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

Mohammad Shah Alam; Mohammad Nazmol Hasan; Zannatul Maowa; Fahima Khatun; K H M Nazmul Hussain Nazir; Mohammad Zahangeer Alam

doi:10.5455/javar.2023.j665

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

J Adv Vet Anim Res. 2023 Jun 30;10(2):157-168. doi: 10.5455/javar.2023.j665. eCollection 2023 Jun.

Authors

Mohammad Shah Alam¹, Mohammad Nazmol Hasan², Zannatul Maowa¹, Fahima Khatun³, K H M Nazmul Hussain Nazir⁴, Mohammad Zahangeer Alam⁵

Affiliations

¹ Department of Anatomy and Histology, Bangabandhu Sheikh Mujibur Rahman Agricultural University, Gazipur, Bangladesh.
² Department of Statistics, Bangabandhu Sheikh Mujibur Rahman Agricultural University, Gazipur, Bangladesh.
³ Department of Pathobiology, Bangabandhu Sheikh Mujibur Rahman Agricultural University, Gazipur, Bangladesh.
⁴ Department of Microbiology and Hygiene, Bangladesh Agricultural University, Mymensingh, Bangladesh.
⁵ Department of Environmental Science, Bangabandhu Sheikh Mujibur Rahman Agricultural University, Gazipur, Bangladesh.

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 antioxidant, 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.

Keywords: COVID-19; N-Acetylcysteine; SARS-CoV-2; mortality; severity; treatment.