Effect of vitamin D supplementation versus placebo on recovery delay among COVID-19 Tunisian patients: a randomized-controlled clinical trial
Hela Abroug, Amani Maatouk, Cyrine Bennasrallah, Wafa Dhouib, Manel Ben Fredj, Imen Zemni, Meriem Kacem, Salma Mhalla, Sarra Nouira, Manel Ben Belgacem, Aymen Nasri, Rim Klii, Chawki Loussaief, Nissaf Ben Alya, Ines Bouanene, Asma Belguith Sriha
Trials, doi:10.1186/s13063-023-07114-5
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 logrank 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.
Authors' contributions
Declarations Ethics approval and consent to participate This study was approved by the Human Subjects Protection Tunisia center (TN2020-NAT-INS-40) and by ClinicalTrial.gov with approval numberClinicalTrials.gov ID: NCT04883203. The research ethical considerations were respected including free, informed, written, clear and loyal consent, confidentiality, protection, and assistance
Consent for publication Not applicable.
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References
Annweiler, Hanotte, De L'eprevier, Sabatier, Lafaie et al., Vitamin D and survival in COVID-19 patients: A quasi-experimental study, J Steroid Biochem Mol Biol
Bayat, Mundodan, Hasnain, Sallam, Khogali et al., Can the cycle threshold (Ct) value of RT-PCR test for SARS CoV2 predict infectivity among close contacts?, J Infect Public Health
Bennasrallah, Zemni, Dhouib, Sriha, Mezhoud et al., Factors associated with a prolonged negative conversion of viral RNA in patients with COVID-19, Int J Infect Dis
Brandão, Chiamolera, Biscolla, Lima, De et al., No association between vitamin D status and COVID-19 infection in São Paulo, Brazil Arch Endocrinol Metab
Brito, Ribeiro, Daltro, Da, De, The possible benefits of vitamin D in COVID-19, Nutr
Bui, Zhu, Hawkins, Cortez-Resendiz, Bellon, Vitamin D regulation of the immune system and its implications for COVID-19: A mini review, SAGE Open Med
Campi, Gennari, Merlotti, Mingiano, Frosali et al., Vitamin D and COVID-19 severity and related mortality: a prospective study in Italy, BMC Infect Dis
Castillo, Costa, Barrios, Díaz, Miranda et al., 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, J Steroid Biochem Mol Biol
Davoudi, Najafi, Aarabi, Tayebi, Nikaeen et al., Lack of association between vitamin D insufficiency and clinical outcomes of patients with COVID-19 infection, BMC Infect Dis
Dramé, Cofais, Hentzien, Proye, Coulibaly et al., Relation between vitamin D and COVID-19 in aged people: A systematic review, Nutrients
Giannini, Passeri, Tripepi, Sella, Fusaro et al., Effectiveness of in-hospital cholecalciferol use on clinical outcomes in comorbid COVID-19 patients: A hypothesis-generating study, Nutrients
Grove, Osokogu, Al-Khudairy, Mehrabian, Zanganeh et al., Association between vitamin D supplementation or serum vitamin D level and susceptibility to SARS-CoV-2 infection or COVID-19 including clinical course, morbidity and mortality outcomes? A systematic review, BMJ Open
Hastie, Mackay, Ho, Celis-Morales, Katikireddi et al., Vitamin D concentrations and COVID-19 infection in UK Biobank, Diabetes Metab Syndr
Hu, Xing, Jia, Ni, Liang et al., Factors associated with negative conversion of viral RNA in patients hospitalized with COVID-19, Sci Total Environ
Kaufman, Niles, Kroll, Bi, Holick, SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels, PloS One
Kim, Outbreak of novel coronavirus (COVID-19): What is the role of radiologists?, Eur Radiol
Kim, Shin, How to do random allocation (randomization), Clin Orthop Surg
Lakkireddy, Gadiga, Malathi, Karra, Raju et al., Impact of daily high dose oral vitamin D therapy on the inflammatory markers in patients with COVID 19 disease, Sci Rep
Mcadam, Cycle threshold values from Severe Acute Respiratory Syndrome Coronavirus-2 Reverse Transcription-Polymerase Chain Reaction Assays, Clin Lab Med
Munshi, Hussein, Toraih, Elshazli, Jardak et al., Vitamin D insufficiency as a potential culprit in critical COVID-19 patients, J Med Virol
Orchard, Baldry, Nasim-Mohi, Monck, Saeed et al., Vitamin-D levels and intensive care unit outcomes of a cohort of critically ill COVID-19 patients, Clin Chem Lab Med
Pan, Liu, Wang, Guo, Hao et al., Association of public health interventions with the epidemiology of the COVID-19 outbreak in Wuhan, China JAMA
Pizzini, Aichner, Sahanic, Böhm, Egger et al., Impact of vitamin D deficiency on COVID-19-A prospective analysis from the CovILD registry, Nutrients
Rastogi, Bhansali, Khare, Suri, Yaddanapudi et al., Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomised, placebo-controlled, study (SHADE study), Postgrad Med J,
doi:10.1136/postgradmedj-2020-139065Rhee, Kanjilal, Baker, Klompas, Duration of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infectivity: When is it safe to discontinue isolation?, Clin Infect Dis Off Publ Infect Dis Soc Am
Rocha, Atallah, Aldrighi, Pires, Santos Puga et al., Insufficient evidence for vitamin D use in COVID-19: A rapid systematic review, Int J Clin Pract
Sabico, Enani, Sheshah, Aljohani, Aldisi et al., Effects of a 2-week 5000 IU versus 1000 IU vitamin D3 supplementation on recovery of Symptoms in Patients with Mild to Moderate Covid-19: A randomized clinical trial, Nutrients
Sadeghi Dousari, Taatimoghadam, Satarzadeh, COVID-19 (Coronavirus Disease 2019): A new coronavirus disease, Infect Drug Resist
Schulz, Altman, Moher, Group, CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials, BMJ
Solís, Salas, Luesmabartolomé, Ballestín, The Effects of Vitamin D supplementation in COVID-19 patients: A systematic review, Int J Mol Sci
Zhou, Yu, Du, Fan, Liu et al., Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study, Lancet Lond Engl
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'Moderate Covid-19: A randomized clinical trial. Nutrients. '
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