Randomized Controlled Trial of Early Outpatient COVID-19 Treatment with High-Titer Convalescent Plasma

BACKGROUND: The efficacy of polyclonal high titer convalescent plasma to prevent serious complications of COVID-19 in outpatients with recent onset of illness is uncertain. METHODS: This multicenter, double-blind randomized controlled trial compared the efficacy and safety of SARS-CoV-2 high titer c...

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Autores principales: Sullivan, David J., Gebo, Kelly A., Shoham, Shmuel, Bloch, Evan M., Lau, Bryan, Shenoy, Aarthi G., Mosnaim, Giselle S., Gniadek, Thomas J., Fukuta, Yuriko, Patel, Bela, Heath, Sonya L., Levine, Adam C., Meisenberg, Barry R., Spivak, Emily S., Anjan, Shweta, Huaman, Moises A., Blair, Janis E., Currier, Judith S., Paxton, James H., Gerber, Jonathan M., Petrini, Joann R., Broderick, Patrick B., Rausch, William, Cordisco, Marie Elena, Hammel, Jean, Greenblatt, Benjamin, Cluzet, Valerie C., Cruser, Daniel, Oei, Kevin, Abinante, Matthew, Hammitt, Laura L., Sutcliffe, Catherine G., Forthal, Donald N., Zand, Martin S., Cachay, Edward R., Raval, Jay S., Kassaye, Seble G., Foster, E. Colin, Roth, Michael, Marshall, Christi E., Yarava, Anusha, Lane, Karen, McBee, Nichol A., Gawad, Amy L., Karlen, Nicky, Singh, Atika, Ford, Daniel E., Jabs, Douglas A., Appel, Lawrence J., Shade, David M., Ehrhardt, Stephan, Baksh, Sheriza N., Laeyendecker, Oliver, Pekosz, Andrew, Klein, Sabra L., Casadevall, Arturo, Tobian, Aaron A.R., Hanley, Daniel F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8722611/
https://www.ncbi.nlm.nih.gov/pubmed/34981068
http://dx.doi.org/10.1101/2021.12.10.21267485
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author Sullivan, David J.
Gebo, Kelly A.
Shoham, Shmuel
Bloch, Evan M.
Lau, Bryan
Shenoy, Aarthi G.
Mosnaim, Giselle S.
Gniadek, Thomas J.
Fukuta, Yuriko
Patel, Bela
Heath, Sonya L.
Levine, Adam C.
Meisenberg, Barry R.
Spivak, Emily S.
Anjan, Shweta
Huaman, Moises A.
Blair, Janis E.
Currier, Judith S.
Paxton, James H.
Gerber, Jonathan M.
Petrini, Joann R.
Broderick, Patrick B.
Rausch, William
Cordisco, Marie Elena
Hammel, Jean
Greenblatt, Benjamin
Cluzet, Valerie C.
Cruser, Daniel
Oei, Kevin
Abinante, Matthew
Hammitt, Laura L.
Sutcliffe, Catherine G.
Forthal, Donald N.
Zand, Martin S.
Cachay, Edward R.
Raval, Jay S.
Kassaye, Seble G.
Foster, E. Colin
Roth, Michael
Marshall, Christi E.
Yarava, Anusha
Lane, Karen
McBee, Nichol A.
Gawad, Amy L.
Karlen, Nicky
Singh, Atika
Ford, Daniel E.
Jabs, Douglas A.
Appel, Lawrence J.
Shade, David M.
Ehrhardt, Stephan
Baksh, Sheriza N.
Laeyendecker, Oliver
Pekosz, Andrew
Klein, Sabra L.
Casadevall, Arturo
Tobian, Aaron A.R.
Hanley, Daniel F.
author_facet Sullivan, David J.
Gebo, Kelly A.
Shoham, Shmuel
Bloch, Evan M.
Lau, Bryan
Shenoy, Aarthi G.
Mosnaim, Giselle S.
Gniadek, Thomas J.
Fukuta, Yuriko
Patel, Bela
Heath, Sonya L.
Levine, Adam C.
Meisenberg, Barry R.
Spivak, Emily S.
Anjan, Shweta
Huaman, Moises A.
Blair, Janis E.
Currier, Judith S.
Paxton, James H.
Gerber, Jonathan M.
Petrini, Joann R.
Broderick, Patrick B.
Rausch, William
Cordisco, Marie Elena
Hammel, Jean
Greenblatt, Benjamin
Cluzet, Valerie C.
Cruser, Daniel
Oei, Kevin
Abinante, Matthew
Hammitt, Laura L.
Sutcliffe, Catherine G.
Forthal, Donald N.
Zand, Martin S.
Cachay, Edward R.
Raval, Jay S.
Kassaye, Seble G.
Foster, E. Colin
Roth, Michael
Marshall, Christi E.
Yarava, Anusha
Lane, Karen
McBee, Nichol A.
Gawad, Amy L.
Karlen, Nicky
Singh, Atika
Ford, Daniel E.
Jabs, Douglas A.
Appel, Lawrence J.
Shade, David M.
Ehrhardt, Stephan
Baksh, Sheriza N.
Laeyendecker, Oliver
Pekosz, Andrew
Klein, Sabra L.
Casadevall, Arturo
Tobian, Aaron A.R.
Hanley, Daniel F.
author_sort Sullivan, David J.
collection PubMed
description BACKGROUND: The efficacy of polyclonal high titer convalescent plasma to prevent serious complications of COVID-19 in outpatients with recent onset of illness is uncertain. METHODS: This multicenter, double-blind randomized controlled trial compared the efficacy and safety of SARS-CoV-2 high titer convalescent plasma to placebo control plasma in symptomatic adults ≥18 years positive for SARS-CoV-2 regardless of risk factors for disease progression or vaccine status. Participants with symptom onset within 8 days were enrolled, then transfused within the subsequent day. The measured primary outcome was COVID-19-related hospitalization within 28 days of plasma transfusion. The enrollment period was June 3, 2020 to October 1, 2021. RESULTS: A total of 1225 participants were randomized and 1181 transfused. In the pre-specified modified intention-to-treat analysis that excluded those not transfused, the primary endpoint occurred in 37 of 589 (6.3%) who received placebo control plasma and in 17 of 592 (2.9%) participants who received convalescent plasma (relative risk, 0.46; one-sided 95% upper bound confidence interval 0.733; P=0.004) corresponding to a 54% risk reduction. Examination with a model adjusting for covariates related to the outcome did not change the conclusions. CONCLUSION: Early administration of high titer SARS-CoV-2 convalescent plasma reduced outpatient hospitalizations by more than 50%. High titer convalescent plasma is an effective early outpatient COVID-19 treatment with the advantages of low cost, wide availability, and rapid resilience to variant emergence from viral genetic drift in the face of a changing pandemic. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT04373460.
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spelling pubmed-87226112022-01-04 Randomized Controlled Trial of Early Outpatient COVID-19 Treatment with High-Titer Convalescent Plasma Sullivan, David J. Gebo, Kelly A. Shoham, Shmuel Bloch, Evan M. Lau, Bryan Shenoy, Aarthi G. Mosnaim, Giselle S. Gniadek, Thomas J. Fukuta, Yuriko Patel, Bela Heath, Sonya L. Levine, Adam C. Meisenberg, Barry R. Spivak, Emily S. Anjan, Shweta Huaman, Moises A. Blair, Janis E. Currier, Judith S. Paxton, James H. Gerber, Jonathan M. Petrini, Joann R. Broderick, Patrick B. Rausch, William Cordisco, Marie Elena Hammel, Jean Greenblatt, Benjamin Cluzet, Valerie C. Cruser, Daniel Oei, Kevin Abinante, Matthew Hammitt, Laura L. Sutcliffe, Catherine G. Forthal, Donald N. Zand, Martin S. Cachay, Edward R. Raval, Jay S. Kassaye, Seble G. Foster, E. Colin Roth, Michael Marshall, Christi E. Yarava, Anusha Lane, Karen McBee, Nichol A. Gawad, Amy L. Karlen, Nicky Singh, Atika Ford, Daniel E. Jabs, Douglas A. Appel, Lawrence J. Shade, David M. Ehrhardt, Stephan Baksh, Sheriza N. Laeyendecker, Oliver Pekosz, Andrew Klein, Sabra L. Casadevall, Arturo Tobian, Aaron A.R. Hanley, Daniel F. medRxiv Article BACKGROUND: The efficacy of polyclonal high titer convalescent plasma to prevent serious complications of COVID-19 in outpatients with recent onset of illness is uncertain. METHODS: This multicenter, double-blind randomized controlled trial compared the efficacy and safety of SARS-CoV-2 high titer convalescent plasma to placebo control plasma in symptomatic adults ≥18 years positive for SARS-CoV-2 regardless of risk factors for disease progression or vaccine status. Participants with symptom onset within 8 days were enrolled, then transfused within the subsequent day. The measured primary outcome was COVID-19-related hospitalization within 28 days of plasma transfusion. The enrollment period was June 3, 2020 to October 1, 2021. RESULTS: A total of 1225 participants were randomized and 1181 transfused. In the pre-specified modified intention-to-treat analysis that excluded those not transfused, the primary endpoint occurred in 37 of 589 (6.3%) who received placebo control plasma and in 17 of 592 (2.9%) participants who received convalescent plasma (relative risk, 0.46; one-sided 95% upper bound confidence interval 0.733; P=0.004) corresponding to a 54% risk reduction. Examination with a model adjusting for covariates related to the outcome did not change the conclusions. CONCLUSION: Early administration of high titer SARS-CoV-2 convalescent plasma reduced outpatient hospitalizations by more than 50%. High titer convalescent plasma is an effective early outpatient COVID-19 treatment with the advantages of low cost, wide availability, and rapid resilience to variant emergence from viral genetic drift in the face of a changing pandemic. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT04373460. Cold Spring Harbor Laboratory 2021-12-21 /pmc/articles/PMC8722611/ /pubmed/34981068 http://dx.doi.org/10.1101/2021.12.10.21267485 Text en https://creativecommons.org/licenses/by-nd/4.0/This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, and only so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Sullivan, David J.
Gebo, Kelly A.
Shoham, Shmuel
Bloch, Evan M.
Lau, Bryan
Shenoy, Aarthi G.
Mosnaim, Giselle S.
Gniadek, Thomas J.
Fukuta, Yuriko
Patel, Bela
Heath, Sonya L.
Levine, Adam C.
Meisenberg, Barry R.
Spivak, Emily S.
Anjan, Shweta
Huaman, Moises A.
Blair, Janis E.
Currier, Judith S.
Paxton, James H.
Gerber, Jonathan M.
Petrini, Joann R.
Broderick, Patrick B.
Rausch, William
Cordisco, Marie Elena
Hammel, Jean
Greenblatt, Benjamin
Cluzet, Valerie C.
Cruser, Daniel
Oei, Kevin
Abinante, Matthew
Hammitt, Laura L.
Sutcliffe, Catherine G.
Forthal, Donald N.
Zand, Martin S.
Cachay, Edward R.
Raval, Jay S.
Kassaye, Seble G.
Foster, E. Colin
Roth, Michael
Marshall, Christi E.
Yarava, Anusha
Lane, Karen
McBee, Nichol A.
Gawad, Amy L.
Karlen, Nicky
Singh, Atika
Ford, Daniel E.
Jabs, Douglas A.
Appel, Lawrence J.
Shade, David M.
Ehrhardt, Stephan
Baksh, Sheriza N.
Laeyendecker, Oliver
Pekosz, Andrew
Klein, Sabra L.
Casadevall, Arturo
Tobian, Aaron A.R.
Hanley, Daniel F.
Randomized Controlled Trial of Early Outpatient COVID-19 Treatment with High-Titer Convalescent Plasma
title Randomized Controlled Trial of Early Outpatient COVID-19 Treatment with High-Titer Convalescent Plasma
title_full Randomized Controlled Trial of Early Outpatient COVID-19 Treatment with High-Titer Convalescent Plasma
title_fullStr Randomized Controlled Trial of Early Outpatient COVID-19 Treatment with High-Titer Convalescent Plasma
title_full_unstemmed Randomized Controlled Trial of Early Outpatient COVID-19 Treatment with High-Titer Convalescent Plasma
title_short Randomized Controlled Trial of Early Outpatient COVID-19 Treatment with High-Titer Convalescent Plasma
title_sort randomized controlled trial of early outpatient covid-19 treatment with high-titer convalescent plasma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8722611/
https://www.ncbi.nlm.nih.gov/pubmed/34981068
http://dx.doi.org/10.1101/2021.12.10.21267485
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