Mechanistic Insight into the role of Vitamin D and Zinc in Modulating Immunity Against COVID-19: A View from an Immunological Standpoint

Biological Trace Element Research https://doi.org/10.1007/s12011-023-03620-4 Mechanistic Insight into the role of Vitamin D and Zinc in Modulating Immunity Against COVID‑19: A View from an Immunological Standpoint Nuzhat Ahsan1 · Mohammad Imran2 · Yousuf Mohammed2 · Fatme Al Anouti3 · Mohammad Idreesh Khan4 · Tanushree Banerjee5 · Mohd Adnan6 · Fauzia Ashfaq7 · Marek Kieliszek8 · Syed Amir Ashraf9 · Afrozul Haq10 Received: 9 December 2022 / Accepted: 1 March 2023 © The Author(s) 2023 Abstract The pathophysiology of coronavirus disease-19 (COVID-19) is characterized by worsened inflammation because of weakened immunity, causing the infiltration of immune cells, followed by necrosis. Consequently, these pathophysiological changes may lead to a life-threatening decline in perfusion due to hyperplasia of the lungs, instigating severe pneumonia, and causing fatalities. Additionally, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause mortality due to viral septic shock, resulting from unrestrained and backfiring immune reactions to the pathogen. Sepsis can cause premature organ failure in COVID-19 patients, as well. Notably, vitamin D and its derivatives and minerals, such as zinc and magnesium, have been reported to improve the immune system against respiratory illnesses. This comprehensive review aims to provide updated mechanistic details of vitamin D and zinc as immunomodulators. Additionally, this review also focuses on their role in respiratory illnesses, while specifically delineating the plausibility of employing them as a preventive and therapeutic agent against current and future pandemics from an immunological perspective. Furthermore, this comprehensive review will attract the attention of health professionals, nutritionists, pharmaceuticals, and scientific communities, as it encourages the use of such micronutrients for therapeutic purposes, as well as promoting their health benefits for a healthy lifestyle and wellbeing. Keywords COVID-19 · SARS-CoV-2 · Vitamin D · Innate immunity · Adaptive immunity · Zinc * Marek Kieliszek 5 Infosys Ltd. SEZ Unit VI, Plot No. 1, Rajiv Gandhi Infotech Park, Hinjawadi Phase I, Pune, Maharashtra 57, India * Syed Amir Ashraf 6 Department of Biology, College of Science, University of Haʼil, P.O. Box 2440, Haʼil, Saudi Arabia * Afrozul Haq 7 Department of Clinical Nutrition, College of Applied Medical Sciences, Jazan University, Jazan 45142, Saudi Arabia 8 Department of Food Biotechnology and Microbiology, Institute of Food Sciences, Warsaw University of Life Sciences—SGGW, Nowoursynowska 159 C, 02‑776 Warsaw, Poland 1 Quantum Biphotonics Division, Quantlase Laboratory LLC, Abu Dhabi, UAE 2 Therapeutic Research Group, Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane 4102, Australia 9 3 College of Natural and Health Sciences, Zayed University, Abu Dhabi, UAE Department of Clinical Nutrition, College of Applied Medical Sciences, University of Haʼil, Haʼil, Saudi Arabia 10 4 Department of Clinical Nutrition, College of Applied Health Sciences in Ar Rass, Qassim University, Ar Rass 51921, Saudi Arabia H.A. University, Imphal, Manipur, India 13 Vol.:(0123456789) N. Ahsan et al. Introduction Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), the novel coronavirus behind the pandemic affecting millions of lives and livelihoods around the world, is a single positive-stranded ribonucleic acid (RNA) virus, which belongs to the family Coronaviridae. It primarily causes respiratory tract infections. In addition, it may be complicated by liver, brain, and gastrointestinal tract diseases [1, 2]. The severity and lethality of the disease have been reported to be due to an intensified inflammation marked by the infiltration of immune cells, necrosis, and edema of lung tissue, causing impaired pulmonary oxygen exchange. COVID-19 manifests predominantly as pneumonia, where an aggressive immune reaction can lead to a “cytokine storm” primarily in the lungs. This immune response involves several cytokines, tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-8 (IL-8), interleukin-12 (IL-12), and interleukin-10 (IL-10), monocyte chemoattractant protein 1 (MCP1) and macrophage inflammatory protein 1A (MIP1A), with interleukin-6 (IL-6) leading the pathological cascade. The inflammatory response leads to what is now termed microvascular COVID-19 lung vessel obstructive thromboinflammatory syndrome (microclots) [3, 4]. Additionally, in older patients, a change in the plasma levels of lymphocytes, thrombocytes, C-reactive protein, and lactate dehydrogenase enzyme can lead to sepsis, aggravation of the symptoms, and a prolonged need for medical care [5, 6]. Clinically, COVID-19 shows a broad range of presentations, ranging from being asymptomatic and non-septic to mild upper respiratory tract infection (URTI), pneumonia, and acute respiratory distress syndrome (ARDS), sepsis, and death. It should be noted that when the clinical frailty scores (CFS) are calculated to assess the risk severity, factors such as age, comorbidities, and sepsis should be attuned [7]. As we face an absence of specific treatment, while the disease continues to spread, re-emerge, and become a vicious circle of infections and reinfections, our understanding of the mechanisms reinforces the fact that a tolerable immune response is fundamental to preventing and treating this viral infection. Therefore, it has become very important for the scientific community to explore existing pharmacological agents that strengthen the immune activity. Vitamins and minerals have been reported to aid the proper functioning of the immune system and protect the host immune response. Therefore, owing to the significant properties of vitamins and minerals as immunomodulators, this review presents an update on the role of vitamin D and zinc as immunomodulators and suggests mechanistic approaches to address the COVID-19 pandemic. 13 Vitamin D was discovered in 1920, followed by the discovery of the vitamin D receptor (VDR) in 1969. At first, vitamin D was known to be a nutritionally essential steroid vitamin; later, it was recognized as an endocrine hormone and was further explored for its as immunomodulatory properties [8]. In humans, vitamin D is present in two physiological forms, vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). Vitamin D3 is synthesized in the skin through the reaction of 7-dehydrocholesterol by ultraviolet B radiation (UVB) to form provitamin D3. Moreover, vitamin D2 is photochemically synthesized in plants, and among the plant sources, mushrooms exposed to radiation have been reported to have a high yield of vitamin D2 [9]. Furthermore, being a nutritionally essential steroid vitamin, vitamin D has been ranked as one of the important immunomodulators, along with its pleiotropic biological significance. Vitamin D supplementation can decrease the ri (...truncated)