Characterization of extracellular vesicles in COVID-19 infection during pregnancy

Introduction: SARS-CoV-2 infection may cause a severe inflammatory response, inflicting severe morbidity and mortality. This risk is modestly increased in pregnant patients. Despite the hypercoagulability and immunosuppression associated with pregnancy, most pregnant women experience a mild COVID-19...

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Main Authors: Ayelet Dangot, Mor Zavaro, Tali Hana Bar-Lev, Lian Bannon, Ayala Zilberman, Eliana Pickholz, Irit Avivi, Anat Aharon
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-07-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2023.1135821/full
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author Ayelet Dangot
Ayelet Dangot
Ayelet Dangot
Mor Zavaro
Mor Zavaro
Tali Hana Bar-Lev
Lian Bannon
Ayala Zilberman
Eliana Pickholz
Eliana Pickholz
Irit Avivi
Irit Avivi
Anat Aharon
Anat Aharon
author_facet Ayelet Dangot
Ayelet Dangot
Ayelet Dangot
Mor Zavaro
Mor Zavaro
Tali Hana Bar-Lev
Lian Bannon
Ayala Zilberman
Eliana Pickholz
Eliana Pickholz
Irit Avivi
Irit Avivi
Anat Aharon
Anat Aharon
author_sort Ayelet Dangot
collection DOAJ
description Introduction: SARS-CoV-2 infection may cause a severe inflammatory response, inflicting severe morbidity and mortality. This risk is modestly increased in pregnant patients. Despite the hypercoagulability and immunosuppression associated with pregnancy, most pregnant women experience a mild COVID-19 infection. Maternal extracellular vesicles (EVs) may interact with endothelial and immune components to facilitate a favorable disease course. This pilot study aimed to explore the characteristics of EVs released during COVID-19 infection occurring during the third trimester of pregnancy.Methods: In this prospective study, blood samples were obtained from 16 healthy non-pregnant (NP), 18 healthy-pregnant (HP), and 22 COVID-19 positive pregnant subjects (CoV-P). Disease course and pregnancy outcomes were assessed and EVs were characterized. Of note, limited volumes of sample acquired from the subjects made it necessary to use smaller and different subsets of samples for each analysis.Results: The majority (91%) of the COVID-19-pregnant subjects (18 mild and 2 moderate disease) experienced good pregnancy-related outcomes. EV concentrations were higher in healthy-pregnant subjects compared to non-pregnant subjects (p = 0.0041) and lower in COVID-19-pregnant subjects compared to healthy-pregnant subjects (p = 0.0150). CD63 exosome marker expression was higher in EVs of healthy-pregnant subjects and COVID-19-pregnant subjects compared to EVs of non-pregnant subjects (p = 0.0149, p = 0.0028, respectively). Similar levels of SARS-CoV-2 entry proteins (ACE-2 and TMPRSS2) were found in all three groups. Cytokine content increased in healthy-pregnant subject-EVs compared to non-pregnant EVs, while IL-2 and IL-6 levels were decreased in COVID-19-pregnant subject-EVs compared to healthy-pregnant subject-EVs (p = 0.043, p = 0.0390, respectively). CD8+, cytotoxic T-cell marker, was lower in non-pregnant EVs compared to healthy-pregnant subject-EVs and to COVID-19-pregnant subjects (p = 0.0108, p < 0.0001, respectively). COVID-19- pregnant subject-EVs demonstrated higher levels of platelet activation marker (CD62P) than non-pregnant (p = 0.0327) and healthy-pregnant subjects (p = 0.0365). Endothelial marker EV-CD144+ was lower in healthy-pregnant subjects versus non-pregnant subjects (p = 0.0093), but similar in COVID-19-pregnant and non-pregnant subjects. Other EVs’ coagulation markers/activity, D-Dimer and fibrinogen levels were similar in healthy-pregnant subjects and COVID-19 positive pregnant subjects.Conclusion: COVID-19 positive pregnant subjects’ EVs demonstrated an attenuated inflammatory response, with no additional activation of the coagulation system.
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spelling doaj.art-56a09c30b517497f9ec2fe26aa10173c2023-07-25T11:01:45ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-07-011110.3389/fcell.2023.11358211135821Characterization of extracellular vesicles in COVID-19 infection during pregnancyAyelet Dangot0Ayelet Dangot1Ayelet Dangot2Mor Zavaro3Mor Zavaro4Tali Hana Bar-Lev5Lian Bannon6Ayala Zilberman7Eliana Pickholz8Eliana Pickholz9Irit Avivi10Irit Avivi11Anat Aharon12Anat Aharon13Hematology Research Laboratory, Tel-Aviv Sourasky Medical Center, Tel Aviv, IsraelObstetrics and Gynecology Department, Lis Hospital for Women, Tel Aviv Sourasky Medical Center, Tel Aviv, IsraelSackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelHematology Research Laboratory, Tel-Aviv Sourasky Medical Center, Tel Aviv, IsraelSackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelHematology Research Laboratory, Tel-Aviv Sourasky Medical Center, Tel Aviv, IsraelDepartment of Medicine F, Tel-Aviv Sourasky Medical Center, Tel Aviv, IsraelObstetrics and Gynecology Department, Lis Hospital for Women, Tel Aviv Sourasky Medical Center, Tel Aviv, IsraelHematology Research Laboratory, Tel-Aviv Sourasky Medical Center, Tel Aviv, IsraelSackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelSackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelHematology Department, Tel-Aviv Sourasky Medical Center, Tel Aviv, IsraelHematology Research Laboratory, Tel-Aviv Sourasky Medical Center, Tel Aviv, IsraelSackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelIntroduction: SARS-CoV-2 infection may cause a severe inflammatory response, inflicting severe morbidity and mortality. This risk is modestly increased in pregnant patients. Despite the hypercoagulability and immunosuppression associated with pregnancy, most pregnant women experience a mild COVID-19 infection. Maternal extracellular vesicles (EVs) may interact with endothelial and immune components to facilitate a favorable disease course. This pilot study aimed to explore the characteristics of EVs released during COVID-19 infection occurring during the third trimester of pregnancy.Methods: In this prospective study, blood samples were obtained from 16 healthy non-pregnant (NP), 18 healthy-pregnant (HP), and 22 COVID-19 positive pregnant subjects (CoV-P). Disease course and pregnancy outcomes were assessed and EVs were characterized. Of note, limited volumes of sample acquired from the subjects made it necessary to use smaller and different subsets of samples for each analysis.Results: The majority (91%) of the COVID-19-pregnant subjects (18 mild and 2 moderate disease) experienced good pregnancy-related outcomes. EV concentrations were higher in healthy-pregnant subjects compared to non-pregnant subjects (p = 0.0041) and lower in COVID-19-pregnant subjects compared to healthy-pregnant subjects (p = 0.0150). CD63 exosome marker expression was higher in EVs of healthy-pregnant subjects and COVID-19-pregnant subjects compared to EVs of non-pregnant subjects (p = 0.0149, p = 0.0028, respectively). Similar levels of SARS-CoV-2 entry proteins (ACE-2 and TMPRSS2) were found in all three groups. Cytokine content increased in healthy-pregnant subject-EVs compared to non-pregnant EVs, while IL-2 and IL-6 levels were decreased in COVID-19-pregnant subject-EVs compared to healthy-pregnant subject-EVs (p = 0.043, p = 0.0390, respectively). CD8+, cytotoxic T-cell marker, was lower in non-pregnant EVs compared to healthy-pregnant subject-EVs and to COVID-19-pregnant subjects (p = 0.0108, p < 0.0001, respectively). COVID-19- pregnant subject-EVs demonstrated higher levels of platelet activation marker (CD62P) than non-pregnant (p = 0.0327) and healthy-pregnant subjects (p = 0.0365). Endothelial marker EV-CD144+ was lower in healthy-pregnant subjects versus non-pregnant subjects (p = 0.0093), but similar in COVID-19-pregnant and non-pregnant subjects. Other EVs’ coagulation markers/activity, D-Dimer and fibrinogen levels were similar in healthy-pregnant subjects and COVID-19 positive pregnant subjects.Conclusion: COVID-19 positive pregnant subjects’ EVs demonstrated an attenuated inflammatory response, with no additional activation of the coagulation system.https://www.frontiersin.org/articles/10.3389/fcell.2023.1135821/fullSARS-CoV-2pregnancyextracellular vesicles (EVs)cytokinecoagulation
spellingShingle Ayelet Dangot
Ayelet Dangot
Ayelet Dangot
Mor Zavaro
Mor Zavaro
Tali Hana Bar-Lev
Lian Bannon
Ayala Zilberman
Eliana Pickholz
Eliana Pickholz
Irit Avivi
Irit Avivi
Anat Aharon
Anat Aharon
Characterization of extracellular vesicles in COVID-19 infection during pregnancy
Frontiers in Cell and Developmental Biology
SARS-CoV-2
pregnancy
extracellular vesicles (EVs)
cytokine
coagulation
title Characterization of extracellular vesicles in COVID-19 infection during pregnancy
title_full Characterization of extracellular vesicles in COVID-19 infection during pregnancy
title_fullStr Characterization of extracellular vesicles in COVID-19 infection during pregnancy
title_full_unstemmed Characterization of extracellular vesicles in COVID-19 infection during pregnancy
title_short Characterization of extracellular vesicles in COVID-19 infection during pregnancy
title_sort characterization of extracellular vesicles in covid 19 infection during pregnancy
topic SARS-CoV-2
pregnancy
extracellular vesicles (EVs)
cytokine
coagulation
url https://www.frontiersin.org/articles/10.3389/fcell.2023.1135821/full
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