Clinical and Molecular Effects of N-Acetylcysteine Treatment in COVID-19-Related Acute Respiratory Distress Syndrome

This single-center, prospective, randomized, double-blind, placebo-controlled clinical trial was conducted in adult patients with PCR-confirmed COVID-19 and acute respiratory distress syndrome (ARDS) admitted to the intensive care unit. Eligible patients were randomly assigned in a 1:1 ratio to receive intravenous N-acetylcysteine (NAC) or placebo in addition to standard care. NAC was administered at a dose of 150 mg/kg on day 1 followed by 50 mg/kg/day on days 2 and 3.

The primary objectives were to evaluate the effects of NAC on inflammatory and thromboinflammatory biomarkers and hypoxia-related molecular pathways. Biochemical parameters including C-reactive protein, D-dimer, ferritin, zinc levels, and PaO₂/FiO₂ ratio were measured at ICU admission and on day 4. Gene expression levels of HIF-1α, ACE2, and CD147 were analyzed in peripheral blood using RT-qPCR.

Secondary objectives included assessment of clinical outcomes such as mortality, length of intensive care unit stay, and need for mechanical ventilation. The study was approved by the institutional ethics committee, and written informed consent was obtained from patients or their legal representatives.

Inclusion criteria

Age ≥18 years

PCR-confirmed SARS-CoV-2 infection

Diagnosis of acute respiratory distress syndrome (ARDS) according to the Berlin criteria

Admission to the intensive care unit

Written informed consent obtained from the patient or legal representative -

Exclusion criteria

Expected mortality within 48 hours of ICU admission

Prior chronic oxygen therapy

Previous COVID-19 treatment initiated at another center

Pregnancy or breastfeeding

Use of antioxidant or anti-inflammatory drugs within 30 days prior to enrollment

Known hypersensitivity to N-acetylcysteine

Use of medications affecting glutathione metabolism

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