Effects of Vitamin D Supplementation on COVID-19 Related Outcomes: A Systematic Review and Meta-Analysis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Search Strategy
2.2. Study Selection
2.3. Data Extraction and Assessment
2.4. Risk of Bias and Quality Assessment
2.5. Statistical Methods
3. Results
3.1. Search Results
3.2. Study Characteristics
3.3. Risk of Bias
3.4. Primary Prevention
3.5. Secondary Prevention
3.6. Tertiary Prevention
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Reference | Design, Setting | Participants | Duration of Intervention | Treatment Arms | Baseline Serum 25OHD (nmol/L) | |
---|---|---|---|---|---|---|
Vitamin D | Control | |||||
Primary Prevention | ||||||
Hosseini et al. [27], 2021 | RCT, Canada | Unvaccinated healthcare workers (25–58 years old, male: 5.9%) | 4–10 weeks | Intervention: vitamin D: bolus 100,000 IU + 10,000 IU/week (n = 19); Control: placebo (n = 15) | 49.56 ± 26.64 | 48.02 ± 15.16 |
Abdulateef et al. [11], 2021 | Retrospective cohort, Iraq | Patients with COVID-19 (15–80 years old, male: 44.4%) | Not specified | Intervention: regularly supplemented with vitamin D prior to COVID-19 exposure (n = 127), “ranging from <1000 IU/day to >4000 IU/day for <1 week to >2 weeks”; Control: no vitamin D supplements (n = 300) | Not reported | Not reported |
Ma et al. [31], 2021 | Prospective cohort, United Kingdom | Adults who have records of COVID-19 test results from UK Biobank (37–73 years old, male: 44.4%) | Not specified | Intervention: regularly supplemented with vitamin D (not specified) prior to COVID-19 exposure (n = 363); Control: no vitamin D supplements (n = 7934) | 56 ± 20.8 | 47 ± 21.1 |
Meltzer et al. [32], 2020 | Retrospective cohort, United States | 489 patients with data for a vitamin D level within 1 year before COVID-19 testing (49.2 ± 18.4 years old, male: 25.0%) | Not specified | Intervention: “regularly supplemented with vitamin D over the past year excluding the 14 days before testing: (≤1000 IU, 2000 IU, ≥3000 IU)” (n = 277); Control: no vitamin D supplements (n = 212) | Not reported | Not reported |
Oristrell et al. [14], 2021 | Retrospective cohort, Spain | Patients with chronic kidney disease (70.2 ± 15.6 years old, male: 42.5%) | 10 months | Intervention: supplemented with vitamin D prior to COVID-19 exposure (10,596 IU/day) from 1 April 2019 to 28 February 2020 (n = 8076); Control: no vitamin D supplements (n = 5,848,776) | Not reported | Not reported |
Secondary Prevention | ||||||
Rastogi et al. [8], 2020 | RCT, India | Asymptomatic or mildly symptomatic cases of COVID-19 (36 to 51 years old, male: 45.0%) | 7 days or more if needed | Intervention: vitamin D: 60,000 IU/day; (n = 16) (with therapeutic target 25 OHD > 125 nmol/day); Control: identical placebo (n = 24) | 21.5 (17.7, 32.7) | 23.8 (20.5, 31.2) |
Sánchez-Zuno et al. [10], 2021 | RCT, Mexico | COVID-19 outpatients 20–74 years old, male: 47.7%) | 14 days | Intervention: 10,000 IU of vitamin D3/day (n = 22); Control: placebo (n = 20) | 50.5 (30.5, 114.7) | 58.5 (30.25, 114) |
Annweiler et al. [4], 2021 | Quasi-experimental with retrospective collection of data, France | Elderly nursing-home residents infected with COVID-19 (63–103 years old, male: 23.7%) | Single bolus | Intervention: single oral dose of 80,000 IU vitamin D3 during COVID-19 or in the preceding month (n = 57); Control: no vitamin D supplements (n = 9) | Not reported | Not reported |
Cangiano et al. [30], 2021 | Prospective cohort, Italy | 157 residents of a nursing home after Sars-CoV-2 spread (80–100 years old, male: 28.5%) | 2 months | Intervention: vit D supplementation: 50,000 IU/month (n = 20); Control: no vitamin D supplementation (n = 78) | Not reported | Not reported |
Cereda et al. [15], 2020 | Retrospective cohort, Italy | COVID-19 outpatients (68.8± 10.6 years old, male: 48.4%) | 3 months | Intervention: supplemented (“mean intake of >1800 IU/day”) (n= 38); Control: no vitamin D supplementation (n = 286) | 82.2 ± 37 | 28.2 ± 21.5 |
Tertiary Prevention | ||||||
Caballero-García et al. [26], 2021 | RCT, Spain | Patients in the recovery phase post hospitalization with COVID-19 infection (62.5 ± 1.5 years old, male: 100.0%) | 6 weeks | Intervention: vitamin D: , IU/day (n = 15); Control: placebo (n = 15) | 52.2 ± 4.5 | 53.0 ± 3.5 |
Castillo et al. [3], 2020 | RCT, Spain | Patients hospitalized with COVID-19 infection (53.14 ± 1 0.77 years old, male: 59.0%) | 4 weeks | Intervention: 21,280 IU/day vitamin D on day 1, 3 and 7, and then weekly until discharge or ICU admission (n = 50); Control: no vitamin D supplementation (n = 26) | Not reported | Not reported |
Lakkireddy et al. [13], 2021 | RCT, India | Patients hospitalized with COVID-19 infection (20–83 years old, male: 75%) | 8–10 days | Intervention: 60,000 IU/day vitamin D (n = 44); Control: no vitamin D supplementation (n = 43) | 40 ±15 | 42.5 ± 15 |
Murai et al. [12], 2021 | RCT, Brazil | Patients hospitalized with COVID-19 infection (56.2 ± 14.4 years old, male: 46.1%) | 20 days | Intervention: single bolus of 200,000 IU vitamin D (n = 120); Control: placebo (n = 120) | 53 ± 25.2 | 51.5 ± 20.2 |
Nogues et al. [25], 2021 | RCT, Spain | Patients hospitalized with COVID-19 infection (30–80 years old, male: 56.0%) | 30 days | Intervention: vitamin D: 21,620 IU on day 1, 10,810 IU on day 3, 7, 15, and 30) (n = 551); Control: placebo (n = 379) | 37.5 (22.5, 70) | 30 (8,47.5) |
Sabico et al. [9], 2021 | RCT, Saudi Arabia | Patients hospitalized with COVID-19 infection (20–75 years, male: 47.8%) | 2 weeks | Intervention: vitamin D: 5000 IU/day (n = 36); Control: 1000 IU/day (n = 33) | 53.4 ± 2.9 | 63.5 ± 3.4 |
Alcala-Diaz et al. [6], 2021 | Retrospective cohort, Spain | Patients hospitalized with COVID-19 infection (69 ± 15 years old, male: 59.0%) | 28 days | Intervention: vitamin D: 21,620 IU on day 1, 10,810 IU on day 3, 7, 14, 21, and 28) (n = 79); Control: no vitamin D supplementation (n = 458) | Not reported | Not reported |
Annweiler et al. [5], 2020 | Quasi-experimental with retrospective collection of data, France | Patients hospitalized with COVID-19 infection (78- 100 years old, male: 51.0%) | Not specified | Group 1: regularly supplemented with vitamin D (50,000 IU/month) (n = 29); Group 2: vitamin D supplementation initiated after COVID-19 diagnosis (80,000 IU bolus) (n = 16); Group 3: no vitamin D supplementation (n = 32) | Not reported | Not reported |
Annweiler et al. [28], 2021 | Quasi-experimental with retrospective collection of data, France | Patients hospitalized with COVID-19 infection (78–100 years old, male: 51.0%) | Not specified | Intervention: regularly supplemented with vitamin D (50,000 IU/month or 800 IU/day) (n = 67); Control: no vitamin D supplementation (n = 28) | 61.6 ± 35.4 | 73.9 ± 32.1 |
Giannini et al. [35], 2021 | Retrospective cohort, Italy | Patients hospitalized with COVID-19 infection (74.0 ± 13.0 years old, male: 75%) | 2 days | Intervention: oral bolus of 200,000 IU vitamin D on the second and third day of hospital stay (n = 36); Control: no vitamin D supplementation (n = 55) | 24 (12, 42) | 36 (19, 77) |
Guven et al. [29], 2021 | Prospective cohort, Turkey | Patients hospitalized with COVID-19 infection (74 (61–82)) years old, male: 61.0%) | Single bolus | Intervention: single dose of 300,000 IU intramuscularly (n = 113); Control: no vitamin D supplementation (n = 62) | 16.6 (12.6, 22.7) | 17.8 (14.2, 20.5) |
Hernandez et al. [34], 2021 | Case–control, Spain | Patients hospitalized with COVID-19 infection (60.0 (59.0–75.0)) years old, male: 60.1%) | More than 3 months prior to hospital admission | Intervention: supplemented with vitamin D (“range from 10,000 IU/month, to 5600 IU/week or 25,000 IU/month”) (n = 19); Control: no vitamin D supplementation (n = 197) | 52.7 ± 14.7 | 34.5 ± 18 |
Nogues et al. [33], 2021 | Prospective cohort, Spain | Patients hospitalized with COVID-19 infection (61.81 ± 15.5 years old, male: 59.0%) | 28 days | Intervention: vitamin D: 21,620 IU on day 1, 10,810 IU on day 3, 7, 14, 21, and 28) (n = 447); Control: no supplementation (n = 391) | 32.5 (20.0, 60.0) | 30 (20, 47.5) |
Study | Selection Bias 1 | Selection Bias 2 | Performance Bias 3 | Attrition Bias 4 | Detection Bias 5 | Reporting Bias 6 | Overall Risk of Bias |
---|---|---|---|---|---|---|---|
Primary prevention | |||||||
Hosseini et al. [27] | Low | Low | Low | Low | Low | Low | Low |
Secondary prevention | |||||||
Rastogi et al. [8] | Some concerns | Some concerns | Some concerns | Low | Some concerns | Some concerns | Some concerns |
Sanchez et al. [10] | Some concerns | Some concerns | Some concerns | Low | Low | Low | Some concerns |
Tertiary prevention | |||||||
Castillo et al. [3] | Low | Low | Low | Some concerns | Low | Low | Low |
Caballero-Garcia et al. [26] | Low | Low | Low | Low | Low | Low | Low |
Lakkireddy et al. [13] | Some concerns | Some concerns | Some concerns | Low | Low | Low | Some concerns |
Murai et al. [12] | Low | Low | Low | Low | Low | Low | Low |
Nogues et al. [25] | Some concerns | Some concerns | Some concerns | Low | Low | Low | Some concerns |
Sabico et al. [9] | Some concerns | Some concerns | Some concerns | Low | Low | Low | Some concerns |
Study | Q1 1 | Q2 2 | Q3 3 | Q4 4 | Q5 5 | Q6 6 | Q7 7 | Q8 8 | Q9 9 | Q10 10 | Overall Risk of Bias |
---|---|---|---|---|---|---|---|---|---|---|---|
Primary prevention | |||||||||||
Abdulateef et al. [11] | Yes | No | Yes | Yes | No | No | Yes | No | Yes | Yes | Some concerns |
Ma et al. [31] | Yes | No | Yes | Yes | No | No | Yes | Yes | Yes | Yes | Some concerns |
Meltzer et al. [32] | Yes | No | Yes | Yes | No | No | Yes | Yes | Yes | Yes | Some concerns |
Oristrell et al. [14] | Yes | No | Yes | Yes | No | Yes | Yes | Yes | Yes | Yes | Low |
Secondary prevention | |||||||||||
Annweiler et al. [4] | Yes | No | No | Yes | Unclear | Yes | Yes | Yes | Yes | Yes | Some concerns |
Cangiano et al. [30] | Yes | No | No | No | Unclear | Yes | Yes | Yes | Yes | Yes | Some concerns |
Cereda et al. [15] | No | No | Yes | Yes | No | Yes | Yes | Yes | Yes | Yes | Some concerns |
Tertiary prevention | |||||||||||
Annweiler et al. [5] | Yes | No | No | Yes | Unclear | No | Yes | Yes | Yes | Yes | Some concerns |
Annweiler et al. [28] | Yes | No | No | Yes | Unclear | No | Yes | Yes | Yes | Yes | Some concerns |
Alcala-Diaz et al. [6] | Yes | No | No | Yes | No | Yes | Yes | Yes | Yes | Yes | Some concerns |
Giannini et al. [35] | Yes | No | No | Yes | Unclear | Yes | Yes | Yes | Yes | Yes | Some concerns |
Guven et al. [29] | Yes | No | Yes | Yes | Unclear | Yes | Yes | No | Yes | Yes | Some concerns |
Nogues et al. [33] | Yes | No | Yes | Yes | Unclear | Yes | Yes | Yes | Yes | Yes | Low |
Hernandez et al. [34] | Yes | No | No | No | Unclear | Yes | Yes | Yes | Yes | Yes | Some concerns |
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Hosseini, B.; El Abd, A.; Ducharme, F.M. Effects of Vitamin D Supplementation on COVID-19 Related Outcomes: A Systematic Review and Meta-Analysis. Nutrients 2022, 14, 2134. https://doi.org/10.3390/nu14102134
Hosseini B, El Abd A, Ducharme FM. Effects of Vitamin D Supplementation on COVID-19 Related Outcomes: A Systematic Review and Meta-Analysis. Nutrients. 2022; 14(10):2134. https://doi.org/10.3390/nu14102134
Chicago/Turabian StyleHosseini, Banafsheh, Asmae El Abd, and Francine M. Ducharme. 2022. "Effects of Vitamin D Supplementation on COVID-19 Related Outcomes: A Systematic Review and Meta-Analysis" Nutrients 14, no. 10: 2134. https://doi.org/10.3390/nu14102134