Abstract: Treatment with Zinc is Associated with Reduced In-Hospital Mortality Among COVID-19 Patients: A Multi-Center Cohort Study Jennifer A. frontera (  jennifer.frontera@nyulangone.org ) NYU Langone Health https://orcid.org/0000-0002-0719-2522 Joseph O. Rahimian NYU Langone Health Shadi Yaghi NYU Langone Health Mengling Liu NYU Langone Health Ariane Lewis NYU Langone Health Adam de Havenon University of Utah Health Shraddha Mainali Ohio State University Foundation: The Ohio State University Joshua Huang NYU Langone Health Erica Scher NYU Langone Health Thomas Wisniewski NYU Langone Health Andrea B. Troxel NYU Langone Health Sharon Meropol NYU Langone Health Laura J. Balcer NYU Langone Health Steven L. Galetta NYU Langone Health Research article Keywords: Zinc, ionophore, treatment, mortality, COVID-19, SARS-CoV-2 DOI: https://doi.org/10.21203/rs.3.rs-94509/v1 License:   This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/10 Abstract 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..