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...
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2021
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oai:doaj.org-article:07416948d53f4c9593ec0c51db106d792021-11-30T11:59:59ZInflammation and Platelet Activation After COVID-19 Vaccines - Possible Mechanisms Behind Vaccine-Induced Immune Thrombocytopenia and Thrombosis1664-322410.3389/fimmu.2021.779453https://doaj.org/article/07416948d53f4c9593ec0c51db106d792021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.779453/fullhttps://doaj.org/toc/1664-3224Introduction 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.Sisse R. OstrowskiSisse R. OstrowskiOle S. SøgaardOle S. SøgaardMartin TolstrupMartin TolstrupNina B. StærkeNina B. StærkeJens LundgrenJens LundgrenLars ØstergaardLars ØstergaardAnne-Mette HvasAnne-Mette HvasFrontiers Media S.A.articleCOVID-19platelet factor 4thrombocytopeniathrombosisvaccinesVITTImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021) |
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COVID-19 platelet factor 4 thrombocytopenia thrombosis vaccines VITT Immunologic diseases. Allergy RC581-607 |
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COVID-19 platelet factor 4 thrombocytopenia thrombosis vaccines VITT Immunologic diseases. Allergy RC581-607 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 |
| 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. |
| format |
article |
| 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 |
| title |
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_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_sort |
inflammation and platelet activation after covid-19 vaccines - possible mechanisms behind vaccine-induced immune thrombocytopenia and thrombosis |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/07416948d53f4c9593ec0c51db106d79 |
| work_keys_str_mv |
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