IMAGE DESCRIPTION: An image of Covid spike proteins with two circular images; one of the word 'apheresis' and the other is a photo of red blood cells. The title reads: Long Covid – Cochrane review of microclots and apheresis. The ME Association logo (bottom right)

Long Covid – Cochrane review of microclots and apheresis 

Yesterday (26.07.23), the Cochrane Library published the following article ‘Plasmapheresis to remove amyloid fibrin(ogen) particles for treating the post‐COVID‐19 condition' which summarises and appraises the research reports on amyloid fibrin(ogen) particles related to Post Covid-19.


The post‐COVID‐19 condition (PCC) consists of a wide array of symptoms including fatigue and impaired daily living. People seek a wide variety of approaches to help them recover.

A new belief, arising from a few laboratory studies, is that ‘microclots' cause the symptoms of PCC. This belief has been extended outside these studies, suggesting that to recover people need plasmapheresis (an expensive process where blood is filtered outside the body). We appraised the laboratory studies, and it was clear that the term ‘microclots' is incorrect to describe the phenomenon being described. The particles are amyloid and include fibrin(ogen); amyloid is not a part of a thrombus which is a mix of fibrin mesh and platelets. Initial acute COVID‐19 infection is associated with clotting abnormalities; this review concerns amyloid fibrin(ogen) particles in PCC only.

We have reported here our appraisal of laboratory studies investigating the presence of amyloid fibrin(ogen) particles in PCC, and of evidence that plasmapheresis may be an effective therapy to remove amyloid fibrin(ogen) particles for treating PCC.

Plain language summary

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).

The ME Association Comment

Despite a having major disagreement about the way in which Cochrane have supported the use of GET for ME/CFS I think this is a fair summary of the situation regarding the possible role of micro-clots in the causation of Long Covid.

In our current state of knowledge the micro-clots link to Long Covid remains a hypothesis.

And there is no sound evidence from proper clinical trials to show that plasmapheresis (apheresis) is a safe and effective treatment for Long Covid.

Dr Charles Shepherd,
Trustee and
Hon. Medical Adviser
to the ME Association.
Member of the 2018-2021 NICE Guideline Committee.
Member of the 2002 Independent Working Group on ME/CFS.

Dr Charles Shepherd
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