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A new article published on the prepress server medRxiv * The first evidence is reported in May 2020 that vitamin D deficiency and inadequate treatment could increase the chances of testing positive for COVID-19. This could shape screening for people at risk for vitamin D deficiency.
Classification of vitamin D deficiency
The study by researchers at the University of Chicago examined more than 4,300 patients with COVID-19, of whom 499 had been screened for vitamin D levels in the past year. Based on this, they were divided into probably deficient (25%), probably adequate (58%) and uncertain (16%).
Vitamin D deficiency was diagnosed by “the most recent 25-hydroxycholecalciferol <20ng / ml or 1,25-dihydroxycholecalciferol <18pg / ml within one year prior to the COVID-19 test".
Vitamin D deficiency linked to positive COVID-19 test
Multiple variables were analyzed in this study. The researchers found that people with vitamin D deficiency in the last test, and who did not receive higher doses of vitamin D (keeping them deficient in all likelihood), are much more likely to become infected with the virus than those with probably sufficient levels. Corresponding infection rates were 22% vs. 12%.
The prevalence of vitamin D deficiency decreased with a higher dose of vitamin D, but the latter was not associated with positive evidence for COVID-19.
Previous trials and meta-analyzes have already suggested that enough vitamin D can prevent COVID-19. Still, this study is the earliest direct connection between vitamin D deficiency and an increased risk of viral disease. Vitamin D treatment can also reduce the risk of other respiratory infections, and coronaviruses play a prominent role in them.
The analysis did not show a significant difference between the patients with low vitamin D levels in the last test who were or were not treated. On the other hand, the study shows that few of these patients actually receive high doses of vitamin D. In other words, reluctance to treat this deficiency adequately is a significant contributor to failure to detect an association.
Factors underlying vitamin D deficiency
Vitamin D deficiency is more common in black Americans because of the dense concentration of the chemical that blocks ultraviolet rays in the skin. Since this community has been disproportionately affected by COVID-19, both in terms of illness and death, it would be advisable to offer them vitamin D testing.
Genetic factors affect the incidence of vitamin D deficiency. This finding may indicate an inheritable component of the risk of viral disease. This could help determine if a COVID-19 test should be done among family members of people who have the infection.
Another question posed by this study is whether vitamin D supplementation could reduce virus transmission. Vitamin D is an immunomodulator, which works through innate immune cells called dendritic cells, as well as adaptive T cells. This leads to further elimination of the virus from the body, as well as suppression of the inflammatory responses that lead to symptomatic disease.
A higher vitamin D level is related to a reduction in IL-6 levels, the latter being a pro-inflammatory cytokine. This is a significant discovery since IL-6 inhibitors are an important drug target for suppressing the cytokine storm that is believed to be related to death and critical illness.
The vitamin can also influence zinc processing, reducing the replication of the coronavirus. All of the above actions are beneficial and can help control viral spread.
However, the anti-inflammatory or immunomodulatory activity of vitamin D could also increase the number of asymptomatic infections and, therefore, possibly increase the number of people infected by secondary contact. The absence of cough, fever and other expected manifestations could confuse the problem by increasing the group of asymptomatic patients. Since this has the potential to increase community spread, it is difficult to measure the degree of protection in people without disabilities.
Limitations and implications
The study has its drawbacks. The observational nature of the study does not allow concluding that vitamin D deficiency causes an increased risk of COVID-19 infection. In fact, vitamin D can be lowered due to multiple medical conditions and behavioral factors that possibly reduce the possibility of proper treatment while increasing the risk of COVID-19.
However, the findings remain unchanged across a wide range of other diseases and age groups.
The study also examined patients who had received vitamin D2 or calcitriol. The use of calcitriol was one of the factors that led to a definition of vitamin D deficiency, as it is often used in patients with chronic kidney disease or hypoparathyroidism. When these cases are excluded, the observed associations generally become stronger.
Another factor is the location and basis of the study: a large number of people with chronic illnesses, health workers, and African Americans, in a northern city in winter. This predisposes to a more significant number of people with vitamin D deficiency. In another population subgroup, this may be less important in determining the risk of COVID-19.
The case for universal vitamin D supplementation
The findings support the finding that a low vitamin D level increases the risk of COVID-19, but treatment that adequately addresses the deficiency reduces the risk. This conclusion is reinforced by the finding that those who were treated with higher doses after having a low level of vitamin D in their last test were not at increased risk. Its possibilities were comparable to those whose latest test results and treatment history suggested adequate levels of vitamin D at the time of the COVID-19 test.
The type and dose of treatment are related to the rate of vitamin D deficiency, and this can be fully explained by administering vitamin D3 at 2000 IU of ≥3000 IU. This relationship shows that treatment is an important factor in determining this risk.
On the other hand, the relationship between treatments for vitamin D deficiency and the risk of COVID-19, and the level of vitamin D and its deficiency, is complex. It highlights the need for randomized trials that can resolve the issue with more meaningful evidence for or against the role of vitamin D deficiency treatment in reducing this risk.
The importance of social distancing and movement restriction in COVID-19 makes low-cost home tests for vitamin D even more valuable in the context of their contribution to deciding on the type of treatment. On the other hand, vitamin D can be administered blindly at 4000 IU or 5000 IU per day due to its known safety, as long as it is not known that the person has any contraindications for this supplement.
Logically, the preventive effect of vitamin D treatment would be more significant among those with low levels of the sun vitamin. Despite this expectation, the researchers advocate that supplementation is available to everyone, and if necessary, for tests targeting high-risk groups likely to have deficient levels of vitamin D and / or COVID-19.
This is more feasible considering that vitamin D supplements are quite safe, COVID-19 testing is limited even today, testing is expensive, and vitamin D levels fluctuate with the seasons due to variable exposure to the strong ultraviolet rays necessary to convert the prodrug into its active form.
The type of analysis done here is fairly simple and lends itself to other situations, with all odds of reaching similar conclusions. This is especially true because vitamin D deficiency is so prevalent in the American population, and particularly in darker-skinned people, the elderly, and those living in nursing homes.
Given these findings, the researchers recommend “expanded vitamin D treatment at the population level and testing and evaluating the effects of those interventions,” due to the strong possibility that vitamin D deficiency increases the risk of COVID. -19. Therefore, this needs to be followed up with more studies at once to understand if positive measures to increase vitamin D levels in deficient people would help reduce the number of new cases of COVID-19. Large-scale interventions targeting people in general, as well as specific interventions for high-risk groups, should be prioritized.
*Important news
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behavior, or be treated as established information.
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