Interactions of Spike-RBD of SARS-CoV-2 and Platelet Factor 4: New Insights in the Etiopathogenesis of Thrombosis

Passariello, Margherita; Vetrei, Cinzia; Amato, Felice; Lorenzo, Claudia De

doi:10.3390/ijms22168562

Cited by 22 publications

(21 citation statements)

References 21 publications

(53 reference statements)

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“…In COVID-19, platelets are usually activated without thrombocytopenia similar to local thromboses such as acute coronary syndrome [18] or acute cerebral infarction [19]. We speculate the spike protein-induced platelet activation via the angiotensin converting enzyme 2 play a role [30]. In this scenario, thrombosis may attribute platelet factor 4, von Willebrand factor, and other substances released from platelets [31].…”

Section: Discussionmentioning

confidence: 98%

Elevated Plasma Soluble C-Type Lectin-like Receptor 2 Is Associated with the Worsening of Coronavirus Disease 2019

Wada

Ichikawa

Ezaki

et al. 2022

JCM

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Although thrombosis in coronavirus disease 2019 (COVID-19) infection has attracted attention, the mechanism underlying its development remains unclear. The relationship between platelet activation and the severity of COVID-19 infection was compared with that involving other infections. Plasma soluble C-type lectin-like receptor 2 (sCLEC-2) levels were measured in 46 patients with COVID-19 infection and in 127 patients with other infections. The plasma sCLEC-2 levels in patients with COVID-19 infection {median (25th, 75th percentile), 489 (355, 668) ng/L} were significantly higher (p < 0.001) in comparison to patients suffering from other pneumonia {276 (183, 459) ng/L}, and the plasma sCLEC-2 levels of COVID-19 patients with severe {641 (406, 781) ng/L} or critical illness {776 (627, 860) ng/L} were significantly higher (p < 0.01, respectively) in comparison to those with mild illness {375 (278, 484) ng/L}. The ratio of the sCLEC-2 levels to platelets in COVID-19 patients with critical illness of infection was significantly higher (p < 0.01, p < 0.001 and p < 0.05, respectively) in comparison to COVID-19 patients with mild, moderate or severe illness. Plasma sCLEC-2 levels were significantly higher in patients with COVID-19 infection than in those with other infections, suggesting that platelet activation is triggered and facilitated by COVID-19 infection.

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Section: Discussionmentioning

confidence: 98%

Elevated Plasma Soluble C-Type Lectin-like Receptor 2 Is Associated with the Worsening of Coronavirus Disease 2019

Wada

Ichikawa

Ezaki

et al. 2022

JCM

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“…These antibodies against seasonal CoV such as OC43 and HKU1 are attributed to mitigate deterioration of COVID-19 [23,24]. If antibodies against the spike domain of seasonal HcoV contribute to the pathogenesis of VITT needs to be further evaluated [25]. We conclude that testing of any SARS-CoV-2 antibodies should be performed from a blood sample obtained before IVIG administration to avoid misinterpretations.…”

Section: Discussionmentioning

confidence: 98%

Complicated Long Term Vaccine Induced Thrombotic Immune Thrombocytopenia—A Case Report

et al. 2021

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Background and Objectives: Vaccine induced thrombotic thrombocytopenia (VITT) may occur after COVID-19 vaccination with recombinant adenoviral vector-based vaccines. VITT can present as cerebral sinus and venous thrombosis (CSVT), often complicated by intracranial hemorrhage. Today it is unclear, how long symptomatic VITT can persist. Here, we report the complicated long-term course of a VITT patient with extremely high titers of pathogenic anti-platelet factor 4 (PF4)-IgG antibodies. Methods: Clinical and laboratory findings are presented, including the course of platelet counts, D-Dimer levels, clinical presentation, imaging, SARS-CoV-2-serological and immunological, platelet activating anti-PF4-IgG, as well as autopsy findings. Results: The patient presented with extended superior sagittal sinus thrombosis with accompanying bifrontal intracerebral hemorrhage. Repeated treatment with intravenous immune globuline (IVIG) resolved recurrent episodes of thrombocytopenia. Moreover, the patient’s serum remained strongly positive for platelet-activating anti-PF4-IgG over three months. After a period of clinical stabilization, the patient suffered a recurrent and fatal intracranial hemorrhage. Conclusions: Complicated VITT with extremely high anti-PF4-IgG titers over three months can induce recurrent thrombocytopenia despite treatment with IVIG and anticoagulation. Plasma exchange, immunoadsorption, and /or immunosuppressive treatment may be considered in complicated VITT to reduce extraordinarily high levels of anti-PF4-IgG. Long-term therapy in such cases must take the individual bleeding risk and CSVT risk into account.

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“…One can hypothesize that IgG complexed with the spike protein and PF4 is the complex that induces VITT in response to mRNA vaccines. It has in fact been shown experimentally that the receptor binding domain (RBD) of the spike protein binds to PF4 [157].…”

Section: Immune Thrombocytopeniamentioning

confidence: 99%

Innate Immune Suppression by SARS-CoV-2 mRNA Vaccinations: The role of G-quadruplexes, exosomes and microRNAs

Seneff

Nigh

Kyriakopoulos³

et al. 2022

Preprint

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The mRNA SARS-CoV-2 vaccines were brought to market in response to the widely perceived public health crises of Covid-19. The utilization of mRNA vaccines in the context of infectious disease had no precedent, but desperate times seemed to call for desperate measures. The mRNA vaccines utilize genetically modified mRNA encoding spike proteins. These alterations hide the mRNA from cellular defenses, promote a longer biological half-life for the proteins, and provoke higher overall spike protein production. However, both experimental and observational evidence reveals a very different immune response to the vaccines compared to the response to infection with SARS-CoV-2. As we will show, the genetic modifications introduced by the vaccine are likely the source of these differential responses. In this paper, we present the evidence that vaccination, unlike natural infection, induces a profound impairment in type I interferon signaling, which has diverse adverse consequences to human health. We explain the mechanism by which immune cells release into the circulation large quantities of exosomes containing spike protein along with critical microRNAs that induce a signaling response in recipient cells at distant sites. We also identify potential profound disturbances in regulatory control of protein synthesis and cancer surveillance. These disturbances are shown to have a potentially direct causal link to neurodegenerative disease, myocarditis, immune thrombocytopenia, Bell’s palsy, liver disease, impaired adaptive immunity, increased tumorigenesis, and DNA damage. We show evidence from adverse event reports in the VAERS database supporting our hypothesis. We believe a comprehensive risk/benefit assessment of the mRNA vaccines excludes them as positive contributors to public health, even in the context of the Covid-19 pandemic.

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Interactions of Spike-RBD of SARS-CoV-2 and Platelet Factor 4: New Insights in the Etiopathogenesis of Thrombosis

Cited by 22 publications

References 21 publications

Elevated Plasma Soluble C-Type Lectin-like Receptor 2 Is Associated with the Worsening of Coronavirus Disease 2019

Elevated Plasma Soluble C-Type Lectin-like Receptor 2 Is Associated with the Worsening of Coronavirus Disease 2019

Complicated Long Term Vaccine Induced Thrombotic Immune Thrombocytopenia—A Case Report

Innate Immune Suppression by SARS-CoV-2 mRNA Vaccinations: The role of G-quadruplexes, exosomes and microRNAs

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