Does Proton Pump Inhibitor Use Lead to a Higher Risk of Coronavirus Disease 2019 Infection and Progression to Severe Disease? a Meta-analysis

Abstract

Previous researches on the association between proton pump inhibitors (PPIs) use and the treatment and prevention of COVID-19 has generated inconsistent findings.Therefore, this meta-analysis was conducted to clarify the outcome in patients who take PPIs.Eight articles with more than 268,683 subjects were included. PPI use was not associated with increased or decreased risk of COVID-19 infection (OR:3.16, 95%CI = 0.74-13.43, P=0.12) or mortality risk of COVID-19 patients (OR=1.91, 95% CI=0.86-4.24, P=0.11). While it can add risk of severe disease (OR=1.54, 95% CI=1.20-1.99, P<0.001;) and secondary infection (OR=4.33, 95% CI=2.57-7.29).In summary, PPI use is not associated with an increased risk of infection and may not change the mortality risk of COVID-19, but appeared to be associated with an increased risk of progression to severe disease and secondary infection. However, more original studies to further clarify the relationship between PPI and COVID-19 are still urgently needed.

People exposed to proton pump inhibitors shortly preceding COVID-19 diagnosis are not at an increased risk of subsequent hospitalizations and mortality: a nation-wide matched cohort study

“…As recently reviewed [12][13][14][15], a number of observational studies addressed the issue of a potential effect of pre-morbid exposure to proton pump inhibitors (PPIs) on the risk of unfavorable outcomes in COVID-19 patients (e.g, death, hospitalizations, intensive care treatment/assisted ventilation). However, only three of them were population-based [12,17,18] and as such were devoid of biases common to studies restricted to hospitalized patients [16].…”

“…The settings were variable [12][13][14][15]: some studies were community-based, but most enrolled hospitalized COVID-19 patients; a variety of definitions of "PPI use" were employed -in respect to dosing and setting (pre-morbid or pre-hospital or in-hospital, "current" [with different definitions]). Estimates pertaining to any of the posted questions were highly heterogeneous [12][13][14][15].…”

“…This seems to be particularly so with development of effective vaccines. The question of pre-morbid (or pre-hospital) PPI use and the risk of poor outcomes (e.g., mechanical ventilation/death) was addressed mostly in studies including hospitalized patients [12][13][14][15]. Such a setting is prone to [16]: a) selection bias -the presumed effect in unselected patients (i.e., not hospitalized) remains unknown; b) collider bias -if there are factors that affect probability of hospitalization (where PPI use is a presumed, tested factor) and if these factors further promote disease progression, then "hospitalization" is a mediator, and by conditioning on it (by patient selection), collider bias is generated resulting in a spurious link between PPI use and poor outcomes.…”

“…Four recent systematic reviews [12][13][14][15] identified a total of 24 primary retrospective cohort or case-control studies aimed to estimate the risk of COVID-19 infection and/or experiencing a severe form (with different indicators of "severe") and/or COVID-19-related mortality associated with PPI use. The settings were variable [12][13][14][15]: some studies were community-based, but most enrolled hospitalized COVID-19 patients; a variety of definitions of "PPI use" were employed -in respect to dosing and setting (pre-morbid or pre-hospital or in-hospital, "current" [with different definitions]). Estimates pertaining to any of the posted questions were highly heterogeneous [12][13][14][15].…”

“…5,6,8 Two questions about pre-COVID PPI use seem to naturally arise from this mechanistic rationale: one pertaining to the risk of infection and the other one to the risk of severe COVID-19. 8 Four recent systematic reviews [12][13][14][15] identified a number of observational studies dealing with these questions.…”