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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.
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1 Sorbonne Université, INSERM UMR 938, Centre de Recherche Saint-Antoine, Hôpital Saint-Antoine, AP-HP, Paris, France (GRID:grid.412370.3) (ISNI:0000 0004 1937 1100); AP-HP Saint-Antoine Hospital, Rheumatology Department, Paris, France (GRID:grid.412370.3) (ISNI:0000 0004 1937 1100)
2 Sorbonne Université, Paris, France (GRID:grid.462844.8) (ISNI:0000 0001 2308 1657)
3 Université de Paris, Imagine Institute Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Paris, France (GRID:grid.508487.6) (ISNI:0000 0004 7885 7602); National Reference Center for Rare Systemic Autoimmune Diseases, AP-HP, APHP-CUP, Hôpital Cochin, Department of Internal Medicine, Paris, France (GRID:grid.411784.f) (ISNI:0000 0001 0274 3893)
4 Institut Pasteur, Translational Immunology Lab, Department of Immunology, Paris, France (GRID:grid.428999.7) (ISNI:0000 0001 2353 6535); National Reference Center for Rare Systemic Autoimmune Diseases, AP-HP, APHP-CUP, Hôpital Cochin, Department of Internal Medicine, Paris, France (GRID:grid.411784.f) (ISNI:0000 0001 0274 3893)
5 Université de Paris, Imagine Institute Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Paris, France (GRID:grid.508487.6) (ISNI:0000 0004 7885 7602)
6 Université de Paris, INSERM, U970, PARCC, Paris, France (GRID:grid.508487.6) (ISNI:0000 0004 7885 7602); Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Laboratoire de Virologie, Service de Microbiologie, Paris, France (GRID:grid.414093.b)
7 Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Laboratoire de Virologie, Service de Microbiologie, Paris, France (GRID:grid.414093.b); Université Paris, Unité de Génomique Fonctionnelle des Tumeurs Solides, Centre de Recherche des Cordeliers, INSERM, Paris, France (GRID:grid.410511.0) (ISNI:0000 0001 2149 7878)
8 Equipe Mobile d’Infectiologie, Hôpital Cochin, AP-HP, APHP-CUP, Paris, France (GRID:grid.411784.f) (ISNI:0000 0001 0274 3893); Université de Paris, INSERM, IAME, Paris, France (GRID:grid.411784.f); Institut Pasteur, Epidemiology and Modelling of Antibiotic Evasion (EMAE), Paris, France (GRID:grid.428999.7) (ISNI:0000 0001 2353 6535)
9 Hôpital Cochin, AP-HP, APHP-CUP, Department of Pulmonology, Paris, France (GRID:grid.411784.f) (ISNI:0000 0001 0274 3893)
10 Université de Paris, Institut Cochin, INSERM U1016, CNRS UMR 8104, Service de Médecine Intensive-Réanimation, Hôpital Cochin, AP-HP-CUP, Paris, France (GRID:grid.411784.f) (ISNI:0000 0001 0274 3893)
11 Institut Pasteur, Cytometry and Biomarkers UTechS, CRT, Paris, France (GRID:grid.428999.7) (ISNI:0000 0001 2353 6535)
12 Institut Pasteur, Translational Immunology Lab, Department of Immunology, Paris, France (GRID:grid.428999.7) (ISNI:0000 0001 2353 6535)
13 Institut Pasteur, Translational Immunology Lab, Department of Immunology, Paris, France (GRID:grid.428999.7) (ISNI:0000 0001 2353 6535); Institut Pasteur, Cytometry and Biomarkers UTechS, CRT, Paris, France (GRID:grid.428999.7) (ISNI:0000 0001 2353 6535)
14 National Reference Center for Rare Systemic Autoimmune Diseases, AP-HP, APHP-CUP, Hôpital Cochin, Department of Internal Medicine, Paris, France (GRID:grid.411784.f) (ISNI:0000 0001 0274 3893); Université de Paris, INSERM, U970, PARCC, Paris, France (GRID:grid.508487.6) (ISNI:0000 0004 7885 7602)