Serum prealbumin deserves more significance in the early triage of COVID-19 patients

Xiao-long Guo 1 , Yan Zhang 2 , Yu-hua Zeng 1 , Feng-ya Zhao 1 , Wei-ping Liu 1 , Li Xiao 1 , Ming-gang Yin 1 ,  and Cheng-li Zhanghttp://orcid.org/https://orcid.org/0000-0002-6478-5017 1
  • 1 Zigong First People’s Hospital, Zigong, P.R. China
  • 2 Neijiang Second People’ Hospital, Neijiang, P.R. China
Xiao-long Guo, Yan Zhang, Yu-hua Zeng, Feng-ya Zhao, Wei-ping Liu, Li Xiao, Ming-gang Yin and Cheng-li ZhangORCID iD: https://orcid.org/0000-0002-6478-5017

To the Editor

Recently, comprehensive analyses of laboratory findings in COVID-19 have been reported in Lancet [1] and JAMA [2]. According to these findings, C-reactive protein (CRP) has been reported as a sensitive inflammatory biomarker for the initial screening of COVID-19. Clinical practice guidelines indicated that routine blood tests and CRP should be performed first in COVID-19 suspected cases on admission [3]. However, CRP is highly aspecific to effectively identify the COVID-19 patients among patients with fever or cough [4].

Given that fever and cough are the earliest common symptoms of COVID-19 [5], [6], the hospital has established rigorous procedures to segregate patients with fever or cough and to prevent a further outbreak of COVID-19 in China. According to our previous study, we found that serum prealbumin, a negative acute phase protein, exhibited a significant change in the early stage of SARS-CoV-2 infection [7]. Prealbumin, which is also known as transthyretin, is mainly produced by the liver, and is consumed in inflammatory responses [8], [9]. Prealbumin levels are is significantly downregulated when stimulated by acute phase cytokines, such as interleukin-6 (IL-6), which increase the synthesis of the positive acute-phase reactants, including CRP, serum amyloid-A and a1-antitrypsin [10]. Thus, we suspect that prealbumin may be a good indicator in SARS-CoV-2 infection.

Here, we enrolled in 51 non-COVID-19 cases (patients merely had fever or cough symptoms) as the control group, and 31 confirmed COVID-19 patients. Prealbumin and CRP values from COVID-19 patients on admission were analyzed and compared with those of the control group. Baseline characteristics of patients in the two groups are shown in Table 1. Although the difference in serum CRP concentrations does not reach statistical significance between the groups (4.1 [1.31–14.69] mg/L vs. 15.2 [1.08–34.4] mg/L, Mann–Whitney U test, p>0.05), serum prealbumin was significantly decreased in COVID-19 patients on admission compared with the control group (141.4 [123.5–153.67] mg/L vs. 228 [193–263.5] mg/L, p<0.001, Mann–Whitney U test) (Figure 1A and B). Furthermore, prealbumin concentration had recovered to normal range after the patients recovered (Supplemental Table S1).

Table 1:

Baseline characteristics of patients in COVID-19 group and control group.

COVID-19 group (n=31)Non-COVID-19 group (n=51)p-Valuea
Age, years
 Mean (SD)40.45 (12.8)29.3 (14.9)0.001
  ≤3914 (45%)42 (82%)
  40–5915 (48%)6 (12%)
  ≥602 (7%)3 (6%)
Sex
 Female16 (52%)26 (51%)0.956
 Male15 (48%)25 (49%)
Common symptoms
 Fever21/3140/510.282
 Cough20/3113/51<0.001
Laboratory findings
 CRP, median (IQR) (0–5 mg/L)4.1 (1.31–14.69)15.2 (1.08–34.4)0.1
 >5 mg/L15/31 (48.39%)36/51 (70.59%)
 Prealbumin, median (IQR) (180–400 mg/L)141.4 (123.5–153.67)228 (193–263.5)<0.001
 <180 mg/L28/31 (90.32%)7/51 (13.73%)

ap-Values indicate differences between COVID-19 group and non-COVID-19 group. p<0.05 was considered statistically significant.

Figure 1:
Figure 1:

Prealbumin and CRP in COVID-19 patients.

(A, B) Distribution of results of prealbumin and CRP in the two groups. © Prealbumin and CRP for diagnosing COVID-19 patients.

Citation: Clinical Chemistry and Laboratory Medicine (CCLM) 58, 10; 10.1515/cclm-2020-0663

In addition, the ROC curve was used to analyse the clinical predictive value of prealbumin and CRP in COVID-19 patients (Figure 1C). The ROC curve results showed that prealbumin was more effective in predicting COVID-19 with an AUC of 0.94 at the best cut-off value of 176.5 mg/L, a sensitivity of 0.903, and a specificity of 0.863 (Supplemental Table S2). These findings suggest that prealbumin has a potential to be an effective biomarker and is more sensitive than CRP, for the early triage of COVID-19 patients.

In the early stage of SARS-CoV-2 infection, serum prealbumin decreased markedly in COVID-19 patients compared with the control group. Combined with common symptoms and epidemiology, prealbumin could act as a surrogate biomarker for the early triage of COVID-19. However, the reliability of this approach should be verified with more clinical data. This inflammation-related biomarker could be helpful to prevent the COVID-19 from spreading and it can be even more reliable and economical once widely applied in clinical laboratory.

Acknowledgments

The authors thank the Department of Fever Clinic and Clinical Laboratory of Zigong First People’s Hospital and Neijiang Second People’ Hospital.

Research funding: This work was supported by the Sichuan Medical Scientific Research Foundation under Grant Q18025.

Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

Competing interests: Authors state no conflict of interest.

Informed consent: Informed consent was obtained from all individuals included in this study.

Ethical approval: Research involving human subjects complied with all relevant national regulations, institutional policies and is in accordance with the tenets of the Helsinki Declaration (as revised in 2013), and has been approved by the authors’ Institutional Review Board.

References

  • 1.

    Chen, N, Zhou, M, Dong, X, Qu, J, Gong, F, Han, Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020;395:507–13. https://doi.org/10.1016/s0140-6736(20)30211-7.

    • Crossref
    • Export Citation
  • 2.

    Richardson, S, Hirsch, JS, Narasimhan, M, Crawford, JM, McGinn, T, Davidson, KW, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA 2020;323:2052–9. https://doi.org/10.1001/jama.2020.6775.

    • Crossref
    • PubMed
    • Export Citation
  • 3.

    National Health Commission of the People’s Republic of China. Protocol on prevention and control of COVID-19 (Edition 6). Available at: https://en.nhc.gov.cn/2020-03/29/c_78468.htm.pdf [Accessed 29 Mar 2020].

  • 4.

    Sproston, NR, Ashworth, JJ. Role of C-reactive protein at sites of inflammation and infection. Front Immunol 2018;9:754. https://doi.org/10.3389/fimmu.2018.00754.

    • Crossref
    • PubMed
    • Export Citation
  • 5.

    Huang, C, Wang, Y, Li, X, Ren, L, Zhao, J, Hu, Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497–506. https://doi.org/10.1016/s0140-6736(20)30183-5.

    • Crossref
    • PubMed
    • Export Citation
  • 6.

    Wang, D, Hu, B, Hu, C, Zhu, F, Liu, X, Zhang, J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020;323:1061–9. https://doi.org/10.1001/jama.2020.1585.

    • Crossref
    • PubMed
    • Export Citation
  • 7.

    Guo, X, Liu, W, Zhong, J, Yin, M, Zhang, C. Laboratory findings in SARS-CoV-2 infections in Zigong, China: key points for serum prealbumin [Letter]. Clin Lab 2020;66:e1151–4. https://doi.org/10.7754/clin.lab.2020.200419.

  • 8.

    Ando, Y, Nakamura, M, Araki, S. Transthyretin-related familial amyloidotic polyneuropathy. Arch Neurol 2005;62:1057–62. https://doi.org/10.1001/archneur.62.7.1057.

    • Crossref
    • PubMed
    • Export Citation
  • 9.

    Ingenbleek, Y, Bernstein, L. The stressful condition as a nutritionally dependent adaptive dichotomy. Nutrition 1999;15:305–20. https://doi.org/10.1016/s0899-9007(99)00009-x.

    • Crossref
    • PubMed
    • Export Citation
  • 10.

    Myron Johnson, A, Merlini, G, Sheldon, J, Ichihara, K. Scientific Division Committee on Plasma Proteins IFoCC, Laboratory M. Clinical indications for plasma protein assays: transthyretin (prealbumin) in inflammation and malnutrition. Clin Chem Lab Med 2007;45:419–26. https://doi.org/10.1515/cclm.2007.051.

Supplementary Material

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  • 1.

    Chen, N, Zhou, M, Dong, X, Qu, J, Gong, F, Han, Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020;395:507–13. https://doi.org/10.1016/s0140-6736(20)30211-7.

    • Crossref
    • Export Citation
  • 2.

    Richardson, S, Hirsch, JS, Narasimhan, M, Crawford, JM, McGinn, T, Davidson, KW, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA 2020;323:2052–9. https://doi.org/10.1001/jama.2020.6775.

    • Crossref
    • PubMed
    • Export Citation
  • 3.

    National Health Commission of the People’s Republic of China. Protocol on prevention and control of COVID-19 (Edition 6). Available at: https://en.nhc.gov.cn/2020-03/29/c_78468.htm.pdf [Accessed 29 Mar 2020].

  • 4.

    Sproston, NR, Ashworth, JJ. Role of C-reactive protein at sites of inflammation and infection. Front Immunol 2018;9:754. https://doi.org/10.3389/fimmu.2018.00754.

    • Crossref
    • PubMed
    • Export Citation
  • 5.

    Huang, C, Wang, Y, Li, X, Ren, L, Zhao, J, Hu, Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497–506. https://doi.org/10.1016/s0140-6736(20)30183-5.

    • Crossref
    • PubMed
    • Export Citation
  • 6.

    Wang, D, Hu, B, Hu, C, Zhu, F, Liu, X, Zhang, J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020;323:1061–9. https://doi.org/10.1001/jama.2020.1585.

    • Crossref
    • PubMed
    • Export Citation
  • 7.

    Guo, X, Liu, W, Zhong, J, Yin, M, Zhang, C. Laboratory findings in SARS-CoV-2 infections in Zigong, China: key points for serum prealbumin [Letter]. Clin Lab 2020;66:e1151–4. https://doi.org/10.7754/clin.lab.2020.200419.

  • 8.

    Ando, Y, Nakamura, M, Araki, S. Transthyretin-related familial amyloidotic polyneuropathy. Arch Neurol 2005;62:1057–62. https://doi.org/10.1001/archneur.62.7.1057.

    • Crossref
    • PubMed
    • Export Citation
  • 9.

    Ingenbleek, Y, Bernstein, L. The stressful condition as a nutritionally dependent adaptive dichotomy. Nutrition 1999;15:305–20. https://doi.org/10.1016/s0899-9007(99)00009-x.

    • Crossref
    • PubMed
    • Export Citation
  • 10.

    Myron Johnson, A, Merlini, G, Sheldon, J, Ichihara, K. Scientific Division Committee on Plasma Proteins IFoCC, Laboratory M. Clinical indications for plasma protein assays: transthyretin (prealbumin) in inflammation and malnutrition. Clin Chem Lab Med 2007;45:419–26. https://doi.org/10.1515/cclm.2007.051.

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    Prealbumin and CRP in COVID-19 patients.

    (A, B) Distribution of results of prealbumin and CRP in the two groups. © Prealbumin and CRP for diagnosing COVID-19 patients.