Long COVID: Could treating microclots relieve symptoms?

• Scientists know little about the underlying mechanisms of long COVID despite widespread reports about it since near the start of the pandemic,
• This lack of knowledge has made diagnosing and developing treatments for this condition challenging.
• COVID-19 affects the lining of the blood vessels, and scientists have investigated whether long COVID symptoms could have links to this.
• A team based in South Africa has released preliminary results of a treatment regime using antiplatelet therapy and anticoagulants to treat people with long COVID.

Long COVID describes the chronic and debilitating symptoms experienced by people with COVID-19 that last for more than 4 weeks after the resolution of the initial infection.

These symptoms include fatigue, shortness of breath and chest pain, cognitive problems, heart palpitations, insomnia, tinnitus, and joint pain.

The Centers for Disease Control and Prevention (CDC) has considered long COVID a disability since July 2021.

Most people with COVID-19 get better within 12 weeks, but scientists do not know how long the condition could last. Nor do they know exactly how many people may develop long COVID. However, estimates suggest over 20% of people who test positive for SARS-CoV-2, the virus that causes COVID-19, could continue to experience chronic symptoms.

Scientists have little understanding of the mechanisms behind the condition, which has made it difficult for them to develop treatments.

Last year, a team from Stellenbosch University in South Africa published results of blood plasma analysis, which revealed that many people with long COVID had microclots.

These microclots were difficult to detect using standard plasma analysis procedures and resisted the body’s ability to dissolve coagulated blood. The scientists also found that the clots “trap” inflammatory molecules.

This work formed the basis of the so-called microclot model, which proposes that small clots in the blood capillaries that prevent oxygen from reaching the tissues may cause long COVID symptoms.

The latest study

Now, the same team has released a preprint outlining details of a further cohort of 845 people with long COVID.

The team analyzed blood samples from 70 people with confirmed long COVID to detect microclots.

The authors also outlined a 1-month-long dual antiplatelet therapy for 24 people with long COVID. The therapy involved the participants taking 75 milligrams (mg) of Clopidogrel and 75 mg of Aspirin once each day before breakfast.

They also received 5 mg of the direct oral anticoagulant Apixiban twice daily and 40 mg each day of a proton pump inhibitor called Pantoprazole. They took Pantoprazole half an hour before eating their main meal to protect the stomach.

The participants took these drugs under strict medical supervision to mitigate severe side effects.

The participants provided a list of symptoms before and after treatment, and the researchers took blood samples at the end of the month of treatment.

The team found that all 70 participants had microclots in their blood and that all 24 people who received the antiplatelet and anticoagulant therapy reported improvements in their long COVID symptoms; they also saw a reduction of microclots.

Limitations to the study

It is important to note that the paper has not yet been peer-reviewed, it is not a clinical trial, and there are no controls.

Prof. Amitava Banerjee, a cardiologist and professor of clinical data science at University College London, is the principal investigator of the STIMULATE ICP study, which is currently seeking ethical approval for a clinical trial.

The trial will, in part, look at how antihistamines, the anti-inflammatory drug colchicine, and the anticoagulant Rivaroxaban, a drug similar to Apixiban, affect people with long COVID.

He told Medical News Today in an interview:

“I think we need to see trials of single agents before we launch into triple agents. I have a lot of experience in cardiology of seeing people on dual and triple therapy, and people have a bleeding complication with that. So we have to be really convinced that we’re not causing harm […]. It seems a big step in this analysis to go straight to the triple therapy.”

Explaining that one of the problems with studying long COVID is that we don’t understand what the underlying mechanisms are, he said:

“We only have ‘what ifs.’ We have evidence of microclots, […] we have evidence of mast cell activation, which is where the antihistamines fit in; we have evidence of inflammation, which is where Colchicine fits in. But there’s probably other things at play as well. So, we need to be both defining the disease and developing treatments at the same time.”

– Prof. Amitava Banerjee

Dr. Melissa Heightman, clinical lead for post-COVID services at University College London Hospitals and co-principal investigator and clinical lead for the STIMULATE IP study, said in a briefing that while the evidence for the microclot model was interesting, questions remain answered:

“One of the things about this [proposed] mechanism is you would expect it to correlate quite closely with the severity of the initial [SARS-CoV-2] infection.” She explains that if there was more significant endothelial injury, you might predict that there would be a greater burden of microclots.

“Of course, that doesn’t match with our clinical experience,” she continues, “where we can see much more severe or equally severe illness in patients who were never hospitalized with COVID-19, compared to post-hospital patients. So, that’s another question I think we need to answer from these preliminary findings.”

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