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06 01, 2021;11 (1): 11462.

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

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 Information
  1. Antonio Julià: Rheumatology Department and Rheumatology Research Group, Vall d'Hebron Hospital Research Institute, 08035, Barcelona, Spain. toni.julia@vhir.org.
  2. Irene Bonafonte-Pardàs: Rheumatology Department and Rheumatology Research Group, Vall d'Hebron Hospital Research Institute, 08035, Barcelona, Spain.
  3. Antonio Gómez: Rheumatology Department and Rheumatology Research Group, Vall d'Hebron Hospital Research Institute, 08035, Barcelona, Spain.
  4. María López-Lasanta: Rheumatology Department and Rheumatology Research Group, Vall d'Hebron Hospital Research Institute, 08035, Barcelona, Spain.
  5. Mireia López-Corbeto: Rheumatology Department and Rheumatology Research Group, Vall d'Hebron Hospital Research Institute, 08035, Barcelona, Spain.
  6. Sergio H Martínez-Mateu: Rheumatology Department and Rheumatology Research Group, Vall d'Hebron Hospital Research Institute, 08035, Barcelona, Spain.
  7. Jordi Lladós: Rheumatology Department and Rheumatology Research Group, Vall d'Hebron Hospital Research Institute, 08035, Barcelona, Spain.
  8. Iván Rodríguez-Nunez: HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA.
  9. Richard M Myers: HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA.
  10. Sara Marsal: Rheumatology Department and Rheumatology Research Group, Vall d'Hebron Hospital Research Institute, 08035, Barcelona, Spain. sara.marsal@vhir.org.
PMID: 34075090 DOI: 10.1038/s41598-021-90797-0

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.

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MeSH Term

Abatacept
Aged
Arthritis, Rheumatoid
B7-1 Antigen
B7-2 Antigen
Bronchoalveolar Lavage Fluid
COVID-19
China
Cytokine Release Syndrome
Female
Humans
Immunosuppressive Agents
Male
Middle Aged
Observational Studies as Topic
RNA-Seq
SARS-CoV-2
Severity of Illness Index
Signal Transduction
Single-Cell Analysis
Spain
United States
Up-Regulation
COVID-19 Drug Treatment

Chemicals

B7-1 Antigen
B7-2 Antigen
CD80 protein, human
CD86 protein, human
Immunosuppressive Agents
Abatacept
Journal Article Research Support, Non-U.S. Gov't

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