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    Identification of a potential therapeutic target against COVID-19

    A study co-directed by Michaela Fontenay

    Identification of a potential therapeutic target against COVID-19

     

    Michaela Fontenay's team* associated with clinician-researchers from Cochin Hospital and Institut Cochin Frédéric Pène** and Luc Mouthon*** and clinicians from Hôtel-Dieu (Delphine Cantin) conducted in collaboration with the teams of Eric Solary (Institut Gustave Roussy) and Florent Ginhoux (Singapore Immunology Network), a study which reveals that patients with a severe form of COVID-19 have a deficiency in the functions of the innate immunity of myeloid cells (neutrophils, monocytes), associated with a very high level of calprotectin in the blood. This study is published in the journal Cell.

     

    Analyzes by spectral flow cytometry, mass cytometry, RNA sequencing at the single cell level (carried out by Olivier Kosmider*) and by conventional cytometry (carried out by Nicolas Chapuis*) ​​of blood samples from 158 patients tested negative by PCR from SARS- CoV-2 or positive with mild, moderate or severe disease, revealed that severe forms of COVID-19 are associated with 1) an explosion in circulating levels of the S100A8 / A9 heterodimer or calprotectin (Muriel Andrieu, CYBIO, Core facilities Department), 2) a reduced quantity of non-classical monocytes and 3) an emergency myelopoiesis which releases immature and dysplastic myeloid cells. The 100- to 1000-fold increased production of calprotectin could trigger this emergency myelopoiesis with immunosuppressive phenotype as observed in cancer or inflammation.

     

     

     

     

    An early diagnosis of a severe form can be proposed by the combination of a calprotectin assay and a routine flow cytometry test that is already implemented in French hematology laboratories to improve the diagnosis of chronic myelomonocytic leukemia.

    These unprecedented results make it possible to consider new therapeutic strategies to counter the worsening of COVID-19, for example by blocking the receptors for calprotectin or emergency myelopoiesis, strategies to be evaluated in clinical trials.

     

     

    * Laboratory of Hematology, Cochin hospital; Normal and Pathological Hematopoiesis team, Institut Cochin DRC Department

    ** Intensive Care Department, Cochin hospital; Team Pulmonary and Systemic Immune Responses during acute and chronic bacterial infections, Institut Cochin 3I Department

    *** Department of Internal Medicine, Cochin hospital; Neutrophils and Vasculitis team, Institut Cochin 3I Department.

     

    Reference

    Silvin A, Chapuis N, Dunsmore G, Goubet A-G, Dubuisson A, Derosa L, Almire C, Hénon C, Kosmider O, Droin N, Rameau P, Catelain C, Alfaro A, Dussiau C, Friedrich C, Sourdeau E, Marin N, Szwebel T-A, Cantin D, Mouthon L, Borderie D, Deloger M, Bredel D, Mouraud S, Drubay D, Andrieu M, Lhonneur A-S, Saada V, Stoclin A, Willekens C, Pommeret F, Griscelli F, Ng L G, Zhang Z, Bost P, Amit I, Barlesi F, Marabelle A, Pène F, Gachot B, André F, Zitvogel L, Ginhoux F,* Fontenay M,* and Solary E*.  Elevated calprotectin and abnormal myeloid cell subsets discriminate severe from mild COVID-19. Cell. 2020 Aug 5:S0092-8674(20)30993-4. doi: 10.1016/j.cell.2020.08.002. Online ahead of print. PMID: 32810439

     

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