Zinc for COVID-19: real-time analysis of all 31 studies

Home

Database of all zinc COVID-19 studies. Submit updates/corrections.

Search:

Restrict: All Early Late Levels


Aug 12	Late	Elavarasi et al., medRxiv, doi:10.1101/2021.08.10.21261855 (Preprint)	death, ↓65.1%, p<0.0001	Clinical features, demography and predictors of outcomes of SARS-CoV-2 infection in a tertiary care hospital in India - a cohort study
	Details Retrospective 2017 hospitalized patients in India, showing lower mortality with zinc treatment.
Aug 12	Details Source PDF Late treatment study Late treatment study
	Elavarasi et al., medRxiv, doi:10.1101/2021.08.10.21261855 (Preprint)
	Clinical features, demography and predictors of outcomes of SARS-CoV-2 infection in a tertiary care hospital in India - a cohort study
	Retrospective 2017 hospitalized patients in India, showing lower mortality with zinc treatment. risk of death, 65.1% lower, RR 0.35, p < 0.001, treatment 486, control 1201, adjusted, OR converted to RR, model 4, multivariate logistic regression, control prevalence approximated with overall prevalence. Elavarasi et al., 8/12/2021, retrospective, India, South Asia, preprint, 26 authors.
	Share Tweet Submit Corrections or Comments
Jul 27	PrEP	Israel et al., Epidemiology and Global Health Microbiology and Infectious Disease, doi:10.7554/eLife.68165 (Peer Reviewed)	hosp., ↓>99.9%, p=0.04	Identification of drugs associated with reduced severity of COVID-19: A case-control study in a large population
	Details Case control study examining medication usage with a healthcare database in Israel, showing lower risk of hospitalization with calcium + zinc supplements (defined as being picked up within 35 days prior to PCR+), however only 10 patients ..
Jul 27	Details Source PDF Pre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study
	Israel et al., Epidemiology and Global Health Microbiology and Infectious Disease, doi:10.7554/eLife.68165 (Peer Reviewed)
	Identification of drugs associated with reduced severity of COVID-19: A case-control study in a large population
	Case control study examining medication usage with a healthcare database in Israel, showing lower risk of hospitalization with calcium + zinc supplements (defined as being picked up within 35 days prior to PCR+), however only 10 patients took the supplements. Other patients may have acquired supplements outside of the healthcare system. risk of hospitalization, >99.9% lower, RR <0.001, p = 0.04, treatment 0 of 10 (0.0%), control 6953 of 20849 (33.3%), OR converted to RR, continuity correction due to zero event, PCR+, cohort 2. Israel et al., 7/27/2021, retrospective, Israel, Middle East, peer-reviewed, 10 authors, this trial uses multiple treatments in the treatment arm (combined with calcium) - results of individual treatments may vary.
	Share Tweet Submit Corrections or Comments
Jul 6	PrEP	Margolin et al., Journal of Evidence-Based Integrative Medicine, doi:10.1177/2515690X211026193 (Peer Reviewed)	cases, ↓94.4%, p=0.003	20-Week Study of Clinical Outcomes of Over-the-Counter COVID-19 Prophylaxis and Treatment
	Details Retrospective 113 outpatients, 53 (patient choice) treated with zinc, quercetin, vitamin C/D/E, l-lysine, and Quina, showing lower cases with treatment.
Jul 6	Details Source PDF Pre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study
	Margolin et al., Journal of Evidence-Based Integrative Medicine, doi:10.1177/2515690X211026193 (Peer Reviewed)
	20-Week Study of Clinical Outcomes of Over-the-Counter COVID-19 Prophylaxis and Treatment
	Retrospective 113 outpatients, 53 (patient choice) treated with zinc, quercetin, vitamin C/D/E, l-lysine, and Quina, showing lower cases with treatment. risk of COVID-19 case, 94.4% lower, RR 0.06, p = 0.003, treatment 0 of 53 (0.0%), control 9 of 60 (15.0%), continuity correction due to zero event. risk of COVID-19 or flu-like illness, 81.1% lower, RR 0.19, p = 0.01, treatment 2 of 53 (3.8%), control 12 of 60 (20.0%). Margolin et al., 7/6/2021, retrospective, USA, North America, peer-reviewed, 5 authors, this trial uses multiple treatments in the treatment arm (combined with quercetin, vitamin C/D/E, l-lysine, and Quina) - results of individual treatments may vary.
	Share Tweet Submit Corrections or Comments
Jun 24	Levels	Beigmohammadi et al., Nutrition, doi:10.1016/j.nut.2021.111400 (Peer Reviewed)		The association between serum levels of micronutrients and the severity of disease in patients with COVID-19
	Details Retrospective 60 ICU patients in Iran, showing that lower levels of vitamin D, magnesium, and zinc were significantly associated with higher APACHE scores (P = 0.001, 0.028, and <0.001, respectively) and higher lung involvement (P = 0.002..
Jun 24	Details Source PDF Levels Analysis of outcomes based on serum levels
	Beigmohammadi et al., Nutrition, doi:10.1016/j.nut.2021.111400 (Peer Reviewed)
	The association between serum levels of micronutrients and the severity of disease in patients with COVID-19
	Retrospective 60 ICU patients in Iran, showing that lower levels of vitamin D, magnesium, and zinc were significantly associated with higher APACHE scores (P = 0.001, 0.028, and <0.001, respectively) and higher lung involvement (P = 0.002, 0.045, and <0.001, respectively). Beigmohammadi et al., 6/24/2021, retrospective, Iran, Middle East, peer-reviewed, 8 authors.
	Share Tweet Submit Corrections or Comments
Jun 20	Late	Notz et al., Nutrients, doi:10.3390/nu13062113 (Peer Reviewed)		Clinical Significance of Micronutrient Supplementation in Critically Ill COVID-19 Patients with Severe ARDS
	Details Retrospective 22 ICU patients, showing most patients had low selenium status biomarkers and low zinc levels, and reporting on treatment with nutrient supplementation including selenium and zinc. Authors conclude that sufficient selenium a..
Jun 20	Details Source PDF Late treatment study Late treatment study
	Notz et al., Nutrients, doi:10.3390/nu13062113 (Peer Reviewed)
	Clinical Significance of Micronutrient Supplementation in Critically Ill COVID-19 Patients with Severe ARDS
	Retrospective 22 ICU patients, showing most patients had low selenium status biomarkers and low zinc levels, and reporting on treatment with nutrient supplementation including selenium and zinc. Authors conclude that sufficient selenium and zinc levels may be important for an adequate immune response in critically ill patients with severe COVID-19 ARDS. Notz et al., 6/20/2021, retrospective, Germany, Europe, peer-reviewed, 13 authors.
	Share Tweet Submit Corrections or Comments
Jun 15	In Vitro	Panchariya et al., bioRxiv, doi:10.1101/2021.06.15.448551 (Preprint) (In Vitro)	in vitro	Zinc2+ ion inhibits SARS-CoV-2 main protease and viral replication in vitro
	Details In Silico and In Vitro study showing that ionic zinc inhibits SARS-CoV-2 main protease (Mpro) and inhibits viral replication. Zinc acetate inhibited viral replication in Vero E6 cells, while zinc glycinate and zinc gluconate did not at n..
Jun 15	Details Source PDF In Vitro In Vitro
	Panchariya et al., bioRxiv, doi:10.1101/2021.06.15.448551 (Preprint) (In Vitro)
	Zinc2+ ion inhibits SARS-CoV-2 main protease and viral replication in vitro
	In Silico and In Vitro study showing that ionic zinc inhibits SARS-CoV-2 main protease (Mpro) and inhibits viral replication. Zinc acetate inhibited viral replication in Vero E6 cells, while zinc glycinate and zinc gluconate did not at non-toxic concentrations. The combination of zinc acetate with zinc ionophore quercetin signficantly improved inhibition at low concentrations. Panchariya et al., 6/15/2021, preprint, 14 authors.
	Share Tweet Submit Corrections or Comments
Jun 12	Levels	Verschelden et al., medRxiv, doi:10.1101/2021.06.09.21258271 (Preprint)		Plasma zinc status and hyperinflammatory syndrome in hospitalized COVID-19 patients: an observational study
	Details Prospective study of 139 hospitalized COVID-19 patients, showing 96% had zinc deficiency. Higher zinc levels were associated with a shorter length of hospitalization. Mortality and ventilation was lower with higher zinc levels, but not re..
Jun 12	Details Source PDF Levels Analysis of outcomes based on serum levels
	Verschelden et al., medRxiv, doi:10.1101/2021.06.09.21258271 (Preprint)
	Plasma zinc status and hyperinflammatory syndrome in hospitalized COVID-19 patients: an observational study
	Prospective study of 139 hospitalized COVID-19 patients, showing 96% had zinc deficiency. Higher zinc levels were associated with a shorter length of hospitalization. Mortality and ventilation was lower with higher zinc levels, but not reaching statistical significance. Verschelden et al., 6/12/2021, preprint, 8 authors.
	Share Tweet Submit Corrections or Comments
Jun 7	Late	Al Sulaiman et al., Research Square, doi:10.21203/rs.3.rs-572942/v1 (Preprint)	death, ↓35.0%, p=0.05	Evaluation of Zinc Sulfate as an Adjunctive Therapy in COVID-19 Critically Ill Patients: a Two Center Propensity-score Matched Study
	Details Retrospective 266 ICU patients showing lower mortality with zinc treatment (very close to statistical significance), and higher odds of acute kidney injury.
Jun 7	Details Source PDF Late treatment study Late treatment study
	Al Sulaiman et al., Research Square, doi:10.21203/rs.3.rs-572942/v1 (Preprint)
	Evaluation of Zinc Sulfate as an Adjunctive Therapy in COVID-19 Critically Ill Patients: a Two Center Propensity-score Matched Study
	Retrospective 266 ICU patients showing lower mortality with zinc treatment (very close to statistical significance), and higher odds of acute kidney injury. risk of death, 35.0% lower, RR 0.65, p = 0.05, treatment 35 of 130 (26.9%), control 45 of 129 (34.9%), adjusted, 30 day, PSM, multivariable Cox proportional hazards. risk of mechanical ventilation, 23.0% lower, RR 0.77, p = 0.52, treatment 20 of 57 (35.1%), control 23 of 54 (42.6%), adjusted, among non-mechanically ventilated patients within 24 hours of ICU admission. Al Sulaiman et al., 6/7/2021, retrospective, propensity score matching, Saudi Arabia, Middle East, preprint, 10 authors.
	Share Tweet Submit Corrections or Comments
May 22	Early	Asimi et al., Endocrine Abstracts, doi:10.1530/endoabs.73.PEP14.2 (Preprint)	ventilation, ↓97.4%, p<0.0001	Selenium, zinc, and vitamin D supplementation affect the clinical course of COVID-19 infection in Hashimoto’s thyroiditis
	Details Retrospective 356 Hashimoto's thyroiditis outpatients, 270 taking vitamin D, zinc, and selenium, showing significantly lower hospitalization with treatment. Authors adjust for age, gender, BMI, and smoking status, reporting statistically ..
May 22	Details Source PDF Early treatment study Early treatment study
	Asimi et al., Endocrine Abstracts, doi:10.1530/endoabs.73.PEP14.2 (Preprint)
	Selenium, zinc, and vitamin D supplementation affect the clinical course of COVID-19 infection in Hashimoto’s thyroiditis
	Retrospective 356 Hashimoto's thyroiditis outpatients, 270 taking vitamin D, zinc, and selenium, showing significantly lower hospitalization with treatment. Authors adjust for age, gender, BMI, and smoking status, reporting statistically significant associations with p<0.001 for hospitalization and mechanical ventilation, however they do not report the adjusted risks. risk of mechanical ventilation, 97.4% lower, RR 0.03, p < 0.001, treatment 0 of 270 (0.0%), control 9 of 86 (10.5%), continuity correction due to zero event, unadjusted. risk of hospitalization, 99.0% lower, RR 0.010, p < 0.001, treatment 0 of 270 (0.0%), control 24 of 86 (27.9%), continuity correction due to zero event, unadjusted. risk of COVID-19 severe case, 99.5% lower, RR 0.005, p < 0.001, treatment 0 of 270 (0.0%), control 51 of 86 (59.3%), continuity correction due to zero event, unadjusted. Asimi et al., 5/22/2021, retrospective, Bosnia and Herzegovina, Europe, preprint, 3 authors, this trial uses multiple treatments in the treatment arm (combined with vitamin D and selenium) - results of individual treatments may vary.
	Share Tweet Submit Corrections or Comments
May 3	Levels	Fromonot et al., Clinical Nutrition, doi:10.1016/j.clnu.2021.04.042 (Peer Reviewed)	hosp., ↓89.2%, p=0.002	Hypozincemia in the early stage of COVID-19 is associated with an increased risk of severe COVID-19
	Details Analysis of 240 consecutive patients in France, showing significantly higher zinc deficiency in COVID-19 patients, and significantly greater risk of hospitalization for COVID-19 patients with zinc deficiency. 2020PI087.
May 3	Details Source PDF Levels Analysis of outcomes based on serum levels
	Fromonot et al., Clinical Nutrition, doi:10.1016/j.clnu.2021.04.042 (Peer Reviewed)
	Hypozincemia in the early stage of COVID-19 is associated with an increased risk of severe COVID-19
	Analysis of 240 consecutive patients in France, showing significantly higher zinc deficiency in COVID-19 patients, and significantly greater risk of hospitalization for COVID-19 patients with zinc deficiency. 2020PI087. risk of hospitalization, 89.2% lower, RR 0.11, p = 0.002, treatment 6 of 110 (5.5%), control 7 of 42 (16.7%), OR converted to RR, within COVID-19 patients. risk of COVID-19 case, 27.6% lower, RR 0.72, p = 0.003, treatment 110 of 188 (58.5%), control 42 of 52 (80.8%). Fromonot et al., 5/3/2021, prospective, France, Europe, peer-reviewed, 6 authors.
	Share Tweet Submit Corrections or Comments
Apr 15	Levels	Skalny et al., Metabolites, doi:10.3390/metabo11040244 (Peer Reviewed)		Serum Zinc, Copper, and Other Biometals Are Associated with COVID-19 Severity Markers
	Details Analysis of serum metal levels in 150 COVID-19 patients and 44 controls, finding that COVID-19 severity was associated with lower serum Ca, Fe, Se, Zn levels when compared to controls.
Apr 15	Details Source PDF Levels Analysis of outcomes based on serum levels
	Skalny et al., Metabolites, doi:10.3390/metabo11040244 (Peer Reviewed)
	Serum Zinc, Copper, and Other Biometals Are Associated with COVID-19 Severity Markers
	Analysis of serum metal levels in 150 COVID-19 patients and 44 controls, finding that COVID-19 severity was associated with lower serum Ca, Fe, Se, Zn levels when compared to controls. Skalny et al., 4/15/2021, peer-reviewed, 14 authors.
	Share Tweet Submit Corrections or Comments
Apr 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
	Details 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 ..
Apr 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. Seet et al., 4/14/2021, Cluster Randomized Controlled Trial, Singapore, Asia, peer-reviewed, 15 authors, this trial compares with another treatment - results may be better when compared to placebo.
	Share Tweet Submit Corrections or Comments
Apr 8	Late	Gadhiya et al., BMJ Open, doi:10.1136/bmjopen-2020-042549 (Peer Reviewed)	death, ↑40.9%, p=0.33	Clinical characteristics of hospitalised patients with COVID-19 and the impact on mortality: a single-network, retrospective cohort study from Pennsylvania state
	Details Retrospective 283 patients in the USA showing higher mortality with all treatments (not statistically significant). Confounding by indication is likely. In the supplementary appendix, authors note that the treatments were usually given fo..
Apr 8	Details Source PDF Late treatment study Late treatment study
	Gadhiya et al., BMJ Open, doi:10.1136/bmjopen-2020-042549 (Peer Reviewed)
	Clinical characteristics of hospitalised patients with COVID-19 and the impact on mortality: a single-network, retrospective cohort study from Pennsylvania state
	Retrospective 283 patients in the USA showing higher mortality with all treatments (not statistically significant). Confounding by indication is likely. In the supplementary appendix, authors note that the treatments were usually given for patients that required oxygen therapy. Oxygen therapy and ICU admission (possibly, the paper includes ICU admission for model 2 in some places but not others) were the only variables indicating severity used in adjustments. risk of death, 40.9% higher, RR 1.41, p = 0.33, treatment 21 of 54 (38.9%), control 34 of 229 (14.8%), adjusted, OR converted to RR, multivariate logistic regression. Gadhiya et al., 4/8/2021, retrospective, USA, North America, peer-reviewed, 4 authors.
	Share Tweet Submit Corrections or Comments
Feb 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?
	Details Retrospective 275 patients showing zinc levels significantly lower in patients with poor outcomes, 840 vs. 970 µg/L, p< 0.0001.
Feb 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. Dubourg et al., 2/13/2021, peer-reviewed, 8 authors.
	Share Tweet Submit Corrections or Comments
Feb 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
	Details 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 ..
Feb 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. Thomas et al., 2/12/2021, Randomized Controlled Trial, USA, North America, peer-reviewed, 11 authors.
	Share Tweet Submit Corrections or Comments
Jan 7	Review	Sethuram et al., Reproductive Sciences, doi:10.1007/s43032-020-00400-6 (Review) (Peer Reviewed)	review	Potential Role of Zinc in the COVID-19 Disease Process and its Probable Impact on Reproduction
	Details Review of zinc deficiency and supplementation for COVID-19, including potential impacts on reproductive health.
Jan 7	Details Source PDF Review Review
	Sethuram et al., Reproductive Sciences, doi:10.1007/s43032-020-00400-6 (Review) (Peer Reviewed)
	Potential Role of Zinc in the COVID-19 Disease Process and its Probable Impact on Reproduction
	Review of zinc deficiency and supplementation for COVID-19, including potential impacts on reproductive health. Sethuram et al., 1/7/2021, peer-reviewed, 3 authors.
	Share Tweet Submit Corrections or Comments
Jan 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
	Details 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..
Jan 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. Joachimiak et al., 1/4/2021, peer-reviewed, 1 author.
	Share Tweet Submit Corrections or Comments
Dec 30 2020	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)
	Details 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 ..
Dec 30 2020	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. McCullough et al., 12/30/2020, peer-reviewed, 58 authors.
	Share Tweet Submit Corrections or Comments
Dec 23 2020	Levels	Gonçalves et al., Nutrition in Clinical Practice, doi:10.1002/ncp.10612 (Peer Reviewed)	severe case, ↓82.3%, p<0.001	Association Between Low Zinc Levels and Severity of Acute Respiratory Distress Syndrome by New Coronavirus SARS-CoV-2
	Details Retrospective 169 ICU patients in Brazil, 214 with low zinc levels, showing an association between low zinc levels and severe ARDS. CAAE 30608,020.9.0000.8114.
Dec 23 2020	Details Source PDF Levels Analysis of outcomes based on serum levels
	Gonçalves et al., Nutrition in Clinical Practice, doi:10.1002/ncp.10612 (Peer Reviewed)
	Association Between Low Zinc Levels and Severity of Acute Respiratory Distress Syndrome by New Coronavirus SARS-CoV-2
	Retrospective 169 ICU patients in Brazil, 214 with low zinc levels, showing an association between low zinc levels and severe ARDS. CAAE 30608,020.9.0000.8114. risk of COVID-19 severe case, 82.3% lower, RR 0.18, p < 0.001, treatment 7 of 55 (12.7%), control 145 of 214 (67.8%), adjusted, OR converted to RR, ≥70 μg/dL, logistic regression. Gonçalves et al., 12/23/2020, retrospective, Brazil, South America, peer-reviewed, 9 authors.
	Share Tweet Submit Corrections or Comments
Dec 15 2020	Late	Darban et al., Journal of Cellular & Molecular Anesthesia, doi:10.22037/jcma.v6i2.32182 (Peer Reviewed)	progression, ↓33.3%, p=1.00	Efficacy of High Dose Vitamin C, Melatonin and Zinc in Iranian Patients with Acute Respiratory Syndrome due to Coronavirus Infection: A Pilot Randomized Trial
	Details Small RCT in Iran with 20 ICU patients, 10 treated with high-dose vitamin C, melatonin, and zinc, not showing significant differences. IRCT20151228025732N52.
Dec 15 2020	Details Source PDF Late treatment study Late treatment study
	Darban et al., Journal of Cellular & Molecular Anesthesia, doi:10.22037/jcma.v6i2.32182 (Peer Reviewed)
	Efficacy of High Dose Vitamin C, Melatonin and Zinc in Iranian Patients with Acute Respiratory Syndrome due to Coronavirus Infection: A Pilot Randomized Trial
	Small RCT in Iran with 20 ICU patients, 10 treated with high-dose vitamin C, melatonin, and zinc, not showing significant differences. IRCT20151228025732N52. risk of disease progression, 33.3% lower, RR 0.67, p = 1.00, treatment 2 of 10 (20.0%), control 3 of 10 (30.0%). ICU time, 6.0% lower, relative time 0.94, p = 0.30, treatment 10, control 10. Darban et al., 12/15/2020, Randomized Controlled Trial, Iran, Middle East, peer-reviewed, 8 authors, this trial uses multiple treatments in the treatment arm (combined with melatonin and vitamin C) - results of individual treatments may vary.
	Share Tweet Submit Corrections or Comments
Nov 30 2020	PrEP	Louca et al., BMJ Nutrition, Prevention & Health, doi:10.1136/bmjnph-2021-000250 (preprint 11/30/20) (Peer Reviewed)	cases, ↓0.9%, p=0.80	Modest effects of dietary supplements during the COVID-19 pandemic: insights from 445 850 users of the COVID-19 Symptom Study app
	Details Survey analysis of dietary supplements showing no significant difference in PCR+ cases with zinc usage. These results are for PCR+ cases only, they do not reflect potential benefits for reducing the severity of cases. A number of biases c..
Nov 30 2020	Details Source PDF Pre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study
	Louca et al., BMJ Nutrition, Prevention & Health, doi:10.1136/bmjnph-2021-000250 (preprint 11/30/20) (Peer Reviewed)
	Modest effects of dietary supplements during the COVID-19 pandemic: insights from 445 850 users of the COVID-19 Symptom Study app
	Survey analysis of dietary supplements showing no significant difference in PCR+ cases with zinc usage. These results are for PCR+ cases only, they do not reflect potential benefits for reducing the severity of cases. A number of biases could affect the results, for example users of the app may not be representative of the general population, and people experiencing symptoms may be more likely to install and use the app. risk of COVID-19 case, 0.9% lower, RR 0.99, p = 0.80, OR converted to RR, United Kingdom, all adjustment model. Louca et al., 11/30/2020, retrospective, United Kingdom, Europe, peer-reviewed, 26 authors.
	Share Tweet Submit Corrections or Comments
Nov 29 2020	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
	Details 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..
Nov 29 2020	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. Abd-Elsalam et al., 11/29/2020, Randomized Controlled Trial, Egypt, Africa, peer-reviewed, 10 authors.
	Share Tweet Submit Corrections or Comments
Nov 18 2020	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
	Details 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..
Nov 18 2020	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. Pormohammad et al., 11/18/2020, peer-reviewed, 3 authors.
	Share Tweet Submit Corrections or Comments
Oct 26 2020	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
	Details 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
Oct 26 2020	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. Frontera et al., 10/26/2020, retrospective, propensity score matching, USA, North America, preprint, median age 64.0, 14 authors, this trial uses multiple treatments in the treatment arm (combined with HCQ) - results of individual treatments may vary.
	Share Tweet Submit Corrections or Comments
Oct 26 2020	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
	Details Retrospective 120 hospitalized patients showing zinc deficiency associated with higher ICU admission.
Oct 26 2020	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 higher ICU admission. risk of death, 44.8% lower, RR 0.55, p = 0.23, treatment 5 of 31 (16.1%), control 26 of 89 (29.2%), ≥84 mcg/dL. 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%), ≥84 mcg/dL. Berrocal et al., 10/26/2020, retrospective, Spain, Europe, preprint, 7 authors.
	Share Tweet Submit Corrections or Comments
Oct 26 2020	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
	Details 79% lower mortality and 82% lower hospitalization with early HCQ+AZ+Z. Retrospective 518 patients (141 treated, 377 control).
Oct 26 2020	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. Derwand et al., 10/26/2020, retrospective, USA, North America, peer-reviewed, 3 authors.
	Share Tweet Submit Corrections or Comments
Oct 20 2020	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
	Details 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.
Oct 20 2020	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. Heller et al., 10/20/2020, peer-reviewed, 14 authors.
	Share Tweet Submit Corrections or Comments
Oct 11 2020	Levels	Vogel-González et al., Nutrients, doi:10.3390/nu13020562 (preprint 10/11/2020) (Peer Reviewed)	death, ↓77.2%, p=0.0005	Low Zinc Levels at Admission Associates with Poor Clinical Outcomes in SARS-CoV-2 Infection
	Details Retrospective 249 PCR+ hospitalized patients in Spain, 58 with zinc levels on admission <50 μg/dL, showing higher mortality and ICU admission, and slower recovery with low zinc levels.
Oct 11 2020	Details Source PDF Levels Analysis of outcomes based on serum levels
	Vogel-González et al., Nutrients, doi:10.3390/nu13020562 (preprint 10/11/2020) (Peer Reviewed)
	Low Zinc Levels at Admission Associates with Poor Clinical Outcomes in SARS-CoV-2 Infection
	Retrospective 249 PCR+ hospitalized patients in Spain, 58 with zinc levels on admission <50 μg/dL, showing higher mortality and ICU admission, and slower recovery with low zinc levels. risk of death, 77.2% lower, RR 0.23, p < 0.001, treatment 9 of 191 (4.7%), control 12 of 58 (20.7%), ≥50 μg/dL. risk of ICU admission, 71.3% lower, RR 0.29, p < 0.001, treatment 34 of 191 (17.8%), control 36 of 58 (62.1%), ≥50 μg/dL. recovery time, 68.0% lower, relative time 0.32, p < 0.001, treatment 191, control 58, ≥50 μg/dL. Vogel-González et al., 10/11/2020, retrospective, Spain, Europe, peer-reviewed, 16 authors.
	Share Tweet Submit Corrections or Comments
Sep 10 2020	Levels	Jothimani (Peer Reviewed)	death, ↓89.7%, p=0.06	COVID-19: Poor outcomes in patients with zinc deficiency
	Details 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,..
Sep 10 2020	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. Jothimani et al., 9/10/2020, prospective, India, South Asia, peer-reviewed, 11 authors.
	Share Tweet Submit Corrections or Comments
Sep 7 2020	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
	Details 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.
Sep 7 2020	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. Yasui et al., 9/7/2020, retrospective, Japan, Asia, peer-reviewed, 10 authors.
	Share Tweet Submit Corrections or Comments
Jul 22 2020	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
	Details 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.
Jul 22 2020	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, multivariate Cox regression. Yao et al., 7/22/2020, retrospective, USA, North America, peer-reviewed, 9 authors.
	Share Tweet Submit Corrections or Comments
Jul 20 2020	Late	Krishnan et al., J Clin Anesth., doi:10.1016/j.jclinane.2020.110005 (Peer Reviewed)	death, ↓17.6%, p=0.18	Clinical comorbidities, characteristics, and outcomes of mechanically ventilated patients in the State of Michigan with SARS-CoV-2 pneumonia
	Details Retrospective 152 mechanically ventilated patients in the USA showing unadjusted lower mortality with vitamin C, vitamin D, HCQ, and zinc treatment, statistically significant only for vitamin C.
Jul 20 2020	Details Source PDF Late treatment study Late treatment study
	Krishnan et al., J Clin Anesth., doi:10.1016/j.jclinane.2020.110005 (Peer Reviewed)
	Clinical comorbidities, characteristics, and outcomes of mechanically ventilated patients in the State of Michigan with SARS-CoV-2 pneumonia
	Retrospective 152 mechanically ventilated patients in the USA showing unadjusted lower mortality with vitamin C, vitamin D, HCQ, and zinc treatment, statistically significant only for vitamin C. risk of death, 17.6% lower, RR 0.82, p = 0.18, treatment 31 of 58 (53.4%), control 61 of 94 (64.9%). Krishnan et al., 7/20/2020, retrospective, USA, North America, peer-reviewed, 13 authors.
	Share Tweet Submit Corrections or Comments
Jun 6 2020	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
	Details Case report on 4 patients treated with high dose zinc. All patients experienced significant improvement after one day.
Jun 6 2020	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. Finzi et al., 6/6/2020, peer-reviewed, 1 author.
	Share Tweet Submit Corrections or Comments
May 8 2020	Late	Carlucci et al., J. Med. Microbiol., Sep 15, 2020, doi: 10.1099/jmm.0.001250 (preprint 5/8) (Peer Reviewed)	death/HPC, ↓37.7%, p=0.002	Zinc sulfate in combination with a zinc ionophore may improve outcomes in hospitalized COVID-19 patients
	Details Retrospective 932 patients showing that the addition of zinc to HCQ+AZ reduced mortality / transfer to hospice, ICU admission, and the need for ventilation.
May 8 2020	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 showing that the addition of zinc to HCQ+AZ reduced mortality / transfer to hospice, ICU admission, and the need for ventilation. risk of combined death/hospice, 37.7% lower, RR 0.62, p = 0.002, treatment 54 of 411 (13.1%), control 119 of 521 (22.8%), adjusted, OR converted to RR, multivariate logistic regression. risk of mechanical ventilation, 18.0% lower, RR 0.82, p = 0.40, treatment 29 of 411 (7.1%), control 62 of 521 (11.9%), adjusted, OR converted to RR, multivariate logistic regression. risk of ICU admission, 23.5% lower, RR 0.77, p = 0.17, treatment 38 of 411 (9.2%), control 82 of 521 (15.7%), adjusted, OR converted to RR, multivariate logistic regression. Carlucci et al., 5/8/2020, retrospective, USA, North America, peer-reviewed, 6 authors.
	Share Tweet Submit Corrections or Comments
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
	Details 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. te Velthuis et al., 1/1/2010, peer-reviewed, 6 authors.
	Share Tweet Submit Corrections or Comments

Please send us corrections, updates, or comments. Vaccines and treatments are both extremely valuable and complementary. All practical, effective, and safe means should be used. Elimination of COVID-19 is a race against viral evolution. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. Denying the efficacy of any method increases the risk of COVID-19 becoming endemic; and increases mortality, morbidity, and collateral damage. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. Treatment protocols for physicians are available from the FLCCC.

Thanks for your feedback! Please search before submitting papers and note that studies are listed under the date they were first available, which may be the date of an earlier preprint.

Submit