Covid-19 Delta variant resulting in multi system thromboembolic disease

Fluss, Gabriella; Cranwell, Victoria; Rao, Ajit; Lee, Joon Sub; Elshafey, Ramy; Wallack, Marc K.; Finlay, David

doi:10.1016/j.avsurg.2022.100101

Cited by 4 publications

(3 citation statements)

References 21 publications

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“…4 G to I) induced by the κ and δ variants, which was greatest in the κ variant. Together, these data indicate that the κ and δ variants induce stronger platelet activation, which is consistent with clinical reports of severe thrombosis in patients infected with these variants [ 11 , 63 , 64 ].…”

Section: Resultssupporting

confidence: 90%

SARS-CoV-2 RBD and Its Variants Can Induce Platelet Activation and Clearance: Implications for Antibody Therapy and Vaccinations against COVID-19

Ma¹,

Liang²,

Zhu³

et al. 2023

Research

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The COVID-19 pandemic caused by SARS-CoV-2 virus is an ongoing global health burden. Severe cases of COVID-19 and the rare cases of COVID-19 vaccine-induced-thrombotic-thrombocytopenia (VITT) are both associated with thrombosis and thrombocytopenia; however, the underlying mechanisms remain inadequately understood. Both infection and vaccination utilize the spike protein receptor-binding domain (RBD) of SARS-CoV-2. We found that intravenous injection of recombinant RBD caused significant platelet clearance in mice. Further investigation revealed the RBD could bind platelets, cause platelet activation, and potentiate platelet aggregation, which was exacerbated in the Delta and Kappa variants. The RBD–platelet interaction was partially dependent on the β3 integrin as binding was significantly reduced in β3 −/− mice. Furthermore, RBD binding to human and mouse platelets was significantly reduced with related αIIbβ3 antagonists and mutation of the RGD (arginine-glycine-aspartate) integrin binding motif to RGE (arginine-glycine-glutamate). We developed anti-RBD polyclonal and several monoclonal antibodies (mAbs) and identified 4F2 and 4H12 for their potent dual inhibition of RBD-induced platelet activation, aggregation, and clearance in vivo, and SARS-CoV-2 infection and replication in Vero E6 cells. Our data show that the RBD can bind platelets partially though αIIbβ3 and induce platelet activation and clearance, which may contribute to thrombosis and thrombocytopenia observed in COVID-19 and VITT. Our newly developed mAbs 4F2 and 4H12 have potential not only for diagnosis of SARS-CoV-2 virus antigen but also importantly for therapy against COVID-19.

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Section: Resultssupporting

confidence: 90%

SARS-CoV-2 RBD and Its Variants Can Induce Platelet Activation and Clearance: Implications for Antibody Therapy and Vaccinations against COVID-19

Ma¹,

Liang²,

Zhu³

et al. 2023

Research

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“…In addition, the mutated SARS‐CoV‐2 virus also has the risk of causing kidney injury. Gabriella reported a case of a Covid‐19 Delta variant positive patient with diffuse thromboembolic disease, including right renal artery thrombosis 112 . The COVID‐19 vaccine has a certain protective effect on infection with SARS‐CoV‐2 mutant strains, and it was observed that four doses of mRNA vaccine can improve the neutralization effect of Delta mutant strains 113 .…”

Section: Clinical Manifestations Of Covid‐19‐associated Kidney Injurymentioning

confidence: 99%

“…Gabriella reported a case of a Covid-19 Delta variant positive patient with diffuse thromboembolic disease, including right renal artery thrombosis. 112 The COVID-19 vaccine has a certain protective effect on infection with SARS-CoV-2 mutant strains, and it was observed that four doses of mRNA vaccine can improve the neutralization effect of Delta mutant strains. 113 and IgG, form immune complexes, and deposit in glomeruli 125 ; SARS-CoV-2 spike protein acts as a superantigen to stimulate T cell activation and the production of inflammatory mediators, 126 mesangiolysis with loss of mesangial cells.…”

Section: Coagulation Abnormalitiesmentioning

confidence: 99%

Pathogenesis and histological changes of nephropathy associated with COVID‐19

Deng

et al. 2022

Journal of Medical Virology

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Coronavirus disease 2019 (COVID‐19) can cause damage to multiple organ, not only to the lungs, but also to the kidneys. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) can cause acute and chronic kidney disease through direct viral infection, indirect injury, and vaccination‐related injury. Like lung injury, kidney injury is also an important aspect affecting the severity and prognosis of SARS‐CoV‐2. This article summarizes the pathogenesis, pathological manifestations, and clinical features of SARS‐CoV‐2 direct or indirect renal injury. Including direct injury, indirect injury, special comorbidities (receiving kidney transplantation and chronic kidney disease), and vaccine‐related renal injury, and exploring the possible therapeutic effect of anti‐SARS‐CoV‐2 therapy on renal injury. The purpose is to provide reference for understanding COVID‐19‐related renal injury, guiding clinical and pathological diagnosis and treatment, and evaluating prognosis.

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Aspirin/enoxaparin sodium/heparin

2023

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Covid-19 Delta variant resulting in multi system thromboembolic disease

Cited by 4 publications

References 21 publications

SARS-CoV-2 RBD and Its Variants Can Induce Platelet Activation and Clearance: Implications for Antibody Therapy and Vaccinations against COVID-19

SARS-CoV-2 RBD and Its Variants Can Induce Platelet Activation and Clearance: Implications for Antibody Therapy and Vaccinations against COVID-19

Pathogenesis and histological changes of nephropathy associated with COVID‐19

Aspirin/enoxaparin sodium/heparin

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