Summary of COVID-19 zinc studies
1. Abdallah et al., Twice daily oral zinc in the treatment of patients with Coronavirus Disease-19: A randomized double-blind controlled trial
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 â¤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]. The inpatient/outpatient subgroups in Figure 2 are incorrect and were corrected by the authors in an update [academic.oup.com]. The paper states 'Conflicts of interest: none declared.' However, the funding statement notes the study was funded by Opalia Recordati, the manufacturer of the evaluated treatment. Furthermore one author has the affiliation 'Medical affairs manager, Opalia Recordati'.
Nov 2022, Clinical Infectious Diseases, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac807/6795268, https://c19p.org/abdallah
2. GĂłmez-Zorrilla et al., Zinc adjuvant treatment in SARS-CoV-2: a randomized clinical trial
71 patient zinc late treatment RCT: 76% lower progression (p=0.05) and 40% improved recovery (p=0.08).RCT 71 hospitalized COVID-19 patients showing significantly lower disease progression with zinc treatment. The zinc group also demonstrated shorter mean recovery time and greater WHO scale improvement at day 14. Antibody levels were higher in the standard care group, which may be a result of greater viral replication without treatment. The control arm had a higher baseline median WHO score and higher oxygen use.
Apr 2025, J. Trace Elements in Medicine and Biology, https://www.sciencedirect.com/science/article/pii/S0946672X25001919, https://c19p.org/gomezzorrilla
3. Seet et al., Positive impact of oral hydroxychloroquine and povidone-iodine throat spray for COVID-19 prophylaxis: an open-label randomized trial
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
4. Mayberry et al., Zinc use is associated with improved outcomes in COVID-19: results from the CRUSH-COVID registry
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
5. Stambouli et al., COVID-19 prophylaxis with Doxycycline and Zinc in Health Care Workers: A prospective randomized double-blind clinical tria
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
6. Elavarasi et al., Clinical features, demography, and predictors of outcomes of SARS-CoV-2 infection at a tertiary care hospital in India: A cohort study
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
7. Gordon et al., A Case-Control Study for the Effectiveness of Oral Zinc in the Prevention and Mitigation of COVID-19
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. The treatment group was monitored via telemedicine every 2-3 weeks, whereas the control group was a retrospective cohort checked via front-desk questionnaires, introducing ascertainment bias. The reported p-value of 0.999 for cardiovascular disease in Table 1 is incorrect. In Table 2, the number of missing values for HgbA1c in the treatment group is reported as 132, which is larger than the group size.
Dec 2021, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2021.756707/full, https://c19p.org/gordon
8. Seely et al., Dietary supplements to reduce symptom severity and duration in people with SARS-CoV-2: a double-blind randomised controlled trial
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
9. Sharif et al., Impact of Zinc, Vitamins C and D on Disease Prognosis among Patients with COVID-19 in Bangladesh: A Cross-Sectional Study
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. Table 2 has a typographical error where the columns for Vitamin C and Vitamin D are duplicates. The OR for "Taking vitamin C, D and zinc as medication" in Table 4 is likely a typo, with the point estimate outside the CI. The study aims to evaluate the risk of infection by comparing COVID-19 PCR-positive patients to a control group of suspected patients who had close contact and symptoms but were PCR-negative, however this introduces selection bias. These estimates are likely to be less reliable and are excluded in our analysis.
Nov 2022, Nutrients, https://www.mdpi.com/2072-6643/14/23/5029, https://c19p.org/sharifz
10. Carlucci et al., Zinc sulfate in combination with a zinc ionophore may improve outcomes in hospitalized COVID-19 patients
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. Medical Microbiology, https://www.microbiologyresearch.org/content/journal/jmm/10.1099/jmm.0.001250, https://c19p.org/carlucciz
11. Patel et al., A pilot double-blind safety and feasibility randomized controlled trial of high-dose intravenous zinc in hospitalized COVID-19 patients
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. In Table 1, lactate for the HDIVZn group is reported as 0.661 +/- 2.1 with a range of 0.8-2.9. The mean (0.661) cannot logically be lower than the minimum value of the range (0.8). Furthermore, the maximum possible SD for a range of 0.8-2.9 is approximately 1.05, making an SD of 2.1 impossible. A similar error exists for the control group. The mean and standard deviation values may have been swapped.
Feb 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.26895, https://c19p.org/patel2
12. Asimi et al., Selenium, zinc, and vitamin D supplementation affect the clinical course of COVID-19 infection in Hashimotoâs thyroiditis
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
13. Ibrahim Alhajjaji et al., Effect of zinc supplementation on symptom reduction and length of hospital stay among pediatric patients with Coronavirus Disease 2019 (COVID-19)
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. Authors claim that zinc administration is associated with elevated serum creatinine and potential kidney injury. However, serum creatinine naturally increases with age and muscle mass in children. Given the zinc group was older, this difference is biologically expected and within normal limits. In Section 3.4, the text states that administering zinc lowered the incidence of 'insomnia' (4.5% vs 26.3%, p=0.004). However, Table 4 reports these percentages for 'anosmia'.
Mar 2023, Saudi Pharmaceutical J., https://www.sciencedirect.com/science/article/pii/S1319016423000415, https://c19p.org/ibrahimalhajjaji
14. Milan et al., Factors Associated with Adverse Outcomes among SARS-CoV-2 Positive Children in a Tertiary Government COVID-19 Referral Hospital in the Philippines
180 patient zinc late treatment study: 56% lower mortality (p=0.09), 13% lower ventilation (p=0.67), and 10% lower ICU admission (p=0.84).Retrospective 180 hospitalized pediatric COVID-19 patients in the Philippines showing lower mortality with vitamin D and zinc, and higher mortality with remdesivir, all without statistical significance. Remdesivir was given to few patients and authors do not provide information on the timing of treatment - confounding by indication may be significant. Table 6 presents an adjusted Cox proportional hazards regression model that includes 14 categorical variables (accounting for ~15 degrees of freedom), suggesting significant risk of overfitting. The study concludes that corticosteroid use is independently associated with an 8.21 times increased hazard of mortality. However, corticosteroids are routinely administered as a standard of care to patients who are clinically deteriorating. Attempting to adjust for this using an overfitted baseline 'severity' variable is likely to be inadequate. The observed association is more likely to be driven by confounding by indication (sicker patients..
Apr 2024, Acta Medica Philippina, https://actamedicaphilippina.upm.edu.ph/index.php/acta/article/view/8392, https://c19p.org/milan
15. Asoudeh et al., The association between dietary intakes of zinc, vitamin C and COVID-19 severity and related symptoms: A cross-sectional study
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
16. Mulhem et al., 3219 hospitalised patients with COVID-19 in Southeast Michigan: a retrospective case cohort study
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
17. Israel et al., Identification of drugs associated with reduced severity of COVID-19: A case-control study in a large population
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
18. Derwand et al., COVID-19 Outpatients â Early Risk-Stratified Treatment with Zinc Plus Low Dose Hydroxychloroquine and Azithromycin: A Retrospective Case Series Study
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). The study compares outcomes with untreated patients in the same community without detailed baseline data or adjustment. In Table 3, the number of patients with reported days since onset of symptoms for Group B is listed as 25 out of a total N=48. The calculated percentage provided in the table is 48%, but should be 52%.
Jul 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/pii/S0924857920304258, https://c19p.org/derwandz
19. Frontera et al., Treatment with Zinc is Associated with Reduced In-Hospital Mortality Among COVID-19 Patients: A Multi-Center Cohort Study
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
20. Alahmari et al., Factors Associated with Length of Hospital Stay among COVID-19 Patients in Saudi Arabia: A Retrospective Study during the First Pandemic Wave
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. In Table 2, every 'GLM Estimate' matches the unadjusted mathematical difference between the raw means of the two groups (e.g., mechanical ventilation: 12.78 - 8.17 = 4.61). Authors claimed to perform a multivariate GLM but appear to have reported unadjusted univariate differences. Table 1 reports 80% of the cohort as Female (n=783) and 20% as Male (n=194). However, the standard errors in Table 2 suggest that these may be reversed.
Jun 2022, Healthcare, https://www.mdpi.com/2227-9032/10/7/1201, https://c19p.org/alahmari
21. Bagheri et al., Supplement Usage Pattern in a Group of COVID-19 Patients in Tehran
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
22. Bejan et al., DrugWAS: Drugâwide Association Studies for COVIDâ19 Drug Repurposing
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
23. Frontera et al., A prospective study of long-term outcomes among hospitalized COVID-19 patients with and without neurological complications
382 patient zinc late treatment study: 33% lower long COVID (p=0.07).Prospective study of 382 hospitalized COVID-19 patients in New York City, showing significantly worse 6-month functional outcomes, activities of daily living, and return to work with neurological complications during initial hospitalization. In Section 3.1, the text states '170/304 (56%) had limited activities of daily living (Barthel <100)'. However, Table 3 shows the abnormal counts are 82/156 and 52/148, which sum to 134/304 (44%). 170 is actually the number of patients with NORMAL ADLs (304-134=170). In Table 3, under 'Abnormal MOCA (<18)', the neurologic group is reported as '55 (46%)' out of N=101. However, 55/101 is 54.5%. The Control group is reported as '51 (55%)' out of N=114. However, 51/114 is 44.7%. Authors appear to have swapped the percentages. Section 3.1 states '47% (81/154) of those working pre-morbidly were unable to return to work'. However, Table 3 shows that 81 (30+51) is the total number of patients who did return to work (81/154 = 52.6%). The number unable to..
Jul 2021, J. the Neurological Sciences, https://www.sciencedirect.com/science/article/pii/S0022510X21001805, https://c19p.org/frontera3
24. Aldwihi et al., Patientsâ Behavior Regarding Dietary or Herbal Supplements before and during COVID-19 in Saudi Arabia
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
25. Mahto et al., Seroprevalence of IgG against SARS-CoV-2 and its determinants among healthcare workers of a COVID-19 dedicated hospital of India
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
28. Shehab et al., Immune-boosting effect of natural remedies and supplements on progress of, and recovery from COVID-19 infection
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
29. Seifi et al., Dietary mineral intakes predict Coronavirus-disease 2019 (COVID-19) incidence and hospitalization in older adults
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. The dietary mineral intakes were collected using a Food Frequency Questionnaire (FFQ) between 2007-2010 during the first phase of the MASHAD study. This data was used to predict COVID-19 incidence and hospitalization between 2020-2022. A gap of 10 to 15 years introduces confounding, as dietary habits may change significantly over time.
Mar 2024, BMC Nutrition, https://bmcnutr.biomedcentral.com/articles/10.1186/s40795-024-00821-5, https://c19p.org/seifi
30. Kyagambiddwa et al., Thirty-Day Outcomes of Young and Middle-Aged Adults Admitted with Severe COVID-19 in Uganda: A Retrospective Cohort Study
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
31. Louca et al., Modest effects of dietary supplements during the COVID-19 pandemic: insights from 445 850 users of the COVID-19 Symptom Study app
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
32. Krishnan et al., Clinical comorbidities, characteristics, and outcomes of mechanically ventilated patients in the State of Michigan with SARS-CoV-2 pneumonia
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. Clinical Anesthesia, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369577/, https://c19p.org/krishnanz
33. Al Sulaiman et al., Evaluation of Zinc Sulfate as an Adjunctive Therapy in COVID-19 Critically Ill Patients: a Two Center Propensity-score Matched Study
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 164 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. Results are subject to immortal time bias: patients in the zinc group received the intervention at variable times during their ICU stay, requiring them to survive long enough to receive it, while control patients only needed to survive 24 hours to be included.
Jun 2021, Critical Care, https://ccforum.biomedcentral.com/articles/10.1186/s13054-021-03785-1, https://c19p.org/alsulaiman
34. Abdulateef et al., COVID-19 severity in relation to sociodemographics and vitamin D use
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. The study observes that patients taking prophylactic vitamins C and D for less than 1 week had a higher proportion of hospital visits compared to those taking them for more than 2 weeks. This fails to account for protopathic bias: patients feeling the early onset of COVID-19 symptoms likely initiated supplement use right before diagnosis, placing them in the '<1 week' category with a higher baseline severity trajectory.
Apr 2021, Open Medicine, https://www.degruyter.com/document/doi/10.1515/med-2021-0273/html, https://c19p.org/abdulateefz
35. Holt et al., Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK)
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.
Mar 2021, Thorax, https://thorax.bmj.com/content/early/2021/11/02/thoraxjnl-2021-217487, https://c19p.org/holtz
36. Adrean et al., Does Prophylactic Oral Zinc Reduce the Risk of Contracting COVID-19?
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. Authors report 'Of the COVID-19-positive patients, 30 routinely took AREDS2 vitamins, while 80 did not take AREDS2 vitamins. Those who took the AREDS2 vitamins did not differ significantly in age, sex, or past ocular history (Table 1).' This claim of similarity appears to only apply to the COVID-19 positive patients. Authors do not provide baseline characteristics of the two exposure cohorts (2,111 AREDS2 users vs. 6,315 non-users). Lack of multivariate adjustment for critical confounders: This is a retrospective observational study comparing COVID-19 rates based on AREDS2 vitamin usage. AREDS2 is indicated for Age-Related Macular Degeneration (AMD), meaning the treatment group is likely to be older. Authors acknowledge that older patients may isolate more, yet they only used a crude 2x2 chi-square test to..
Oct 2022, Cureus, https://www.cureus.com/articles/119536-does-prophylactic-oral-zinc-reduce-the-risk-of-contracting-covid-19, https://c19p.org/adrean
37. Gadhiya et al., Clinical characteristics of hospitalised patients with COVID-19 and the impact on mortality: a single-network, retrospective cohort study from Pennsylvania state
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
38. Rosenthal et al., Risk Factors Associated With In-Hospital Mortality in a US National Sample of Patients With COVID-19
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
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]. The 'both' (combination) treatment group had much higher rates of diabetes (29.3% vs 6.0% in SOC), hypertension (46.6% vs 28.0%), and dyslipidemia (41.4% vs 18.0%), yet the statistical analysis did not adjust for these major confounders. This likely biased the results against the active treatment arm and undermined the futility stopping criteria. The treatment groups were also older, with the combination group mean age of 48.7 vs. 42 for the control group. The reported mean 'Time to 50% reduction' in Table 2 appears to only include patients who successfully achieved the reduction, effectively excluding the worst outcomes ..
Feb 2021, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2776305, https://c19p.org/thomas
40. Nimer et al., The impact of vitamin and mineral supplements usage prior to COVID-19 infection on disease severity and hospitalization
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
41. Kaplan et al., ReszinateâA Phase 1/2 Randomized Clinical Trial of Zinc and Resveratrol Utilizing Home Patient-Obtained Nasal and Saliva Viral Sampling
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. The SSRN manuscript ID is "EBIOM-D-21-03006," which is EBioMedicine's submission numbering format, suggesting that the paper may have been rejected by EBioMedicine and published elswhere. The treatment group had a much wider age range (20-73) compared to the placebo group (18-55), leading to a significant difference in variance (Levene's test p=0.002). While acknowledged by the authors, this baseline asymmetry suggests randomization did not fully balance the groups in this small cohort. Although the authors performed a post-hoc adjustment for age, the imbalance in a very small sample size limits the robustness of the findings. Co-author JDG reports receiving research support, grants, and personal..
Sep 2021, Frontiers in Drug Discovery, https://www.frontiersin.org/journals/drug-discovery/articles/10.3389/fddsv.2022.910124/full, https://c19p.org/kaplan