Bottom-up analysis of emergent properties of N-acetylcysteine as an adjuvant therapy for COVID-19

Abstract

N-acetylcysteine (NAC) is an abundantly available antioxidant with a wide range of antidotal properties currently best studied for its use in treating acetaminophen overdose. It has a robustly established safety profile with easily tolerated side effects and presents the Food and Drug Administration's approval for use in treating acetaminophen overdose patients. It has been proven efficacious in off-label uses, such as in respiratory diseases, heart disease, cancer, human immunodeficiency virus infection, and seasonal influenza. Clinical trials have recently shown that NAC's capacity to replenish glutathione stores may significantly improve coronavirus disease 2019 (COVID-19) outcomes, especially in high risk individuals. Interestingly, individuals with glucose 6-phosphate dehydrogenase deficiency have been shown to experience even greater benefit. The same study has concluded that NAC's ability to mitigate the impact of the cytokine storm and prevent elevation of liver enzymes, C-reactive protein, and ferritin is associated with higher success rates weaning from the ventilator and return to normal function in COVID-19 patients. Considering the background knowledge of biochemistry, current uses of NAC in clinical practice, and newly acquired evidence on its potential efficacy against COVID-19, it is worthwhile to investigate further whether this agent can be used as a treatment or adjuvant for COVID-19.

Repurposing the antioxidant and anti-inflammatory agent N-acetyl cysteine for treating COVID-19

“…We do not agree with the notion that NAC is an agent for curing SARS-CoV-2 infections[ 1 ]. There are several arguments against the antiviral effect of NAC.…”

“…With interest, we read the review article by Dominari et al [ 1 ] about the putative therapeutic effect of N-acetyl cysteine (NAC) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients. The authors raise several arguments in favour of a beneficial effect of NAC for coronavirus disease 2019 (COVID-19), discuss preliminary results about ongoing studies with NAC in COVID-19, and conclude that the results of available trials are not clear.…”

Therapeutic potential of N-acetyl cysteine during COVID-19 epoch

“…The impact of coronavirus disease 2019 (COVID-19) pandemic resulting in substantial mortalities and morbidities has driven the quest to accelerate the treatment options for containment of this public health emergency. We read with interest the review by Dominari et al [ 1 ]. The authors have reviewed the pharmacology, efficacy, and safety of N-acetyl cysteine (NAC) as an adjuvant therapy of COVID-19.…”

“…As documented in the review, adverse effects from NAC could vary from mild gastrointestinal symptoms to severe anaphylactoid reactions[ 1 ]. Abnormal hemostatic activity, such as anticoagulant and platelet-inhibiting properties with increased bleeding risk, has been documented in patients receiving NAC[ 5 ].…”

“…The possible benefits of NAC in COVID-19 seem to outweigh the risks, but an important issue plaguing the usefulness of NAC is its uncertain efficacy in mild cases[ 7 ] and potential of unregulated use in the current scenario where there are limited drugs available for the management of COVID-19. Hence, as is rightly stressed upon by the author[ 1 ], before the use of NAC in COVID-19 spreads, further research is warranted to avoid another failure story[ 8 ]. Clinical trials are already underway to establish efficacy of NAC in COVID-19[ 9 , 10 ], and recent review by Wong et al [ 11 ] (2021) elaborated the potential role of NAC as adjunctive remedy for COVID-19[ 11 ].…”