Monocytopenia, monocyte morphological anomalies and hyperinflammation characterise severe COVID-19 in type 2 diabetes.
Identifieur interne : 000A96 ( Main/Exploration ); précédent : 000A95; suivant : 000A97Monocytopenia, monocyte morphological anomalies and hyperinflammation characterise severe COVID-19 in type 2 diabetes.
Auteurs : Fawaz Alzaid [France] ; Jean-Baptiste Julla [France] ; Marc Diedisheim [France] ; Charline Potier [France] ; Louis Potier [France] ; Gilberto Velho [France] ; Bénédicte Gaborit [France] ; Philippe Manivet [France] ; Stéphane Germain [France] ; Tiphaine Vidal-Trecan [France] ; Ronan Roussel [France] ; Jean-Pierre Riveline [France] ; Elise Dalmas [France] ; Nicolas Venteclef [France] ; Jean-François Gautier [France]Source :
- EMBO molecular medicine [ 1757-4684 ] ; 2020.
Abstract
Early in the COVID-19 pandemic, type 2 diabetes (T2D) was marked as a risk factor for severe disease and mortality. Inflammation is central to the aetiology of both conditions where variations in immune responses can mitigate or aggravate disease course. Identifying at-risk groups based on immunoinflammatory signatures is valuable in directing personalised care and developing potential targets for precision therapy. This observational study characterised immunophenotypic variation associated with COVID-19 severity in T2D. Broad-spectrum immunophenotyping quantified 15 leucocyte populations in peripheral circulation from a cohort of 45 hospitalised COVID-19 patients with and without T2D. Lymphocytopenia and specific loss of cytotoxic CD8+ lymphocytes were associated with severe COVID-19 and requirement for intensive care in both non-diabetic and T2D patients. A morphological anomaly of increased monocyte size and monocytopenia restricted to classical CD14Hi CD16- monocytes was specifically associated with severe COVID-19 in patients with T2D requiring intensive care. Increased expression of inflammatory markers reminiscent of the type 1 interferon pathway (IL6, IL8, CCL2, INFB1) underlaid the immunophenotype associated with T2D. These immunophenotypic and hyperinflammatory changes may contribute to increased voracity of COVID-19 in T2D. These findings allow precise identification of T2D patients with severe COVID-19 as well as provide evidence that the type 1 interferon pathway may be an actionable therapeutic target for future studies.
DOI: 10.15252/emmm.202013038
PubMed: 32816392
PubMed Central: PMC7461002
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Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Paris Sciences et Lettres (PSL) Research University, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Center for Interdisciplinary Research in Biology (CIRB), College de France - Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Paris Sciences et Lettres (PSL) Research University, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Vidal Trecan, Tiphaine" sort="Vidal Trecan, Tiphaine" uniqKey="Vidal Trecan T" first="Tiphaine" last="Vidal-Trecan">Tiphaine Vidal-Trecan</name><affiliation wicri:level="3"><nlm:affiliation>Department of Diabetes, Clinical Investigation Centre (CIC-9504), Lariboisière Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Diabetes, Clinical Investigation Centre (CIC-9504), Lariboisière Hospital, Assistance Publique - Hôpitaux de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Roussel, Ronan" sort="Roussel, Ronan" uniqKey="Roussel R" first="Ronan" last="Roussel">Ronan Roussel</name><affiliation wicri:level="3"><nlm:affiliation>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Department of Diabetology, Endocrinology and Nutrition, Bichat Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Diabetology, Endocrinology and Nutrition, Bichat Hospital, Assistance Publique - Hôpitaux de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Riveline, Jean Pierre" sort="Riveline, Jean Pierre" uniqKey="Riveline J" first="Jean-Pierre" last="Riveline">Jean-Pierre Riveline</name><affiliation wicri:level="3"><nlm:affiliation>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Department of Diabetes, Clinical Investigation Centre (CIC-9504), Lariboisière Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Diabetes, Clinical Investigation Centre (CIC-9504), Lariboisière Hospital, Assistance Publique - Hôpitaux de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Dalmas, Elise" sort="Dalmas, Elise" uniqKey="Dalmas E" first="Elise" last="Dalmas">Elise Dalmas</name><affiliation wicri:level="3"><nlm:affiliation>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Venteclef, Nicolas" sort="Venteclef, Nicolas" uniqKey="Venteclef N" first="Nicolas" last="Venteclef">Nicolas Venteclef</name><affiliation wicri:level="3"><nlm:affiliation>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Gautier, Jean Francois" sort="Gautier, Jean Francois" uniqKey="Gautier J" first="Jean-François" last="Gautier">Jean-François Gautier</name><affiliation wicri:level="3"><nlm:affiliation>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Department of Diabetes, Clinical Investigation Centre (CIC-9504), Lariboisière Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Diabetes, Clinical Investigation Centre (CIC-9504), Lariboisière Hospital, Assistance Publique - Hôpitaux de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32816392</idno><idno type="pmid">32816392</idno><idno type="doi">10.15252/emmm.202013038</idno><idno type="pmc">PMC7461002</idno><idno type="wicri:Area/Main/Corpus">000541</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000541</idno><idno type="wicri:Area/Main/Curation">000541</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000541</idno><idno type="wicri:Area/Main/Exploration">000541</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Monocytopenia, monocyte morphological anomalies and hyperinflammation characterise severe COVID-19 in type 2 diabetes.</title><author><name sortKey="Alzaid, Fawaz" sort="Alzaid, Fawaz" uniqKey="Alzaid F" first="Fawaz" last="Alzaid">Fawaz Alzaid</name><affiliation wicri:level="3"><nlm:affiliation>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Julla, Jean Baptiste" sort="Julla, Jean Baptiste" uniqKey="Julla J" first="Jean-Baptiste" last="Julla">Jean-Baptiste Julla</name><affiliation wicri:level="3"><nlm:affiliation>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Department of Diabetes, Clinical Investigation Centre (CIC-9504), Lariboisière Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Diabetes, Clinical Investigation Centre (CIC-9504), Lariboisière Hospital, Assistance Publique - Hôpitaux de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Diedisheim, Marc" sort="Diedisheim, Marc" uniqKey="Diedisheim M" first="Marc" last="Diedisheim">Marc Diedisheim</name><affiliation wicri:level="3"><nlm:affiliation>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Department of Diabetology, Cochin Hospital, Assistance Publique Hôpitaux de Paris, Université de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Diabetology, Cochin Hospital, Assistance Publique Hôpitaux de Paris, Université de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Potier, Charline" sort="Potier, Charline" uniqKey="Potier C" first="Charline" last="Potier">Charline Potier</name><affiliation wicri:level="3"><nlm:affiliation>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Potier, Louis" sort="Potier, Louis" uniqKey="Potier L" first="Louis" last="Potier">Louis Potier</name><affiliation wicri:level="3"><nlm:affiliation>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Department of Diabetology, Endocrinology and Nutrition, Bichat Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Diabetology, Endocrinology and Nutrition, Bichat Hospital, Assistance Publique - Hôpitaux de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Velho, Gilberto" sort="Velho, Gilberto" uniqKey="Velho G" first="Gilberto" last="Velho">Gilberto Velho</name><affiliation wicri:level="3"><nlm:affiliation>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Gaborit, Benedicte" sort="Gaborit, Benedicte" uniqKey="Gaborit B" first="Bénédicte" last="Gaborit">Bénédicte Gaborit</name><affiliation wicri:level="3"><nlm:affiliation>INSERM, INRA, Aix Marseille University, C2VN, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INSERM, INRA, Aix Marseille University, C2VN, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Manivet, Philippe" sort="Manivet, Philippe" uniqKey="Manivet P" first="Philippe" last="Manivet">Philippe Manivet</name><affiliation wicri:level="3"><nlm:affiliation>Endocrinology, Metabolic Diseases and Nutrition Department, Assistance Publique Hôpitaux de Marseille, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Endocrinology, Metabolic Diseases and Nutrition Department, Assistance Publique Hôpitaux de Marseille, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Centre de Ressources Biologique "biobank Lariboisière", BB-0033-00064, APHP, Nord, Université de Paris, Paris Diderot, Hôpital Lariboisière, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre de Ressources Biologique "biobank Lariboisière", BB-0033-00064, APHP, Nord, Université de Paris, Paris Diderot, Hôpital Lariboisière, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Germain, Stephane" sort="Germain, Stephane" uniqKey="Germain S" first="Stéphane" last="Germain">Stéphane Germain</name><affiliation wicri:level="3"><nlm:affiliation>Center for Interdisciplinary Research in Biology (CIRB), College de France - Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Paris Sciences et Lettres (PSL) Research University, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Center for Interdisciplinary Research in Biology (CIRB), College de France - Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Paris Sciences et Lettres (PSL) Research University, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Vidal Trecan, Tiphaine" sort="Vidal Trecan, Tiphaine" uniqKey="Vidal Trecan T" first="Tiphaine" last="Vidal-Trecan">Tiphaine Vidal-Trecan</name><affiliation wicri:level="3"><nlm:affiliation>Department of Diabetes, Clinical Investigation Centre (CIC-9504), Lariboisière Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Diabetes, Clinical Investigation Centre (CIC-9504), Lariboisière Hospital, Assistance Publique - Hôpitaux de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Roussel, Ronan" sort="Roussel, Ronan" uniqKey="Roussel R" first="Ronan" last="Roussel">Ronan Roussel</name><affiliation wicri:level="3"><nlm:affiliation>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Department of Diabetology, Endocrinology and Nutrition, Bichat Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Diabetology, Endocrinology and Nutrition, Bichat Hospital, Assistance Publique - Hôpitaux de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Riveline, Jean Pierre" sort="Riveline, Jean Pierre" uniqKey="Riveline J" first="Jean-Pierre" last="Riveline">Jean-Pierre Riveline</name><affiliation wicri:level="3"><nlm:affiliation>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Department of Diabetes, Clinical Investigation Centre (CIC-9504), Lariboisière Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Diabetes, Clinical Investigation Centre (CIC-9504), Lariboisière Hospital, Assistance Publique - Hôpitaux de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Dalmas, Elise" sort="Dalmas, Elise" uniqKey="Dalmas E" first="Elise" last="Dalmas">Elise Dalmas</name><affiliation wicri:level="3"><nlm:affiliation>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Venteclef, Nicolas" sort="Venteclef, Nicolas" uniqKey="Venteclef N" first="Nicolas" last="Venteclef">Nicolas Venteclef</name><affiliation wicri:level="3"><nlm:affiliation>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Gautier, Jean Francois" sort="Gautier, Jean Francois" uniqKey="Gautier J" first="Jean-François" last="Gautier">Jean-François Gautier</name><affiliation wicri:level="3"><nlm:affiliation>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Department of Diabetes, Clinical Investigation Centre (CIC-9504), Lariboisière Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Diabetes, Clinical Investigation Centre (CIC-9504), Lariboisière Hospital, Assistance Publique - Hôpitaux de Paris, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author></analytic><series><title level="j">EMBO molecular medicine</title><idno type="eISSN">1757-4684</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Early in the COVID-19 pandemic, type 2 diabetes (T2D) was marked as a risk factor for severe disease and mortality. Inflammation is central to the aetiology of both conditions where variations in immune responses can mitigate or aggravate disease course. Identifying at-risk groups based on immunoinflammatory signatures is valuable in directing personalised care and developing potential targets for precision therapy. This observational study characterised immunophenotypic variation associated with COVID-19 severity in T2D. Broad-spectrum immunophenotyping quantified 15 leucocyte populations in peripheral circulation from a cohort of 45 hospitalised COVID-19 patients with and without T2D. Lymphocytopenia and specific loss of cytotoxic CD8<sup>+</sup> lymphocytes were associated with severe COVID-19 and requirement for intensive care in both non-diabetic and T2D patients. A morphological anomaly of increased monocyte size and monocytopenia restricted to classical CD14<sup>Hi</sup> CD16<sup>-</sup> monocytes was specifically associated with severe COVID-19 in patients with T2D requiring intensive care. Increased expression of inflammatory markers reminiscent of the type 1 interferon pathway (IL6, IL8, CCL2, INFB1) underlaid the immunophenotype associated with T2D. These immunophenotypic and hyperinflammatory changes may contribute to increased voracity of COVID-19 in T2D. These findings allow precise identification of T2D patients with severe COVID-19 as well as provide evidence that the type 1 interferon pathway may be an actionable therapeutic target for future studies.</div></front></TEI><pubmed><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">32816392</PMID><DateRevised><Year>2020</Year><Month>09</Month><Day>11</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1757-4684</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2020</Year><Month>Aug</Month><Day>20</Day></PubDate></JournalIssue><Title>EMBO molecular medicine</Title><ISOAbbreviation>EMBO Mol Med</ISOAbbreviation></Journal><ArticleTitle>Monocytopenia, monocyte morphological anomalies and hyperinflammation characterise severe COVID-19 in type 2 diabetes.</ArticleTitle><Pagination><MedlinePgn>e13038</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.15252/emmm.202013038</ELocationID><Abstract><AbstractText>Early in the COVID-19 pandemic, type 2 diabetes (T2D) was marked as a risk factor for severe disease and mortality. Inflammation is central to the aetiology of both conditions where variations in immune responses can mitigate or aggravate disease course. Identifying at-risk groups based on immunoinflammatory signatures is valuable in directing personalised care and developing potential targets for precision therapy. This observational study characterised immunophenotypic variation associated with COVID-19 severity in T2D. Broad-spectrum immunophenotyping quantified 15 leucocyte populations in peripheral circulation from a cohort of 45 hospitalised COVID-19 patients with and without T2D. Lymphocytopenia and specific loss of cytotoxic CD8<sup>+</sup> lymphocytes were associated with severe COVID-19 and requirement for intensive care in both non-diabetic and T2D patients. A morphological anomaly of increased monocyte size and monocytopenia restricted to classical CD14<sup>Hi</sup> CD16<sup>-</sup> monocytes was specifically associated with severe COVID-19 in patients with T2D requiring intensive care. Increased expression of inflammatory markers reminiscent of the type 1 interferon pathway (IL6, IL8, CCL2, INFB1) underlaid the immunophenotype associated with T2D. These immunophenotypic and hyperinflammatory changes may contribute to increased voracity of COVID-19 in T2D. These findings allow precise identification of T2D patients with severe COVID-19 as well as provide evidence that the type 1 interferon pathway may be an actionable therapeutic target for future studies.</AbstractText><CopyrightInformation>© 2020 The Authors. Published under the terms of the CC BY 4.0 license.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y" EqualContrib="Y"><LastName>Alzaid</LastName><ForeName>Fawaz</ForeName><Initials>F</Initials><Identifier Source="ORCID">https://orcid.org/0000-0003-3056-3640</Identifier><AffiliationInfo><Affiliation>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y" EqualContrib="Y"><LastName>Julla</LastName><ForeName>Jean-Baptiste</ForeName><Initials>JB</Initials><AffiliationInfo><Affiliation>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Diabetes, Clinical Investigation Centre (CIC-9504), Lariboisière Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Diedisheim</LastName><ForeName>Marc</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Diabetology, Cochin Hospital, Assistance Publique Hôpitaux de Paris, Université de Paris, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Potier</LastName><ForeName>Charline</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Potier</LastName><ForeName>Louis</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Diabetology, Endocrinology and Nutrition, Bichat Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Velho</LastName><ForeName>Gilberto</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gaborit</LastName><ForeName>Bénédicte</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>INSERM, INRA, Aix Marseille University, C2VN, Marseille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Manivet</LastName><ForeName>Philippe</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Endocrinology, Metabolic Diseases and Nutrition Department, Assistance Publique Hôpitaux de Marseille, Marseille, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Centre de Ressources Biologique "biobank Lariboisière", BB-0033-00064, APHP, Nord, Université de Paris, Paris Diderot, Hôpital Lariboisière, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Germain</LastName><ForeName>Stéphane</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Center for Interdisciplinary Research in Biology (CIRB), College de France - Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Paris Sciences et Lettres (PSL) Research University, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vidal-Trecan</LastName><ForeName>Tiphaine</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Department of Diabetes, Clinical Investigation Centre (CIC-9504), Lariboisière Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Roussel</LastName><ForeName>Ronan</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Diabetology, Endocrinology and Nutrition, Bichat Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Riveline</LastName><ForeName>Jean-Pierre</ForeName><Initials>JP</Initials><AffiliationInfo><Affiliation>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Diabetes, Clinical Investigation Centre (CIC-9504), Lariboisière Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dalmas</LastName><ForeName>Elise</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Venteclef</LastName><ForeName>Nicolas</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gautier</LastName><ForeName>Jean-François</ForeName><Initials>JF</Initials><Identifier Source="ORCID">https://orcid.org/0000-0001-6458-2001</Identifier><AffiliationInfo><Affiliation>Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de Paris, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Diabetes, Clinical Investigation Centre (CIC-9504), Lariboisière Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>ANR-19-CE14-0005</GrantID><Agency>Agence Nationale de la Recherche (ANR)</Agency><Country></Country></Grant><Grant><GrantID>ERC-EpiFAT 725790</GrantID><Agency>EC | H2020 | H2020 Priority Excellent Science | H2020 European Research Council (ERC)</Agency><Country></Country></Grant><Grant><Agency>Société Francophone du Diabète (SFD)</Agency><Country></Country></Grant><Grant><Agency>Assistance Publique - Hôpitaux de Paris (AP-HP)</Agency><Country></Country></Grant><Grant><Agency>Institut National de la Santé et de la Recherche Médicale (Inserm)</Agency><Country></Country></Grant><Grant><Agency>European Foundation for the Study of Diabetes (EFSD)</Agency><Country></Country></Grant><Grant><Agency>CNRS-INSERM (ATIP-Avenir)</Agency><Country></Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>08</Month><Day>20</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>EMBO Mol Med</MedlineTA><NlmUniqueID>101487380</NlmUniqueID><ISSNLinking>1757-4676</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">COVID-19</Keyword><Keyword MajorTopicYN="N">SARS-CoV-2</Keyword><Keyword MajorTopicYN="N">inflammation</Keyword><Keyword MajorTopicYN="N">monocyte</Keyword><Keyword MajorTopicYN="N">type 2 diabetes</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>06</Month><Day>30</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2020</Year><Month>08</Month><Day>17</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>08</Month><Day>19</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>8</Month><Day>21</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>8</Month><Day>21</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>8</Month><Day>21</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>aheadofprint</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32816392</ArticleId><ArticleId IdType="doi">10.15252/emmm.202013038</ArticleId><ArticleId IdType="pmc">PMC7461002</ArticleId></ArticleIdList><ReferenceList><Title>References</Title><Reference><Citation>Alzaid F, Lagadec F, Albuquerque M, Ballaire R, Orliaguet L, Hainault I, Blugeon C, Lemoine S, Lehuen A, Saliba DG et al (2016) IRF5 governs liver macrophage activation that promotes hepatic fibrosis in mice and humans. 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Cell Metab 31: 1068-1077</Citation></Reference></ReferenceList></PubmedData></pubmed><affiliations><list><country><li>France</li></country><region><li>Provence-Alpes-Côte d'Azur</li><li>Île-de-France</li></region><settlement><li>Marseille</li><li>Paris</li></settlement></list><tree><country name="France"><region name="Île-de-France"><name sortKey="Alzaid, Fawaz" sort="Alzaid, Fawaz" uniqKey="Alzaid F" first="Fawaz" last="Alzaid">Fawaz Alzaid</name></region><name sortKey="Dalmas, Elise" sort="Dalmas, Elise" uniqKey="Dalmas E" first="Elise" last="Dalmas">Elise Dalmas</name><name sortKey="Diedisheim, Marc" sort="Diedisheim, Marc" uniqKey="Diedisheim M" first="Marc" last="Diedisheim">Marc Diedisheim</name><name sortKey="Diedisheim, Marc" sort="Diedisheim, Marc" uniqKey="Diedisheim M" first="Marc" last="Diedisheim">Marc Diedisheim</name><name sortKey="Gaborit, Benedicte" sort="Gaborit, Benedicte" uniqKey="Gaborit B" first="Bénédicte" last="Gaborit">Bénédicte Gaborit</name><name sortKey="Gautier, Jean Francois" sort="Gautier, Jean Francois" uniqKey="Gautier J" first="Jean-François" last="Gautier">Jean-François Gautier</name><name sortKey="Gautier, Jean Francois" sort="Gautier, Jean Francois" uniqKey="Gautier J" first="Jean-François" last="Gautier">Jean-François Gautier</name><name sortKey="Germain, Stephane" sort="Germain, Stephane" uniqKey="Germain S" first="Stéphane" last="Germain">Stéphane Germain</name><name sortKey="Julla, Jean Baptiste" sort="Julla, Jean Baptiste" uniqKey="Julla J" first="Jean-Baptiste" last="Julla">Jean-Baptiste Julla</name><name sortKey="Julla, Jean Baptiste" sort="Julla, Jean Baptiste" uniqKey="Julla J" first="Jean-Baptiste" last="Julla">Jean-Baptiste Julla</name><name sortKey="Manivet, Philippe" sort="Manivet, Philippe" uniqKey="Manivet P" first="Philippe" last="Manivet">Philippe Manivet</name><name sortKey="Manivet, Philippe" sort="Manivet, Philippe" uniqKey="Manivet P" first="Philippe" last="Manivet">Philippe Manivet</name><name sortKey="Potier, Charline" sort="Potier, Charline" uniqKey="Potier C" first="Charline" last="Potier">Charline Potier</name><name sortKey="Potier, Louis" sort="Potier, Louis" uniqKey="Potier L" first="Louis" last="Potier">Louis Potier</name><name sortKey="Potier, Louis" sort="Potier, Louis" uniqKey="Potier L" first="Louis" last="Potier">Louis Potier</name><name sortKey="Riveline, Jean Pierre" sort="Riveline, Jean Pierre" uniqKey="Riveline J" first="Jean-Pierre" last="Riveline">Jean-Pierre Riveline</name><name sortKey="Riveline, Jean Pierre" sort="Riveline, Jean Pierre" uniqKey="Riveline J" first="Jean-Pierre" last="Riveline">Jean-Pierre Riveline</name><name sortKey="Roussel, Ronan" sort="Roussel, Ronan" uniqKey="Roussel R" first="Ronan" last="Roussel">Ronan Roussel</name><name sortKey="Roussel, Ronan" sort="Roussel, Ronan" uniqKey="Roussel R" first="Ronan" last="Roussel">Ronan Roussel</name><name sortKey="Velho, Gilberto" sort="Velho, Gilberto" uniqKey="Velho G" first="Gilberto" last="Velho">Gilberto Velho</name><name sortKey="Venteclef, Nicolas" sort="Venteclef, Nicolas" uniqKey="Venteclef N" first="Nicolas" last="Venteclef">Nicolas Venteclef</name><name sortKey="Vidal Trecan, Tiphaine" sort="Vidal Trecan, Tiphaine" uniqKey="Vidal Trecan T" first="Tiphaine" last="Vidal-Trecan">Tiphaine Vidal-Trecan</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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