key: cord-0736540-mv0kn0at
authors: He, Bangshun; Zhong, Aifang; Wu, Qiuyue; Liu, Xiong; Lin, Jie; Chen, Chao; He, Yiming; Guo, Yanju; Zhang, Man; Zhu, Peiran; Wu, Jian; Wang, Changjun; Wang, Shukui; Xia, Xinyi
title: Tumor biomarkers predict clinical outcome of COVID-19 patients
date: 2020-06-11
journal: J Infect
DOI: 10.1016/j.jinf.2020.05.069
sha: 9a1565b177405d1fb55fc326c5122138097ce4bd
doc_id: 736540
cord_uid: mv0kn0at

nan

A recent article in Journal of Infection by Fu and colleagues have summarized the clinical characteristics of coronavirus disease 2019 (COVID-19) in China, and described that those with medical comorbidities tend to have more severe clinical symptoms and higher case-fatality rate, according to data of 43 studies involving 3600 patients. 1 Of the data from China, 81% cases were mild, 14% were severe, and 5% were critical, and the casefatality rate was 2.3% in all cases and 49.0% in critical cases. 2 Older age and comorbidities, such as cardiovascular disease, confer a higher risk for severe disease, and young and otherwise healthy patients are also at risk for complications. 3 ARDS (Acute respiratory distress syndrome) and respiratory failure, sepsis, acute cardiac injury and heart failure were the most common critical complications during exacerbation of COVID-19. Several laboratory outcomes indicated the severity and the clinical outcome of COVID-19 patients. Previous studies reported that tumor biomarkers, such as carcino embryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), neuron-specific enolase (NSE), squamous cell carcinoma antigen (SCCA) and Pro-Gastrin Releasing Peptide (Pro-GRP), were elevated in the patients with benign lung disorders, such as pneumonia and pulmonary fibrosis. 4 , 5 , 6 We would like to share our findings that the role of tumor markers related lung cancer in COVID-19 patients as predictive indicators for clinical outcome.

A total of 129 patients diagnosed as COVID-19, with 20 moderate (15.50%), 73 severe (56.59%) and 36 critical severe cases (27.91%) on admission, were included in this study. In addition, a total of 80 age-and gender-matched health individuals were enrolled as controls. The patients self-reported medical history of comorbidities were recorded on admission and were classified as hypertension, cardiovascular disease, diabetes (type 2), chronic obstructive pulmonary disease (COPD) and others. Of 129 cases, 114 cases (88.37%) were discharged from hospital for their recovery from COVID-19, and 15 cases (11.63%) were deceased during the treatment, shown in Supplementary Table 1. For the characteristics of patients, we observed that the mean age of patients was significantly different among the subgroup of severity, and the mean age of patients with critical severe was significant higher than those who with severe or moderate. The distribution of patients with diabetes, chronic kidney disease and others comorbidities have significant differences among the sub-groups of disease severity. Most deceased cases (14/15) were with the critical severe COVID-19 and one with severe COVID-19. Patients who deceased have significant higher ration of comorbidities of chronic kidney disease (p = 0.001), shown in Table 1 .

The plasma concentration of all the five biomarkers were significantly elevated in cases than those in controls (p all < 0.01). In addition, the significant differences of plasma level of CEA, CYFRA21-1 and SCCA were observed among the subgroups of severity of disease and clinical outcome ( Table 1 ) and plasma level of CEA, CYFRA21-1, SCCA were significantly increased with the advance serverity of disease. Whereas, there were no significant differences of NSE and proGRP contration amonge the different severity subgroups, shown in Supplementary Figure 1 .

To further analyze prognostic role of tumor biomarker in COVID-19 patients, a logistic regression was applied to measure the associations of tumor biomarkers level to risk of death. Crude OR, OR adjusted for age and gender (model 1), and OR adjusted for molel1 plus comordities (model 2) were used to assess the relative risk, respectively. The results revealed that increased level of CEA (OR = 1.13, 95%CI:1.03-1.23, p = 0.010; adjust model 1 OR Table 2 ), indicating that dynamic monitor for the three biomarkers could predict the clinical outcome of COVID-19 patients.

This study revealed that age, diabetes, chronic kidney disease and other diseases were associated with the severity of COVID-19 patients. In which, chronic kidney disease was also regarded as a risk of death of COVID-19 patients, which was consistent the result of publised data. 7 Acutally, the most common cause of death in COVID-19 patients is viral pneumonia leading to inflammatory response results in the progression to multi-organ failure. Therefore, those patients have history of diabetes, chronic kidney disease were more susceptiable to develop multi-organ failure and lead to death. Tumor biomarkers related lung cancer that CEA, CYFRA21-1, NSE, SCCA, ProGRP were previously reported to be elevated in the pneumonia patients 5 or benign lung diseases. 6 , 8 In this study, we observed that all five tumor biomarkers were significantly increased in the plasma of COVID-19 patients than those in health controls, that CEA, CYFRA21-1 and SCCA were significantly different among the subgroups of severity of disease and clinical outcome, and that CEA, CYFRA21-1, SCCA could predicte the clinical outcome of COVID-19 patients. This study firstly reported the role of tumor biomarkers in COVID-19 patients.

In short, we concluded that the concentrations of tumor biomarkers of CEA, CYFRA21-1, NSE, SCCA, ProGRP were elevated in COVID-19 patients, and that CEA, CYFRA21-1, SCCA could predicte the clinical outcome of COVID-19 patients.

The authors declare no competing interests

Clinical characteristics of coronavirus disease 2019 (COVID-19) in China: A systematic review and metaanalysis

Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72314 Cases From the Chinese Center for Disease Control and Prevention

Estimates of the severity of coronavirus disease 2019: a model-based analysis

Evaluation of cytokeratin 19 serum fragments (CYFRA 21-1) in patients with lung cancer: results of a multicenter trial

Identifying the Best Marker Combination in CEA, CA125, CY211, NSE, and SCC for Lung Cancer Screening by Combining ROC Curve and Logistic Regression Analyses: Is It Feasible?

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Determining the cut-off value of pro-gastrin releasing peptide (ProGRP) in lung cancer according to population characteristics

Kidney disease is associated with in-hospital death of patients with COVID-19

Serum carcinoembryonic antigen correlates with severity of idiopathic pulmonary fibrosis

China Aifang Zhong # Medical Technical Support Division, Changzhou Medical District, the 904th Hospital

We thank Dr. Qiwen Deng (Nanjing First Hospital, Nanjing Medical University) for his help in analyzing data. We thank all the patients who consented to donate their data for analysis and all the medical staff members of Huoshengshan hospital. We would also thank the editor and peer reviewers for their hard work for this article.This study was financially supported by grants Key 

Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.jinf.2020.05.069 .