Complement C3 identified as a unique risk factor for disease severity among young COVID-19 patients in Wuhan, China

Abstract Given that a substantial proportion of the subgroup of COVID-19 patients that face a severe disease course are younger than 60 years, it is critical to understand the disease-specific characteristics of young COVID-19 patients. Risk factors for a severe disease course for young COVID-19 pat...

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Autores principales:	Weiting Cheng, Roman Hornung, Kai Xu, Cai hong Yang, Jian Li
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bf0987fb957e4e128ff8609f92061f50
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spelling	oai:doaj.org-article:bf0987fb957e4e128ff8609f92061f502021-12-02T14:26:25ZComplement C3 identified as a unique risk factor for disease severity among young COVID-19 patients in Wuhan, China10.1038/s41598-021-82810-32045-2322https://doaj.org/article/bf0987fb957e4e128ff8609f92061f502021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82810-3https://doaj.org/toc/2045-2322Abstract Given that a substantial proportion of the subgroup of COVID-19 patients that face a severe disease course are younger than 60 years, it is critical to understand the disease-specific characteristics of young COVID-19 patients. Risk factors for a severe disease course for young COVID-19 patients and possible non-linear influences remain unknown. Data were analyzed from COVID-19 patients with clinical outcome in a single hospital in Wuhan, China, collected retrospectively from Jan 24th to Mar 27th. Clinical, demographic, treatment and laboratory data were collected from patients' medical records. Uni- and multivariable analysis using logistic regression and random forest, with the latter allowing the study of non-linear influences, were performed to investigate the clinical characteristics of a severe disease course. A total of 762 young patients (median age 47 years, interquartile range [IQR] 38–55, range 18–60; 55.9% female) were included, as well as 714 elderly patients as a comparison group. Among the young patients, 362 (47.5%) had a severe/critical disease course and the mean age was statistically significantly higher in the severe subgroup than in the mild subgroup (59.3 vs. 56.0, Student's t-test: p < 0.001). The uni- and multivariable analysis suggested that several covariates such as elevated levels of serum amyloid A (SAA), C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased lymphocyte counts influence disease severity independently of age. Elevated levels of complement C3 (odds ratio [OR] 15.6, 95% CI 2.41–122.3; p = 0.039) are particularly associated with the risk of developing severe COVID-19 specifically in young patients, whereas no such influence seems to exist for elderly patients. Additional analysis suggests that the influence of complement C3 in young patients is independent of age, gender, and comorbidities. Variable importance values and partial dependence plots obtained using random forests delivered additional insights, in particular indicating non-linear influences of risk factors on disease severity. This study identified increased levels of complement C3 as a unique risk factor for adverse outcomes specific to young COVID-19 patients.Weiting ChengRoman HornungKai XuCai hong YangJian LiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Weiting Cheng Roman Hornung Kai Xu Cai hong Yang Jian Li Complement C3 identified as a unique risk factor for disease severity among young COVID-19 patients in Wuhan, China
description	Abstract Given that a substantial proportion of the subgroup of COVID-19 patients that face a severe disease course are younger than 60 years, it is critical to understand the disease-specific characteristics of young COVID-19 patients. Risk factors for a severe disease course for young COVID-19 patients and possible non-linear influences remain unknown. Data were analyzed from COVID-19 patients with clinical outcome in a single hospital in Wuhan, China, collected retrospectively from Jan 24th to Mar 27th. Clinical, demographic, treatment and laboratory data were collected from patients' medical records. Uni- and multivariable analysis using logistic regression and random forest, with the latter allowing the study of non-linear influences, were performed to investigate the clinical characteristics of a severe disease course. A total of 762 young patients (median age 47 years, interquartile range [IQR] 38–55, range 18–60; 55.9% female) were included, as well as 714 elderly patients as a comparison group. Among the young patients, 362 (47.5%) had a severe/critical disease course and the mean age was statistically significantly higher in the severe subgroup than in the mild subgroup (59.3 vs. 56.0, Student's t-test: p < 0.001). The uni- and multivariable analysis suggested that several covariates such as elevated levels of serum amyloid A (SAA), C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased lymphocyte counts influence disease severity independently of age. Elevated levels of complement C3 (odds ratio [OR] 15.6, 95% CI 2.41–122.3; p = 0.039) are particularly associated with the risk of developing severe COVID-19 specifically in young patients, whereas no such influence seems to exist for elderly patients. Additional analysis suggests that the influence of complement C3 in young patients is independent of age, gender, and comorbidities. Variable importance values and partial dependence plots obtained using random forests delivered additional insights, in particular indicating non-linear influences of risk factors on disease severity. This study identified increased levels of complement C3 as a unique risk factor for adverse outcomes specific to young COVID-19 patients.
format	article
author	Weiting Cheng Roman Hornung Kai Xu Cai hong Yang Jian Li
author_facet	Weiting Cheng Roman Hornung Kai Xu Cai hong Yang Jian Li
author_sort	Weiting Cheng
title	Complement C3 identified as a unique risk factor for disease severity among young COVID-19 patients in Wuhan, China
title_short	Complement C3 identified as a unique risk factor for disease severity among young COVID-19 patients in Wuhan, China
title_full	Complement C3 identified as a unique risk factor for disease severity among young COVID-19 patients in Wuhan, China
title_fullStr	Complement C3 identified as a unique risk factor for disease severity among young COVID-19 patients in Wuhan, China
title_full_unstemmed	Complement C3 identified as a unique risk factor for disease severity among young COVID-19 patients in Wuhan, China
title_sort	complement c3 identified as a unique risk factor for disease severity among young covid-19 patients in wuhan, china
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/bf0987fb957e4e128ff8609f92061f50
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Complement C3 identified as a unique risk factor for disease severity among young COVID-19 patients in Wuhan, China

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