Is N-acetylcysteine effective in treating patients with coronavirus disease 2019? A meta-analysis

Abstract

Background: Coronavirus disease 2019 (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). It has brought tremendous challenges to public health and medical systems around the world. The current strategy for drug repurposing has accumulated some evidence on the use of N-acetylcysteine (NAC) in treating patients with COVID-19. However, the evidence remains debated. Methods: We performed the systematic review and meta-analysis that complies with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Five databases and reference lists were searched from inception to May 14, 2022. Studies evaluating the efficacy of NAC in treating patients with COVID-19 were regarded as eligible. The review was registered prospectively on PROSPERO (CRD42022332791). Results: Of 778 records identified from the preliminary search, four studies were enrolled in the final qualitative review and quantitative meta-analysis. A total of 355 patients were allocated into the NAC group and the control group. The evaluated outcomes included intubation rate, improvement, duration of intensive unit stay and hospital stay and mortality. The pooled results showed nonsignificant differences in intubation rate (OR, 0.55; 95% CI, 0.16-1.89; p = 0.34; I2 = 75%), improvement of oxygenation ([MD], 80.84; 95% CI, -38.16 to 199.84; p = 0.18; I2 = 98%), ICU stay (MD, -0.74; 95% CI, -3.19 to 1.71; p = 0.55; I2 = 95%), hospital stay (MD, -1.05; 95% CI, -3.02 to 0.92; p = 0.30; I2 = 90%), and mortality (OR, 0.58; 95% CI, 0.23-1.45; p = 0.24; I2 = 54%). Subsequent trial sequential analysis (TSA) showed conclusive nonsignificant results for mortality, while the TSA for the other outcomes suggested that a larger sample size is essential. Conclusions: The current evidence reveals NAC is not beneficial for treating patients with COVID- 19 with regard to respiratory outcome, mortality, duration of ICU stay and hospital stay.

Effectiveness of N-acetylcysteine in treating patients with coronavirus disease 2019 may be in doubt but in uncertainty

“…10 Furthermore, the IV dose of NAC varies greatly among three studies (21 g/d, 40 mg/kg/d, and 1.2 to 1.5 g/d, respectively. 10 It is hard to use "un-uniform" doses of NAC to compare and/or summarize their results. We are relatively doubtful for the in-effectiveness of NAC in the management of patients with COVID-19.…”

“…4,8,9 Therefore, a prompt and immediate effective treatment may be needed to prevent the occurrence of critical illness, life-threatening status or even mortality. 9,10 Unfortunately, the availability and accessibility of therapeutic agents to COVID-19 are inadequate, given their expensive cost, prescription requirement, and insufficient production capacity to catch up the speed of spread of COVID-19 pandemics, contributing to an urgent need of focusing on repurposing licensed drugs (antiviral and immunomodulating) or agents that had existing clinical or nonclinical toxicology data for the alternative therapeutics to COVID-19. 4,10 A publication in the March issue of the Journal of the Chinese Medical Association entitled "Is N-acetylcysteine effective in treating patients with coronavirus disease 2019?…”

“…A meta-analysis." attempted to discuss the potential candidate (N-acetylcysteine: NAC, a traditional pharmacological effect on promoting respiratory hygiene) by drug repurposing for the treatment of COVID-19, 10 based on its potential antioxidative and anti-inflammatory effects. [11][12][13][14] The authors conducted a systematic review and meta-analysis, including four studies and 355 patients to compare the outcomes between the use and nonuse of NAC in the management of patients with COVID-19.…”

“…[11][12][13][14] The authors conducted a systematic review and meta-analysis, including four studies and 355 patients to compare the outcomes between the use and nonuse of NAC in the management of patients with COVID-19. 10 The evaluated outcomes included intubation rate (three studies), oxygenation index (three studies), intensive care unit (ICU) stay (two studies), hospital stay (three studies), and mortality (three studies). 10 The results revealed none of the aforementioned evaluated items showed a statistically significant difference between the use and nonuse of NAC in the management of patients with COVID-19, with odd ratio (OR) of 0.55, 95% confidence interval (CI) 0.16 to 1.89; difference in means (DM) 80.84, 95% CI −38.16 to 199.84; DM −0.74, 95% CI −3.19 to 1.71; MD −1.05, 95% CI −3.02 to 0.92; and OR 0.58, 95% CI 0.23 to 1.45, respectively.…”

“…15 Based on the results obtained from a meta-analysis, the authors suggested the certainty of evidence about the use of NAC for the treatment of patients with COVID-19 was very low; thus, the authors did not recommend the routine use of NAC for patients with COVID-19 in clinical practice. 15 Based on the absence of benefits from both meta-analyses, 10,15 it is hard to suggest the routine use of NAC in the management of patients with COVID-19. Furthermore, one study also failed to support the role of NAC for patients with COVID-19, even the study has conducted to use inhalation route.…”