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).
Keywords: Bisphosphonate; COVID-19; epidemiology; global health; human; medicine; retrospective cohort study.
The COVID-19 pandemic challenged the world to rapidly develop strategies to combat the virus responsible for the disease. While several effective vaccines and new drugs have since become available, these therapies are not always easy to access and take time to generate and distribute. To address these challenges, researchers have tried to find ways to repurpose existing medications that are already commonly used and known to be safe. One potential candidate are bisphosphonates, a family of drugs used to reduce bone loss in patients with osteoporosis. Bisphosphonates have been shown to boost the immune response to viral infections, and it has been observed that patients prescribed these drugs are less likely to develop or die from pneumonia. But whether bisphosphonates are effective against COVID-19 had not been fully explored. To investigate, Thompson, Wang et al. analyzed insurance claims data from about 8 million patients between January 2019 and June 2020, including around 450,000 individuals that had filled a prescription for bisphosphonates. Patients prescribed bisphosphonates were then compared to non-users that were similar in terms of their gender, age, the type of health insurance they had, their access to healthcare, and other health comorbidities. The study revealed that bisphosphonate users were around three to five times less likely to be tested for, diagnosed with, or hospitalized for COVID-19 during the first four months of the pandemic. They were also less commonly diagnosed with other respiratory infections in 2019, like bronchitis or pneumonia. Although the results suggest that bisphosphonates provide some protection against COVID-19, they cannot directly prove it. Verifying that bisphosphonates can treat or prevent COVID-19 and/or other respiratory infections requires more studies that follow patients in real-time rather than studying previously collected data. If such studies confirm the link, bisphosphonates could be a helpful tool to protect against COVID-19 or other virus outbreaks. The drugs are widely available, safe, and affordable, and therefore may provide an alternative for patients who cannot access other medications or vaccines.
© 2023, Thompson, Wang et al.