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Long COVID: High blood-clotting markers linked with reduced exercise capacity

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 long COVID who also had abnormal exercise testing results.

Individuals with elevated blood clotting marker levels were four times more likely to show persistent deficits in exercise capacity.

These results suggest that individuals with long COVID should be screened for impaired exercise capacity and markers associated with blood clotting. The study’s author, Dr. Nithya Prasannan, a researcher at the University College London Hospital, says:

“I hope that people will view this research as a step forward in understanding what causes long COVID, which will hopefully help us guide future treatment options.”

Abnormalities associated with blood clotting

According to the World Health Organization, more than 500 million individuals across the globe have been diagnosed with COVID-19 so far. Although estimates vary widely, a recent meta-analysis suggests that nearly one-third of all individuals with COVID-19 may experience persistent symptoms 3 months after symptom onset.

These COVID-19 symptoms that linger for at least three months after a SARS-CoV-2 infection have been collectively described as ‘long COVIDTrusted Source’ or ‘post-acute COVID-19 syndromeTrusted Source’. Some of the common symptoms of long COVID include impaired exercise capacity, fatigue, breathlessness, muscle pain, brain fog, and headaches.

Despite the growing number of individuals with long COVID, the mechanisms underlying these persistent symptoms of COVID-19 are not well-understood.

Recent studies have shown that individuals with long COVID are more likely to develop small clotsTrusted Source in blood capillaries and show abnormalities in the levels of factors that promote blood clotting. Such micro clots can interfere with the supply of oxygen and nutrients to the body and potentially result in long COVID symptoms such as fatigue.

Blood clotting factors

Acute COVID-19 is associated with an increased risk of blood clots. Consistently, individuals with acute COVID-19 are more likely to show elevated levels of proteins that promote blood clotting.

One such protein is the von Willebrand Factor (VWF), which helps to form a clot to seal off damaged blood vessels at the injury site. Subsequently, an enzyme called ADAMTS13 cleaves the VWF protein into smaller fragments to reduce its activity and prevent the formation of clots in blood vessels.

An elevated ratio of VWF to ADAMTS13 is associated with an increased risk of blood clots in acute COVID-19. Such a condition involving an increased risk of blood clots is referred to as a prothrombotic state.

In the present study, the authors investigated whether such a prothrombotic state was associated with the severity of long COVID symptoms, including exercise capacity.

Impaired exercise capacity

The present study consisted of 330 individuals who had persistent symptoms 3 or more months after the SARS-CoV-2 infection and were visiting an outpatient long COVID clinic. The majority (83%) had never been in hospital.

At the time of the visit, the researchers administered two tests to assess the participants’ endurance and exercise capacity. These exercise tests involved walking at a normal pace for 6 minutes and repeatedly switching from a sitting to a standing position for a minute.

The researchers used an oxygen monitor to measure blood oxygen levels during the test. They also measured changes in the levels of blood lactate, which is produced by the body when there is an insufficient supply of oxygen to sustain the activity of muscles.

To assess the risk of blood clotting, the researchers used blood samples to categorize the 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 around 28% of the study’s participants had abnormal VWF/ADAMTS13 levels. The VWF/ADAMTS13 ratio was not correlated with the severity of long COVID symptoms, including headaches, fatigue, and cognitive deficits.

However, abnormal VWF/ADAMTS13 levels were associated with impaired exercise capacity, as measured by blood oxygen and lactate levels. Nearly 20% of participants showed impaired exercise capacity, and 55% of individuals within this group had elevated VWF/ADAMTS13 levels.

Elevated VWF/ADAMTS13 levels were four times more likely in individuals with impaired exercise capacity than those with normal performance in the exercise tests. In addition, the levels of VWF and the blood-clotting protein Factor VIII were also higher in individuals with impaired exercise capacity.

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