Double-blind, Randomized, Placebo-controlled Trial With N-acetylcysteine for Treatment of Severe Acute Respiratory Syndrome Caused by Coronavirus Disease 2019 (COVID-19)

Clin Infect Dis. 2021 Jun 1;72(11):e736-e741. doi: 10.1093/cid/ciaa1443.


Background: A local increase in angiotensin 2 after inactivation of angiotensin-converting enzyme 2 by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may induce a redox imbalance in alveolar epithelium cells, causing apoptosis, increased inflammation and, consequently, impaired gas exchange. We hypothesized that N-acetylcysteine (NAC) administration could restore this redox homeostasis and suppress unfavorable evolution in patients with coronavirus disease 2019 (COVID-19).

Methods: This was a double-blind, randomized, placebo-controlled, single-center trial conducted at the Emergency Department of Hospital das Clínicas, São Paulo, Brazil, to determine whether NAC in high doses can avoid respiratory failure in patients with COVID-19. We enrolled 135 patients with severe COVID-19 (confirmed or suspected), with an oxyhemoglobin saturation <94% or respiratory rate >24 breaths/minute. Patients were randomized to receive NAC 21 g (~300 mg/kg) for 20 hours or dextrose 5%. The primary endpoint was the need for mechanical ventilation. Secondary endpoints were time of mechanical ventilation, admission to the intensive care unit (ICU), time in ICU, and mortality.

Results: Baseline characteristics were similar between the 2 groups, with no significant differences in age, sex, comorbidities, medicines taken, and disease severity. Also, groups were similar in laboratory tests and chest computed tomography scan findings. Sixteen patients (23.9%) in the placebo group received endotracheal intubation and mechanical ventilation, compared with 14 patients (20.6%) in the NAC group (P = .675). No difference was observed in secondary endpoints.

Conclusions: Administration of NAC in high doses did not affect the evolution of severe COVID-19.

Clinical trials registration: Brazilian Registry of Clinical Trials (REBEC): U1111-1250-356 (

Keywords: pneumonia; angiotensin; mechanical ventilation.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / therapeutic use
  • Brazil
  • COVID-19 Drug Treatment*
  • Double-Blind Method
  • Humans
  • Respiration, Artificial
  • SARS-CoV-2
  • Treatment Outcome


  • Acetylcysteine