Main Article Content
Abstract
Highlights:
- Vitamin D supplementations in different doses yield different outcomes.
- Multi-day vitamin D administration of 1000-6000 IU in patients with COVID-19 has more positive impacts than a single high dose of vitamin D.
- Patient morbidity, length of hospitalization, and patient mortality improved with multi-day vitamin D administration.
Abstract:
This meta-analysis aimed to determine whether there is any optimal dose of vitamin D for morbidity, length of hospitalization, and mortality in patients with COVID-19. We conducted a comprehensive search in three online databases for eligible studies until February 28, 2022. Odds ratio (OR) and standardized mean difference (SMD) were applied as summary statistics of primary outcomes. The study quality of the literatures collected was assesed using the Cochrane risk of bias tool version 2 (RoB 2). Eight randomized clinical trials (RCT) were included in the study. In our analysis, we found that there was no significant difference in morbidity when vitamin D was administered to COVID-19 patients [OR=0.50 (95% CI=0.13-1.96); SMD=-0.14 (95% CI=-0.55-0.28)]. Duration of hospitalization [SMD=-0.12 (95% CI=-0.39-0.15)] and mortality [OR 0.47 (95% CI=0.19-1.17)] of COVID-19 patients in five studies also showed no significant difference compared to patients who do not take vitamin D. However, when we analyzed two other studies, we found that in patients who did not take vitamin D, mortality was lower [SMD=0.43 (95% CI=0.29, 0.58)]. Compared to a single high dose of vitamin D, the multi-day vitamin D administration of 1000-6000 IU in patients with COVID-19 resulted in improved patient morbidity, length of hospitalization, and patient mortality.
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References
- Apaydin M, Can AG, Kizilgul M, et al (2018). The effects of single high-dose or daily low-dosage oral colecalciferol treatment on vitamin D levels and muscle strength in postmenopausal women. BMC Endocr Disord 18, 48.
- Beigmohammadi MT, Bitarafan S, Abdollahi A, et al (2021). The association between serum levels of micronutrients and the severity of disease in patients with COVID-19. Nutrition 91–92, 111400.
- Brenner H (2021). Vitamin D supplementation to prevent COVID-19 infections and deaths”Accumulating evidence from epidemiological and intervention studies calls for immediate action. Nutrients 13, 411.
- Camargo CA, Sluyter J, Stewart AW, et al (2020). Effect of monthly high-dose vitamin D supplementation on acute respiratory infections in older adults: A randomized controlled trial. Clin Infect Dis 71, 311–7.
- Cannata-Andía JB, Díaz-Sottolano A, Fernández P, et al (2022). A single-oral bolus of 100,000 IU of cholecalciferol at hospital admission did not improve outcomes in the COVID-19 disease: the COVID-VIT-D”a randomised multicentre international clinical trial. BMC Med 20, 83.
- Carpagnano G, Di Lecce V, Quaranta V, et al (2021). Vitamin D deficiency as a predictor of poor prognosis in patients with acute respiratory failure due to COVID-19. J Endocrinol Invest 44, 765–71.
- Cascella M, Rajnik M, Aleem A, et al (2022). Features, evaluation, and treatment of coronavirus (COVID-19). StatPearls.
- Centers for Disease Control and Prevention (2022). Coronavirus disease 2019 (COVID-19).
- Gao S, Guo H, Luo G (2022). Omicron variant (B.1.1.529) of SARS"CoV"2, a global urgent public health alert! J Med Virol 94, 1255–6.
- Grant W, Lahore H, McDonnell S, et al (2020). Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients 12, 988.
- Lakkireddy M, Gadiga SG, Malathi R, et al (2021). Impact of daily high dose oral vitamin D therapy on the inflammatory markers in patients with COVID 19 disease. Sci Rep 11, 10641.
- Maghbooli Z, Sahraian MA, Jamalimoghadamsiahkali S, et al (2021). Treatment with 25-hydroxyvitamin D3 (calcifediol) is associated with a reduction in the blood neutrophil-to-lymphocyte ratio marker of disease severity in hospitalized patients with COVID-19: A pilot multicenter, randomized, placebo-controlled, double-bli. Endocr Pract 27, 1242–51.
- Malaguarnera L (2020). Vitamin D3 as potential treatment adjuncts for COVID-19. Nutrients 12, 3512.
- Martineau AR, Forouhi NG (2020). Vitamin D for COVID-19: A case to answer? Lancet Diabetes Endocrinol 8, 735–6.
- Mazess RB, Bischoff"Ferrari HA, Dawson"Hughes B (2021). Vitamin D: Bolus is bogus”A narrative review. JBMR Plus.
- Mitchell F (2020). Vitamin-D and COVID-19: Do deficient risk a poorer outcome? Lancet Diabetes Endocrinol 8, 570.
- Murai IH, Fernandes AL, Antonangelo L, et al (2021a). 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 76, e3549.
- Murai IH, Fernandes AL, Sales LP, et al (2021b). Effect of a single high dose of vitamin D3 on hospital length of stay in patients with moderate to severe COVID-19. JAMA 325, 1053.
- Ohaegbulam KC, Swalih M, Patel P, et al (2020). Vitamin D supplementation in COVID-19 patients: A clinical case series. Am J Ther 27, e485–90.
- Page MJ, McKenzie JE, Bossuyt PM, et al (2021). The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJn71.
- Pal R, Banerjee M, Bhadada S, et al (2022). Vitamin D supplementation and clinical outcomes in COVID-19: A systematic review and meta-analysis. J Endocrinol Invest 45, 53–68.
- Quesada-Gomez JM, Entrenas-Castillo M, Bouillon R (2020). Vitamin D receptor stimulation to reduce acute respiratory distress syndrome (ARDS) in patients with coronavirus SARS-CoV-2 infections. J Steroid Biochem Mol Biol 202, 105719.
- Rawaf S, Allen LN, Stigler FL, et al (2020). Lessons on the COVID-19 pandemic, for and by primary care professionals worldwide. Eur J Gen Pract 26, 129–33.
- Sabico S, Enani MA, Sheshah E, et al (2021). 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 13, 2170.
- Sánchez-Zuno GA, González-Estevez G, Matuz-Flores MG, et al (2021). Vitamin D levels in COVID-19 outpatients from Western Mexico: Clinical correlation and effect of its supplementation. J Clin Med 10, 2378.
- Sutadji JC, Widodo ADW, Indiastuti D (2021). Mortality Comparison of Using Anti Interleukin-6 Therapy and Using Standard Treatment in Severe Covid-19. Folia Medica Indonesiana, 57, 158–165.
- Soliman AR, Abdelaziz TS, Fathy A (2022). Impact of vitamin D therapy on the progress COVID-19: Six weeks follow-up study of vitamin D deficient elderly diabetes patients. Proc Singapore Healthc 31.
- Stasi C, Fallani S, Voller F, et al (2020). Treatment for COVID-19: An overview. Eur J Pharmacol 889, 173644.
- Vimaleswaran KS, Forouhi NG, Khunti K (2021). Vitamin D and COVID-19. BMJn544.
References
Apaydin M, Can AG, Kizilgul M, et al (2018). The effects of single high-dose or daily low-dosage oral colecalciferol treatment on vitamin D levels and muscle strength in postmenopausal women. BMC Endocr Disord 18, 48.
Beigmohammadi MT, Bitarafan S, Abdollahi A, et al (2021). The association between serum levels of micronutrients and the severity of disease in patients with COVID-19. Nutrition 91–92, 111400.
Brenner H (2021). Vitamin D supplementation to prevent COVID-19 infections and deaths”Accumulating evidence from epidemiological and intervention studies calls for immediate action. Nutrients 13, 411.
Camargo CA, Sluyter J, Stewart AW, et al (2020). Effect of monthly high-dose vitamin D supplementation on acute respiratory infections in older adults: A randomized controlled trial. Clin Infect Dis 71, 311–7.
Cannata-Andía JB, Díaz-Sottolano A, Fernández P, et al (2022). A single-oral bolus of 100,000 IU of cholecalciferol at hospital admission did not improve outcomes in the COVID-19 disease: the COVID-VIT-D”a randomised multicentre international clinical trial. BMC Med 20, 83.
Carpagnano G, Di Lecce V, Quaranta V, et al (2021). Vitamin D deficiency as a predictor of poor prognosis in patients with acute respiratory failure due to COVID-19. J Endocrinol Invest 44, 765–71.
Cascella M, Rajnik M, Aleem A, et al (2022). Features, evaluation, and treatment of coronavirus (COVID-19). StatPearls.
Centers for Disease Control and Prevention (2022). Coronavirus disease 2019 (COVID-19).
Gao S, Guo H, Luo G (2022). Omicron variant (B.1.1.529) of SARS"CoV"2, a global urgent public health alert! J Med Virol 94, 1255–6.
Grant W, Lahore H, McDonnell S, et al (2020). Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients 12, 988.
Lakkireddy M, Gadiga SG, Malathi R, et al (2021). Impact of daily high dose oral vitamin D therapy on the inflammatory markers in patients with COVID 19 disease. Sci Rep 11, 10641.
Maghbooli Z, Sahraian MA, Jamalimoghadamsiahkali S, et al (2021). Treatment with 25-hydroxyvitamin D3 (calcifediol) is associated with a reduction in the blood neutrophil-to-lymphocyte ratio marker of disease severity in hospitalized patients with COVID-19: A pilot multicenter, randomized, placebo-controlled, double-bli. Endocr Pract 27, 1242–51.
Malaguarnera L (2020). Vitamin D3 as potential treatment adjuncts for COVID-19. Nutrients 12, 3512.
Martineau AR, Forouhi NG (2020). Vitamin D for COVID-19: A case to answer? Lancet Diabetes Endocrinol 8, 735–6.
Mazess RB, Bischoff"Ferrari HA, Dawson"Hughes B (2021). Vitamin D: Bolus is bogus”A narrative review. JBMR Plus.
Mitchell F (2020). Vitamin-D and COVID-19: Do deficient risk a poorer outcome? Lancet Diabetes Endocrinol 8, 570.
Murai IH, Fernandes AL, Antonangelo L, et al (2021a). 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 76, e3549.
Murai IH, Fernandes AL, Sales LP, et al (2021b). Effect of a single high dose of vitamin D3 on hospital length of stay in patients with moderate to severe COVID-19. JAMA 325, 1053.
Ohaegbulam KC, Swalih M, Patel P, et al (2020). Vitamin D supplementation in COVID-19 patients: A clinical case series. Am J Ther 27, e485–90.
Page MJ, McKenzie JE, Bossuyt PM, et al (2021). The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJn71.
Pal R, Banerjee M, Bhadada S, et al (2022). Vitamin D supplementation and clinical outcomes in COVID-19: A systematic review and meta-analysis. J Endocrinol Invest 45, 53–68.
Quesada-Gomez JM, Entrenas-Castillo M, Bouillon R (2020). Vitamin D receptor stimulation to reduce acute respiratory distress syndrome (ARDS) in patients with coronavirus SARS-CoV-2 infections. J Steroid Biochem Mol Biol 202, 105719.
Rawaf S, Allen LN, Stigler FL, et al (2020). Lessons on the COVID-19 pandemic, for and by primary care professionals worldwide. Eur J Gen Pract 26, 129–33.
Sabico S, Enani MA, Sheshah E, et al (2021). 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 13, 2170.
Sánchez-Zuno GA, González-Estevez G, Matuz-Flores MG, et al (2021). Vitamin D levels in COVID-19 outpatients from Western Mexico: Clinical correlation and effect of its supplementation. J Clin Med 10, 2378.
Sutadji JC, Widodo ADW, Indiastuti D (2021). Mortality Comparison of Using Anti Interleukin-6 Therapy and Using Standard Treatment in Severe Covid-19. Folia Medica Indonesiana, 57, 158–165.
Soliman AR, Abdelaziz TS, Fathy A (2022). Impact of vitamin D therapy on the progress COVID-19: Six weeks follow-up study of vitamin D deficient elderly diabetes patients. Proc Singapore Healthc 31.
Stasi C, Fallani S, Voller F, et al (2020). Treatment for COVID-19: An overview. Eur J Pharmacol 889, 173644.
Vimaleswaran KS, Forouhi NG, Khunti K (2021). Vitamin D and COVID-19. BMJn544.