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 Hendricks; Brijesh 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 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

doi:10.1371/journal.pone.0294892

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 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

Neurology

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Abstract

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 language	English (US)
Article number	e0294892
Journal	PloS one
Volume	19
Issue number	3 March
DOIs	https://doi.org/10.1371/journal.pone.0294892
State	Published - Mar 2024

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Zhou, R., Johnson, K. E., Rousseau, J. F., Rathouz, P. J., Wilcox, A. B., Lee, A. M., Graves, A., Anzalone, A., Manna, A., Saha, A., Olex, A., Zhou, A., Williams, A. E., Southerland, A., Girvin, A. T., Walden, A., Sharathkumar, A. A., Amor, B., Bates, B., ... Tanner Zhang, X. (2024). 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. PloS one, 19(3 March), Article e0294892. https://doi.org/10.1371/journal.pone.0294892

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. / Zhou, Richard; Johnson, Kaitlyn E.; Rousseau, Justin F. et al.
In: PloS one, Vol. 19, No. 3 March, e0294892, 03.2024.

Research output: Contribution to journal › Article › peer-review

Zhou, R, Johnson, KE, Rousseau, JF, Rathouz, PJ, Wilcox, AB, Lee, AM, Graves, A, Anzalone, A, Manna, A, Saha, A, Olex, A, Zhou, A, Williams, AE, Southerland, A, Girvin, AT, Walden, A, Sharathkumar, AA, Amor, B, Bates, B, Hendricks, B, Patel, B, Alexander, C, Bramante, C, Ward-Caviness, C, Madlock-Brown, C, Suver, C, Chute, C, Dillon, C, Wu, C, Schmitt, C, Takemoto, C, Housman, D, Gabriel, D, Eichmann, DA, Mazzotti, D, Brown, D, Boudreau, E, Hill, E, Zampino, E, Carlson Marti, E, Pfaff, ER, French, E, Koraishy, FM, Mariona, F, Prior, F, Sokos, G, Martin, G, Lehmann, H, Spratt, H, Mehta, H, Liu, H, Sidky, H, Hayanga, JWA, Pincavitch, J, Clark, J, Harper, JR, Islam, J, Ge, J, Gagnier, J, Saltz, JH, Saltz, J, Loomba, J, Buse, J, Mathew, J, Rutter, JL, McMurry, JA, Guinney, J, Starren, J, Crowley, K, Bradwell, KR, Walters, KM, Wilkins, K, Gersing, KR, Cato, KD, Murray, K, Kostka, K, Northington, L, Pyles, LA, Misquitta, L, Cottrell, L, Portilla, L, Deacy, M, Bissell, MM, Clark, M, Emmett, M, Saltz, MM, Palchuk, MB, Haendel, M, Adams, M, Temple-O'Connor, M, Kurilla, MG, Morris, M, Qureshi, N, Safdar, N, Garbarini, N, Sharafeldin, N, Sadan, O, Francis, PA, Burgoon, PW, Robinson, P, Payne, PRO, Fuentes, R, Jawa, R, Erwin-Cohen, R, Patel, R, Moffitt, RA, Zhu, RL, Kamaleswaran, R, Hurley, R, Miller, RT, Pyarajan, S, Michael, SG, Bozzette, S, Mallipattu, S, Vedula, S, Chapman, S, O'Neil, ST, Setoguchi, S, Hong, SS, Johnson, S, Bennett, TD, Callahan, T, Topaloglu, U, Sheikh, U, Gordon, V, Subbian, V, Kibbe, WA, Hernandez, W, Beasley, W, Cooper, W, Hillegass, W & Tanner Zhang, X 2024, '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', PloS one, vol. 19, no. 3 March, e0294892. https://doi.org/10.1371/journal.pone.0294892

Zhou R, Johnson KE, Rousseau JF, Rathouz PJ, Wilcox AB, Lee AM et al. 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. PloS one. 2024 Mar;19(3 March):e0294892. doi: 10.1371/journal.pone.0294892

@article{f67d87f5f3434e469dbaff9b4ee08650,

title = "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",

abstract = "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.",

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

note = "Publisher Copyright: {\textcopyright} 2024 Zhou et al.",

year = "2024",

month = mar,

doi = "10.1371/journal.pone.0294892",

language = "English (US)",

volume = "19",

journal = "PloS one",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "3 March",

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TY - JOUR

T1 - Comparative effectiveness of dexamethasone in treatment of hospitalized COVID-19 patients in the United States during the first year of the pandemic

T2 - Findings from the National COVID Cohort Collaborative (N3C) data repository

AU - Zhou, Richard

AU - Johnson, Kaitlyn E.

AU - Rousseau, Justin F.

AU - Rathouz, Paul J.

AU - Wilcox, Adam B.

AU - Lee, Adam M.

AU - Graves, Alexis

AU - Anzalone, Alfred

AU - Manna, Amin

AU - Saha, Amit

AU - Olex, Amy

AU - Zhou, Andrea

AU - Williams, Andrew E.

AU - Southerland, Andrew

AU - Girvin, Andrew T.

AU - Walden, Anita

AU - Sharathkumar, Anjali A.

AU - Amor, Benjamin

AU - Bates, Benjamin

AU - Hendricks, Brian

AU - Patel, Brijesh

AU - Alexander, Caleb

AU - Bramante, Carolyn

AU - Ward-Caviness, Cavin

AU - Madlock-Brown, Charisse

AU - Suver, Christine

AU - Chute, Christopher

AU - Dillon, Christopher

AU - Wu, Chunlei

AU - Schmitt, Clare

AU - Takemoto, Cliff

AU - Housman, Dan

AU - Gabriel, Davera

AU - Eichmann, David A.

AU - Mazzotti, Diego

AU - Brown, Don

AU - Boudreau, Eilis

AU - Hill, Elaine

AU - Zampino, Elizabeth

AU - Carlson Marti, Emily

AU - Pfaff, Emily R.

AU - French, Evan

AU - Koraishy, Farrukh M.

AU - Mariona, Federico

AU - Prior, Fred

AU - Sokos, George

AU - Martin, Greg

AU - Lehmann, Harold

AU - Spratt, Heidi

AU - Mehta, Hemalkumar

AU - Liu, Hongfang

AU - Sidky, Hythem

AU - Hayanga, J. W.Awori

AU - Pincavitch, Jami

AU - Clark, Jaylyn

AU - Harper, Jeremy Richard

AU - Islam, Jessica

AU - Ge, Jin

AU - Gagnier, Joel

AU - Saltz, Joel H.

AU - Saltz, Joel

AU - Loomba, Johanna

AU - Buse, John

AU - Mathew, Jomol

AU - Rutter, Joni L.

AU - McMurry, Julie A.

AU - Guinney, Justin

AU - Starren, Justin

AU - Crowley, Karen

AU - Bradwell, Katie Rebecca

AU - Walters, Kellie M.

AU - Wilkins, Ken

AU - Gersing, Kenneth R.

AU - Cato, Kenrick Dwain

AU - Murray, Kimberly

AU - Kostka, Kristin

AU - Northington, Lavance

AU - Pyles, Lee Allan

AU - Misquitta, Leonie

AU - Cottrell, Lesley

AU - Portilla, Lili

AU - Deacy, Mariam

AU - Bissell, Mark M.

AU - Clark, Marshall

AU - Emmett, Mary

AU - Saltz, Mary Morrison

AU - Palchuk, Matvey B.

AU - Haendel, Melissa

AU - Adams, Meredith

AU - Temple-O'Connor, Meredith

AU - Kurilla, Michael G.

AU - Morris, Michele

AU - Qureshi, Nabeel

AU - Safdar, Nasia

AU - Garbarini, Nicole

AU - Sharafeldin, Noha

AU - Sadan, Ofer

AU - Francis, Patricia A.

AU - Burgoon, Penny Wung

AU - Robinson, Peter

AU - Payne, Philip R.O.

AU - Fuentes, Rafael

AU - Jawa, Randeep

AU - Erwin-Cohen, Rebecca

AU - Patel, Rena

AU - Moffitt, Richard A.

AU - Zhu, Richard L.

AU - Kamaleswaran, Rishi

AU - Hurley, Robert

AU - Miller, Robert T.

AU - Pyarajan, Saiju

AU - Michael, Sam G.

AU - Bozzette, Samuel

AU - Mallipattu, Sandeep

AU - Vedula, Satyanarayana

AU - Chapman, Scott

AU - O'Neil, Shawn T.

AU - Setoguchi, Soko

AU - Hong, Stephanie S.

AU - Johnson, Steve

AU - Bennett, Tellen D.

AU - Callahan, Tiffany

AU - Topaloglu, Umit

AU - Sheikh, Usman

AU - Gordon, Valery

AU - Subbian, Vignesh

AU - Kibbe, Warren A.

AU - Hernandez, Wenndy

AU - Beasley, Will

AU - Cooper, Will

AU - Hillegass, William

AU - Tanner Zhang, Xiaohan

PY - 2024/3

Y1 - 2024/3

N2 - 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.

AB - 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.

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U2 - 10.1371/journal.pone.0294892

DO - 10.1371/journal.pone.0294892

M3 - Article

C2 - 38512832

AN - SCOPUS:85188415917

SN - 1932-6203

VL - 19

JO - PloS one

JF - PloS one

IS - 3 March

M1 - e0294892

ER -

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

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