Overload of Inflammatory Molecules “Trapped” in Micro Blood Clots May Cause Long COVID Symptoms

First evidence of inflammatory microclots in the blood of individuals suffering from Lung COVID: This may be the cause of some of the persistent symptoms experienced by persons with Lung COVID.

New research indicates that an overload of various inflammatory molecules, literally “locked up” in insoluble microscopic blood clots (microclots), may be at the root of some of the lingering symptoms people with lung COVID experience.

This unexpected finding was made by Prof. Resia Pretorius, a researcher in the Department of Physiological Sciences at Stellenbosch University (SU), when she started looking at microclots and their molecular contents in blood samples from individuals with lung COVID. The findings have since been peer-reviewed and published in the journal Cardiovascular Diabetology in August 2021.

“We found high levels of several inflammatory molecules entrapped in microclots present in the blood of individuals with Lung COVID. Some of the entrapped molecules contain clotting proteins such as fibrinogen, as well as alpha(2) antiplasmin,” explains Prof. Pretorius.

Alpha(2) antiplasmin is a molecule that prevents the breakdown of blood clots, while fibrinogen is the main clotting protein. Under normal circumstances, the body’s plasmin-antiplasmin system maintains a fine balance between blood clotting (the process by which blood thickens and clots to prevent blood loss after injury) and fibrinolysis (the process by which the fibrin in the coagulated blood is broken down to prevent blood loss). clots form).

With high levels of alpha (2) antiplasmin in the blood of COVID-19 patients and individuals suffering from Lung COVID, the body’s ability to break down the clots is significantly inhibited.

Fluorescent image of healthy blood plasma (left) compared to the plasma microclots of a person with Lung COVID on the right. Credit: Resia Pretorius

The insolubility of the microclots became apparent when Dr. Maré Vlok, a senior analyst in the mass spectrometry unit at SU’s central analytical facilities, noted that the blood plasma samples from individuals with acute COVID and Lung COVID continued to deposit insoluble pellets at the bottom of the microclots. tubes after dilution (a process called trypsinization).

He informed Prof. Pretorius of this observation and she investigated it further. They are now the first research group to report on finding microclots in the blood samples of individuals with lung COVID, using fluorescence microscopy and proteomics analysis, solving yet another puzzle related to the disease.

Of particular interest is the concomitant presence of persistent aberrant microclots and a pathological fibrinolytic system,” they write in the research paper. This implies that the balance between plasmin and antiplasmin may be central to pathologies in Lung COVID, providing further evidence that COVID-19, and now Lung COVID, have significant cardiovascular and coagulation pathologies.

Further research is recommended on a therapy regimen to support coagulation and function of the fibrinolytic system in individuals with persistent long-term COVID symptoms.

In collaboration with vascular internist Dr. Jaco Laubscher of Mediclinic Stellenbosch (a co-author of the paper), they now plan to perform the same analysis on a larger sample of patients. To date, they have collected blood from one hundred Lung COVID individuals who participated in the Lung COVID Registry launched in May 2021, as well as from 30 healthy individuals. The research is funded by the Long COVID Research Charitable Trust, a trust established with an initial donation from Mr Koos Pretorius of ENSafrica. It is intended that this trust will be used as a vehicle to raise more money for research into the causes and effective treatment of people suffering from Lung COVID.

Reference: “Persistent coagulation protein pathology in Lung COVID/Post-Acute Sequelae of COVID-19 (PASC) is associated with elevated levels of antiplasmin” by Etheresia Pretorius, Mare Vlok, Chantelle Venter, Johannes A. Bezuidenhout, Gert Jacobus Laubscher, Janami Steenkamp and Douglas B. Kell, Aug. 23, 2021, Cardiovascular Diabetology.
DOI: 10.1186/s12933-021-01359-7