Long COVID: pathophysiological factors and abnormalities of coagulation

Turner, Simone; Khan, Mehrunnisha; Putrino, David; Woodcock, Ashley; Kell, Douglas B.; Pretorius, Etheresia

doi:10.1016/j.tem.2023.03.002

Cited by 65 publications

(61 citation statements)

References 213 publications

(283 reference statements)

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“…At a population level, the net benefits of vaccination against COVID-19 have been clearly established. However, as spike protein alone has been demonstrated to induce microclots in vitro [36] and a minority of those vaccinated with a spike protein based vaccine develop Long COVID-like syndrome, we believe this offers a crucial insight into Long COVID aetiology [7][8][9]11]. Supporting this, and in line with evidence presented above for Long COVID, several cases have been reported of post-COVID-19 vaccine retinal vascular occlusion (summarised in [160]), attributed to Susac syndrome (an autoimmune endotheliopathy) and microthrombi, with potential links to hyperviscosity syndrome.…”

Section: Co-pathologiesmentioning

confidence: 97%

“…For many patients, several of these pathologies may co-exist and interact. Current ideas include mast cell activation syndrome (MCAS), neuroinflammation, viral reactivation, SARS-CoV-2 and/or spike protein persistence, autoimmunity, and gut dysbiosis [9,79]. An increasingly recognised pathology is related to microclots, platelet hyperactivation, and endothelial dysfunction [36,40,43,[80][81][82].…”

Section: Long Covid As a Coagulopathymentioning

confidence: 99%

“…The sympathetic and parasympathetic fibres innervate the muscle layer of vessels, whereas only parasympathetic fibres innervate the endothelial layer, making parasympathetic fibres more susceptible to the consequences of endothelial inflammation [32]. Nerve ischaemia has been proposed as an aetiology [9]. Resultant dysautonomia, where sympathetic function predominates, which is found in a moderate to severe range in two thirds of Long COVID patients, is independent of initial infection severity [32,141] and is associated with exercise intolerance [142].…”

Section: Co-pathologiesmentioning

confidence: 99%

“…Increased cases of POTS have been observed after SARS-CoV-2 infection and (five times less frequently) vaccination [143,159].There is increasing recognition that Long COVID symptoms, diagnoses, and pathophysiology can also be triggered after SARS-CoV-2 vaccination in some patients [7,8,10,11] where spike protein persistence has been implicated [7][8][9]. With the same illnesses occurring after vaccination and infection, some have suggested spike protein (rather than whole virus) persistence can drive Long COVID and POTS pathology [7][8][9]11,143]. At a population level, the net benefits of vaccination against COVID-19 have been clearly established.…”

Section: Co-pathologiesmentioning

confidence: 99%

“…Long COVID is estimated to affect > 200 million people globally; the majority being from those considered "mild" cases [3,4], and nearly a third from asymptomatic infection [5,6]. Long COVID-like presentations have also been described after SARS-CoV-2 vaccination [7][8][9][10][11]. The average Long COVID sufferer experiences 56 symptoms across nine body systems [1], with fatigue, cognitive dysfunction, dyspnoea, exercise intolerance, post-exertional symptom exacerbation (PESE), sleep disorders, and myalgia being most common [1,3,[12][13][14].…”

Section: Introductionmentioning

confidence: 99%

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Long COVID is primarily a Spike protein Induced Thrombotic Vasculitis

Carroll

2023

Preprint

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Long COVID describes an array of often debilitating symptoms in the aftermath of SARS-CoV-2 infection, with similar symptomatology affecting some people post-vaccination. With an estimated > 200 million Long COVID patients worldwide and cases still rising, the effects on quality of life and the economy are significant, thus warranting urgent attention to understand the pathophysiology. Herein we describe our perspective that Long COVID is a continuation of acute COVID-19 pathology, whereby coagulopathy is the main driver of disease and can cause or exacerbate other pathologies common in Long COVID, such as mast cell activation syndrome and dysautonomia. Considering the SARS-CoV-2 spike protein can independently induce fibrinaloid microclots, platelet activation, and endotheliitis, we predict that persistent spike protein will be a key mechanism driving the continued coagulopathy in Long COVID. We discuss several treatment targets to address the coagulopathy, and predict that (particularly early) treatment with combination anticoagulant and antiplatelet drugs will bring significant relief to many patients, supported by a case study. To help focus attention on such treatment targets, we propose Long COVID should be referred to as Spike protein Induced Thrombotic Vasculitis (SITV). These ideas require urgent testing, especially as the world tries to co-exist with COVID-19.

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Section: Co-pathologiesmentioning

confidence: 97%

Section: Long Covid As a Coagulopathymentioning

confidence: 99%

Section: Co-pathologiesmentioning

confidence: 99%

Section: Co-pathologiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Long COVID is primarily a Spike protein Induced Thrombotic Vasculitis

Carroll

2023

Preprint

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Unraveling the enigma of long COVID: novel aspects in pathogenesis, diagnosis, and treatment protocols

Baig,

Rosko,

Jaeger

et al. 2024

Inflammopharmacol

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The Oral-Vascular-Pulmonary Infection Route: a Pathogenic Mechanism Linking Oral Health Status to Acute and Post-Acute COVID-19

Lloyd-Jones,

Pontes,

Molayem

et al. 2023

Curr Oral Health Rep

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Purpose of Review In recent years, much attention has focused on the role of poor oral health in the development or worsening of systemic diseases, including COVID-19. The mouth is an important site of cellular infection early in the disease course of COVID-19. We review how oral pathology, and specifically viral infection within the oral cavity, may mediate the disease severity and duration of COVID-19. In particular, the previously reported model of SARS-CoV-2 vascular delivery from the mouth to the lungs via the bloodstream is revisited. Recent Findings We previously proposed that an oral-vascular-pulmonary route of infection could facilitate severe lung disease in COVID-19. This pathway could also explain the vital link between periodontitis and COVID-19 severity, including higher mortality risk. This model of pathogenesis is reconsidered in light of recent findings regarding the involvement of the mouth as a viral reservoir, and pathological processes in the blood, pulmonary vasculature, and elsewhere in the body. Oral dysbiosis in COVID-19 and the effect of oral hygiene in mitigating disease severity are discussed. The evidence for viral persistence in the mouth and intravascular viral passage from the mouth to the rest of the body via blood is also discussed in the context of post-acute COVID (long COVID). Summary High viral load in the mouth and poor oral health status are associated with COVID-19 disease severity, increasing the risk of death. Pathophysiological links between viral activity in the mouth, oral health status, and disease outcome in the lungs and blood provide a rationale for further evaluation of the oral-vascular-systemic pathway in patients with acute COVID-19 and long COVID. The potential benefits of oral hygiene protocols and periodontal procedures in COVID-19 also warrant further investigation.

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Long COVID: pathophysiological factors and abnormalities of coagulation

Cited by 65 publications

References 213 publications

Long COVID is primarily a Spike protein Induced Thrombotic Vasculitis

Long COVID is primarily a Spike protein Induced Thrombotic Vasculitis

Unraveling the enigma of long COVID: novel aspects in pathogenesis, diagnosis, and treatment protocols

The Oral-Vascular-Pulmonary Infection Route: a Pathogenic Mechanism Linking Oral Health Status to Acute and Post-Acute COVID-19

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