Neutrophilic Inflammation, Immunothrombosis May Distinguish Severe COVID-19 From Influenza

Neutrophil white blood cells
Severe coronavirus disease 2019 (COVID-19) is associated with immunothrombotic, neutrophil-containing vessel occlusions in the lung.

Severe coronavirus disease 2019 (COVID-19) is associated with immunothrombotic, neutrophil-containing vessel occlusions in the lung, with neutrophils representing the primary immune cell component associated with clinical deterioration, according to study results published in the Journal of Thrombosis and Haemostasis.

The study included 27 patients with COVID-19 who were part of the COVID-19 Registry of LMU University Hospital Munich (German Clinical Trials Register ID: DRKS00021225). All patients required hospitalization and intensive care treatment. In addition, the researchers analyzed histologic specimens from 6 patients with COVID-19, 4 patients with H1N1 influenza, and 3 patients with seasonal influenza.

Investigators phenotyped peripheral blood leukocytes in control individuals and patients without COVID-19 pneumonia compared with patients with COVID-19 on normal wards and requiring intensive care treatment. The researchers found comparable leukocyte counts between patients with COVID-19 on normal wards and healthy controls. However, there was expansion of the neutrophil granulocyte compartment and elevated leukocyte counts in patients with COVID-19 requiring intensive care.

Compared with lung specimens from patients with influenza, specimens of COVID-19 found more vascular neutrophil recruitment, NETosis, and subsequent immunothrombosis. Additionally, the researchers observed a strong association between activated neutrophils and monocytes.

In an analysis combining clinical COVID-19 case data with comprehensive immune cell phenotyping and bronchoalveolar lavage fluid single RNA sequencing (scRNA-seq) data, the investigators found that a HLADRlow CD9low monocyte population expanded in cases of severe COVID-19. According to the investigators, this results in a release of neutrophil chemokines in the lung, which may explain neutrophil expansion and pulmonary recruitment noted in late stages of severe COVID-19.

Limitations of this study were the small number of patients and collected histologic specimens.

Based on their findings, the researchers suggest that “[t]argeting neutrophil- monocyte partnership might be valuable therapeutic approach to dampen disease progression in COVID-19.”


Nicolai L, Leunig A, Brambs S, et al. Vascular neutrophilic inflammation and immunothrombosis distinguish severe COVID-19 from influenza pneumonia. J Thromb Haemost. Published online November 20, 2020. doi:10.1111/jth.15179