Therapeutic prevention of COVID-19 in elderly: a case–control study
Frederic Blanc, Cedric Waechter, Thomas Vogel, Benoit Schorr, Catherine Demuynck, Catherine Martin Hunyadi, Maxence Meyer, Denata Mutelica, Nadjiba Bougaa, Samira Fafi-Kremer, Lidia Calabrese, Elise Schmitt, Delphine Imperiale, Catherine Jehl, Alexandre Boussuge, Carmen Suna, François Weill, Alexia Matzinger, Candice Muller, Patrick Karcher, Georges Kaltenbach, Erik Sauleau
GeroScience, doi:10.1007/s11357-021-00397-z
15 days prior to RT-PCR (including antihypertensive drugs, antipsychotics, antibiotics, nonsteroidal anti-inflammatory drugs, proton pump inhibitors (PPIs), oral antidiabetics (OADs), corticosteroids, immunosuppressants), comorbidities, symptoms, laboratory values, and clinical outcome were all collected. COVID-pos patients more frequently had a history of diabetes (P = .016) and alcoholism (P = .023), a lower leukocyte count (P = .014) and a higher mortality rate -29.2% versus 14.4% -(P = .014) when compared to COVID-neg patients. Patients on PPIs were 2.3 times less likely (odds ratio [OR] = 0.4381, 95% confidence interval [CI] [0.2331, 0.8175], P = .0053) to develop COVID-19 infection, compared to those not on PPIs. No other treatment decreased or increased this risk. COVID-pos patients on antipsychotics (P = .0013) and OADs (P = .0153), particularly metformin (P = .0237), were less likely to die. Thus, patients on treatment with PPI were less likely to develop COVID-19 infection, and those on antipsychotics or metformin had a lower risk of mortality. However, prospective studies, including clinical trials, are needed to confirm or not these findings.
Author contribution
Data and materials availability After publication, the data will be made available to others on reasonable requests to the corresponding author. A proposal with detailed description of study objectives and statistical analysis plan will be needed for evaluation of the reasonability of requests. Additional materials might also be required during the process of evaluation. Deidentified participant data will be provided after approval from the corresponding author.
Declarations Ethics approval and consent to participate Ethics committee "Faculté de Médecine de Strasbourg" number CE-2020-68.
Consent for publication Yes.
Conflict of interest The authors declare no competing interests.
Supplementary Information The online version contains supplementary material available at https:// doi. org/ 10. 1007/ s11357-021-00397-z. Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
Cetin, Increased risk of death associated with the use of proton pump inhibitors in dementia patients and controls -a pharmacoepidemiological claims data analysis, Eur J Neurol,
doi:10.1111/ene.14252
Chang, Letter: suppression of herpetic recurrence by chlorpromazine, N Engl J Med
Chen, Clinical characteristics and outcomes of older patients with coronavirus disease 2019 (COVID-19) in Wuhan, China (2019): a single-centered, retrospective study, J Gerontol Ser A,
doi:10.1093/gerona/glaa089
Crouse, Grimes, Li, Might, Ovalle et al., Metformin use is associated with reduced mortality in a diverse population with COVID-19 and diabetes, Front Endocrinol,
doi:10.3389/fendo.2020.600439
Geerlings, Hoepelman, Immune dysfunction in patients with diabetes mellitus (DM), FEMS Immunol Med Microbiol
Gomm, Association of proton pump inhibitors with risk of dementia: a pharmacoepidemiological claims data analysis, JAMA Neurol,
doi:10.1001/jamaneurol.2015.4791
Gordon, A SARS-CoV-2-human protein-protein interaction map reveals drug targets and potential drugrepurposing
Grasselli, Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region Italy, JAMA,
doi:10.1001/jama.2020.5394
Gurwitz, Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics, Drug Dev Res,
doi:10.1002/ddr.21656
Homolak, Kodvanj, Widely available lysosome targeting agents should be considered as a potential therapy for COVID-19
Hreinsson, Palsdóttir, Bjornsson, The association of drugs with severity and specific causes of acute lower gastrointestinal bleeding, J Clin Gastroenterol
Hálfdánarson, Proton-pump inhibitors among adults: a nationwide drug-utilization study, Ther Adv Gastroenterol,
doi:10.1177/1756284818777943
Jones-Brando, Buthod, Holland, Yolken, Torrey, Metabolites of the antipsychotic agent clozapine inhibit the replication of human immunodeficiency virus type 1, Schizophr Res,
doi:10.1016/s0920-9964(97)00007-8
Klompas, Coronavirus disease 2019 (COVID-19): protecting hospitals from the invisible, Ann Intern Med,
doi:10.7326/m20-0751
Lee, Proton pump inhibitors enhance the effects of cytotoxic agents in chemoresistant epithelial ovarian carcinoma, Oncotarget,
doi:10.18632/oncotarget.5319
Lee, Severe clinical outcomes of COVID-19 associated with proton pump inhibitors: a nationwide cohort study with propensity score matching, Gut,
doi:10.1136/gutjnl-2020-322248
Luxenburger, Treatment with proton pump inhibitors increases the risk of secondary infections and ARDS in hospitalized patients with COVID-19: coincidence or underestimated risk factor?, J Intern Med,
doi:10.1111/joim.1312110.1111/joim.13121
Mehta, Yeligar, Elon, Brown, Guidot, Alcoholism causes alveolar macrophage zinc deficiency and immune dysfunction, Am J Respir Crit Care Med
Moatti, The French response to COVID-19: intrinsic difficulties at the interface of science, public health, and policy
Richardson, Hirsch, Narasimhan, Crawford, Mcginn et al., Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City Area, JAMA,
doi:10.1001/jama.2020.6775
Simmons, Reeves, Rennekamp, Amberg, Piefer et al., Characterization of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike glycoprotein-mediated viral entry, Proc Natl Acad Sci U S A,
doi:10.1073/pnas.0306446101
Spugnini, Lansoprazole as a rescue agent in chemoresistant tumors: a phase I/II study in companion animals with spontaneously occurring tumors, J Transl Med,
doi:10.1186/1479-5876-9-221
Team, Vital surveillances: the epidemiological characteristics of an outbreak of 2019 Novel coronavirus diseases (COVID-19)-China, 2020 China, CDC Wkly
Vaduganathan, Vardeny, Michel, Mcmurray, Pfeffer et al., Renin-angiotensin-aldosterone system inhibitors in patients with Covid-19, N Engl J Med,
doi:10.1056/NEJMsr2005760
Voysey, Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK, Lancet,
doi:10.1016/S0140-6736(20)32661-1.
Who E, COVID-19 weekly surveillance report
Wunderlich, Fey, Sydow, Antiviral effect of haloperidol on Rauscher murine leukemia virus, Archiv fur Geschwulstforschung
Yang, Shen, Targeting the endocytic pathway and autophagy process as a novel therapeutic strategy in COVID-19, Int J Biol Sci,
doi:10.7150/ijbs.45498
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