The role of vitamin D in H1N1 influenza and SARS-CoV-2 infection

Low vitamin D levels lead to poor outcomes following acute respiratory infection (e.g., influenza). This is why high doses of vitamin D supplements have been recommended to reduce the severity of seasonal influenza. During the ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), scientists renewed their interest in studying the role of vitamin D in protecting individuals from severe infection.

Background

Previous studies have shown that vitamin D supplementation is beneficial for treating COVID-19. These studies have shown that low levels of vitamin D circulation (serum 25(OH)D, 25D) were correlated with a high mortality rate among COVID-19 patients.

Scientists reported that vitamin D and the active form of vitamin D (1,25(OH)2D, 1,25D) play a significant role in the anti-viral response. However, the extent of the effect may vary with different viruses. A previous in vitro study revealed that 1,25D treatment of T cells from individuals infected with human immunodeficiency virus (HIV) showed a significant decrease in viral RNA transcription by direct decrease of NF-kB, which reactivates proviral HIV. However, similar in vitro treatment on epithelial cells of patients infected with respiratory syncytial virus (RSV) did not affect viral replication.

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Scientists revealed that the production of cytokines (e.g., TNFa, IL-5, IL-1b, IL-6, IL-10 and type I interferons) and antimicrobial peptides (e.g., cathelicidin, b-defensin, etc.,) at mucosal surface play an important role in the innate immune response against viruses. Many studies have reported that 1,25D and other vitamin D analogs induce the production of cathelicidin in response to viral infection.

Since studies have reported that cathelicidin LL-37 can effectively kill viruses, such as influenza, researchers believe it could also inhibit the SARS-CoV-2 virus. Another important attribute of 1,25D is that it reduces IFNg, IL-6, and TNF levels and restricts inflammatory responses.

Research has also shown that vitamin D targets lung epithelial cells due to the presence of vitamin D receptors (VDR). A previous study using a mice model demonstrated that mice treated with 1,25D precursors were also protected from subsequent H1N1 influenza infection.

About the study

Using animal models, a new study posted to the bioRxiv* preprint server focused on determining Vitamin D's role in SARS-CoV-2 and H1N1 influenza. In this study, researchers determined the effect of vitamin D supplements on the lung anti-viral response in animal models.

The current study utilized two animal models, i.e., mice and hamsters. The experimental findings from both the animal models suggested that vitamin D supplements effectively reduced lung inflammation following SARS-CoV-2 and H1N1 influenza infection.

Scientists found that D- mice had lung infections even without viral infection. A previous study by the same group of researchers reported that feeding D- diets to mice inhibited the production of 1,25D (Cyp KO), which resulted in severe vitamin D deficiency. The current study reported severe influenza infection in D- Cyp KO, while minimal infection was observed in D+ WT mice.

The authors reported that following influenza infection, the survival of D+ Cyp KO mice was significantly less compared to D+ WT mice. Similarly, researchers observed that the introduction of vitamin D supplement significantly lowered lung inflammation and Ifnb expression in the lung of mice after SARS-CoV-2 infection.  

Scientists observed that vitamin D treatments did not show any effect on the expression of viral RNA (SARS-CoV-2 or H1N1 influenza) in the lungs of both hamsters and mice. However, it controlled the hosts’ inflammatory response to viruses in the lungs. 

A high dose of vitamin D treatment (D++) exhibited a similar level of protection from SARS-CoV-2 in mice. Additionally, 25D treatment supported a faster recovery in SARS-CoV-2 infected mice. The finding of this study is supported by previous studies that reported 25D treated mice exhibited a reduction in lung inflammation. However, vitamin D treatment showed an insignificant effect on weight loss and lethality following H1N1 infection.

Researchers reported that SARS-CoV-2 infection-induced Cyp27B1 and Cyp24A1 in the lungs of mice infected with SARS-CoV-2. The current study stated that the ability of the host to produce Cyp27B1 is essential for the survival of mice with H1N1 infection. The dietary supplements, i.e., only a high dose of vitamin D supplement (D++), increased the concentration of 25D in serum.

Conclusion

The study's results strongly indicated that vitamin D and 1,25D treatment could effectively protect the lungs from COVID-19 infection. More clinical studies are required to understand better the underlying mechanism by which vitamin D regulates anti-viral response in the lungs.

*Important notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Dr. Priyom Bose

Priyom holds a Ph.D. in Plant Biology and Biotechnology from the University of Madras, India. She is an active researcher and an experienced science writer. Priyom has also co-authored several original research articles that have been published in reputed peer-reviewed journals. She is also an avid reader and an amateur photographer.