tetano
Editor, Senior Moderator
Front Cell Dev Biol
. 2022 Jan 6;9:781267.
doi: 10.3389/fcell.2021.781267. eCollection 2021.
5-Hydroxymethylcytosine Signatures in Circulating Cell-Free DNA as Early Warning Biomarkers for COVID-19 Progression and Myocardial Injury
Hang-Yu Chen[SUP] 1 2 [/SUP], Xiao-Xiao Li[SUP] 1 [/SUP], Chao Li[SUP] 1 [/SUP], Hai-Chuan Zhu[SUP] 3 [/SUP], Hong-Yan Hou[SUP] 4 [/SUP], Bo Zhang[SUP] 4 [/SUP], Li-Ming Cheng[SUP] 4 [/SUP], Hui Hu[SUP] 5 [/SUP], Zhong-Xin Lu[SUP] 5 [/SUP], Jia-Xing Liu[SUP] 3 [/SUP], Ze-Ruo Yang[SUP] 6 [/SUP], Lei Zhang[SUP] 6 [/SUP], Nuo Xu[SUP] 6 [/SUP], Long Chen[SUP] 2 [/SUP], Chuan He[SUP] 7 [/SUP], Chao-Ran Dong[SUP] 8 [/SUP], Qing-Gang Ge[SUP] 1 [/SUP], Jian Lin[SUP] 1 2 [/SUP]
Affiliations
Abstract
Background: The symptoms of coronavirus disease 2019 (COVID-19) range from moderate to critical conditions, leading to death in some patients, and the early warning indicators of the COVID-19 progression and the occurrence of its serious complications such as myocardial injury are limited. Methods: We carried out a multi-center, prospective cohort study in three hospitals in Wuhan. Genome-wide 5-hydroxymethylcytosine (5hmC) profiles in plasma cell-free DNA (cfDNA) was used to identify risk factors for COVID-19 pneumonia and develop a machine learning model using samples from 53 healthy volunteers, 66 patients with moderate COVID-19, 99 patients with severe COVID-19, and 38 patients with critical COVID-19. Results: Our warning model demonstrated that an area under the curve (AUC) for 5hmC warning moderate patients developed into severe status was 0.81 (95% CI 0.77-0.85) and for severe patients developed into critical status was 0.92 (95% CI 0.89-0.96). We further built a warning model on patients with and without myocardial injury with the AUC of 0.89 (95% CI 0.84-0.95). Conclusion: This is the first study showing the utility of 5hmC as an accurate early warning marker for disease progression and myocardial injury in patients with COVID-19. Our results show that phosphodiesterase 4D and ten-eleven translocation 2 may be important markers in the progression of COVID-19 disease.
Keywords: 5hmC; COVID-19; PDE4D; machine learning; myocardial injury.
. 2022 Jan 6;9:781267.
doi: 10.3389/fcell.2021.781267. eCollection 2021.
5-Hydroxymethylcytosine Signatures in Circulating Cell-Free DNA as Early Warning Biomarkers for COVID-19 Progression and Myocardial Injury
Hang-Yu Chen[SUP] 1 2 [/SUP], Xiao-Xiao Li[SUP] 1 [/SUP], Chao Li[SUP] 1 [/SUP], Hai-Chuan Zhu[SUP] 3 [/SUP], Hong-Yan Hou[SUP] 4 [/SUP], Bo Zhang[SUP] 4 [/SUP], Li-Ming Cheng[SUP] 4 [/SUP], Hui Hu[SUP] 5 [/SUP], Zhong-Xin Lu[SUP] 5 [/SUP], Jia-Xing Liu[SUP] 3 [/SUP], Ze-Ruo Yang[SUP] 6 [/SUP], Lei Zhang[SUP] 6 [/SUP], Nuo Xu[SUP] 6 [/SUP], Long Chen[SUP] 2 [/SUP], Chuan He[SUP] 7 [/SUP], Chao-Ran Dong[SUP] 8 [/SUP], Qing-Gang Ge[SUP] 1 [/SUP], Jian Lin[SUP] 1 2 [/SUP]
Affiliations
- PMID: 35071229
- PMCID: PMC8770986
- DOI: 10.3389/fcell.2021.781267
Abstract
Background: The symptoms of coronavirus disease 2019 (COVID-19) range from moderate to critical conditions, leading to death in some patients, and the early warning indicators of the COVID-19 progression and the occurrence of its serious complications such as myocardial injury are limited. Methods: We carried out a multi-center, prospective cohort study in three hospitals in Wuhan. Genome-wide 5-hydroxymethylcytosine (5hmC) profiles in plasma cell-free DNA (cfDNA) was used to identify risk factors for COVID-19 pneumonia and develop a machine learning model using samples from 53 healthy volunteers, 66 patients with moderate COVID-19, 99 patients with severe COVID-19, and 38 patients with critical COVID-19. Results: Our warning model demonstrated that an area under the curve (AUC) for 5hmC warning moderate patients developed into severe status was 0.81 (95% CI 0.77-0.85) and for severe patients developed into critical status was 0.92 (95% CI 0.89-0.96). We further built a warning model on patients with and without myocardial injury with the AUC of 0.89 (95% CI 0.84-0.95). Conclusion: This is the first study showing the utility of 5hmC as an accurate early warning marker for disease progression and myocardial injury in patients with COVID-19. Our results show that phosphodiesterase 4D and ten-eleven translocation 2 may be important markers in the progression of COVID-19 disease.
Keywords: 5hmC; COVID-19; PDE4D; machine learning; myocardial injury.