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

• Published in: Scientific reports Vol. 11; no. 1; pp. 11462 - 14
• Main Authors: Julià, Antonio, Bonafonte-Pardàs, Irene, Gómez, Antonio, López-Lasanta, María, López-Corbeto, Mireia, Martínez-Mateu, Sergio H., Lladós, Jordi, Rodríguez-Nunez, Iván, Myers, Richard M., Marsal, Sara
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.06.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/154/555; 692/699/249/2510; 692/699/255/2514; Abatacept - pharmacology; Abatacept - therapeutic use; Aged; Antagonism; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - immunology; B7-1 Antigen - metabolism; B7-2 Antigen - metabolism; Blood; Bronchoalveolar Lavage Fluid - cytology; Bronchus; CD80 antigen; China; Coronaviruses; COVID-19; COVID-19 - blood; COVID-19 - complications; COVID-19 - immunology; COVID-19 Drug Treatment; Cytokine Release Syndrome - immunology; Cytokine Release Syndrome - prevention & control; Cytokine Release Syndrome - virology; Cytokine storm; Cytokines; Epidemiology; Female; Humanities and Social Sciences; Humans; Immune response; Immunosuppressive Agents - pharmacology; Immunosuppressive Agents - therapeutic use; Inflammation; Male; Middle Aged; multidisciplinary; Observational Studies as Topic; Pandemics; Ribonucleic acid; RNA; RNA-Seq; SARS-CoV-2 - immunology; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Severity of Illness Index; Signal Transduction - drug effects; Signal Transduction - immunology; Single-Cell Analysis; Spain; United States; Up-Regulation - drug effects; Up-Regulation - immunology; United States; China; Spain
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-90797-0

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.