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0 0.5 1 1.5 2+ Mortality 37% Improvement Relative Risk Mortality (b) 24% Zinc for COVID-19  Frontera et al.  LATE TREATMENT Is late treatment with zinc + HCQ beneficial for COVID-19? PSM retrospective 3,473 patients in the USA Lower mortality with zinc + HCQ (p=0.015) Frontera et al., Research Square, October 2020 Favors zinc Favors control

Treatment with Zinc is Associated with Reduced In-Hospital Mortality Among COVID-19 Patients: A Multi-Center Cohort Study

Frontera et al., Research Square, doi:10.21203/
Oct 2020  
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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
This study includes HCQ and zinc.
risk of death, 37.0% lower, HR 0.63, p = 0.01, treatment 121 of 1,006 (12.0%), control 424 of 2,467 (17.2%), NNT 19, adjusted per study, PSM.
risk of death, 24.0% lower, HR 0.76, p = 0.02, treatment 121 of 1,006 (12.0%), control 424 of 2,467 (17.2%), NNT 19, adjusted per study, regression.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Frontera et al., 26 Oct 2020, retrospective, propensity score matching, USA, 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.
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This PaperZincAll
Treatment with Zinc is Associated with Reduced In-Hospital Mortality Among COVID-19 Patients: A Multi-Center Cohort Study
Jennifer A Frontera, Joseph O Rahimian, Shadi Yaghi, Mengling Liu, Ariane Lewis, Adam De Havenon, Shraddha Mainali, Joshua Huang, Erica Scher, Thomas Wisniewski, Andrea B Troxel, Sharon Meropol, Laura J Balcer, Steven L Galetta
Background: Zinc impairs replication of RNA viruses such as SARS-CoV-1, and may be effective against SARS-CoV-2. However, to achieve adequate intracellular zinc levels, administration with an ionophore, which increases intracellular zinc levels, may be necessary. We evaluated the impact of zinc with an ionophore (Zn+ionophore) on COVID-19 in-hospital mortality rates. Methods: A multicenter cohort study was conducted of 3,473 adult hospitalized patients with reverse-transcriptase-polymerase-chain-reaction (RT-PCR) positive SARS-CoV-2 infection admitted to four New York City hospitals between March 10 through May 20, 2020. Exclusion criteria were: death or discharge within 24h, comfort-care status, clinical trial enrollment, treatment with an IL-6 inhibitor or remdesivir. Patients who received Zn+ionophore were compared to patients who did not using multivariable time-dependent cox proportional hazards models for time to in-hospital death adjusting for confounders including age, sex, race, BMI, diabetes, week of admission, hospital location, sequential organ failure assessment (SOFA) score, intubation, acute renal failure, neurological events, treatment with corticosteroids, azithromycin or lopinavir/ritonavir and the propensity score of receiving Zn+ionophore. A sensitivity analysis was performed using a propensity score-matched cohort of patients who did or did not receive Zn+ionophore matched by age, sex and ventilator status. Results: Among 3,473 patients (median age 64, 1947 [56%] male, 522 [15%] ventilated, 545[16%] died), 1,006 (29%) received Zn+ionophore. Zn+ionophore was associated with a 24% reduced risk of in-hospital mortality (12% of those who received Zn+ionophore died versus 17% who did not; adjusted Hazard Ratio [aHR] 0.76, 95% CI 0.60-0.96, P=0.023). More patients who received Zn+ionophore were discharged home (72% Zn+ionophore vs 67% no Zn+ionophore, P=0.003) Neither Zn nor the ionophore alone were associated with decreased mortality rates. Propensity scorematched sensitivity analysis (N=1356) validated these results (Zn+ionophore aHR for mortality 0.63, 95%CI 0.44-0.91, P=0.015). There were no signi cant interactions for Zn+ionophore with other COVID-19 speci c medications. Conclusions: Zinc with an ionophore was associated with increased rates of discharge home and a 24% reduced risk of in-hospital mortality among COVID-19 patients, while neither zinc alone nor the ionophore alone reduced mortality. Further randomized trials are warranted. Summery In this study of 3,473 hospitalized COVID-19 patients, treatment with zinc and an ionophore was associated with a 24% reduced risk of in-hospital mortality in multivariable Cox regression analysis. A sensitivity analysis in a propensity score-matched cohort supported this nding.
Figure 2 Forest plot of subgroups evaluating the impact of treatment with zinc plus an ionophore on in-hospital mortality Supplementary Files This is a list of supplementary les associated with this preprint. Click to download. SupplementaryAppendixZincBMCID.docx
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Late treatment
is less effective
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