TABLE 1.
Characteristics of studies examining the links between vitamin D and COVID‐19
| Study design | Sample size | Main findings | References |
|---|---|---|---|
| Correlation analysis of data | 88 countries | Countries lying near to the equator had fewer COVID‐19 fatalities than those lying farther away; latitude accounted for 16% of this difference | 103 |
| Cohort study | 105 | Lack of vitamin D was linked to increased care requirements and the development of cytokine storms | 104 |
| Retrospective cohort study | 107 | SARS‐CoV‐2‐positive individuals showed lower levels of 25(OH)D | 105 |
| Retrospective cohort study | 4314 | A higher risk of COVID‐19 was associated with inadequate vitamin D levels | 106 |
| Retrospective study | 185 | Lack of vitamin D was linked to an increased risk of invasive mechanical ventilation or death | 107 |
| Randomized prospective open‐label study | 87 | In people with hypovitaminosis D, vitamin D supplementation reduced inflammatory markers | 108 |
| Retrospective cohort study | 56 | A lack of vitamin D in patients with COVID‐19 reported greater levels of inflammatory markers along with considerably reduced level of hemoglobin and lymphocyte counts | 52 |
| Parallel pilot randomized open‐label trial | 76 | In patients who needed to be admitted to the ICU, high dosage calcifediol lessened the severity of COVID‐19 | 109 |
| Multi‐center parallel double‐blind RCT | 240 | When compared with placebo, a single high dose of cholecalciferol had no effect on hospital stay, death, ICU admission, or the need for ventilation | 110 |
| RCT | 40 | A higher percentage of asymptomatic or slightly symptomatic patients on high dosage vitamin D—25(OH)D >50 ng/mL achieved a negative SARS‐CoV‐2 RNA at less than 21 days—than those with vitamin D deficiency | 111 |
| Quasi‐randomized trial | 66 | In an elderly population, vitamin D administration before or after COVID‐19 decreased disease severity and fatality rates | 112 |
| Systematic review and meta‐analysis | 6 retrospective articles | A helpful prognostic indicator of COVID‐19 results could be vitamin D levels | 113 |
| Living Cochrane systematic review | 3 RCTs | The available information is insufficient to definitively determine the advantages or disadvantages of vitamin D supplementation as a COVID‐19 treatment | 114 |
| Open‐label, multicenter, superiority RCT | NA | In SARS‐CoV‐2‐positive patients exhibiting at least one symptom of elevated risk, a single dose of 50 000 IU of vitamin D was compared with a single dose of 200 000 IU of vitamin D. Incomplete results | 115 |
| Quasi‐experimental study | 77 | Before COVID‐19, regular vitamin D administration decreased mortality in elderly individuals at the 3‐month follow up | 116 |
| Systematic review and meta‐analysis | 21 studies | Low vitamin D levels are correlated with severe COVID‐19 illness, which may be explained by the fact that 25(OH)D is inversely correlated with pro‐inflammatory cytokines like interleukin‐6, an increase in C‐reactive protein, and cardiac insufficiency, which are related to the severity of COVID‐19 and its unfavorable outcomes. A 25(OH)D shortage and sensitivity to infection by COVID‐19 have not been linked causally, despite a linkage between higher vitamin D levels, immunological responses, and a better prognosis in other viral infections, according to testing and blood vitamin D tests in SARS‐CoV‐2 patients | 62, 117, 118 |
| Cohort study | 43 | If they did not need oxygen therapy, patients were given 500 μg/day of vitamin B12, 150 mg/day of magnesium, and 1000 IU/day of vitamin D3 (DMB) when they were admitted. Patients who received DMB had much less deterioration to the point of needing oxygen therapy or intensive care support, even after adjusting for demographics and hypertension | 119 |
| Retrospective cohort study | 499 | The incidence of COVID‐19 was associated with vitamin D deficiency status in addition to age and non‐white race. The likelihood of testing positive for COVID‐19 was not substantially associated with the amount of vitamin D supplementation | 120 |
| Retrospective observational analysis | 191 779 | Patients with inadequate 25(OH)D scores had a greater incidence of SARS‐CoV‐2 than patients with sufficient values and those with levels under 55 ng/mL | 121 |
| Observational study | 154 | Patients who were asymptomatic had mean vitamin D levels that were noticeably higher than patients who were gravely unwell. In people who were extremely unwell, vitamin D deficiency was more common. 90 out of 154 patients had vitamin D deficiency (29 asymptomatic; 61 severely ill). Patients with vitamin D deficiency had greater levels of inflammatory markers, an inflammatory response, and a higher mortality rate in their serum (21% vs 3.1%). Patients with severe COVID‐19 had noticeably low levels of vitamin D | 122 |
| Retrospective observational study | 42 | Patients with severe vitamin D deficiency had a 50% chance of dying after 10 days in the hospital, whereas those with insufficiency or moderate deficiency had a 5% chance. Hypovitaminosis D was found to be highly prevalent in 19 patients with acute respiratory failure who were receiving treatment in the ICU, which was associated with a significant mortality risk | 123 |
| Observational study | NA | Government statistics data on mortality were inversely associated with the mean vitamin D levels reported in various states and territories | 124 |
| Retrospective observational study | 444 | A lower incidence of COVID‐19 mortality was associated with the administration of cholecalciferol booster | 125 |
| Retrospective observational trial | 186 | Independent of age, chronic lung illness, and the severity score from the chest computed tomography, vitamin D deficiency at admission was linked to mortality | 126 |
| Retrospective observational study | 149 | A lower level of serum 25(OH)D was linked to higher mortality in COVID‐19 patients | 127 |
| Retrospective observational study | 464 | After sex was ruled out as a factor in COVID‐19 severity or fatality, levels of 25(OH)D <12 ng/mL were found to be strongly associated with an elevated risk of fatal disease and severe sickness | 128 |
| Cohort study | 646 | There is no proven link between low vitamin D levels and COVID‐19 severity or fatality | 129 |
| Observational cohort study | 445 | There was a link between hypocalcemia and the severity of COVID‐19, but there was no linkage between vitamin D and the severity or advancement of the disease. It is also accepted that calcium and vitamin D interact | 130 |
| Retrospective observational study | 1549 | But not mortality, hospital admission and critical care were associated with low vitamin D levels | 131 |
| Retrospective cohort study | 144 | The level of serum vitamin D was negatively linked with hospital mortality and the requirement for mechanical ventilation | 132 |
| Prospective observational study | 410 | There is no link between a vitamin D deficiency and the prevalence of severe COVID‐19, a rise in oxygen use, hospital admissions, or death. There was no appreciable change in the outcome in vitamin D‐deficient patients treated with cholecalciferol | 133 |
| Retrospective, multicenter, non‐randomized cohort study | 537 | After COVID‐19 diagnosis, calcifediol medication was significantly linked to a lower 30‐day mortality rate | 134 |
| Observational study | 157 | It was discovered that vitamin D supplementation had an adverse relationship with mortality in COVID‐19 patients | 135 |
| Cohort study | 1486 | The incidence of COVID‐19 was higher in patients with Parkinson's disease who were younger, heavier, and had chronic obstructive pulmonary disease. Patients who took vitamin D supplements had a lower likelihood of developing it | 136 |
| Retrospective study | 91 | In patients with comorbidities, two doses of 200 000 IU of vitamin D given on consecutive days can enhance outcomes (ICU admission, mortality) | 137 |
| Case‐control study | 60 039 | Statins that raised levels of 25(OH)D, such as rosuvastatin, were the only ones to have a protective effect in COVID‐19 | 138 |
| Retrospective survival study | 16 401 | Following the administration of vitamin D (calcifediol) 15‐30 days before hospitalization, there was a significant decrease in mortality | 139 |
| RCT | 69 | For 2 weeks, patients with mild to severe symptoms of COVID‐19 required less time to recover when given 5000 IU of vitamin D daily rather than 1000 IU. Over time, the interleukin‐6 and body mass index levels in both groups decreased | 140 |
| Population‐based cohort study | 108 343 | Infection rates were more likely to increase with lower serum 25(OH)D levels than disease severity or mortality. Patients with COVID‐19 who received vitamin D supplements compared with those who did not receive any supplements | 59 |
| Clinical case series | 4 | Treatment with calcifediol significantly decreased mortality and ICU admission in hospitalized COVID‐19 patients | 141 |
| Observational study | 838 | Treatment with calcifediol significantly decreased mortality and ICU admission in COVID‐19 patients who were hospitalized | 142 |
| Prospective study | 8297 | A decrease in COVID‐19 incidence was associated with routine vitamin D intake | 67 |
Abbreviations: COVID‐19, coronavirus disease 2019; RCT, randomized controlled trial; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2.