Regulation of the acetylcholine/α7nAChR anti-inflammatory pathway in COVID-19 patients
Abstract The cholinergic system has been proposed as a potential regulator of COVID-19-induced hypercytokinemia. We investigated whole-blood expression of cholinergic system members and correlated it with COVID-19 severity. Patients with confirmed SARS-CoV-2 infection and healthy aged-matched contro...
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Nature Portfolio
2021
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oai:doaj.org-article:b06c7440cdec4f2babb923e5174194fc2021-12-02T15:02:40ZRegulation of the acetylcholine/α7nAChR anti-inflammatory pathway in COVID-19 patients10.1038/s41598-021-91417-72045-2322https://doaj.org/article/b06c7440cdec4f2babb923e5174194fc2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91417-7https://doaj.org/toc/2045-2322Abstract The cholinergic system has been proposed as a potential regulator of COVID-19-induced hypercytokinemia. We investigated whole-blood expression of cholinergic system members and correlated it with COVID-19 severity. Patients with confirmed SARS-CoV-2 infection and healthy aged-matched controls were included in this non-interventional study. A whole blood sample was drawn between 9–11 days after symptoms onset, and peripheral leukocyte phenotyping, cytokines measurement, RNA expression and plasma viral load were determined. Additionally, whole-blood expression of native alpha-7 nicotinic subunit and its negative dominant duplicate (CHRFAM7A), choline acetyltransferase and acetylcholine esterase (AchE) were determined. Thirty-seven patients with COVID-19 (10 moderate, 11 severe and 16 with critical disease) and 14 controls were included. Expression of CHRFAM7A was significantly lower in critical COVID-19 patients compared to controls. COVID-19 patients not expressing CHRFAM7A had higher levels of CRP, more extended pulmonary lesions and displayed more pronounced lymphopenia. COVID-19 patients without CHRFAM7A expression also showed increased TNF pathway expression in whole blood. AchE was also expressed in 30 COVID-19 patients and in all controls. COVID-19-induced hypercytokinemia is associated with decreased expression of the pro-inflammatory dominant negative duplicate CHRFAM7A. Expression of this duplicate might be considered before targeting the cholinergic system in COVID-19 with nicotine.Alice CourtiesJeremy BoussierJérôme HadjadjNader YatimLaura BarnabeiHélène PéréDavid VeyerSolen KernéisNicolas CarlierFrédéric PèneFrédéric Rieux-LaucatBruno CharbitVincent BondetDarragh DuffyFrancis BerenbaumBenjamin TerrierJérémie SellamNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021) |
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Medicine R Science Q Alice Courties Jeremy Boussier Jérôme Hadjadj Nader Yatim Laura Barnabei Hélène Péré David Veyer Solen Kernéis Nicolas Carlier Frédéric Pène Frédéric Rieux-Laucat Bruno Charbit Vincent Bondet Darragh Duffy Francis Berenbaum Benjamin Terrier Jérémie Sellam Regulation of the acetylcholine/α7nAChR anti-inflammatory pathway in COVID-19 patients |
| description |
Abstract The cholinergic system has been proposed as a potential regulator of COVID-19-induced hypercytokinemia. We investigated whole-blood expression of cholinergic system members and correlated it with COVID-19 severity. Patients with confirmed SARS-CoV-2 infection and healthy aged-matched controls were included in this non-interventional study. A whole blood sample was drawn between 9–11 days after symptoms onset, and peripheral leukocyte phenotyping, cytokines measurement, RNA expression and plasma viral load were determined. Additionally, whole-blood expression of native alpha-7 nicotinic subunit and its negative dominant duplicate (CHRFAM7A), choline acetyltransferase and acetylcholine esterase (AchE) were determined. Thirty-seven patients with COVID-19 (10 moderate, 11 severe and 16 with critical disease) and 14 controls were included. Expression of CHRFAM7A was significantly lower in critical COVID-19 patients compared to controls. COVID-19 patients not expressing CHRFAM7A had higher levels of CRP, more extended pulmonary lesions and displayed more pronounced lymphopenia. COVID-19 patients without CHRFAM7A expression also showed increased TNF pathway expression in whole blood. AchE was also expressed in 30 COVID-19 patients and in all controls. COVID-19-induced hypercytokinemia is associated with decreased expression of the pro-inflammatory dominant negative duplicate CHRFAM7A. Expression of this duplicate might be considered before targeting the cholinergic system in COVID-19 with nicotine. |
| format |
article |
| author |
Alice Courties Jeremy Boussier Jérôme Hadjadj Nader Yatim Laura Barnabei Hélène Péré David Veyer Solen Kernéis Nicolas Carlier Frédéric Pène Frédéric Rieux-Laucat Bruno Charbit Vincent Bondet Darragh Duffy Francis Berenbaum Benjamin Terrier Jérémie Sellam |
| author_facet |
Alice Courties Jeremy Boussier Jérôme Hadjadj Nader Yatim Laura Barnabei Hélène Péré David Veyer Solen Kernéis Nicolas Carlier Frédéric Pène Frédéric Rieux-Laucat Bruno Charbit Vincent Bondet Darragh Duffy Francis Berenbaum Benjamin Terrier Jérémie Sellam |
| author_sort |
Alice Courties |
| title |
Regulation of the acetylcholine/α7nAChR anti-inflammatory pathway in COVID-19 patients |
| title_short |
Regulation of the acetylcholine/α7nAChR anti-inflammatory pathway in COVID-19 patients |
| title_full |
Regulation of the acetylcholine/α7nAChR anti-inflammatory pathway in COVID-19 patients |
| title_fullStr |
Regulation of the acetylcholine/α7nAChR anti-inflammatory pathway in COVID-19 patients |
| title_full_unstemmed |
Regulation of the acetylcholine/α7nAChR anti-inflammatory pathway in COVID-19 patients |
| title_sort |
regulation of the acetylcholine/α7nachr anti-inflammatory pathway in covid-19 patients |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/b06c7440cdec4f2babb923e5174194fc |
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