Vitamin D supplementation in patients with COVID-19: randomized, double-blind and placebo controlled clinical trial

• Grant number: 20/05752-4
• Support Opportunities: Regular Research Grants
• Duration: July 01, 2020 - June 30, 2022
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Rosa Maria Rodrigues Pereira
• Grantee: Rosa Maria Rodrigues Pereira
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Bruno Gualano ; Eloisa Silva Dutra de Oliveira Bonfá
• Associated research grant: 16/00006-7 - Evaluation of bone metabolism parameters by HR-pQCT and histomorphometry in rheumatoid arthritis and juvenile idiopathic arthritis patients: association with clinical and genetic variables, AP.TEM
• Associated scholarship(s): 20/11102-2 - Vitamin D supplementation in patients with COVID-19: randomized, double-blind and placebo controlled clinical trial, BP.PD

Abstract

Coronavirus disease 2019 (COVID-19) was declared an emergency public health problem by the World Health Organization (WHO) in March 2020. Since then, several initiatives by the medical and scientific community have sought alternatives to treat infected individuals, as well as identifying risk or protective factors for the contamination and prognosis of patients. In this perspective, vitamin D supplementation can improve some important outcomes in critically ill patients, being considered a potent immunomodulatory agent. Vitamin D deficiency is a common outcome in critically ill patients, thus making it a modifiable risk factor with great potential for reducing hospital stay and intensive care and mortality. In addition, several studies confirm the beneficial effect of regular physical activity on the immune system, which is indicated as a protective factor for other types of viral infections, such as rhinovirus, herpes and influenza. The main endpoint of this project is to verify the possible effects of vitamin D supplementation on the clinical outcomes associated with COVID-19. In addition, our second other endpoints is to verify the relationship between the level of habitual physical activity of infected patients and clinical outcomes. This is a randomized, placebo-controlled, double-blind clinical trial study. Patients admitted at Hospital das Clinicas, Faculdade de Medicina da USP (HCFMUSP) diagnosed with flu syndrome with hospitalization admission criteria will be recruited and randomized for the treatment group (conventional treatment + vitamin D supplementation [100,000 IU on admission, followed by 100,000 IU after 5 days] or control (conventional treatment + placebo supplementation on the same days). Patients will be assessed for: 1) clinical and demographic characteristics (eg, sociodemographic data, comorbidities, drugs use); 2) prognosis (e.g., length of stay, mortality, number of cases admitted to Intensive Care Units, length of use of ventilators, number and severity of symptoms); 3) blood collection (eg, PCR for diagnosis of the virus and assessment of serum levels of 25-hydroxyvitamin D (25OHD), laboratory parameters included in the institutional guideline HCFMUSP for the management of treatment of patients with COVID19 (eg, CRP, D-dimer), calcium and creatinine (the last two, safety outcomes), at hospitalization and on the day of discharge; 4) level of habitual physical activity (through a questionnaire). The demographic data and clinical characteristics of the patients at the time of admission, as well as the patient's prognosis will be obtained through a specific questionnaire obtained from the HC-FMUSP electronic medical record (Prontmed) or direct contact with family members and / or patients. Blood samples will be collected for laboratory analysis at the time of admission, and according to a routine hospital protocol. An aliquot will be stored for later analysis of 25OHD and biorepository, on the hospital admission (day zero), day 7, day 14 and before discharge/death. The level of physical activity will be assessed only at the time of admission. This project has the potential to reveal, in an unprecedented way, whether vitamin D supplementation is safe and effective as an adjuvant treatment to COVID-19. In addition, the study will provide information, for the first time, about the influence of the level of physical activity on the prognosis of this disease. The findings may inform new clinical and public health measures to combat COVID-19 (AU)

Scientific publications

(9)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MURAI, IGOR H.; FERNANDES, ALAN L.; SALES, LUCAS P.; PINTO, ANA J.; GOESSLER, KARLA F.; DURAN, CAMILA S. C.; SILVA, CARLA B. R.; FRANCO, ANDRE S.; MACEDO, MARINA B.; DALMOLIN, HENRIQUE H. H.; et al. 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. JAMA, v. 325, n. 11, FEB 2021. (20/11102-2, 15/26937-4, 17/13552-2, 19/24782-4, 19/18039-7, 20/05752-4, 16/00006-7)

FERNANDES, ALAN L. L.; PEREIRA, ROSA M. R.. Frailty in the context of COVID-19 pandemic: A life-threatening condition. FRONTIERS IN MEDICINE, v. 9, p. 7-pg., 2022-08-24. (20/11102-2, 20/07098-0, 20/05752-4)

IGOR H. MURAI; ALAN L. FERNANDES; LEILA ANTONANGELO; BRUNO GUALANO; ROSA MARIA RODRIGUES PEREIRA. Effect of a Single High-Dose Vitamin D3 on the Length of Hospital Stay of Severely 25-Hydroxyvitamin D-Deficient Patients with COVID-19. Clinics, v. 76, 2021-11-26. (20/05752-4, 20/11102-2, 19/24782-4)

REIS, BRUNA Z.; FERNANDES, ALAN L.; SALES, LUCAS P.; SANTOS, MAYARA D.; DOS SANTOS, CAROLINE C.; PINTO, ANA J.; GOESSLER, KARLA F.; FRANCO, ANDRE S.; DURAN, CAMILA S. C.; SILVA, CARLA B. R.; et al. Influence of vitamin D status on hospital length of stay and prognosis in hospitalized patients with moderate to severe COVID-19: a multicenter prospective cohort study. AMERICAN JOURNAL OF CLINICAL NUTRITION, v. 114, n. 2, p. 598-604, AUG 2021. (17/13552-2, 15/26937-4, 19/18039-7, 16/00006-7, 20/05752-4, 19/24782-4, 20/11102-2)

MURAI, IGOR H.; FERNANDES, ALAN L.; ANTONANGELO, LEILA; GUALANO, BRUNO; RODRIGUES PEREIRA, ROSA MARIA. Effect of a Single High-Dose Vitamin D-3 on the Length of Hospital Stay of Severely 25-Hydroxyvitamin D-Deficient Patients with COVID-19. Clinics, v. 76, 2021. (20/11102-2, 19/24782-4, 20/05752-4)

FERNANDES, ALAN L.; MURAI, IGOR H.; REIS, BRUNA Z.; SALES, LUCAS P.; SANTOS, MAYARA D.; PINTO, ANA J.; GOESSLER, KARLA F.; DURAN, CAMILA S. C.; SILVA, CARLA B. R.; FRANCO, ANDRE S.; et al. Effect of a single high dose of vitamin D-3 on cytokines, chemokines, and growth factor in patients with moderate to severe COVID-19. AMERICAN JOURNAL OF CLINICAL NUTRITION, v. 115, n. 3, p. 9-pg., 2022-03-04. (20/11102-2, 19/18039-7, 19/24782-4, 20/05752-4)

PINTO, ANA J.; GOESSLER, KARLA F.; FERNANDES, ALAN L.; MURAI, IGOR H.; SALES, LUCAS P.; REIS, BRUNA Z.; SANTOS, MAYARA DINIZ; ROSCHEL, HAMILTON; PEREIRA, ROSA M. R.; GUALANO, BRUNO. No independent associations between physical activity and clinical outcomes among hospitalized patients with moderate to severe COVID-19. JOURNAL OF SPORT AND HEALTH SCIENCE, v. 10, n. 6, p. 690-696, DEC 2021. (16/00006-7, 20/05752-4, 15/26937-4, 19/18039-7, 19/24782-4, 17/13552-2, 20/11102-2)

FERNANDES, ALAN L. L.; SALES, LUCAS P. P.; SANTOS, MAYARA D. D.; CAPARBO, VALERIA F. F.; MURAI, IGOR H. H.; PEREIRA, ROSA M. R.. Persistent or new symptoms 1 year after a single high dose of vitamin D-3 in patients with moderate to severe COVID-19. FRONTIERS IN NUTRITION, v. 9, p. 10-pg., 2022-09-13. (20/11102-2, 19/24782-4, 20/07098-0, 20/05752-4)

MURAI, IGOR H.; FERNANDES, ALAN L.; SALES, LUCAS P.; PINTO, ANA J.; GOESSLER, KARLA F.; DURAN, CAMILA S. C.; SILVA, CARLA B. R.; FRANCO, ANDRE S.; MACEDO, MARINA B.; DALMOLIN, HENRIQUE H. H.; et al. 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. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, v. 325, n. 11, p. 8-pg., 2021-02-17. (20/11102-2, 16/00006-7, 19/24782-4, 15/26937-4, 19/18039-7, 20/05752-4, 17/13552-2)