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Proton pump inhibitor on susceptibility to COVID-19 and its severity: a systematic review and meta-analysis

Pranata et al., Pharmacological Reports, doi:10.1007/s43440-021-00263-x, PROSPERO CRD42020224286
Apr 2021  
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Severe case -85% Improvement Relative Risk Case -56% PPIs for COVID-19  Pranata et al.  META ANALYSIS c19early.org FavorsPPI Favorscontrol 0 0.5 1 1.5 2+
PPIs for COVID-19
1st treatment shown to increase risk in September 2020, now with p = 0.00000012 from 39 studies.
5,100+ studies for 109 treatments. c19early.org
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.
8 meta analyses show significant harm with PPIs for mortality1-3, severity1,2,4-8, and cases2.
Currently there are 39 PPIs 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%].
risk of severe case, 85.0% higher, OR 1.85, p = 0.01, RR approximated with OR.
risk of case, 56.0% higher, OR 1.56, p = 0.47, RR approximated with OR.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Pranata et al., 11 Apr 2021, peer-reviewed, 8 authors, trial PROSPERO CRD42020224286. Contact: sherlylawrensia@gmail.com, joshuahenrina@gmail.com, antonia.lukito@uph.edu, lukito_ant@yahoo.com, lukito@uph.edu, raymond_pranata@hotmail.com, ianhuang2108@gmail.com, lim.michael.a@gmail.com, tutykuswardhani@unud.ac.id, tutykuswardhani@yahoo.com, dnwib.dps@centrin.net.id.
This PaperPPIsAll
Proton pump inhibitor on susceptibility to COVID-19 and its severity: a systematic review and meta-analysis
Raymond Pranata, Ian Huang, Sherly Lawrensia, Joshua Henrina, Michael Anthonius Lim, Antonia Anna Lukito, Raden Ayu Tuty Kuswardhani, I Dewa Nyoman Wibawa
Pharmacological Reports, doi:10.1007/s43440-021-00263-x
Background The negative impacts of proton pump inhibitor (PPI), including the risk of pneumonia and mortality, have been reported previously. This meta-analysis aimed to address the current interest of whether the administration of PPI could increase the susceptibility and risk of poor outcome in COVID-19. Methods We performed a systematic literature search from PubMed, Embase, EBSCOhost, and EuropePMC databases up until 3 December 2020. The main outcome was composite poor outcome which comprised of mortality and severe COVID-19. Severe COVID-19 in this study was defined as patients with COVID-19 that fulfill the criteria for severe CAP, including the need for intensive unit care or mechanical ventilation. The secondary outcome was susceptibility, based on cohort comparing COVID-19 positive and COVID-19 negative participants. Results There were a total of 290,455 patients from 12 studies in this meta-analysis. PPI use was associated with increased composite poor outcome (OR 1.85 [1.13, 3 .03], p = 0.014; I 2 90.26%). Meta-regression analysis indicate that the association does not vary by age (OR 0.97 [0.92, 1.02], p = 0.244), male (OR 1.05 [0.99, 1.11], p = 0.091), hypertension (OR 9.98 [0.95, 1.02], p = 0.317), diabetes (OR 0.99 [0.93, 1.05], p = 0.699), chronic kidney disease (OR 1.01 [0.93, 1.10], p = 0.756), nonsteroidal anti-inflammatory drug use (OR 1.02 [0.96, 1.09], p = 0.499), and pre-admission/in-hospital PPI use (OR 0.77 [0.26, 2.31], p = 0.644). PPI use was not associated with the susceptibility to COVID-19 (OR 1.56 [0.48, 5 .05], p = 0.46; I 2 99.7%). Conclusion This meta-analysis showed a potential association between PPI use and composite poor outcome, but not susceptibility.
Declarations Conflict of interest The authors declare that they have no conflict of interest. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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' '2020;158:1831–3. https://doi.org/10.1053/j.gastro.2020.02.055 (e3).', 'journal-title': 'Gastroenterology'}, { 'key': '263_CR33', 'doi-asserted-by': 'publisher', 'first-page': '142', 'DOI': '10.2174/1389200219666171207125351', 'volume': '19', 'author': 'A Corsonello', 'year': '2017', 'unstructured': 'Corsonello A, Lattanzio F, Bustacchini S, Garasto S, Cozza A, Schepisi ' 'R, et al. Adverse events of proton pump inhibitors: potential ' 'mechanisms. Curr Drug Metab. 2017;19:142–54. ' 'https://doi.org/10.2174/1389200219666171207125351.', 'journal-title': 'Curr Drug Metab'}, { 'key': '263_CR34', 'doi-asserted-by': 'publisher', 'first-page': '215', 'DOI': '10.1111/j.1365-2710.2008.00907.x', 'volume': '33', 'author': 'MR Namazi', 'year': '2008', 'unstructured': 'Namazi MR, Jowkar F. A succinct review of the general and immunological ' 'pharmacologic effects of proton pump inhibitors. J Clin Pharm Ther. ' '2008;33:215–7. https://doi.org/10.1111/j.1365-2710.2008.00907.x.', 'journal-title': 'J Clin Pharm Ther'}, { 'key': '263_CR35', 'doi-asserted-by': 'publisher', 'first-page': '1566', 'DOI': '10.1111/jgh.14157', 'volume': '33', 'author': 'T Qiu', 'year': '2018', 'unstructured': 'Qiu T, Zhou J, Zhang C. Acid-suppressive drugs and risk of kidney ' 'disease: a systematic review and meta-analysis. J Gastroenterol Hepatol. ' '2018;33:1566–73. https://doi.org/10.1111/jgh.14157.', 'journal-title': 'J Gastroenterol Hepatol'}, { 'key': '263_CR36', 'doi-asserted-by': 'publisher', 'first-page': '3153', 'DOI': '10.1681/ASN.2015121377', 'volume': '27', 'author': 'Y Xie', 'year': '2016', 'unstructured': 'Xie Y, Bowe B, Li T, Xian H, Balasubramanian S, Al-Aly Z. Proton pump ' 'inhibitors and risk of incident CKD and progression to ESRD. 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Clin Med Insights Circ Respir Pulm Med. ' '2020;14:1179548420959165. https://doi.org/10.1177/1179548420959165.', 'journal-title': 'Clin Med Insights Circ Respir Pulm Med'}, { 'key': '263_CR39', 'doi-asserted-by': 'publisher', 'first-page': '205435812093857', 'DOI': '10.1177/2054358120938573', 'volume': '7', 'author': 'MA Lim', 'year': '2020', 'unstructured': 'Lim MA, Pranata R, Huang I, Yonas E, Soeroto AY, Supriyadi R. Multiorgan ' 'failure with emphasis on acute kidney injury and severity of COVID-19: ' 'systematic review and meta-analysis. Can J Kidney Heal Dis. ' '2020;7:205435812093857. https://doi.org/10.1177/2054358120938573.', 'journal-title': 'Can J Kidney Heal Dis'}, { 'key': '263_CR40', 'doi-asserted-by': 'publisher', 'DOI': '10.1111/1744-9987.13597', 'author': 'R Andhika', 'year': '2020', 'unstructured': 'Andhika R, Huang I, Wijaya I. Severity of COVID-19 in end-stage kidney ' 'disease patients on chronic dialysis. Ther Apher Dial. 2020. ' 'https://doi.org/10.1111/1744-9987.13597.', 'journal-title': 'Ther Apher Dial'}], 'container-title': 'Pharmacological Reports', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://link.springer.com/content/pdf/10.1007/s43440-021-00263-x.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/article/10.1007/s43440-021-00263-x/fulltext.html', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/content/pdf/10.1007/s43440-021-00263-x.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2021, 11, 18]], 'date-time': '2021-11-18T05:12:15Z', 'timestamp': 1637212335000}, 'score': 1, 'resource': {'primary': {'URL': 'https://link.springer.com/10.1007/s43440-021-00263-x'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2021, 4, 11]]}, 'references-count': 40, 'journal-issue': {'issue': '6', 'published-print': {'date-parts': [[2021, 12]]}}, 'alternative-id': ['263'], 'URL': 'http://dx.doi.org/10.1007/s43440-021-00263-x', 'relation': {}, 'ISSN': ['1734-1140', '2299-5684'], 'subject': [], 'container-title-short': 'Pharmacol. 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