S409 Gender-Specific Susceptibility to SARS-CoV-2 Infection Among Patients With Gastroesophageal Reflux Disease (GERD) Using Proton Pump Inhibitors (PPI): A Nationwide Study

Abstract

Introduction: Gender is profoundly understudied in research especially when related to infectious diseases. Our aim was to examine gender-specific differences in COVID-19 diagnosis among GERD patients using PPIs. Methods: Data was analyzed from a large database (Explorys, IBM) that provides electronic health records of patients from 26 major integrated US health care systems. Only adults with diagnosis of GERD from January 1999-May 2021 and COVID-19 from December 2019-May 2021 were included. Gender, PPI use, age, heart disease (HD), chronic kidney disease (CKD), diabetes mellitus (DM), chronic obstructive pulmonary disease (COPD) were covariates of interest. Univariate and multivariate analyses were used for statistical analysis. The presence of effect modification by gender or PPI use was examined. Results: Among 6229810 GERD patients, 4067200 (65.3%) used PPIs. COVID-19 was diagnosed in 4790 (0.12%)(34% males vs 66% females). In univariate analysis, PPI users had highest odds of infection OR 2.74 [2.55-2.94, P< 0.001]. Among co-morbidities, odds of COVID-19 was highest for CKD OR 1.82 [1.70-1.93, P=0.003], DM OR 1.65 [1.55-1.73, P< 0.001], HTN OR 1.61 [1.52-1.70, P< 0.001], HD OR 1.38 [1.3-1.45, P=0.001] but lower for COPD OR 1.09 [1.02-1.17, P< 0.007]. In multivariate model, PPI use alone had the highest association with COVID-19 adjusted odds (aOR) 2.5 [2.25-2.8, P< 0.001]. In CKD aOR 2.23 [1.8-2.7, P< 0.001] but risk was modified if they used PPI aOR 0.71 [0.6-0.9, P< 0.001]. In HTN aOR 1.5 [1.2-1.6, P< 0.001] and DM aOR 1.3 [1.2-1.4, P< 0.001]. GERD patients with COPD had aOR 1.1 [0.9-1.4, P=0.21] but risk was reduced to 0.7 [0.6-0.91, P=0.20] if they used PPIs. With HD aOR 0.93 [0.8-1.1, P=0.4] but PPI use modified their risk to aOR 1.32 [1.1-1.6, P=0.001]. If model was stratified by gender, female PPI users had the highest susceptibility to COVID-19 aOR 2.68 [2.4-3.0, P< 0.001] vs male aOR 1.8 [1.51-2.1, P< 0.001]. PPI use was protective for those with COPD: males aOR 0.54 [0.39-0.73, P=0.001] vs females aOR 0.95 [0.70-1.28, p< 0.001]. Males with GERD and CKD had aOR 3.1 [2.3-4.1, P< 0.001] vs female aOR 1.8 [1.2-2.3, P< 0.001]. Susceptibility to COVID-19 was modified in patients with HD if they used PPIs: males OR 1.32 [1.1-1.6, P=0.001] vs female OR 1.8 [1.4-2.4, P< 0.001]. Conclusion: In GERD patients, females PPI users had higher odds of COVID-19 diagnosis compared to males if they had no comorbidities. GERD patients with CKD had the highest risk of COVID-19, especially if they were males.Figure 1.: Multivariable regression model. A forest plot showing odds ratio and 95% confidence interval for COVID-19 diagnosis among patients with gastroesophageal reflux disease (GERD) with select co-morbidities. Model stratified by gender. Effect modification by proton pump inhibitors (PPI) use was also examined. Abbreviations: CKD, chronic kidney disease; HTN, hypertension; DM, diabetes mellitus.Table 1.: Baseline Characteristics of Patients with Gastroesophageal Reflux Disease Included in the Study. Abbreviations: PPI, proton pump inhibitor; COPD, chronic obstructive pulmonary disease; CKD, chronic kidney disease; CI, confidence interval.