Table 7.
Vitamin D supplementation and COVID-19. Evidence from intervention studies.
| Study | Type of study | Sample | Age (years) | Sex | Intervention | Control | Follow up | Results |
|---|---|---|---|---|---|---|---|---|
| Ma et al., 174 UK | Prospective study of an intervention | 8297 adults with COVID-19 test results in the UK biobank I: 363 VIT-D users C: 7934 VIT-D non-users |
I: 59.1 SD 8.1 C: 57.4 SD 8.6 (p < 0.001) |
I: M 39% F 61% C: M 50% F 50% |
Habitual use of VIT-D | No VIT-D use | COVID-19 test results for ca. 4 months | Risk of COVID 19 infection I: 13.5%, C: 16.8% Unadjusted OR 0.78 CI 0.57, 1.05) (p = 0.105) Adjusted OR 0.67 CI 0.46, 0.98 (p = 0.038) |
| Murai et al. 173 | Multi-centre RCT, double blind | 237 of 240 randomised pts hospitalised with moderate to severe COVID-19 infection I: 119 C: 118 |
Mean I: 56.5 SD 13.8 C: 56.0 SD 15.0 (NS) |
I: M 59%, F 41% C: M 53% F 55% (NS) |
5000 µg VIT-D3 as a single dose | Placebo | Ca. 4 months | Median LOS I: 7 IQR 4, 10 days C: 7 IQR 5, 13 days HR 1.07 CI 0.82, 1.39 (p = 0.59) In-hospital mortality I: 7.6%, C: 5.1% Δ 2,5 CI −4.1, 9.2% (p = 0.43) Admission to ICU I: 16.0%, C: 21.2% Δ −5.2 CI −15.1, 4.7% (p = 0.30) |
| Annweiler et al., 176 France a | Post hoc open label intervention study | 66 pts, nursing home residents I: 57 C: 9 |
Mean I: 87.7 SD 9.3 C: 87.4 SD 7.2 (NS) |
I: M 23% F 77% C: M33% F 67% (NS) |
2000 µg VIT-D3 Bolus VIT-D in the week following a suspected or confirmed COVID-19 infection or in the preceding month |
None | Mean 36 SD 17 days |
Death I: 17.5%, C: 55.6%) Adjusted HR 0.11 CI 0.03, 0.48 (p = 0.003) Survival time I: Longer survival (p = 0.002) Severity of COVID-19 I: Inverse OS CI (p = 0.001) |
| Annweiler et al., 177 France | Post hoc open label intervention study | 77 pts hospitalised in a geriatric unit I1: 29 I2: 16 C: 32 |
I1: 88 IQR 87, 93 I2: 85 IQR 84–89 C: 88 IQR 84–92 (NS) b |
I1: M 31% F 69% I2: M 69% F 31% C: M 59% F 41% (p = 0.02) |
I1: Bolus VIT-D3 po taken regularly during the year before the COVID-19 pandemic, either 1250 µg VIT-D3 every month or 2000–2500 µg VIT-D3 every 2–3 months I2: Bolus VIT 3 po 2000 µg VIT-D3 within a few hours after COVD-19 diagnosis and no previous VIT-D supplements |
None | 14 days (from hospitalisation) |
Death
I1: 6.9%, I2: 18.8%, C 31.3% Adjusted HR I1 versus C 0.07 CI 0.01, 0.61 (p = 0.017) Adjusted HR I2 versus C 0.37 CI 0.06, 2.21 (0.28) Survival time I1 versus C: longer survival (p = 0.015) I2 versus C: no difference in survival time (p = 0.32) I1 versus I2: no difference in survival time (p = 0.32) Severity of COVID-19 I1 versus C: fewer pts with severe COVI-19 (p = 0.033) I2 versus C: no difference (p = 0.40) |
| Entrenas Castillo et al., 172 Spain | Open label trial, blinded at the point of analysis | 76 pts hospitalised with COVID-19 infection I: 50 C: 26 |
Mean I: 53.1 SD 10.8 C: 52.8 SD 9.4 (NS) |
I: M 54% F 46% C: M 69% F 31% (NS) |
532 µg 25(OH)D3 (=2660 µg VIT D3) on admission, 266 µg 25(OH)D3 (=1330 µg VIT D3) on day 3 and 7 and then weekly until ICU admission or discharge | None | Until ICU admission, death, or hospital discharge | Admission to ICU I: 2%, C: 50%, Adjusted OR 0.03 CI 0.003, 0.25 Death in ICU I: 0%, C: 15.4% c (p = 0.894) d |
| Rastogi et al., 175 India | RCT (SHADE study) | 40 pts with mild or asymptomatic COVID-19 infection with VIT-D deficiency, i.e., 25(OH)D conc <20 ng/ml I: 16 C: 24 |
Median I: 50 IQR 36, 51 C: 47.5 IQR 39.3, 49.2 (NS) |
I: M 38% F 62% C: M 58% F 42% (NS) |
1500 µg VIT D3 for 7 days with a serum conc of >50 ng/ml 25(OH)D as therapeutic target If after 7 days 25(OH)D <50 ng/ml 1500 µg VIT D3 for a further 7 days until day 14 |
Placebo | 21 days | COVID-19 RNA −ve after 21 days I: 62.5%, C: 20.8% (p < 0.018) No difference in mean duration to COVID-19 −ve ↓ fibrinogen I: more ↓ (p < 0.01) Other inflammatory parameters: No difference regarding D-dimer, CRP, ferritin, procalcitonin |
| Hernandez et al., 178 Spain | Retrospective study of an intervention (case control) | 216 pts hospitalised with COVID-19 infection I: 19 C: 197 |
Median I: 60 IQR 59, 75 C: 61 IQR 47.5, 70 (NS) |
I: M 37% F 63% C: M 62% F 38% (p = 0.03) |
Oral vitamin D supplements >3 months | No VIT-D use | 21 days | Median LOS I: 8 IQR 6, 14 days C: 12 IQR 8.0, 16.0 days (p = 1.07) ICU admission I: 5.3%, C: 25.4% (p = 0.05) Death I: 10.5%, C: 10.4% (p = 0.999) |
a
Conversion factor from µg to IU = 40, 1 µg cholecalciferol = 0.2 µg 25(OH)D.
b
Not specified by authors whether mean or median, in view of IQR use most likely median.
c
Of all ICU patients.
d
Own calculation.
1 IU = 0.025 µg cholecalciferol or 0.005 µg 25(OH)D.
C, control; CI, 95% confidence interval; conc, concentration; COVID-19, coronavirus disease 2019; F, female; HR, hazard ratio; I, intervention; ICU, intensive care unit; IU, international units; LOS, length of stay; M, male; NS, not significant; OR, odds ratio; po, per os; pts, participants; RCT, randomised controlled trial; re, regarding; SD, standard deviation; VIT-D: vitamin D; −ve, negative; Δ, difference.