Risk of symptomatic venous thromboembolism in mild and moderate COVID-19: A comparison of two prospective European cohorts

Douillet, Delphine; Riou, Jérémie; Penaloza, Andréa; Moumneh, Thomas; Soulié, Caroline; Savary, Dominique; Morin, François; Mahieu, Rafaël; Roy, Pierre‐Marie

doi:10.1016/j.thromres.2021.10.001

Cited by 16 publications

(8 citation statements)

References 30 publications

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“…Coagulopathies [84][85][86][87][88][89][90][91][92][93][94][95][96][97][98][99][100][101][102], and especially the formation of extensive microclots in vivo, are a hallmark of both COVID [85,[103][104][105][106][107][108][109][110][111][112][113][114][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: 67%

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

confidence: 67%

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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“…After adjusting for comorbid conditions, patients in the moderate cohort had an absolute increase in risk for thrombosis of 1.69%. 32 …”

Section: Discussionmentioning

confidence: 99%

One-Year Adverse Outcomes Among US Adults With Post–COVID-19 Condition vs Those Without COVID-19 in a Large Commercial Insurance Database

DeVries¹,

Shambhu²,

Sloop³

et al. 2023

JAMA Health Forum

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ImportanceMany individuals experience ongoing symptoms following the onset of COVID-19, characterized as postacute sequelae of SARS-CoV-2 or post–COVID-19 condition (PCC). Less is known about the long-term outcomes for these individuals.ObjectiveTo quantify 1-year outcomes among individuals meeting a PCC definition compared with a control group of individuals without COVID-19.Design, Setting, and ParticipantsThis case-control study with a propensity score–matched control group included members of commercial health plans and used national insurance claims data enhanced with laboratory results and mortality data from the Social Security Administration’s Death Master File and Datavant Flatiron data. The study sample consisted of adults meeting a claims-based definition for PCC with a 2:1 matched control cohort of individuals with no evidence of COVID-19 during the time period of April 1, 2020, to July 31, 2021.ExposuresIndividuals experiencing postacute sequelae of SARS-CoV-2 using a Centers for Disease Control and Prevention–based definition.Main Outcomes and MeasuresAdverse outcomes, including cardiovascular and respiratory outcomes and mortality, for individuals with PCC and controls assessed over a 12-month period.ResultsThe study population included 13 435 individuals with PCC and 26 870 individuals with no evidence of COVID-19 (mean [SD] age, 51 [15.1] years; 58.4% female). During follow-up, the PCC cohort experienced increased health care utilization for a wide range of adverse outcomes: cardiac arrhythmias (relative risk [RR], 2.35; 95% CI, 2.26-2.45), pulmonary embolism (RR, 3.64; 95% CI, 3.23-3.92), ischemic stroke (RR, 2.17; 95% CI, 1.98-2.52), coronary artery disease (RR, 1.78; 95% CI, 1.70-1.88), heart failure (RR, 1.97; 95% CI, 1.84-2.10), chronic obstructive pulmonary disease (RR, 1.94; 95% CI, 1.88-2.00), and asthma (RR, 1.95; 95% CI, 1.86-2.03). The PCC cohort also experienced increased mortality, as 2.8% of individuals with PCC vs 1.2% of controls died, implying an excess death rate of 16.4 per 1000 individuals.Conclusions and RelevanceThis case-control study leveraged a large commercial insurance database and found increased rates of adverse outcomes over a 1-year period for a PCC cohort surviving the acute phase of illness. The results indicate a need for continued monitoring for at-risk individuals, particularly in the area of cardiovascular and pulmonary management.

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“…2 These thromboses are primarily venous, although arterial thromboses have been described, 4 and there is a clear association between the presence and extent of thrombosis and the severity of the illness. [5][6][7] Hence, considerable research has focused on how the SARS-CoV-2 virus interacts with the blood clotting system 8,9 in conjunction with the endothelium 3,10 to promote thrombosis. The AstraZeneca vaccine, in particular, has also been associated with the formation of venous thromboses, 11 although at a much lower incidence.…”

Section: Discussionmentioning

confidence: 99%

Non-thrombotic superficial venous phlebitis secondary to Covid-19 vaccine or subsequent Covid-19 infection

Whiteley

Holdstock

2022

SAGE Open Medical Case Reports

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A 43-year-old woman presented with localised areas of prominent, tender superficial veins in her right arm and both legs, and chest pain, following the second dose of AstraZeneca vaccine and possible contemporaneous Covid-19 infection. Electrocardiogram, troponin and d-dimer had all been normal. However, a venous duplex ultrasound scan showed a perivenous inflammation without thrombosis in the areas of her limbs with prominent tender veins, but not elsewhere. We suggest that patients may present with prominent and tender superficial veins secondary to non-thrombotic phlebitis following Covid-19 infection or the AstraZeneca vaccine, which appears to be self-limiting. In addition, this case raises the possibility that Covid-19 infection or the AstraZeneca vaccine may directly affect cells in the vein wall, resulting in phlebitis without any evidence of thrombosis or microthrombosis. This phenomenon appears to be transient and self-limiting.

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Risk of symptomatic venous thromboembolism in mild and moderate COVID-19: A comparison of two prospective European cohorts

Cited by 16 publications

References 30 publications

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

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

One-Year Adverse Outcomes Among US Adults With Post–COVID-19 Condition vs Those Without COVID-19 in a Large Commercial Insurance Database

Non-thrombotic superficial venous phlebitis secondary to Covid-19 vaccine or subsequent Covid-19 infection

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