N-acetylcysteine efficacy in patients hospitalized with COVID-19 pneumonia: a systematic review and meta-analysis

Abstract

Background: N-Acetylcysteine (NAC) is a mucolytic agents with anti-inflammatory properties that has been suggested as an adjunctive therapy in patients with COVID-19 pneumonia. Objectives: We conducted a systematic review and meta-analysis to evaluate available evidence on the possible beneficial effects of NAC on SARS-COV-2 infection. Methods: In September 2022, we conducted a comprehensive search on Pubmed/Medline and Embase on randomized controlled trials (RCTs) and observational studies on NAC in patients with COVID-19 pneumonia. Study selection, data extraction and risk of bias assessment was performed by two independent authors. RCTs and observational studies were analyzed separately. Results: We included 3 RCTs and 5 non-randomized studies on the efficacy of NAC in patients with COVID-19, enrolling 315 and 20826 patients respectively. Regarding in-hospital mortality, the summary effect of all RCTs was OR: 0.85 (95% CI: 0.43 to 1.67, I2=0%) and for non-randomized studies OR: 1.02 (95% CI: 0.47 to 2.23, I2=91%). Need for ICU admission was only reported by 1 RCT (OR: 0.86, 95% CI:0.44-1.69, p=0.66), while all included RCTs reported need for invasive ventilation (OR:0.91, 95% CI:0.54 to 1.53, I2=0). Risk of bias was low for all included RCTs, but certainty of evidence was very low for all outcomes due to serious imprecision and indirectness. Conclusion: The certainty of evidence in the included studies was very low, thus recommendations for clinical practice cannot be yet made. For all hard clinical outcomes point estimates in RCTs are close to the line of no effect, while observational studies have a high degree of heterogeneity with some of them suggesting favorable results in patients receiving NAC. More research is warranted to insure that NAC is both effective and safe in patients with COVID-19 pneumonia.

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

“…15 Need for ICU admission and invasive ventilation was 0.86 of OR (95% CI 0.44-1.69) and 0.91 of OR (95% CI 0.54-1.53), 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.…”

“…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.…”

“…Although the meta-analyses failed to support the clinical benefits of NAC in the management of patients with COVID-19, some observational studies (real world data) have shown favorable results in patients with COVID-19 receiving NAC treatment. 15 Due to the conflicted data, a lots of uncertainties of NAC effect and the discrepancy between in theory and in practice still bother us. It may be too mature to make a conclusion as in-effectiveness of NAC for the treatment of patients with COVID-19.…”

“…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.…”