Evidence of SARS-CoV-2 spike protein on retrieved thrombi from COVID-19 patients

Michele, Manuela De; d’Amati, Giulia; Leopizzi, Martina; Iacobucci, Marta; Berto, Irene; Lorenzano, Svetlana; Mazzuti, Laura; Turriziani, Ombretta; Schiavo, Oscar G.; Toni, Danilo

doi:10.1186/s13045-022-01329-w

Cited by 20 publications

(21 citation statements)

References 11 publications

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“…Although SARS-CoV-2 proteins are synthesized in the cytosol, some viral proteins are also detectable in the nucleus, including Nsp1, Nsp5, Nsp9, Nsp13, Nsp14, and Nsp16 [ 71 ]. This becomes important as recent research has shown that the S protein also localizes in the nucleus and inhibits DNA damage repair by impeding key DNA repair protein BRCA1, and recruitment of 53BP1 to the damage site [ 72 ].…”

Section: Resultsmentioning

confidence: 99%

Recent Developments in the Understanding of Immunity, Pathogenesis and Management of COVID-19

Yegiazaryan

Abnousian

Alexander

et al. 2022

IJMS

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Coronaviruses represent a diverse family of enveloped positive-sense single stranded RNA viruses. COVID-19, caused by Severe Acute Respiratory Syndrome Coronavirus-2, is a highly contagious respiratory disease transmissible mainly via close contact and respiratory droplets which can result in severe, life-threatening respiratory pathologies. It is understood that glutathione, a naturally occurring antioxidant known for its role in immune response and cellular detoxification, is the target of various proinflammatory cytokines and transcription factors resulting in the infection, replication, and production of reactive oxygen species. This leads to more severe symptoms of COVID-19 and increased susceptibility to other illnesses such as tuberculosis. The emergence of vaccines against COVID-19, usage of monoclonal antibodies as treatments for infection, and implementation of pharmaceutical drugs have been effective methods for preventing and treating symptoms. However, with the mutating nature of the virus, other treatment modalities have been in research. With its role in antiviral defense and immune response, glutathione has been heavily explored in regard to COVID-19. Glutathione has demonstrated protective effects on inflammation and downregulation of reactive oxygen species, thereby resulting in less severe symptoms of COVID-19 infection and warranting the discussion of glutathione as a treatment mechanism.

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Section: Resultsmentioning

confidence: 99%

Recent Developments in the Understanding of Immunity, Pathogenesis and Management of COVID-19

Yegiazaryan

Abnousian

Alexander

et al. 2022

IJMS

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“…Interestingly, we recently described SP in a retrieved thrombus from MCA of one of the two AIS patients with COVID-19 having detectable serum SP level ( 9 ).…”

Section: Discussionmentioning

confidence: 99%

“…We recently detected the SP, but not the nucleocapsid protein (NP) or the SARS-CoV-2 RNA, in thrombi retrieved from the middle cerebral artery (MCA) of three COVID-19 patients with large vessel occlusion related acute ischemic stroke (AIS) and in a thrombus retrieved from the coronary artery of a COVID-19 positive patient with acute myocardial infarction, supporting a potential role of sSP, independently of the whole virus, in clot formation ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 infection predicts larger infarct volume in patients with acute ischemic stroke

Michele

Lorenzano

Rivabene

et al. 2023

Front. Cardiovasc. Med.

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Background and purposeAcute ischemic stroke (AIS) is a fearful complication of Coronavirus Disease-2019 (COVID-19). Aims of this study were to compare clinical/radiological characteristics, endothelial and coagulation dysfunction between acute ischemic stroke (AIS) patients with and without COVID-19 and to investigate if and how the SARS-CoV-2 spike protein (SP) was implicated in triggering platelet activation.MethodsWe enrolled AIS patients with COVID-19 within 12 h from onset and compared them with an age- and sex-matched cohort of AIS controls without COVID-19. Neuroimaging studies were performed within 24 h. Blood samples were collected in a subset of 10 patients.ResultsOf 39 AIS patients, 22 had COVID-19 and 17 did not. Admission levels of Factor VIII and von Willebrand factor antigen were significantly higher in COVID-19 patients and positively correlated with the infarct volume. In multivariate linear regression analyses, COVID-19 was an independent predictor of infarct volume (B 20.318, Beta 0.576, 95%CI 6.077–34.559; p = 0.011). SP was found in serum of 2 of the 10 examined COVID-19 patients. Platelets from healthy donors showed a similar degree of procoagulant activation induced by COVID-19 and non-COVID-19 patients' sera. The anti-SP and anti-FcγRIIA blocking antibodies had no effect in modulating platelet activity in both groups.ConclusionsSARS-CoV-2 infection seems to play a major role in endothelium activation and infarct volume extension during AIS.

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“…There are three major system biology findings of COVID-19 that need to be explained by molecular events. Vascular clots, particular micro clots in pulmonary vessels [23,24], enlarged arteries with echogenic, probably thickened-colloidal, blood flow [25] and a histochemical finding of SARS-CoV-2 virions, or at least Spike protein, can be found at the core of the thrombi [24,26].…”

Section: Covid-19 Vascular Pathologiesmentioning

confidence: 99%

The COVID-19 antibody responses, isotypes and glycosylation: Why SARS-CoV-2 Spike protein complex binding of IgG3 is potentiated in some and immuno-pathologies manifest

Iles¹

2023

Preprint

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COVID-19 syndrome does not occur in all who are infected with SARS-CoV-2, and symptoms vary. The anti-SARS CoV-2 Spike immune responses is confounded by the Spike proteins ability to bind Igγ3 heavy chains. This appears to be via sialic acid glycans found on the O-Linked glycosylation moieties of this heavy chain extended neck domain. Furthermore glycosylation of light chains, particularly Kappa (κ), is an associated feature of antibodies binding to SARS-CoV-2 antigens nucleocapsid and Spike protein. COVID-19 recovered patients had increased IgG1 and IgM levels and un-glycosylated κ λ light chains; possibly In order to counter this immune system subjugation of IgG3. These molecular finding, together with our previous finding that Spike protein binds glycated human serum albumin (HSA), may explain the micro-vascular inflammatory clots that are a causative feature of COVID-19 acute respiratory syndrome (ARDS). The postulated molecular sequelae are that SARS-CoV-2 virion, entering the blood circulation, being coated with IgG3 and glycated HSA forms a colloid and deposits into micro-focal clots which are also inflammatory. It is not that all IgG3 and albumin is being bound by the virus; this depends on the affinity the SARS-CoV2 virion has for binding an individual IgG3 and albumin due to glycosylation and glycation status. The degree of glycosylation and terminal sialyation of an individuals antibodies is both a genetic and age-maturity dependant feature of the immune system. The degree of HSA glycation is also age related feature particularly related to type 2 diabetes. Thereby establishing the molecular basis of the association of severe COVID-19 disease syndrome and deaths with diabetes, metabolic disorders, and old age. Furthermore, already having cardiovascular disease, with hardened arteries, SARS-CoV2-glycated HSA-IgG3 deposition is going to exacerbate an already compromised circulatory physiology. The binding of IgG3 might also drives a shift in the immune repertoire response to SAR-CoV-2 anti-spike antibodies of increased IgG1 and prolonged IgM levels. This may be associated with Long Covid. In summary, SARS-CoV-2 Spike protein binding of IgG3, via sialic acid glycan residues, along with increased glycosylated κ-light chains and glycated-HSA may form a focal amyloid-like precipitate within blood vessels which in turn leads to the inflammatory micro-thrombosis characteristic of COVID-19 immuno-pathology.

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Evidence of SARS-CoV-2 spike protein on retrieved thrombi from COVID-19 patients

Cited by 20 publications

References 11 publications

Recent Developments in the Understanding of Immunity, Pathogenesis and Management of COVID-19

Recent Developments in the Understanding of Immunity, Pathogenesis and Management of COVID-19

SARS-CoV-2 infection predicts larger infarct volume in patients with acute ischemic stroke

The COVID-19 antibody responses, isotypes and glycosylation: Why SARS-CoV-2 Spike protein complex binding of IgG3 is potentiated in some and immuno-pathologies manifest

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