Pathology of lung-specific thrombosis and inflammation in COVID-19

Rafael R Khismatullin; Anastasia A Ponomareva; Chandrasekaran Nagaswami; Rozalina A Ivaeva; Kathleen T Montone; John W Weisel; Rustem I Litvinov

doi:10.1111/jth.15532

Pathology of lung-specific thrombosis and inflammation in COVID-19

J Thromb Haemost. 2021 Dec;19(12):3062-3072. doi: 10.1111/jth.15532. Epub 2021 Sep 28.

Authors

Rafael R Khismatullin^{1

2}, Anastasia A Ponomareva^{2

3}, Chandrasekaran Nagaswami¹, Rozalina A Ivaeva², Kathleen T Montone⁴, John W Weisel¹, Rustem I Litvinov^{1

2}

Affiliations

¹ Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
² Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russian Federation.
³ Kazan Institute of Biochemistry and Biophysics, FRC KSC of RAS, Kazan, Russian Federation.
⁴ Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.

Abstract

Background: Infection by SARS-CoV-2 produces significant pulmonary pathology including endothelial damage with resultant thrombotic events. While pathologic features were described, there are limited data on the relationship of these changes to the inflammatory response and the production of thromboses.

Objective: To investigate pathology of COVID-19-related immunothrombosis.

Patients/methods: Tissue samples from lung, kidney, brain and heart that were collected from 45 patients who died of COVID-19. Histopathological examination was performed after H&E and Picro-Mallory staining in combination with (immuno)fluorescence to visualize neutrophil extracellular traps. Ultrastructural alterations in lungs were studied with scanning and transmission electron microscopy.

Results: Inflammatory changes and thrombosis were substantially more pronounced in the lung than in the kidney, heart, and brain. The most common pathologic finding was diffuse alveolar damage. In addition, most lung samples showed thrombi in vessels. The cause of death in single cases was massive pulmonary embolism. Ultrastructural examination revealed neutrophils attached to endothelium, perhaps as a step towards transendothelial migration. In addition, platelets were identified in the midst of fibrin as individual procoagulant balloon-like cells. Ultrastructural examination demonstrated numerous virion-like particles.

Conclusions: Studying (ultra)structural features of the autopsy lung samples from patients with COVID-19 has provided evidence for a pathogenic link between inflammation and thrombosis. The major features in the lungs of COVID-19 patients comprised primary inflammatory thrombosis associated with diffuse alveolar damage. The lungs had pronounced circulatory changes with inflammation-dependent intravascular blood clotting, whereas heart, brain, and kidneys had predominantly degenerative changes that were distinct from the lung pathology.

Keywords: COVID-19; blood coagulation; inflammation; lungs; thrombosis.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

COVID-19*
Humans
Inflammation
Lung
SARS-CoV-2
Thrombosis*

Abstract

Publication types

MeSH terms

Grants and funding