Inflammation and Platelet Activation After COVID-19 Vaccines - Possible Mechanisms Behind Vaccine-Induced Immune Thrombocytopenia and Thrombosis
Introduction of vaccines against COVID-19 has provided the most promising chance to control the world-wide COVID-19 pandemic. However, the adenovirus-vector based Oxford/AstraZeneca [ChAdOx1] (AZ) and Johnson & Johnson [Ad26.CoV2.S] COVID-19 vaccines have been linked with serious thromboembo...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-11-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.779453/full |
| _version_ | 1818723134892670976 |
|---|---|
| author | Sisse R. Ostrowski Sisse R. Ostrowski Ole S. Søgaard Ole S. Søgaard Martin Tolstrup Martin Tolstrup Nina B. Stærke Nina B. Stærke Jens Lundgren Jens Lundgren Lars Østergaard Lars Østergaard Anne-Mette Hvas Anne-Mette Hvas |
| author_facet | Sisse R. Ostrowski Sisse R. Ostrowski Ole S. Søgaard Ole S. Søgaard Martin Tolstrup Martin Tolstrup Nina B. Stærke Nina B. Stærke Jens Lundgren Jens Lundgren Lars Østergaard Lars Østergaard Anne-Mette Hvas Anne-Mette Hvas |
| author_sort | Sisse R. Ostrowski |
| collection | DOAJ |
| description | Introduction of vaccines against COVID-19 has provided the most promising chance to control the world-wide COVID-19 pandemic. However, the adenovirus-vector based Oxford/AstraZeneca [ChAdOx1] (AZ) and Johnson & Johnson [Ad26.CoV2.S] COVID-19 vaccines have been linked with serious thromboembolic events combined with thrombocytopenia, denominated Vaccine-induced Immune Thrombocytopenia and Thrombosis (VITT). The pathogenesis of COVID-19 VITT remain incompletely understood; especially the initial events that trigger platelet activation, platelet factor (PF)4 release, complex formation and PF4 antibody production are puzzling. This is a prospective study investigating the impact of different COVID-19 vaccines on inflammation (CRP, TNF-α, IL-1β, IL-6, IL-8, IL-10), vascular endothelial activation (syndecan-1, thrombomodulin, E-selectin, ICAM-1, ICAM-3, VCAM-1), platelet activation (P-selectin, TGF-β, sCD40L) and aggregation (Multiplate® impedance aggregometry), whole blood coagulation (ROTEM®), thrombin generation and PF4 antibodies to reveal potential differences between AZ and mRNA vaccines in individuals without VITT. The study included 80 (55 AZ and 55 mRNA) vaccinated individuals and 55 non-vaccinated age- and gender matched healthy controls. The main findings where that both vaccines enhanced inflammation and platelet activation, though AZ vaccination induced a more pronounced increase in several inflammatory and platelet activation markers compared to mRNA vaccination and that post-vaccination thrombin generation was higher following AZ vaccination compared to mRNA vaccination. No difference in neither the PF4 antibody level nor the proportion of individuals with positive PF4 antibodies were observed between the vaccine groups. This is the first study to report enhanced inflammation, platelet activation and thrombin generation following AZ vaccination compared to mRNA vaccination in a head-to-head comparison. We speculate that specific components of the AZ adenovirus vector may serve as initial trigger(s) of (hyper)inflammation, platelet activation and thrombin generation, potentially lowering the threshold for a cascade of events that both trigger complications related to excessive inflammation, platelet and coagulation activation as observed in epidemiological studies and promote development of VITT when combined with high-titer functionally active PF4 antibodies. |
| first_indexed | 2024-12-17T21:05:42Z |
| format | Article |
| id | doaj.art-07416948d53f4c9593ec0c51db106d79 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-17T21:05:42Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-07416948d53f4c9593ec0c51db106d792022-12-21T21:32:35ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-11-011210.3389/fimmu.2021.779453779453Inflammation and Platelet Activation After COVID-19 Vaccines - Possible Mechanisms Behind Vaccine-Induced Immune Thrombocytopenia and ThrombosisSisse R. Ostrowski0Sisse R. Ostrowski1Ole S. Søgaard2Ole S. Søgaard3Martin Tolstrup4Martin Tolstrup5Nina B. Stærke6Nina B. Stærke7Jens Lundgren8Jens Lundgren9Lars Østergaard10Lars Østergaard11Anne-Mette Hvas12Anne-Mette Hvas13Department of Clinical Immunology, Copenhagen Hospital Biobank Unit, Rigshospitalet, University of Copenhagen, Copenhagen, DenmarkDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkDepartment Infectious Disease, Aarhus University Hospital, Aarhus, DenmarkDepartment of Clinical Medicine, Aarhus University, Aarhus, DenmarkDepartment Infectious Disease, Aarhus University Hospital, Aarhus, DenmarkDepartment of Clinical Medicine, Aarhus University, Aarhus, DenmarkDepartment Infectious Disease, Aarhus University Hospital, Aarhus, DenmarkDepartment of Clinical Medicine, Aarhus University, Aarhus, DenmarkDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkDepartment of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, DenmarkDepartment Infectious Disease, Aarhus University Hospital, Aarhus, DenmarkDepartment of Clinical Medicine, Aarhus University, Aarhus, DenmarkDepartment of Clinical Medicine, Aarhus University, Aarhus, DenmarkDepartment Clinical Biochemistry, Aarhus University Hospital, Aarhus University, Aarhus, DenmarkIntroduction of vaccines against COVID-19 has provided the most promising chance to control the world-wide COVID-19 pandemic. However, the adenovirus-vector based Oxford/AstraZeneca [ChAdOx1] (AZ) and Johnson & Johnson [Ad26.CoV2.S] COVID-19 vaccines have been linked with serious thromboembolic events combined with thrombocytopenia, denominated Vaccine-induced Immune Thrombocytopenia and Thrombosis (VITT). The pathogenesis of COVID-19 VITT remain incompletely understood; especially the initial events that trigger platelet activation, platelet factor (PF)4 release, complex formation and PF4 antibody production are puzzling. This is a prospective study investigating the impact of different COVID-19 vaccines on inflammation (CRP, TNF-α, IL-1β, IL-6, IL-8, IL-10), vascular endothelial activation (syndecan-1, thrombomodulin, E-selectin, ICAM-1, ICAM-3, VCAM-1), platelet activation (P-selectin, TGF-β, sCD40L) and aggregation (Multiplate® impedance aggregometry), whole blood coagulation (ROTEM®), thrombin generation and PF4 antibodies to reveal potential differences between AZ and mRNA vaccines in individuals without VITT. The study included 80 (55 AZ and 55 mRNA) vaccinated individuals and 55 non-vaccinated age- and gender matched healthy controls. The main findings where that both vaccines enhanced inflammation and platelet activation, though AZ vaccination induced a more pronounced increase in several inflammatory and platelet activation markers compared to mRNA vaccination and that post-vaccination thrombin generation was higher following AZ vaccination compared to mRNA vaccination. No difference in neither the PF4 antibody level nor the proportion of individuals with positive PF4 antibodies were observed between the vaccine groups. This is the first study to report enhanced inflammation, platelet activation and thrombin generation following AZ vaccination compared to mRNA vaccination in a head-to-head comparison. We speculate that specific components of the AZ adenovirus vector may serve as initial trigger(s) of (hyper)inflammation, platelet activation and thrombin generation, potentially lowering the threshold for a cascade of events that both trigger complications related to excessive inflammation, platelet and coagulation activation as observed in epidemiological studies and promote development of VITT when combined with high-titer functionally active PF4 antibodies.https://www.frontiersin.org/articles/10.3389/fimmu.2021.779453/fullCOVID-19platelet factor 4thrombocytopeniathrombosisvaccinesVITT |
| spellingShingle | Sisse R. Ostrowski Sisse R. Ostrowski Ole S. Søgaard Ole S. Søgaard Martin Tolstrup Martin Tolstrup Nina B. Stærke Nina B. Stærke Jens Lundgren Jens Lundgren Lars Østergaard Lars Østergaard Anne-Mette Hvas Anne-Mette Hvas Inflammation and Platelet Activation After COVID-19 Vaccines - Possible Mechanisms Behind Vaccine-Induced Immune Thrombocytopenia and Thrombosis Frontiers in Immunology COVID-19 platelet factor 4 thrombocytopenia thrombosis vaccines VITT |
| title | Inflammation and Platelet Activation After COVID-19 Vaccines - Possible Mechanisms Behind Vaccine-Induced Immune Thrombocytopenia and Thrombosis |
| title_full | Inflammation and Platelet Activation After COVID-19 Vaccines - Possible Mechanisms Behind Vaccine-Induced Immune Thrombocytopenia and Thrombosis |
| title_fullStr | Inflammation and Platelet Activation After COVID-19 Vaccines - Possible Mechanisms Behind Vaccine-Induced Immune Thrombocytopenia and Thrombosis |
| title_full_unstemmed | Inflammation and Platelet Activation After COVID-19 Vaccines - Possible Mechanisms Behind Vaccine-Induced Immune Thrombocytopenia and Thrombosis |
| title_short | Inflammation and Platelet Activation After COVID-19 Vaccines - Possible Mechanisms Behind Vaccine-Induced Immune Thrombocytopenia and Thrombosis |
| title_sort | inflammation and platelet activation after covid 19 vaccines possible mechanisms behind vaccine induced immune thrombocytopenia and thrombosis |
| topic | COVID-19 platelet factor 4 thrombocytopenia thrombosis vaccines VITT |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.779453/full |
| work_keys_str_mv | AT sisserostrowski inflammationandplateletactivationaftercovid19vaccinespossiblemechanismsbehindvaccineinducedimmunethrombocytopeniaandthrombosis AT sisserostrowski inflammationandplateletactivationaftercovid19vaccinespossiblemechanismsbehindvaccineinducedimmunethrombocytopeniaandthrombosis AT olessøgaard inflammationandplateletactivationaftercovid19vaccinespossiblemechanismsbehindvaccineinducedimmunethrombocytopeniaandthrombosis AT olessøgaard inflammationandplateletactivationaftercovid19vaccinespossiblemechanismsbehindvaccineinducedimmunethrombocytopeniaandthrombosis AT martintolstrup inflammationandplateletactivationaftercovid19vaccinespossiblemechanismsbehindvaccineinducedimmunethrombocytopeniaandthrombosis AT martintolstrup inflammationandplateletactivationaftercovid19vaccinespossiblemechanismsbehindvaccineinducedimmunethrombocytopeniaandthrombosis AT ninabstærke inflammationandplateletactivationaftercovid19vaccinespossiblemechanismsbehindvaccineinducedimmunethrombocytopeniaandthrombosis AT ninabstærke inflammationandplateletactivationaftercovid19vaccinespossiblemechanismsbehindvaccineinducedimmunethrombocytopeniaandthrombosis AT jenslundgren inflammationandplateletactivationaftercovid19vaccinespossiblemechanismsbehindvaccineinducedimmunethrombocytopeniaandthrombosis AT jenslundgren inflammationandplateletactivationaftercovid19vaccinespossiblemechanismsbehindvaccineinducedimmunethrombocytopeniaandthrombosis AT larsøstergaard inflammationandplateletactivationaftercovid19vaccinespossiblemechanismsbehindvaccineinducedimmunethrombocytopeniaandthrombosis AT larsøstergaard inflammationandplateletactivationaftercovid19vaccinespossiblemechanismsbehindvaccineinducedimmunethrombocytopeniaandthrombosis AT annemettehvas inflammationandplateletactivationaftercovid19vaccinespossiblemechanismsbehindvaccineinducedimmunethrombocytopeniaandthrombosis AT annemettehvas inflammationandplateletactivationaftercovid19vaccinespossiblemechanismsbehindvaccineinducedimmunethrombocytopeniaandthrombosis |