Israeli study
obesity, death, chronic kidney disease, asthma, diabetes
OBESITY, DISEASE, LIVER DISEASE, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, CEREBROVASCULAR ACCIDENT, ASTHMA, DYSLIPIDEMIA, REGRESSION, REGRESSION, HYPERTENSION, DIABETES
A retrospective, multi-center study was conducted in Hadassah and Ichilov Medical Centers. A total of 150,976 participants were diagnosed positive for SARS-COV-2 following WHO interim guidance (The retrospective study was designed to assess initial relationships between metabolic regulating drug use and COVID-19 clinical outcomes (28-day mortality and duration of hospitalization, ICU admission, mechanical ventilation, oxygen supplementation, disease severity at baseline, and inflammatory marker changes) versus a control group that did not take any drug of this type.COVID-19 poses a significant risk in older patients and patients with comorbidities (Comparisons were conducted between hospitalized COVID-19 patients using one or more metabolic regulating drugs (fibrates, thiazolidinediones, metformin, SGLT2 inhibitors, statins, or telmisartan [IRE1α inhibitor]) versus control patients not taking any metabolic regulating drugs. Baseline values are defined as measurements taken upon hospital admission. Statistical analyses were performed using SAS v9.4 (SAS, SAS Institute Cary, NC USA) software and R-3.6.3 (R Foundation for Statistical Computing, Vienna, Austria). Continuous variables were summarized by a median and interquartile range (IQR) and categorical variables by a count and percentage. Statistical testing was two-sided. A p-value <0.05 was considered statistically significant. Missing data was not imputed. Nominal p-values are presented since this was an exploratory study. Demographic and baseline clinical characteristics, comorbidities, and laboratory examinations, as well as initial univariate clinical outcomes, were compared between the groups (drugs versus no drugs) by data type using a two-sample t-test or Fisher’s exact test as appropriate.The relative risk of hospitalization, ICU admission, and 28-day all-cause-mortality of COVID-19 patients versus the general hospital population (1-year period, 5-year period, and 10-year period prior to study start date in patients 30 years and older) are presented with 95% confidence interval and level of significance (Wald test).Dynamic changes of inflammatory markers were depicted using locally weighted scatterplot smoothing (Lowess) plotting Time-to-event data is presented with Kaplan-Meier plots. Time-to-events are measured in days from the date of hospital admission to the date of in-hospital death, and release from the hospital or last follow-up or 28 days whichever is sooner. Cox regression was performed to compare time-to-event data between the groups adjusting for covariates that may have been imbalanced between the groups. We did not perform matching since Cox regression models applied to the entire study cohort can effectively address confounding attributable to observed covariates and maximize power by using all data available. Hazard ratios are comparing drug to control group, adjusted for covariates (age, sex, current smoker, asthma, chronic obstructive pulmonary disease, cerebrovascular accident, chronic heart disease, chronic liver disease, chronic kidney disease, obesity, diabetes, hypertension, and dyslipidemia) with a level of significance and 95% confidence interval. In cases of monotone likelihood (non-convergence of likelihood function), Firth’s penalized maximum likelihood bias reduction method for Cox regression was implemented. Cox Regression with Firth’s Penalized Likelihood has been shown to provide a solution in the case of monotone likelihood (non-convergence of likelihood function) and was shown to outperform Wald confidence intervals in these cases (