Cédric Annweiler1,2,3, Mélinda Beaudenon4, Jennifer Gautier4, Romain Simon4, Vincent Dubée5,6, Justine Gonsard7, Elsa Parot-Schinkel7,8. 1. Department of Geriatric Medicine and Memory Clinic, Research Center on Autonomy and Longevity, Angers University Hospital, F-49933, Angers, France. Cedric.Annweiler@chu-angers.fr. 2. UPRES EA 4638, University of Angers, Angers, France. Cedric.Annweiler@chu-angers.fr. 3. Robarts Research Institute, Department of Medical Biophysics, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, Canada. Cedric.Annweiler@chu-angers.fr. 4. Department of Geriatric Medicine and Memory Clinic, Research Center on Autonomy and Longevity, Angers University Hospital, F-49933, Angers, France. 5. CRCINA, Inserm, Université de Nantes, Université d'Angers, 44200, Angers, Nantes, France. 6. Service des Maladies Infectieuses et Tropicales, CHU, Angers, France. 7. Delegation for clinical research and innovation, Angers University Hospital, Angers, France. 8. Biostatistics and methodology department, Angers University Hospital, Angers, France.
Abstract
BACKGROUND: With the lack of effective therapy, chemoprevention, and vaccination against SARS-CoV-2, focusing on the immediate repurposing of existing drugs gives hope of curbing the COVID-19 pandemic. A recent unbiased genomics-guided tracing of the SARS-CoV-2 targets in human cells identified vitamin D among the three top-scoring molecules manifesting potential infection mitigation patterns. Growing pre-clinical and epidemiological observational data support this assumption. We hypothesized that vitamin D supplementation may improve the prognosis of COVID-19. The aim of this trial is to compare the effect of a single oral high dose of cholecalciferol versus a single oral standard dose on all-cause 14-day mortality rate in COVID-19 older adults at higher risk of worsening. METHODS: The COVIT-TRIAL study is an open-label, multicenter, randomized controlled superiority trial. Patients aged ≥ 65 years with COVID-19 (diagnosed within the preceding 3 days with RT-PCR and/or chest CT scan) and at least one worsening risk factor at the time of inclusion (i.e., age ≥ 75 years, or SpO2 ≤ 94% in room air, or PaO2/FiO2 ≤ 300 mmHg), having no contraindications to vitamin D supplementation, and having received no vitamin D supplementation > 800 IU/day during the preceding month are recruited. Participants are randomized either to high-dose cholecalciferol (two 200,000 IU drinking vials at once on the day of inclusion) or to standard-dose cholecalciferol (one 50,000 IU drinking vial on the day of inclusion). Two hundred sixty participants are recruited and followed up for 28 days. The primary outcome measure is all-cause mortality within 14 days of inclusion. Secondary outcomes are the score changes on the World Health Organization Ordinal Scale for Clinical Improvement (OSCI) scale for COVID-19, and the between-group comparison of safety. These outcomes are assessed at baseline, day 14, and day 28, together with the serum concentrations of 25(OH)D, creatinine, calcium, and albumin at baseline and day 7. DISCUSSION: COVIT-TRIAL is to our knowledge the first randomized controlled trial testing the effect of vitamin D supplementation on the prognosis of COVID-19 in high-risk older patients. High-dose vitamin D supplementation may be an effective, well-tolerated, and easily and immediately accessible treatment for COVID-19, the incidence of which increases dramatically and for which there are currently no scientifically validated treatments. TRIAL REGISTRATION: ClinicalTrials.gov NCT04344041 . Registered on 14 April 2020 TRIAL STATUS: Recruiting. Recruitment is expected to be completed in April 2021.
BACKGROUND: With the lack of effective therapy, chemoprevention, and vaccination against SARS-CoV-2, focusing on the immediate repurposing of existing drugs gives hope of curbing the COVID-19 pandemic. A recent unbiased genomics-guided tracing of the SARS-CoV-2 targets in human cells identified vitamin D among the three top-scoring molecules manifesting potential infection mitigation patterns. Growing pre-clinical and epidemiological observational data support this assumption. We hypothesized that vitamin D supplementation may improve the prognosis of COVID-19. The aim of this trial is to compare the effect of a single oral high dose of cholecalciferol versus a single oral standard dose on all-cause 14-day mortality rate in COVID-19 older adults at higher risk of worsening. METHODS: The COVIT-TRIAL study is an open-label, multicenter, randomized controlled superiority trial. Patients aged ≥ 65 years with COVID-19 (diagnosed within the preceding 3 days with RT-PCR and/or chest CT scan) and at least one worsening risk factor at the time of inclusion (i.e., age ≥ 75 years, or SpO2 ≤ 94% in room air, or PaO2/FiO2 ≤ 300 mmHg), having no contraindications to vitamin D supplementation, and having received no vitamin D supplementation > 800 IU/day during the preceding month are recruited. Participants are randomized either to high-dose cholecalciferol (two 200,000 IU drinking vials at once on the day of inclusion) or to standard-dose cholecalciferol (one 50,000 IU drinking vial on the day of inclusion). Two hundred sixty participants are recruited and followed up for 28 days. The primary outcome measure is all-cause mortality within 14 days of inclusion. Secondary outcomes are the score changes on the World Health Organization Ordinal Scale for Clinical Improvement (OSCI) scale for COVID-19, and the between-group comparison of safety. These outcomes are assessed at baseline, day 14, and day 28, together with the serum concentrations of 25(OH)D, creatinine, calcium, and albumin at baseline and day 7. DISCUSSION: COVIT-TRIAL is to our knowledge the first randomized controlled trial testing the effect of vitamin D supplementation on the prognosis of COVID-19 in high-risk older patients. High-dose vitamin D supplementation may be an effective, well-tolerated, and easily and immediately accessible treatment for COVID-19, the incidence of which increases dramatically and for which there are currently no scientifically validated treatments. TRIAL REGISTRATION: ClinicalTrials.gov NCT04344041 . Registered on 14 April 2020 TRIAL STATUS: Recruiting. Recruitment is expected to be completed in April 2021.
Authors: Juan Kong; Xiangdong Zhu; Yongyan Shi; Tianjing Liu; Yunzi Chen; Ishir Bhan; Qun Zhao; Ravi Thadhani; Yan Chun Li Journal: Mol Endocrinol Date: 2013-11-06
Authors: Weihua Yuan; Wei Pan; Juan Kong; Wei Zheng; Frances L Szeto; Kari E Wong; Ronald Cohen; Anna Klopot; Zhongyi Zhang; Yan Chun Li Journal: J Biol Chem Date: 2007-08-09 Impact factor: 5.157
Authors: Rachel C A Dancer; Dhruv Parekh; Sian Lax; Vijay D'Souza; Shengxing Zheng; Chris R Bassford; Daniel Park; D G Bartis; Rahul Mahida; Alice M Turner; Elizabeth Sapey; Wenbin Wei; Babu Naidu; Paul M Stewart; William D Fraser; Kenneth B Christopher; Mark S Cooper; Fang Gao; David M Sansom; Adrian R Martineau; Gavin D Perkins; David R Thickett Journal: Thorax Date: 2015-04-22 Impact factor: 9.139
Authors: Markus Hoffmann; Hannah Kleine-Weber; Simon Schroeder; Nadine Krüger; Tanja Herrler; Sandra Erichsen; Tobias S Schiergens; Georg Herrler; Nai-Huei Wu; Andreas Nitsche; Marcel A Müller; Christian Drosten; Stefan Pöhlmann Journal: Cell Date: 2020-03-05 Impact factor: 41.582
Authors: G Fond; M Masson; R Richieri; T Korchia; D Etchecopar-Etchart; P-L Sunhary de Verville; C Lançon; L Boyer Journal: Encephale Date: 2021-03-14 Impact factor: 1.291
Authors: Zahra Raisi-Estabragh; Adrian R Martineau; Elizabeth M Curtis; Rebecca J Moon; Andrea Darling; Susan Lanham-New; Kate A Ward; Cyrus Cooper; Patricia B Munroe; Steffen E Petersen; Nicholas C Harvey Journal: Aging Clin Exp Res Date: 2021-06-12 Impact factor: 3.636