Monocytopenia, monocyte morphological anomalies and hyperinflammation characterise severe COVID‐19 in type 2 diabetes
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...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2020-09-01
|
| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.202013038 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849343191583555584 |
|---|---|
| author | Fawaz Alzaid Jean‐Baptiste Julla Marc Diedisheim Charline Potier Louis Potier Gilberto Velho Bénédicte Gaborit Philippe Manivet Stéphane Germain Tiphaine Vidal‐Trecan Ronan Roussel Jean‐Pierre Riveline Elise Dalmas Nicolas Venteclef Jean‐François Gautier |
| author_facet | Fawaz Alzaid Jean‐Baptiste Julla Marc Diedisheim Charline Potier Louis Potier Gilberto Velho Bénédicte Gaborit Philippe Manivet Stéphane Germain Tiphaine Vidal‐Trecan Ronan Roussel Jean‐Pierre Riveline Elise Dalmas Nicolas Venteclef Jean‐François Gautier |
| author_sort | Fawaz Alzaid |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-7c72d6f547d64ae5b2a37caae2a48163 |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2020-09-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-7c72d6f547d64ae5b2a37caae2a481632025-08-20T03:43:10ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842020-09-01121011210.15252/emmm.202013038Monocytopenia, monocyte morphological anomalies and hyperinflammation characterise severe COVID‐19 in type 2 diabetesFawaz Alzaid0Jean‐Baptiste Julla1Marc Diedisheim2Charline Potier3Louis Potier4Gilberto Velho5Bénédicte Gaborit6Philippe Manivet7Stéphane Germain8Tiphaine Vidal‐Trecan9Ronan Roussel10Jean‐Pierre Riveline11Elise Dalmas12Nicolas Venteclef13Jean‐François Gautier14Cordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de ParisCordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de ParisCordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de ParisCordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de ParisCordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de ParisCordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de ParisINSERM, INRA, Aix Marseille University, C2VNEndocrinology, Metabolic Diseases and Nutrition Department, Assistance Publique Hôpitaux de MarseilleCenter 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 UniversityDepartment of Diabetes, Clinical Investigation Centre (CIC‐9504), Lariboisière Hospital, Assistance Publique – Hôpitaux de ParisCordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de ParisCordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de ParisCordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de ParisCordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de ParisCordeliers Research Centre, INSERM, IMMEDIAB Laboratory, Sorbonne Université, Université de ParisAbstract 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.https://doi.org/10.15252/emmm.202013038COVID‐19inflammationmonocyteSARS‐CoV-2type 2 diabetes |
| spellingShingle | Fawaz Alzaid Jean‐Baptiste Julla Marc Diedisheim Charline Potier Louis Potier Gilberto Velho Bénédicte Gaborit Philippe Manivet Stéphane Germain Tiphaine Vidal‐Trecan Ronan Roussel Jean‐Pierre Riveline Elise Dalmas Nicolas Venteclef Jean‐François Gautier Monocytopenia, monocyte morphological anomalies and hyperinflammation characterise severe COVID‐19 in type 2 diabetes EMBO Molecular Medicine COVID‐19 inflammation monocyte SARS‐CoV-2 type 2 diabetes |
| title | Monocytopenia, monocyte morphological anomalies and hyperinflammation characterise severe COVID‐19 in type 2 diabetes |
| title_full | Monocytopenia, monocyte morphological anomalies and hyperinflammation characterise severe COVID‐19 in type 2 diabetes |
| title_fullStr | Monocytopenia, monocyte morphological anomalies and hyperinflammation characterise severe COVID‐19 in type 2 diabetes |
| title_full_unstemmed | Monocytopenia, monocyte morphological anomalies and hyperinflammation characterise severe COVID‐19 in type 2 diabetes |
| title_short | Monocytopenia, monocyte morphological anomalies and hyperinflammation characterise severe COVID‐19 in type 2 diabetes |
| title_sort | monocytopenia monocyte morphological anomalies and hyperinflammation characterise severe covid 19 in type 2 diabetes |
| topic | COVID‐19 inflammation monocyte SARS‐CoV-2 type 2 diabetes |
| url | https://doi.org/10.15252/emmm.202013038 |
| work_keys_str_mv | AT fawazalzaid monocytopeniamonocytemorphologicalanomaliesandhyperinflammationcharacteriseseverecovid19intype2diabetes AT jeanbaptistejulla monocytopeniamonocytemorphologicalanomaliesandhyperinflammationcharacteriseseverecovid19intype2diabetes AT marcdiedisheim monocytopeniamonocytemorphologicalanomaliesandhyperinflammationcharacteriseseverecovid19intype2diabetes AT charlinepotier monocytopeniamonocytemorphologicalanomaliesandhyperinflammationcharacteriseseverecovid19intype2diabetes AT louispotier monocytopeniamonocytemorphologicalanomaliesandhyperinflammationcharacteriseseverecovid19intype2diabetes AT gilbertovelho monocytopeniamonocytemorphologicalanomaliesandhyperinflammationcharacteriseseverecovid19intype2diabetes AT benedictegaborit monocytopeniamonocytemorphologicalanomaliesandhyperinflammationcharacteriseseverecovid19intype2diabetes AT philippemanivet monocytopeniamonocytemorphologicalanomaliesandhyperinflammationcharacteriseseverecovid19intype2diabetes AT stephanegermain monocytopeniamonocytemorphologicalanomaliesandhyperinflammationcharacteriseseverecovid19intype2diabetes AT tiphainevidaltrecan monocytopeniamonocytemorphologicalanomaliesandhyperinflammationcharacteriseseverecovid19intype2diabetes AT ronanroussel monocytopeniamonocytemorphologicalanomaliesandhyperinflammationcharacteriseseverecovid19intype2diabetes AT jeanpierreriveline monocytopeniamonocytemorphologicalanomaliesandhyperinflammationcharacteriseseverecovid19intype2diabetes AT elisedalmas monocytopeniamonocytemorphologicalanomaliesandhyperinflammationcharacteriseseverecovid19intype2diabetes AT nicolasventeclef monocytopeniamonocytemorphologicalanomaliesandhyperinflammationcharacteriseseverecovid19intype2diabetes AT jeanfrancoisgautier monocytopeniamonocytemorphologicalanomaliesandhyperinflammationcharacteriseseverecovid19intype2diabetes |