SARS-CoV-2 Omicron variant infection affects blood platelets, a comparative analysis with Delta variant

IntroductionIn November 2021, the SARS-CoV-2 Omicron variant of concern has emerged and is currently dominating the COVID-19 pandemic over the world. Omicron displays a number of mutations, particularly in the spike protein, leading to specific characteristics including a higher potential for transm...

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Main Authors: Cédric Garcia, Baptiste Compagnon, Agnès Ribes, Sophie Voisin, Fanny Vardon-Bounes, Bernard Payrastre
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-09-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1231576/full
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author Cédric Garcia
Cédric Garcia
Baptiste Compagnon
Baptiste Compagnon
Agnès Ribes
Agnès Ribes
Sophie Voisin
Sophie Voisin
Fanny Vardon-Bounes
Fanny Vardon-Bounes
Bernard Payrastre
Bernard Payrastre
author_facet Cédric Garcia
Cédric Garcia
Baptiste Compagnon
Baptiste Compagnon
Agnès Ribes
Agnès Ribes
Sophie Voisin
Sophie Voisin
Fanny Vardon-Bounes
Fanny Vardon-Bounes
Bernard Payrastre
Bernard Payrastre
author_sort Cédric Garcia
collection DOAJ
description IntroductionIn November 2021, the SARS-CoV-2 Omicron variant of concern has emerged and is currently dominating the COVID-19 pandemic over the world. Omicron displays a number of mutations, particularly in the spike protein, leading to specific characteristics including a higher potential for transmission. Although Omicron has caused a significant number of deaths worldwide, it generally induces less severe clinical signs compared to earlier variants. As its impact on blood platelets remains unknown, we investigated platelet behavior in severe patients infected with Omicron in comparison to Delta.MethodsClinical and biological characteristics of severe COVID-19 patients infected with the Omicron (n=9) or Delta (n=11) variants were analyzed. Using complementary methods such as flow cytometry, confocal imaging and electron microscopy, we examined platelet activation, responsiveness and phenotype, presence of virus in platelets and induction of selective autophagy. We also explored the direct effect of spike proteins from the Omicron or Delta variants on healthy platelet signaling.ResultsSevere Omicron variant infection resulted in platelet activation and partial desensitization, presence of the virus in platelets and selective autophagy response. The intraplatelet processing of Omicron viral cargo was different from Delta as evidenced by the distribution of spike protein-positive structures near the plasma membrane and the colocalization of spike and Rab7. Moreover, spike proteins from the Omicron or Delta variants alone activated signaling pathways in healthy platelets including phosphorylation of AKT, p38MAPK, LIMK and SPL76 with different kinetics.DiscussionAlthough SARS-CoV-2 Omicron has different biological characteristics compared to prior variants, it leads to platelet activation and desensitization as previously observed with the Delta variant. Omicron is also found in platelets from severe patients where it induces selective autophagy, but the mechanisms of intraplatelet processing of Omicron cargo, as part of the innate response, differs from Delta, suggesting that mutations on spike protein modify virus to platelet interactions.
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spelling doaj.art-a0b1b7e716284a9faa601e982ef3efc22023-09-28T05:45:40ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-09-011410.3389/fimmu.2023.12315761231576SARS-CoV-2 Omicron variant infection affects blood platelets, a comparative analysis with Delta variantCédric Garcia0Cédric Garcia1Baptiste Compagnon2Baptiste Compagnon3Agnès Ribes4Agnès Ribes5Sophie Voisin6Sophie Voisin7Fanny Vardon-Bounes8Fanny Vardon-Bounes9Bernard Payrastre10Bernard Payrastre11Inserm UMR1297 and Université Toulouse 3, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse, FranceCentre Hospitalier Universitaire de Toulouse, Laboratoire d’Hématologie, Toulouse, FranceInserm UMR1297 and Université Toulouse 3, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse, FranceCentre Hospitalier Universitaire de Toulouse, Pôle Anesthésie-Réanimation, Toulouse, FranceInserm UMR1297 and Université Toulouse 3, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse, FranceCentre Hospitalier Universitaire de Toulouse, Laboratoire d’Hématologie, Toulouse, FranceInserm UMR1297 and Université Toulouse 3, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse, FranceCentre Hospitalier Universitaire de Toulouse, Laboratoire d’Hématologie, Toulouse, FranceInserm UMR1297 and Université Toulouse 3, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse, FranceCentre Hospitalier Universitaire de Toulouse, Pôle Anesthésie-Réanimation, Toulouse, FranceInserm UMR1297 and Université Toulouse 3, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse, FranceCentre Hospitalier Universitaire de Toulouse, Laboratoire d’Hématologie, Toulouse, FranceIntroductionIn November 2021, the SARS-CoV-2 Omicron variant of concern has emerged and is currently dominating the COVID-19 pandemic over the world. Omicron displays a number of mutations, particularly in the spike protein, leading to specific characteristics including a higher potential for transmission. Although Omicron has caused a significant number of deaths worldwide, it generally induces less severe clinical signs compared to earlier variants. As its impact on blood platelets remains unknown, we investigated platelet behavior in severe patients infected with Omicron in comparison to Delta.MethodsClinical and biological characteristics of severe COVID-19 patients infected with the Omicron (n=9) or Delta (n=11) variants were analyzed. Using complementary methods such as flow cytometry, confocal imaging and electron microscopy, we examined platelet activation, responsiveness and phenotype, presence of virus in platelets and induction of selective autophagy. We also explored the direct effect of spike proteins from the Omicron or Delta variants on healthy platelet signaling.ResultsSevere Omicron variant infection resulted in platelet activation and partial desensitization, presence of the virus in platelets and selective autophagy response. The intraplatelet processing of Omicron viral cargo was different from Delta as evidenced by the distribution of spike protein-positive structures near the plasma membrane and the colocalization of spike and Rab7. Moreover, spike proteins from the Omicron or Delta variants alone activated signaling pathways in healthy platelets including phosphorylation of AKT, p38MAPK, LIMK and SPL76 with different kinetics.DiscussionAlthough SARS-CoV-2 Omicron has different biological characteristics compared to prior variants, it leads to platelet activation and desensitization as previously observed with the Delta variant. Omicron is also found in platelets from severe patients where it induces selective autophagy, but the mechanisms of intraplatelet processing of Omicron cargo, as part of the innate response, differs from Delta, suggesting that mutations on spike protein modify virus to platelet interactions.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1231576/fullCOVID-19plateletsomicron variantLC3Bspikeautophagy
spellingShingle Cédric Garcia
Cédric Garcia
Baptiste Compagnon
Baptiste Compagnon
Agnès Ribes
Agnès Ribes
Sophie Voisin
Sophie Voisin
Fanny Vardon-Bounes
Fanny Vardon-Bounes
Bernard Payrastre
Bernard Payrastre
SARS-CoV-2 Omicron variant infection affects blood platelets, a comparative analysis with Delta variant
Frontiers in Immunology
COVID-19
platelets
omicron variant
LC3B
spike
autophagy
title SARS-CoV-2 Omicron variant infection affects blood platelets, a comparative analysis with Delta variant
title_full SARS-CoV-2 Omicron variant infection affects blood platelets, a comparative analysis with Delta variant
title_fullStr SARS-CoV-2 Omicron variant infection affects blood platelets, a comparative analysis with Delta variant
title_full_unstemmed SARS-CoV-2 Omicron variant infection affects blood platelets, a comparative analysis with Delta variant
title_short SARS-CoV-2 Omicron variant infection affects blood platelets, a comparative analysis with Delta variant
title_sort sars cov 2 omicron variant infection affects blood platelets a comparative analysis with delta variant
topic COVID-19
platelets
omicron variant
LC3B
spike
autophagy
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1231576/full
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