TABLE 1.
Characteristics and major outcomes of selected studies included in the scoping review evaluating the effect of nutrients on patients with COVID-191
| Study, year; study design (country) (reference) | Sample size (target population) | Exposure, dosage, duration | Control group | Reported outcome | Conclusions |
|---|---|---|---|---|---|
| Anderson et al., 2020; clinical trial (China) (29) | 50 patients with moderate to severe COVID-19 infection | Ascorbic acid: 100 mg/(kg ⸱ d) or 7 g Intravenous continuous infusion of ascorbic acid for 25–28 d | — | No mortality; 3–5 d shorter hospital stays | Adjunctive care of hospitalized COVID-19 patients by ascorbic acid |
| Zhang et al., 2020; randomized controlled clinical trial (Wuhan) (23) | 44 ICU patients: 22 patients in each group Mean age: 67.4 ± 12.4 y, 67% male | Ascorbic acid: 24 g/d HDIVC for 7 d | Placebo: bacteriostatic water for injection | ↓ IL-6; ↓Total bilirubin and ICU mortality of severe patients; ↑PaO2/FiO2 | Protective clinical effect and alternative treatment options for HDIVC |
| Hiedra et al., 2020; clinical trial, a case series (USA) (30) | 17 patients requiring 30% or more FiO2; 64 ± 14 y; 41% females | Ascorbic acid: 3 g daily intravenous vitamin C; Median: 3 d (range: 0–11 d) | — | ↓ Inflammatory markers (ferritin and D-dimer); ↓ FiO2 requirements | The potential therapeutic use of intravenous vitamin C in patients with moderate to severe COVID-19 |
| Zhao et al., 2021; retrospective case series study (China) (34) | 12 patients: 6 patients in each group; Mean age: 56 y in severe disease group and 63 y in the critical group | Ascorbic acid: 162.7 mg/(kg ⸱ d) or 11.39 g for severe patients, 178.6 or 12.50 g for critical patients for 7 d | — | ↓ Significant CRP from day 0 to 3 and 7; The normal level of lymphocyte and CD4 + T-cell counts; ↑PaO2/FiO2SOFA score improvement | Beneficial in terms of the inflammatory response, immune and organ function, especially in severe compared with critical patients |
| Carlucci et al., 2020; retrospective observational study (USA) (22) | Zinc sulfate + medication, n = 411;Medication alone, n = 521 | Zinc sulfate: 220 mg capsule twice daily (50 mg elemental zinc) for 5 d | HCQ (400 mg followed by 200 mg twice daily for 5 d); azithromycin (500 mg once daily) | No effect on the length of hospitalization, ICU duration, and duration of ventilation; ↑ Frequency of being discharged home; ↓ In mortality among patients who did not need ICU | A potential therapeutic as well as the synergistic mechanism of zinc sulfate with HCQ, if used early on in presentation with COVID-19 |
| Yao et al., 2020; retrospective study (USA) (35) | 242 patients: Zinc sulfate group: 196 patient Mean age: 65 y Control group: 46 patients, Mean age: 71 y | Zinc sulfate: Zinc + medication, 440 mg daily (100 mg elemental Zn) for a short period | Medication alone including HCQ, lopinavir/ritonavir, steroids, and IL-6 receptor inhibitors | No significant association between zinc and a change in risk of in-hospital mortality | No association between zinc and the survival of hospitalized patients with COVID-19 |
| Finzi, 2020; case report (USA) (32) | 26-y-old woman | Zinc: 150 mg daily for 14 d | — | Improvement in cough and body aches and fatigue after 1 d; Full recovery after 2 wk | Symptomatic improvement in 4 patients with COVID-19 |
| 41-y-old woman | Zinc: 138 mg daily for 10 d | — | Improvement in PaO2 and fever began 1 d after zinc; Recovery after 10 d | ||
| 57-y-old woman | Zinc: Nine days: one or two 23 mg daily, Day 10: 161 mg, Day 11: 115 mg, Next 10 d: 115 mg daily; For 21 d | — | Gradual improvement in symptoms like dry cough, chest pain, intense neck muscle pain, fever, headache, and shortness of breath at rest | ||
| 63-y-old man | Zinc: Day 1: 69 mg, Day 2: 207 mg, Next 10 d: 184 mg; For 12 + 1 d | — | Improvement in fever, headaches, and muscle pain on the second day; Symptoms continued to improve over the next 10 d | ||
| Abd-Elsalam et al., 2020; randomized, multicenter trial (Egypt) (27) | 96 patients received both HCQ and zinc, 95 received HCQ only | Zinc: 220 mg twice daily for 28 d | HCQ: 400 mg twice daily on the first day, then 200 mg twice daily for 5 d | No significant difference between the 2 groups in terms of the need for MV and the overall mortality rates | Zinc supplements did not enhance the clinical efficacy of HCQ |
| Khan et al., 2020; case report (USA) (21) | Woman, 74-y-old | Zinc sulfate: 220 mg 3 times/d; Continuous intravenous infusion of vitamin C: 11 g per 24 h for 10 d | — | Fewer days on MV (5 d); shorter ICU stay (6 d); Earlier recovery in critical COVID-19 patients | Rapid recovery and shortened length of MV and ICU stay in the patients |
| Thomas et al., 2021; randomized clinical trial (USA) (28) | 214 patients; mean (SD) age of 45.2 (14.6) y and 132 (61.7%) women | 3 groups: Zinc gluconate (50 mg); Ascorbic acid (8000 mg); Both supplements for 10 d | Usual care without supplementation | No significant reduction in primary and secondary endpoints; 50% Symptomatic improvement at a mean (SD) of: 6.7 (4.4) d for the usual care group, 5.5 (3.7) d for the ascorbic acid group, 5.9 (4.9) d for the zinc gluconate group, 5.5 (3.4) d for the group receiving both (overall P = 0.45). | No significant decrease in the duration of symptoms in treatment with high-dose zinc gluconate, ascorbic acid, or a combination of the 2 supplements compared with standard of care |
| Ohaegbulam et al., 2020; clinical case series (USA) (33) | 41-y-old Hispanic man; vitamin D deficient | Ergocalciferol 50,000 IU daily for 5 d | — | On day 5, no fever; ↓CRP; Undetectable concentrations of IL-6; Doubling of serum vitamin D | The higher dose of vitamin D was related to lower lengths of stay and oxygen requirements by day 6 |
| 57-y-old Hispanic woman; vitamin D deficient | Ergocalciferol 50,000 IU daily for 5 d | — | Improvements in the leukocytosis, inflammatory markers; undetectable concentrations of IL-6; more than doubling of vitamin D concentrations | ||
| 74-y-old Hispanic man; vitamin D deficient | Cholecalciferol 1000 IU daily for 5 d | — | Minimal improvement of vitamin D concentrations; ↑CRP, ferritin and ESR concentrations; undetectable IL-6 concentrations; Improved respiratory status | ||
| 53-y-old African-American man; vitamin D deficient | Cholecalciferol 1000 IU daily for 5 d | — | On hospital day 6: minimal increase in vitamin D; a slight decrease in CRP concentrations; ↑Ferritin; Doubling of IL-6 concentrations | ||
| Castillo et al., 2020; pilot randomized clinical study (Spain) (24) | 76 patients (45 men (59%) and 31 women); 50 with 25(OH)D3; 26 without 25(OH)D3; Mean age: 53 ± 10 y | 25(OH)D3: First day: 0.532 mg (21,280 IU) oral; On day 3 and 7: 0.266 mg (10,640 IU), then weekly until discharge or ICU admission | HCQ; azithromycin | 2% of patients in the treatment group required ICU admission with no mortality; all were discharged; 50% of untreated patients required admission to the ICU, 2 patients died and the remaining 11 were discharged | Significant reduction in the need for ICU treatment and disease severity of the patients requiring hospitalization due to proven COVID-19 |
| Annweiler et al., 2020; quasi-experimental study (France) (31) | 77 participants (mean ± SD age: 88 ± 5 y; 49.4% women); Group 1: 29; Group 2: 16; Group 3: 32 | Cholecalciferol: Group 1: 50,000 IU per month, or 80,000 IU or 100,000 IU every 2–3 mo; Group 2: 80,000 IU within a few hours of the diagnosis | Group 3: no vitamin D supplements | Significant longer survival time in group 1 compared with group 3; no difference between groups 2 and 3; ↓ Significant in the risk of OSCI score >5 in group 1 compared with group 3 | Regular bolus vitamin D supplementation was associated with less severe COVID-19 and better survival in frail elderly |
| Giannini et al., 2020; retrospective study (Italy) (36) | Ninety-one patients (aged 74 ± 13 y); 55% were male; 36 patients: cholecalciferol; 55 patients: the best available treatment | Cholecalciferol: 400,000 IU bolus oral cholecalciferol (200,000 IU) in 2 consecutive days | HCQ, glucocorticoids, tocilizumab, lopinavir/ritonavir, azithromycin, and/or other antibiotics | 43 (47.3%) patients experienced the combined endpoint of transfer to ICU and/or death | The positive effect of high-dose cholecalciferol on the combined endpoint was significantly amplified with increasing comorbidity burden |
| Ling et al., 2020; cross-sectional multicenter observational study (UK) (37) | 151 patients received cholecalciferol booster therapy | Cholecalciferol: Different regimens of cholecalciferol booster therapy: 20,000 IU, 40,000 IU, 50,000 IU; for different duration from every 2 wk to daily; for 7 and 14 d | — | Regardless of baseline serum 25(OH)D concentrations, cholecalciferol is associated with a reduced risk of mortality in acute in-patients admitted with COVID-19 | No association between vitamin D status and COVID-19 mortality |
| Rastogi et al., 2020; randomized, placebo-controlled (India) (25) | Forty patients: Intervention group (n = 16), Control group (n = 24) | Cholecalciferol: Daily 60,000 IU cholecalciferol for 7 d | Placebo | Significantly more participants in the intervention group became SARS-CoV-2 RNA negative compared with the placebo group; Significant reduction in fibrinogen unlike other inflammatory biomarkers (D-dimer and CRP) | A greater proportion of vitamin D–deficient individuals turned SARS-CoV-2 RNA negative; Significant decrease in fibrinogen in vitamin D group |
| Murai et al., 2021; multicenter, double-blind, randomized, placebo-controlled trial (Brazil) (26) | 240 hospitalized patients (moderate to severe): supplement group 120; placebo group 120; Mean age: 56.2 ± 14.4 y 43.9% women | Cholecalciferol: A single oral dose of 200,000 IU cholecalciferol | Placebo | No significant difference between the 2 groups in primary and secondary outcomes | A single high dose of cholecalciferol did not make any changes in the supplement group compared with the placebo group. |
| Cereda et al., 2020; Prospective study (Italy) (38) | 324 COVID-19 cases: Vitamin D supplement group 38 (11.7%) | Vitamin D: Mean intake: 58,846 IU/mo | — | — | Supplementation was not associated with either hospitalization or in-hospital mortality; Higher risk of death for supplement users |
| Tan et al., 2020; cohort study (Singapore) (39) | 43 COVID-19 participants aged ≥50 y; 17 patients in DMB; 26 patients in the control group | Cholecalciferol, 1000 IU; oral magnesium, 150 mg; oral vitamin B-12, 500 μg For about 5 d (4–7 d) | — | Fewer patients treated with DMB required initiation of oxygen therapy during their hospitalization compared with the controls | Significant decrease in the proportion of patients with clinical deterioration requiring oxygen support and/or ICU |
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Ordered based on the nutrients assessed in the manuscript. COVID-19, coronavirus disease 2019; CRP, C-reactive protein; DMB, vitamin D, magnesium, and vitamin B-12; ESR, erythrocyte sedimentation rate; HCQ, hydroxychloroquine; HDIVC, high-dose intravenous vitamin C; ICU, intensive care unit; MV, mechanical ventilation; OSCI, Ordinal Scale for Clinical Improvement; PaO2/FiO2, partial pressure of oxygen/fraction of inspired oxygen; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SOFA, Sequential Organ Failure Assessment; 25(OH)D, 25-hydroxyvitamin D; 25(OH)D3, 25-hydroxyvitamin D3.