Cargando…

SARS-CoV-2 Infection of Rhesus Macaques Treated Early with Human COVID-19 Convalescent Plasma

Human clinical studies investigating use of convalescent plasma (CP) for treatment of coronavirus disease 2019 (COVID-19) have produced conflicting results. Outcomes in these studies may vary at least partly due to different timing of CP administration relative to symptom onset. The mechanisms of ac...

Descripción completa

Detalles Bibliográficos
Autores principales: Deere, Jesse D., Carroll, Timothy D., Dutra, Joseph, Fritts, Linda, Sammak, Rebecca Lee, Yee, JoAnn L., Olstad, Katherine J., Reader, J. Rachel, Kistler, Amy, Kamm, Jack, Di Germanio, Clara, Shaan Lakshmanappa, Yashavanth, Elizaldi, Sonny R., Roh, Jamin W., Simmons, Graham, Watanabe, Jennifer, Pollard, Rachel E., Usachenko, Jodie, Immareddy, Ramya, Schmidt, Brian A., O’Connor, Shelby L., DeRisi, Joseph, Busch, Michael P., Iyer, Smita S., Van Rompay, Koen K. A., Hartigan-O’Connor, Dennis J., Miller, Christopher J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8612156/
https://www.ncbi.nlm.nih.gov/pubmed/34817208
http://dx.doi.org/10.1128/Spectrum.01397-21
_version_ 1784603423478382592
author Deere, Jesse D.
Carroll, Timothy D.
Dutra, Joseph
Fritts, Linda
Sammak, Rebecca Lee
Yee, JoAnn L.
Olstad, Katherine J.
Reader, J. Rachel
Kistler, Amy
Kamm, Jack
Di Germanio, Clara
Shaan Lakshmanappa, Yashavanth
Elizaldi, Sonny R.
Roh, Jamin W.
Simmons, Graham
Watanabe, Jennifer
Pollard, Rachel E.
Usachenko, Jodie
Immareddy, Ramya
Schmidt, Brian A.
O’Connor, Shelby L.
DeRisi, Joseph
Busch, Michael P.
Iyer, Smita S.
Van Rompay, Koen K. A.
Hartigan-O’Connor, Dennis J.
Miller, Christopher J.
author_facet Deere, Jesse D.
Carroll, Timothy D.
Dutra, Joseph
Fritts, Linda
Sammak, Rebecca Lee
Yee, JoAnn L.
Olstad, Katherine J.
Reader, J. Rachel
Kistler, Amy
Kamm, Jack
Di Germanio, Clara
Shaan Lakshmanappa, Yashavanth
Elizaldi, Sonny R.
Roh, Jamin W.
Simmons, Graham
Watanabe, Jennifer
Pollard, Rachel E.
Usachenko, Jodie
Immareddy, Ramya
Schmidt, Brian A.
O’Connor, Shelby L.
DeRisi, Joseph
Busch, Michael P.
Iyer, Smita S.
Van Rompay, Koen K. A.
Hartigan-O’Connor, Dennis J.
Miller, Christopher J.
author_sort Deere, Jesse D.
collection PubMed
description Human clinical studies investigating use of convalescent plasma (CP) for treatment of coronavirus disease 2019 (COVID-19) have produced conflicting results. Outcomes in these studies may vary at least partly due to different timing of CP administration relative to symptom onset. The mechanisms of action of CP include neutralizing antibodies but may extend beyond virus neutralization to include normalization of blood clotting and dampening of inflammation. Unresolved questions include the minimum therapeutic titer in the CP units or CP recipient as well as the optimal timing of administration. Here, we show that treatment of macaques with CP within 24 h of infection does not reduce viral shedding in nasal or lung secretions compared to controls and does not detectably improve any clinical endpoint. We also demonstrate that CP administration does not impact viral sequence diversity in vivo, although the selection of a viral sequence variant in both macaques receiving normal human plasma was suggestive of immune pressure. Our results suggest that CP, administered to medium titers, has limited efficacy, even when given very early after infection. Our findings also contribute information important for the continued development of the nonhuman primate model of COVID-19. These results should inform interpretation of clinical studies of CP in addition to providing insights useful for developing other passive immunotherapies and vaccine strategies. IMPORTANCE Antiviral treatment options for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain very limited. One treatment that was explored beginning early in the pandemic (and that is likely to be tested early in future pandemics) is plasma collected from people who have recovered from coronavirus disease 2019 (COVID-19), known as convalescent plasma (CP). We tested if CP reduces viral shedding or disease in a nonhuman primate model. Our results demonstrate that administration of CP 1 day after SARS-CoV-2 infection had no significant impact on viral loads, clinical disease, or sequence diversity, although treatment with normal human plasma resulted in selection of a specific viral variant. Our results demonstrate that passive immunization with CP, even during early infection, provided no significant benefit in a nonhuman primate model of SARS-CoV-2 infection.
format Online
Article
Text
id pubmed-8612156
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher American Society for Microbiology
record_format MEDLINE/PubMed
spelling pubmed-86121562021-11-29 SARS-CoV-2 Infection of Rhesus Macaques Treated Early with Human COVID-19 Convalescent Plasma Deere, Jesse D. Carroll, Timothy D. Dutra, Joseph Fritts, Linda Sammak, Rebecca Lee Yee, JoAnn L. Olstad, Katherine J. Reader, J. Rachel Kistler, Amy Kamm, Jack Di Germanio, Clara Shaan Lakshmanappa, Yashavanth Elizaldi, Sonny R. Roh, Jamin W. Simmons, Graham Watanabe, Jennifer Pollard, Rachel E. Usachenko, Jodie Immareddy, Ramya Schmidt, Brian A. O’Connor, Shelby L. DeRisi, Joseph Busch, Michael P. Iyer, Smita S. Van Rompay, Koen K. A. Hartigan-O’Connor, Dennis J. Miller, Christopher J. Microbiol Spectr Research Article Human clinical studies investigating use of convalescent plasma (CP) for treatment of coronavirus disease 2019 (COVID-19) have produced conflicting results. Outcomes in these studies may vary at least partly due to different timing of CP administration relative to symptom onset. The mechanisms of action of CP include neutralizing antibodies but may extend beyond virus neutralization to include normalization of blood clotting and dampening of inflammation. Unresolved questions include the minimum therapeutic titer in the CP units or CP recipient as well as the optimal timing of administration. Here, we show that treatment of macaques with CP within 24 h of infection does not reduce viral shedding in nasal or lung secretions compared to controls and does not detectably improve any clinical endpoint. We also demonstrate that CP administration does not impact viral sequence diversity in vivo, although the selection of a viral sequence variant in both macaques receiving normal human plasma was suggestive of immune pressure. Our results suggest that CP, administered to medium titers, has limited efficacy, even when given very early after infection. Our findings also contribute information important for the continued development of the nonhuman primate model of COVID-19. These results should inform interpretation of clinical studies of CP in addition to providing insights useful for developing other passive immunotherapies and vaccine strategies. IMPORTANCE Antiviral treatment options for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain very limited. One treatment that was explored beginning early in the pandemic (and that is likely to be tested early in future pandemics) is plasma collected from people who have recovered from coronavirus disease 2019 (COVID-19), known as convalescent plasma (CP). We tested if CP reduces viral shedding or disease in a nonhuman primate model. Our results demonstrate that administration of CP 1 day after SARS-CoV-2 infection had no significant impact on viral loads, clinical disease, or sequence diversity, although treatment with normal human plasma resulted in selection of a specific viral variant. Our results demonstrate that passive immunization with CP, even during early infection, provided no significant benefit in a nonhuman primate model of SARS-CoV-2 infection. American Society for Microbiology 2021-11-24 /pmc/articles/PMC8612156/ /pubmed/34817208 http://dx.doi.org/10.1128/Spectrum.01397-21 Text en Copyright © 2021 Deere et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Deere, Jesse D.
Carroll, Timothy D.
Dutra, Joseph
Fritts, Linda
Sammak, Rebecca Lee
Yee, JoAnn L.
Olstad, Katherine J.
Reader, J. Rachel
Kistler, Amy
Kamm, Jack
Di Germanio, Clara
Shaan Lakshmanappa, Yashavanth
Elizaldi, Sonny R.
Roh, Jamin W.
Simmons, Graham
Watanabe, Jennifer
Pollard, Rachel E.
Usachenko, Jodie
Immareddy, Ramya
Schmidt, Brian A.
O’Connor, Shelby L.
DeRisi, Joseph
Busch, Michael P.
Iyer, Smita S.
Van Rompay, Koen K. A.
Hartigan-O’Connor, Dennis J.
Miller, Christopher J.
SARS-CoV-2 Infection of Rhesus Macaques Treated Early with Human COVID-19 Convalescent Plasma
title SARS-CoV-2 Infection of Rhesus Macaques Treated Early with Human COVID-19 Convalescent Plasma
title_full SARS-CoV-2 Infection of Rhesus Macaques Treated Early with Human COVID-19 Convalescent Plasma
title_fullStr SARS-CoV-2 Infection of Rhesus Macaques Treated Early with Human COVID-19 Convalescent Plasma
title_full_unstemmed SARS-CoV-2 Infection of Rhesus Macaques Treated Early with Human COVID-19 Convalescent Plasma
title_short SARS-CoV-2 Infection of Rhesus Macaques Treated Early with Human COVID-19 Convalescent Plasma
title_sort sars-cov-2 infection of rhesus macaques treated early with human covid-19 convalescent plasma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8612156/
https://www.ncbi.nlm.nih.gov/pubmed/34817208
http://dx.doi.org/10.1128/Spectrum.01397-21
work_keys_str_mv AT deerejessed sarscov2infectionofrhesusmacaquestreatedearlywithhumancovid19convalescentplasma
AT carrolltimothyd sarscov2infectionofrhesusmacaquestreatedearlywithhumancovid19convalescentplasma
AT dutrajoseph sarscov2infectionofrhesusmacaquestreatedearlywithhumancovid19convalescentplasma
AT frittslinda sarscov2infectionofrhesusmacaquestreatedearlywithhumancovid19convalescentplasma
AT sammakrebeccalee sarscov2infectionofrhesusmacaquestreatedearlywithhumancovid19convalescentplasma
AT yeejoannl sarscov2infectionofrhesusmacaquestreatedearlywithhumancovid19convalescentplasma
AT olstadkatherinej sarscov2infectionofrhesusmacaquestreatedearlywithhumancovid19convalescentplasma
AT readerjrachel sarscov2infectionofrhesusmacaquestreatedearlywithhumancovid19convalescentplasma
AT kistleramy sarscov2infectionofrhesusmacaquestreatedearlywithhumancovid19convalescentplasma
AT kammjack sarscov2infectionofrhesusmacaquestreatedearlywithhumancovid19convalescentplasma
AT digermanioclara sarscov2infectionofrhesusmacaquestreatedearlywithhumancovid19convalescentplasma
AT shaanlakshmanappayashavanth sarscov2infectionofrhesusmacaquestreatedearlywithhumancovid19convalescentplasma
AT elizaldisonnyr sarscov2infectionofrhesusmacaquestreatedearlywithhumancovid19convalescentplasma
AT rohjaminw sarscov2infectionofrhesusmacaquestreatedearlywithhumancovid19convalescentplasma
AT simmonsgraham sarscov2infectionofrhesusmacaquestreatedearlywithhumancovid19convalescentplasma
AT watanabejennifer sarscov2infectionofrhesusmacaquestreatedearlywithhumancovid19convalescentplasma
AT pollardrachele sarscov2infectionofrhesusmacaquestreatedearlywithhumancovid19convalescentplasma
AT usachenkojodie sarscov2infectionofrhesusmacaquestreatedearlywithhumancovid19convalescentplasma
AT immareddyramya sarscov2infectionofrhesusmacaquestreatedearlywithhumancovid19convalescentplasma
AT schmidtbriana sarscov2infectionofrhesusmacaquestreatedearlywithhumancovid19convalescentplasma
AT oconnorshelbyl sarscov2infectionofrhesusmacaquestreatedearlywithhumancovid19convalescentplasma
AT derisijoseph sarscov2infectionofrhesusmacaquestreatedearlywithhumancovid19convalescentplasma
AT buschmichaelp sarscov2infectionofrhesusmacaquestreatedearlywithhumancovid19convalescentplasma
AT iyersmitas sarscov2infectionofrhesusmacaquestreatedearlywithhumancovid19convalescentplasma
AT vanrompaykoenka sarscov2infectionofrhesusmacaquestreatedearlywithhumancovid19convalescentplasma
AT hartiganoconnordennisj sarscov2infectionofrhesusmacaquestreatedearlywithhumancovid19convalescentplasma
AT millerchristopherj sarscov2infectionofrhesusmacaquestreatedearlywithhumancovid19convalescentplasma