COVID-19 treated by Vitamin D (example: ICU reduced by 5X) – 20th meta-analysis Oct 13, 2021

Vitamin D supplementation to treat SARS-CoV-2 positive patients. Evidence from meta-analysis

Cardiol J. 2021 Oct 13. doi: 10.5603/CJ.a2021.0122
Luiza Szarpak 1 2, Krzysztof J Filipiak 3, Aleksandra Gasecka 4 5, Wladyslaw Gawel 2 6, Dorota Koziel 7, Milosz J Jaguszewski 8, Jaroslaw Chmielewski 9, Anatolii Gozhenko 10, Karol Bielski 2 11, Pawel Wroblewski 12, Ivan Savytskyi 10, Lukasz Szarpak 13 14, Zubaid Rafique 15 Poland

Background: Vitamin D is a likely candidate for treatment as its immune modulating characteristics have effects on coronavirus disease 2019 (COVID-19) patients. It was sought herein, to summarize the studies published to date regarding the vitamin D supplementation to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients.

Methods: A systematic review and meta-analysis were performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The primary outcome were 14-day and in-hospital mortality reported as an odds ratio (OR) with the associated 95% confidence interval (CI).

Results: Eight articles were included in the review with a combined total of 2,322 individual patients, 786 in the vitamin D supplementation group and 1,536 in the control group. The use of vitamin D compared to the group without vitamin D supplementation was associated with a

• lower 14-day mortality (18.8% vs. 31.3%, respectively; OR = 0.51; 95% CI: 0.12-2.19; p = 0.36), a
• lower in-hospital mortality (5.6% vs. 16.1%; OR = 0.56; 95% CI: 0.23-1.37; I² = 74%; p = 0.20), the
• rarer intensive care unit admission (6.4% vs. 23.4%; OR = 0.19; 95% CI: 0.06-0.54; I² = 77%; p = 0.002) as well as
• rarer mechanical ventilation (6.5% vs. 18.9%; OR = 0.36; 95% CI: 0.16-0.80; I² = 0.48; p = 0.01).

Conclusions: Vitamin D supplementation in SARS-CoV-2 positive patients has the potential to positively impact patients with both mild and severe symptoms. As several high-quality randomized control studies have demonstrated a benefit in hospital mortality, vitamin D should be considered a supplemental therapy of strong interest. Should vitamin D prove to reduce hospitalization rates and symptoms outside of the hospital setting, the cost and benefit to global pandemic mitigation efforts would be substantial.

DISCUSSION section

Though global vaccination against the SARS-CoV-2 virus has been ongoing since late 2020 and the various vaccines continue to be effective at preventing hospitalizations [25], more infectious variants of SARS-CoV-2 are fueling a rebound in infections among the unvaccinated [26]. As most countries will not achieve herd immunity from vaccination efforts until well into 2022, COVID-19 will likely continue to occupy hospital systems in countries all over the world [27]. Treatment for hospitalized COVID-19 patients will also limit access to essential medical services for people suffering from chronic and degenerative diseases [28].
As a consequence, research into potential therapeutic agents such as azithromycin and chloroquine have made headlines [29, 30], however these strategies proved futile and even dangerous [31, 32]. Additionally, the use of Lopinavir, Ritonavir, Remdesivir, Oseltamivir, Ribavirin to treat COVID-19 also proved not to be effective [33, 34].

At this time, vitamin D, which has immunomodulating characteristics and has been shown to be associated with better outcomes in upper respiratory tract infections, should be a candidate of interest in mitigating COVID-19 [35, 36]. This inexpensive and readily available supplement could be rapidly and widely implemented with minimal risk of detriment to the general public. The implementation of which could result in decreased ICU admissions that could reduce the number of occupied ICU beds and result in better clinical outcomes [36]. In one randomized control ICU study, supplemental vitamin D administered to COVID-19 patients, alongside existing therapy, was associated with lower ICU admission and mortality [21]. The inclusion criteria included COVID positive patients with clinical and radiological findings of ARDS and resulted in a reduction in ICU treatment and a reduction of symptoms.

It must be noted that the groups did not differ at the baseline with the control group presenting more often with hypertension while the clinical group was slightly older [37].

It has been hypothesized that the benefits of vitamin D in patients suffering from ARDS are due to the activation of the vitamin D receptor (VDR) pathway, resulting in a decrease of cytokine expression [38], a central cause of rapid deterioration [39]. Additionally, vitamin D deficiency in ICU patients is common [40] and may indicate that other complications in COVID-19 infections are the result of this deficiency [13]. When a combination of vitamin D/magnesium/vitamin B12 were administered the older patients, this combination was found to reduce the need for the more advanced procedures without adding significant costs [46]. The rationale for this combination lies in the fact that magnesium enhances vitamin D activity and plays a pivotal role in the immune system [41, 42]. Additionally, vitamin B12 stabilizes the gut microbiota, which has also played a pivotal role in a patient’s overall health [43, 44]. These observations are reinforced by other studies where vitamin D administered in frail elderly patients was associated with better survival rate and less severe COVID-19 course [45].

However, other studies have found that the administration of vitamin D in COVID-19 patients conveyed no clinical benefit in terms of severity of disease, while also being associated with a twofold increase in mortality rate [21]. It can be hypothesized that late administration of vitamin D in the presence of severe inflammation could impair the metabolism of vitamin D [46], resulting in a buildup of the metabolites.
The last study included in this review found that the administration of vitamin D administration had no effect on the severity of the course of COVID-19 infections [47]. It should be noted that the protocol of this trial included the administration of a onetime dose of 200,000 IU of vitamin D among hospitalized patients with moderate or severe disease. It is not clear if this one dose regiment is sufficient as many patients with upper respiratory tract conditions display, e.g., asthma, impaired function of the CYP2R1 (vitamin D 25-hydroxylase) [48] which is an enzyme that catalyzes the formation of vitamin D3 to 25-hydroxyvitamin D3 (25(OH)D3), which reduces the biologically active form of vitamin D.

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