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

Exhaustion, brain fog, and headaches are common in post-COVID-19 condition, sometimes called “long covid”. Social media and newspapers report the theory that this is caused by “microclots” which cause a shortage of oxygen to body tissues. This has led patients to seek expensive treatment through plasmapheresis, a procedure that takes blood out of the body and filters it.

A partnership between Liverpool School of Tropical Medicine, Guy’s and St Thomas’ NHS Foundation Trust, University of Leeds, and University College London, sought to examine the evidence around the “microclots” theory. Specialist methodologists (Tilly Fox, Dr Rebecca Kuehn, and Professor Paul Garner) and specialists in thrombotic disorders, vascular biology, molecular biology and infectious diseases (Professor Beverley J Hunt, Professor Robert AS Ariens, Professor Greg J Towers, and Dr Robert Lever) worked together and summarised the evidence in a Cochrane review.

Background

People with post-COVID-19 condition experience a range of distressing and disabling symptoms that persist for more than 12 weeks after their initial SARS-CoV-2 infection. An estimated 10% to 20% of people with a SARS-CoV-2 infection may be diagnosed with post-COVID-19 condition, yet the exact mechanisms of what causes this disease are still disputed. Those affected may struggle to find solutions to manage their indications and aid their recovery.

Findings

The research on “microclots” was conducted mainly by one research group carrying out several laboratory analyses on human blood. The particles described by these authors do not contain the components that make up a clot, so the term “microclot” is misleading. The Cochrane authors therefore used the term amyloid fibrin(ogen) particles as this was judged as more accurate.

The review team searched for evidence from laboratory experiments up to 27 October 2022. The five studies identified used blood samples from volunteers who self-reported as having post-COVID-19 condition. In three of these studies samples were analysed alongside healthy controls or patients with type 2 diabetes.

The studies showed that amyloid fibrin(ogen) particles were present in the blood samples from patients with post-COVID-19, healthy controls, and patients with type 2 diabetes. The review authors concluded that the presence of amyloid fibrin(ogen) particles is not unique to post-COVID-19 condition.

The Cochrane review team also tried to determine if the amount or size of the particles differed between samples from people with post-COVID-19 condition and controls, but only one of the included studies used methods to investigate this. The authors of this study stated the particles in post-COVID-19 blood samples may be larger and more numerous, but there was overlap in values between the groups.

Synthesis specialist and Cochrane author Tilly Fox stated, “Our quality appraisal of these studies revealed problems with the conduct and the presentation of the findings. The methods were often not well-described, and we were particularly surprised by the lack of comparison between control and post-COVID-19 condition groups in four of the studies.”

The review authors conducted a search of the literature on 21 October 2022 to determine if there is any evidence from randomized controlled trials (RCTs) that plasmapheresis is safe and effective for removing these amyloid fibrin(ogen) particles but found no completed studies. Two ongoing trials that are investigating plasmapheresis for post-COVID-19 were identified but they do not plan to assess the removal of amyloid fibrin(ogen) particles.

Specialist in thrombosis and haemostasis, Professor Beverley J Hunt added, “We were concerned about the lack of evidence to support the use of plasmapheresis, which is not free from complications in patients with post-COVID-19 condition”.

In summary, this Cochrane review shows that the particles described are more accurately termed amyloid fibrin(ogen) and occur in normal controls and other clinical conditions. There is currently no evidence indicating that amyloid fibrin(ogen) particles contribute to post-COVID-19 condition, and no justification for people to seek treatment with plasmapheresis to remove amyloid fibrin(ogen) particles.

Fox T, Hunt BJ, Ariens RAS, Towers GJ, Lever R, Garner P, Kuehn R. Plasmapheresis to remove amyloid fibrin(ogen) particles for treating the post‐COVID‐19 condition. Cochrane Database of Systematic Reviews 2023, Issue 7. Art. No.: CD015775. DOI: 10.1002/14651858.CD015775

Useful links:

• Summary of the Cochrane review (abstract) and the plain language summary can be accessed here
• Long covid patients travel abroad for expensive and experimental “blood washing”. BMJ 2022;378:o1671 https://doi.org/10.1136/bmj.o1671

The editorial base of the Cochrane Infectious Diseases Group is funded by UK aid from the UK government for the benefit of low- and middle-income countries (project number 300342-104). The views expressed do not necessarily reflect the UK government’s official policies. 

Any queries regarding this publication can be directed to info [at] lstmed [dot] ac [dot] uk. This news article was first published on the LSTM website.