Serum butyrylcholinesterase activity as a predictor of severity and mortality in COVID-19 patients

Abstract Previous studies suggest that butyrylcholinesterase (BChE), an enzyme involved in the cholinergic anti-inflammatory pathway, may be linked to inflammation, disease severity, and risk of death in COVID-19 patients. Extending earlier work on BChE and COVID-19 severity, this study investigates...

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Main Authors: Tomáš Fazekaš, Lucia Kováčik, Morteza Motahari Rad, Xavier Gabaldó Barrios, Simona Mihaela Iftimie, Jordi Camps, Anna Hrabovská
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-07017-2
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author Tomáš Fazekaš
Lucia Kováčik
Morteza Motahari Rad
Xavier Gabaldó Barrios
Simona Mihaela Iftimie
Jordi Camps
Anna Hrabovská
author_facet Tomáš Fazekaš
Lucia Kováčik
Morteza Motahari Rad
Xavier Gabaldó Barrios
Simona Mihaela Iftimie
Jordi Camps
Anna Hrabovská
author_sort Tomáš Fazekaš
collection DOAJ
description Abstract Previous studies suggest that butyrylcholinesterase (BChE), an enzyme involved in the cholinergic anti-inflammatory pathway, may be linked to inflammation, disease severity, and risk of death in COVID-19 patients. Extending earlier work on BChE and COVID-19 severity, this study investigates additional factors such as age, sex, vaccination status, and symptom profiles. We analyzed 462 patients with polymerase chain reaction (PCR)-confirmed COVID-19 from the first epidemic wave in Spain, examining the association between BChE activity, clinical outcomes, demographic factors, and symptoms. The cohort consisted of 78 asymptomatic patients, 200 patients with mild symptoms, 122 patients with severe symptoms, and 62 critically ill patients. Of the patients in the severe symptoms group and critically ill patients, 26 died within 30 days of diagnosis. Our results showed that BChE activity was not affected by sex but decreased significantly with age (P < 0.0001). Patients with severe COVID-19 symptoms and critically ill patients exhibited lower BChE activity than asymptomatic or mildly symptomatic individuals (P < 0.0001). Furthermore, lower BChE activity was observed in patients with respiratory symptoms, such as pneumonia (P = 0.0027) and dyspnea (P = 0.0120), while higher BChE activity was seen in patients with neurological symptoms, such as anosmia (P < 0.0001), ageusia (P = 0.0012), and headache (P = 0.0005). No significant association was found between BChE activity and gastrointestinal, algesic, musculoskeletal, or systemic inflammatory symptoms. Additionally, vaccinated patients, particularly those who received two doses, had lower BChE activity compared to unvaccinated individuals (P = 0.0465). In conclusion, serum BChE activity is significantly associated with the severity, mortality, and specific symptoms of COVID-19, and is influenced by age and vaccination status. These findings imply that BChE may be a potential biomarker to support prognosis and risk stratification in COVID-19 patients. However, further research is needed to understand the underlying mechanisms and to validate the role of BChE in clinical practice.
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spelling doaj-art-ec502127bfc74c90867c501683ef7e382025-08-20T03:37:22ZengNature PortfolioScientific Reports2045-23222025-07-0115111110.1038/s41598-025-07017-2Serum butyrylcholinesterase activity as a predictor of severity and mortality in COVID-19 patientsTomáš Fazekaš0Lucia Kováčik1Morteza Motahari Rad2Xavier Gabaldó Barrios3Simona Mihaela Iftimie4Jordi Camps5Anna Hrabovská6Department of Physical Chemistry of Drugs, Faculty of Pharmacy, Comenius University BratislavaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University BratislavaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University BratislavaMicrobiology Laboratory, Hospital Universitari de Sant Joan, Institut d’Investigació Sanitària Pere Virgili, Universitat Rovira i VirgiliDepartment of Internal Medicine, Hospital Universitari de Sant Joan, Institut d’Investigació Sanitària Pere Virgili, Universitat Rovira i VirgiliBiochemical Research Unit, Hospital Universitari de Sant Joan, Institut d’Investigació Sanitària Pere Virgili, Universitat Rovira i VirgiliDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University BratislavaAbstract Previous studies suggest that butyrylcholinesterase (BChE), an enzyme involved in the cholinergic anti-inflammatory pathway, may be linked to inflammation, disease severity, and risk of death in COVID-19 patients. Extending earlier work on BChE and COVID-19 severity, this study investigates additional factors such as age, sex, vaccination status, and symptom profiles. We analyzed 462 patients with polymerase chain reaction (PCR)-confirmed COVID-19 from the first epidemic wave in Spain, examining the association between BChE activity, clinical outcomes, demographic factors, and symptoms. The cohort consisted of 78 asymptomatic patients, 200 patients with mild symptoms, 122 patients with severe symptoms, and 62 critically ill patients. Of the patients in the severe symptoms group and critically ill patients, 26 died within 30 days of diagnosis. Our results showed that BChE activity was not affected by sex but decreased significantly with age (P < 0.0001). Patients with severe COVID-19 symptoms and critically ill patients exhibited lower BChE activity than asymptomatic or mildly symptomatic individuals (P < 0.0001). Furthermore, lower BChE activity was observed in patients with respiratory symptoms, such as pneumonia (P = 0.0027) and dyspnea (P = 0.0120), while higher BChE activity was seen in patients with neurological symptoms, such as anosmia (P < 0.0001), ageusia (P = 0.0012), and headache (P = 0.0005). No significant association was found between BChE activity and gastrointestinal, algesic, musculoskeletal, or systemic inflammatory symptoms. Additionally, vaccinated patients, particularly those who received two doses, had lower BChE activity compared to unvaccinated individuals (P = 0.0465). In conclusion, serum BChE activity is significantly associated with the severity, mortality, and specific symptoms of COVID-19, and is influenced by age and vaccination status. These findings imply that BChE may be a potential biomarker to support prognosis and risk stratification in COVID-19 patients. However, further research is needed to understand the underlying mechanisms and to validate the role of BChE in clinical practice.https://doi.org/10.1038/s41598-025-07017-2COVID-19ButyrylcholinesteraseSeverityMortalitySymptomsEllman’s assay
spellingShingle Tomáš Fazekaš
Lucia Kováčik
Morteza Motahari Rad
Xavier Gabaldó Barrios
Simona Mihaela Iftimie
Jordi Camps
Anna Hrabovská
Serum butyrylcholinesterase activity as a predictor of severity and mortality in COVID-19 patients
Scientific Reports
COVID-19
Butyrylcholinesterase
Severity
Mortality
Symptoms
Ellman’s assay
title Serum butyrylcholinesterase activity as a predictor of severity and mortality in COVID-19 patients
title_full Serum butyrylcholinesterase activity as a predictor of severity and mortality in COVID-19 patients
title_fullStr Serum butyrylcholinesterase activity as a predictor of severity and mortality in COVID-19 patients
title_full_unstemmed Serum butyrylcholinesterase activity as a predictor of severity and mortality in COVID-19 patients
title_short Serum butyrylcholinesterase activity as a predictor of severity and mortality in COVID-19 patients
title_sort serum butyrylcholinesterase activity as a predictor of severity and mortality in covid 19 patients
topic COVID-19
Butyrylcholinesterase
Severity
Mortality
Symptoms
Ellman’s assay
url https://doi.org/10.1038/s41598-025-07017-2
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