Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Sep 28;11(10):2436.
doi: 10.3390/microorganisms11102436.

Utilizing Protein-Peptide Hybrid Microarray for Time-Resolved Diagnosis and Prognosis of COVID-19

Peiyan Zheng  1 , Baolin Liao  2 , Jiao Yang  3 , Hu Cheng  3   4 , Zhangkai J Cheng  1 , Huimin Huang  1 , Wenting Luo  1 , Yiyue Sun  3   4 , Qiang Zhu  5 , Yi Deng  3   4 , Lan Yang  3 , Yuxi Zhou  3 , Wenya Wu  3   4 , Shanhui Wu  1 , Weiping Cai  2 , Yueping Li  2 , Xiaoneng Mo  2 , Xinghua Tan  2 , Linghua Li  2 , Hongwei Ma  3 , Baoqing Sun  1
Affiliations

Utilizing Protein-Peptide Hybrid Microarray for Time-Resolved Diagnosis and Prognosis of COVID-19

Peiyan Zheng et al. Microorganisms. .

Abstract

The COVID-19 pandemic has highlighted the urgent need for accurate, rapid, and cost-effective diagnostic methods to identify and track the disease. Traditional diagnostic methods, such as PCR and serological assays, have limitations in terms of sensitivity, specificity, and timeliness. To investigate the potential of using protein-peptide hybrid microarray (PPHM) technology to track the dynamic changes of antibodies in the serum of COVID-19 patients and evaluate the prognosis of patients over time. A discovery cohort of 20 patients with COVID-19 was assembled, and PPHM technology was used to track the dynamic changes of antibodies in the serum of these patients. The results were analyzed to classify the patients into different disease severity groups, and to predict the disease progression and prognosis of the patients. PPHM technology was found to be highly effective in detecting the dynamic changes of antibodies in the serum of COVID-19 patients. Four polypeptide antibodies were found to be particularly useful for reflecting the actual status of the patient's recovery process and for accurately predicting the disease progression and prognosis of the patients. The findings of this study emphasize the multi-dimensional space of peptides to analyze the high-volume signals in the serum samples of COVID-19 patients and monitor the prognosis of patients over time. PPHM technology has the potential to be a powerful tool for tracking the dynamic changes of antibodies in the serum of COVID-19 patients and for improving the diagnosis and prognosis of the disease.

Keywords: PPHM assay; SARS-CoV-2; receptor binding domain (RBD) probe; sero-IgG dynamic (IsD) events; serological assays.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 3
Figure 3
ECSP IsD curves reveal differential IgG dynamics in humoral immune responses among three patient groups. (A) A heat map was produced according to the response rates for ECSPs among the three indicated patient groups, based on PPHM-2 screening within the discovery cohort. The yellow box indicates ECSPs which yield moderate response rates (~50%) among patients generally, but which exhibit a low response rate among a single patient group. The ECSPs from the yellow box are detailed at the bottom of the panel. (B) Calculation of the response rate for the identified ECSPs in each patient group. (C) The IsD curves detected using P-N37~P-N30, N protein, and RBD probes in each of the three patient groups. Data for each time point are shown as the mean + SEM (the average of data for at least three samples). The differential IsD curve patterns were observed in different patient groups during different stages of disease course (defined with the dashed grey line). The color design for the ECSP IsD curves for the patient groups is the same as in Figure 3B. (D) The overlaps of ECSP IsD curves of P-N37~P-N40 in the three patient groups. The characteristics of the ECSP IsD curve of P-N38 in the Critical patient group can be used as an index to indicate poor prognosis.
Figure 1
Figure 1
The representative patient information of the three groups, as well as the detection time and results of PPHM COVID−19. (A) A total of 14 patients of group 1 obtained an earlier diagnosis because of a situation in which two or more anti-ECSP IgGs entered the sero-positive period earlier than the anti-RBD IgG; (B) 17 patients were categorized into Group 2; (C) 9 patients were categorized into Group 3.
Figure 2
Figure 2
ECSP IsD curves outperformed infection-related biomarkers in predicting COVID-19 prognosis. (A) The predictive ability of ECSP IsD curves in patients with different severity levels at different periods. (B) The dynamic changes in both IL-6 levels (purple) and CRP levels (blue) for three COVID-19 patients from the Critical patient group. The threshold for normal levels of IL-6 and CRP are presented with dashed lines of the corresponding color. High levels of IL-6 and CRP indicate poor disease prognosis. (C) The ECSP IsD curves of P-N37~P-N40 (bottom) and the dynamic changes of PCR results detected at different time points (top) for Patient #4 (left). the color design used for these four ECSP IsD curves is the same as in Figure 3D, and the threshold for a valid IgG signal is presented as a dashed line. The dynamic changes in the IL-6 level for Patient #4 (right); a normal IL-6 level is presented as a dashed line.
Figure 4
Figure 4
The model for time-resolved diagnosis of COVID-19 disease progression and prognosis (PPHM-MPAD-IsD “PMI” model).
See this image and copyright information in PMC

References

    1. Wu F., Zhao S., Yu B., Chen Y.M., Wang W., Song Z.G., Hu Y., Tao Z.W., Tian J.H., Pei Y.Y., et al. A new coronavirus associated with human respiratory disease in China. Nature. 2020;579:265–269. doi: 10.1038/s41586-020-2008-3. - DOI - PMC - PubMed
    1. Zhou P., Yang X.L., Wang X.G., Hu B., Zhang L., Zhang W., Si H.R., Zhu Y., Li B., Huang C.L., et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579:270–273. doi: 10.1038/s41586-020-2012-7. - DOI - PMC - PubMed
    1. Zhu N., Zhang D., Wang W., Li X., Yang B., Song J., Zhao X., Huang B., Shi W., Lu R., et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N. Engl. J. Med. 2020;382:727–733. doi: 10.1056/NEJMoa2001017. - DOI - PMC - PubMed
    1. Gromova O.A., Torshin I.Y., Semenov V.A., Putilina M.V., Chuchalin A.G. Direct and indirect neurological manifestations of COVID-19. Zhurnal Nevrol. I Psikhiatrii Im. SS Korsakova. 2020;120:11–21. doi: 10.17116/jnevro202012011111. - DOI - PubMed
    1. Chen N., Zhou M., Dong X., Qu J., Gong F., Han Y., Qiu Y., Wang J., Liu Y., Wei Y., et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet. 2020;395:507–513. doi: 10.1016/S0140-6736(20)30211-7. - DOI - PMC - PubMed

LinkOut - more resources