The Possible Role of Vitamin D in lowering Mortality in COVID-19 PatientsJuly 12, 2020
The recent global outbreak of COVID-19 imposed catastrophic impacts on every society, specifically among elderly populations. Currently, no treatment or vaccine against the virus is available. Consequently, there is a significant need to look at potential approaches that can reduce the number of severe COVID-19 cases and thus reduce the mortality rate associated with the disease. It has also been proposed that the immune system in some patients may manage COVID-19 better than in others.
However, the potential causes or mechanisms underlying this have yet to be determined. Temporal analysis of the number of confirmed, deceased, and recovered cases across the world reveal patterns as to how COVID-19 has impacted different populations, which may help improve our understanding of the defense mechanism of the immune system against COVID-19 as well as aid in developing effective treatment options. Data show that the mortality rate of COVID-19 varies dramatically across countries. For example, a higher case fatality ratio has been reported in Spain, Italy, and the UK compared to that of the US and Germany. The cause for these disparities is not well understood. Several hypotheses have been proposed, including the emergence and circulation of different strains of the virus, idiosyncrasies in COVID-19 testing strategies and policies across countries, quality and access to health care, demographic factors such as the prevalence of elderly within a given population, and socioeconomic factors.
Aging can lead to a weakening of the innate immune system which may play a role in the development of severe COVID-19. Specifically, a weak innate immune system response in the elderly can lead to a higher load of SARS-CoV-2 and a consequent overactivation of the adaptive immune system, leading to an increased level of cytokine production.
The role of Vitamin D in regulating the immune system has been supported by multiple studies. Vitamin D can suppress cytokine production by simultaneously boosting the innate immune system (thus reducing the viral load) and decreasing the overactivation of the adaptive immune system to immediately respond to the viral load. Some researchers have suggested the potential role of Vit D in suppressing cytokine storm during the 1918-
1919 viral influenza pandemic. Moreover, the role of Vitamin D in enhancing an immune response in flu and previous coronaviruses has been suggested in several studies. It is this ability of Vitamin D in suppressing cytokine production that motivated their focus on Vitamin D deficiency and its association with severe COVID-19.
According to the study, no randomized blinded experiment has yet reported Vitamin D status and cytokine levels in patients with COVID-19. In spite of this, it is still possible to investigate the association between Vitamin D status and unregulated inflammation and cytokine production leading to severe COVID-19 based on a potential link between Vitamin D deficiency and C-reactive proteins (CRP). CRPs are produced primarily in the liver in response to inflammation to minimize damage to tissues from autoimmunity, infection, and other causes. The inflammatory cells’ ability to convert Vitamin D metabolites into calcitriol (the active form of Vit D) and to express the nuclear receptor of Vitamin D suggests a potential inverse association between CRP and Vitamin D, which is also supported by epidemiological studies. They have partially addressed some of the concerns regarding association between Vitamin D and other risk factors of COVID-19 A-CMR including heart disease, diabetes, age, and obesity in each country via regression analysis.
Large-scale data shows that different countries have differing adaptive average case mortality rates (A-CMR) among confirmed cases. Screening strategies notably impact A-CMR, as countries with aggressive COVID19 screening show decreased A-CMR. Their analysis of mean 25-hydroxyvitamin D (25(OH)D) across countries with similar testing strategies determined a possible link between Vitamin D status and A-CMR. Their analysis shows other chronic factors such as the elderly ratio of population, the prevalence of diabetes, prevalence of CHD in a country have less impact on A-CMR than Vitamin D deficiency.
Their hypothesis on the role of unregulated inflammation in COVID-19 complications is consistent with findings such as an increase in the rate of complications with age, low rate of complications in children, and adverse outcomes with ibuprofen, and suggests that it might be of interest to study Vitamins D’s role in COVID in controlled observational or clinical trials. Their analysis of high CRP in healthy subjects (CRP ³ 0.2 mg/dL) showed an inverse relation between Vitamin D status and high C-Reactive Protein (CRP) which is an indicator of low-grade inflammation in healthy subjects. They showed elderly and subjects from low-income families are at a higher risk of the low-grade inflammations attributed to high CRP. They calculated an OR of 1.8 with 95%CI (1.2 to 2.6) among the elderly (age ³ 60 yo) in low-income families and an Odds Ratio (OR) of 1.9 with 95%CI (1.4 to 2.7) among the elderly (age ³ 60 yo) in high-income families. COVID-19 patient-level data shows a notable OR of 3.4 with 95%CI (2.15 to 5.4) for high CRP in severe COVID-19 patients (CRP ³ 1 mg/dL). Based on retrospective data and indirect evidence we see a possible role of Vit D in reducing complications attributed to unregulated inflammation and cytokine storm however we emphasize that we do not have the patient-level data to suggest that Vit D is therapeutic.
Full study download it here https://www.medrxiv.org/content/10.1101/2020.04.08.20058578v4.full.pdf