TABLE 2.

Overview of the interventional studies included in the systematic review.

Study (year)	Location	Sample size (male/female)	Mean age (years)	Design	Intervention	Control	Main findings	Study quality a
Vitamin C
Zhang et al. (2021)	China	56 (36/20)	67	Parallel double‐blind randomized controlled trial	24 g/d IV vitamin C for 7 days	Matched placebo	↔ IMVFD28, ↓ Mortality, ↔ Length of hospitalization, ↔ Disease complications, ↔ SOFA, ↑ PaO2/FiO2, ↓ IL‐6, ↔ MAP, ↓ TBIL, ↔ WBC, ↔ PCT, ↔ CRP, ↔ Cr, ↔ BUN, ↔ PT	Positive
Hiedra et al. (2020)	USA	17 (10/7)	64	Pre‐post trial	3 g/d IV vitamin C for 3 days	–	↓ D‐dimer, ↓ Ferritin, ↔ FiO2	Neutral
Vitamin D
Castillo et al. (2020)	Spain	76 (45/31)	53	Parallel randomized controlled trial	Oral calcifediol with dose of 0.532 mg at hospital admission, 0.266 mg on 3th and 7th day, and 0.266 mg/wk until discharge or ICU admission	Control group	↓ ICU admission	Positive
Annweiler, Corvaisier et al. (2020)	France	77 (39/38)	88	Quasi‐experimental trial	Oral vitamin D3 with dose of 50,000 IU/mo or 80,000–100,000 IU/2–3 mo over the preceding year 80,000 IU oral vitamin D3 after COVID‐19 diagnosis	Control group	↓ Mortality, ↓ OSCI, ↑ Survival ↔ Mortality, ↔ OSCI, ↔ Survival	Neutral
Rastogi et al. (2022)	India	40 (20/20)	49	Parallel randomized controlled trial	60,000 IU/d oral vitamin D3 for 7 days	Matched placebo	↓ Fibrinogen, ↔ D‐dimer, ↔ CRP, ↔ PCT, ↔ Ferritin	Positive
Annweiler, Hanotte, et al. (2020)	France	66 (15/51)	88	Quasi‐experimental trial	80,000 IU oral vitamin D3 either in the week following the suspicion or diagnosis of COVID‐19 or during the previous month	Control group	↓ Mortality, ↓ OSCI, ↑ Survival	Neutral
Zinc
Yao et al. (2021)	USA	242 (138/104)	68	Quasi‐experimental trial	100 mg/d oral elemental zinc	Control group	↔ Mortality, ↔ Survival	Neutral
Derwand et al. (2020)	USA	518 (NR)	58	Quasi‐experimental trial	50 mg/d oral elemental zinc with 400 mg/d hydroxychloroquine and 500 mg/d azithromycin for 5 days	Control group	↓ Hospitalization, ↔ Mortality	Neutral
Carlucci et al. (2020)	USA	932 (584/348)	62	Quasi‐experimental trial	100 mg/d oral elemental zinc for 5 days	Control group	↔ Length of hospitalization, ↓ ICU admission, ↓ Ventilation requirement, ↔ Oxygen flow rate, ↔ FiO2, ↑ Discharged home	Neutral

Note: ↓, decrease; ↑, increase; ↔, no difference.

Abbreviations: BUN, blood urea nitrogen; Cr, creatinine; CRP, C‐reactive protein; d, day; FiO₂, fraction of inspired oxygen; ICU, intensive care unit; IL‐6, interleukin‐6; IMVFD28, invasive mechanical ventilation‐free days in 28 days; IV, intravenous; MAP, mean arterial pressure; mo, month; NR, not reported; OSCI, ordinal scale for clinical improvement; PaO₂, arterial oxygen partial pressure; PCT, procalcitonin; PT, prothrombin time; SOFA, sequential organ failure assessment; TBIL, total bilirubin; WBC, white blood cell count; wk, week.

^a Based on the Academy of Nutrition and Dietetics Quality Criteria Checklist (QCC) for Primary Research.