1????, D-dimer levels, and PADUA scores were measured by ELISA and quantitative-assay methods. Data analysis used were Mann-Whitney test, Wilcoxon test, and Spearman-rho correlation test. Result: After the eighth day of therapy, the NAC group had a statistically significantly reduction in IL-1????(pg/mL) (1,48[-4,23-6,68] vs -0,43[-3,40-2,0], p=0.03) and D-dimer(µg/mL) (0,75[-5,98-6,45] vs -0,03[-8,07-1,00], p<0,001) levels than the control group, but not in PADUA scores (1,05[0-3] vs 0,94[0-1], p=0,458). In a subanalysis of NAC's group, IL-1???? was found to be quite strongly correlated with D-dimer (r=0,508, p<0,001). Conclusion: Our findings show that supplementary NAC reduces hyperinflammation and hypercoagulopathy in Covid-19 patients by suppressing IL-1???? and lowering D-dimer, and thus could be used as a supplement to Covid-19 therapy.