Pre-hospitalization proton pump inhibitor use and clinical outcomes in COVID-19

Ramachandran, Preethi; Perisetti, Abhilash; Gajendran, Mahesh; Jean-Louis, Farla; Bansal, Pardeep; Dwivedi, Alok; Goyal, Hemant

doi:10.1097/meg.0000000000002013

Cited by 40 publications

(33 citation statements)

References 33 publications

(40 reference statements)

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“…Only 4 studies 12,19,20 reported the association between current PPI use and mortality alone, including 4150 current PPI users (Supplementary Table 7). The overall analysis showed an RR of 1.33 (95% CI, 0.71-2.48) in current PPI users compared with never users, although estimates differed between studies with low risk of bias, RR 0.85 (95% CI, 0.70-1.03), and high risk of bias, RR 2.37 (1.53-3.67) (interaction test: P < .0001) (Figure 2).…”

Section: Meta-analysis Of Coronavirus Disease 2019 Mortalitymentioning

confidence: 99%

Proton Pump Inhibitor Use Is Not Strongly Associated With SARS-CoV-2 Related Outcomes: A Nationwide Study and Meta-analysis

Israelsen

Ernst

Lundh

et al. 2021

Clinical Gastroenterology and Hepatology

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Background and aims Proton pump inhibitor (PPI) use has been associated with increased risk of SARS-CoV-2 infection and severe outcomes. However, meta-analyses show unclear results leading to uncertainty regarding the safety of PPI use during the ongoing COVID-19 pandemic. Methods We conducted a nationwide observational study including all SARS-CoV-2 cases (n=83,224) in Denmark as of December 1, 2020. The association of current PPI use with risk of infection was examined in a case-control design. We investigated the risk of severe outcomes, including mechanical ventilation, ICU admission or death, in current PPI users (n=4,473) compared to never users. Propensity score matching was applied to control for confounding. Finally, we performed an updated meta-analysis on risk of SARS-CoV-2 infection and COVID-19 mortality attributable to PPI use. Results Current PPI use was associated with increased risk of infection; adjusted odds ratio (OR) 1.08 (95% CI 1.03-1.13). Among SARS-CoV-2 cases, PPI use was associated with increased risk of hospital admission; adjusted relative risk (RR) 1.13 (1.03-1.24), but not with other severe outcomes. The updated meta-analysis showed no association between PPI use and risk of infection or mortality; pooled OR 1.00 (95% CI 0.75-1.32) and RR 1.33 (95% CI 0.71-2.48). Conclusion Current PPI use may be associated with an increased risk of SARS-CoV-2 infection and hospital admission, but these results with minimally elevated estimates are most likely subject to residual confounding. No association was found for severe outcomes. The results from the meta-analysis indicated no impact of current PPI use on COVID-19 outcomes.

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Section: Meta-analysis Of Coronavirus Disease 2019 Mortalitymentioning

confidence: 99%

Proton Pump Inhibitor Use Is Not Strongly Associated With SARS-CoV-2 Related Outcomes: A Nationwide Study and Meta-analysis

Israelsen

Ernst

Lundh

et al. 2021

Clinical Gastroenterology and Hepatology

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“…Taking into account the study by Hariyanto et al [ 53 ], we included data on the severity of the disease, specifically for 16 patients and 77 patients with shock, respectively, in the PPI-group and in the non-PPI-group[ 50 ], 18 patients and 30 patients had secondary infection, respectively, in the PPI-group and in the non-PPI-group[ 31 ]. A study by García-Menaya et al [ 55 ] included data related to severity and mortality of the disease, but they were calculated for patients with and without allergic conditions and for overall patients.…”

Section: Resultsmentioning

confidence: 99%

Paradoxical relationship between proton pump inhibitors and COVID-19: A systematic review and meta-analysis

Zippi¹,

Fiorino²,

Budriesi³

et al. 2021

WJCC

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BACKGROUND The proton pump inhibitors (PPIs), used to reduce gastric acid secretion, represent one of the most widely used pharmaceutical classes in the world. Their consumption as a risk factor for the evolution of severe forms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been investigated as well as the mortality of these patients. These risks also appear to be linked to the duration and the dosage. On the other hand, several studies have emerged with regard to the protective or therapeutic effects of these drugs. More and more evidence underlines the immunomodulatory and anti-fibrotic role of PPIs. In addition, their ability to alkalize the contents of endosomes and lysosomes serves as an obstacle to the entry of the virus into the host cells. AIM To identify studies on the relationship between the intake of PPIs and coronavirus disease 2019 (COVID-19) in patients affected by SARS-CoV-2 infection, with the main objective of evaluating the outcomes related to severity and mortality. METHODS A literature review was performed in November 2020. The MEDLINE/PubMed, Cochrane Library, EMBASE and Google Scholar databases were searched for all relevant articles published in English on this topic. The search terms were identified by means of controlled vocabularies, such as the National Library of Medicine’s MESH (Medical Subject Headings) and keywords. The MESH terms and keywords used were as follows: “COVID-19”, “proton pump inhibitors”, ”PPIs”, “SARS-CoV-2”, “outcomes”, “severity” and “mortality”. The inclusion criteria regarding the studies considered in our analysis were: meta-analysis, case-control, hospital-based case-control, population-based case-control, retrospective studies, online survey, as well as cohort-studies, while articles not published as full reports, such as conference abstracts, case reports and editorials were excluded. We tried to summarize and pool all the data if available. RESULTS A total of 9 studies were found that described the use of PPIs, of which only 5 clearly reported the severity and mortality data in SARS-CoV-2 patients. Our pooled incidence analysis of severe events did not differ between patients with and without PPIs (odds ratio 1.65, 95% confidence interval: 0.62-4.35) ( P = 0.314), or for mortality (odds ratio 1.77, 95% confidence interval: 0.62-5.03) ( P = 0.286). CONCLUSION Detailed and larger case studies are needed to accurately understand the role of PPIs in this viral infection.

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“…Almario showed that PPI use is associated with a higher likelihood of testing positive for SARS-CoV-2 infection 5 . The basis for these findings is presently purely speculative and is explored in detail in the aforementioned publications [5][6][7] . Importantly, PPIs represent a medication that could be safely suspended during acute COVID-19 illness given their indication is commonly for symptomatic relief.…”

Section: Proton Pump Inhibitorsmentioning

confidence: 99%

“…A limited number of studies have examined certain classes of medication in the context of SARS-CoV-2 infection, revealing several robust associations [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] . Some point to the clear opportunity for adjusting prescriptions to the benefit of patients admitted with COVID-19 with greater understanding of how the disease interacts with commonly used agents 6 .…”

Section: Introductionmentioning

confidence: 99%

Pharmacological Predictors of Morbidity and Mortality in COVID‐19

Oddy

McCaul

Keeling

et al. 2021

The Journal of Clinical Pharma

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De-identified individual participant data will be available including data dictionaries. Specifically, a case may be submitted for provision of individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices). Study documentation including the study protocol and statistical analysis plan may also be requested. Data will be available following publication ending 5 years after this date as per data handling measures specified in the study protocol. Access will be granted to requestors submitting a methodologically sound proposal to the corresponding author CO

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Pre-hospitalization proton pump inhibitor use and clinical outcomes in COVID-19

Cited by 40 publications

References 33 publications

Proton Pump Inhibitor Use Is Not Strongly Associated With SARS-CoV-2 Related Outcomes: A Nationwide Study and Meta-analysis

Proton Pump Inhibitor Use Is Not Strongly Associated With SARS-CoV-2 Related Outcomes: A Nationwide Study and Meta-analysis

Paradoxical relationship between proton pump inhibitors and COVID-19: A systematic review and meta-analysis

Pharmacological Predictors of Morbidity and Mortality in COVID‐19

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