The Effects of 10,000 IU Vitamin D Supplementation on Improvement of Clinical Outcomes, Inflammatory and Coagulation Markers in Moderate COVID-19 Patients: A Randomized-Controlled Trial

Background & aims: Vitamin D supplementation as an immunomodulator has been identified as a potential strat-egy to prevent and treat Coronavirus disease 2019 (COVID-19). We aimed to analyze the effect of 10,000 IU vitamin D3 supplementation on 25(OH)D levels on primary clinical out-comes (conversion length), inflammatory markers (Total Lymphocyte Count (TLC), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR)) and coagulation marker (D-Dimer) in moderate COVID-19 patients at Wahidin Sudirohusodo Hospital, Makassar, Indonesia.Methods: We conducted a single-blind randomized -con-trolled trial on the confirmed moderate COVID-19 patients above 18 years old and low vitamin D status. Each of inter-vention and control groups were supplemented of 10,000 IU and 1000 IU cholecalciferol that taken daily for 2 weeks. Levels of 25(OH)D were analyzed for the primary endpoint (conversion length), then correlated to secondary endpoints (Length of Stay (LOS)), clinical manifestations improvement, and markers TLC, NLR, PLR, and D-Dimer serum, handgrip strength (HGS) as functional capacity measurement, after ad-justed to age, sex, nutritional status based on body mass in- dex (BMI) and Subjective Global Assessment (SGA) tool, co -morbidities, and anti-coagulant administration. Medical nutri-tional therapy was given and presented as energy, protein, carbohydrate, and fat achievement, and vitamin D intake was also calculated.Results: A significant effects was found in 60 samples with pre-intervention vitamin D deficiency (61.7%) and insuffi-ciency (38.3%) status, and 10,000 IU of vitamin D3 supple-mentation could increase 25(OH)D levels within 2 weeks to reach sufficiency status (16.7%). The Vitamin D3 supplemen-tation of 10,000 IU and 1000 IU could significantly increase 25(OH)D levels compared to the control group of 1000 IU (4.61 +/- 5.43 vs.-0.29 +/- 2.72; P <0.0001) and it was correlated to primary clinical outcome, which is length of conversion (6.53 +/- 1.17 vs 10.47 +/- 2.56; P < 0.0001). The increase in HGS (6.61 +/- 3.01 vs. 4.04 +/- 4.44; P = 0.011), LOS (11.63 +/- 2.5 vs. 14.73 +/- 3.45; P = 0.001), and improvement in clinical mani-festations were found to be significant in both groups. We an-alyzed changes the effect of vitamin D supplementation in TLC, NLR, and D-Dimer as marker of coagulopathy associated COVID-19 on both groups that showed were not significant. Positive and significant correlation was only showed on PLR levels after intervention (r=0.368; P=0.045).Conclusion: Supplementation of vitamin D3 10,000 IU in moderate COVID-19 patients had a significant effect on 25(OH)D level, length of conversion, LOS, functional capacity, and PLR levels, but it has negative correlation in TLC, NLR, and D-Dimer levels.This study has been registered in the ClinicalTrial.gov data-base with the identification number NCT05126602.