Characterization of low-density granulocytes in COVID-19

PLoS Pathog. 2021 Jul 6;17(7):e1009721. doi: 10.1371/journal.ppat.1009721. eCollection 2021 Jul.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • COVID-19 / blood
  • COVID-19 / immunology*
  • Case-Control Studies
  • Cohort Studies
  • Convalescence
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Granulocytes / classification*
  • Granulocytes / cytology
  • Humans
  • Immune Tolerance / immunology
  • Male
  • Middle Aged
  • Scavenger Receptors, Class E / analysis
  • Severity of Illness Index


  • OLR1 protein, human
  • Scavenger Receptors, Class E

Grants and funding

This work was financed by grants by the Academy of Finland to T.S. (321809 and 328807), O.V. (336490), S.H. (323499), A.K. (336439 and 335527); grants by the Helsinki University Hospital funds to P.T.P. (M7100YLIT2) and to O.V. (TYH 2018322); EU Horizon 2020 programme VEO (grant 874735) to O.V.; Finnish governmental subsidy for Health Science Research (TYH 2021315) to A.K. The funders had no role in study design, data collection and analysis, nor decision to publish, or preparation of the manuscript. Academy of Finland: Helsinki University Hospital funds: EU Horizon 2020 programme VEO: