Monocytopenia, monocyte morphological anomalies and hyperinflammation characterise severe COVID‐19 in type 2 diabetes

• Published in: EMBO molecular medicine Vol. 12; no. 10; pp. e13038 - n/a
• Main Authors: Alzaid, Fawaz, Julla, Jean‐Baptiste, Diedisheim, Marc, Potier, Charline, Potier, Louis, Velho, Gilberto, Gaborit, Bénédicte, Manivet, Philippe, Germain, Stéphane, Vidal‐Trecan, Tiphaine, Roussel, Ronan, Riveline, Jean‐Pierre, Dalmas, Elise, Venteclef, Nicolas, Gautier, Jean‐François
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.10.2020; EMBO Press; Wiley Open Access; John Wiley and Sons Inc; Springer Nature
• Subjects: Adaptive immunology; Aged; Antigens; CD16 antigen; CD8 antigen; Chemokine CCL2 - genetics; Chemokine CCL2 - metabolism; Coronaviruses; COVID-19; COVID-19 - complications; COVID-19 - pathology; COVID-19 - virology; Cytokines; Cytotoxicity; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - pathology; EMBO19; EMBO21; EMBO23; Emerging diseases; Endocrinology and metabolism; Female; Glucose; Hemoglobin; Human health and pathology; Humans; Hypertension; Hypotheses; Immune response; Immunology; Immunophenotyping; Infectious diseases; Inflammation; Inflammation - etiology; Innate immunity; Interferon; Interleukin 6; Interleukin 8; Interleukin-6 - genetics; Interleukin-6 - metabolism; Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - metabolism; Life Sciences; Lipopolysaccharide Receptors - metabolism; Lymphocytes; Lymphopenia; Lymphopenia - diagnosis; Male; Metabolism; Middle Aged; monocyte; Monocyte chemoattractant protein 1; Monocytes; Monocytes - cytology; Monocytes - pathology; Monocytes - physiology; Morphology; Mortality; Pandemics; Principal components analysis; Risk Factors; Risk groups; SARS-CoV-2 - isolation & purification; SARS‐CoV-2; Severe acute respiratory syndrome coronavirus 2; Severity of Illness Index; Therapeutic targets; type 2 diabetes; monocyte; type 2 diabetes; COVID‐19; SARS‐CoV-2; inflammation; COVID-19; SARS-CoV-2; Virology & Host Pathogen Interaction; type 2 diabetes Subject Categories Immunology; Microbiology; Metabolism
• ISSN: 1757-4676; 1757-4684; 1757-4684
• DOI: 10.15252/emmm.202013038

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 CD14 Hi 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. Synopsis The study demonstrates that COVID‐19 affects different circulating immune cells depending on diabetic status. Type‐2 diabetic (T2D) patients with COVID‐19 lose a specific subtype of monocytes, which is associated with changes in cell morphology and highly inflammatory gene expression profile. Patients with T2D are at higher risk of dying or suffering from severe forms of COVID‐19. COVID‐19 infection causes a decrease in circulating lymphocyte and monocyte populations associated with severity of disease in patients with T2D. Monocytes undergo morphological changes and highly express inflammatory markers reminiscent of the type‐1 interferon response in T2D. Inflammatory and cellular responses to COVID‐19 from patients with T2D are associated with a need for intensive care. Graphical Abstract The study demonstrates that COVID‐19 affects different circulating immune cells depending on diabetic status. Type‐2 diabetic (T2D) patients with COVID‐19 lose a specific subtype of monocytes, which is associated with changes in cell morphology and highly inflammatory gene expression profile.