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

Fox, Tilly, Hunt, Beverley J, Ariens, Robert AS, Towers, Greg J, Lever, Robert, Garner, Paul ORCID: and Kuehn, Rebecca (2023) 'Plasmapheresis to remove amyloid fibrin(ogen) particles for treating the post‐COVID‐19 condition'. The Cochrane Database of Systematic Reviews, Vol 2023, Issue 7, eCD015775.

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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.

Laboratory studies review

To summarize and appraise the research reports on amyloid fibrin(ogen) particles related to PCC.

Randomized controlled trials review

To assess the evidence of the safety and efficacy of plasmapheresis to remove amyloid fibrin(ogen) particles in individuals with PCC from randomized controlled trials.

Search methods
Laboratory studies review

We searched for all relevant laboratory studies up to 27 October 2022 using a comprehensive search strategy which included the search terms ‘COVID’, ‘amyloid’, ‘fibrin’, ‘fibrinogen’.

Randomized controlled trials review

We searched the following databases on 21 October 2022: Cochrane COVID‐19 Study Register; MEDLINE (Ovid); Embase (Ovid); and BIOSIS Previews (Web of Science). We also searched the WHO International Clinical Trials Registry Platform and for trials in progress.

Selection criteria
Laboratory studies review

Laboratory studies that investigate the presence of amyloid fibrin(ogen) particles in plasma samples from patients with PCC were eligible. This included studies with or without controls.

Randomized controlled trials review

Studies were eligible if they were of randomized controlled design and investigated the effectiveness or safety of plasmapheresis for removing amyloid fibrin(ogen) particles for treating PCC.

Data collection and analysis
Two review authors applied study inclusion criteria to identify eligible studies and extracted data.

Laboratory studies review

We assessed the risk of bias of included studies using pre‐developed methods for laboratory studies. We planned to perform synthesis without meta‐analysis (SWiM) as described in our protocol.

Randomized controlled trials review

We planned that if we identified any eligible studies, we would assess risk of bias and report results with 95% confidence intervals. The primary outcome was recovery, measured using the Post‐COVID‐19 Functional Status Scale (absence of symptoms related to the illness, ability to do usual daily activities, and a return to a previous state of health and mind).

Main results
Laboratory studies review

We identified five laboratory studies. Amyloid fibrin(ogen) particles were identified in participants across all studies, including those with PCC, healthy individuals, and those with diabetes. The results of three studies were based on visual images of amyloid fibrin(ogen) particles, which did not quantify the amount or size of the particles identified. Formal risk of bias assessment showed concerns in how the studies were conducted and reported. This means the results were insufficient to support the belief that amyloid fibrin(ogen) particles are associated with PCC, or to determine whether there is a difference in the amount or size of amyloid fibrin(ogen) particles in the plasma of people with PCC compared to healthy controls.

Randomized controlled trials review

We identified no trials meeting our inclusion criteria.

Authors' conclusions
In the absence of reliable research showing that amyloid fibrin(ogen) particles contribute to the pathophysiology of PCC, there is no rationale for plasmapheresis to remove amyloid fibrin(ogen) particles in PCC. Plasmapheresis for this indication should not be used outside the context of a well‐conducted randomized controlled trial.

Item Type: Article
Subjects: WC Communicable Diseases > Virus Diseases > Viral Respiratory Tract Infections. Respirovirus Infections > WC 506 COVID-19
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):
Depositing User: Christianne Esparza
Date Deposited: 08 Aug 2023 15:04
Last Modified: 08 Aug 2023 15:05


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