Abstract: medRxiv preprint doi: https://doi.org/10.1101/2021.08.22.21262216; this version posted August 25, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. COVID-19 and Vitamin D (Co-VIVID Study): a systematic review and meta-analysis of randomized controlled trials Running title: COVID-19 and Vitamin D (Co-VIVID Study) Seshadri Reddy Varikasuvu a*, Balachandar Thangappazham b, Hemanth Raj c a Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Deoghar, Jharkhand, India b StepOne NGO, Pegasus Block, Malleswaram West, Bengaluru, Karnataka, India c Department of Medicine, Mount Medical Centre, Tamil Nadu, India *Corresponding author: Dr. Seshadri Reddy Varikasuvu Assistant Professor, Department of Biochemistry All India Institute of Medical Sciences AIIMS, Deoghar, Jharkhand-814142, India Phone: +91 81 0 61 45 001 E-mail: lifeschemistry@live.com https://orcid.org/0000-0002-2230-4676 1 NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2021.08.22.21262216; this version posted August 25, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Abstract Background: Vitamin D levels have been reported to be associated with COVID-19 susceptibility, severity and mortality events.. We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the use of vitamin D intervention on COVID-19 outcomes. Methods: Literature search was conducted using PubMed, Cochrane library, and ClinicalTrials.gov databases (latest search on August 5, 2021). We included RCTs reporting the use of vitamin D intervention to control/placebo group in COVID-19. Two independent researchers did literature search, abstracted data, and the risk of bias assessment. Results: A total of 6 RCTs with 551 COVID-19 patients were included. The overall collective evidence pooling all the outcomes across all RCTs indicated the beneficial use of vitamin D intervention in COVID-19 (relative risk, RR = 0.60, 95% CI 0.40 to 0.92, Z=2.33, p=0.02, I2 = 48%). However, no statistical significance was observed for individual outcomes of ICU care (RR = 0.11, 95% CI 0.15 to 1.30, Z=1.48, p=0.14, I2 = 66%) and mortality (RR = 0.78, 95% CI 0.25 to 2.40, Z=0.66, p=0.02, I2 = 33%), though decreased rates were noted. The rates of RT-CR positivity was significantly decreased in the intervention group as compared to the non-vitamin D groups (RR = 0.46, 95% CI 0.24 to 0.89, Z=2.31, p=0.02, I2 = 0%). Conclusion: COVID-19 patients supplemented with vitamin D are more likely to demonstrate fewer rates of ICU admission, mortality events and RT-PCR positivity. However, no statistical significance has been achieved for individual outcomes of ICU and deaths. More RCTs and completion of ongoing trials largely needed to precisely establish the association between vitamin D use and COVID-19. Keywords: Cholecalciferol; COVID-19; Randomized controlled trial; SARS-Cov-2; Vitamin D 2 medRxiv preprint doi: https://doi.org/10.1101/2021.08.22.21262216; this version posted August 25,..