Treatment with proton pump inhibitors is associated with secondary bacterial infections and sepsis in patients with COVID-19: a retrospective analysis of their joint impact on in-hospital prognosis

Secondary bacterial infections (SBIs) contribute to worse in-hospital outcomes in patients with Coronavirus disease 2019 (COVID-19). Treatment with proton pump inhibitors (PPIs) is associated with an increased risk of bacterial infections in different clinical settings. However, the association between PPI treatment prior to hospital admission and the occurrence of either SBIs or secondary bacterial sepsis (SBS) as well as their joint impact on clinical outcomes of patients hospitalized for COVID-19 are not clarified. We retrospectively analyzed preadmission PPI use, in-hospital occurrence of SBIs and SBS, and in-hospital outcomes of a cohort of patients hospitalized for COVID-19. Among 1087 patients, 447 (41%) were on PPI treatment prior to hospital admission. During the hospital stay, 197 (18%) and 223 (20%) patients were diagnosed with SBIs and SBS, respectively. The composite endpoint of intensive care unit (ICU) admission/in-hospital death was met by 214 (20%) patients. Preadmission PPI treatment was independently associated with up to a 2.1-fold and 1.7-fold increased risk of SBIs and SBS, respectively. The occurrence of SBS was independently associated with up to a 2.2-fold increased risk of ICU admission/in-hospital death. A significant preadmission PPI treatment x SBS interaction emerged in predicting ICU admission/in-hospital death ( = 5.221, p = 0.023). PPI treatment prior to hospital admission for COVID-19 is associated with an increased risk of SBIs and SBS. In addition, it interacts with SBS in predicting in-hospital prognosis. An appropriate use of PPIs may attenuate the risk of adverse clinical outcomes during hospitalization for COVID-19.