Clinical, laboratory and immunohistochemical characterization of in situ pulmonary arterial thrombosis in fatal COVID-19

Quartuccio, Luca; Sonaglia, Arianna; Casarotto, Letizia; McGonagle, Dennis; Loreto, Carla Di; Pegolo, Enrico

doi:10.1016/j.thromres.2022.09.012

Cited by 6 publications

(8 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…46 47 The demonstration that the recombinant spike protein of SARS-CoV-2 is capable per se to bind to the blood platelets and trigger their aggregation provides an important biological support to real-world evidence garnered from postmortem studies, where it was evidenced that extensive pulmonary thrombosis in COVID-19 is characterized by thrombi mostly composed of platelets and fibrin. 48 The presence of a large number of circulating platelet aggregates has also been reported in nearly 90% of patients with symptomatic SARS-CoV-2 infection, and the number of such aggregates is directly associated with clinical severity, pulmonary failure, and risk of death. 49 A deep understanding of the role played by the platelets in patients with SARS-CoV-2 infection, along with their active participation to enhance the risk of developing thrombotic episodes, has paramount therapeutic implications, especially concerning the possibility to add antiplatelet therapies to the standard anticoagulant regimen in COVID-19 patients with more severe illness.…”

Section: Discussionmentioning

confidence: 99%

Effects of Recombinant SARS-CoV-2 Spike Protein Variants on Platelet Morphology and Activation

Vettori

Carpenè

Salvagno

et al. 2023

Semin Thromb Hemost

View full text Add to dashboard Cite

Platelets are central elements of hemostasis and also play a pivotal role in the pathogenesis of thrombosis in coronavirus disease 2019. This study was planned to investigate the effects of different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recombinant spike protein variants on platelet morphology and activation. Citrated whole blood collected from ostensibly healthy subjects was challenged with saline (control sample) and with 2 and 20 ng/mL final concentration of SARS-CoV-2 recombinant spike protein of Ancestral, Alpha, Delta, and Omicron variants. Platelet count was found to be decreased with all SARS-CoV-2 recombinant spike protein variants and concentrations tested, achieving the lowest values with 20 ng/mL Delta recombinant spike protein. The mean platelet volume increased in all samples irrespective of SARS-CoV-2 recombinant spike protein variants and concentrations tested, but especially using Delta and Alpha recombinant spike proteins. The values of both platelet function analyzer-200 collagen-adenosine diphosphate and collagen-epinephrine increased in all samples irrespective of SARS-CoV-2 recombinant spike protein variants and concentrations tested, and thus reflecting platelet exhaustion, and displaying again higher increases with Delta and Alpha recombinant spike proteins. Most samples where SARS-CoV-2 recombinant spike proteins were added were flagged as containing platelet clumps. Morphological analysis revealed the presence of a considerable number of activated platelets, platelet clumps, platelet-monocyte, and platelet-neutrophils aggregates, especially in samples spiked with Alpha and Delta recombinant spike proteins at 20 ng/mL. These results provide support to the evidence that SARS-CoV-2 is capable of activating platelets through its spike protein, though such effect varies depending on different spike protein variants.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of Recombinant SARS-CoV-2 Spike Protein Variants on Platelet Morphology and Activation

Vettori

Carpenè

Salvagno

et al. 2023

Semin Thromb Hemost

View full text Add to dashboard Cite

show abstract

“…Nonpulmonary in situ thrombosis in the right ventricle was also described in COVID-19 patients [ 14 , 15 ]. COVID-19-associated pulmonary intravascular coagulopathy is a complex disease “orchestrated” by a severe and dysregulated proinflammatory response that can lead to immunothrombosis [ 2 , 16 ]. The prothrombotic state in patients with COVID-19 is reminiscent of this immunothrombosis process, a result of the crosstalk between the immune and hemostatic systems and characterized by the production of microthrombi in small capillaries, in which endothelial cells (ECs) adopt a proadhesive phenotype in contact with SARS-CoV-2 [ 17 , 18 , 19 ].…”

Section: Covid-19-associated Pulmonary Thrombosis Is An In Situ Immun...mentioning

confidence: 99%

“…In patients with in situ pulmonary thrombosis, in-depth immune pathology analysis by immunohistochemistry supports the inflammatory nature of arterial thrombi composed of white blood cells, especially neutrophils, CD 3 + and CD 20 + lymphocytes, fibrin, red blood cells, and platelets, but not megakaryocytes [ 16 ]. Regional thrombosis of the lung microvasculature also showed compressed deformed red blood cells (RBCs), including polyhedrocytes and different morphological types of fibrin structures coated with sparse spherical microparticles, which could comprise virions or cellular ectosomes [ 15 ].…”

Section: Covid-19-associated Pulmonary Thrombosis Is An In Situ Immun...mentioning

confidence: 99%

“…Thrombocytopathy, abnormal hyper-reactivity phenotypes, and significantly elevated levels of platelet adhesion and activation mediators contribute to immunothrombi, especially in severe and critical SARS-CoV-2 infection [ 2 , 4 , 11 , 16 , 19 , 94 , 95 , 96 , 97 , 100 , 101 , 102 , 103 , 104 , 105 , 113 , 114 , 115 , 127 ].…”

Section: Figurementioning

confidence: 99%

“…Functional, ultrastructure changes of RBCs and eryptosis contribute to thrombotic diathesis [ 11 , 15 , 16 , 19 , 43 , 93 , 143 ].…”

Section: Figurementioning

confidence: 99%

See 2 more Smart Citations

Mechanisms of COVID-19 Associated Pulmonary Thrombosis: A Narrative Review

2023

View full text Add to dashboard Cite

COVID-19, the infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is frequently associated with pulmonary thrombotic events, especially in hospitalized patients. Severe SARS-CoV-2 infection is characterized by a proinflammatory state and an associated disbalance in hemostasis. Immune pathology analysis supports the inflammatory nature of pulmonary arterial thrombi composed of white blood cells, especially neutrophils, CD3+ and CD20+ lymphocytes, fibrin, red blood cells, and platelets. Immune cells, cytokines, chemokines, and the complement system are key drivers of immunothrombosis, as they induce the damage of endothelial cells and initiate proinflammatory and procoagulant positive feedback loops. Neutrophil extracellular traps induced by COVID-19-associated “cytokine storm”, platelets, red blood cells, and coagulation pathways close the inflammation–endotheliopathy–thrombosis axis, contributing to SARS-CoV-2-associated pulmonary thrombotic events. The hypothesis of immunothrombosis is also supported by the minor role of venous thromboembolism with chest CT imaging data showing peripheral blood clots associated with inflammatory lesions and the high incidence of thrombotic events despite routine thromboprophylaxis. Understanding the complex mechanisms behind COVID-19-induced pulmonary thrombosis will lead to future combination therapies for hospitalized patients with severe disease that would target the crossroads of inflammatory and coagulation pathways.

show abstract

CXCL10 May Be Responsible for Susceptibility to Pulmonary Embolism in COVID-19 Patients

Liu,

Si,

Bai

et al. 2023

JIR

View full text Add to dashboard Cite

Background Although the potential of coronavirus disease 2019 (COVID-19) patients to develop pulmonary embolism (PE) is widely recognized, the underlying mechanism has not been completely elucidated. This study aimed to identify genes common to COVID-19 and PE to reveal the underlying pathogenesis of susceptibility to PE in COVID-19 patients. Methods COVID-19 genes were obtained from the GEO database and the OMIM, CTD, GeneCards, and DisGeNET databases; PE genes were obtained from the OMIM, CTD, GeneCards, and DisGeNET databases. We overlapped the genes of COVID-19 and PE to obtain common genes for additional analysis, including functional enrichment, protein–protein interaction, and immune infiltration analysis. Hub genes were identified using cytoHubba, a plugin of Cytoscape, and validated using the independent datasets GSE167000 and GSE13535. The genes validated by the above datasets were further validated in clinical samples. Results We obtained 36 genes shared by PE and COVID-19. Functional enrichment and immune infiltration analyses revealed the involvement of cytokines and immune activation. Five genes (CCL2, CXCL10, ALB, EGF, and MKI67) were identified as hub genes common to COVID-19 and PE. CXCL10 was validated in both independent datasets (GSE167000 and GSE13535). Serum levels of CXCL10 in the COVID-19 group and the COVID-19 combined with PE group were significantly higher than those in the healthy control group (P<0.001). In addition, there were significant differences between the COVID-19 group and the COVID-19 combined with PE group (P<0.01). Conclusion Our study reveals common genes shared by PE and COVID-19 and identifies CXCL10 as a possible cause of susceptibility to PE in COVID-19 patients.

show abstract

Clinical, laboratory and immunohistochemical characterization of in situ pulmonary arterial thrombosis in fatal COVID-19

Cited by 6 publications

References 56 publications

Effects of Recombinant SARS-CoV-2 Spike Protein Variants on Platelet Morphology and Activation

Effects of Recombinant SARS-CoV-2 Spike Protein Variants on Platelet Morphology and Activation

Mechanisms of COVID-19 Associated Pulmonary Thrombosis: A Narrative Review

CXCL10 May Be Responsible for Susceptibility to Pulmonary Embolism in COVID-19 Patients

Contact Info

Product

Resources

About