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COVID-19, Vitamin D

Vitamin D Insufficiency (VDI) Leads to Severe COVID-19 Symptoms

Easily correctable condition of Vitamin D Insufficiency (VDI) has very severe implications for COVID-19. In countries worst affected by COVID-19 such as Italy, Spain and Greece, Vitamin D insufficiency (VDI) rates were high in the range of 70-90%.; on the other hand, in Norway and Denmark, where COVID-19 was less severe, VDI rates were 15-30% suggesting strong correlation between VDI and COVID-19. It is hypothesized that VDI aggravates COVID-19 severity by its prothrombic effects and deregulation of immune response. Furthermore, in Wuhan, COVID-19 Associated Coagulopathy (CAC) was present in 71.4% of non-survivors vs. 0.6% in survivors. Patients with VDI having severe COVID-19 symptoms also had CAC, viz. blood clotting in micro vessels that was associated with high mortality.


Rajeev Soni, Ph.D., June 02, 2020


unveiling

The COVID-19 pandemic that has infected ~6.4 million people worldwide and resulted in death of ~380,000 people has brought the entire world on its knees with respect to the economic state of affairs. With the vaccine still far in sight, there is a need for a deeper understanding of the disease so that adequate precautions can be taken to avoid getting inflicted with the disease. The age old saying, “Prevention is better than cure”, is extremely apt in case of COVID-19 disease as the entire scientific world is grappling to understand the nature and complexity of this disease so as to find preventive measures to control its spread.

A number of studies have been performed to understand the life cycle of the SARS-CoV-2 virus, its virulence in people of different ages and the recovery rate of the people infected with the virus1,2. One of the factors that could have been overlooked is the Vitamin D status of the populations that could influence the severity of COVID-19 disease as more people are advised to stay indoors. In studies across Europe, it has been observed that COVID-19 had been severe in Italy, Spain and Greece which had vitamin D insufficiency (VDI) rates of 70-90% as compared to VDI of 15-30% in Norway and Denmark where the COVID-19 disease was not as severe3. People’s diet in Scandinavian countries are rich in Vitamin D due to high fatty fish intake and dairy supplements that are fortified with Vitamin D3.

In a recent study performed at a single, tertiary care academic medical centre on 20 subjects, a direct correlation was found between the levels of Vitamin D and the severity of COVID-19 disease. 11 of these patients were admitted to ICU and had VDI, 7 of them having levels below 20ng/mL while rest had even lower levels. Out of 11 patients in ICU, 62.5% had CAC (COVID-19 Associated Coagulopathy) while 92.5% had lymphopenia suggesting that VDI aggravates COVID-19 severity by its prothrombic effects and deregulation of immune response4. In Wuhan, CAC was present in 71.4% of non-survivors vs. 0.6% in survivors5. Vitamin D has been shown to play an essential role in modulating both the innate and adaptive immune response6, 7 while VDI is associated with increased risk of CVD and death8.

In another retrospective multicentre study of 212 cases with laboratory-confirmed infection of SARS-CoV-2, serum vitamin D levels were lowest in critical cases, but highest in mild cases9. Data analysis revealed that for each standard deviation increase in serum vitamin D, the odds of having a mild clinical outcome rather than a severe one was increased ~7.94 times, while interestingly, the odds of having a mild clinical outcome rather than a critical outcome were increased ~19.61 times9. This suggests that an increase in vitamin D levels in the body could either improve clinical outcomes, while a decrease in vitamin D levels in the body could intensify the clinical outcomes in COVID-19 patients.

These studies showing a positive/improved clinical response in COVID-19 patients with increased levels of vitamin D and a negative/poor clinical response with low vitamin D levels warrant further investigation on the role of vitamin D in COVID-19 disease and provides a way forward for clinicians and policy makers to undertake large population trials to evaluate this as a preventive measure to fight against COVID-19.


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References:

1. Weiss SR and Navas-Martin S. 2005. Coronavirus pathogenesis and the emerging pathogen severe acute respiratory syndrome coronavirus. Microbiol. Mol. Biol. Rev. 2005 Dec;69(4):635-64. DOI: https://doi.org/10.1128/MMBR.69.4.635-664.2005

2. Soni R., 2020. ISARIC Study Indicates How Social Distancing Could Be Fine-tuned in Near Future to Optimise ‘Protecting Lives’ and ‘Kickstart National Economy’. Posted May 01, 2020. Scientific European. Available online at https://www.scientificeuropean.co.uk/isaric4c-study-indicates-how-social-distancing-could-be-fine-tuned-in-near-future-to-optimise-protecting-lives-and-kickstart-national-economy Accessed on 30 May 2020.

3. Scharla SH., 1998. Prevalence of subclinical vitamin D deficiency in different European countries. Osteoporosis Int. 8 Suppl 2, S7-12 (1998). DOI: https://doi.org/10.1007/PL00022726

4. Lau, FH., Majumder, R., et al 2020. Vitamin D insufficiency is prevalent in severe COVID-19. Pre-print medRxiv. Posted 28 April 2020. DOI: https://doi.org/10.1101/2020.04.24.20075838 or https://www.medrxiv.org/content/10.1101/2020.04.24.20075838v1

5. Tang N, Li D, et al 2020. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. Journal of Thrombosis and Haemostasis 18, 844–847 (2020). First published:19 February 2020. DOI: https://doi.org/10.1111/jth.14768

6. Liu PT., Stenger S., et al. 2006. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 311, 1770–1773 (2006). DOI: https://doi.org/10.1126/science.1123933

7. Edfeldt K., Liu PT., et al 2010. T-cell cytokines differentially control human monocyte antimicrobial responses by regulating vitamin D metabolism. Proc. Natl. Acad. Sci. U.S.A. 107, 22593–22598 (2010). DOI: https://doi.org/10.1073/pnas.1011624108

8. Forrest KYZ and Stuhldreher WL 2011. Prevalence and correlates of vitamin D deficiency in US adults. Nutrition Research 31, 48–54 (2011). DOI: https://doi.org/10.1016/j.nutres.2010.12.001

9. Alipio M. Vitamin D Supplementation Could Possibly Improve Clinical Outcomes of Patients Infected with Coronavirus-2019 (COVID-19) (April 9, 2020). Available at SSRN: https://ssrn.com/abstract=3571484 or http://dx.doi.org/10.2139/ssrn.3571484

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