Proton pump inhibitors and the risk of severe COVID-19: a post-hoc analysis from the Korean nationwide cohort

We appreciate the comment and discussion from Dr Roulet1 on our original article.2 The author criticised that (1) our study did not consider the dose-dependent exposure to proton pump inhibitors (PPIs); (2) our study did not investigate the relationship of PPI use in hospitalised patients with COVID-19 during treatment for COVID-19 and (3) although our study accounted for protopathic bias by excluding new non-steroidal anti-inflammatory drug users, protopathic bias occurred in patients who responded to the early digestive symptoms of COVID-19. We acknowledge that plausible academic concerns have been raised, which might improve the original discussion and extend the insight into the association between PPI usage and COVID-19.1 We have performed a post-hoc analysis from the Korean nationwide cohort, addressing these concern. Data were obtained from the Korean nationwide cohort study, which includes patients (≥18 years) who underwent SARS-CoV-2 testing between 1 January and 15 May 2020.2–4 We performed propensity score matching between current PPI users (prehospitalisation PPI usage) and non-users among patients with laboratory-confirmed COVID-19 (n=4785), as previously described.2 Posthospitalisation PPI usage was defined as in-hospital PPI use in general wards, not intensive care units. The outcomes were a composite endpoint 1 (requirement of oxygen therapy, intensive care unit admission, administration of invasive ventilation or death) and a composite endpoint 2 …