The role of some important antioxidants in major clinical outcomes of subjects with COVID-19

In a recent review published in Food Science and Nutrition, researchers investigated the role of antioxidants such as selenium, zinc, α-lipoic acid, and vitamins A, E, D, and C in improving the clinical outcomes of coronavirus disease 2019 (COVID-19).

Background

Recent research on COVID-19 has indicated that oxidative stress could be one of the main reasons behind the pathogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Comorbidities such as cardiovascular diseases and diabetes mellitus increase the risk of severe COVID-19 because these conditions elevate oxidative stress levels in the body. The binding of the SARS-CoV-2 spike protein with the angiotensin-converting enzyme 2 receptor is believed to disrupt the renin-angiotensin system and increase oxidative stress.

Oxidative stress is thought to weaken the immune system and cause inflammation and cell death. Considering the extensive involvement of oxidative stress in COVID-19 clinical outcomes, antioxidants, which repair oxidative damage to cellular components, could provide potential therapeutic avenues to manage the severity of the disease.

About the study

In the present review, the researchers focused on six non-enzymatic antioxidants, which included two minerals (selenium and zinc), four vitamins (A, D, E, and C), and one quasi-vitamin (α-lipoic acid). They selected observational and interventional studies that included COVID-19 patients and excluded studies on animal models and ex vivo or in vitro experiments.

Observational studies were chosen based on an extensive inclusion criterion, which included factors like robust study design, outcomes of interest such as hospitalization and inflammatory biomarkers, exposure of interest consisting of different levels of the antioxidants in supplements or food, and results being reported in terms of odds ratio, hazard ratio, β coefficient, and relative risk.

Interventional studies were selected for including randomized controlled, pre- or post-, and quasi-experimental trials; and for investigating the effect of antioxidant infusions or supplements on the clinical outcomes of COVID-19.

Studies with descriptive observational data, imprecise estimates, and studies that administered the antioxidants of interest with other nutrients, as well as non-peer-reviewed publications, commentaries, editorials, and case reports, were excluded.

Results

The findings of the review suggest that vitamins C and D and minerals zinc and selenium could be highly beneficial in improving many of the clinical outcomes of COVID-19 and lowering the severity of the disease. Vitamin C supplementation was seen to reduce inflammatory biomarker levels and mortality and increase the Horowitz index, which is used to assess the lung function of patients on ventilators.

Observational studies reported that insufficient vitamin D was linked to severe COVID-9 manifestations such as hypoxia, fever, and lymphocytopenia. Supplementation with vitamin D reduced ventilation and intensive care unit (ICU) admission requirements. Studies also found vitamin D levels to be inversely associated with the levels of inflammatory biomarkers such as C-reactive protein (CRP), ferritin, D-dimer, and neutrophil and lymphocyte concentrations. 

The review also discussed the beneficial effects of mineral antioxidants. Observational studies indicated that selenium could play a role in decreasing mortality rates in COVID-19 cases. Serum zinc levels were inversely related to the severity of COVID-19 symptoms.

Studies showed that oral zinc sulfate supplements significantly reduced the need for ventilation, hospitalization, and ICU admission. Inflammatory and infection biomarkers such as CRP, interleukins, erythrocyte sedimentation rate, and procalcitonin were inversely proportional to serum zinc levels.

For the antioxidants α-lipoic acid, and vitamins A and E, no observational or interventional studies were available. However, the authors discussed the importance of vitamin A in enhancing the immune system by promoting the production of immunoglobulins, maintaining the epithelia and mucin layers of the respiratory tracts, and regulating the genes involved in inflammatory responses.

Similarly, vitamin E is believed to play a role in protecting cells from reactive oxidative species, T cell function, and the production of antibodies. The involvement of α-lipoic acid in reducing oxidative stress and inhibiting the activation of inflammatory transcription factors was also mentioned in the review.

Conclusions

Overall, the findings of the review indicate that antioxidants such as vitamins C and D and minerals such as selenium and zinc are potential avenues for ameliorating many of the severe manifestations of COVID-19. Still, more studies are required to form conclusions. Despite the absence of observational or interventional studies on the roles of vitamins A and E and α-lipoic acid, the biological roles these antioxidants play in the body indicate their potential as therapeutic agents against COVID-19.