https://doi.org/10.4081/monaldi.2021.1803
Which impact for proton pump inhibitors in SARS-CoV-2 pneumonia
Submitted: February 14, 2021
Accepted: June 8, 2021
Published: October 19, 2021
Accepted: June 8, 2021
Abstract Views: 1087
PDF: 525
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Identification of risk factors for severe outcome of SARS-CoV-2 infection is an important issue in COVID-19 management. Much attention has been focused on comorbidities as well as drugs taken by patients. Usage of proton pump inhibitors (PPIs) appears to potentially influence disease course. These drugs are known to reduce stomach acid and also modulate the immune system. Their use, prior to and during COVID-19 infection, seems to predispose to the development of more severe pneumonia and therefore to a greater risk of mortality. Instead, the use of histamine receptor 2 antagonists (H2RAs) seems to be associated with a better outcome in patients with COVID-19, in terms of symptoms, risk of intubation and death. As PPIs are essential for treatment of many disorders, usage of these drugs should be balanced considering the benefits and risk ratio, in order to guarantee their correct use for the necessary time. It remains to be clarified whether the detrimental effects, in terms of COVID-19 severe outcome, are due to PPIs or to the underlying disease for which they are administered. New controlled-randomized trials are required to better understand their impact in SARS-CoV-2 infections.
*Vanvitelli/Monaldi COVID Group: Adriano Cristinziano, Carolina Delle Donne, Cecilia Calabrese, Fabio Perrotta, Filippo Scialò, Francesco Lassandro, Gennaro Mazzarella, Giorgio Paoli, Leonardo De Luca, Maria Galdo, Miriam Buonincontro, Roberta Cianci, Rosalba Donizzetti, Stefano Sanduzzi Zamparelli, Tullio Valente, Vito D’Agnano, Vittorio Bisogni
Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese center for disease control and prevention. JAMA 2020;323:1239.
DOI: https://doi.org/10.1001/jama.2020.2648
Sagnelli C, Celia B, Monari C, et al. Management of SARS-CoV-2 pneumonia. J Med Virol 2021 Mr;93:1276-87.
DOI: https://doi.org/10.1002/jmv.26470
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497-506.
DOI: https://doi.org/10.1016/S0140-6736(20)30183-5
Aziz M, Perisetti A, Lee-Smith WM, et al. Taste changes (Dysgeusia) in COVID-19: a systematic review and metaanalysis. Gastroenterology 2020;159:1132-3.
DOI: https://doi.org/10.1053/j.gastro.2020.05.003
Aziz M, Haghbin H, Lee-Smith W, at al. Gastrointestinal predictors of severe COVID-19: syste- matic review and meta-analysis. Ann Gastroenterol 2020;33:1-16.
Perrotta, F., Corbi, G., Mazzeo, G., at al. COVID-19 and the elderly: insights into pathogenesis and clinical decision-making. Aging Clin Exper Res 2020;32:1599-608.
DOI: https://doi.org/10.1007/s40520-020-01631-y
Iadevaia C, Perrotta F, Mazzeo G, at al. Incidental diagnosis of lung adenocarcinoma following coronavirus OC 43 severe pneumonia. Monaldi Arch Chest Dis 2020;90:1313.
DOI: https://doi.org/10.4081/monaldi.2020.1313
Nigro E, Perrotta F, Polito R, et al. Metabolic perturbations and severe COVID-19 disease: Implication of molecular pathways. Int J Endocrinol 2020;2020:8896536.
DOI: https://doi.org/10.1155/2020/8896536
Pottegård A, Kurz X, Moore N, et al. Considerations for pharmacoepidemiological analyses in the SARS-CoV-2 pandemic. Pharmacoepidemiol Drug Saf 2020;29:825-31.
DOI: https://doi.org/10.1002/pds.5029
Hariyanto TI, Kurniawan A. Metformin use is associated with reduced mor- tality rate from coronavirus disease 2019 (COVID-19) infection. Obes Med 2020;19:100290.
DOI: https://doi.org/10.1016/j.obmed.2020.100290
Pranata R, Permana H, Huang I, et al. The use of renin angiotensin system inhibitor on mortality in patients with coronavirus disease 2019 (COVID-19): a systematic review and meta-analysis. Diabetes Metab Syndr 2020;14:983–90.
DOI: https://doi.org/10.1016/j.dsx.2020.06.047
Hariyanto TI, Kurniawan A. Statin therapy did not improve the in-hospital out- come of coronavirus disease 2019 (COVID-19) infection. Diabetes Metab Syndr 2020;14:1613–15.
DOI: https://doi.org/10.1016/j.dsx.2020.08.023
Wang CH, Li CH, Hsieh R, et al. Proton pump in- hibitors therapy and the risk of pneumonia: a systematic review and meta– analysis of randomized controlled trials and observational studies. Expert Opin Drug Saf 2019;18:163–72.
DOI: https://doi.org/10.1080/14740338.2019.1577820
Vaezi MF, Yang YX, Howden CW. Complications of proton pump inhibitor therapy. Gastroenterology 2017;153:35-48.
DOI: https://doi.org/10.1053/j.gastro.2017.04.047
Moayyedi P, Delaney BC, Vakil N, et al. The efficacy of pro- ton pump inhibitors in nonulcer dyspepsia: a systematic review and economic analysis. Gastroenterology 2004;127:1329–37.
DOI: https://doi.org/10.1053/j.gastro.2004.08.026
Luxenburger H, Sturm L, Biever P, et al. Treatment with proton pump inhibitors increases the risk of secondary infections and ARDS in hospital- ized patients with COVID-19: coincidence or underestimated risk factor? J Intern Med 2021;289:121-4.
DOI: https://doi.org/10.1111/joim.13121
Argenziano MG, Bruce SL, Slater CL, et al. Characterization and clinical course of 1000 patients with coronavirus disease 2019 in New York: retrospective case series. BMJ 2020;369:m1996.
DOI: https://doi.org/10.1136/bmj.m1996
Lee SW, Ha EK, Yeniova AO, et al. Severe clinical outcomes of COVID-19 associated with proton pump inhibitors: a nation-wide cohort study with propensity score matching. Gut 2021;70:76-84.
DOI: https://doi.org/10.1136/gutjnl-2020-322248
Shin JM, Sachs G. Pharmacology of proton pump inhibitors. Curr Gastroenterol Rep 2008;10:528–34.
DOI: https://doi.org/10.1007/s11894-008-0098-4
Trifan A, Stanciu C, Girleanu I, et al. Proton pump inhibitors therapy and risk of Clostridium difficile infection: systematic review and meta-analysis. World J Gastroenterol 2017;23:6500–15.
DOI: https://doi.org/10.3748/wjg.v23.i35.6500
Kanno T, Matsuki T, Oka M, et al. Gastric acid reduction leads to an alteration in lower intestinal microflora. Biochem Biophys Res Commun 2009;381:666–70.
DOI: https://doi.org/10.1016/j.bbrc.2009.02.109
Seto CT, Jeraldo P, Orenstein R, et al. Prolonged use of a proton pump inhibitor reduces microbial diversity: Implications for Clostridium difficile susceptibility. Microbiome 2014;2:42.
DOI: https://doi.org/10.1186/2049-2618-2-42
Darnell ME, Subbarao K, Feinstone SM, et al. Inactivation of the coronavirus that induces severe acute respiratory syndrome, SARS-CoV. J Virol Methods 2004;121:85–91.
DOI: https://doi.org/10.1016/j.jviromet.2004.06.006
Trottein F, Sokol H. Potential causes and consequences of gastrointestinal disorders during a SARS-CoV-2 infection. Cell Rep 2020;32:107915.
DOI: https://doi.org/10.1016/j.celrep.2020.107915
Xiao F, Tang M, Zheng X, et al. Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology 2020;158:1831-3.e3.
DOI: https://doi.org/10.1053/j.gastro.2020.02.055
Scialo F, Daniele A, Amato F, et al. ACE2: The major cell entry receptor for SARS-CoV-2. Lung 2020;198:867–77.
DOI: https://doi.org/10.1007/s00408-020-00408-4
Lamers MM, Beumer J, van der Vaart J, et al. SARS-CoV-2 productively infects human gut enterocytes. Science 2020;369:50-4.
DOI: https://doi.org/10.1126/science.abc1669
Perrotta F, Matera MG, Cazzola M, Bianco A. Severe respiratory SARS-CoV2 infection: Does ACE2 receptor matter? Respir Med 2020;168:105996.
DOI: https://doi.org/10.1016/j.rmed.2020.105996
Hamming I, Timens W, Bulthuis ML, et al. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol 2004;203:631–7.
DOI: https://doi.org/10.1002/path.1570
Zhang H, Liao YS, Gong J, et al. Clinical characteristics of coronavirus disease (COVID-19) patients with gastrointestinal symptoms: a report of 164 cases. Dig Liver Dis 2020;52:1076-9.
DOI: https://doi.org/10.1016/j.dld.2020.04.034
Sultan S, Altayar O, Siddique SM, et al. AGA Institute rapid review of the GI and liver manifestations of COVID-19, meta-analysis of international data, and recommendations for the consultative management of patients with COVID-19. Gastroenterology 2020;159:320-34.e27.
DOI: https://doi.org/10.1053/j.gastro.2020.05.001
Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020;181:271–80.
DOI: https://doi.org/10.1016/j.cell.2020.02.052
Dhar D, Mohanty A. Gut microbiota and Covid-19 - possible link and implications. Virus Res 2020;285:198018.
DOI: https://doi.org/10.1016/j.virusres.2020.198018
Boccia M, Aronne L, Celia B, et al. COVID-19 and coagulative axis: review of emerging aspects in a novel disease. Monaldi Arch Chest 2020;90:1300.
DOI: https://doi.org/10.4081/monaldi.2020.1300
Monteleone G, Sarzi-Puttini PC, Ardizzone S. Preventing COVID-19-induced pneumonia with anticytokine therapy. Lancet Rheumatol 2020;2:e255–6.
DOI: https://doi.org/10.1016/S2665-9913(20)30092-8
Zhou J, Li C, Zhao G, et al. Human intestinal tract serves as an alternative infection route for Middle East Respiratory Syndrome coronavirus. Sci Adv 2017;3:eaao4966.
DOI: https://doi.org/10.1126/sciadv.aao4966
Eom, C.-S., Jeon, C. Y., Lim, J.-W et al. Use of acid-suppressive drugs and risk of pneumonia: a systematic review and meta-analysis. Can Med Assoc J 2011;183:310-9.
DOI: https://doi.org/10.1503/cmaj.092129
Laheij RJF, Sturkenboom MCJM, Hassing R-J, et al. Risk of community-acquired pneumonia and use of gastric acid–suppressive drugs. JAMA 2004;292:1955-60.
DOI: https://doi.org/10.1001/jama.292.16.1955
Altman KW, Waltonen JD, Hammer ND, et al. Proton pump (H+/K+-ATPase) expression in human laryngeal seromucinous glands. Otolaryngol Head Neck Surg 2005;133:718-24.
DOI: https://doi.org/10.1016/j.otohns.2005.07.036
Savarino V, Di Mario F, Scarpignato C. Proton pump inhibitors in GORD: An overview of their pharmacology, efficacy and safety. Pharmacol Res 2009;59:135-53.
DOI: https://doi.org/10.1016/j.phrs.2008.09.016
Aybay C, Imir T, Okur H. The effect of omeprazole on human natural killer cell activity. Gen Pharmacol 1995;26:1413-8.
DOI: https://doi.org/10.1016/0306-3623(94)00301-3
Zedtwitz-Liebenstein K, Wenisch C, Patruta S, et al. Omeprazole treatment diminishes intra- and extracellular neutrophil reactive oxygen production and bactericidal activity. Crit Care Med 2002;30:1118-22.
DOI: https://doi.org/10.1097/00003246-200205000-00026
Lambert AA, Lam JO, Paik JJ, et al. Risk of community-acquired pneumonia with outpatient proton-pump inhibitor therapy: A systematic review and meta-analysis. PLoS One, 2015;10:e0128004.
DOI: https://doi.org/10.1371/journal.pone.0128004
Charpiat B, Bleyzac N, Tod M. Proton pump inhibitors are risk factors for viral infections: Even for COVID-19? Clin Drug Investig 2020;40:897-9.
DOI: https://doi.org/10.1007/s40261-020-00963-x
Corsonello A, Lattanzio F, Bustacchini S, et al. Adverse events of proton pump inhibitors: potential mechanisms. Curr Drug Metab 2018;19:142–54.
DOI: https://doi.org/10.2174/1389200219666171207125351
Matera MG, Rogliani P, Bianco A, Cazzola M. Pharmacological management of adult patients with acute respiratory distress syndrome. Expert Opin Pharmacother 2020;21:2169–83.
DOI: https://doi.org/10.1080/14656566.2020.1801636
Yoshida N, Yoshikawa T, Tanaka Y, et al. A new mechanism for anti-inflammatory actions of proton pump inhibitors – inhibitory effects on neutrophil–endothelial cell interactions. Aliment Pharmacol Ther 2000;14:7S4-81.
DOI: https://doi.org/10.1046/j.1365-2036.2000.014s1074.x
Savarino V, Marabotto E, Furnari M, et al. Latest insights into the hot question of proton pump inhibitor safety - a narrative review. Dig Liver Dis 2020;52:842–52.
DOI: https://doi.org/10.1016/j.dld.2020.04.020
Savarino V, Dulbecco P, Savarino E. Are proton pump inhibitors really so dan- gerous? Dig Liver Dis 2016;48:851–9.
DOI: https://doi.org/10.1016/j.dld.2016.05.018
Bhaskar S, Sinha a, Banach M, et al. Cytokine storm in COVID-19-immunopathological mechanisms, clinical considerations, and therapeutic approaches: The reprogram consortium position paper. Front Immunol 2020;11:1648.
DOI: https://doi.org/10.3389/fimmu.2020.01648
Taghizadeh-Hesary F, Akbari H. The powerful immune system against powerful COVID-19: A hypothesis. Med Hypotheses 2020;140:109762.
DOI: https://doi.org/10.1016/j.mehy.2020.109762
Kouhapey S, Shariati L, Boshtam M, et al. The molecular story of COVID-19; NAD+ depletion addresses all questions in this infection. Preprints 2020;2020030346.
Gommers LM, Hoenderop JG, Bindels RJ, de Baaij JH. Hypomagnesemia in type 2 diabetes: A vicious circle? Diabetes 2016;65:3-13.
DOI: https://doi.org/10.2337/db15-1028
Revathi R, Amaldas J. A clinical study of serum phosphate and magnesium in type II diabetes mellitus. Int J Med Res Health Sci 2014;3:808-12.
DOI: https://doi.org/10.5958/2319-5886.2014.00005.8
Roush GC, Sica DA. Diuretics for hypertension: A review and update. Am J Hypertens 2016;29:1130-7.
DOI: https://doi.org/10.1093/ajh/hpw030
Chen XM, Li Y, Guo WL, et al. [Prevalence of laryngopharyngeal reflux disease in Fuzhou region of China].[Article in Chinese]. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2016;51:909‐9.
Freedberg DE, Conigliaro J, Wang TC, et al. Famotidine use is associated with improved clinical outcomes in hospitalized COVID-19 patients: A propensity score matched retrospective cohort study. Gastroenterology 2020;159:1129-31.e3.
DOI: https://doi.org/10.1053/j.gastro.2020.05.053
Janowitz T, Gablenz E, Pattinson D, et al. Famotidine use and quantitative symptom tracking for COVID-19 in non-hospitalised patients: A case series. Gut 2020;69:1592-7.
DOI: https://doi.org/10.1136/gutjnl-2020-321852
Bourinbaiar AS, Fruhstorfer EC. The effect of histamine type 2 receptor antagonists on human immunodeficiency virus (HIV) replication: Identification of a new class of antiviral agents. Life Sci 1996;59:365-70.
Malone RW, Tisdall P, Fremont-Smith P, et al. COVID-19: famotidine, histamine, mast cells, and mechanisms. Preprint ResearchSquare 2020;rs-30934.
DOI: https://doi.org/10.21203/rs.3.rs-30934/v2
Anand K, Ziebuhr J, Wadhwani P, et al. Coronavirus main proteinase (3CLpro) structure: Basis for design of anti-SARS drugs. Science 2003;300:1763–7.
DOI: https://doi.org/10.1126/science.1085658
Wu C, Liu Y, Yang Y, et al. Analysis of therapeutic targets for SARS-CoV- 2 and discovery of potential drugs by computational methods. Acta Pharm Sin B 2020;10:766–88.
DOI: https://doi.org/10.1016/j.apsb.2020.02.008
Kritas SK, Ronconi G, Caraffa A, et al. Mast cells contribute to coronavirus-induced inflammation: New anti-inflammatory strategy. J Biol Regul Homeost Agents 2020;34:9–14.
Eliezer M, Hautefort C, Hamel A, et al. Sudden and complete olfactory loss of function as a possible symptom of COVID-19. JAMA Otolaryngol Head Neck Surg 2020;146:674–75.
DOI: https://doi.org/10.1001/jamaoto.2020.0832
Giacomelli A, Pezzati L, Conti F, et al. Self-reported olfactory and taste disorders in SARS-CoV-2 patients: A cross-sectional study. Clin Infect Dis 2020;71:889–90.
DOI: https://doi.org/10.1093/cid/ciaa330
Metcalfe DD, Baram D, Mekori YA. Mast cells. Physiol Rev 1997;77:1033–79.
DOI: https://doi.org/10.1152/physrev.1997.77.4.1033
Theoharides TC, Alysandratos KD, Angelidou A, et al. Mast cells and inflammation. Biochim Biophys Acta 2012;1822:21–33.
DOI: https://doi.org/10.1016/j.bbadis.2010.12.014
Marshall J S, Portales-Cervantes L, Leong E. Mastcell responses to viruses and pathogen products. Int J Mol Sci 2019;20:4241.
DOI: https://doi.org/10.3390/ijms20174241
Caughey GH, Raymond W W, WoltersPJ. Angiotensin II generationby mast cell alpha- and beta-chymases. Biochim Biophys Acta 2000;1480:245–57.
DOI: https://doi.org/10.1016/S0167-4838(00)00076-5
Almario CV, Chey WD, Spiegel BMR. Increased risk of COVID-19 among users of proton pump inhibitors. Am J Gastroenterol 2020;115:1707-15.
DOI: https://doi.org/10.14309/ajg.0000000000000798
Dhaun N, Webb DJ. Endothelins in cardiovascular biology and therapeutics. Nat Rev Cardiol 2019;16:491-502.
DOI: https://doi.org/10.1038/s41569-019-0176-3
Bianco A, Valente T, Perrotta F, et al. Remarkable vessel enlargement within lung consolidation in COVID-19 compared to AH1N1 pneumonia: a retrospective study in Italy. Heliyon 2021;7:e07112.
DOI: https://doi.org/10.1016/j.heliyon.2021.e07112
Mather JF, Seip RL, McKay RG. Impact of famotidine use on clinical outcomes of hospitalized patients with COVID-19. Am J Gastroenterol 2020;115:1617-23.
DOI: https://doi.org/10.14309/ajg.0000000000000832
How to Cite
Mazzeo, Grazia, Luigi Aronne, Domenica Francesca Mariniello, Valentino Allocca, Maria Ilaria Palma, Francesco Saverio Cerqua, Carlo Iadevaia, et al. 2021. “Which Impact for Proton Pump Inhibitors in SARS-CoV-2 Pneumonia”. Monaldi Archives for Chest Disease 91 (4). https://doi.org/10.4081/monaldi.2021.1803.
Copyright (c) 2021 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- Alice Biffi, Giulia Dei, Federica De Giacomi, Anna Stainer, Lorenzo Olmo Parma, Maria Rosa Pozzi, Paola Faverio, Alberto Pesci, Non-specific interstitial pneumonia and features of connective tissue disease: What are the consequences of a different point of view? , Monaldi Archives for Chest Disease: Vol. 88 No. 3 (2018)
- Gianfranco Beghi, Antonio De Tanti, Paolo Serafini, Chiara Bertolino, Antonietta Celentano, Graziella Taormina, Monitoring of hospital acquired pneumonia in patients with severe brain injury on first access to intensive neurological rehabilitation: First year of observation , Monaldi Archives for Chest Disease: Vol. 88 No. 1 (2018)
- S. Al-Muhairi, T. Zoubeidi, M. Ellis, M. Gary Nicholls, W. Safa, J. Joseph, Demographics and microbiological profile of Pneumonia in United Arab Emirates , Monaldi Archives for Chest Disease: Vol. 65 No. 1 (2006): Pulmonary series
- M. Confalonieri, M. Kodric, M. Santagiuliana, C. Longo, M. Biolo, R. Cifaldi, C. Torregiani, M. Jevnikar, To use or not to use corticosteroids for pneumonia? A clinician’s perspective , Monaldi Archives for Chest Disease: Vol. 77 No. 2 (2012): Pulmonary series
- Angel Estella, Usefulness of CURB-65 and Pneumonia Severity Index for Influenza A H1N1v pneumonia , Monaldi Archives for Chest Disease: Vol. 77 No. 3-4 (2012): Pulmonary series
- Neeta Singla, Amitesh Gupta, U.K. Khalid, Ravindra Kumar Dewan, Rupak Singla, Clinical profile, risk factors, disease severity, and outcome for COVID-19 disease in patients with tuberculosis on treatment under the National Tuberculosis Elimination Program: a cohort of 1400 patients , Monaldi Archives for Chest Disease: Early Access
- P.A. Canessa, L. Pratticò, M. Sivori, P. Magistrelli, F. Fedeli, A. Cavazza, G. Calcina, Acute Fibrinous and Organising Pneumonia in Whipple’s disease , Monaldi Archives for Chest Disease: Vol. 69 No. 4 (2008): Pulmonary series
- Chi Fong Wong, See Wan Yan, Wai Mui Wong, Ronnie S.L. Ho, Exogenous lipoid pneumonia associated with oil pulling: Report of two cases , Monaldi Archives for Chest Disease: Vol. 88 No. 3 (2018)
- Matteo Petroncini, Leonardo Valentini, Piergiorgio Solli, Pietro Bertoglio, Giant lung bulla as a late-onset complication of mild SARS-CoV-2 pneumonia , Monaldi Archives for Chest Disease: Vol. 94 No. 3 (2024)
- C. Carbonelli, A. Roggeri, A. Cavazza, M. Zompatori, L. Zucchi, Relapsing bronchiolitis obliterans organising pneumonia and chronic sarcoidosis in an atopic asthmatic patient , Monaldi Archives for Chest Disease: Vol. 69 No. 1 (2008): Pulmonary series
You may also start an advanced similarity search for this article.
