Increased ACE2 Levels and Mortality Risk of Patients With COVID-19 on Proton Pump Inhibitor Therapy

{ 'indexed': {'date-parts': [[2023, 7, 21]], 'date-time': '2023-07-21T21:30:47Z', 'timestamp': 1689975047131}, 'reference-count': 34, 'publisher': 'Ovid Technologies (Wolters Kluwer Health)', 'issue': '8', 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'published-print': {'date-parts': [[2021, 8]]}, 'abstract': '<jats:sec>\n' ' <jats:title>INTRODUCTION:</jats:title>\n' ' <jats:p>Proton pump inhibitor (PPI) use was recently reported to be associated ' 'with increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and ' 'worse clinical outcomes. The underlying mechanism(s) for this association are ' 'unclear.</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>METHODS:</jats:title>\n' ' <jats:p>We performed a prospective study of hospitalized coronavirus disease 2019 ' '(COVID-19) patients and COVID-negative controls to understand how PPI use may affect ' 'angiotensin-converting enzyme 2 (ACE2) expression and stool SARS-CoV-2 RNA. Analysis of a ' 'retrospective cohort of hospitalized patients with COVID-19 from March 15, 2020 to August 15, ' '2020 in 6 hospitals was performed to evaluate the association of PPI use and mortality. ' 'Covariates with clinical relevance to COVID-19 outcomes were included to determine predictors ' 'of in-hospital mortality.</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>RESULTS:</jats:title>\n' ' <jats:p>Control PPI users had higher salivary <jats:italic ' 'toggle="yes">ACE2</jats:italic> mRNA levels than nonusers, 2.39 ± 1.15 vs 1.22 ± 0.92 ' '(<jats:italic toggle="yes">P</jats:italic> = 0.02), respectively. Salivary ACE2 levels and ' 'stool SARS-CoV-2 RNA detection rates were comparable between users and nonusers of PPI. In ' '694 hospitalized patients with COVID-19 (age = 58 years, 46% men, and 65% black), mortality ' 'rate in PPI users and nonusers was 30% (68/227) vs 12.1% (53/439), respectively. Predictors ' 'of mortality by logistic regression were PPI use (adjusted odds ratio [aOR] = 2.72, ' '<jats:italic toggle="yes">P</jats:italic> &lt; 0.001), age (aOR = 1.66 per decade, ' '<jats:italic toggle="yes">P</jats:italic> &lt; 0.001), race (aOR = 3.03, <jats:italic ' 'toggle="yes">P</jats:italic> = 0.002), cancer (aOR = 2.22, <jats:italic ' 'toggle="yes">P</jats:italic> = 0.008), and diabetes (aOR = 1.95, <jats:italic ' 'toggle="yes">P</jats:italic> = 0.003). The PPI-associated mortality risk was higher in black ' 'patients (aOR = 4.16, 95% confidence interval: 2.28–7.59) than others (aOR = 1.62, 95% ' 'confidence interval: 0.82–3.19, <jats:italic toggle="yes">P</jats:italic> = 0.04 for ' 'interaction).</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>DISCUSSION:</jats:title>\n' ' <jats:p>COVID-negative PPI users had higher salivary <jats:italic ' 'toggle="yes">ACE2</jats:italic> expression. PPI use was associated with increased mortality ' 'risk in patients with COVID-19, particularly African Americans.</jats:p>\n' ' </jats:sec>', 'DOI': '10.14309/ajg.0000000000001311', 'type': 'journal-article', 'created': {'date-parts': [[2021, 5, 28]], 'date-time': '2021-05-28T13:09:00Z', 'timestamp': 1622207340000}, 'page': '1638-1645', 'source': 'Crossref', 'is-referenced-by-count': 12, 'title': 'Increased ACE2 Levels and Mortality Risk of Patients With COVID-19 on Proton Pump Inhibitor ' 'Therapy', 'prefix': '10.14309', 'volume': '116', 'author': [ { 'given': 'Julia J.', 'family': 'Liu', 'sequence': 'first', 'affiliation': [ { 'name': 'Division of Gastroenterology and Hepatology, University of ' 'Arkansas for Medical Sciences, Little Rock, Arkansas, USA;'}, { 'name': 'Current affiliation: Morehouse School of Medicine, Atlanta, ' 'Georgia, USA;'}]}, { 'given': 'Meredith E.', 'family': 'Sloan', 'sequence': 'additional', 'affiliation': [ { 'name': 'Division of Gastroenterology, University of Mississippi Medical ' 'Center (UMMC), Jackson, Mississippi, USA;'}]}, { 'given': 'Anna H.', 'family': 'Owings', 'sequence': 'additional', 'affiliation': [ { 'name': 'Division of Gastroenterology, University of Mississippi Medical ' 'Center (UMMC), Jackson, Mississippi, USA;'}]}, { 'given': 'Erika', 'family': 'Figgins', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Oral Immunology and Infectious Diseases, ' 'University of Louisville School of Dentistry, Louisville, ' 'Kentucky, USA;'}]}, { 'given': 'Josee', 'family': 'Gauthier', 'sequence': 'additional', 'affiliation': [ { 'name': 'Division of Gastroenterology, Department of Medicine, University ' 'of Florida, Gainesville, Florida, USA;'}]}, { 'given': 'Raad', 'family': 'Gharaibeh', 'sequence': 'additional', 'affiliation': [ { 'name': 'Division of Gastroenterology, Department of Medicine, University ' 'of Florida, Gainesville, Florida, USA;'}]}, { 'given': 'Tanya', 'family': 'Robinson', 'sequence': 'additional', 'affiliation': [ { 'name': 'Division of Gastroenterology, University of Mississippi Medical ' 'Center (UMMC), Jackson, Mississippi, USA;'}]}, { 'given': 'Haley', 'family': 'Williams', 'sequence': 'additional', 'affiliation': [ { 'name': 'Division of Gastroenterology, University of Mississippi Medical ' 'Center (UMMC), Jackson, Mississippi, USA;'}]}, { 'given': 'Campbell B.', 'family': 'Sindel', 'sequence': 'additional', 'affiliation': [ { 'name': 'Division of Gastroenterology, University of Mississippi Medical ' 'Center (UMMC), Jackson, Mississippi, USA;'}]}, { 'given': 'Fremel', 'family': 'Backus', 'sequence': 'additional', 'affiliation': [ { 'name': 'UMMC Center for Informatics and Analytics, Jackson, Mississippi, ' 'USA;'}]}, { 'given': 'Krishna', 'family': 'Ayyalasomayajula', 'sequence': 'additional', 'affiliation': [ { 'name': 'UMMC Center for Informatics and Analytics, Jackson, Mississippi, ' 'USA;'}]}, { 'given': 'Adam', 'family': 'Parker', 'sequence': 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