Convalescent plasma in Covid-19: Possible mechanisms of action

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible of the coronavirus disease 2019(COVID-19) pandemic. Therapeutic options including antimalarials, antivirals, and vaccines are under study.Meanwhile the current pandemic has called attention over old therapeutic tools to trea...

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Autores:
Rojas, Manuel
Rodríguez, Yhojan
Monsalve, Diana M.
Acosta Ampudia, Yeny
Camacho, Bernardo
Gallo, Juan Esteban
Rojas Villarraga, Adriana
Ramírez Santana, Carolina
Díaz Coronado, Juan C.
Manrique, Rubén
Mantilla, Rubén D.
Shonenfeld, Yehuda
Anaya, Juan Manuel
Tipo de recurso:
Article of journal
Fecha de publicación:
2020
Institución:
Fundación Universitaria de Ciencias de la Salud - FUCS
Repositorio:
Repositorio Digital Institucional ReDi
Idioma:
eng
OAI Identifier:
oai:repositorio.fucsalud.edu.co:001/1719
Acceso en línea:
https://repositorio.fucsalud.edu.co/handle/001/1719
Palabra clave:
Coronavirus
COVID-19
SARS-COV-2
Convalecencia
Citocinas
Inmunoglobinas intravenosas
Anticuerpos neutralizantes
Anticuerpos
Rights
openAccess
License
Atribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0)
id FUCS2_4ed4bfaf47934ca83e880e4d6aa01dba
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network_acronym_str FUCS2
network_name_str Repositorio Digital Institucional ReDi
repository_id_str
dc.title.eng.fl_str_mv Convalescent plasma in Covid-19: Possible mechanisms of action
title Convalescent plasma in Covid-19: Possible mechanisms of action
spellingShingle Convalescent plasma in Covid-19: Possible mechanisms of action
Coronavirus
COVID-19
SARS-COV-2
Convalecencia
Citocinas
Inmunoglobinas intravenosas
Anticuerpos neutralizantes
Anticuerpos
title_short Convalescent plasma in Covid-19: Possible mechanisms of action
title_full Convalescent plasma in Covid-19: Possible mechanisms of action
title_fullStr Convalescent plasma in Covid-19: Possible mechanisms of action
title_full_unstemmed Convalescent plasma in Covid-19: Possible mechanisms of action
title_sort Convalescent plasma in Covid-19: Possible mechanisms of action
dc.creator.fl_str_mv Rojas, Manuel
Rodríguez, Yhojan
Monsalve, Diana M.
Acosta Ampudia, Yeny
Camacho, Bernardo
Gallo, Juan Esteban
Rojas Villarraga, Adriana
Ramírez Santana, Carolina
Díaz Coronado, Juan C.
Manrique, Rubén
Mantilla, Rubén D.
Shonenfeld, Yehuda
Anaya, Juan Manuel
dc.contributor.author.none.fl_str_mv Rojas, Manuel
Rodríguez, Yhojan
Monsalve, Diana M.
Acosta Ampudia, Yeny
Camacho, Bernardo
Gallo, Juan Esteban
Rojas Villarraga, Adriana
Ramírez Santana, Carolina
Díaz Coronado, Juan C.
Manrique, Rubén
Mantilla, Rubén D.
Shonenfeld, Yehuda
Anaya, Juan Manuel
dc.subject.proposal.spa.fl_str_mv Coronavirus
COVID-19
SARS-COV-2
Convalecencia
Citocinas
Inmunoglobinas intravenosas
Anticuerpos neutralizantes
topic Coronavirus
COVID-19
SARS-COV-2
Convalecencia
Citocinas
Inmunoglobinas intravenosas
Anticuerpos neutralizantes
Anticuerpos
dc.subject.decs.none.fl_str_mv Anticuerpos
description Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible of the coronavirus disease 2019(COVID-19) pandemic. Therapeutic options including antimalarials, antivirals, and vaccines are under study.Meanwhile the current pandemic has called attention over old therapeutic tools to treat infectious diseases.Convalescent plasma (CP) constitutes thefirst option in the current situation, since it has been successfully usedin other coronaviruses outbreaks. Herein, we discuss the possible mechanisms of action of CP and their re-percussion in COVID-19 pathogenesis, including direct neutralization of the virus, control of an overactiveimmune system (i.e., cytokine storm, Th1/Th17 ratio, complement activation) and immunomodulation of ahypercoagulable state. All these benefits of CP are expected to be better achieved if used in non-criticallyhospitalized patients, in the hope of reducing morbidity and mortality.
publishDate 2020
dc.date.issued.none.fl_str_mv 2020-07
dc.date.accessioned.none.fl_str_mv 2021-08-20T15:14:55Z
dc.date.available.none.fl_str_mv 2021-08-20T15:14:55Z
dc.type.spa.fl_str_mv Artículo de revista
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url https://repositorio.fucsalud.edu.co/handle/001/1719
dc.language.iso.spa.fl_str_mv eng
language eng
dc.relation.ispartof.none.fl_str_mv Autoimmunity Reviews e-ISSN:1873-0183 Vol.19 Núm.7 (2020)
dc.relation.citationendpage.spa.fl_str_mv 102554
dc.relation.citationissue.spa.fl_str_mv 7
dc.relation.citationstartpage.spa.fl_str_mv 102554
dc.relation.citationvolume.spa.fl_str_mv 19
dc.relation.ispartofjournal.spa.fl_str_mv Autoimmunity Reviews
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eu_rights_str_mv openAccess
rights_invalid_str_mv Atribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0)
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dc.format.extent.spa.fl_str_mv 9 p.
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dc.publisher.spa.fl_str_mv Research Center for Autoimmune Diseases
dc.publisher.place.spa.fl_str_mv Holanda
dc.source.spa.fl_str_mv https://www.sciencedirect.com/science/article/pii/S1568997220301166
institution Fundación Universitaria de Ciencias de la Salud - FUCS
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spelling Rojas, Manuelb247aa564a478cb82b9c90d6e191bdc2Rodríguez, Yhojan8246e304321cbb75a19d4257c2330c23Monsalve, Diana M.3f68520233b9817a72e2dae4eea1619bAcosta Ampudia, Yenyb4f0c7e62e1aa24474436273a30dc094Camacho, Bernardo4829e24ffb6696a117d169cf55717ad3Gallo, Juan Estebanf1eddc17707236ced4ef277a2bd74795Rojas Villarraga, Adrianaca14b4d53539f7bfee7279c6aa39a8d3Ramírez Santana, Carolinac2a9afa2411dede95bd37d3aba1e68aaDíaz Coronado, Juan C.7ca5c76158c1bfd6966eb9a6e4397af2Manrique, Rubéncd9b26a838084dc5ed42a23084f277b0Mantilla, Rubén D.aff491b30aea37f3e748020e3d1f54cdShonenfeld, Yehuda56a2355d73291926a2b674e5aae4ddd1Anaya, Juan Manuel2be53f18c94f183a1c463ada18a12a962021-08-20T15:14:55Z2020-072021-08-20T15:14:55ZResearch Center for Autoimmune DiseasesHolandaSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible of the coronavirus disease 2019(COVID-19) pandemic. Therapeutic options including antimalarials, antivirals, and vaccines are under study.Meanwhile the current pandemic has called attention over old therapeutic tools to treat infectious diseases.Convalescent plasma (CP) constitutes thefirst option in the current situation, since it has been successfully usedin other coronaviruses outbreaks. Herein, we discuss the possible mechanisms of action of CP and their re-percussion in COVID-19 pathogenesis, including direct neutralization of the virus, control of an overactiveimmune system (i.e., cytokine storm, Th1/Th17 ratio, complement activation) and immunomodulation of ahypercoagulable state. All these benefits of CP are expected to be better achieved if used in non-criticallyhospitalized patients, in the hope of reducing morbidity and mortality.https://www.sciencedirect.com/science/article/pii/S15689972203011669 p.application/pdfConvalescent plasma in Covid-19: Possible mechanisms of actionArtículo de revistahttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionTexthttp://purl.org/coar/version/c_970fb48d4fbd8a85https://repositorio.fucsalud.edu.co/handle/001/1719engAutoimmunity Reviews e-ISSN:1873-0183 Vol.19 Núm.7 (2020)102554710255419Autoimmunity Reviewsinfo:eu-repo/semantics/openAccessAtribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0)https://creativecommons.org/licenses/by-nd/4.0/http://purl.org/coar/access_right/c_abf2CoronavirusCOVID-19SARS-COV-2ConvalecenciaCitocinasInmunoglobinas intravenosasAnticuerpos neutralizantesAnticuerposPublicationORIGINALConvalescent plasma in Covid-19. 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