Clinical Outcomes of Zinc Supplementation Among COVID-19 Patients.

BACKGROUND: Zinc supplementation is frequently prescribed during the treatment of COVID-19. However, the evidence supporting the efficacy of this intervention is mixed. OBJECTIVE: Establish the clinical utility of zinc supplementation to alter disease severity in COVID- 19 illness. METHODS: We performed a multicenter, retrospective, observational chart review of patients admitted to Ascension St. John Hospital or Detroit Medical Center from January 1st, 2020 to May 31st, 2020. All included patients received concomitant hydroxychloroquine due to its zinc ionophore activity. Our primary outcome was a change in Sequential Organ Failure Assessment (SOFA) score with secondary outcomes including all-cause mortality, need for intubation, and QTc prolongation as a safety outcome. RESULTS: We identified 489 patients who received zinc and 587 patients who did not. The primary outcome showed a small difference in the change in SOFA score in patients receiving zinc in univariate analysis (1.08 vs. 1.43, p=0.02), but this difference was not significant after adjustment for confounding factors such as receipt of corticosteroids and ICU admission. Mortality was not different between those that received zinc compared to those that did not (32.7% vs. 35.9%, p=0.268). CONCLUSION: Our retrospective study, including 1064 patients hospitalized in Detroit, demonstrated no differences in mortality or disease severity with zinc combination. Furthermore, prospective studies are needed to establish the utility of zinc in the treatment of COVID-19.

Azithromycin Versus Beta-lactams in Hospitalized Patients with Acute Exacerbations of COPD.

BACKGROUND: There is a lack of data comparing azithromycin to alternative antibiotic choices in managing COPD exacerbations, making appropriate antibiotic selection controversial. OBJECTIVE: To compare treatment failure in hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) receiving azithromycin or beta-lactams. DESIGN: Retrospective, multicenter cohort study using logistic regression for multivariable analysis. Patients were included if they were at least 18 years old, admitted with AECOPD, and received at least two consecutive days of either a beta-lactam or azithromycin. Patients were excluded if they received concomitant azithromycin and beta-lactam antibiotics during the first 2 days, had a history of other severe underlying pulmonary diseases, pregnancy, COVID-19, alpha-1 antitrypsin deficiency, or received a corticosteroid for a diagnosis other than COPD. PARTICIPANTS: Five hundred ninety-five patients were included, of which 428 (72%) received azithromycin and 167 patients (28%) received a beta-lactam. MAIN MEASURES: The primary endpoint was treatment failure rate in patients receiving azithromycin versus beta-lactams, which was a composite endpoint defined as in-hospital mortality, admission to intensive care, initiation of invasive mechanical ventilation, initiation of a new antibiotic, steroid therapy escalation, or readmission due to AECOPD within 30 days. KEY RESULTS: The composite primary outcome occurred in 84 patients (19.6%) in the azithromycin group and 54 (32.3%) in the beta-lactam group (p<0.01). The difference in the composite outcome was a result of higher rates of new antibiotics during admission (12.6% vs 4.2%; p<0.01) and higher readmission within 30 days (19.3% vs 12.4%; p=0.032). After controlling for potential confounders, beta-lactams continued to demonstrate a higher risk for treatment failure (OR, 2.30; 95% CI, 1.46-3.63). There was no difference in adverse effects between the groups. CONCLUSION: Azithromycin was associated with less treatment failure in AECOPD which was driven by lower readmission rates and prescription of new antimicrobials.

Mechanisms and Potential Roles of Glucose-Lowering Agents in COVID-19: A Review.

OBJECTIVE: To explore mechanistic benefits of glucose-lowering agents that extend beyond glycemic control with the potential to mitigate coronavirus disease 2019 (COVID-19) complications. DATA SOURCES: The following PubMed literature search terms were used from July 2020 to January 2, 2021: diabetes, COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), glucose-lowering agents, and pharmacology. STUDY SELECTION AND DATA EXTRACTION: English-language studies reporting on the association between diabetes, COVID-19 adverse outcomes, and the potential roles of glucose-lowering agents were reviewed. DATA SYNTHESIS: Selected glucose-lowering agents have benefits beyond glycemic control, with the potential to reduce the risks of severe complications during SARS-CoV-2 infection. Key benefits include anti-inflammatory, anticoagulant, immune modulating, and enzyme/receptor effects. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review summarizes the current knowledge of glucose-lowering agents and their potential roles in COVID-19 outcomes. Considering beneficial mechanisms on COVID-19 outcomes that extend beyond glycemic control as well as safety profiles, current data suggest that dipeptidyl peptidase-IV (DPP-IV) inhibitors and metformin may have the most promise and warrant further investigation. CONCLUSIONS: Certain glucose-lowering agents may offer additional benefits beyond glucose control-namely, by modulating the mechanisms contributing to adverse outcomes related to COVID-19 in patients with diabetes. DPP-IV inhibitors and metformin appear to have the most promise. However, current published literature on diabetes medications and COVID-19 should be interpreted with caution. Most published studies are retrospective and consist of convenience samples, and some lack adequate analytical approaches with confounding biases. Ongoing trials aim to evaluate the effects of glucose-lowering agents in reducing the severity of COVID-19 outcomes.