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Levels |
Dubourg et al., Journal of Microbiology, Immunology and Infection, doi:10.1016/j.jmii.2021.01.012 (Peer Reviewed) |
Low blood zinc concentrations in patients with poor clinical outcome during SARS-CoV-2 infection: is there a need to supplement with Zinc COVID-19 patients? |
| Retrospective 275 patients showing zinc levels significantly lower in patients with poor outcomes, 840 vs. 970 µg/L, p< 0.0001. |
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Sufficiency
Analysis of outcomes based on serum sufficiency
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| Dubourg et al., Journal of Microbiology, Immunology and Infection, doi:10.1016/j.jmii.2021.01.012 (Peer Reviewed) |
| Low blood zinc concentrations in patients with poor clinical outcome during SARS-CoV-2 infection: is there a need to supplement with Zinc COVID-19 patients? |
Retrospective 275 patients showing zinc levels significantly lower in patients with poor outcomes, 840 vs. 970 µg/L, p< 0.0001.
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Early |
Thomas et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2021.0369 (Peer Reviewed) |
recov. time, ↓11.9%, p=0.38 |
Effect of High-Dose Zinc and Ascorbic Acid Supplementation vs Usual Care on Symptom Length and Reduction Among Ambulatory Patients With SARS-CoV-2 Infection: The COVID A to Z Randomized Clinical Trial |
| Small 214 low-risk outpatient RCT showing non-statistically significant faster recovery with zinc and with vitamin C. The zinc dosage appears low, 50mg zinc glcuonate (7mg elemental zinc). Study performed in the USA where zinc deficiency .. |
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Early treatment study
Early treatment study
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| Thomas et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2021.0369 (Peer Reviewed) |
| Effect of High-Dose Zinc and Ascorbic Acid Supplementation vs Usual Care on Symptom Length and Reduction Among Ambulatory Patients With SARS-CoV-2 Infection: The COVID A to Z Randomized Clinical Trial |
Small 214 low-risk outpatient RCT showing non-statistically significant faster recovery with zinc and with vitamin C. The zinc dosage appears low, 50mg zinc glcuonate (7mg elemental zinc). Study performed in the USA where zinc deficiency is relatively uncommon. NCT04342728.The dose of zinc is a tenth of that shown to reduce duration of colds in other studies [1].
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recovery time, 11.9% lower, relative time 0.88, p = 0.38, treatment 58, control 50, mean time to a 50% reduction in symptoms, p value approximated with combined p value in study.
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Review |
McCullough et al., Reviews in Cardiovascular Medicine, doi:10.31083/j.rcm.2020.04.264 (Review) (Peer Reviewed) |
review |
Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19) |
| Review urging early treatment of COVID-19 with sequential multidrug treatment that has been shown to be safe and effective. Proposed treatment includes zinc, vitamin D & C, quercetin, and depending on age, comorbidities, and symptoms may .. |
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Review
Review
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| McCullough et al., Reviews in Cardiovascular Medicine, doi:10.31083/j.rcm.2020.04.264 (Review) (Peer Reviewed) |
| Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19) |
| Review urging early treatment of COVID-19 with sequential multidrug treatment that has been shown to be safe and effective. Proposed treatment includes zinc, vitamin D & C, quercetin, and depending on age, comorbidities, and symptoms may include >=2 of HCQ, ivermectin, favipiravir; AZM/DOXY; corticosteroids; colchicine; bamlanivimab; aspirin; LMWH; and supplemental oxygen.
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Late |
Frontera et al., Research Square, doi:10.21203/rs.3.rs-94509/v1 (Preprint) |
death, ↓37.0%, p=0.01 |
Treatment with Zinc is Associated with Reduced In-Hospital Mortality Among COVID-19 Patients: A Multi-Center Cohort Study |
| Retrospective 3,473 hospitalized patients showing 37% lower mortality with HCQ+zinc.
PSM aHR 0.63, p=0.015
regression aHR 0.76, p = 0.023 |
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Late treatment study
Late treatment study
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| Frontera et al., Research Square, doi:10.21203/rs.3.rs-94509/v1 (Preprint) |
| Treatment with Zinc is Associated with Reduced In-Hospital Mortality Among COVID-19 Patients: A Multi-Center Cohort Study |
Retrospective 3,473 hospitalized patients showing 37% lower mortality with HCQ+zinc.PSM aHR 0.63, p=0.015
regression aHR 0.76, p = 0.023
risk of death, 37.0% lower, RR 0.63, p = 0.01, treatment 121 of 1006 (12.0%), control 424 of 2467 (17.2%), adjusted, PSM.
risk of death, 24.0% lower, RR 0.76, p = 0.02, treatment 121 of 1006 (12.0%), control 424 of 2467 (17.2%), adjusted, regression.
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Levels |
Berrocal et al., Research Square, doi:10.21203/rs.3.rs-95524/v1 (Preprint) |
death, ↓44.8%, p=0.23 |
Zinc and Vitamin A Deficiency Predisposes to the Need for Intubation and ICU Admission in Patients With COVID-19. An Observational Study |
| Retrospective 120 hospitalized patients showing zinc deficiency associated with a higher ICU admission rate (61.8% vs.29%; p = 0.002) and a higher rate of intubation (87.5% vs. 12.5%; p = 0.002). |
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Sufficiency
Analysis of outcomes based on serum sufficiency
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| Berrocal et al., Research Square, doi:10.21203/rs.3.rs-95524/v1 (Preprint) |
| Zinc and Vitamin A Deficiency Predisposes to the Need for Intubation and ICU Admission in Patients With COVID-19. An Observational Study |
Retrospective 120 hospitalized patients showing zinc deficiency associated with a higher ICU admission rate (61.8% vs.29%; p = 0.002) and a higher rate of intubation (87.5% vs. 12.5%; p = 0.002).
risk of death, 44.8% lower, RR 0.55, p = 0.23, treatment 5 of 31 (16.1%), control 26 of 89 (29.2%).
risk of ICU admission, 53.0% lower, RR 0.47, p = 0.003, treatment 9 of 31 (29.0%), control 55 of 89 (61.8%).
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Early |
Derwand et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106214 (preprint 7/3) (Peer Reviewed) |
death, ↓79.4%, p=0.12 |
COVID-19 Outpatients – Early Risk-Stratified Treatment with Zinc Plus Low Dose Hydroxychloroquine and Azithromycin: A Retrospective Case Series Study |
| 79% lower mortality and 82% lower hospitalization with early HCQ+AZ+Z. Retrospective 518 patients (141 treated, 377 control). |
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Early treatment study
Early treatment study
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| Derwand et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106214 (preprint 7/3) (Peer Reviewed) |
| COVID-19 Outpatients – Early Risk-Stratified Treatment with Zinc Plus Low Dose Hydroxychloroquine and Azithromycin: A Retrospective Case Series Study |
79% lower mortality and 82% lower hospitalization with early HCQ+AZ+Z. Retrospective 518 patients (141 treated, 377 control).
risk of death, 79.4% lower, RR 0.21, p = 0.12, treatment 1 of 141 (0.7%), control 13 of 377 (3.4%), OR converted to RR.
risk of hospitalization, 81.6% lower, RR 0.18, p < 0.001, treatment 4 of 141 (2.8%), control 58 of 377 (15.4%), OR converted to RR.
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PrEP |
Heller et al., Redox Biology, doi:10.1016/j.redox.2020.101764 (Peer Reviewed) |
Prediction of Survival Odds in COVID-19 by Zinc, Age and Selenoprotein P as Composite Biomarker |
| Analysis of 35 COVID-19 patients showing a significant correlation for serum zinc levels between COVID-19 patients and controls, and between COVID-19 survivors and non-survivors. |
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Pre-Exposure Prophylaxis study
Pre-Exposure Prophylaxis study
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| Heller et al., Redox Biology, doi:10.1016/j.redox.2020.101764 (Peer Reviewed) |
| Prediction of Survival Odds in COVID-19 by Zinc, Age and Selenoprotein P as Composite Biomarker |
Analysis of 35 COVID-19 patients showing a significant correlation for serum zinc levels between COVID-19 patients and controls, and between COVID-19 survivors and non-survivors.
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Late |
Vogel-González et al., medRxiv, doi:10.1101/2020.10.07.20208645 (Preprint) |
Low zinc levels at clinical admission associates with poor outcomes in COVID-19 |
| Shows a correlation between serum zinc levels and COVID-19 outcome. Almost all patients received HCQ. |
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Late treatment study
Late treatment study
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| Vogel-González et al., medRxiv, doi:10.1101/2020.10.07.20208645 (Preprint) |
| Low zinc levels at clinical admission associates with poor outcomes in COVID-19 |
| Shows a correlation between serum zinc levels and COVID-19 outcome. Almost all patients received HCQ.
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Levels |
Jothimani (Peer Reviewed) |
death, ↓89.7%, p=0.06 |
COVID-19: Poor outcomes in patients with zinc deficiency |
| Prospective study of zinc levels in 47 hospitalized COVID-19 patients and 45 healthy controls. COVID-19 patients had significantly lower zinc levels (74.5 vs. 105.8 median μg/dl, p < 0.001). 57.4% of COVID-19 patients were zinc deficient,.. |
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Sufficiency
Analysis of outcomes based on serum sufficiency
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| Jothimani (Peer Reviewed) |
| COVID-19: Poor outcomes in patients with zinc deficiency |
Prospective study of zinc levels in 47 hospitalized COVID-19 patients and 45 healthy controls. COVID-19 patients had significantly lower zinc levels (74.5 vs. 105.8 median μg/dl, p < 0.001). 57.4% of COVID-19 patients were zinc deficient, and they had higher rates of complications, ARDS, prolonged hospital stay, and increased mortality.
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risk of death, 89.7% lower, RR 0.10, p = 0.06, treatment 0 of 20 (0.0%), control 5 of 27 (18.5%), continuity correction due to zero event.
risk of ICU admission, 92.4% lower, RR 0.08, p = 0.02, treatment 0 of 20 (0.0%), control 7 of 27 (25.9%), continuity correction due to zero event.
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Levels |
Yasui et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.09.008 (Peer Reviewed) |
ventilation, ↓92.5%, p=0.001 |
Analysis of the predictive factors for a critical illness of COVID-19 during treatment － relationship between serum zinc level and critical illness of COVID-19 |
| Retrospective 62 hospitalized patients, 29 with serum zinc data, showing significantly lower serum zinc levels for severe COVID-19 cases (intubation) compared with mild and moderate cases, p = 0.005. Authors recommend zinc supplementation. |
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Sufficiency
Analysis of outcomes based on serum sufficiency
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| Yasui et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.09.008 (Peer Reviewed) |
| Analysis of the predictive factors for a critical illness of COVID-19 during treatment － relationship between serum zinc level and critical illness of COVID-19 |
Retrospective 62 hospitalized patients, 29 with serum zinc data, showing significantly lower serum zinc levels for severe COVID-19 cases (intubation) compared with mild and moderate cases, p = 0.005. Authors recommend zinc supplementation.
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risk of ventilation, 92.5% lower, RR 0.08, p = 0.001, treatment 1 of 20 (5.0%), control 6 of 9 (66.7%), zinc >= 70μg/dL.
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Late |
Carlucci et al., J. Med. Microbiol., Sep 15, 2020, doi: 10.1099/jmm.0.001250 (preprint 5/8) (Peer Reviewed) |
death/hospice, ↓37.8%, p=0.002 |
Zinc sulfate in combination with a zinc ionophore may improve outcomes in hospitalized COVID-19 patients |
| Retrospective 932 patients. Addition of Zinc to HCQ+AZ reduces mortality / transfer to hospice, ICU admission, and the need for ventilation.
Reduction in mortality or transfer to hospice adjusted odds ratio OR 0.56, p = 0.002; increase i.. |
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Late treatment study
Late treatment study
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| Carlucci et al., J. Med. Microbiol., Sep 15, 2020, doi: 10.1099/jmm.0.001250 (preprint 5/8) (Peer Reviewed) |
| Zinc sulfate in combination with a zinc ionophore may improve outcomes in hospitalized COVID-19 patients |
Retrospective 932 patients. Addition of Zinc to HCQ+AZ reduces mortality / transfer to hospice, ICU admission, and the need for ventilation.Reduction in mortality or transfer to hospice adjusted odds ratio OR 0.56, p = 0.002; increase in being discharged home, adjusted OR 1.53, p = 0.008.
risk of combined death/hospice, 37.8% lower, RR 0.62, p = 0.002, treatment 411, control 521, OR converted to RR.
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In Vitro |
te Velthuis et al., PLOS Pathogens 2010, 6:11, doi:10.1371/journal.ppat.1001176 (Peer Reviewed) (In Vitro) |
in vitro |
Zn2+ Inhibits Coronavirus and Arterivirus RNA Polymerase Activity In Vitro and Zinc Ionophores Block the Replication of These Viruses in Cell Culture |
| Shows that the combination of Zn2+ and a zinc ionophore (pyrithione) at low concentrations inhibits the replication of SARS-CoV and equine arteritis virus (EAV) in cell culture. Recommends further study of the use of zinc-ionophores as an.. |
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In Vitro
In Vitro
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| te Velthuis et al., PLOS Pathogens 2010, 6:11, doi:10.1371/journal.ppat.1001176 (Peer Reviewed) (In Vitro) |
| Zn2+ Inhibits Coronavirus and Arterivirus RNA Polymerase Activity In Vitro and Zinc Ionophores Block the Replication of These Viruses in Cell Culture |
| Shows that the combination of Zn2+ and a zinc ionophore (pyrithione) at low concentrations inhibits the replication of SARS-CoV and equine arteritis virus (EAV) in cell culture. Recommends further study of the use of zinc-ionophores as antiviral compounds.
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