Optimizing Use of Immunosuppressive Therapeutics and Thromboprophylaxis: Associations with Severe Disease and Death Among Adults Hospitalized with COVID-19 in the United States
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Date
2021-12-16
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Johns Hopkins University
Abstract
Background. As of December 15, 2021, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused more than 50 million infections and 800,000 deaths in the United States. Given the novelty of the virus, the identification of high risk groups and understanding of optimal treatment regimens remains a pressing global health priority. This dissertation sought to improve understanding of therapeutics among adults hospitalized with COVID-19.
Methods. First, we used electronic health record data from an academic medical system to assess whether adults with COVID-19 with chronic pharmacologic immunosuppression have worse short-term clinical outcomes than non-immunosuppressed adults. Second, we used a national electronic health record repository of COVID-19 patients in the United States to evaluate whether the risks associated with immunosuppression vary by medication class. Third, we used electronic health records to evaluate the comparative effectiveness of high-intensity versus standard thromboprophylaxis among adults hospitalized with COVID-19.
Results. Overall, there was no evidence of increased risk of invasive mechanical ventilation or in-hospital death among individuals taking chronic immunosuppressive medications, such as those to manage autoimmune disorders, treat cancer, or prevent solid organ transplant rejection. Further analyses of the nation-wide cohort continued to find no increased risk of invasive mechanical ventilation with long-term immunosuppression, and no increased risk of death with 302 of 303 drugs examined. Rituximab, a treatment for lymphoma and rheumatologic conditions, was associated with a significantly increased risk of death. Separately, our study of over 50,000 adults within the HCA CHARGE database did not find reductions in risk of clinical worsening, severe disease or death with high-intensity thromboprophylaxis regimens after accounting for time-varying exposure definitions and relevant confounders.
Conclusions. While many important questions remain, this dissertation provides robust evidence suggesting the general safety of chronic immunosuppressive medicines, as well as the absence of benefit of high-intensity thromboprophylaxis, among U.S. adults hospitalized with COVID-19.
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pharmacoepidemiology, COVID-19, drug safety, immunosuppression, thromboprophylaxis