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1.
J Hematol Oncol ; 15(1): 108, 2022 Aug 16.
Article in English | MEDLINE | ID: covidwho-1993373

ABSTRACT

The pathophysiology of COVID-19-associated coagulopathy is complex and not fully understood. SARS-CoV-2 spike protein (SP) may activate platelets and interact with fibrin(ogen). We aimed to investigate whether isolated SP can be present in clots retrieved in COVID-19 patients with acute ischemic stroke (by mechanical thrombectomy) and myocardial infarction. In this pilot study, we could detect SP, but not nucleocapsid protein, on platelets of COVID-19 patients' thrombi. In addition, in all three COVID-19 thrombi analyzed for molecular biology, no SARS-CoV-2 RNA could be detected by real-time polymerase chain reaction. These data could support the hypothesis that free SP, besides the whole virus, may be the trigger of platelet activation and clot formation in COVID-19.


Subject(s)
COVID-19 , Ischemic Stroke , Thrombosis , COVID-19/complications , Humans , Pilot Projects , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Thrombosis/etiology , Thrombosis/metabolism
3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335499

ABSTRACT

The pathophysiology of COVID-19-associated coagulopathy is complex and not fully understood. SARS-CoV-2 spike protein (SP) may activate platelets and interacts with fibrin(ogen). We aimed to investigate the possible evidence of isolated SP in clots retrieved in COVID-19 patients with acute ischemic stroke (by mechanical thrombectomy) and myocardial infarction. In this pilot study we could detect SP, but not nucleocapsid protein, on platelets of COVID-19 + patients’ thrombi. In addition, in all the three COVID-19 + thrombi analyzed for molecular biology, no SARS-CoV-2 RNA could be detected by real time-polymerase chain reaction. These data confirm the hypothesis that free SP besides the whole virus, may be the trigger of platelet activation and clot formation in COVID-19.

4.
Circ Res ; 130(8): 1187-1203, 2022 04 15.
Article in English | MEDLINE | ID: covidwho-1789065

ABSTRACT

The risk of stroke and cerebrovascular disease complicating infection with SARS-CoV-2 has been extensively reported since the onset of the pandemic. The striking efforts of many scientists in cooperation with regulators and governments worldwide have rapidly brought the development of a large landscape of vaccines against SARS-CoV-2. The novel DNA and mRNA vaccines have offered great flexibility in terms of antigen production and led to an unprecedented rapidity in effective and safe vaccine production. However, as mass vaccination has progressed, rare but catastrophic cases of thrombosis have occurred in association with thrombocytopenia and antibodies against PF4 (platelet factor 4). This catastrophic syndrome has been named vaccine-induced immune thrombotic thrombocytopenia. Rarely, ischemic stroke can be the symptom onset of vaccine-induced immune thrombotic thrombocytopenia or can complicate the course of the disease. In this review, we provide an overview of stroke and cerebrovascular disease as a complication of the SARS-CoV-2 infection and outline the main clinical and radiological characteristics of cerebrovascular complications of vaccinations, with a focus on vaccine-induced immune thrombotic thrombocytopenia. Based on the available data from the literature and from our experience, we propose a therapeutic protocol to manage this challenging condition. Finally, we highlight the overlapping pathophysiologic mechanisms of SARS-CoV-2 infection and vaccination leading to thrombosis.


Subject(s)
COVID-19 , Stroke , Thrombocytopenia , Thrombosis , Vaccines , COVID-19/complications , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Platelet Factor 4/adverse effects , SARS-CoV-2 , Stroke/epidemiology , Stroke/etiology , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnosis , Thrombosis/etiology , Vaccination/adverse effects , Vaccines/adverse effects
5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-309242

ABSTRACT

Background: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare syndrome of unclear aetiology occurring after DNA-based vaccinations against COVID-19. The aim of this study was to investigate the DNA vaccine-encoded Sars-cov-2 soluble spike protein (SP). as a potential trigger of platelet activation in VITT. Methods. We studied three VITT patients and seven healthy controls (HCs) within 3 weeks from the first dose of ChAdOx1 nCoV-19, and one non vaccinated HC. Serum levels of SP and soluble angiotensin-converting enzyme 2 (sACE2), ACE2 expression in platelets and platelet response to VITT serum stimulation were studied. A thrombus retrieved during mechanical thrombectomy from one VITT patients, was analysed by immunohistochemistry for SP and ACE2. Neutrophil extracellular traps (NETs) markers and coagulation parameters were also measured. Results. We detected serum SP (up to 35 days post-vaccination) and sACE2 in all VITT patients, and respectively in two and three out of 7 vaccinated HCs. Only platelets from one non-vaccinated HC expressed ACE2. VITT sera markedly activated platelets and this activation was inhibited by both anti-SP and anti-FcγRIIA blocking antibodies. The thrombus showed positive immunohistochemical labelling of platelets using an anti-SP antibody with reduced ACE2 expression, compared to a thrombus from a pre-pandemic stroke patient. Markers of endothelial dysfunction, NETs and hypercoagulability state were present in all VITT sera. Conclusions. The present data provides first evidence that DNA vaccine-encoded Sars-cov-2 SP is detectable in VITT sera (several weeks post-vaccination) and in a platelet-rich thrombus, and that may contribute to the initial platelet stimulation in VITT patients.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-309241

ABSTRACT

Vaccine induced thrombotic thrombocytopenia is a new syndrome recently described in young adults within two weeks from the first dose of the ChAdOx1 nCoV-19 vaccine and characterized by cerebral venous thrombosis. We report two cases of malignant middle cerebral artery (MCA) infarct and thrombocytopenia within 10 days after vaccination with ChAdOx1 nCoV-19. Patient 1 was a 57-year-old woman who underwent decompressive craniectomy despite two successful mechanical thrombectomies. Patient 2 was a 55-year-old woman who developed a fatal bilateral malignant MCA infarct. Both the patients had pulmonary and portal vein thrombosis and high level of antibodies to platelet factor 4-polyanion complexes.

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