Targeting of the CD80/86 proinflammatory axis as a therapeutic strategy to prevent severe COVID-19

Abstract An excessive immune response known as cytokine storm is the hallmark of severe COVID-19. The cause of this cytokine rampage is yet not known. Based on recent epidemiological evidence, we hypothesized that CD80/86 signaling is essential for this hyperinflammation, and that blocking this proi...

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Autores principales:	Antonio Julià, Irene Bonafonte-Pardàs, Antonio Gómez, María López-Lasanta, Mireia López-Corbeto, Sergio H. Martínez-Mateu, Jordi Lladós, Iván Rodríguez-Nunez, Richard M. Myers, Sara Marsal
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3b112fda678c47dda3f345ff8082ddcb
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spelling	oai:doaj.org-article:3b112fda678c47dda3f345ff8082ddcb2021-12-02T15:56:57ZTargeting of the CD80/86 proinflammatory axis as a therapeutic strategy to prevent severe COVID-1910.1038/s41598-021-90797-02045-2322https://doaj.org/article/3b112fda678c47dda3f345ff8082ddcb2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90797-0https://doaj.org/toc/2045-2322Abstract An excessive immune response known as cytokine storm is the hallmark of severe COVID-19. The cause of this cytokine rampage is yet not known. Based on recent epidemiological evidence, we hypothesized that CD80/86 signaling is essential for this hyperinflammation, and that blocking this proinflammatory axis could be an effective therapeutic approach to protect against severe COVID-19. Here we provide exploratory evidence that abatacept, a drug that blocks CD80/86 co-stimulation, produces changes at the systemic level that are highly antagonistic of the proinflammatory processes elicited by COVID-19. Using RNA-seq from blood samples from a longitudinal cohort of n = 38 rheumatic patients treated with abatacept, we determined the immunological processes that are significantly regulated by this treatment. We then analyzed available blood RNA-seq from two COVID19 patient cohorts, a very early cohort from the epicenter of the pandemic in China (n = 3 COVID-19 cases and n = 3 controls), and a recent and larger cohort from the USA (n = 49 severe and n = 51 mild COVD-19 patients). We found a highly significant antagonism between SARS-CoV-2 infection and COVID-19 severity with the systemic response to abatacept. Analysis of previous single-cell RNA-seq data from bronchoalveolar lavage fluid from mild and severe COVID-19 patients and controls, reinforce the implication of the CD80/86 proinflammatory axis. Our functional results further support abatacept as a candidate therapeutic approach to prevent severe COVID-19.Antonio JuliàIrene Bonafonte-PardàsAntonio GómezMaría López-LasantaMireia López-CorbetoSergio H. Martínez-MateuJordi LladósIván Rodríguez-NunezRichard M. MyersSara MarsalNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Antonio Julià Irene Bonafonte-Pardàs Antonio Gómez María López-Lasanta Mireia López-Corbeto Sergio H. Martínez-Mateu Jordi Lladós Iván Rodríguez-Nunez Richard M. Myers Sara Marsal Targeting of the CD80/86 proinflammatory axis as a therapeutic strategy to prevent severe COVID-19
description	Abstract An excessive immune response known as cytokine storm is the hallmark of severe COVID-19. The cause of this cytokine rampage is yet not known. Based on recent epidemiological evidence, we hypothesized that CD80/86 signaling is essential for this hyperinflammation, and that blocking this proinflammatory axis could be an effective therapeutic approach to protect against severe COVID-19. Here we provide exploratory evidence that abatacept, a drug that blocks CD80/86 co-stimulation, produces changes at the systemic level that are highly antagonistic of the proinflammatory processes elicited by COVID-19. Using RNA-seq from blood samples from a longitudinal cohort of n = 38 rheumatic patients treated with abatacept, we determined the immunological processes that are significantly regulated by this treatment. We then analyzed available blood RNA-seq from two COVID19 patient cohorts, a very early cohort from the epicenter of the pandemic in China (n = 3 COVID-19 cases and n = 3 controls), and a recent and larger cohort from the USA (n = 49 severe and n = 51 mild COVD-19 patients). We found a highly significant antagonism between SARS-CoV-2 infection and COVID-19 severity with the systemic response to abatacept. Analysis of previous single-cell RNA-seq data from bronchoalveolar lavage fluid from mild and severe COVID-19 patients and controls, reinforce the implication of the CD80/86 proinflammatory axis. Our functional results further support abatacept as a candidate therapeutic approach to prevent severe COVID-19.
format	article
author	Antonio Julià Irene Bonafonte-Pardàs Antonio Gómez María López-Lasanta Mireia López-Corbeto Sergio H. Martínez-Mateu Jordi Lladós Iván Rodríguez-Nunez Richard M. Myers Sara Marsal
author_facet	Antonio Julià Irene Bonafonte-Pardàs Antonio Gómez María López-Lasanta Mireia López-Corbeto Sergio H. Martínez-Mateu Jordi Lladós Iván Rodríguez-Nunez Richard M. Myers Sara Marsal
author_sort	Antonio Julià
title	Targeting of the CD80/86 proinflammatory axis as a therapeutic strategy to prevent severe COVID-19
title_short	Targeting of the CD80/86 proinflammatory axis as a therapeutic strategy to prevent severe COVID-19
title_full	Targeting of the CD80/86 proinflammatory axis as a therapeutic strategy to prevent severe COVID-19
title_fullStr	Targeting of the CD80/86 proinflammatory axis as a therapeutic strategy to prevent severe COVID-19
title_full_unstemmed	Targeting of the CD80/86 proinflammatory axis as a therapeutic strategy to prevent severe COVID-19
title_sort	targeting of the cd80/86 proinflammatory axis as a therapeutic strategy to prevent severe covid-19
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3b112fda678c47dda3f345ff8082ddcb
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Targeting of the CD80/86 proinflammatory axis as a therapeutic strategy to prevent severe COVID-19

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