Treatment with Zinc is Associated with Reduced In-Hospital Mortality Among COVID-19 Patients: A Multi-Center Cohort Study
et al., Research Square, doi:10.21203/rs.3.rs-94509/v1, Oct 2020
Retrospective 3,473 hospitalized patients showing higher mortality with azithromycin, without statistical significance. Authors note the removal of azithromycin from the treatment guidelines in April 2020, introducing confounding by time.
Standard of Care (SOC) for COVID-19 in the study country,
the USA, is very poor with very low average efficacy for approved treatments1.
Only expensive, high-profit treatments were approved for early treatment. Low-cost treatments were excluded, reducing the probability of early treatment due to access and cost barriers, and eliminating complementary and synergistic benefits seen with many low-cost treatments.
This study is excluded in the after exclusion results of meta-analysis:
substantial confounding by time likely due to declining usage over the early stages of the pandemic when overall treatment protocols improved dramatically.
|
risk of death, 22.0% higher, HR 1.22, p = 0.07, treatment 2,014, control 1,459, adjusted per study.
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| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
Frontera et al., 26 Oct 2020, retrospective, USA, preprint, median age 64.0, 14 authors.
DOI record:
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"abstract": "<jats:title>Abstract</jats:title>\n <jats:p><jats:bold>Background:</jats:bold> 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.<jats:bold>Methods: </jats:bold>A multicenter cohort study was conducted of 3,473<jats:bold> </jats:bold>adult hospitalized<jats:bold> </jats:bold>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.<jats:bold>Results: </jats:bold>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 score-matched 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 significant interactions for Zn+ionophore with other COVID-19 specific medications.<jats:bold>Conclusions: </jats:bold>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.</jats:p>",
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Late treatment
is less effective
is less effective
fronteraaz