Vascular neutrophilic inflammation and immunothrombosis distinguish severe COVID-19 from influenza pneumonia.
J Thromb Haemost
; 19(2): 574-581, 2021 02.
Article
in English
| MEDLINE | ID: covidwho-939789
ABSTRACT
OBJECTIVE:
Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to severe pneumonia, but also thrombotic complications and non-pulmonary organ failure. Recent studies suggest intravascular neutrophil activation and subsequent immune cell-triggered immunothrombosis as a central pathomechanism linking the heterogenous clinical picture of coronavirus disease 2019 (COVID-19). We sought to study whether immunothrombosis is a pathognomonic factor in COVID-19 or a general feature of (viral) pneumonia, as well as to better understand its upstream regulation. APPROACH ANDRESULTS:
By comparing histopathological specimens of SARS-CoV-2 with influenza-affected lungs, we show that vascular neutrophil recruitment, NETosis, and subsequent immunothrombosis are typical features of severe COVID-19, but less prominent in influenza pneumonia. Activated neutrophils were typically found in physical association with monocytes. To explore this further, we combined clinical data of COVID-19 cases with comprehensive immune cell phenotyping and bronchoalveolar lavage fluid scRNA-seq data. We show that a HLADRlow CD9low monocyte population expands in severe COVID-19, which releases neutrophil chemokines in the lungs, and might in turn explain neutrophil expansion and pulmonary recruitment in the late stages of severe COVID-19.CONCLUSIONS:
Our data underline an innate immune cell axis causing vascular inflammation and immunothrombosis in severe SARS-CoV-2 infection.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Thrombosis
/
Vasculitis
/
Influenza, Human
/
COVID-19
/
Immunity, Innate
/
Lung
/
Neutrophils
Type of study:
Diagnostic study
/
Prognostic study
Topics:
Long Covid
Limits:
Humans
Language:
English
Journal:
J Thromb Haemost
Journal subject:
Hematology
Year:
2021
Document Type:
Article
Affiliation country:
Jth.15179
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