Impact of interleukin-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and antibody responses in patients with COVID-19: A prospective cohort study

Background: The virological and immunological effects of the immunomodulatory drugs used for COVID-19 remain unknown. We evaluated the impact of interleukin (IL)-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and the antibody response in patients with COVID-19. Methods: Prospective cohort...

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Autores: Masia, M, Fernandez-Gonzalez, M, Padilla, S, Ortega, P, Garcia, JA, Agullo, V, Garcia-Abellan, J, Telenti, G, Guillen, L, Gutierrez, F
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
Repositorio:r-FISABIO. Repositorio Institucional de Producción Científica
OAI Identifier:oai:fisabio.fundanetsuite.com:p9059
Acceso en línea:https://fisabio.portalinvestigacion.com/publicaciones/9059
Access Level:acceso abierto
Palabra clave:Tocilizumab
SARS-CoV-2
COVID-19
Viral kinetics
Antibody responses
Anti-cytokine therapy
S-IgG
N-IgG
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spelling Impact of interleukin-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and antibody responses in patients with COVID-19: A prospective cohort studyMasia, MFernandez-Gonzalez, MPadilla, SOrtega, PGarcia, JAAgullo, VGarcia-Abellan, JTelenti, GGuillen, LGutierrez, FTocilizumabSARS-CoV-2COVID-19Viral kineticsAntibody responsesAnti-cytokine therapyS-IgGN-IgGBackground: The virological and immunological effects of the immunomodulatory drugs used for COVID-19 remain unknown. We evaluated the impact of interleukin (IL)-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and the antibody response in patients with COVID-19. Methods: Prospective cohort study in patients admitted with COVID-19. Serial nasopharyngeal and plasma samples were measured for SARS-CoV-2 RNA and S-IgG/N-IgG titers, respectively. Findings: 138 patients with confirmed infection were included; 76 (55%) underwent IL-6 blockade. Median initial SOFA (p = 0.016) and SARS-CoV-2 viral load (p<0.001, Mann-Whitney-Wilcoxon test) were significantly higher among anti-IL-6 users. Patients under IL-6 blockade showed delayed viral clearance in the Kaplan-Meier curves (HR 0.35 [95%CI] [0.15.0.81], log-rank p = 0.014), but an adjusted propensity score matching model did not demonstrate a significant relationship of IL-6 blockade with viral clearance (HR 1.63 [0.35.7.7]). Cox regression showed an inverse association between SARS-CoV-2 RNA clearance and the initial viral load (HR 0.35 [0 .11.0.89]). Patients under the IL-6 blocker showed shorter median time to seropositivity, higher peak antibody titers, and higher cumulative proportion of seropositivity in the Kaplan Meier curves (HR 3.1 [1.9.5] for S-IgG; and HR 3.0 [1.9.4.9] for N-IgG; log-rank p<0.001 for both). However, no significant differences between groups were found in either S-IgG (HR 1.56 [0.41.6.0]) nor N-IgG (HR 0.96 [0.26.3.5]) responses in an adjusted propensity score analysis. Interpretation: Our results suggest that in patients infected with SARS-CoV-2, IL-6 blockade does not impair the viral specific antibody responses. Although a delayed viral clearance was observed, it was driven by a higher initial viral load. The study supports the safety of this therapy in patients with COVID-19. Funding: Instituto de salud Carlos III (Spain). (c) 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)ELSEVIER2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fisabio.portalinvestigacion.com/publicaciones/9059EBioMedicineISSN: 23523964reponame:r-FISABIO. Repositorio Institucional de Producción Científicainstname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)Inglésinfo:eu-repo/semantics/openAccessoai:fisabio.fundanetsuite.com:p90592026-06-11T12:45:17Z
dc.title.none.fl_str_mv Impact of interleukin-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and antibody responses in patients with COVID-19: A prospective cohort study
title Impact of interleukin-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and antibody responses in patients with COVID-19: A prospective cohort study
spellingShingle Impact of interleukin-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and antibody responses in patients with COVID-19: A prospective cohort study
Masia, M
Tocilizumab
SARS-CoV-2
COVID-19
Viral kinetics
Antibody responses
Anti-cytokine therapy
S-IgG
N-IgG
title_short Impact of interleukin-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and antibody responses in patients with COVID-19: A prospective cohort study
title_full Impact of interleukin-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and antibody responses in patients with COVID-19: A prospective cohort study
title_fullStr Impact of interleukin-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and antibody responses in patients with COVID-19: A prospective cohort study
title_full_unstemmed Impact of interleukin-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and antibody responses in patients with COVID-19: A prospective cohort study
title_sort Impact of interleukin-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and antibody responses in patients with COVID-19: A prospective cohort study
dc.creator.none.fl_str_mv Masia, M
Fernandez-Gonzalez, M
Padilla, S
Ortega, P
Garcia, JA
Agullo, V
Garcia-Abellan, J
Telenti, G
Guillen, L
Gutierrez, F
author Masia, M
author_facet Masia, M
Fernandez-Gonzalez, M
Padilla, S
Ortega, P
Garcia, JA
Agullo, V
Garcia-Abellan, J
Telenti, G
Guillen, L
Gutierrez, F
author_role author
author2 Fernandez-Gonzalez, M
Padilla, S
Ortega, P
Garcia, JA
Agullo, V
Garcia-Abellan, J
Telenti, G
Guillen, L
Gutierrez, F
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Tocilizumab
SARS-CoV-2
COVID-19
Viral kinetics
Antibody responses
Anti-cytokine therapy
S-IgG
N-IgG
topic Tocilizumab
SARS-CoV-2
COVID-19
Viral kinetics
Antibody responses
Anti-cytokine therapy
S-IgG
N-IgG
description Background: The virological and immunological effects of the immunomodulatory drugs used for COVID-19 remain unknown. We evaluated the impact of interleukin (IL)-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and the antibody response in patients with COVID-19. Methods: Prospective cohort study in patients admitted with COVID-19. Serial nasopharyngeal and plasma samples were measured for SARS-CoV-2 RNA and S-IgG/N-IgG titers, respectively. Findings: 138 patients with confirmed infection were included; 76 (55%) underwent IL-6 blockade. Median initial SOFA (p = 0.016) and SARS-CoV-2 viral load (p<0.001, Mann-Whitney-Wilcoxon test) were significantly higher among anti-IL-6 users. Patients under IL-6 blockade showed delayed viral clearance in the Kaplan-Meier curves (HR 0.35 [95%CI] [0.15.0.81], log-rank p = 0.014), but an adjusted propensity score matching model did not demonstrate a significant relationship of IL-6 blockade with viral clearance (HR 1.63 [0.35.7.7]). Cox regression showed an inverse association between SARS-CoV-2 RNA clearance and the initial viral load (HR 0.35 [0 .11.0.89]). Patients under the IL-6 blocker showed shorter median time to seropositivity, higher peak antibody titers, and higher cumulative proportion of seropositivity in the Kaplan Meier curves (HR 3.1 [1.9.5] for S-IgG; and HR 3.0 [1.9.4.9] for N-IgG; log-rank p<0.001 for both). However, no significant differences between groups were found in either S-IgG (HR 1.56 [0.41.6.0]) nor N-IgG (HR 0.96 [0.26.3.5]) responses in an adjusted propensity score analysis. Interpretation: Our results suggest that in patients infected with SARS-CoV-2, IL-6 blockade does not impair the viral specific antibody responses. Although a delayed viral clearance was observed, it was driven by a higher initial viral load. The study supports the safety of this therapy in patients with COVID-19. Funding: Instituto de salud Carlos III (Spain). (c) 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fisabio.portalinvestigacion.com/publicaciones/9059
url https://fisabio.portalinvestigacion.com/publicaciones/9059
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv ELSEVIER
publisher.none.fl_str_mv ELSEVIER
dc.source.none.fl_str_mv EBioMedicine
ISSN: 23523964
reponame:r-FISABIO. Repositorio Institucional de Producción Científica
instname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
instname_str Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
reponame_str r-FISABIO. Repositorio Institucional de Producción Científica
collection r-FISABIO. Repositorio Institucional de Producción Científica
repository.name.fl_str_mv
repository.mail.fl_str_mv
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