Can NAC Treat COVID? A Review of Clinical Evidence

October 7, 2025 •

3 min read

During the COVID-19 pandemic, N-acetylcysteine (NAC), a precursor to the potent antioxidant glutathione, was investigated as a potential therapy. The question of can NAC treat COVID-19 sparked numerous studies, yielding inconsistent results regarding its clinical effectiveness against the disease.

Quick Summary

Meta-analyses of randomized controlled trials generally show no significant clinical benefit for N-acetylcysteine in treating COVID-19 patients, despite theoretical antioxidant and anti-inflammatory properties.

Key Points

Inconclusive Clinical Efficacy: Controlled trials generally show that N-acetylcysteine (NAC) does not improve major clinical outcomes like mortality or the need for mechanical ventilation in COVID-19 patients.
Antioxidant and Anti-inflammatory Actions: NAC acts as a precursor to glutathione, providing antioxidant and anti-inflammatory effects that theoretically could benefit patients with viral infections.
Mixed Results from Smaller Studies: Some smaller studies and meta-analyses reported positive effects, such as reduced inflammatory markers or shorter recovery times, but these findings are often limited by study design or inconsistencies.
Adjunctive Therapy, Not Standalone Cure: Current evidence does not support using NAC as a standalone treatment for COVID-19, and its routine use is not recommended for SARS-CoV-2 infections.
Potential in Long COVID: Preliminary findings suggest NAC may help alleviate some symptoms of Long COVID, like shortness of breath and fatigue, by affecting microvascular inflammation, but larger studies are needed.
Well-Established Safety Profile: NAC is generally considered safe and well-tolerated, with side effects being typically mild and related to the route of administration.
Standard Therapy Remains Key: Standard-of-care treatments for COVID-19, such as approved antiviral agents and supportive care, are the primary recommended approaches, not NAC.

Exploring the Rationale for NAC in COVID-19

N-acetylcysteine (NAC) is a well-established medication with mucolytic, antioxidant, and anti-inflammatory properties. It is commonly used as an antidote for acetaminophen overdose and has been explored for various respiratory conditions. During the COVID-19 pandemic, its ability to modulate oxidative stress and inflammation led to investigations into whether NAC could treat COVID-19 and potentially mitigate the severe inflammatory response.

Potential Mechanisms of Action Against SARS-CoV-2

The rationale for using NAC against COVID-19 is based on several pharmacological actions:

Replenishes Glutathione (GSH): NAC is a precursor to cysteine, essential for the synthesis of glutathione (GSH), a key cellular antioxidant. GSH deficiency is linked to severe COVID-19, and increasing these levels could help combat oxidative stress.
Anti-inflammatory Effects: NAC may inhibit NF-κB, a transcription factor involved in inflammation, potentially reducing pro-inflammatory cytokines associated with severe COVID-19.
Potential Antiviral Activity: Laboratory studies suggest NAC might interfere with viral replication, although evidence for SARS-CoV-2 is limited.
Mucolytic Effects: As a mucolytic, NAC can help break down mucus, potentially assisting in clearing airways.

Clinical Evidence: Conflicting Trial Results

Clinical studies on NAC for COVID-19 have produced conflicting outcomes. Some smaller and observational studies indicated potential benefits, such as improved outcomes in severely ill patients or reduced inflammatory markers. However, larger, randomized controlled trials (RCTs) have often not found significant differences in key outcomes like the need for mechanical ventilation, ICU admission, or mortality between NAC and placebo groups. Differences in study designs and patient populations likely contribute to these inconsistencies.

Results from Meta-analyses

Systematic reviews and meta-analyses provide a broader view of the clinical evidence. A comprehensive meta-analysis from February 2024, evaluating five RCTs, concluded that NAC did not improve clinical outcomes in COVID-19 patients. Pooled data showed no significant difference in mortality, need for mechanical ventilation, or hospital stay duration, leading the authors not to recommend routine NAC use for SARS-CoV-2 infections. An earlier meta-analysis in June 2023 noted some potential positive effects but acknowledged significant study limitations and heterogeneity.

NAC and Long COVID

Research is also exploring NAC's role in Long COVID. One case report suggested NAC supplementation improved dyspnea and fatigue in patients with Long COVID, possibly by addressing microvascular inflammation. These are preliminary findings requiring further research.

A Comparison of NAC in COVID-19 Clinical Trials


Feature	Supportive Case/Cohort Studies	Conflicting RCTs and Meta-analyses
Study Type	Observational cohorts, case reports, and smaller trials	Randomized controlled trials (RCTs) and systematic meta-analyses
Key Outcome	Improved oxygenation and reduced inflammatory markers like CRP and ferritin.	No significant difference in mortality, ICU stay, or mechanical ventilation.
Patient Focus	Some focus on severely ill or ventilated patients.	Varied, including mild-to-moderate and severe cases.
Study Size	Often small cohorts or case series.	Larger populations, with meta-analyses pooling hundreds of patients.
Conclusion	NAC shows promise as an adjuvant therapy.	Routine use is not recommended due to lack of evidence for improved clinical outcomes.

Conclusion

Despite the theoretical benefits based on its antioxidant, anti-inflammatory, and mucolytic properties, clinical trial evidence does not currently support the routine use of N-acetylcysteine as a treatment for acute COVID-19 infection. Comprehensive meta-analyses indicate no significant improvement in critical outcomes. While its potential role in Long COVID is being explored, standard-of-care treatments remain the primary approach for acute COVID-19. Any decision regarding NAC use should be made in consultation with a healthcare provider, considering the available clinical evidence which does not endorse it as a general COVID-19 treatment.

Frequently Asked Questions

While NAC has antioxidant properties that may support immune function, there is no strong clinical evidence to support its use specifically for the prevention of COVID-19. Studies are needed to confirm any prophylactic benefit.

Based on the evidence from meta-analyses of randomized controlled trials, the routine use of NAC for patients with SARS-CoV-2 infection is not recommended.

NAC increases glutathione levels, providing antioxidant effects. It can also act as a mucolytic and has anti-inflammatory and potential antiviral properties. It is believed to disrupt viral processes, although more research is required.

Meta-analyses of clinical trials found no significant difference in key outcomes like mortality, ICU admission, or length of stay between patients treated with NAC and control groups. Some smaller studies had conflicting results.

Common side effects include gastrointestinal issues like nausea, vomiting, and diarrhea. Intravenous administration can cause allergic reactions, and inhalation may lead to bronchospasm, especially in asthmatic individuals.

Yes, NAC has been used for decades as a mucolytic agent to break down mucus in chronic respiratory diseases like bronchitis, COPD, and cystic fibrosis.

The conflicting results can be attributed to differences in study size, design, patient severity, NAC dosage, timing, and administration route. Small, early studies often have limitations that are addressed in larger, more rigorous trials.

Preliminary research suggests NAC might help alleviate some Long COVID symptoms like dyspnea and fatigue, potentially by reducing microvascular inflammation and coagulation issues. However, definitive, larger-scale studies are still needed.