Journal
SCIENTIFIC REPORTS
Volume 11, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41598-021-91417-7
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Funding
- Fonds IMMUNOV, for Innovation in Immunopathology
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- Institut Pasteur
- Agence National de la Recherche [ANR-10-IAHU-01, ANR-10-LABX-69-01]
- Agence National de la Recherche
- FAST Foundation (French Friends of Sheba Tel Hashomer Hospital)
- French Society of Rheumatology
- Assistance Publique des Hopitaux de Paris
- Institut Imagine M.D.-Ph.D. fellowship program
- Fondation Bettencourt Schueller
- EUR G.E.N.E. program of the Universite de Paris IdEx - French Government through its Investments for the Future program [ANR-17-EURE-0013, ANR18-IDEX-0001]
- Agence Nationale de la Recherche (ANR) [ANR-17-EURE-0013] Funding Source: Agence Nationale de la Recherche (ANR)
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The expression of cholinergic system members may be associated with COVID-19 severity and inflammatory response. The decreased expression of a negative dominant duplicate CHRFAM7A is correlated with COVID-19-induced hypercytokinemia.
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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