- Researchers do not yet fully understand the mechanisms underlying the symptoms of prolonged COVID.
- A new study shows that 28% of people with prolonged COVID show higher levels of markers associated with blood clot formation.
- Abnormal levels of these markers were associated with impaired exercise capacity, but not other prolonged symptoms of COVID.
- These results could inform future research on treatments to reduce such abnormalities associated with blood clotting in people with prolonged COVID.
A recent study published in the journal blood advances found elevated levels of blood clotting markers in more than one in two (55%) people with prolonged COVID who also had abnormal exercise test results.
People with elevated levels of blood coagulation markers were four times more likely to show persistent deficits in exercise capacity.
These results suggest that people with prolonged COVID should be screened for impaired exercise capacity and markers associated with blood clotting. The author of the study, Dr. Nithya Prasannanresearcher at University College London Hospital, says:
“I hope people see this research as a step forward in understanding the causes of long-term COVID, which will hopefully help us guide future treatment options.”
According to the World Health Organization, more than 500 million people around the world have been diagnosed with COVID-19 so far. Although estimates vary widely, a recent study meta-analysis suggests that nearly a third of all people with COVID-19 may experience persistent symptoms 3 months after symptom onset.
These COVID-19 symptoms that persist for at least three months after a SARS-CoV-2 infection have been collectively described as ‘long covid‘ either ‘Post-acute syndrome of COVID-19‘. Some of the common symptoms of prolonged COVID include decreased exercise capacity, fatigue, shortness of breath, muscle pain, mental confusion, and headaches.
Despite the increasing number of people with prolonged COVID, the mechanisms underlying these persistent symptoms of COVID-19 are not well understood.
Recent studies have shown that people with prolonged COVID are more likely to develop small clots in the blood capillaries and show abnormalities in the levels of factors that promote blood coagulation. Such microclots can interfere with the body’s supply of oxygen and nutrients, potentially leading to prolonged COVID symptoms such as fatigue.
Acute COVID-19 is associated with an increased risk of blood clots. Consistently, people with acute COVID-19 are more likely to show elevated levels of proteins that promote blood clotting.
One of those proteins is von Willebrand factor (VWF), which helps form a clot to seal off damaged blood vessels at the site of injury. Subsequently, an enzyme called ADAMTS13 breaks down the VWF protein into smaller pieces to reduce its activity and prevent clots from forming in blood vessels.
a high relationship of VWF to ADAMTS13 is associated with an increased risk of blood clots in acute cases of COVID-19. Such a condition involving an increased risk of blood clots is known as prothrombotic state.
In the present study, the authors investigated whether such a prothrombotic state was associated with the severity of prolonged COVID symptoms, including exercise capacity.
The present study consisted of 330 people who had persistent symptoms 3 or more months after SARS-CoV-2 infection and were visiting a long-term COVID outpatient clinic. The majority (83%) had never been to the hospital.
At the time of the visit, the researchers administered two tests to assess the participants’ endurance and exercise capacity. These exercise tests consisted of walking at a normal pace for 6 minutes and repeatedly changing from a sitting to standing position for one minute.
The researchers used an oxygen monitor to measure blood oxygen levels during the test. They also measured changes in blood lactate levels, which is produced by the body when there is an insufficient supply of oxygen to sustain muscle activity.
To assess the risk of blood clotting, the researchers used blood samples to categorize participants into two groups based on whether their VWF/ADAMTS13 ratio was normal (less than 1.5) or abnormal (greater than or equal to 1 ,5).
The researchers found that about 28% of study participants had abnormal levels of VWF/ADAMTS13. The VWF/ADAMTS13 ratio did not correlate with the severity of long-term COVID symptoms, including headaches, fatigue, and cognitive deficits.
However, abnormal levels of VWF/ADAMTS13 were associated with decreased exercise capacity, as measured by blood oxygen and lactate levels. Nearly 20% of participants showed decreased exercise capacity and 55% of people in this group had elevated VWF/ADAMTS13 levels.
Elevated VWF/ADAMTS13 levels were four times more likely in people with impaired exercise capacity than in those with normal performance on exercise tests. In addition, levels of VWF and the blood coagulation protein factor VIII were also higher in people with decreased exercise capacity.
Dr. Artur Fedorowskiprofessor at Karolinska University Hospital, Stockholm, Sweden, spoke with MNT about the study He w
“The higher VWF/ADAMTS13 ratio may suggest that some long-COVID patients have a predisposition to microclot generation, which could affect normal blood flow through several crucial areas, such as the pulmonary or cerebral circulation. Thus, under normal conditions, the patient may feel normal and compensated, while physical or mental exertion may reveal a lack of compensatory reserve and produce characteristic symptoms.
“This hypothesis is mechanistically very attractive, but we must keep in mind that most patients with long-standing COVID had a normal VWF/ADAMTS13 ratio. Either the detected abnormality is just one of the many symptom-generating mechanisms of prolonged COVID, or there may be no causal association.”
“Instead, the actual mechanism of COVID may cause symptoms and a higher prothrombotic ratio in some susceptible patients,” added Dr. Fedorowski.
Addressing future research directions, Dr. Prasannan said MNT“Assessment of the VWF/ADAMTS13 relationship has become part of routine investigations conducted in long-COVID patients.”
“As part of current ongoing research in the Hemostasis Research Unit, a shear flow-based assay (a platform that mimics blood flow through blood vessels) is being used to assess microclot formation in patients. with prolonged COVID.”
