PMID- 35185561 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220223 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 13 DP - 2022 TI - The Association Between Proton Pump Inhibitors and COVID-19 is Confounded by Hyperglycemia in a Population-Based Study. PG - 791074 LID - 10.3389/fphar.2022.791074 [doi] LID - 791074 AB - Background and Aims: There is conflicting evidence regarding the association between proton pump inhibitors (PPI) and the risk of acquisition and severity of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Aim: To evaluate the association between PPI exposure and infection and development of severe disease in patients infected with SARS-CoV2in a large population-based historical cohort. Methods: Data were extracted from a health maintenance organization database in Israel that insures over 1,200,000 individuals from across the country. All patients who underwent SARS-CoV-2 testing between March and November 2020 were included. Logistic regression and matched analyses were used to compare patients prescribed and exposed to PPIs to those not prescribed PPIs regarding SARS-CoV-2 positivity. In addition, among SARS-CoV-2 positive patients (n = 44,397) the likelihood of developing severe disease, defined by a composite endpoint of death, ICU admission and prolonged hospitalization, was compared in those exposed and not exposed to PPIs. Results: Among 255,355 adult patients who underwent SARS-CoV-2 testing by PCR, 44,397 (17.4%) were positive for SARS-CoV-2 and 12,066 (4.7%) patients were prescribed PPIs in the 3 months before testing. In a multivariable logistic regression model controlling for age, gender, smoking status, BMI, diabetes mellitus, hypertension, COPD, history of ischemic heart disease and fasting blood glucose (FBG) levels, no significant association was found between PPIs and SARS-CoV-2 positivity (p = 0.09 aOR 0.94, 95% CI - 0.88-1.01). Among SARS-CoV-2 positive patients, 910 (2%) had a severe infection. Multivariate logistic regression controlling for the abovementioned confounders, showed no such association between PPIs and severe COVID-19 (p = 0.28). Elevated FBG levels were significantly associated with both PPI exposure (p < 0.001) and severe COVID-19 infection (p < 0.001). These results were reinforced by a matched analysis (n = 655 pairs). Conclusion: PPIs are spuriously associated with severe COVID-19 due to the presence of elevated FBG as a confounder. Our study accounted for the FBG levels of patients and known risk factors for severe COVID-19 infection, which may be the reason for the discrepancy in prior studies. These results may aid in understanding potential confounders when evaluating potential associations of PPIs with other respiratory or viral diseases. CI - Copyright (c) 2022 Shafrir, Benson, Katz, Hershcovici, Bitan, Paltiel, Calderon-Margalit, Safadi and Shauly-Aharonov. FAU - Shafrir, Asher AU - Shafrir A AD - Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. AD - Meuhedet Health Medical Organization, Jerusalem, Israel. AD - Institute of Gastroenterology and Hepatology, Hadassah University Medical Center, Jerusalem, Israel. FAU - Benson, Ariel A AU - Benson AA AD - Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. AD - Institute of Gastroenterology and Hepatology, Hadassah University Medical Center, Jerusalem, Israel. FAU - Katz, Lior H AU - Katz LH AD - Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. AD - Institute of Gastroenterology and Hepatology, Hadassah University Medical Center, Jerusalem, Israel. FAU - Hershcovici, Tiberiu AU - Hershcovici T AD - Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. AD - Institute of Gastroenterology and Hepatology, Hadassah University Medical Center, Jerusalem, Israel. FAU - Bitan, Menachem AU - Bitan M AD - Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. AD - Meuhedet Health Medical Organization, Jerusalem, Israel. FAU - Paltiel, Ora AU - Paltiel O AD - Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. AD - Braun School of Public Health and Community Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. AD - Department of Hematology, Hadassah University Medical Center, Jerusalem, Israel. FAU - Calderon-Margalit, Ronit AU - Calderon-Margalit R AD - Braun School of Public Health and Community Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. FAU - Safadi, Rifaat AU - Safadi R AD - Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. AD - Institute of Gastroenterology and Hepatology, Hadassah University Medical Center, Jerusalem, Israel. FAU - Shauly-Aharonov, Michal AU - Shauly-Aharonov M AD - Braun School of Public Health and Community Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. AD - The Jerusalem College of Technology, Jerusalem, Israel. LA - eng PT - Journal Article DEP - 20220204 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC8854493 OTO - NOTNLM OT - COVID - 19 OT - SARS-CoV-2 OT - hyperglycaemia OT - impaired fasting blood glucose OT - proton pump inhibitor COIS- Authors AS and MB were employed by the company Meuhedet Health Medical Organization. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/02/22 06:00 MHDA- 2022/02/22 06:01 PMCR- 2022/02/04 CRDT- 2022/02/21 06:00 PHST- 2021/10/07 00:00 [received] PHST- 2022/01/12 00:00 [accepted] PHST- 2022/02/21 06:00 [entrez] PHST- 2022/02/22 06:00 [pubmed] PHST- 2022/02/22 06:01 [medline] PHST- 2022/02/04 00:00 [pmc-release] AID - 791074 [pii] AID - 10.3389/fphar.2022.791074 [doi] PST - epublish SO - Front Pharmacol. 2022 Feb 4;13:791074. doi: 10.3389/fphar.2022.791074. eCollection 2022.