Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial

Han Sol Park; Anna Yin; Caelan Barranta; John S. Lee; Christopher A. Caputo; Jaiprasath Sachithanandham; Maggie Li; Steve Yoon; Ioannis Sitaras; Anne Jedlicka; Yolanda Eby; Malathi Ram; Reinaldo E. Fernandez; Owen R. Baker; Aarthi G. Shenoy; Giselle S. Mosnaim; Yuriko Fukuta; Bela Patel; Sonya L. Heath; Adam C. Levine; Barry R. Meisenberg; Emily S. Spivak; Shweta Anjan; Moises A. Huaman; Janis E. Blair; Judith S. Currier; James H. Paxton; Jonathan M. Gerber; Joann R. Petrini; Patrick B. Broderick; William Rausch; Marie Elena Cordisco; Jean Hammel; Benjamin Greenblatt; Valerie C. Cluzet; Daniel Cruser; Kevin Oei; Matthew Abinante; Laura L. Hammitt; Catherine G. Sutcliffe; Donald N. Forthal; Martin S. Zand; Edward R. Cachay; Jay S. Raval; Seble G. Kassaye; Christi E. Marshall; Anusha Yarava; Karen Lane; Nichol A. McBee; Amy L. Gawad; Nicky Karlen; Atika Singh; Daniel E. Ford; Douglas A. Jabs; Lawrence J. Appel; David M. Shade; Bryan Lau; Stephan Ehrhardt; Sheriza N. Baksh; Janna R. Shapiro; Jiangda Ou; Yu Bin Na; Maria D. Knoll; Elysse Ornelas-Gatdula; Netzahualcoyotl Arroyo-Curras; Thomas J. Gniadek; Patrizio Caturegli; Jinke Wu; Nelson Ndahiro; Michael J. Betenbaugh; Alyssa Ziman; Daniel F. Hanley; Arturo Casadevall; Shmuel Shoham; Evan M. Bloch; Kelly A. Gebo; Aaron A.R. Tobian; Oliver Laeyendecker; Andrew Pekosz; Sabra L. Klein; David J. Sullivan

doi:10.1172/jci.insight.178460

Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial

Han Sol Park, Anna Yin, Caelan Barranta, John S. Lee, Christopher A. Caputo, Jaiprasath Sachithanandham, Maggie Li, Steve Yoon, Ioannis Sitaras, Anne Jedlicka, Yolanda Eby, Malathi Ram, Reinaldo E. Fernandez, Owen R. Baker, Aarthi G. Shenoy, Giselle S. Mosnaim, Yuriko Fukuta, Bela Patel, Sonya L. Heath, Adam C. LevineBarry R. Meisenberg, Emily S. Spivak, Shweta Anjan, Moises A. Huaman, Janis E. Blair, Judith S. Currier, James H. Paxton, Jonathan M. Gerber, Joann R. Petrini, Patrick B. Broderick, William Rausch, Marie Elena Cordisco, Jean Hammel, Benjamin Greenblatt, Valerie C. Cluzet, Daniel Cruser, Kevin Oei, Matthew Abinante, Laura L. Hammitt, Catherine G. Sutcliffe, Donald N. Forthal, Martin S. Zand, Edward R. Cachay, Jay S. Raval, Seble G. Kassaye, Christi E. Marshall, Anusha Yarava, Karen Lane, Nichol A. McBee, Amy L. Gawad, Nicky Karlen, Atika Singh, Daniel E. Ford, Douglas A. Jabs, Lawrence J. Appel, David M. Shade, Bryan Lau, Stephan Ehrhardt, Sheriza N. Baksh, Janna R. Shapiro, Jiangda Ou, Yu Bin Na, Maria D. Knoll, Elysse Ornelas-Gatdula, Netzahualcoyotl Arroyo-Curras, Thomas J. Gniadek, Patrizio Caturegli, Jinke Wu, Nelson Ndahiro, Michael J. Betenbaugh, Alyssa Ziman, Daniel F. Hanley, Arturo Casadevall, Shmuel Shoham, Evan M. Bloch, Kelly A. Gebo, Aaron A.R. Tobian, Oliver Laeyendecker, Andrew Pekosz, Sabra L. Klein, David J. Sullivan

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

2 Scopus citations

Abstract

BACKGROUND. COVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined. METHODS. This secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low posttransfusion antibody levels was established by 2 methods: (i) analyzing virus neutralization-equivalent anti-Spike receptor-binding domain immunoglobulin G (anti-S-RBD IgG) responses in donors or (ii) receiver operating characteristic (ROC) curve analysis. RESULTS. SARS-CoV-2 anti-S-RBD IgG antibody was volume diluted 21.3-fold into posttransfusion seronegative recipients from matched donor units. Virus-specific antibody delivered was approximately 1.2 mg. The high-antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP-recipient analysis for antibody thresholds correlated to reduced hospitalizations found a statistical significant association between early transfusion and high antibodies versus all other CCP recipients (or control plasma), with antibody cutoffs established by both methods-donor-based virus neutralization cutoffs in posttransfusion recipients (0/85 [0%] versus 15/276 [5.6%]; P = 0.03) or ROC-based cutoff (0/94 [0%] versus 15/267 [5.4%]; P = 0.01). CONCLUSION. In unvaccinated, seronegative CCP recipients, early transfusion of plasma units in the upper 30% of study donors' antibody levels reduced outpatient hospitalizations. High antibody level plasma units, given early, should be reserved for therapeutic use.

Original language	English
Article number	e178460
Journal	JCI insight
Volume	9
Issue number	8
DOIs	https://doi.org/10.1172/jci.insight.178460
State	Published - 2024
Externally published	Yes

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10.1172/jci.insight.178460

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Park, H. S., Yin, A., Barranta, C., Lee, J. S., Caputo, C. A., Sachithanandham, J., Li, M., Yoon, S., Sitaras, I., Jedlicka, A., Eby, Y., Ram, M., Fernandez, R. E., Baker, O. R., Shenoy, A. G., Mosnaim, G. S., Fukuta, Y., Patel, B., Heath, S. L., ... Sullivan, D. J. (2024). Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial. JCI insight, 9(8), Article e178460. https://doi.org/10.1172/jci.insight.178460

@article{f423cff50bcf4c2083216bfae6dfa67c,

title = "Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial",

abstract = "BACKGROUND. COVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined. METHODS. This secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low posttransfusion antibody levels was established by 2 methods: (i) analyzing virus neutralization-equivalent anti-Spike receptor-binding domain immunoglobulin G (anti-S-RBD IgG) responses in donors or (ii) receiver operating characteristic (ROC) curve analysis. RESULTS. SARS-CoV-2 anti-S-RBD IgG antibody was volume diluted 21.3-fold into posttransfusion seronegative recipients from matched donor units. Virus-specific antibody delivered was approximately 1.2 mg. The high-antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP-recipient analysis for antibody thresholds correlated to reduced hospitalizations found a statistical significant association between early transfusion and high antibodies versus all other CCP recipients (or control plasma), with antibody cutoffs established by both methods-donor-based virus neutralization cutoffs in posttransfusion recipients (0/85 [0%] versus 15/276 [5.6%]; P = 0.03) or ROC-based cutoff (0/94 [0%] versus 15/267 [5.4%]; P = 0.01). CONCLUSION. In unvaccinated, seronegative CCP recipients, early transfusion of plasma units in the upper 30% of study donors' antibody levels reduced outpatient hospitalizations. High antibody level plasma units, given early, should be reserved for therapeutic use.",

author = "Park, {Han Sol} and Anna Yin and Caelan Barranta and Lee, {John S.} and Caputo, {Christopher A.} and Jaiprasath Sachithanandham and Maggie Li and Steve Yoon and Ioannis Sitaras and Anne Jedlicka and Yolanda Eby and Malathi Ram and Fernandez, {Reinaldo E.} and Baker, {Owen R.} and Shenoy, {Aarthi G.} and Mosnaim, {Giselle S.} and Yuriko Fukuta and Bela Patel and Heath, {Sonya L.} and Levine, {Adam C.} and Meisenberg, {Barry R.} and Spivak, {Emily S.} and Shweta Anjan and Huaman, {Moises A.} and Blair, {Janis E.} and Currier, {Judith S.} and Paxton, {James H.} and Gerber, {Jonathan M.} and Petrini, {Joann R.} and Broderick, {Patrick B.} and William Rausch and Cordisco, {Marie Elena} and Jean Hammel and Benjamin Greenblatt and Cluzet, {Valerie C.} and Daniel Cruser and Kevin Oei and Matthew Abinante and Hammitt, {Laura L.} and Sutcliffe, {Catherine G.} and Forthal, {Donald N.} and Zand, {Martin S.} and Cachay, {Edward R.} and Raval, {Jay S.} and Kassaye, {Seble G.} and Marshall, {Christi E.} and Anusha Yarava and Karen Lane and McBee, {Nichol A.} and Gawad, {Amy L.} and Nicky Karlen and Atika Singh and Ford, {Daniel E.} and Jabs, {Douglas A.} and Appel, {Lawrence J.} and Shade, {David M.} and Bryan Lau and Stephan Ehrhardt and Baksh, {Sheriza N.} and Shapiro, {Janna R.} and Jiangda Ou and Na, {Yu Bin} and Knoll, {Maria D.} and Elysse Ornelas-Gatdula and Netzahualcoyotl Arroyo-Curras and Gniadek, {Thomas J.} and Patrizio Caturegli and Jinke Wu and Nelson Ndahiro and Betenbaugh, {Michael J.} and Alyssa Ziman and Hanley, {Daniel F.} and Arturo Casadevall and Shmuel Shoham and Bloch, {Evan M.} and Gebo, {Kelly A.} and Tobian, {Aaron A.R.} and Oliver Laeyendecker and Andrew Pekosz and Klein, {Sabra L.} and Sullivan, {David J.}",

note = "Publisher Copyright: Copyright: {\textcopyright} 2024, Park et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.",

year = "2024",

doi = "10.1172/jci.insight.178460",

language = "English",

volume = "9",

journal = "JCI insight",

issn = "2379-3708",

publisher = "American Society for Clinical Investigation",

number = "8",

}

Park, HS, Yin, A, Barranta, C, Lee, JS, Caputo, CA, Sachithanandham, J, Li, M, Yoon, S, Sitaras, I, Jedlicka, A, Eby, Y, Ram, M, Fernandez, RE, Baker, OR, Shenoy, AG, Mosnaim, GS, Fukuta, Y, Patel, B, Heath, SL, Levine, AC, Meisenberg, BR, Spivak, ES, Anjan, S, Huaman, MA, Blair, JE, Currier, JS, Paxton, JH, Gerber, JM, Petrini, JR, Broderick, PB, Rausch, W, Cordisco, ME, Hammel, J, Greenblatt, B, Cluzet, VC, Cruser, D, Oei, K, Abinante, M, Hammitt, LL, Sutcliffe, CG, Forthal, DN, Zand, MS, Cachay, ER, Raval, JS, Kassaye, SG, Marshall, CE, Yarava, A, Lane, K, McBee, NA, Gawad, AL, Karlen, N, Singh, A, Ford, DE, Jabs, DA, Appel, LJ, Shade, DM, Lau, B, Ehrhardt, S, Baksh, SN, Shapiro, JR, Ou, J, Na, YB, Knoll, MD, Ornelas-Gatdula, E, Arroyo-Curras, N, Gniadek, TJ, Caturegli, P, Wu, J, Ndahiro, N, Betenbaugh, MJ, Ziman, A, Hanley, DF, Casadevall, A, Shoham, S, Bloch, EM, Gebo, KA, Tobian, AAR, Laeyendecker, O, Pekosz, A, Klein, SL & Sullivan, DJ 2024, 'Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial', JCI insight, vol. 9, no. 8, e178460. https://doi.org/10.1172/jci.insight.178460

TY - JOUR

T1 - Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial

AU - Park, Han Sol

AU - Yin, Anna

AU - Barranta, Caelan

AU - Lee, John S.

AU - Caputo, Christopher A.

AU - Sachithanandham, Jaiprasath

AU - Li, Maggie

AU - Yoon, Steve

AU - Sitaras, Ioannis

AU - Jedlicka, Anne

AU - Eby, Yolanda

AU - Ram, Malathi

AU - Fernandez, Reinaldo E.

AU - Baker, Owen R.

AU - Shenoy, Aarthi G.

AU - Mosnaim, Giselle S.

AU - Fukuta, Yuriko

AU - Patel, Bela

AU - Heath, Sonya L.

AU - Levine, Adam C.

AU - Meisenberg, Barry R.

AU - Spivak, Emily S.

AU - Anjan, Shweta

AU - Huaman, Moises A.

AU - Blair, Janis E.

AU - Currier, Judith S.

AU - Paxton, James H.

AU - Gerber, Jonathan M.

AU - Petrini, Joann R.

AU - Broderick, Patrick B.

AU - Rausch, William

AU - Cordisco, Marie Elena

AU - Hammel, Jean

AU - Greenblatt, Benjamin

AU - Cluzet, Valerie C.

AU - Cruser, Daniel

AU - Oei, Kevin

AU - Abinante, Matthew

AU - Hammitt, Laura L.

AU - Sutcliffe, Catherine G.

AU - Forthal, Donald N.

AU - Zand, Martin S.

AU - Cachay, Edward R.

AU - Raval, Jay S.

AU - Kassaye, Seble G.

AU - Marshall, Christi E.

AU - Yarava, Anusha

AU - Lane, Karen

AU - McBee, Nichol A.

AU - Gawad, Amy L.

AU - Karlen, Nicky

AU - Singh, Atika

AU - Ford, Daniel E.

AU - Jabs, Douglas A.

AU - Appel, Lawrence J.

AU - Shade, David M.

AU - Lau, Bryan

AU - Ehrhardt, Stephan

AU - Baksh, Sheriza N.

AU - Shapiro, Janna R.

AU - Ou, Jiangda

AU - Na, Yu Bin

AU - Knoll, Maria D.

AU - Ornelas-Gatdula, Elysse

AU - Arroyo-Curras, Netzahualcoyotl

AU - Gniadek, Thomas J.

AU - Caturegli, Patrizio

AU - Wu, Jinke

AU - Ndahiro, Nelson

AU - Betenbaugh, Michael J.

AU - Ziman, Alyssa

AU - Hanley, Daniel F.

AU - Casadevall, Arturo

AU - Shoham, Shmuel

AU - Bloch, Evan M.

AU - Gebo, Kelly A.

AU - Tobian, Aaron A.R.

AU - Laeyendecker, Oliver

AU - Pekosz, Andrew

AU - Klein, Sabra L.

AU - Sullivan, David J.

PY - 2024

Y1 - 2024

N2 - BACKGROUND. COVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined. METHODS. This secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low posttransfusion antibody levels was established by 2 methods: (i) analyzing virus neutralization-equivalent anti-Spike receptor-binding domain immunoglobulin G (anti-S-RBD IgG) responses in donors or (ii) receiver operating characteristic (ROC) curve analysis. RESULTS. SARS-CoV-2 anti-S-RBD IgG antibody was volume diluted 21.3-fold into posttransfusion seronegative recipients from matched donor units. Virus-specific antibody delivered was approximately 1.2 mg. The high-antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP-recipient analysis for antibody thresholds correlated to reduced hospitalizations found a statistical significant association between early transfusion and high antibodies versus all other CCP recipients (or control plasma), with antibody cutoffs established by both methods-donor-based virus neutralization cutoffs in posttransfusion recipients (0/85 [0%] versus 15/276 [5.6%]; P = 0.03) or ROC-based cutoff (0/94 [0%] versus 15/267 [5.4%]; P = 0.01). CONCLUSION. In unvaccinated, seronegative CCP recipients, early transfusion of plasma units in the upper 30% of study donors' antibody levels reduced outpatient hospitalizations. High antibody level plasma units, given early, should be reserved for therapeutic use.

AB - BACKGROUND. COVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined. METHODS. This secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low posttransfusion antibody levels was established by 2 methods: (i) analyzing virus neutralization-equivalent anti-Spike receptor-binding domain immunoglobulin G (anti-S-RBD IgG) responses in donors or (ii) receiver operating characteristic (ROC) curve analysis. RESULTS. SARS-CoV-2 anti-S-RBD IgG antibody was volume diluted 21.3-fold into posttransfusion seronegative recipients from matched donor units. Virus-specific antibody delivered was approximately 1.2 mg. The high-antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP-recipient analysis for antibody thresholds correlated to reduced hospitalizations found a statistical significant association between early transfusion and high antibodies versus all other CCP recipients (or control plasma), with antibody cutoffs established by both methods-donor-based virus neutralization cutoffs in posttransfusion recipients (0/85 [0%] versus 15/276 [5.6%]; P = 0.03) or ROC-based cutoff (0/94 [0%] versus 15/267 [5.4%]; P = 0.01). CONCLUSION. In unvaccinated, seronegative CCP recipients, early transfusion of plasma units in the upper 30% of study donors' antibody levels reduced outpatient hospitalizations. High antibody level plasma units, given early, should be reserved for therapeutic use.

UR - http://www.scopus.com/inward/record.url?scp=85191105724&partnerID=8YFLogxK

U2 - 10.1172/jci.insight.178460

DO - 10.1172/jci.insight.178460

M3 - Article

C2 - 38483534

AN - SCOPUS:85191105724

SN - 2379-3708

VL - 9

JO - JCI insight

JF - JCI insight

IS - 8

M1 - e178460

ER -

Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial

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