Vitamin A Deficiency, COVID-19, and Rhino-Orbital Mucormycosis (Black Fungus): An Analytical Perspective.

Mucormycosis is a rare but serious opportunistic fungal disease characterized by rhino-orbito-cerebral and pulmonary involvement. It is mainly seen in people with secondary immunosuppression, isolated vitamin A deficiency, measles, and AIDS patients. It showed a rise during the second wave of the COVID-19 epidemic in the spring of 2021 in India, especially in diabetic COVID-19 patients. Vitamin A deficiency is known to cause nutritional immunodeficiency and hence leading the way to increased opportunistic fungal, bacterial, and viral infections. In the eye, it causes keratitis, night blindness, xerophthalmia, conjunctivitis, Bitot spots, keratomalacia, and retinopathy. It also causes decreased tear secretion and deterioration of the anatomical/physiological defense barrier of the eye. The negative impact of vitamin A deficiency has been previously demonstrated in measles, AIDS, and COVID-19. We think that mucormycosis in COVID-19 might be rendered by vitamin A deficiency and that vitamin A supplementation may have preventive and therapeutic values against mucormycosis and other ocular symptoms associated with COVID-19. However, any vitamin A treatment regimen needs to be based on laboratory and clinical data and supervised by medical professionals.

Retinol Depletion in COVID-19.

Background and aims: COVID-19 has been a devastating pandemic. There are indications that vitamin A is depleted during infections. Vitamin A is important in development and immune homeostasis. It has been used successfully in measles, RSV and AIDS infections. In this study, we aimed to measure the serum retinol levels in severe COVID-19 patients to assess the importance of vitamin A in the COVID-19 pathogenesis. Methods: The serum retinol level was measured in two groups of patients: the COVID-19 group, which consisted of 27 severe COVID-19 patients hospitalized in the intensive care unit with respiratory failure, and the control group, which consisted of 23 patients without COVID-19 symptoms. Results: The mean serum retinol levels were 0.37 mg/L in the COVID-19 group and 0.52 mg/L in the control group. The difference between the serum retinol levels in the two groups was statistically significant. There was no significant difference in retinol levels between different ages and genders within the COVID-19 group. Comorbidity did not affect serum retinol levels. Conclusion: The serum retinol level was significantly lower in patients with severe COVID-19, and this difference was independent of age or underlying comorbidity. Our data show that retinol and retinoic acid signaling might be important in immunopathogenesis of COVID-19.

A novel hypothesis for COVID-19 pathogenesis: Retinol depletion and retinoid signaling disorder.

The SARS-CoV-2 virus has caused a worldwide COVID-19 pandemic. In less than a year and a half, more than 200 million people have been infected and more than four million have died. Despite some improvement in the treatment strategies, no definitive treatment protocol has been developed. The pathogenesis of the disease has not been clearly elucidated yet. A clear understanding of its pathogenesis will help develop effective vaccines and drugs. The immunopathogenesis of COVID-19 is characteristic with acute respiratory distress syndrome and multiorgan involvement with impaired Type I interferon response and hyperinflammation. The destructive systemic effects of COVID-19 cannot be explained simply by the viral tropism through the ACE2 and TMPRSS2 receptors. In addition, the recently identified mutations cannot fully explain the defect in all cases of Type I interferon synthesis. We hypothesize that retinol depletion and resulting impaired retinoid signaling play a central role in the COVID-19 pathogenesis that is characteristic for dysregulated immune system, defect in Type I interferon synthesis, severe inflammatory process, and destructive systemic multiorgan involvement. Viral RNA recognition mechanism through RIG-I receptors can quickly consume a large amount of the body's retinoid reserve, which causes the retinol levels to fall below the normal serum levels. This causes retinoid insufficiency and impaired retinoid signaling, which leads to interruption in Type I interferon synthesis and an excessive inflammation. Therefore, reconstitution of the retinoid signaling may prove to be a valid strategy for management of COVID-19 as well for some other chronic, degenerative, inflammatory, and autoimmune diseases.