N-acetylcysteine reduces severity and mortality in COVID-19 patients: A systematic review and meta-analysis

Abstract

Objectives: Recent clinical studies suggest that oxidative stress is one of the key players in the pathogenesis of coronavirus disease 2019 (COVID-19), and N-acetylcysteine (NAC), a potent anti¬oxidant, has been shown to improve clinical outcomes in COVID-19 patients. We conducted a systematic review and meta-analysis of the literature published on the therapeutic intervention of NAC on COVID-19 infection. Methods: We searched PubMed, Google Scholar, and Science Direct. We identified and screened eight studies with 20,503 participants, including 2,852 in the NAC-treated group and 17,651 in the placebo group, which reported the effect of NAC on COVID-19 infection. A meta-analysis was performed using forest plots under fixed effect estimates based on the standardized mean difference (SMD) and risk ratio (RR). Results: Pooled analysis showed that NAC was associated with lower mortality in patients with COVID-19 compared with the placebo group [RR, 0.65; (95% CI: 0.56 to 0.75); p < 0.0001]. Similarly, C-reactive protein (CRP) [SMD, −0.32; (95% CI: −56 to −0.09); p = 0.0070] and D-dimer [SMD, −0.35, (95% CI: −0.59 to −0.10; p = 0.0062] levels were significantly decreased, and the oxygenation marker, PaO2/FiO2 ratio, was increased in the NAC-treated group compared with the placebo group [SMD, 0.76; (95% CI: 0.48 to 1.03); p < 0.0001]. Conclusion: Although the number of included studies was minimal, this meta-analysis suggests that NAC may have a positive effect on COVID-19 outcomes, specifically, a significant decrease in CRP and D-dimer levels and a significant increase in oxygen saturation, which decreased mortality. We have also presented a comprehensive review of the role and mechanisms of NAC in patients with COVID-19.

An Updated Prioritization of Geroscience- Guided FDA-Approved Drugs Repurposed to Target Aging

“…78 In a meta-analysis of mixed studies, NAC was shown to reduce mortality (RR = 0.65 [0.56-0.75]). 79 COVID-19 mortality data in SGLT2i users is inconclusive, with a RCT and a meta-analysis both reporting no significant results while another metaanalysis reported pre-admission use to be associated with decreased mortality in diabetics (OR 0.69 [0.56 -0.87]). 76,80,81 No significant results were reported in studies of bisphosphonates, MB, ACEi/ARB, or aspirin; however, the meta-analysis of RCTs and aspirin only investigated anti-platelet level dosing, not anti-inflammatory.…”

Advances in the Use of N-Acetylcysteine in Chronic Respiratory Diseases

“…As the levels of GSH decline with age [ 45 ], positive effects of supplementation with NAC in combination with glycine on changes associated with aging have been successfully tested in clinical trials [ 46 , 47 ]. Because GSH concentrations also decrease in various disorders with abundant oxidative stress [ 48 ], NAC has been used in a variety of respiratory diseases, including COPD [ 49 ], IPF [ 19 ], lung silicosis [ 50 ], COVID-19 [ 51 , 52 ], or obstructive sleep apnea [ 53 ], as well as in multidrug-resistant infections [ 54 ], cardiovascular diseases [ 55 ], type 2 diabetes [ 56 ], chronic nephropathy [ 57 ], or infertility due to polycystic ovaria [ 58 ].…”