Use of Early Donated COVID-19 Convalescent Plasma Is Optimal to Preserve the Integrity of Lymphatic Endothelial Cells
Convalescent plasma therapy (CPT) has gained significant attention since the onset of the coronavirus disease 2019 (COVID-19) pandemic. However, clinical trials designed to study the efficacy of CPT based on antibody concentrations were inconclusive. Lymphatic transport is at the interplay between t...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/3/365 |
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| author | Nada Amri Rémi Bégin Nolwenn Tessier Laurent Vachon Louis Villeneuve Philippe Bégin Renée Bazin Lionel Loubaki Catherine Martel |
| author_facet | Nada Amri Rémi Bégin Nolwenn Tessier Laurent Vachon Louis Villeneuve Philippe Bégin Renée Bazin Lionel Loubaki Catherine Martel |
| author_sort | Nada Amri |
| collection | DOAJ |
| description | Convalescent plasma therapy (CPT) has gained significant attention since the onset of the coronavirus disease 2019 (COVID-19) pandemic. However, clinical trials designed to study the efficacy of CPT based on antibody concentrations were inconclusive. Lymphatic transport is at the interplay between the immune response and the resolution of inflammation from peripheral tissues, including the artery wall. As vascular complications are a key pathogenic mechanism in COVID-19, leading to inflammation and multiple organ failure, we believe that sustaining lymphatic vessel function should be considered to define optimal CPT. We herein sought to determine what specific COVID-19 convalescent plasma (CCP) characteristics should be considered to limit inflammation-driven lymphatic endothelial cells (LEC) dysfunction. CCP donated 16 to 100 days after the last day of symptoms was characterized and incubated on inflammation-elicited adult human dermal LEC (aHDLEC). Plasma analysis revealed that late donation correlates with higher concentration of circulating pro-inflammatory cytokines. Conversely, extracellular vesicles (EVs) derived from LEC are more abundant in early donated plasma (r = −0.413, <i>p</i> = 0.004). Thus, secretion of LEC-EVs by an impaired endothelium could be an alarm signal that instigate the self-defense of peripheral lymphatic vessels against an excessive inflammation. Indeed, in vitro experiments suggest that CCP obtained rapidly following the onset of symptoms does not damage the aHDLEC junctions as much as late-donated plasma. We identified a particular signature of CCP that would counteract the effects of an excessive inflammation on the lymphatic endothelium. Accordingly, an easy and efficient selection of convalescent plasma based on time of donation would be essential to promote the preservation of the lymphatic and immune system of infected patients. |
| first_indexed | 2024-03-09T13:00:38Z |
| format | Article |
| id | doaj.art-44dc8c2728644b6fb06373c18ba54979 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T13:00:38Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-44dc8c2728644b6fb06373c18ba549792023-11-30T21:55:04ZengMDPI AGPharmaceuticals1424-82472022-03-0115336510.3390/ph15030365Use of Early Donated COVID-19 Convalescent Plasma Is Optimal to Preserve the Integrity of Lymphatic Endothelial CellsNada Amri0Rémi Bégin1Nolwenn Tessier2Laurent Vachon3Louis Villeneuve4Philippe Bégin5Renée Bazin6Lionel Loubaki7Catherine Martel8Faculty of Medicine, Université de Montréal, Pavillon Roger-Gaudry, 2900 Edouard Montpetit Blvd, Montreal, QC H3T 1J4, CanadaFaculty of Medicine, Université de Montréal, Pavillon Roger-Gaudry, 2900 Edouard Montpetit Blvd, Montreal, QC H3T 1J4, CanadaFaculty of Medicine, Université de Montréal, Pavillon Roger-Gaudry, 2900 Edouard Montpetit Blvd, Montreal, QC H3T 1J4, CanadaFaculty of Medicine, Université de Montréal, Pavillon Roger-Gaudry, 2900 Edouard Montpetit Blvd, Montreal, QC H3T 1J4, CanadaMontreal Heart Institute, 5000 Belanger Street, Montreal, QC H1T 1C8, CanadaDepartment of Pediatrics, CHU Sainte-Justine, 3175 Chem. de la Côte-Sainte-Catherine, Montreal, QC H3T 1C5, CanadaMedical Affairs and Innovation, Héma-Québec, 1070 Avenue des Sciences-de-la-Vie, Québec, QC G1V 5C3, CanadaMedical Affairs and Innovation, Héma-Québec, 1070 Avenue des Sciences-de-la-Vie, Québec, QC G1V 5C3, CanadaFaculty of Medicine, Université de Montréal, Pavillon Roger-Gaudry, 2900 Edouard Montpetit Blvd, Montreal, QC H3T 1J4, CanadaConvalescent plasma therapy (CPT) has gained significant attention since the onset of the coronavirus disease 2019 (COVID-19) pandemic. However, clinical trials designed to study the efficacy of CPT based on antibody concentrations were inconclusive. Lymphatic transport is at the interplay between the immune response and the resolution of inflammation from peripheral tissues, including the artery wall. As vascular complications are a key pathogenic mechanism in COVID-19, leading to inflammation and multiple organ failure, we believe that sustaining lymphatic vessel function should be considered to define optimal CPT. We herein sought to determine what specific COVID-19 convalescent plasma (CCP) characteristics should be considered to limit inflammation-driven lymphatic endothelial cells (LEC) dysfunction. CCP donated 16 to 100 days after the last day of symptoms was characterized and incubated on inflammation-elicited adult human dermal LEC (aHDLEC). Plasma analysis revealed that late donation correlates with higher concentration of circulating pro-inflammatory cytokines. Conversely, extracellular vesicles (EVs) derived from LEC are more abundant in early donated plasma (r = −0.413, <i>p</i> = 0.004). Thus, secretion of LEC-EVs by an impaired endothelium could be an alarm signal that instigate the self-defense of peripheral lymphatic vessels against an excessive inflammation. Indeed, in vitro experiments suggest that CCP obtained rapidly following the onset of symptoms does not damage the aHDLEC junctions as much as late-donated plasma. We identified a particular signature of CCP that would counteract the effects of an excessive inflammation on the lymphatic endothelium. Accordingly, an easy and efficient selection of convalescent plasma based on time of donation would be essential to promote the preservation of the lymphatic and immune system of infected patients.https://www.mdpi.com/1424-8247/15/3/365COVID-19lymphaticsconvalescent plasma therapyendotheliumextracellular vesicles |
| spellingShingle | Nada Amri Rémi Bégin Nolwenn Tessier Laurent Vachon Louis Villeneuve Philippe Bégin Renée Bazin Lionel Loubaki Catherine Martel Use of Early Donated COVID-19 Convalescent Plasma Is Optimal to Preserve the Integrity of Lymphatic Endothelial Cells Pharmaceuticals COVID-19 lymphatics convalescent plasma therapy endothelium extracellular vesicles |
| title | Use of Early Donated COVID-19 Convalescent Plasma Is Optimal to Preserve the Integrity of Lymphatic Endothelial Cells |
| title_full | Use of Early Donated COVID-19 Convalescent Plasma Is Optimal to Preserve the Integrity of Lymphatic Endothelial Cells |
| title_fullStr | Use of Early Donated COVID-19 Convalescent Plasma Is Optimal to Preserve the Integrity of Lymphatic Endothelial Cells |
| title_full_unstemmed | Use of Early Donated COVID-19 Convalescent Plasma Is Optimal to Preserve the Integrity of Lymphatic Endothelial Cells |
| title_short | Use of Early Donated COVID-19 Convalescent Plasma Is Optimal to Preserve the Integrity of Lymphatic Endothelial Cells |
| title_sort | use of early donated covid 19 convalescent plasma is optimal to preserve the integrity of lymphatic endothelial cells |
| topic | COVID-19 lymphatics convalescent plasma therapy endothelium extracellular vesicles |
| url | https://www.mdpi.com/1424-8247/15/3/365 |
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