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PPIs for COVID-19
37 studies from 526 scientists
221,083 patients in 15 countries
46% higher risk in 37 studies CI 27-68%
40% higher mortality in 20 studies CI 17-67%
COVID-19 PPI studies. Oct 2024. c19early.org
0 0.5 1 1.5+ All studies -46% With exclusions -44% Mortality -40% Hospitalization -9% Cases 2% Viral clearance 12% Prophylaxis -33% Late -288% FavorsPPI Favorscontrol
Oct 12
Covid Analysis PPIs for COVID-19: real-time meta analysis of 37 studies
Meta analysis shows 40% [17‑67%] higher mortality, and pooled analysis using the most serious outcome reported shows 46% [27‑68%] higher risk. Potential mechanisms of harm include increased expression of ACE2, impair..
Jul 16
Zeng et al., eLife, doi:10.7554/elife.94973 Associations of proton pump inhibitors with susceptibility to influenza, pneumonia, and COVID-19: Evidence from a large population-based cohort study
46% higher mortality (p=0.02), 33% higher severe cases (p=0.004), and 8% more cases (p=0.1). UK Biobank retrospective with 160,923 patients showing increased risks of influenza, pneumonia, COVID-19 severity, and COVID-19 mortality with proton pump inhibitor (PPI) use.
Jun 30
Al-Momani et al., Annals of Medicine, doi:10.1080/07853890.2024.2355581 Proton pump inhibitors and gastrointestinal symptoms among patients with COVID-19 infection
100% higher mortality (p=0.39), 48% higher ventilation (p=0.54), and 25% higher ICU admission (p=0.64). Retrospective 254 hospitalized COVID-19 patients in Jordan showing higher rates of gastrointestinal symptoms such as abdominal pain and diarrhea with proton pump inhibitor (PPI) use. There were no significant differences for mortality, ve..
Jun 27
Hirsch et al., The Journal of Pediatrics, doi:10.1016/j.jpeds.2024.114179 Proton Pump Inhibitors and Risk of COVID-19 Infection in Children
15% lower hospitalization (p=0.27) and 15% fewer cases (p=0.002). Retrospective 116,209 pediatric patients showing lower risk of COVID-19 with PPI use. There was no significant difference for hospitalization.
May 5
Cheung et al., Journal of Gastroenterology and Hepatology, doi:10.1111/jgh.16601 Proton pump inhibitors associated with severe COVID‐19 among two‐dose but not three‐dose vaccine recipients
49% higher mortality (p=0.005), 36% higher severe cases (p=0.27), 20% higher hospitalization (p=0.0003), and 9% more cases (p<0.0001). Retrospective 627,514 patients in Hong Kong showing slightly higher risk of COVID-19 with pre-vaccination proton pump inhibitor (PPI) use in two-dose or three-dose vaccine recipients, and higher risk of hospitalization and severe outcomes..
Apr 15
Gramont et al., Age and Ageing, doi:10.1093/ageing/afae082 Proton pump inhibitors and risk of severe COVID-19 in older people
59% higher severe cases (p=0.002). Retrospective 834 elderly patients in France showing higher risk of severe COVID-19 with PPI use, and increasing risk with increasing dosage.
Mar 30
Wardhana et al., International Journal of Biomedical Science and Travel Medicine, doi:10.22225/ijbstm.1.1.2024.19-23 Different Outcome in COVID-19 Patients with or without PPI Use: A Systematic Review and Meta-analysis
99% higher severe cases (p=0.01). Meta analysis of 7 studies with over 30,000 COVID-19 patients showing 2 times higher risk of worse outcomes with proton pump inhibitor (PPI) use.
Dec 31
2023
Patil et al., Gastro Hep Advances, doi:10.1016/j.gastha.2022.08.004 Factors Associated With Poor Outcomes Among Patients With SARS-CoV-2 Coronavirus Infection and Gastrointestinal Symptoms
48% higher mortality (p<0.0001), 119% higher ARDS (p<0.0001), 88% worse results (p<0.0001), and 73% higher need for oxygen therapy (p<0.0001). Retrospective 19,915 hospitalized COVID-19 patients with gastrointestinal symptoms, showing that use of proton pump inhibitors or H2 receptor antagonists was associated with higher mortality, ARDS, sepsis, and ventilator or oxygen require..
Nov 17
2023
Elkanzi et al., Academic Journal of Gastroenterology & Hepatology, doi:10.33552/AJGH.2023.03.000568 Effect of Preadmission Proton Pump Inhibitor (PPI) on the clinical outcome of Covid-19 Hospitalised Patients during the Pandemic
17% higher mortality (p=0.49), 25% higher ICU admission (p=0.05), 126% higher progression (p=0.14), and 19% shorter hospitalization (p=0.18). Retrospective 309 hospitalized patients showing higher risk of severe cases (ASA≥3) with PPI use.
Oct 1
2023
Lassalle et al., JAMA Pediatrics, doi:10.1001/jamapediatrics.2023.2900 Proton Pump Inhibitor Use and Risk of Serious Infections in Young Children
Analysis of 1.2 million children in France showing increased risk of serious infection with proton pump inhibitor (PPI) use. PPI exposure was associated with higher risk of infections in the digestive tract, ear/nose/throat, lower respira..
Mar 31
2023
Shokri et al., Annales Pharmaceutiques Françaises, doi:10.1016/j.pharma.2022.08.013 What is the role of proton pump inhibitors consumption on the clinical presentation and severity of COVID-19 infection?
81% higher severe cases (p=0.05) and 78% higher mortality (p=0.21). Retrospective 670 COVID-19 patients in Iran showing significantly higher COVID-19 severity scores and more symptomatic presentation in patients with a history of proton pump inhibitor (PPI) use. Adjusted results are only provided for seve..
Mar 21
2023
Kim et al., Journal of Korean Medical Science, doi:10.3346/jkms.2023.38.e99 Histamine-2 Receptor Antagonists and Proton Pump Inhibitors Are Associated With Reduced Risk of SARS-CoV-2 Infection Without Comorbidities Including Diabetes, Hypertension, and Dyslipidemia: A Propensity Score-Matched Nationwide Cohort Study
28% higher mortality (p=0.63), 75% higher ventilation (p=0.37), 150% higher ICU admission (p=0.11), and 21% higher progression (p=0.6). PSM retrospective in South Korea, showing lower risk of COVID-19 cases with H2RA (including famotidine) and PPI use, but no significant difference in severe outcomes (results provided for the combined groups only).
Oct 5
2022
Kodvanj et al., British Journal of Clinical Pharmacology, doi:10.1111/bcp.15525 People exposed to proton‐pump inhibitors shortly preceding COVID‐19 diagnosis are not at an increased risk of subsequent hospitalizations and mortality: A nationwide matched cohort study
7% lower mortality (p=0.12) and 4% higher hospitalization (p=0.32). Retrospective 433,609 COVID-19 patients in Croatia showing no significant difference in mortality or hospitalization risk with proton-pump inhibitor (PPI) use before COVID-19 diagnosis compared to matched controls with PPI-requiring morbi..
Aug 31
2022
Dahabra et al., Gastroenterology Research, doi:10.14740/gr1545 Proton Pump Inhibitors Use and Increased Risk of Spontaneous Bacterial Peritonitis in Cirrhotic Patients: A Retrospective Cohort Analysis
Retrospective 107,750 cirrhotic patients showing increased risk of spontaneous bacterial peritonitis (SBP) with proton pump inhibitor (PPI) use. PPI use was the strongest predictor of SBP, with patients on PPIs 4.24 times more likely to d..
Aug 3
2022
Liwang et al., Journal Of The Indonesian Medical Association, doi:10.47830/jinma-vol.72.2-2022-802 High vs Low Dose Proton Pump Inhibitor (PPI) related Mortality in Hospitalized Coronavirus Disease-19 (COVID-19): A Retrospective Cohort Study
204% higher mortality (p=0.02). Retrospective hospitalized COVID-19 patients in Indonesia showing higher mortality with high dose proton pump inhibitor (PPI) use compared to low dose.
May 9
2022
Shupp et al., Scientific Reports, doi:10.1038/s41598-022-11680-0 Proton pump inhibitor therapy usage and associated hospitalization rates and critical care outcomes of COVID-19 patients
19% lower mortality (p=0.32) and 10% higher hospitalization (p=0.51). Retrospective 2,594 COVID-19 patients in the United States showing no significant association between proton pump inhibitor (PPI) use and COVID-19 severity, including need for hospitalization or 30-day mortality. There was increasing mort..
Feb 28
2022
Fatima et al., Tropical Medicine and Infectious Disease, doi:10.3390/tropicalmed7030037 The Use of Proton Pump Inhibitors and COVID-19: A Systematic Review and Meta-Analysis
12% higher mortality (p=0.05), 84% higher severe cases (p<0.0001), and 5% more cases (p=0.01). Meta-analysis of 14 studies with 477,157 COVID-19 patients showing PPI use was associated with higher cases, poor outcomes, and mortality.
Feb 19
2022
Wu et al., Journal of Global Health, doi:10.7189/jogh.12.05005 Use of proton pump inhibitors are associated with higher mortality in hospitalized patients with COVID-19
197% higher mortality (p=0.0004) and 10% worse viral clearance (p=0.02). Retrospective 4,634 hospitalized COVID-19 patients in China, showing higher mortality and slower viral clearance with proton pump inhibitor (PPI) use. Authors hypothesize that PPIs may increase susceptibility to COVID-19 by increasing ACE..
Feb 4
2022
Shafrir et al., Frontiers in Pharmacology, doi:10.3389/fphar.2022.791074 The Association Between Proton Pump Inhibitors and COVID-19 is Confounded by Hyperglycemia in a Population-Based Study
47% higher severe cases (p=0.32) and 8% fewer cases (p=0.06). Retrospective 255,355 adults in Israel showing no significant association between proton pump inhibitor (PPI) use and SARS-CoV-2 positivity or COVID-19 severity.
Jan 31
2022
Yan et al., Japanese Journal of Infectious Diseases, doi:10.7883/yoken.JJID.2021.074 Does Proton Pump Inhibitor Use Lead to a Higher Risk of Coronavirus Disease 2019 Infection and Progression to Severe Disease? a Meta-analysis
91% higher mortality (p=0.09), 67% higher severe cases (p<0.0001), 362% worse results (p<0.0001), and 64% more cases (p=0.39). Meta-analysis of 14 studies with over 268,683 subjects showing proton pump inhibitor (PPI) use was associated with increased risk of severe disease and increased risk of secondary infection. Mortality and cases were higher, without statis..
Jan 31
2022
Yao et al., Therapeutic Advances in Gastroenterology, doi:10.1177/17562848221104365 Impact of proton pump inhibitors on the in-hospital outcome of COVID-19 patients: a retrospective study
600% higher severe cases (p<0.0001). Retrospective 3,024 hospitalized COVID-19 patients in China showing increased risk of the composite outcome of ICU admission, mechanical ventilation, or death with proton pump inhibitor (PPI) use. Intravenous administration was significan..
Nov 30
2021
Ramachandran et al., European Journal of Gastroenterology & Hepatology, doi:10.1097/MEG.0000000000002013 Pre-hospitalization proton pump inhibitor use and clinical outcomes in COVID-19
92% higher mortality (p=0.02) and 80% higher progression (p=0.02). Retrospective 295 hospitalized COVID-19 patients showing higher mortality and acute respiratory distress syndrome (ARDS) with pre-hospitalization proton pump inhibitor (PPI) use. Authors hypothesize that hypochlorhydria caused by PPIs may..
Oct 18
2021
Shah et al., Gut, doi:10.1136/gutjnl-2021-325701 Proton-pump inhibitor use is not associated with severe COVID-19-related outcomes: a propensity score-weighted analysis of a national veteran cohort
3% lower mortality (p=0.66), 21% higher ventilation (p=0.06), 13% higher ICU admission (p=0.06), and 5% higher hospitalization (p=0.26). Retrospective 14,958 US veterans who tested positive for SARS-CoV-2, showing no significant difference in severe COVID-19 outcomes (mechanical ventilation, death, ICU admission, or hospitalization) with proton pump inhibitor (PPI) use com..
Sep 30
2021
Israelsen et al., Clinical Gastroenterology and Hepatology, doi:10.1016/j.cgh.2021.05.011 Proton Pump Inhibitor Use Is Not Strongly Associated With SARS-CoV-2 Related Outcomes: A Nationwide Study and Meta-analysis
5% lower mortality (p=0.7), 8% higher ventilation (p=0.73), 5% higher ICU admission (p=0.8), and 22% higher hospitalization (p=0.005). Retrospective 83,224 SARS-CoV-2 cases and 332,799 controls in Denmark showing increased risk of infection and hospital admission with proton pump inhibitor (PPI) use, but no significant association with ICU admission or mortality.
Aug 31
2021
Toubasi et al., Archives of Medical Research, doi:10.1016/j.arcmed.2021.03.004 Proton Pump Inhibitors: Current Use and the Risk of Coronavirus Infectious Disease 2019 Development and its Related Mortality. Meta-analysis
67% higher mortality (p<0.0001) and 19% more cases (p=0.61). Meta-analysis of 6 studies with 195,230 participants showing significantly higher COVID-19 mortality with PPI use.
Aug 20
2021
Jimenez et al., Frontiers in Medicine, doi:10.3389/fmed.2021.637885 Acid pH Increases SARS-CoV-2 Infection and the Risk of Death by COVID-19
124% higher mortality (p<0.0001). In Vitro study showing lower pH increased ACE2 expression and viral load on SARS-CoV-2 infection, and retrospective study showing proton pump inhibitor use, which is correlated with low gastric pH-related diseases, was associated with hig..
May 31
2021
D'Silva et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2021.01.008 Proton pump inhibitor use and risk for recurrent Clostridioides difficile infection: a systematic review and meta-analysis
Meta-analysis of 16 studies with 57,477 patients showing significantly higher risk of recurrent Clostridioides difficile infection (CDI) in patients prescribed proton pump inhibitors (PPIs) compared to those not prescribed PPIs. The assoc..
May 27
2021
Liu et al., American Journal of Gastroenterology, doi:10.14309/ajg.0000000000001311 Increased ACE2 Levels and Mortality Risk of Patients With COVID-19 on Proton Pump Inhibitor Therapy
127% higher mortality (p=0.001). Prospective study showing COVID- PPI users had higher salivary ACE2 expression, and retrospective analysis of 694 hospitalized COVID-19 patients, showing higher mortality with PPI use.
Apr 30
2021
Cheung et al., Gastroenterology, doi:10.1053/j.gastro.2020.05.098 Association Between Famotidine Use and COVID-19 Severity in Hong Kong: A Territory-wide Study
25% lower severe cases (p=0.8). Retrospective 952 COVID-19 patients in Hong Kong, showing no significant difference in severe disease with famotidine use or PPI use.
Apr 30
2021
Morán Blanco et al., Pulmonary Pharmacology & Therapeutics, doi:10.1016/j.pupt.2021.101989 Antihistamines and azithromycin as a treatment for COVID-19 on primary health care – A retrospective observational study in elderly patients
31% fewer symptomatic cases (p=0.34). Retrospective 84 elderly nursing home residents in Spain showing no mortality, hospitalization, or ICU admission with early treatment with antihistamines alone or in combination with azithromycin.
Apr 11
2021
Pranata et al., Pharmacological Reports, doi:10.1007/s43440-021-00263-x Proton pump inhibitor on susceptibility to COVID-19 and its severity: a systematic review and meta-analysis
85% higher severe cases (p=0.01) and 56% more cases (p=0.47). Meta-analysis of 12 studies with 290,455 patients showing increased risk of poor outcomes with proton pump inhibitor (PPI) use in COVID-19 patients, but not increased susceptibility.
Mar 31
2021
Elmunzer et al., Gastroenterology, doi:10.1053/j.gastro.2020.11.007 Association Between Preadmission Acid Suppressive Medication Exposure and Severity of Illness in Patients Hospitalized With COVID-19
13% lower mortality (p=0.31) and 2% higher ventilation (p=0.89). Retrospective 1,846 hospitalized COVID-19 patients in North America showing no significant association between preadmission proton pump inhibitor (PPI) use and mechanical ventilation or mortality. Results do not account for the risk of..
Feb 28
2021
Zhang et al., Journal of Inflammation Research, doi:10.2147/JIR.S292303 Analysis of the Effect of Proton-Pump Inhibitors on the Course of COVID-19
11% longer hospitalization (p=0.29), 6% higher hospital discharge (p=0.82), and 37% improved viral clearance (p=0.05). Retrospective 154 hospitalized moderate COVID-19 patients in China showing no significant difference in viral clearance time or hospital stay duration with proton pump inhibitor (PPI) use. There was no association between PPI use and vira..
Feb 22
2021
McKeigue et al., BMC Medicine, doi:10.1186/s12916-021-01907-8 Relation of severe COVID-19 to polypharmacy and prescribing of psychotropic drugs: the REACT-SCOT case-control study
44% higher severe cases (p<0.0001). Retrospective 4,251 severe COVID-19 cases and 36,738 matched controls in Scotland showing increased risk of severe COVID-19 with PPI use and antihistamine H1RA use. Adjusted results are only provided for the patients not in care homes (2,..
Jan 31
2021
Fan et al., Gastroenterology, doi:10.1053/j.gastro.2020.09.028 Effect of Acid Suppressants on the Risk of COVID-19: A Propensity Score-Matched Study Using UK Biobank
17% higher mortality (p=0.69) and 22% more cases (p=0.15). PSM retrospective 9,469 UK Biobank participants tested for COVID-19, showing no significant association between proton pump inhibitor (PPI) or histamine-2 receptor antagonist (H2RA) use and risk of SARS-CoV-2 infection or COVID-19 mortali..
Dec 31
2020
Hariyanto et al., Digestive and Liver Disease, doi:10.1016/j.dld.2020.10.001 Proton pump inhibitor use is associated with increased risk of severity and mortality from coronavirus disease 2019 (COVID-19) infection
72% higher mortality (p=0.04) and 35% higher severe cases (p=0.002). Meta analysis of 6 studies with 5,884 COVID-19 patients showing significantly higher severity and mortality with proton pump inhibitor (PPI) usage.
Dec 4
2020
Zhou et al., Gut, doi:10.1136/gutjnl-2020-323668 Proton pump inhibitor or famotidine use and severe COVID-19 disease: a propensity score-matched territory-wide study
165% higher severe cases (p=0.0001). Retrospective 4,445 COVID+ patients in China, showing higher risk of combined death/intubation/ICU with famotidine and with PPIs.
Nov 10
2020
Li et al., Gut, doi:10.1136/gutjnl-2020-323366 Do proton pump inhibitors influence SARS-CoV-2 related outcomes? A meta-analysis
67% higher severe cases (p=0.003). Meta analysis of 16 studies from 10 countries with a total of 318,261 participants, showing current proton pump inhibitor (PPI) use was associated with higher risk of severe COVID-19 outcomes, but not with increased susceptibility to SARS..
Oct 27
2020
Mas Romero et al., PLOS ONE, doi:10.1371/journal.pone.0241030 COVID-19 outbreak in long-term care facilities from Spain. Many lessons to learn
26% lower mortality (p=0.44) and 8% more symptomatic cases (p=0.54). Retrospective 1,084 residents from 6 long-term care facilities in Spain showing no signficant difference in cases and mortality with PPI use in unadjusted results.
Oct 20
2020
Kow et al., Journal of Internal Medicine, doi:10.1111/joim.13183 Use of proton pump inhibitors and risk of adverse clinical outcomes from COVID‐19: a meta‐analysis
46% higher severe cases (p<0.0001) and 191% worse results (p=0.0006). Meta analysis of 5 studies with 37,372 total patients showing significantly increased odds of severe/fatal COVID-19 and significantly higher risk of secondary infections with proton pump inhibitor (PPI) use.
Sep 16
2020
García-Menaya et al., Frontiers in Pharmacology, doi:10.3389/fphar.2020.570721 Outcomes and Laboratory and Clinical Findings of Asthma and Allergic Patients Admitted With Covid-19 in a Spanish University Hospital
228% higher mortality (p=0.008) and 392% higher ICU admission (p=0.02). Retrospective 113 hospitalized COVID-19 patients in Spain showing higher mortality and ICU admission with PPI use.
Aug 25
2020
Almario et al., American Journal of Gastroenterology, doi:10.14309/ajg.0000000000000798 Increased Risk of COVID-19 Among Users of Proton Pump Inhibitors
179% more cases (p=0.0001). Survey of 53,130 individuals with a history of GI symptoms showing increased risk of COVID-19 positivity with proton pump inhibitor (PPI) use, especially twice-daily PPI use. There was a dose-response relationship between PPI use and COVI..
Jul 31
2020
Luxenburger et al., Journal of Internal Medicine, doi:10.1111/joim.13121 Treatment with proton pump inhibitors increases the risk of secondary infections and ARDS in hospitalized patients with COVID‐19: coincidence or underestimated risk factor?
248% higher mortality (p=0.02), 124% higher ARDS (p=0.02), and 86% worse results (p=0.03). Retrospective 152 hospitalized COVID-19 patients showing increased risk of secondary infections, ARDS, and mortality with proton pump inhibitor (PPI) use. Authors hypothesize that reduced gastric acid production from PPIs leads to bacteri..
Jul 30
2020
Lee et al., Gut, doi:10.1136/gutjnl-2020-322248 Severe clinical outcomes of COVID-19 associated with proton pump inhibitors: a nationwide cohort study with propensity score matching
79% higher severe cases (p=0.009) and 10% fewer cases (p=0.11). PSM retrospective 132,316 patients in South Korea, showing significantly higher risk of severe COVID-19 with PPI use, but no significant difference in cases.
Jul 25
2020
Vila‐Corcoles et al., The Journal of Clinical Hypertension, doi:10.1111/jch.13948 Use of distinct anti‐hypertensive drugs and risk for COVID‐19 among hypertensive people: A population‐based cohort study in Southern Catalonia, Spain
9% more cases (p=0.58). Retrospective 34,936 hypertensive outpatients in Spain showing no significant difference in COVID-19 cases with PPIs and antihistamine H1RAs.
May 29
2020
Argenziano et al., BMJ, doi:10.1136/bmj.m1996 Characterization and clinical course of 1000 patients with coronavirus disease 2019 in New York: retrospective case series
1% lower ICU admission (p=1) and 9% higher hospitalization (p=0.01). Retrospective 1,000 hospitalized COVID-19 patients in New York City showing high rates of acute kidney injury, inpatient dialysis, prolonged intubation times, and length of stay compared to previous cohorts.
May 21
2020
Freedberg et al., Gastroenterology, doi:10.1053/j.gastro.2020.05.053 Famotidine Use Is Associated With Improved Clinical Outcomes in Hospitalized COVID-19 Patients: A Propensity Score Matched Retrospective Cohort Study
34% higher combined mortality/intubation (p=0.01). PSM retrospective 1,620 hospitalized patients in the USA, showing higher risk of combined death/intubation with PPI treatment.
May 2
2020
Blanc et al., Preprints, doi:10.20944/preprints202005.0016.v1 Interest of Proton Pump Inhibitors in Reducing the Occurrence of COVID-19: A Case-Control Study
56% fewer cases (p=0.005). Retrospective 179 elderly patients in France, showing higher risk of COVID-19 cases with acetaminophen use, without statistical significance.
Mar 23
2020
Yan et al., medRxiv, doi:10.1101/2020.03.19.20038539 Clinical Characteristics of Coronavirus Disease 2019 in Hainan, China
240% higher severe cases (p<0.0001). Retrospective 168 hospitalized COVID-19 patients in China showing higher risk of severe cases with acid suppression drugs.
Jun 1
2017
Tariq et al., JAMA Internal Medicine, doi:10.1001/jamainternmed.2017.0212 Association of Gastric Acid Suppression With Recurrent Clostridium difficile Infection
Meta-analysis of 16 observational studies with 7,703 patients showing increased risk of recurrent C. difficile infection with gastric acid suppressant use (PPIs alone or PPIs/H2RAs).
Dec 31
2015
Xu et al., Genetics and Molecular Research, doi:10.4238/2015.July.3.25 Proton pump inhibitor use and risk of spontaneous bacterial peritonitis in cirrhotic patients: a systematic review and meta-analysis
Meta analysis of 17 observational studies with 8,204 patients showing 2-fold increased risk of spontaneous bacterial peritonitis (SBP) and overall bacterial infection with proton pump inhibitor (PPI) use in cirrhotic patients with ascites..
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