Oxidative Stress and Hyper-Inflammation as Major Drivers of Severe COVID-19 and Long COVID: Implications for the Benefit of High-Dose Intravenous Vitamin C

Abstract

Oxidative stress is a pivotal point in the pathophysiology of COVID-19 and presumably also in Long-COVID. Inflammation and oxidative stress are mutually reinforcing each other, thus contributing to the systemic hyperinflammatory state and coagulopathy which are cardinal pathological mechanisms of severe stages. COVID-19 patients, like other critically ill patients e.g. with pneumonia, very often show severe deficiency of the antioxidant vitamin C. So far, it has not been investigated how long this deficiency lasts or whether patients with long COVID symptoms also suffer from deficiencies. A vitamin C deficit has serious pathological consequences because vitamin C is one of the most effective antioxidants, but also co-factor of many enzymatic processes that affect the immune and nervous system, blood circulation and energy metabolism. Because of its anti-oxidative, anti-inflammatory, endothelial-restoring, and immunomodulatory effects the supportive intravenous (iv) use of supraphysiological doses has been investigated so far in 12 controlled or observational studies with altogether 1578 inpatients with COVID-19. In these studies an improved oxygenation, a decrease in inflammatory markers and a faster recovery were observed. In addition, early treatment with iv high dose vitamin C seems to reduce the risks of severe courses of the disease such as pneumonia and also mortality. Persistent inflammation, thrombosis and a dysregulated immune response (auto-immune phenomena and/or persistent viral load) seem to be major contributors to Long-COVID. Oxidative stress and inflammation are involved in the development and progression of fatigue and neuro-psychiatric symptoms in various diseases by disrupting tissue (e.g. autoantibodies), blood flow (e.g. immune thrombosis) and neurotransmitter metabolism (e.g. excitotoxicity). In oncological diseases, other viral infections and autoimmune diseases, which are often associated with fatigue, cognitive disorders, pain and depression similar to Long-COVID, iv high dose vitamin C was shown to significantly relieve these symptoms. Supportive iv vitamin C in acute COVID-19 might therefore reduce the risk of severe courses and also the development of Long-COVID.

Study of Albumin Oxidation in COVID-19 Pneumonia Patients: Possible Mechanisms and Consequences

“…It is still premature to confirm whether or not lung involvement or signs of ongoing heart inflammation occur as a temporary response to COVID-19 infection and will spontaneously be resolved over time and whether COVID-19 affects other inflammation-related complications or basic diseases, such as intestinal diseases [ 14 , 15 , 16 , 17 ]. Oxidative stress may also play an important role in the development of symptoms from Long COVID [ 18 ].…”

Hydroxytyrosol Recovers SARS-CoV-2-PLpro-Dependent Impairment of Interferon Related Genes in Polarized Human Airway, Intestinal and Liver Epithelial Cells

“…Our data and other reported evidence suggest that SARS-CoV-2 PLpro/NSP3 may be a highly attractive and druggable target not only in acute COVID-19 but also in long-COVID [ 41 , 42 ]. Moreover, several lines of evidence demonstrated that inflammation and oxidative stress mutually reinforce each other in COVID-19 and presumably also in long-COVID, highlighting the major role of oxidative unbalance as a trigger of both acute and chronic inflammation [ 27 , 43 ]. Therefore, it is plausible that natural antioxidant molecules may counteract SARS-CoV-2 redox status derangement and consequent inflammation representing a possible therapy for improving signs and symptoms of long-COVID syndrome [ 26 , 27 , 44 ].…”

“…HXT is a phenolic compound found in the leaves and fruits of olive with antioxidant, anti-inflammatory and antimicrobial activities [ 20 , 21 ]. The antiviral activity of olive leaf metabolites against SARS-CoV-2 was reported in several in silico computational studies [ 43 , 44 ]. In particular, Yu et al tested several viral targets, such as viral proteases (Mpro/3CLpro, PLpro), TLRs, ACE2, RBD, NSP15, HSPA5 SBDβ, TMPRSS2, S protein and furin [ 46 ].…”

Tracing the cell-type-specific modules of immune responses during COVID-19 progression using scDisProcema

“…Brown module was responsible for the immune responses of various cytokines, which might play an important role in the progression and prognosis of patients [53] , [54] . The grey module plays a vital role in oxygen transport and oxidative stress, the latter is an important part of the pathogenesis of COVID-19 [55] and interacts with the patients’ inflammatory response [56] . In addition, through PPI network analysis, we found that most of the identified hub genes were involved in MCODEs related to the cell invasion process induced by viruses, indicating the significant role of these genes in responding to virus infection.…”