Incidence of venous thromboembolic events in COVID-19 patients after hospital discharge: A systematic review and meta-analysis

Zuin, Marco; Engelen, Matthias M; Barco, Stefano; Spyropoulos, Alex C.; Vanassche, Thomas; Hunt, Beverley J.; Vandenbriele, Christophe; Verhamme, Peter; Kucher, Nils; Rashidi, Farid; Zuliani, Giovanni; Konstantinides, Stavros; Roncon, Loris

doi:10.1016/j.thromres.2021.11.029

Cited by 45 publications

(47 citation statements)

References 20 publications

(85 reference statements)

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“…We postulate that the difference observed between the two waves may indicate underdiagnosis of pulmonary embolism, particularly during the first wave and especially considering the discrepancy with reference data from the literature, which estimates a prevalence of pulmonary embolism of at least 15% among hospitalized patients and a 6-week cumulative incidence of 1–2% after hospital discharge [8] , [24] . Indeed, one cannot exclude that the increased number of in situ pulmonary thrombosis detected during the course of the pandemic could partly explain this rise [25] .…”

Section: Discussionmentioning

confidence: 76%

Deaths related to pulmonary embolism and cardiovascular events before and during the 2020 COVID-19 pandemic: An epidemiological analysis of data from an Italian high-risk area

Voci

Fedeli

Farmakis

et al. 2022

Thrombosis Research

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Section: Discussionmentioning

confidence: 76%

Deaths related to pulmonary embolism and cardiovascular events before and during the 2020 COVID-19 pandemic: An epidemiological analysis of data from an Italian high-risk area

Voci

Fedeli

Farmakis

et al. 2022

Thrombosis Research

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“…Coagulopathies [ 84–102 ], and especially the formation of extensive microclots in vivo , are a hallmark of both COVID [ 85 , 103–115 ] and long COVID [ 116 , 117 ], and we have demonstrated that these microclots too are amyloid in character [ 108 , 109 , 116 ]. Importantly, the addition of purified, recombinant SARS-CoV-2 S1 spike protein to coagulation-competent normal plasma is sufficient to induce the formation of anomalous clots [ 118 ] that adopt amyloid states that are also resistant to fibrinolysis [ 108 ].…”

Section: Amyloid Fibrin Microclots (Fibrinaloids) In Covid-19 and Lon...mentioning

confidence: 99%

A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications

Kell

Laubscher

Pretorius

2022

Biochemical Journal

198

212

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Post-acute sequelae of COVID (PASC), usually referred to as ‘Long COVID’ (a phenotype of COVID-19), is a relatively frequent consequence of SARS-CoV-2 infection, in which symptoms such as breathlessness, fatigue, ‘brain fog’, tissue damage, inflammation, and coagulopathies (dysfunctions of the blood coagulation system) persist long after the initial infection. It bears similarities to other post-viral syndromes, and to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Many regulatory health bodies still do not recognize this syndrome as a separate disease entity, and refer to it under the broad terminology of ‘COVID’, although its demographics are quite different from those of acute COVID-19. A few years ago, we discovered that fibrinogen in blood can clot into an anomalous ‘amyloid’ form of fibrin that (like other β-rich amyloids and prions) is relatively resistant to proteolysis (fibrinolysis). The result, as is strongly manifested in platelet-poor plasma (PPP) of individuals with Long COVID, is extensive fibrin amyloid microclots that can persist, can entrap other proteins, and that may lead to the production of various autoantibodies. These microclots are more-or-less easily measured in PPP with the stain thioflavin T and a simple fluorescence microscope. Although the symptoms of Long COVID are multifarious, we here argue that the ability of these fibrin amyloid microclots (fibrinaloids) to block up capillaries, and thus to limit the passage of red blood cells and hence O2 exchange, can actually underpin the majority of these symptoms. Consistent with this, in a preliminary report, it has been shown that suitable and closely monitored ‘triple’ anticoagulant therapy that leads to the removal of the microclots also removes the other symptoms. Fibrin amyloid microclots represent a novel and potentially important target for both the understanding and treatment of Long COVID and related disorders.

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“…The term coagulopathies is used to describe any kind of dysregulation of the blood coagulation system. Coagulopathies [ 82 , 285–302 ] are a hallmark of both acute COVID [ 82 , 84 , 86 , 303–319 ] and Long COVID [ 88 , 89 , 320 ], and spike protein may be activated by clotting factors [ 321 ]. Acute COVID-19 is associated with both a hypercoagulable state and with bleeding; the resolution of the apparent paradox is temporal [ 82 ] since the hypercoagulation can use up elements such as von Willebrand factor (VWF) that are then insufficient for normal coagulation to occur.…”

Section: Coagulopathiesmentioning

confidence: 99%

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

Kell

2022

Biochemical Journal

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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 started; reperfusion is a necessary corollary when it finishes. We rehearse the mechanistic evidence for these occurrences here, in terms of their manifestation as oxidative stress, hyperinflammation, mast cell activation, the production of marker metabolites and related activities. Such microclot-based phenomena can explain both the breathlessness/fatigue and the post-exertional malaise that may be observed in these conditions, as well as many other observables. The recognition of these processes implies, mechanistically, that therapeutic benefit is potentially to be had from antioxidants, from anti-inflammatories, from iron chelators, and via suitable, safe fibrinolytics, and/or anti-clotting agents. We review the considerable existing evidence that is consistent with this, and with the biochemical mechanisms involved.

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Incidence of venous thromboembolic events in COVID-19 patients after hospital discharge: A systematic review and meta-analysis

Cited by 45 publications

References 20 publications

Deaths related to pulmonary embolism and cardiovascular events before and during the 2020 COVID-19 pandemic: An epidemiological analysis of data from an Italian high-risk area

Deaths related to pulmonary embolism and cardiovascular events before and during the 2020 COVID-19 pandemic: An epidemiological analysis of data from an Italian high-risk area

A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications

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

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