Association between Bisphosphonate use and COVID-19 related outcomes
- Cerner Enviza, United States
- Harvard Medical School, United States
- Ludwig-Maximilians-University, Germany
Abstract
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: 7,906,603 patients for whom continuous medical and prescription insurance information was available were selected. 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 U.H.v.A.) and a CRI Irvington postdoctoral fellowship, CRI2453 (to P.H.).
Data availability
Excel spreadsheets of source data are provided as supplemental information for figures 1C, 2B, 3A-D, and 4B-E.The administrative claims data used in this study cannot be made publicly available as it as it is a business product of Komodo Health, who contracts with insurers to develop the combined de-identified dataset under agreements that no patient-level data is permitted outside of the Komodo Health analytics environment. All analyses for this current study were performed in the Komodo Health analytics environment.An interested researcher may contact the corresponding author listed in this article by electronic mail at the address listed, who can then further connect them to a researcher at the company who is familiar with the study. The data was analyzed using Microsoft Excel software.
Article and author information
Author details
Ulrich H von Andrian
Funding
National Institute of Allergy and Infectious Diseases (AI155865)
- Ulrich H von Andrian
National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR068383)
- Ulrich H von Andrian
MassCPR (Evergrande COVID‐19 Response Fund Award)
- Ulrich H von Andrian
Cancer Research Institute (CRI2453)
- Pavel Hanč
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: The study protocol was reviewed by Pearl IRB (Indianapolis, IN) and was determined to be Exempt according to FDA 21 CFR 56.104 and 45CFR46.104(b)(4): (4) Secondary Research Uses of Data or Specimens on 02/08/2021.Protocol #21-ACUT-101
Copyright
© 2023, Thompson et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Association between Bisphosphonate use and COVID-19 related outcomes
eLife 12:e79548.
https://doi.org/10.7554/eLife.79548
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