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

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 Nacetylcysteine (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 G6PDdeficient 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.

Tmprss2 specific miRNAs as promising regulators for SARS-CoV-2 entry checkpoint

“…However, their efficacy in COVID-19 management is still in its infancy. Moreover, the case studies based on treatments from Imatinib and Colchicine were uncontrolled and restricted in nature ( Della-Torre et al, 2020 ; Ibrahim et al, 2020 ; Morales-Ortega et al, 2020 ). At present, the mainstream therapies are involving aforesaid axis and have proved its significance in the management of CoV-2 replication, but the role of other secondary targets cannot be ruled out in controlling the infection of the virus.…”

G6PD deficiency, redox homeostasis, and viral infections: implications for SARS-CoV-2 (COVID-19)

“…For instance, glutathione can inactivate dengue and chikungunya viruses in the blood [53,54]. N-acetylcysteine (NAC) attenuates influenza-like symptoms and COVID-19-induced inflammation [55,56]. On the other hand, selenium deficiency in mice is associated with enhanced enteroviruses virulence and the development of myocardial lesions [57,58].…”

Paracetamol-Induced Glutathione Consumption: Is There a Link With Severe COVID-19 Illness?

“…All the above evidences seem to have a clinical relevance: Polonikov, studying four moderate-severe COVID-19 cases, found that while the three patients with normal/high plasma levels of GSH recovered rapidly, the one with low GSH levels, high plasma ROS and ROS/GSH ratio experienced the most severe illness and, at the date of publication, was still sick (Polonikov, 2020). In another case report, two COVID-19 pneumonia patients were successfully treated with high doses of supplemental intravenous glutathione and oral NAC (Horowitz et al, 2020); finally, Ibrahim et al reported the case of a group of nine severely ill patients successfully treated with NAC (Ibrahim et al, 2020). Notably, these three independent reports-although referring to only fifteen cases-reciprocally strengthen each other in highlighting the relevance of poor GSH levels in COVID-19 clinical progression as well as the importance of maintaining/repleting GSH pools as a countermeasure against SARS-CoV2 virulence.…”