Association between bisphosphonate use and COVID-19 related outcomes.
Autor: | Thompson J; Cerner Enviza, Malvern, United States., Wang Y; Dept. of Immunology, Harvard Medical School, Boston, United States., Dreischulte T; Institute of General Practice and Family Medicine, University Hospital of Ludwig Maximilians-University Munich, Munich, Germany., Barreiro O; Dept. of Immunology, Harvard Medical School, Boston, United States., Gonzalez RJ; Dept. of Immunology, Harvard Medical School, Boston, United States., Hanč P; Dept. of Immunology, Harvard Medical School, Boston, United States., Matysiak C; Dept. of Immunology, Harvard Medical School, Boston, United States., Neely HR; Dept. of Immunology, Harvard Medical School, Boston, United States., Rottenkolber M; Institute of General Practice and Family Medicine, University Hospital of Ludwig Maximilians-University Munich, Munich, Germany., Haskell T; Cerner Enviza, Malvern, United States., Endres S; Center of Integrated Protein Science Munich and Division of Clinical Pharmacology, University Hospital, LMU Munich, Germany, Munich, Germany., von Andrian UH; Dept. of Immunology, Harvard Medical School, Boston, United States. |
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Jazyk: | angličtina |
Zdroj: | ELife [Elife] 2023 Aug 03; Vol. 12. Date of Electronic Publication: 2023 Aug 03. |
DOI: | 10.7554/eLife.79548 |
Abstrakt: | Background: Although there are several efficacious vaccines against COVID-19, vaccination rates in many regions around the world remain insufficient to prevent continued high disease burden and emergence of viral variants. Repurposing of existing therapeutics that prevent or mitigate severe COVID-19 could help to address these challenges. The objective of this study was to determine whether prior use of bisphosphonates is associated with reduced incidence and/or severity of COVID-19. Methods: A retrospective cohort study utilizing payer-complete health insurance claims data from 8,239,790 patients with continuous medical and prescription insurance January 1, 2019 to June 30, 2020 was performed. The primary exposure of interest was use of any bisphosphonate from January 1, 2019 to February 29, 2020. Bisphosphonate users were identified as patients having at least one bisphosphonate claim during this period, who were then 1:1 propensity score-matched to bisphosphonate non-users by age, gender, insurance type, primary-care-provider visit in 2019, and comorbidity burden. Main outcomes of interest included: (a) any testing for SARS-CoV-2 infection; (b) COVID-19 diagnosis; and (c) hospitalization with a COVID-19 diagnosis between March 1, 2020 and June 30, 2020. Multiple sensitivity analyses were also performed to assess core study outcomes amongst more restrictive matches between BP users/non-users, as well as assessing the relationship between BP-use and other respiratory infections (pneumonia, acute bronchitis) both during the same study period as well as before the COVID outbreak. Results: A total of 7,906,603 patients for whom continuous medical and prescription insurance information was available were selected. A total of 450,366 bisphosphonate users were identified and 1:1 propensity score-matched to bisphosphonate non-users. Bisphosphonate users had lower odds ratios (OR) of testing for SARS-CoV-2 infection (OR = 0.22; 95%CI:0.21-0.23; p<0.001), COVID-19 diagnosis (OR = 0.23; 95%CI:0.22-0.24; p<0.001), and COVID-19-related hospitalization (OR = 0.26; 95%CI:0.24-0.29; p<0.001). Sensitivity analyses yielded results consistent with the primary analysis. Bisphosphonate-use was also associated with decreased odds of acute bronchitis (OR = 0.23; 95%CI:0.22-0.23; p<0.001) or pneumonia (OR = 0.32; 95%CI:0.31-0.34; p<0.001) in 2019, suggesting that bisphosphonates may protect against respiratory infections by a variety of pathogens, including but not limited to SARS-CoV-2. Conclusions: Prior bisphosphonate-use was associated with dramatically reduced odds of SARS-CoV-2 testing, COVID-19 diagnosis, and COVID-19-related hospitalizations. Prospective clinical trials will be required to establish a causal role for bisphosphonate-use in COVID-19-related outcomes. Funding: This study was supported by NIH grants, AR068383 and AI155865, a grant from MassCPR (to UHvA) and a CRI Irvington postdoctoral fellowship, CRI2453 (to PH). Competing Interests: JT, TH are full time employees of Cerner Health and have received support for attending ISPOR 2022 from Cerner Enviza (previously Kantar Health). The authors have no other competing interests to declare, YW, OB, RG, PH, CM, HN, MR No competing interests declared, TD received payments/honoraria from Techniker Krankenkasse (public insurance fund) for editing a report on COVID-19 treatments, and research grants from BMBF (German federal ministry for research) and from the Innovationsfond (German federal research fund for health services research). The author has no other competing interests to declare, SE received grants from BMBF (German Federal Ministry for Research) and Bio-M (Munich Cluster Organisation). The author received royalties/licenses from TCR2, Cambridge, MA, USA and Carina Biotech Ltd, Mawson Lakes, Australia. The author received honoraria for chairing the Scientific committee at Else Kröner Fresenius Foundation (non-profit), acting as scientific advisor for the Paul-Martini-Foundation (non-profit) and textbook editor and author for Elsevier. The author received payment for expert testimony from CMS Hasche Sigle, Law firm and Gilde Healthcare, Utrecht, Netherlands (private equity investor). The author holds stock options at TCR2, Cambridge, MA, USA. Patents have been issued for Bispecific antibody molecules with antigentransfected T cells and their use in medicine, and PD1-CD28 fusions proteins and their use in medicine. Patents are pending for CXCR6 transduced T cells for targeted tumor therapy, Improving adoptive cellular therapy, CCR8 transduced T cells for targeted tumor therapy and CSF1R-targeted immunotherapies. The author has no other competing interests to declare, Uv received the following grants unrelated to this project; HMS-AbbVie Alliance, Program Area 1; Project 1: 'Host-virus interaction dynamics in nasal mucosa and associated lymphoid tissues', Gates Foundation, OPP1155348 'Mucosal Vaccine Consortium' and Moderna-HMS ARTiMIS Alliance. Ulrich H von Andrian was granted the following patents unrelated to this project; US Patents #9539210, 8932595, 8277812, 8906381, 8343497 licensed to Selecta Biosciences, and US Patent #11111472 licensed to SQZ. The author is a paid consultant of AbbVie, Avenge Bio, Beam Therapeutics, Bluesphere Bio, FL72, DNAlite, Gate Biosciences, Gentibio, Intergalactic, intrECate Biotherapeutics, Interon, Institute for Protein Innovation, Mallinckrodt Pharmaceuticals, Moderna, Monopteros Biotherapeutics, Morphic Therapeutics, Rubius, Selecta and SQZ. The author holds stock/stock options at Avenge Bio, Beam, Bluesphere, FL72, IntrECate, Interon, Moderna, Monopteros, Morphic, Rubius, Selecta and SQZ. The author received payment/honoraria for a Keynote Lecture at 'Applied Pharmaceutical Nanotechnology 2019', Cambridge, MA (organized by Pfizer), Nov. 2019 and Mallinckrodt Mini-Symposium, Oct. 2019. The author received support as a speaker at the following conferences: Ethics in Medicine Seminar, San Servolo Italy, May 2022; Keystone Symposium 'B and T cell Memory'; Keystone Symposium 'Stromal Cells in Immunity and Disease', Feb. 2020; and HIV Prevention Workshop, South Africa, Nov. 2019. The author is an inventor on the following pending patents: Ziegler et al. 'Methods and composition for modulating immune response and immune homeostasis', Docket # BROD-4830US; Thiriot et al. 'Modulating phenotype and function of high endothelial venules' Provisional docket # 00742-304001, von Andrian and Thiriot. 'Microvessel endothelial cells and uses thereof' Provisional docket #HRVY 026-001. The author holds a leadership/fiduciary role on the Monopteros Biotherapeutics Board of Directors, intrECate Biotherapeutics Board of Directors and Councilor of the American Association of Immunologists. The author has no other competing interests to declare (© 2023, Thompson, Wang et al.) |
Databáze: | MEDLINE |
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