Comparative effectiveness of dexamethasone in treatment of hospitalized COVID-19 patients in the United States during the first year of the pandemic: Findings from the National COVID Cohort Collaborative (N3C) data repository

Richard Zhou, Kaitlyn E. Johnson, Justin F. Rousseau, Paul J. Rathouz, Adam B. Wilcox, Adam M. Lee, Alexis Graves, Alfred Anzalone, Amin Manna, Amit Saha, Amy Olex, Andrea Zhou, Andrew E. Williams, Andrew Southerland, Andrew T. Girvin, Anita Walden, Anjali A. Sharathkumar, Benjamin Amor, Benjamin Bates, Brian HendricksBrijesh Patel, Caleb Alexander, Carolyn Bramante, Cavin Ward-Caviness, Charisse Madlock-Brown, Christine Suver, Christopher Chute, Christopher Dillon, Chunlei Wu, Clare Schmitt, Cliff Takemoto, Dan Housman, Davera Gabriel, David A. Eichmann, Diego Mazzotti, Don Brown, Eilis Boudreau, Elaine Hill, Elizabeth Zampino, Emily Carlson Marti, Emily R. Pfaff, Evan French, Farrukh M. Koraishy, Federico Mariona, Fred Prior, George Sokos, Greg Martin, Harold Lehmann, Heidi Spratt, Hemalkumar Mehta, Hongfang Liu, Hythem Sidky, J. W.Awori Hayanga, Jami Pincavitch, Jaylyn Clark, Jeremy Richard Harper, Jessica Islam, Jin Ge, Joel Gagnier, Joel H. Saltz, Joel Saltz, Johanna Loomba, John Buse, Jomol Mathew, Joni L. Rutter, Julie A. McMurry, Justin Guinney, Justin Starren, Karen Crowley, Katie Rebecca Bradwell, Kellie M. Walters, Ken Wilkins, Kenneth R. Gersing, Kenrick Dwain Cato, Kimberly Murray, Kristin Kostka, Lavance Northington, Lee Allan Pyles, Leonie Misquitta, Lesley Cottrell, Lili Portilla, Mariam Deacy, Mark M. Bissell, Marshall Clark, Mary Emmett, Mary Morrison Saltz, Matvey B. Palchuk, Melissa A. Haendel, Meredith Adams, Meredith Temple-O'Connor, Michael G. Kurilla, Michele Morris, Nabeel Qureshi, Nasia Safdar, Nicole Garbarini, Noha Sharafeldin, Ofer Sadan, Patricia A. Francis, Penny Wung Burgoon, Peter Robinson, Philip R.O. Payne, Rafael Fuentes, Randeep Jawa, Rebecca Erwin-Cohen, Rena Patel, Richard A. Moffitt, Richard L. Zhu, Rishi Kamaleswaran, Robert Hurley, Robert T. Miller, Saiju Pyarajan, Sam G. Michael, Samuel Bozzette, Sandeep Mallipattu, Satyanarayana Vedula, Scott Chapman, Shawn T. O'Neil, Soko Setoguchi, Stephanie S. Hong, Steve Johnson, Tellen D. Bennett, Tiffany Callahan, Umit Topaloglu, Usman Sheikh, Valery Gordon, Vignesh Subbian, Warren A. Kibbe, Wenndy Hernandez, Will Beasley, Will Cooper, William Hillegass, Xiaohan Tanner Zhang

Research output: Contribution to journalArticlepeer-review


Background Dexamethasone was approved for use in hospitalized COVID-19 patients early in the pandemic based on the RECOVERY trial, but evidence is still needed to support its real-world effectiveness in heterogeneous populations of patients with a wide range of comorbidities. Methods COVID-19 inpatients represented within the National COVID Cohort Collaborative (N3C) Data Enclave, prior to vaccine availability, were studied. Primary outcome was in-hospital death; secondary outcome was combined in-hospital death and severe outcome defined by use of ECMO or mechanical ventilation. Missing data were imputed with single imputation. Dexamethasone-treated patients were propensity score (PS) matched to non-dexamethasone- treated controls, stratified by remdesivir treatment and based on demographics, baseline laboratory values, comorbidities, and amount of missing data before imputation. Treatment benefit was quantified using logistic regression. Further sensitivity analyses were performed using clinical adjusters in matched groups and in strata defined by quartiles of PS. Results Dexamethasone treatment was associated with reduced risk of in-hospital mortality for n = 1,263 treated, matched 1:3 to untreated, patients not receiving remdesivir (OR = 0.77, 95% CI: 0.62 to 0.95, p = 0.017), and for n = 804 treated, matched 1:1 to untreated, patients receiving remdesivir (OR = 0.74, 95% CI: 0.53 to 1.02, p = 0.054). Treatment showed secondary outcome benefit. In sensitivity analyses, treatment effect generally remained similar with some heterogeneity of benefit across quartiles of PS, possibly reflecting concentration of benefit among the more severely affected. Conclusions We add evidence that dexamethasone provides benefit with respect to mortality and severe outcomes in a diverse, national hospitalized sample, prior to vaccine availability.

Original languageEnglish
Article numbere0294892
JournalPLoS ONE
Issue number3 March
StatePublished - Mar 2024


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