Changes in the blood, not the heart, may underlie cardiac thrombosis in COVID-19 patients

Date:
December 7, 2021
Source:
Elsevier
Summary:
Treatment targeting immune-regulating neutrophil activation may
reduce pathological thrombosis in COVID-19 patients, researchers
report.



FULL STORY ========================================================================== Researchers examined autopsy tissue samples of hearts from patients
who died early in the COVID-19 pandemic. Frequent and extensive blood
clots (thromboses) within heart vessels were found as anticipated, but
the type of changes in the endothelial cells lining the heart that are typically observed in thromboses were absent. Instead, data indicated the likely culprit to be hypercoagulability of the blood caused by activated neutrophils, a type of white blood cell. Their findings are published
in The American Journal of Pathology, published by Elsevier.


==========================================================================
"My laboratory has a long history of defining endothelial cell alterations
that produce pathologies, including thrombosis, and we expected to confirm
the widely held assumption that local endothelial cell alterations were responsible for thrombosis of the cardiac vessels in COVID-19 patients," explained lead investigator Jordan S. Pober, MD, PhD, Department of Immunobiology, Yale University School of Medicine, New Haven, CT,
USA. "Instead, we found that the cardiac thrombi contained neutrophils
that expressed changes known to promote coagulation, including changes
that are associated with cell death and inflammation." Hospitalized
patients with SARS-CoV-2 infection have an increased risk of developing myocardial injury. However, numerous studies have rarely detected viral
protein or RNA within the hearts of patients who died from COVID-19,
despite evidence of abundant virus presence in the lungs of the same
patients.

Thrombosis of micro and macro coronary vessels has most consistently characterized the hearts of individuals who succumbed to COVID-19,
but the underlying cause remains unknown.

Dr. Pober and his colleagues examined heart tissue from seven autopsies of COVID-19 patients performed early in the pandemic, before anticoagulation treatment was commonly administered, and compared these specimens to
autopsy tissue from 12 COVID-19-negative controls, with and without
heart disease, using multiparameter fluorescence microscopy to analyze
the composition of the thrombosed vessels. All patients in the COVID-19
group had severe pneumonia.

One patient experienced a sudden cardiac arrest outside of the hospital,
two patients developed sepsis, and one patient had recurrent acute
leukemia with thrombocytopenia. The COVID-19-negative controls included
six patients with pre-existing cardiac disease.

Thrombosis was the most common pathological finding in the COVID-19 group
with a greatly elevated frequency of microthrombi and total number of macrothrombi compared to the COVID-19-negative controls. Despite the
widespread evidence of thrombosis, no evidence of myocyte death or acute inflammation typically associated with myocardial infarction was detected
in the COVID-19 group.

The vessels of the heart were examined for signs of endothelial cell
injury, which can promote thrombosis through release of microparticles containing procoagulative tissue factor, or by endothelial cell sloughing
that can expose platelet activating collagen. The investigators failed to
find such endothelial changes at sites of thrombosis. Instead, they saw
that the cardiac thrombi in four of the six COVID-19 patients contained neutrophils that expressed procoagulant changes in the blood, such as citrullination of histones associated with formation of neutrophil extracellular traps (NETs). Some images suggest NETS that appear to
be directly associated with platelets. Neutrophil- rich macrothrombi
composed of 30% or more neutrophils were common in the COVID- 19 group
but not in control tissue specimens.

Dr. Pober commented, "Our data challenge the view that alterations
in the heart vessel wall are the primary cause of COVID-19
cardiac thrombosis. Current treatments of severe COVID-19 include anticoagulation, but the best strategy is still not clear. In light
of our findings, reducing neutrophil responses could be an important
target for therapeutic intervention. This and many other advances in
the understanding of disease continue to be provided by autopsies,
and I am grateful to the pathologists who performed them for this
study at both Brigham and Women's Hospital and Yale." Peter Libby, MD,
a cardiologist and vascular biologist at Boston's Brigham and Women's
Hospital and the Harvard Medical School, a long-time collaborator of
Dr. Pober's, stated: "For several years we have studied neutrophils
and their prothrombotic products known as NETs in the context of
clots that form in the larger coronary arteries. The finding of
neutrophil involvement in the smaller blood vessels that course
through the heart muscle in COVID-19 extends our understanding of
cardiac injury that we often see in patients with severe SARS- CoV-2
infection. Brigham pathologists Robert F. Padera, Jr., MD, PhD, and
Richard N. Mitchell, MD, PhD, helped us enormously by providing tissue
samples for these analyses early on in our experience with this pandemic." ========================================================================== Story Source: Materials provided by Elsevier. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Justin E. Johnson, Declan McGuone, Mina L. Xu, Dan Jane-Wit,
Richard N.

Mitchell, Peter Libby, Jordan S. Pober. Coronavirus Disease 2019
(COVID- 19) Coronary Vascular Thrombosis. The American Journal of
Pathology, 2021; DOI: 10.1016/j.ajpath.2021.09.004 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/12/211207152557.htm

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