Rapid and Effective Vitamin D Supplementation May Present Better Clinical Outcomes in COVID-19 (SARS-CoV-2) Patients by Altering Serum INOS1, IL1B, IFNg, Cathelicidin-LL37, and ICAM1

Abstract

Background: We aimed to establish an acute treatment protocol to increase serum vitamin D, evaluate the effectiveness of vitamin D3 supplementation, and reveal the potential mechanisms in COVID-19. Methods: We retrospectively analyzed the data of 867 COVID-19 cases. Then, a prospective study was conducted, including 23 healthy individuals and 210 cases. A total of 163 cases had vitamin D supplementation, and 95 were followed for 14 days. Clinical outcomes, routine blood biomarkers, serum levels of vitamin D metabolism, and action mechanism-related parameters were evaluated. Results: Our treatment protocol increased the serum 25OHD levels significantly to above 30 ng/mL within two weeks. COVID-19 cases (no comorbidities, no vitamin D treatment, 25OHD <30 ng/mL) had 1.9-fold increased risk of having hospitalization longer than 8 days compared with the cases with comorbidities and vitamin D treatment. Having vitamin D treatment decreased the mortality rate by 2.14 times. The correlation analysis of specific serum biomarkers with 25OHD indicated that the vitamin D action in COVID-19 might involve regulation of INOS1, IL1B, IFNg, cathelicidin-LL37, and ICAM1. Conclusions: Vitamin D treatment shortened hospital stay and decreased mortality in COVID-19 cases, even in the existence of comorbidities. Vitamin D supplementation is effective on various target parameters; therefore, it is essential for COVID-19 treatment.

The Interaction of Vitamin D and Corticosteroids: A Mortality Analysis of 26,508 Veterans Who Tested Positive for SARS-CoV-2

“…Considerable discordance exists regarding the effectiveness of Vit D in the treatment of COVID-19, with some reports suggesting a beneficial effect [ 15 , 16 , 17 , 28 , 29 , 31 , 41 , 45 , 53 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 ] and others no change [ 26 , 27 , 30 , 32 , 33 , 34 , 35 , 36 , 37 , 44 , 107 , 108 , 109 ]. The reasons for these disparate findings are likely complex and multifactorial, with varying doses, duration, and timing of Vit D administration along with patient populations and sample sizes all playing roles [ 110 ].…”

“…Indeed, the opposite appears to be the case in that the mortality risk among hospitalized patients receiving both Vit D and CRTs was statistically lower than that for patients using CRTs in the absence of Vit D. While hospitalization status was considered a surrogate marker of disease severity in our analysis, we recognize that different patients might have presented to the hospital with varying states of acute illness [ 109 ]. We also acknowledge that the response to Vit D in patients with already high levels at the time of hospital admission may be more beneficial than efforts aimed at increasing levels within a brief window with treatment [ 105 ]. In future analyses, we will aim to delineate individual dose levels by model covariates and outcome variables.…”

“…Patients in the ICU are, in general, at risk of having lower levels of 25-hydroxyvitamin D (25D) and suboptimal cellular oxygenation for various reasons (e.g., fluid resuscitation, renal failure, cardiac/respiratory failure, and gastrointestinal bleeding) [ 150 ]. When administered in this setting, Vit D replacement therapy may, in theory, reduce mortality by increasing hemoglobulin levels, decreasing hepcidin concentrations, and facilitating oxygenation at the cellular level [ 105 ]. Thus, aspects of Vit D use noted in the current paper may also apply overall to hospitalized patients with severe illness, warranting a study of Vit D in this broader population while considering a possible interaction with CRT use in the study design.…”

Vitamin D’s Role in Reducing Risk of SARS-CoV-2 and COVID-19 Incidence, Severity, and Death

“…Two approaches were attempted with mixed results. The most comprehensive trial of vitamin D 3 supplementation with COVID-19 patients was a trial conducted in Turkey [ 9 ]. Of 867 COVID-19 patients, 160 patients with initial 25(OH)D concentrations of <30 ng/mL were treated with 224,000 to 500,000 IU over periods from 3 to 7 days to achieve >30 ng/mL.…”

Preventing the Adverse Effects of SARS-CoV-2 Infection and COVID-19 through Diet, Supplements, and Lifestyle

“…One reason for limited beneficial effects of vitamin D supplementation in this trial may be that the low doses did not raise 25(OH)D concentrations rapidly enough to significantly affect the course of the disease. It is thought that providing much higher doses [ 7 ] or using calcifediol [25(OH)D] may have achieved more favorable clinical benefits [ 8 ].…”