Proton pump inhibitor use is associated with increased risk of severity and mortality from coronavirus disease 2019 (COVID-19) infection

Hariyanto et al., Digestive and Liver Disease, doi:10.1016/j.dld.2020.10.001, Dec 2020
Mortality -72% improvement lower risk ← → higher risk Severe case -35% Proton Pump Inhibitors  Hariyanto et al.  META ANALYSIS c19early.org Hariyanto et al., Digestive and Liver .., Dec 2020 0 0.5 1 1.5 2+ RR
PPIs for COVID-19
1st treatment shown to increase risk in September 2020, now with p = 0.000000048 from 40 studies.
6,300+ studies for 210+ treatments. c19early.org
Meta Analysis
Meta analysis of 6 studies with 5,884 COVID-19 patients showing significantly higher severity and mortality with proton pump inhibitor (PPI) usage.
8 meta analyses show significant harm with proton pump inhibitors for mortality1-3, severity1,2,4-8, and cases2.
Currently there are 40 proton pump inhibitors for COVID-19 studies, showing 40% higher mortality [17‑67%], 14% higher ventilation [-1‑32%], 15% higher ICU admission [1‑30%], 9% higher hospitalization [3‑16%], and 2% fewer cases [-6‑10%].
Important missing comments or errors? Let us know.
risk of death, 72.0% higher, RR 1.72, p = 0.04.
risk of severe case, 35.0% higher, RR 1.35, p = 0.002.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Hariyanto et al., 31 Dec 2020, peer-reviewed, 3 authors.
Abstract: Digestive and Liver Disease 52 (2020) 1410–1412 Contents lists available at ScienceDirect Digestive and Liver Disease journal homepage: www.elsevier.com/locate/dld Correspondence Proton pump inhibitor use is associated with increased risk of severity and mortality from coronavirus disease 2019 (COVID-19) infection Dear Editor, World Health Organization (WHO) first declared coronavirus disease 2019 (COVID-19) as a pandemic in March 2020, and now, six months after that, the number of positive and death cases are still increasing. This global pandemic has caused a significant impact on health, social, and economic aspects around the world. Thus, identification of the risk factors that contribute to the development of severe infections is important to enabling risk stratification, optimizing the hospital resources reallocation, and guiding public health recommendations and interventions. Several medications have been demonstrated to be associated with a reduction in poor outcomes from COVID-19 such as anticoagulant and metformin, while other medications did not alter outcomes of COVID-19 infections such as ACE inhibitors, angiotensin II receptor blocker (ARB), and statin [1-3]. During normal times, proton pump inhibitors (PPIs) are among the drugs which are most commonly used by patients because of their efficacy in relieving dyspepsia and GERD symptoms, also because of their relatively affordable price [4]. In a previous meta-analysis study, it has been shown that the use of proton pump inhibitors (PPIs) may increase the risk of pneumonia even though the heterogeneity of the study is high [5]. Unfortunately, until now, the evidence regarding the link between the use of PPI and COVID-19 outcomes is still conflicting. This article aims to give better evidence for the association between PPI usage and in-hospital outcomes (severity and mortality) of COVID-19 infection. A search of the literature was conducted on Google scholar using the keywords “proton pump inhibitors” OR “PPI” OR “clinical characteristics” OR “medications” OR “risk factors” AND “coronavirus disease 2019” OR “COVID-19”, between 2019 and present time (September 10th, 2020) with language restricted to English only. The title, abstract, and full text of all articles identified that matched the search criteria were assessed, and those reporting the rate of PPI usage in COVID-19 patients with a clinically validated definition of “severe disease” and “mortality” were included in this meta-analysis. The references of all identified studies were also analyzed (forward and backward citation tracking) to identify other potentially eligible articles. A meta-analysis was performed using Review Manager 5.4 (Cochrane Collaboration) software. Dichotomous variables were calculated using the Mantel-Haenszel formula with random-effects models. The heterogeneity was assessed by using the I2 statistic with a value of < 25%, 26–50%, and > 50% were considered as low, moderate, and high degrees of heterogeneity, respectively. The effect estimate was reported as risk ratio (RR) along with its 95% confidence intervals (CIs) for dichotomous variables, respectively. P-value was two-tailed, and the statistical significance was set at ≤ 0.05. A total of 7300 records were obtained through systematic electronic searches and other ways. After screening titles, abstracts, and full texts, 6 studies [6-11] with a total of 5884 COVID-19 patients were included in the meta-analysis (Table 1). The individual and pooled..
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