Characterization of low-density granulocytes in COVID-19

• DOI: 10.1371/journal.ppat.1009721
• Publication Date: 2021-07-06T17:40:54Z
• Authors: Luz E. Cabrera; Pirkka T. Pekkarinen; Maria Alander; Kirsten H. A. Nowlan; Ngoc Anh Nguyen; Suvi Jokiranta; Suvi Kuivanen; Anu Patjas; Sointu Mero; Sari H. Pakkanen; Santtu Heinonen; Anu Kantele; Olli Vapalahti; Eliisa Kekäläinen; Tomas Strandin
• Keywords: Adult; Male; 0301 basic medicine; QH301-705.5; Severity of Illness Index; ACTIVATION; Cohort Studies; 03 medical and health sciences; NETTING NEUTROPHILS; Immune Tolerance; Humans; Biology (General); Biochemistry, cell and molecular biology; Aged; 11832 Microbiology and virology; 0303 health sciences; NEUTROPHIL EXTRACELLULAR TRAPS; COVID-19; Convalescence; RC581-607; Middle Aged; Scavenger Receptors, Class E; 3. Good health; Case-Control Studies; CELLS; Acute Disease; Disease Progression; Female; Immunologic diseases. Allergy; RESPONSES; Research Article; Follow-Up Studies; Granulocytes

Severe COVID-19 is characterized by extensive pulmonary complications, to which host immune responses are believed to play a role. As the major arm of innate immunity, neutrophils are one of the first cells recruited to the site of infection where their excessive activation can contribute to lung pathology. Low-density granulocytes (LDGs) are circulating neutrophils, whose numbers increase in some autoimmune diseases and cancer, but are poorly characterized in acute viral infections. Using flow cytometry, we detected a significant increase of LDGs in the blood of acute COVID-19 patients, compared to healthy controls. Based on their surface marker expression, COVID-19-related LDGs exhibit four different populations, which display distinctive stages of granulocytic development and most likely reflect emergency myelopoiesis. Moreover, COVID-19 LDGs show a link with an elevated recruitment and activation of neutrophils. Functional assays demonstrated the immunosuppressive capacities of these cells, which might contribute to impaired lymphocyte responses during acute disease. Taken together, our data confirms a significant granulocyte activation during COVID-19 and suggests that granulocytes of lower density play a role in disease progression.