Reactive oxygen species as an initiator of toxic innate immune responses to SARS-CoV-2 in an ageing population, consider N-acetylcysteine as early therapeutic intervention

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301821/pdf/main.pdf

Toxicology Reports

journal homepage: www.elsevier.com/locate/toxrep

Reactive oxygen species as an initiator of toxic innate immune responses to SARS-CoV-2 in an ageing population, consider N-acetylcysteine as early therapeutic intervention

Aikaterini Nasia,i, Stephanie McArdleb, Gustav Gaudernackc, Gabriel Westmand, Cornelis Meliefe,f, Johan Rockbergg, Ramon Arense, Demetrios Kouretash, Jan Sjölind, Sara Mangsboa,i,*

aCOVID-19 SARS-CoV2 N-acetylcysteine Antioxidants Oxidative stress

ABSTRACT

During the current COVID-19 pandemic, a need for evaluation of already available drugs for treatment of the disease is crucial. Hereby, based on literature review from the current pandemic and previous outbreaks with corona viruses we analyze the impact of the virus infection on cell stress responses and redox balance. High levels of mortality are noticed in elderly individuals infected with SARS-CoV2 and during the previous SARS- CoV1 outbreak. Elderly individuals maintain a chronic low level of inflammation which is associated with oxidative stress and inflammatory cytokine production, a condition that increases the severity of viral infections in this population. Coronavirus infections can lead to alterations of redox balance in infected cells through modulation of NAD + biosynthesis, PARP function along with altering proteasome and mitochondrial function in the cell thereby leading to enhanced cell stress responses which further exacerbate inflammation. ROS production can increase IL-6 production and lipid peroxidation resulting in cell damage. Therefore, early treatment with anti-oxidants such as NAC during COVID-19 can be a way to bypass the excessive inflammation and cell damage that lead to severe infection, thus early NAC as intervention should be evaluated in a clinical trial setting.