Effect of vitamin D supplementation versus placebo on recovery delay among COVID-19 Tunisian patients: a randomized-controlled clinical trial

Abstract

Introduction The present study aimed to determine the impact of vitamin D supplementation (VDs) on recovery delay among COVID-19 patients. Methods We performed a randomized controlled clinical trial at the national COVID-19 containment center in Monastir (Tunisia), from May to August 2020. Simple randomization was done in a 1:1 allocation ratio. We included patients aged more than 18 years who had confirmed reverse transcription-polymerase chain reaction (RT-PCR) and who remained positive on the 14th day. The intervention group received VDs (200,000 IU/1 ml of cholecalciferol); the control group received a placebo treatment (physiological saline (1 ml)). We measured the recovery delay and the cycle threshold (Ct) values in RT-PCR for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The log-rank test and hazard ratios (HR) were calculated. Results A total of 117 patients were enrolled. The mean age was 42.7 years (SD 14). Males represented 55.6%. The median duration of viral RNA conversion was 37 days (95% confidence interval (CI): 29–45.50) in the intervention group and 28 days (95% CI: 23–39) in the placebo group (p=0.010). HR was 1.58 (95% CI: 1.09–2.29, p=0.015). Ct values revealed a stable trend over time in both groups. Conclusion VDs was not associated with a shortened recovery delay when given to patients for whom the RT-PCR remained positive on the 14th day. Trial registration This study was approved by the Human Subjects Protection Tunisia center (TN2020-NAT-INS-40) on April 28, 2020, and by ClinicalTrial.gov on May 12, 2021 with approval number ClinicalTrials.gov ID: NCT04883203.

Vitamin D, acute respiratory infections, and Covid-19: the curse of small-size randomised trials. A critical review with meta-analysis of randomised trials

“…After full article reading, nine articles [16,28,[31][32][33][34][35][36][37] were selected for review and 14 articles were excluded. Reasons for exclusion were: high vs. low dose VDS [38][39][40], no specific numbers of patients who were admitted in ICU [14,15,30,[41][42][43][44][45], failure of randomization [29], and not a randomised trial [46,47]. Characteristics of the nine selected randomised trials are summarized in Table 1.…”

Pharmacological evaluation of vitamin D in COVID-19 and long COVID-19: recent studies confirm clinical validation and highlight metformin to improve VDR sensitivity and efficacy

“…All randomized controlled trials confirm the clinical safety of high doses of vitamin D supplements, however, benefit has not been observed in any of the COVID-19 outcomes including length of hospital stay, disease incidence, number of days on respiratory support, mortality, admission to Intensive care unit, and prognosis. Four randomized controlled trials(44% of studies) evaluated the effect of a single oral bolus dose of cholecalciferol (100,000–500,000 IU) on length of hospital stay and respiratory deterioration, and found no effect in 649 patients with insufficient vitamin D level (Cannata-Andía et al 2022 ; Mariani et al 2022 ; Jaun et al 2023 ; Abroug et al 2023 ). Eight cohort studies and eight randomized controlled studies involving 3359 patients with COVID-19 were included in the only meta- analysis study (Zhang et al 2023 ).…”

A Narrative Review on the Potential Role of Vitamin D3 in the Prevention, Protection, and Disease Mitigation of Acute and Long COVID-19

“…In contrast, Abroug et al showed in a randomized controlled trial (RCT) that if a single vitamin D 3 treatment of 200,000 IU was given to individuals with moderate to severe SARS-CoV-2 infection but after 14 days after initial diagnosis, such a treatment does not appear to have a significant effect on shortened recovery time in vitamin D-treated individuals compared to participants given a placebo [ 41 ].…”