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

• Published in: Toxicology reports 2020-01, Vol.7, p.768-771
• Main Authors: Nasi, Aikaterini, McArdle, Stephanie, Gaudernack, Gustav, Westman, Gabriel, Melief, Cornelis, Rockberg, Johan, Arens, Ramon, Kouretas, Demetrios, Sjölin, Jan, Mangsbo, Sara
• Format: Article
• Language: English
• Subjects: 3 dioxygenase; acetylcysteine; aging; angiotensin converting enzyme 2; Antioxidants; Biologi med inriktning mot molekylär immunologi; Biology with specialization in Molecular Immunology; C reactive protein; cell stress; coronavirus disease 2019; COVID-19; cryopyrin; cytokine production; cytokine release; group 2d secretory phospholipase a2; homeostasis; human; immune response; Immunologi; Immunology; Infectious Diseases; Infektionssjukdomar; inflammasome; innate immunity; interferon; interleukin 6; mortality; N-acetylcysteine; neutrophil cytosol factor 1; nicotinamide adenine dinucleotide adenosine diphos; nonhuman; oxidation reduction reaction; oxidative phosphorylation; Oxidative stress; peptides and proteins; priority journal; proteasome; protein expression; reactive oxygen metabolite; reduced nicotinamide adenine dinucleotide phosphat; Regular; SARS-CoV2; Severe acute respiratory syndrome coronavirus 2; toll like receptor 4; tryptophan 2; tumor necrosis factor; unclassified drug; viremia
• ISSN: 2214-7500; 2214-7500
• DOI: 10.1016/j.toxrep.2020.06.003

[Display omitted] •Viral infections cause oxidative stress which may be exaggerated by inflammaging.•Oxidative stress coping mechanisms can be affected by genetic/environmental factors.•SARS-CoV has been reported to modulate PARP function and thereby NAD + biosynthesis.•Cellular homeostasis and redox imbalances by SARS-CoV2 can cause stress responses.•Antioxidants such as NAC could limit ROS mediated tissue damage during COVID-19. 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.