Zinc for COVID-19: real-time analysis of all 15 studies

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4/14	PEP	Seet et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.04.035 (Peer Reviewed)	severe case, ↓49.7%, p=0.03	Positive impact of oral hydroxychloroquine and povidone-iodine throat spray for COVID-19 prophylaxis: an open-label randomized trial
	Prophylaxis RCT in Singapore with 3,037 low risk patients, showing lower serious cases, lower symptomatic cases, and lower confirmed cases of COVID-19 with all treatments (ivermectin, HCQ, PVP-I, and Zinc + vitamin C) compared to vitamin ..
4/14	Details Source PDF Post Exposure Prophylaxis study Post Exposure Prophylaxis study
	Seet et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.04.035 (Peer Reviewed)
	Positive impact of oral hydroxychloroquine and povidone-iodine throat spray for COVID-19 prophylaxis: an open-label randomized trial
	Prophylaxis RCT in Singapore with 3,037 low risk patients, showing lower serious cases, lower symptomatic cases, and lower confirmed cases of COVID-19 with all treatments (ivermectin, HCQ, PVP-I, and Zinc + vitamin C) compared to vitamin C. Meta-analysis of vitamin C in 6 previous trials shows a benefit of 16%, so the actual benefit of ivermectin, HCQ, and PVP-I may be higher. Cluster RCT with 40 clusters. There were no hospitalizations and no deaths. NCT04446104. risk of COVID-19 severe case, 49.7% lower, RR 0.50, p = 0.03, treatment 33 of 634 (5.2%), control 64 of 619 (10.3%). risk of COVID-19 case, 26.9% lower, RR 0.73, p = 0.03, treatment 300 of 634 (47.3%), control 433 of 619 (70.0%), adjusted, OR converted to RR, model 6.
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2/13	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.
2/13	Details Source PDF Levels Analysis of outcomes based on serum 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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2/12	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 ..
2/12	Details Source PDF Early treatment study Early treatment study
	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]. [1] patrickholford.com/blog/vitamin-c-speeds-up-covid-recovery 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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1/4	Review	Joachimiak et al., PLOS Neglected Tropical Diseases, doi:10.1371/journal.pntd.0008895 (Review) (Peer Reviewed)	review	Zinc against COVID-19? Symptom surveillance and deficiency risk groups
	Literature review concluding that zinc should be included as part of preventative supplementation for COVID-19, in general for support of immune health, and should also be considered in the context of zinc deficiency acquired during a vir..
1/4	Details Source PDF Review Review
	Joachimiak et al., PLOS Neglected Tropical Diseases, doi:10.1371/journal.pntd.0008895 (Review) (Peer Reviewed)
	Zinc against COVID-19? Symptom surveillance and deficiency risk groups
	Literature review concluding that zinc should be included as part of preventative supplementation for COVID-19, in general for support of immune health, and should also be considered in the context of zinc deficiency acquired during a viral infection and host immune response.
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12/30	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 ..
12/30	Details Source PDF Review Review
	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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11/29	Late	Abd-Elsalam et al., Biological Trace Element Research, doi:10.1007/s12011-020-02512-1 (Peer Reviewed)	death, ↓1.0%, p=0.99	Do Zinc Supplements Enhance the Clinical Efficacy of Hydroxychloroquine?: a Randomized, Multicenter Trial
	191 patient RCT in Egypt comparing the addition of zinc to HCQ, not showing a significant difference. Clinical recovery at 28 days was 79.2% in the zinc group and 77.9% control, p = 0.969. Mechanical ventilation was used with 4 patients..
11/29	Details Source PDF Late treatment study Late treatment study
	Abd-Elsalam et al., Biological Trace Element Research, doi:10.1007/s12011-020-02512-1 (Peer Reviewed)
	Do Zinc Supplements Enhance the Clinical Efficacy of Hydroxychloroquine?: a Randomized, Multicenter Trial
	191 patient RCT in Egypt comparing the addition of zinc to HCQ, not showing a significant difference. Clinical recovery at 28 days was 79.2% in the zinc group and 77.9% control, p = 0.969. Mechanical ventilation was used with 4 patients in the zinc group and 6 control. There were 5 deaths in each group. No information on baseline zinc values was recorded. We note that Egypt has a low rate of zinc deficiency so supplementation is less likely to be helpful in Egypt [1, 2] [1] ncbi.nlm.nih.gov/pmc/articles/PMC3510072/ [2] ncbi.nlm.nih.gov/pmc/articles/PMC3510072/bin/pone.0050568.s003.xls risk of death, 1.0% lower, RR 0.99, p = 0.99, treatment 5 of 96 (5.2%), control 5 of 95 (5.3%). risk of mechanical ventilation, 34.0% lower, RR 0.66, p = 0.54, treatment 4 of 96 (4.2%), control 6 of 95 (6.3%). risk of no recovery, 5.8% lower, RR 0.94, p = 0.97, treatment 20 of 96 (20.8%), control 21 of 95 (22.1%). hospitalization time, 3.6% lower, relative time 0.96, p = 0.55, treatment 96, control 95.
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11/18	In Silico	Pormohammad et al., International Journal of Molecular Medicine, doi:10.3892/ijmm.2020.4790 (Peer Reviewed)		Zinc and SARS‑CoV‑2: A molecular modeling study of Zn interactions with RNA‑dependent RNA‑polymerase and 3C‑like proteinase enzymes
	In Silico analysis supporting the hypothesis that Zn would bind and regulate the enzymatic activities of 3CLpro and RdRp of SARS‑CoV-2 and therefore inhibit viral replication. Since Zn has established immune health benefits, is readily av..
11/18	Details Source PDF In Silico In Silico
	Pormohammad et al., International Journal of Molecular Medicine, doi:10.3892/ijmm.2020.4790 (Peer Reviewed)
	Zinc and SARS‑CoV‑2: A molecular modeling study of Zn interactions with RNA‑dependent RNA‑polymerase and 3C‑like proteinase enzymes
	In Silico analysis supporting the hypothesis that Zn would bind and regulate the enzymatic activities of 3CLpro and RdRp of SARS‑CoV-2 and therefore inhibit viral replication. Since Zn has established immune health benefits, is readily available, inexpensive and safe, the authors propose that Zn could help ameliorate COVID-19.
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10/26	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
10/26	Details Source PDF Late treatment study Late treatment study
	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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10/26	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).
10/26	Details Source PDF Levels Analysis of outcomes based on serum levels
	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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10/26	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).
10/26	Details Source PDF Early treatment study Early treatment study
	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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10/20	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.
10/20	Details Source PDF Pre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study
	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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10/11	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.
10/11	Details Source PDF Late treatment study Late treatment study
	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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9/10	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,..
9/10	Details Source PDF Levels Analysis of outcomes based on serum levels
	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. 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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9/7	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.
9/7	Details Source PDF Levels Analysis of outcomes based on serum levels
	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. risk of mechanical 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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7/22	Late	Yao et al., Chest, doi:10.1016/j.chest.2020.06.082 (Peer Reviewed)	death, ↓34.0%, p=0.09	The Minimal Effect of Zinc on the Survival of Hospitalized Patients With COVID-19
	Retrospective 242 hospitalized patients in the USA showing adjusted hazard ratio for zinc treatment, aHR 0.66 [0.41-1.07]. [1] notes that the study would be more informative if baseline serum zinc levels were known.
7/22	Details Source PDF Late treatment study Late treatment study
	Yao et al., Chest, doi:10.1016/j.chest.2020.06.082 (Peer Reviewed)
	The Minimal Effect of Zinc on the Survival of Hospitalized Patients With COVID-19
	Retrospective 242 hospitalized patients in the USA showing adjusted hazard ratio for zinc treatment, aHR 0.66 [0.41-1.07]. [1] notes that the study would be more informative if baseline serum zinc levels were known. [1] ncbi.nlm.nih.gov/pmc/articles/PMC7836617/ risk of death, 34.0% lower, RR 0.66, p = 0.09, treatment 73 of 196 (37.2%), control 21 of 46 (45.7%), adjusted.
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6/6	Late	Finzi et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.06.006 (Peer Reviewed)		Treatment of SARS-CoV-2 with high dose oral zinc salts: A report on four patients
	Case report on 4 patients treated with high dose zinc. All patients experienced significant improvement after one day.
6/6	Details Source PDF Late treatment study Late treatment study
	Finzi et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.06.006 (Peer Reviewed)
	Treatment of SARS-CoV-2 with high dose oral zinc salts: A report on four patients
	Case report on 4 patients treated with high dose zinc. All patients experienced significant improvement after one day.
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5/8	Late	Carlucci et al., J. Med. Microbiol., Sep 15, 2020, doi: 10.1099/jmm.0.001250 (preprint 5/8) (Peer Reviewed)	death/HPC, ↓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..
5/8	Details Source PDF Late treatment study Late treatment study
	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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2010	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..
2010	Details Source PDF In Vitro In Vitro
	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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