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 Jan 14;20(2):1564.
doi: 10.3390/ijerph20021564.

Circulating Peptidome Is Strongly Altered in COVID-19 Patients

Gianluca Baldanzi  1   2 , Beatrice Purghè  1   2 , Beatrice Ragnoli  3 , Pier Paolo Sainaghi  1   4 , Roberta Rolla  5 , Annalisa Chiocchetti  2   5 , Marcello Manfredi  1   2 , Mario Malerba  1   3
Affiliations

Circulating Peptidome Is Strongly Altered in COVID-19 Patients

Gianluca Baldanzi et al. Int J Environ Res Public Health. .

Abstract

Whilst the impact of coronavirus disease 2019 (COVID-19) on the host proteome, metabolome, and lipidome has been largely investigated in different bio-fluids, to date, the circulating peptidome remains unexplored. Thus, the present study aimed to apply an untargeted peptidomic approach to provide insight into alterations of circulating peptides in the development and severity of SARS-CoV-2 infection. The circulating peptidome from COVID-19 severe and mildly symptomatic patients and negative controls was characterized using LC-MS/MS analysis for identification and quantification purposes. Database search and statistical analysis allowed a complete characterization of the plasma peptidome and the detection of the most significant modulated peptides that were impacted by the infection. Our results highlighted not only that peptide abundance inversely correlates with disease severity, but also the involvement of biomolecules belonging to inflammatory, immune-response, and coagulation proteins/processes. Moreover, our data suggested a possible involvement of changes in protein degradation patterns. In the present research, for the first time, the untargeted peptidomic approach enabled the identification of circulating peptides potentially playing a crucial role in the progression of COVID-19.

Keywords: COVID-19; biomarkers; peptidomics; protein degradation; respiratory disease.

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 1
Figure 1
Experimental design of the study. Plasma samples from subjects who tested negative for COVID-19 (n = 12) and from COVID-19 positive patients divided into two groups depending on disease severity, namely, severe (n = 11) and mildly symptomatic patients (n = 12), were used. Circulating peptides were extracted through a strong anion exchange sorbent. Peptides were then characterized using an LC-MS system and the identified and modulated peptides were elaborated with bioinformatics to identify peptides influenced by SARS-CoV-2 infection.
Figure 2
Figure 2
(a) Venn Diagram of identified peptides in severe and mildly symptomatic COVID-19 positive patients, and negative controls; (b) hierarchical heatmap of identified peptides highlighting the three clusters of samples, with negative controls in green, COVID-19 mild in red, and COVID-19 severe in blue.
Figure 3
Figure 3
PLS-DA (a) and VIP score (b) summarizing the most prominent peptides contributing to the observed phenotypic variations in the COVID-19 peptidome.
Figure 4
Figure 4
Peptide network and pathways (a), complement and coagulation cascades (red dots) and activation of C3 and C5 (violet dots); pie chart of peptide classes (b).
See this image and copyright information in PMC

References

    1. WHO WHO Coronavirus (COVID-19) Dashboard. [(accessed on 13 September 2021)]. Available online: https://covid19.who.int.
    1. D’Alessandro A., Thomas T., Dzieciatkowska M., Hill R.C., Francis R.O., Hudson K.E., Zimring J.C., Hod E.A., Spitalnik S.L., Hansen K.C. Serum Proteomics in COVID-19 Patients: Altered Coagulation and Complement Status as a Function of IL-6 Level. J. Proteome Res. 2020;19:4417–4427. doi: 10.1021/acs.jproteome.0c00365. - DOI - PMC - PubMed
    1. Battaglini D., Lopes-Pacheco M., Castro-Faria-Neto H.C., Pelosi P., Rocco P.R.M. Laboratory Biomarkers for Diagnosis and Prognosis in COVID-19. Front. Immunol. 2022;13:857573. doi: 10.3389/fimmu.2022.857573. - DOI - PMC - PubMed
    1. Gordon D.E., Hiatt J., Bouhaddou M., Rezelj V.V., Ulferts S., Braberg H., Jureka A.S., Obernier K., Guo J.Z., Batra J., et al. Comparative Host-Coronavirus Protein Interaction Networks Reveal Pan-Viral Disease Mechanisms. Science. 2020;370:eabe9403. doi: 10.1126/science.abe9403. - DOI - PMC - PubMed
    1. Feng L., Yin Y.-Y., Liu C.-H., Xu K.-R., Li Q.-R., Wu J.-R., Zeng R. Proteome-Wide Data Analysis Reveals Tissue-Specific Network Associated with SARS-CoV-2 Infection. J. Mol. Cell Biol. 2020;12:946–957. doi: 10.1093/jmcb/mjaa033. - DOI - PMC - PubMed

Publication types