Plasmapheresis to remove amyloid fibrin(ogen) particles for treating the post-COVID-19 condition

26 Jul 2023

What is the evidence that 'microclots' cause the post‐COVID‐19 syndrome, and is removal using plasmapheresis justified?

Key messages

1. The term 'microclots' is not the correct term for the particles being investigated in people with post‐COVID‐19 syndrome, as they are not clots. The term 'amyloid fibrin(ogen) particles' is more appropriate.

2. The evidence shows that amyloid fibrin(ogen) particles are found in healthy people and those with other diseases, so they are not unique to post‐COVID‐19 condition.

3. Patients should not receive plasmapheresis for this indication outside the context of a properly conducted placebo (dummy)‐controlled randomized clinical trial (a type of study where participants are randomly assigned to one of two or more treatment groups).

What did we want to find out?

Post‐COVID‐19 condition (sometimes called 'long COVID') refers to a condition in which a patient experiences a variety of symptoms for at least 12 weeks after having initial (acute) COVID‐19 infection. Symptoms can range in severity and include fatigue, brain fog, and headaches, and lead to impaired quality of life. The cause of post‐COVID‐19 condition (PCC) is a source of debate. One theory is that it is caused by small clots in the blood, termed 'microclots' by the authors of a set of laboratory studies that investigate them. The particles described appear to contain proteins called amyloid and fibrin(ogen), so we refer to them as amyloid fibrin(ogen) particles to reflect their components.

It has been suggested that these particles could be removed from the blood using a technique called plasmapheresis, in which the blood is removed from the body and the plasma component of a patient's blood is filtered by a machine to remove any particles. If these particles were responsible for the symptoms of PCC, removing them may treat patients of their symptoms. The rationale for this treatment in PCC is unproven, and is associated with potential risks to patients.

What did we do?

We wanted to investigate the theory that amyloid fibrin(ogen) particles could be the cause of post‐COVID‐19 condition.

The review was done in two steps, as follows.

1. A review of laboratory studies that investigate whether amyloid fibrin(ogen) particles are found in blood samples from people with post‐COVID‐19 condition. This research is found in full detail in Appendix 1.

2. A review of randomized trials that investigate whether plasmapheresis is a safe and effective treatment for removing amyloid fibrin(ogen) particles in people with post‐COVID‐19 condition.

What did we find?

Laboratory studies review

We identified five studies that assessed whether amyloid fibrin(ogen) particles were present in the blood of patients with post‐COVID‐19 condition. The studies identified these particles in healthy controls, those with type 2 diabetes, and those with PCC, meaning they are not unique to PCC. We also identified problems with how these studies were conducted and how the findings were presented, for example it is unclear whether these particles were found in all participants with PCC, or only some.

Randomized controlled trials review

We found no studies where patients with post‐COVID‐19 condition had undergone plasmapheresis with the intention of removing amyloid fibrin(ogen) particles. We also did not find any ongoing trials that are investigating this.

What are the limitations of the evidence?

The evidence is unable to demonstrate if amyloid fibrin(ogen) particles contribute to the post‐COVID‐19 condition. Our analysis did not consider other supposed mechanisms for the post‐COVID‐19 condition and plasmapheresis in the context of other such mechanisms.

How up‐to‐date is this review?

We conducted a search for studies on 21 October 2022 (randomized controlled trials) and 27 October 2022 (laboratory studies).