Vitamin D attenuates COVID-19 complications via modulation of proinflammatory cytokines, antiviral proteins, and autophagy

ABSTRACT

Introduction

Global emergence of coronavirus disease-19 (COVID-19) has clearly shown variable severity, mortality, and frequency between and within populations worldwide. These striking differences have made many biological variables attractive for future investigations. One of these variables, vitamin D, has been implicated in COVID-19 with rapidly growing scientific evidence.

Areas covered

The review intended to systematically explore the sources, and immunomodulatory role of vitamin D in COVID-19. Search engines and data sources including Google Scholar, PubMed, NCBI, Scopus, and Web of Science were used for data collection. The search terms used were Vitamin D, COVID-19, immune system, and antiviral mechanism. Overall, 232 sources of information were collected and 188 were included in this review.

Expert opinion

Interaction of vitamin D and vitamin D receptor (VDR) triggers the cellular events to modulate the immune system by regulation of many genes. Vitamin D operates as a double-edged sword against COVID-19. First, in macrophages, it promotes the production of antimicrobial and antiviral proteins like β-defensin 2 and cathelicidin, and these proteins inhibit the replication of viral particles and promote the clearance of virus from the cells by autophagy. Second, it suppresses cytokine storm and inflammatory processes in COVID-19.

KEYWORDS:

• Vitamin D
• photosynthesis
• immune system
• mechanism of action
• COVID-19

Article highlights

• Vitamin D is synthesized by the human skin cells under UVB radiation and activated in the liver and kidneys.

• Vitamin D deficiency has been positively linked with increased chances of infection, severity, and mortality by respiratory infections including COVID-19.

• VRD-Vitamin D interaction results in the regulation of many genes associated with immune system and promotes the innate and adaptive immune response against respiratory infections.

• It enhances the production of antibacterial and antiviral proteins including beta-defensins and cathelicidin to inhibit the cellular entry and subsequent proliferation of virus particles.

• In the macrophages, vitamin D promotes autophagy and clearance of virus particles by upregulation of calcium/nitric oxide, immunomodulatory proteins, and downregulation of mTOR pathway.

• Future studies on anti-inflammatory and antiproliferative mechanisms involving vitamin D an development and application of appropriate animal models are recommended to combat COVID-19 or any upcoming similar pandemic.

Declaration of interest

The author(s) have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers in this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This research was funded by the Deanship of Scientific Research at Princess Nourah bint Abdulrahman University through the Fast-track Research Funding Program to support publication in the top journal (Grant no.42-FTTJ-20).