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Summary of COVID-19 zinc studies

Studies   Meta Analysis   Hide extended summaries

470 patient zinc early treatment RCT: 30% lower mortality (p=0.27), 38% lower combined mortality/ICU admission (p=0.04), 54% lower ICU admission (p=0.01), and 42% lower need for oxygen therapy (p=0.009).
RCT 470 patients with symptoms ≤7 days, showing significantly lower ICU admission and combined mortality/ICU admission with zinc treatment. Greater benefit was seen for patients treated within 3 days. 25mg elemental zinc bid for 15 days. See also [academic.oup.com] and the author's reply [academic.oup.com].

Nov 2022, Clinical Infectious Diseases, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac807/6795268, https://c19p.org/abdallah

1,253 patient zinc prophylaxis RCT: 50% fewer symptomatic cases (p=0.0007) and 27% fewer cases (p=0.03).
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.

Apr 2021, Int. J. Infectious Diseases, https://www.ijidonline.com/article/S1201-9712(21)00345-3/fulltext, https://c19p.org/seetz

2,028 patient zinc early treatment study: 53% lower mortality (p<0.0001), 64% lower ventilation (p<0.0001), 60% lower ICU admission (p<0.0001), and 58% lower combined mortality/ICU admission (p<0.0001).
Retrospective 2,028 COVID patients in the USA, showing significantly lower mortality, ventilation, ICU admission, and progression to ARDS with zinc use, defined as at least one dose from one week prior to admission to 48 hours after admission.

Dec 2021, Critical Care Medicine, https://journals.lww.com/ccmjournal/Citation/2022/01001/195__ZINC_USE_IS_ASSOCIATED_WITH_IMPROVED_OUTCOMES.161.aspx, https://c19p.org/mayberry

115 patient zinc prophylaxis RCT: 68% fewer symptomatic cases (p=0.36), 5% fewer cases (p=1), and 21% improved viral load (p<0.0001).
Prophylaxis RCT with 59 zinc + doxycycline, 56 doxycycline, and 57 placebo healthcare workers, showing lower symptomatic cases and significantly improved Ct values with the addition of zinc to doxycycline treatment. Doxycycline 100mg/day and zinc 15 mg/day.

Jun 2022, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971222003496, https://c19p.org/stambouli

1,687 patient zinc late treatment study: 65% lower mortality (p<0.0001).
Retrospective 2017 hospitalized patients in India, showing lower mortality with zinc treatment.

Aug 2021, Lung India, https://journals.lww.com/lungindia/Fulltext/2022/01000/Clinical_features,_demography,_and_predictors_of.5.aspx, https://c19p.org/elavarasiz

200 patient zinc prophylaxis study: 85% fewer symptomatic cases (p=0.02).
Prospective study of zinc supplementation with 104 patients randomized to receive 10mg, 25mg, or 50mg of zinc picolinate daily, and a matched sample of 96 control patients from the adjacent clinic that did not routinely recommend/use zinc, showing significantly lower symptomatic COVID-19 with treatment.

Dec 2021, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2021.756707/full, https://c19p.org/gordon

90 patient zinc late treatment RCT: 14% improved recovery (p=0.41).
Early terminated low-risk population (no hospitalization) very late treatment (mean 8 days) RCT with 44 patients treated with vitamin C, D, K, and zinc, and 46 control patients, showing no significant differences. Authors acknowledge that the very late treatment is a major limitation, noting that in an ideal setting, "patients would begin taking therapeutic interventions immediately after noticing symptoms". Authors note that patients already had a low symptom burden at baseline and that "it is likely that the majority of the participants had almost fully recovered before starting treatment." Authors note that most participants were young, had few comorbidities and had excellent self-rated health at baseline, leaving less room for improvement. There was low compliance with completing surveys. Data from only 64% of patients was in the main analysis. Authors claim "high internal validity", but the loss of data was statistically significantly..

Sep 2023, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2023-073761, https://c19p.org/seelyz

zinc prophylaxis study: 40% lower severe cases (p=0.0001).
Retrospective 962 COVID-19 patients in Bangladesh, showing significantly lower severity with vitamin C, vitamin D, and zinc supplementation, and improved results from the combination of all three.

Nov 2022, Nutrients, https://www.mdpi.com/2072-6643/14/23/5029, https://c19p.org/sharifz

932 patient zinc late treatment study: 38% lower combined mortality/hospice (p=0.002), 18% lower ventilation (p=0.4), and 23% lower ICU admission (p=0.17).
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 2020, J. Med. Microbiol., Sep 15, 2020, https://www.microbiologyresearch.org/content/journal/jmm/10.1099/jmm.0.001250, https://c19p.org/carlucciz

518 patient zinc early treatment study: 79% lower mortality (p=0.12) and 82% lower hospitalization (p=0.001).
79% lower mortality and 82% lower hospitalization with early HCQ+AZ+Z. Retrospective 518 patients (141 treated, 377 control).

Jul 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/pii/S0924857920304258, https://c19p.org/derwandz

977 patient zinc late treatment study: 30% shorter hospitalization (p<0.0001).
Retrospective 977 hospitalized patients in Saudi Arabia, showing significantly shorter hospitalization with zinc treatment.

Jun 2022, Healthcare, https://www.mdpi.com/2227-9032/10/7/1201, https://c19p.org/alahmari

33 patient zinc late treatment RCT: 20% lower mortality (p=1).
Small early terminated RCT with 33 hospitalized patients in Australia, 15 treated with zinc, showing no significant difference in clinical outcomes. Treatment increased zinc levels above the deficiency cutoff. Intravenous zinc 0.5mg/kg/day (elemental zinc concentration 0.24mg/kg/day) for up to 7 days. ACTRN12620000454976.

Feb 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.26895, https://c19p.org/patel2

356 patient zinc early treatment study: 97% lower ventilation (p<0.0001), 99% lower hospitalization (p<0.0001), and 100% lower severe cases (p<0.0001).
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.

May 2021, Endocrine Abstracts, https://www.endocrine-abstracts.org/ea/0073/ea0073pep14.2, https://c19p.org/asimiz

101 patient zinc late treatment study: 88% lower mortality (p=0.13), 26% lower ventilation (p=0.75), 3% lower ICU admission (p=1), and 73% lower progression (p=0.004).
Retrospective 101 hospitalized pediatric patients in Saudi Arabia, showing zinc treatment associated with lower respiratory failure and shorter hospitalization in unadjusted results. Patients receiving zinc were older. Authors note elevated serum creatinine and the possibility of kidney injury.

Mar 2023, Saudi Pharmaceutical J., https://www.sciencedirect.com/science/article/pii/S1319016423000415, https://c19p.org/ibrahimalhajjaji

250 patient zinc prophylaxis study: 57% lower severe cases (p=0.03).
Retrospective 250 recovered COVID-19 patients, showing lower risk of severe cases with higher zinc intake.

Mar 2023, Clinical Nutrition ESPEN, https://www.sciencedirect.com/science/article/pii/S2405457723000803, https://c19p.org/asoudehz

3,219 patient zinc late treatment study: 46% lower mortality (p<0.0001).
Retrospective database analysis of 3,219 hospitalized patients in the USA. Very different results in the time period analysis (Table S2), and results significantly different to other studies for the same medications (e.g., heparin OR 3.06 [2.44-3.83]) suggest significant confounding by indication and confounding by time.

Apr 2021, BMJ Open, https://bmjopen.bmj.com/content/11/4/e042042.info, https://c19p.org/mulhemz

20,859 patient zinc prophylaxis study: 100% lower hospitalization (p=0.04).
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.

Jul 2021, Epidemiology and Global Health Microbiology and Infectious Disease, https://elifesciences.org/articles/68165, https://c19p.org/israel2z

3,473 patient zinc late treatment PSM study: 37% lower mortality (p=0.02).
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 2020, Research Square, https://www.researchsquare.com/article/rs-94509/v1, https://c19p.org/frontera2

510 patient zinc prophylaxis study: 60% lower severe cases (p=0.41) and 41% lower hospitalization (p=0.37).
Retrospective 510 patients in Iran, showing lower risk of severity with vitamin D (statistically significant) and zinc (not statistically significant) supplementation. IR.TUMS.VCR.REC.1398.1063.

Aug 2021, J. Family & Reproductive Health, https://europepmc.org/article/PMC/PMC7868648, https://c19p.org/bagheriz

9,267 patient zinc prophylaxis study: 18% lower ventilation (p=0.78) and 30% lower ICU admission (p=0.6).
Retrospective 9,748 COVID-19 patients in the USA showing lower ventilation and ICU admission with zinc prophylaxis, without statistical significance.

Feb 2021, Clinical Pharmacology & Therapeutics, https://onlinelibrary.wiley.com/doi/10.1002/cpt.2376, https://c19p.org/bejanz

20 patient zinc ICU RCT: 33% lower progression (p=1) and 6% shorter ICU admission (p=0.3).
Small RCT in Iran with 20 ICU patients, 10 treated with high-dose vitamin C, melatonin, and zinc, not showing significant differences.

Dec 2020, J. Cellular & Molecular Anesthesia, https://journals.sbmu.ac.ir/jcma/article/view/32182, https://c19p.org/darbanz

738 patient zinc early treatment study: 24% lower hospitalization (p=0.16).
Retrospective survey-based analysis of 738 COVID-19 patients in Saudi Arabia, showing lower hospitalization with vitamin C, turmeric, zinc, and nigella sativa, and higher hospitalization with vitamin D. For vitamin D, most patients continued prophylactic use. For vitamin C, the majority of patients continued prophylactic use. For nigella sativa, the majority of patients started use during infection. Authors do not specify the fraction of prophylactic use for turmeric and zinc.

May 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/18/10/5086, https://c19p.org/aldwihiz

689 patient zinc prophylaxis study: 37% lower IgG positivity (p=0.35).
Retrospective 689 healthcare workers in India, showing no significant difference in IgG positivity with zinc prophylaxis.

Feb 2021, American J. Blood Research, https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8010601/, https://c19p.org/mahtoz

242 patient zinc late treatment study: 34% lower mortality (p=0.09).
Retrospective 242 hospitalized patients in the USA showing adjusted hazard ratio for zinc treatment, aHR 0.66 [0.41-1.07]. [ncbi.nlm.nih.gov] notes that the study would be more informative if baseline serum zinc levels were known.

Jul 2020, Chest, https://journal.chestnet.org/article/S0012-3692(20)31961-9/fulltext, https://c19p.org/yao2

144 patient zinc late treatment study: 41% lower mortality (p=0.41).
Prospective study of 144 hospitalized COVID-19 patients in the DRC and South Sudan, showing lower mortality with zinc treatment, without statistical significance.

Oct 2022, PLOS Global Public Health, https://journals.plos.org/plosone/article?id=10.1371/journal.pgph.0000924, https://c19p.org/doocyz

253 patient zinc prophylaxis study: 47% lower severe cases (p=0.24).
Retrospective survey-based analysis of 349 COVID-19 patients, showing a lower risk of severe cases with vitamin D, zinc, turmeric, and honey prophylaxis in unadjusted analysis, without statistical significance. REC/UG/2020/03.

Feb 2022, Tropical J. Pharmaceutical Research, https://www.tjpr.org/admin/12389900798187/2022_21_2_14.pdf, https://c19p.org/shehabz

191 patient zinc late treatment RCT: 1% lower mortality (p=0.99), 34% lower ventilation (p=0.54), 6% improved recovery (p=0.97), and 4% shorter hospitalization (p=0.55).
191 patient RCT in Egypt comparing the addition of zinc to HCQ, not showing a significant difference. No information on baseline zinc values was recorded. Egypt has a low rate of zinc deficiency so supplementation may be less likely to be helpful [ncbi.nlm.nih.gov, ncbi.nlm.nih.gov]. For several issues with this trial, see [osf.io]. See also [link.springer.com]. The primary outcome was changed from viral clearance to "improvement or mortality" in the last month of the trial. The pre-specified outcome was not reported.

Nov 2020, Biological Trace Element Research, https://link.springer.com/article/10.1007/s12011-020-02512-1, https://c19p.org/abdelsalam2z

zinc prophylaxis study: 31% lower hospitalization (p=0.02).
Analysis of 1,957 older adults showing lower risk of COVID-19 hospitalization with higher dietary zinc intake. Each unit increase in zinc intake was associated with a 31% reduction in the risk of COVID-19 hospitalization after adjustments. A dynamical system model showed that consumption of zinc < 9.7mg per day was associated with a 1.5 times greater risk of COVID-19 infection.

Mar 2024, BMC Nutrition, https://bmcnutr.biomedcentral.com/articles/10.1186/s40795-024-00821-5, https://c19p.org/seifi

246 patient zinc late treatment study: 25% lower mortality (p=0.28).
Retrospective 246 severe COVID-19 patients in Uganda, showing lower mortality with zinc treatment in unadjusted results, without statistical significance.

May 2023, Infection and Drug Resistance, https://www.dovepress.com/thirty-day-outcomes-of-young-and-middle-aged-adults-admitted-with-seve-peer-reviewed-fulltext-article-IDR, https://c19p.org/kyagambiddwaz

135 patient zinc prophylaxis study: 18% lower severe cases (p=1).
Retrospective 448 pregnant women with COVID-19. Patients with calcium, zinc, and magnesium supplementation, or magnesium only, had a significantly higher titer of SARS-CoV-2 anti-RBD antibodies. There was no statistically significant difference in severe cases based on supplementation.

Mar 2022, Nutrients, https://www.mdpi.com/2072-6643/14/7/1445, https://c19p.org/citu

105 patient zinc prophylaxis study: 20% lower mortality (p=0.71).
Case control study of 105 COVID-19 patients in India, 55 with mucormycosis and 50 without, showing zinc prophylaxis and diabetes both associated with mucormycosis in unadjusted results. This is likely confounded because zinc supplementation is commonly used with diabetes [academic.oup.com], and Arora et al. show lower risk of mucormycosis with zinc prophylaxis, aOR 0.05 [0.01–0.19] [Arora]. There was no significant difference in mortality based on zinc prophylaxis in unadjusted results.

Feb 2022, Cureus, https://www.cureus.com/articles/87998-role-of-zinc-and-clinicopathological-factors-for-covid-19-associated-mucormycosis-cam-in-a-rural-hospital-of-central-india-a-case-control-study, https://c19p.org/kumar4

164 patient zinc ICU PSM study: 36% lower mortality (p=0.11), 25% longer ICU admission (p=0.28), and 6% longer hospitalization (p=0.61).
Retrospective 266 ICU patients showing lower mortality with zinc treatment, reaching statistical significance only for 30 day mortality, and lower odds of acute kidney injury, without statistical significance. NRC21R/287/07.

Jun 2021, Critical Care, https://ccforum.biomedcentral.com/articles/10.1186/s13054-021-03785-1, https://c19p.org/alsulaiman

372,720 patient zinc prophylaxis study: 1% fewer cases (p=0.8).
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.

Nov 2020, BMJ Nutrition, Prevention & Health, https://nutrition.bmj.com/content/4/1/149, https://c19p.org/loucaz

152 patient zinc late treatment study: 18% lower mortality (p=0.18).
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 2020, J Clin Anesth., https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369577/, https://c19p.org/krishnanz

428 patient zinc prophylaxis study: 13% lower hospitalization (p=0.83).
Survey of 428 recovered COVID-19 patients in Iraq, showing fewer hospital visits for patients on prophylactic vitamin C or D. Hospitalization was lower for those on vitamin C, D, or zinc, without statistical significance.

Apr 2021, Open Medicine, https://www.degruyter.com/document/doi/10.1515/med-2021-0273/html, https://c19p.org/abdulateefz

15,227 patient zinc prophylaxis study: 7% fewer cases (p=0.77).
Prospective survey-based study with 15,227 people in the UK, showing lower risk of COVID-19 cases with vitamin A, vitamin D, zinc, selenium, probiotics, and inhaled corticosteroids; and higher risk with metformin and vitamin C. Statistical significance was not reached for any of these. Except for vitamin D, the results for treatments we follow were only adjusted for age, sex, duration of participation, and test frequency. NCT04330599. COVIDENCE UK.

Mar 2021, Thorax, https://thorax.bmj.com/content/early/2021/11/02/thoraxjnl-2021-217487, https://c19p.org/holtz

283 patient zinc late treatment study: 41% higher mortality (p=0.33).
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.

Apr 2021, BMJ Open, https://bmjopen.bmj.com/content/11/4/e042549.info, https://c19p.org/gadhiyaz

zinc late treatment study: 16% higher mortality (p=0.003).
Retrospective database analysis of 64,781 hospitalized patients in the USA, showing lower mortality with vitamin C or vitamin D (authors do not distinguish between the two), and higher mortality with zinc and HCQ, statistically significant for zinc. Authors excluded hospital-based outpatient visits, without explanation. Confounding by indication is likely, adjustments do not appear to include any information on COVID-19 severity at baseline.

Dec 2020, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/article-abstract/2773971, https://c19p.org/rosenthalz

8,426 patient zinc prophylaxis study: 12% more cases (p=0.58).
Retrospective 8,426 patients in the USA, showing no significant difference in cases with zinc prophylaxis. Severity results were not reported due to the small number of events.

Oct 2022, Cureus, https://www.cureus.com/articles/119536-does-prophylactic-oral-zinc-reduce-the-risk-of-contracting-covid-19, https://c19p.org/adrean

2,148 patient zinc prophylaxis study: 25% higher hospitalization (p=0.21) and 13% higher severe cases (p=0.46).
Retrospective 2,148 COVID-19 recovered patients in Jordan, showing no significant differences in the risk of severity and hospitalization with zinc prophylaxis.

Feb 2022, Bosnian J. Basic Medical Sciences, https://www.bjbms.org/ojs/index.php/bjbms/article/view/7009, https://c19p.org/nimerz

118 patient zinc ICU study: 81% higher mortality (p=0.44).
Retrospective 118 ICU patients in Saudi Arabia showing no significant differences in unadjusted results with zinc, vitamin D, and favipiravir treatment.

Aug 2021, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034121002495, https://c19p.org/assiriz

108 patient zinc early treatment RCT: 44% higher hospitalization (p=0.72) and 12% faster recovery (p=0.38).
Small 214 low-risk outpatient RCT showing non-statistically significant faster recovery with zinc and with vitamin C. Study performed in the USA where zinc deficiency is relatively uncommon. The zinc dosage is relatively low, 50mg zinc gluconate (7mg elemental zinc), one tenth of that shown to reduce the duration of colds in other studies [patrickholford.com].

Feb 2021, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2776305, https://c19p.org/thomas

30 patient zinc late treatment RCT: 14% higher ventilation (p=1), 14% higher ICU admission (p=1), and 14% higher hospitalization (p=1).
Small RCT of zinc plus resveratrol in COVID-19+ outpatients, showing no significant differences in viral clearance or symptoms. Although the treatment group was older (46.3 vs. 38.5) and had more severe baseline symptoms, they had similar symptomatic recovery by the second week.

Sep 2021, SSRN, https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3934228, https://c19p.org/kaplan
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