Therapeutic blockade of inflammation in severe COVID-19 infection with intravenous N-acetylcysteine

Clin Immunol. 2020 Oct;219:108544. doi: 10.1016/j.clim.2020.108544. Epub 2020 Jul 22.

Abstract

Glucose 6-phosphate dehydrogenase (G6PD) deficiency facilitates human coronavirus infection due to glutathione depletion. G6PD deficiency may especially predispose to hemolysis upon coronavirus disease-2019 (COVID-19) infection when employing pro-oxidant therapy. However, glutathione depletion is reversible by N-acetylcysteine (NAC) administration. We describe a severe case of COVID-19 infection in a G6PD-deficient patient treated with hydroxychloroquine who benefited from intravenous (IV) NAC beyond reversal of hemolysis. NAC blocked hemolysis and elevation of liver enzymes, C-reactive protein (CRP), and ferritin and allowed removal from respirator and veno-venous extracorporeal membrane oxygenator and full recovery of the G6PD-deficient patient. NAC was also administered to 9 additional respirator-dependent COVID-19-infected patients without G6PD deficiency. NAC elicited clinical improvement and markedly reduced CRP in all patients and ferritin in 9/10 patients. NAC mechanism of action may involve the blockade of viral infection and the ensuing cytokine storm that warrant follow-up confirmatory studies in the setting of controlled clinical trials.

Keywords: C-reactive protein; COVID-19; Coronavirus 19; Extracorporeal membrane oxygenation; Ferritin; Glucose 6-phosphate dehydrogenase; Glutathione; Mechanistic target of rapamycin; N-acetylcysteine; Respirator.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylcysteine / therapeutic use*
  • Adult
  • Antioxidants / therapeutic use*
  • Antirheumatic Agents / therapeutic use
  • Betacoronavirus / pathogenicity*
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • COVID-19
  • Coronavirus Infections / blood
  • Coronavirus Infections / complications
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / virology
  • Cytokine Release Syndrome / blood
  • Cytokine Release Syndrome / complications
  • Cytokine Release Syndrome / drug therapy*
  • Cytokine Release Syndrome / virology
  • Drug Administration Schedule
  • Ferritins / blood
  • Fibrin Fibrinogen Degradation Products / metabolism
  • Glucosephosphate Dehydrogenase Deficiency / blood
  • Glucosephosphate Dehydrogenase Deficiency / complications
  • Glucosephosphate Dehydrogenase Deficiency / drug therapy*
  • Glucosephosphate Dehydrogenase Deficiency / virology
  • Humans
  • Hydroxychloroquine / therapeutic use
  • Inflammation / prevention & control
  • Male
  • Pandemics
  • Pneumonia, Viral / blood
  • Pneumonia, Viral / complications
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / virology
  • SARS-CoV-2
  • Treatment Outcome

Substances

  • Antioxidants
  • Antirheumatic Agents
  • Biomarkers
  • Fibrin Fibrinogen Degradation Products
  • fibrin fragment D
  • Hydroxychloroquine
  • C-Reactive Protein
  • Ferritins
  • Acetylcysteine