COVID-19: The virus and the vasculature

Date:
August 7, 2020
Source:
Ludwig-Maximilians-Universita"t Mu"nchen
Summary:
In severe cases of COVID-19, the infection can lead to obstruction
of the blood vessels in the lung, heart and kidneys. Researchers
have now shown that activated immune cells and blood platelets
play a major role in these pathologies.



FULL STORY ==========================================================================
In severe cases of COVID-19, the infection can lead to
obstruction of the blood vessels in the lung, heart and
kidneys. Ludwig-Maximilians-Universitaet (LMU) in Munich researchers
have now shown that activated immune cells and blood platelets play a
major role in these pathologies.


==========================================================================
The novel coronavirus SARS-CoV-2 infects the respiratory tract and in
severe cases, the infection can result in lung failure, which necessitates
the use of mechanical ventilation. In addition, these patients develop
further complications, such as pulmonary embolisms or thromboses (clots)
in their veins. Whether or not virus-associated respiratory failure
is functionally related to the systemic increase in the incidence of intravascular clot formation has remained unclear. However, a new study
led by LMU clinicians Leo Nicolai and Konstantin Stark, which appears
in the journal Circulation, has identified a link between virus-induced
changes in the blood vessels of the lung and the increased thrombotic
risk. Upon post-mortem examination of the lungs of COVID-19 patients who
had died of the disease, Nicolai and colleagues found many microclots
within the finest branches of the pulmonary vasculature.

Similar observations were made in the heart and the kidney.

These clots were primarily made up of platelets and activated immune
cells, in particular neutrophils. Detailed analysis of the thrombi
suggested that an activating interaction between platelets and neutrophils
is responsible for promoting intravascular coagulation. Neutrophils
belong to the innate immune system and their principal task is to fight invading pathogens. Their involvement in abnormal clotting has led to the designation of this process as immunothrombosis. In COVID-19 patients,
the stimulation of clot formation eventually compromises the supply of
blood to nearby tissues. This in turn ultimately leads to respiratory
failure, while the tendency to trigger clotting becomes systemic.

Using multidimensional flow cytometry assays, the LMU researchers
showed that in COVID-19 patients who had suffered lung failure and
required mechanical ventilation, the numbers of activated neutrophils
and platelets in the circulation were greatly enhanced. Since the two
cell types reciprocally activate each other, these interactions lead
to the formation of obstructive blood clots in the lung. In addition,
activated neutrophils extrude mesh-like complexes made up of DNA and cytoplasmatic proteins, which are known as neutrophil extracellular traps (NETs). These normally serve to trap and destroy bacterial and viral
pathogens, but they also play a significant role in immunothrombosis
by stabilizing thrombi. While this process is initially localized in
the lung exacerbating respiratory failure and result in a systemic
thrombogenic state.

"These findings contribute to a better understanding of the
pathophysiology that underlie disease progression in COVID-19," says
Konstantin Stark. "The study also identifies immunothrombosis as a
promising target for the prevention and treatment of lung failure and thrombotic complications that arise in cases of COVID-19."

========================================================================== Story Source: Materials provided by
Ludwig-Maximilians-Universita"t_Mu"nchen. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Leo Nicolai, Alexander Leunig, Sophia Brambs, Rainer Kaiser, Tobias
Weinberger, Michael Weigand, Maximilian Muenchhoff, Johannes
C. Hellmuth, Stephan Ledderose, Heiko Schulz, Clemens Scherer,
Martina Rudelius, Michael Zoller, Dominik Ho"chter, Oliver Keppler,
Daniel Teupser, Bernhard Zwissler, Michael Bergwelt-Baildon,
Stefan Ka"a"b, Steffen Massberg, Kami Pekayvaz, Konstantin
Stark. Immunothrombotic Dysregulation in COVID-19 Pneumonia is
Associated with Respiratory Failure and Coagulopathy. Circulation,
2020; DOI: 10.1161/CIRCULATIONAHA.120.048488 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200807093804.htm

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