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Long COVID immune phenotypes identified for blockade

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  • Research Highlight
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  • Jared B. Fudge1 

Nature Biotechnology

volume 41page 470 (2023)Cite this article

Symptoms of severe long COVID may include lung fibrosis, and a precise, detailed profile of associated immunopathology has been missing until now. Writing in Proceedings of the National Academy of Sciences USA, Cui et al. use published single-cell transcriptomics data from human lung-tissue samples to explore the onset of fibrosis, alongside a new humanized mouse model for long COVID. A series of unique immune hallmarks serve as a basis to investigate potential therapeutic strategies for the ever-growing cohort of patients with long COVID.

Leukocytes and pulmonary fibroblasts from patients with long COVID had unique gene-expression profiles compared to those from healthy, matched control individuals. Pathways related to the pro-inflammatory cytokine and anti-inflammatory myokine interleukin-6 (IL-6) were upregulated in alveolar macrophages from these patients, consistent with previous reports of cytokine storms. Neutrophils and lung fibroblasts were enriched for profibrotic pathways and associated with increased deposition of extracellular matrix proteins. Immunofluorescence assays validated the enrichment of proteins involved in innate immune activation and profibrosis pathways in lung tissue from patients with long COVID, probably mediated by the transcription factor JUN.

Next, the authors developed a humanized mouse model of SARS-CoV-2 infection. Fibrosis symptoms appeared in 75% of treated mice four weeks after exposure. Neutrophil and macrophage recruitment further recapitulated patient pathology in the mouse model. Treatments using anti-IL-6 and anti-CD47 antibodies were administered for two weeks, and this was sufficient to restore lung morphology, reduce fibrosis and ameliorate recruitment of neutrophils and macrophages to the affected tissue.

This study pinpoints the role of fibrosis and inflammation pathways in initial long-COVID pathology and offers clinical targets related to the innate immune response.

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  1. Nature Biotechnology

    Jared B. Fudge

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Jared B. Fudge.

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Fudge, J.B. Long COVID immune phenotypes identified for blockade.
Nat Biotechnol 41, 470 (2023).

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Long COVID immune phenotypes identified for blockade Reviewed by RP on April 18, 2023 Rating: 5

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