key: cord-0717177-utlfshgo authors: Pal, Rimesh; Banerjee, Mainak title: Spurious Undermining Of The Adjuvant Role Of Vitamin D In COVID-19 date: 2021-07-23 journal: Diabetes Metab Syndr DOI: 10.1016/j.dsx.2021.102230 sha: 2d4222bd88f414c17813556c1aad4c9a77a793a4 doc_id: 717177 cord_uid: utlfshgo nan We read with great interest the systematic review and meta-analysis by Rawat At the outset of our letter, we must thank Pal & Banerjee [1] for their constructive criticism to our meta-analysis of randomized and quasi-randomized trials [2] , that reported no benefit of vitamin D supplementation in SARS-CoV-2 infected patients. Our meta-analysis included 3 RCTs [3] [4] [5] and two quasiexperimental studies [6, 7] and amongst them one RCT did not report mortality or any other clinical endpoints. We understand limitation of mixing quasiexperimental or observational studies with RCTs for data analysis [8] , however, pooled analysis from two RCTs also reported no mortality benefit [RR (95% CI) 0.58 (0.05-7.18), p=0.67]. In our original analysis, other patients' centric secondary outcomes such as requirement of mechanical ventilation and intensive care unit admission were not reduced with vitamin D supplementation and only RCTs were included in that analysis. Another meta-analysis by Pal et al [9] , referred in this letter, that included 13 RCTs and observational studies, reported benefit of vitamin D, both in adjusted and unadjusted analysis. It's worth mentioning that, adjusted analysis has also it's limitation, as one can only adjust known baseline variables and can't be considered as an alternative to RCT. Observational studies included in the meta-analysis by Pal et al [9] has some serious limitations, detailed discussion of which is beyond the scope of this letter. It's worth mentioning that majority of the observational studies didn't J o u r n a l P r e -p r o o f Vitamin D supplementation and COVID-19 treatment: A systematic review and metaanalysis Vitamin D supplementation and clinical outcomes in COVID-19: a systematic review and meta-analysis Methods to systematically review and meta-analyse observational studies: a systematic scoping review of recommendations Vitamin D and survival in COVID-19 patients: A quasi-experimental study Effect of a Single High Dose of Vitamin D 3 on Hospital Length of Stay in Patients With Moderate to Severe COVID-19: A Randomized Clinical Trial Spurious Undermining Of The Adjuvant Role Of Vitamin D In COVID-19 Vitamin D supplementation and COVID-19 treatment: A systematic review and metaanalysis Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study. The Journal of steroid biochemistry and molecular biology Effect of a single high dose of vitamin D3 on hospital length of stay in patients with moderate to severe COVID-19: a randomized clinical trial Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomised Vitamin D and survival in COVID-19 patients: A quasiexperimental study Vitamin D Supplementation Associated to Better Survival in Hospitalized Frail Elderly COVID-19 Patients: The GERIA-COVID Quasi-Experimental Study Challenges in meta-analyses with observational studies Vitamin D supplementation and clinical outcomes in COVID-19: a systematic review and meta-analysis report baseline disease severity such as PaO2/ FiO2 ratio or APACHE II score etc., seriously limiting the values of adjusted analysis.With the limitation of current available evidence, it is prudent to assume both meta-analyses as 'hypothesis generating' and used for estimation of sample sizes for future RCTs.