2022
DOI: 10.1042/bcj20220154
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The potential role of ischaemia–reperfusion injury in chronic, relapsing diseases such as rheumatoid arthritis, Long COVID, and ME/CFS: evidence, mechanisms, and therapeutic implications

Abstract: Ischaemia–reperfusion (I–R) injury, initiated via bursts of reactive oxygen species produced during the reoxygenation phase following hypoxia, is well known in a variety of acute circumstances. We argue here that I–R injury also underpins elements of the pathology of a variety of chronic, inflammatory diseases, including rheumatoid arthritis, ME/CFS and, our chief focus and most proximally, Long COVID. Ischaemia may be initiated via fibrin amyloid microclot blockage of capillaries, for instance as exercise is … Show more

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Cited by 40 publications
(72 citation statements)
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“…We suggest that this phenomenon might directly be due to autoantibodies that develop against antibodies or other molecules that are entrapped inside the fibrinaloid microclots. It appears that the long-term sequelae of many viral infections [ 94 , 95 ], including long COVID [ 96 , 97 ] may be attributed to autoimmunity. These microclots contain many different proteins that may present new epitopes if a conformational change has taken place.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…We suggest that this phenomenon might directly be due to autoantibodies that develop against antibodies or other molecules that are entrapped inside the fibrinaloid microclots. It appears that the long-term sequelae of many viral infections [ 94 , 95 ], including long COVID [ 96 , 97 ] may be attributed to autoimmunity. These microclots contain many different proteins that may present new epitopes if a conformational change has taken place.…”
Section: Discussionmentioning
confidence: 99%
“…Autoantibodies formed against actin lead to muscle weakness [98]. In ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome), autoimmunity is well described [94]; and might also play an important role in long COVID because some autoantibodies share elements of epitope with the SARS-CoV-2 virus [99]. It has also been suggested that some of the viral sequences are amyloidogenic [100,101].…”
Section: Immunoglobulins Of Interestmentioning
confidence: 99%
“…Dysregulation of coagulation, and in particular the formation of fibrin amyloid microclots that are resistant to proteolysis and can then cause ischaemia-reperfusion injury ( 9, 11 ), is a key part of the pathogenesis of Long COVID. In fact, we would argue that whilst there may be many mechanisms at play in the pathogenesis of Long COVID, the common pathological process is thrombotic endotheliitis .…”
Section: Discussionmentioning
confidence: 99%
“…Post-Acute Sequelae of COVID-19 (PASC) or Long COVID is a major global health burden with its symptoms significantly impacting physical and cognitive function, health-related quality of life, and participation in society (1-9). The mechanisms for the persistent symptoms can be narrowed down to 1) viral persistence, 2) microclotting and platelet hyperactivation, 3) autoantibodies, 4) immune dysregulation, 5) widespread organ damage, and the 6) reactivation of dormant viruses (9)(10)(11)(12). SARS-CoV-2 (COVID-19) viral remnants including RNA and spike protein have been identified in patients with Long COVID.…”
Section: Introductionmentioning
confidence: 99%
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