open access

Vol 29, No 2 (2022)
Original Article
Submitted: 2021-08-27
Accepted: 2021-09-06
Early publication date: 2021-10-08
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Vitamin D supplementation to treat SARS-CoV-2 positive patients. Evidence from meta-analysis

Luiza Szarpak12, Krzysztof J. Filipiak3, Aleksandra Gasecka45, Wladyslaw Gawel26, Dorota Koziel7, Milosz J. Jaguszewski8, Jaroslaw Chmielewski9, Anatolii Gozhenko10, Karol Bielski211, Pawel Wroblewski12, Ivan Savytskyi10, Lukasz Szarpak213, Zubaid Rafique14
DOI: 10.5603/CJ.a2021.0122
·
Pubmed: 34642923
·
Cardiol J 2022;29(2):188-196.
Affiliations
  1. Institute of Outcomes Research, Polonia University, Czestochowa, Poland
  2. Outcomes Research Unit, Polish Society of Disaster Medicine, Warsaw, Poland
  3. Institute of Outcomes Research, Maria Sklodowska-Curie Medical Academy, Warsaw, Poland
  4. Laboratory of Experimental Clinical Chemistry, Amsterdam University Medical Center, Amsterdam, the Netherlands
  5. 1st Chair and Department of Cardiology, Medical University of Warsaw, Poland
  6. Department of Surgery, The Silesian Hospital in Opava, Czech Republic
  7. Jan Kochanowski University, Kielce, Poland
  8. 1st Department of Cardiology, Medical University of Gdansk, Poland
  9. College of Rehabiliation, Warsaw, Poland
  10. International European University, Kiev, Ukraine
  11. Emergency Medical Service and Medical Transport Dispatcher, Warsaw, Poland
  12. Department of Emergency Medical Service, Wroclaw Medical University, Wroclaw, Poland
  13. Maria Sklodowska-Curie Bialystok Oncology Center, Bialystok, Poland
  14. Henry JN Taub Department of Emergency Medicine, Baylor College of Medicine Houston, TX, United States

open access

Vol 29, No 2 (2022)
Original articles — COVID-19
Submitted: 2021-08-27
Accepted: 2021-09-06
Early publication date: 2021-10-08

Abstract

Background: Vitamin D is a likely candidate for treatment as its immune modulating characteristics have effects on coronavirus disease 2019 (COVID-19) patients. It was sought herein, to summarize the studies published to date regarding the vitamin D supplementation to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients.
Methods: A systematic review and meta-analysis were performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The primary outcome were 14-day and in-hospital mortality reported as an odds ratio (OR) with the associated 95% confidence interval (CI).
Results: Eight articles were included in the review with a combined total of 2,322 individual patients, 786 in the vitamin D supplementation group and 1,536 in the control group. The use of vitamin D compared to the group without vitamin D supplementation was associated with a lower 14-day mortality (18.8% vs. 31.3%, respectively; OR = 0.51; 95% CI: 0.12–2.19; p = 0.36), a lower in-hospital mortality (5.6% vs. 16.1%; OR = 0.56; 95% CI: 0.23–1.37; I2 = 74%; p = 0.20), the rarer intensive care unit admission (6.4% vs. 23.4%; OR = 0.19; 95% CI: 0.06–0.54; I2 = 77%; p = 0.002) as well as rarer mechanical ventilation (6.5% vs. 18.9%; OR = 0.36; 95% CI: 0.16–0.80; I2 = 0.48; p = 0.01).
Conclusions: Vitamin D supplementation in SARS-CoV-2 positive patients has the potential to positively impact patients with both mild and severe symptoms. As several high-quality randomized control studies have demonstrated a benefit in hospital mortality, vitamin D should be considered a supplemental therapy of strong interest. Should vitamin D prove to reduce hospitalization rates and symptoms outside of the hospital setting, the cost and benefit to global pandemic mitigation efforts would be substantial.

Abstract

Background: Vitamin D is a likely candidate for treatment as its immune modulating characteristics have effects on coronavirus disease 2019 (COVID-19) patients. It was sought herein, to summarize the studies published to date regarding the vitamin D supplementation to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients.
Methods: A systematic review and meta-analysis were performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The primary outcome were 14-day and in-hospital mortality reported as an odds ratio (OR) with the associated 95% confidence interval (CI).
Results: Eight articles were included in the review with a combined total of 2,322 individual patients, 786 in the vitamin D supplementation group and 1,536 in the control group. The use of vitamin D compared to the group without vitamin D supplementation was associated with a lower 14-day mortality (18.8% vs. 31.3%, respectively; OR = 0.51; 95% CI: 0.12–2.19; p = 0.36), a lower in-hospital mortality (5.6% vs. 16.1%; OR = 0.56; 95% CI: 0.23–1.37; I2 = 74%; p = 0.20), the rarer intensive care unit admission (6.4% vs. 23.4%; OR = 0.19; 95% CI: 0.06–0.54; I2 = 77%; p = 0.002) as well as rarer mechanical ventilation (6.5% vs. 18.9%; OR = 0.36; 95% CI: 0.16–0.80; I2 = 0.48; p = 0.01).
Conclusions: Vitamin D supplementation in SARS-CoV-2 positive patients has the potential to positively impact patients with both mild and severe symptoms. As several high-quality randomized control studies have demonstrated a benefit in hospital mortality, vitamin D should be considered a supplemental therapy of strong interest. Should vitamin D prove to reduce hospitalization rates and symptoms outside of the hospital setting, the cost and benefit to global pandemic mitigation efforts would be substantial.

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Keywords

COVID-19, SARS-CoV-2, vitamin D, calciferol, systematic review, meta-analysis

Supp./Additional Files (2)
Supplementary Table 1. Patient characteristics of included studies
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About this article
Title

Vitamin D supplementation to treat SARS-CoV-2 positive patients. Evidence from meta-analysis

Journal

Cardiology Journal

Issue

Vol 29, No 2 (2022)

Article type

Original Article

Pages

188-196

Early publication date

2021-10-08

Page views

7391

Article views/downloads

2529

DOI

10.5603/CJ.a2021.0122

Pubmed

34642923

Bibliographic record

Cardiol J 2022;29(2):188-196.

Keywords

COVID-19
SARS-CoV-2
vitamin D
calciferol
systematic review
meta-analysis

Authors

Luiza Szarpak
Krzysztof J. Filipiak
Aleksandra Gasecka
Wladyslaw Gawel
Dorota Koziel
Milosz J. Jaguszewski
Jaroslaw Chmielewski
Anatolii Gozhenko
Karol Bielski
Pawel Wroblewski
Ivan Savytskyi
Lukasz Szarpak
Zubaid Rafique

References (48)
  1. da Silva FC, Barbosa CP. The impact of the COVID-19 pandemic in an intensive care unit (ICU): Psychiatric symptoms in healthcare professionals. Prog Neuropsychopharmacol Biol Psychiatry. 2021; 110: 110299.
  2. Wang X, Pan Z, Cheng Z. Association between 2019-nCoV transmission and N95 respirator use. J Hosp Infect. 2020; 105(1): 104–105.
  3. Barycka K, Szarpak L, Filipiak KJ, et al. Comparative effectiveness of N95 respirators and surgical/face masks in preventing airborne infections in the era of SARS-CoV2 pandemic: A meta-analysis of randomized trials. PLoS One. 2020; 15(12): e0242901.
  4. Szarpak L, Smereka J, Filipiak KJ, et al. Cloth masks versus medical masks for COVID-19 protection. Cardiol J. 2020; 27(2): 218–219.
  5. Saban M, Shachar T. The silent effect of COVID-19 on emergency departments: How to avoid complacency? Disaster Emerg Med J. 2020; 5: 224–226.
  6. Alfano V, Ercolano S. The efficacy of lockdown against COVID-19: a cross-country panel analysis. Appl Health Econ Health Policy. 2020; 18(4): 509–517.
  7. Gibson PG, Qin L, Puah SH. COVID-19 acute respiratory distress syndrome (ARDS): clinical features and differences from typical pre-COVID-19 ARDS. Med J Aust. 2020; 213(2): 54–56.e1.
  8. Ruetzler K, Szarpak L, Filipiak K, et al. The COVID-19 pandemic — a view of the current state of the problem. Disaster Emerg Med J. 2020; 5: 106–107.
  9. Nurminen V, Seuter S, Carlberg C. Primary vitamin D target genes of human monocytes. Front Physiol. 2019; 10.
  10. Medrano M, Carrillo-Cruz E, Montero I, et al. Vitamin D: effect on haematopoiesis and immune system and clinical applications. Int J Mol Sci. 2018; 19(9).
  11. Szarpak L, Rafique Z, Gasecka A, et al. A systematic review and meta-analysis of effect of vitamin D levels on the incidence of COVID-19. Cardiol J. 2021; 28(5): 647–654.
  12. Rehan VK, Torday JS, Peleg S, et al. 1Alpha,25-dihydroxy-3-epi-vitamin D3, a natural metabolite of 1alpha,25-dihydroxy vitamin D3: production and biological activity studies in pulmonary alveolar type II cells. Mol Genet Metab. 2002; 76(1): 46–56.
  13. Quesada-Gomez JM, Entrenas-Castillo M, Bouillon R. Vitamin D receptor stimulation to reduce acute respiratory distress syndrome (ARDS) in patients with coronavirus SARS-CoV-2 infections: Revised Ms SBMB 2020_166. J Steroid Biochem Mol Biol. 2020; 202: 105719.
  14. Page M, McKenzie J, Bossuyt P, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021: n71.
  15. Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol. 2005; 5: 13.
  16. Cochrane. Cochrane Handbook for Systematic Reviews of Interventions; 2019. www.training.cochrane.org/handbook (Access: 1 July 2019).
  17. Castillo ME, Costa LE, Barrios JV, 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. 2020; 203: 105751.
  18. Murai I, Fernandes A, Sales L, et al. Effect of vitamin D3 supplementation vs placebo on hospital length of stay in patients with severe COVID-19: a multicenter, double-blind, randomized controlled trial. medRxiv. 2021.
  19. Alcala-Diaz JF, Limia-Perez L, Gomez-Huelgas R, et al. Calcifediol treatment and hospital mortality due to COVID-19: a cohort study. Nutrients. 2021; 13(6).
  20. Annweiler G, Corvaisier M, Gautier J, et al. Vitamin D supplementation associated to better survival in hospitalized frail elderly COVID-19 patients: the GERIA-COVID quasi-experimental study. Nutrients. 2020; 12(11): 3377.
  21. Cereda E, Bogliolo L, Lobascio F, et al. Vitamin D supplementation and outcomes in coronavirus disease 2019 (COVID-19) patients from the outbreak area of Lombardy, Italy. Nutrition. 2021; 82: 111055.
  22. Hernández JL, Nan D, Fernandez-Ayala M, et al. Vitamin D Status in Hospitalized Patients with SARS-CoV-2 Infection. J Clin Endocrinol Metab. 2021; 106(3): e1343–e1353.
  23. Nogues X, Ovejero D, Pineda-Moncusí M, et al. Calcifediol treatment and COVID-19-related outcomes. J Clin Endocrinol Metab. 2021; 106(10): e4017–e4027.
  24. Tan CW, Ho LP, Kalimuddin S, et al. Cohort study to evaluate the effect of vitamin D, magnesium, and vitamin B in combination on progression to severe outcomes in older patients with coronavirus (COVID-19). Nutrition. 2020; 79-80: 111017.
  25. Xing K, Tu XY, Liu M, et al. Efficacy and safety of COVID-19 vaccines: a systematic review. Zhongguo Dang Dai Er Ke Za Zhi. 2021; 23(3): 221–228.
  26. Callaway E. Delta coronavirus variant: scientists brace for impact. Nature. 2021; 595(7865): 17–18.
  27. Li R, Rivers C, Tan Qi, et al. The demand for inpatient and ICU beds for COVID-19 in the US: lessons from Chinese cities. medRxiv. 2020.
  28. The Lancet Rheumatology.Too long to wait: the impact of COVID-19 on elective surgery. Lancet Rheumatol. 2021; 3(2): e83.
  29. Schwartz RA, Suskind RM. Azithromycin and COVID-19: Prompt early use at first signs of this infection in adults and children, an approach worthy of consideration. Dermatol Ther. 2020; 33(4): e13785.
  30. Borba MG, Val FF, Sampaio VS, et al. Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a randomized clinical trial. JAMA Netw Open. 2020; 3(4): e208857.
  31. Kow CS, Hasan SS. Azithromycin in patients with COVID-19: Friend or foe? Clin Microbiol Infect. 2021; 27(1): 136–137.
  32. Ho TC, Wang YH, Chen YL, et al. Chloroquine and hydroxychloroquine: efficacy in the treatment of the COVID-19. Pathogens. 2021; 10(2).
  33. Perveen RA, Nasir M, Talha KA, et al. Systematic review on current antiviral therapy in COVID-19 pandemic. Med J Malaysia. 2020; 75(6): 710–716.
  34. Szarpak Ł, Dzieciątkowski T, Jaguszewski MJ, et al. Is remdesivir important in clinical practice as a treatment of COVID-19? A study based on meta-analysis data. Pol Arch Intern Med. 2021; 131(1): 96–97.
  35. Bradley R, Schloss J, Brown D, et al. The effects of vitamin D on acute viral respiratory infections: A rapid review. Adv Integr Med. 2020; 7(4): 192–202.
  36. Town JA, Churpek MM, Yuen TC, et al. Relationship between ICU bed availability, ICU readmission, and cardiac arrest in the general wards. Crit Care Med. 2014; 42(9): 2037–2041.
  37. Singh AK, Gupta R, Ghosh A, et al. Diabetes in COVID-19: Prevalence, pathophysiology, prognosis and practical considerations. Diabetes Metab Syndr. 2020; 14(4): 303–310.
  38. Szarpak Ł, Nowak B, Kosior D, et al. Cytokines as predictors of COVID-19 severity: evidence from a meta-analysis. Pol Arch Intern Med. 2021; 131(1): 98–99.
  39. Tang Lu, Yin Z, Hu Yu, et al. Controlling cytokine storm is vital in COVID-19. Front Immunol. 2020; 11: 570993.
  40. Mata-Granados JM, Vargas-Vasserot J, Ferreiro-Vera C, et al. Evaluation of vitamin D endocrine system (VDES) status and response to treatment of patients in intensive care units (ICUs) using an on-line SPE-LC-MS/MS method. J Steroid Biochem Mol Biol. 2010; 121(1-2): 452–455.
  41. Dai Qi, Zhu X, Manson JE, et al. Magnesium status and supplementation influence vitamin D status and metabolism: results from a randomized trial. Am J Clin Nutr. 2018; 108(6): 1249–1258.
  42. Sassi F, Tamone C, D'Amelio P. Vitamin D: nutrient, hormone, and immunomodulator. Nutrients. 2018; 10(11).
  43. Lurz E, Horne RG, Määttänen P, et al. Vitamin B12 deficiency alters the gut microbiota in a murine model of colitis. Front Nutr. 2020; 7: 83.
  44. Zheng D, Liwinski T, Elinav E. Interaction between microbiota and immunity in health and disease. Cell Res. 2020; 30(6): 492–506.
  45. Annweiler C, Hanotte B, Grandin de l'Eprevier C, et al. Vitamin D and survival in COVID-19 patients: A quasi-experimental study. J Steroid Biochem Mol Biol. 2020; 204: 105771.
  46. Reijven PLM, Soeters PB, Reijven PLM, et al. Vitamin D: A magic bullet or a myth? Clin Nutr. 2020; 39(9): 2663–2674.
  47. Murai IH, Fernandes AL, Sales LP, et al. Effect of a single high dose of vitamin D3 on hospital length of stay in patients with moderate to severe COVID-19: a randomized clinical trial. JAMA. 2021; 325(11): 1053–1060.
  48. Jolliffe DA, Stefanidis C, Wang Z, et al. Vitamin d metabolism is dysregulated in asthma and chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2020; 202(3): 371–382.

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