Impact of daily high dose oral vitamin D therapy on the inflammatory markers in patients with COVID 19 disease.

In a prospective open-label interventional clinical trial in India of 87 hospitalized COVID-19 patients with mild to moderate illness and hypovitaminosis D (< 30 ng/ml or < 75 nmol/L), high-dose oral vitamin D therapy (60,000 IU for 8-10 days) resulted in a significant reduction of inflammatory markers associated with COVID-19 (neutrophil/lymphocyte (N/L) ratio, C-reactive protein (CRP), lactate dehydrogenase (LDH), interleukin-6 (IL6) and ferritin).

• Intensive care support was required for 9 subjects (VD group: n = 4, NVD group: n = 5) and 7 of them died (VD group: n = 2, NVD group: n = 5).
• Mean vitamin D levels increased from 16±6 ng/ml (40±15 nmol/l) to 89±32 ng/ml (222±80 nmol/l) after Pulse D therapy in the VD group.
• Following Pulse D therapy, all the measured inflammatory markers were significantly reduced in the VD group. However, analysis of inflammatory markers in the NVD group before and after treatment did not show significant reduction except CRP. On the contrary levels of IL6 and ferritin increased but were not significant statistically.
• The difference in the reduction of inflammatory markers between the two groups (NVD vs VD) was significant with the reduction in the VD group being markedly higher than the NVD group.

Eighty-seven COVID-19 patients (65 men, 74.7%; 22 women, 25.3%) > 18 years with hypovitaminosis D (< 30 ng/ml or < 75 nmol/L) and mild to moderate COVID-19 illness (SpO2 > 90%) completed the study. Patients with severe illness; patients who had taken high dose vitamin D (60,000 IUs) in the last 3 months; patients with active malignancy, chronic renal disease, or HIV; and pregnant and breastfeeding mothers were excluded. The mean age of patients who completed the study was 45±13 years, ranging from 20–83 years.

• This study included patients from a single center in India and may not be generalizable to all COVID-19 patient populations.
• The study included a very limited number of patients (n=87) and no formal sample size calculation was performed. In addition, the patient population was skewed heavily towards men.
• These results only apply to hospitalized COVID-19 patients, they do not address whether earlier stages of the disease respond to calcifediol treatment.
• The study was not double-blinded.

Immune dysregulation in COVID-19 is marked by increased inflammatory biomarkers such as N/L ratio, CRP, LDH, IL6 and Ferritin. Vitamin D is a potential immunomodulator and its adjunctive role in the treatment of COVID-19 is established by this study. Improvement of serum vitamin D levels to 80–100 ng/ml (200-250 nmol/l) significantly reduced the inflammatory markers without any side effects.

• This was a randomized prospective open label parallel assignment interventional clinical trial carried out in India at Gandhi Medical College, Hospital Secunderabad in collaboration with Nizam’s Institute of Medical Sciences, Hyderabad.
• Subjects were randomized into vitamin D (VD) and non-vitamin D (NVD) groups. Owing to randomization, the VD group was comprised of 84% men (37 men, 7 women) while the NVD group was 65% men (28 men, 15 women).
• The VD group received Pulse D therapy (targeted daily supplementation of 60,000 IUs of vitamin D as an oral syrup) for either 8 days (BMI 16-25) or 10 days (BMI >25) in addition to standard treatment for COVID-19. The NVD group received standard COVID-19 treatment alone.
• COVID-19 patients with hypovitaminosis D (< 30 ng/ml or < 75 nmol/L) were evaluated for inflammatory markers (neutrophil/lymphocyte (N/L) ratio, C-reactive protein (CRP), lactate dehydrogenase (LDH), interleukin-6 (IL6) and ferritin) along with serum vitamin D levels on Day 0 and Day 9 or 11 as per their respective BMI category.
• Differences in the variables between the two groups were analyzed for statistical significance.

Lakkireddy M, Gadiga SG, Malathi RD, Karra ML, Raju ISSVPM, Ragini, Chinapaka S, Baba KSSS, Kandakatla M. Impact of daily high dose oral vitamin D therapy on the inflammatory markers in patients with COVID 19 disease. Sci Rep. 2021 May 20;11(1):10641. doi: 10.1038/s41598-021-90189-4. PMID: 34017029; PMCID: PMC8138022.