Understanding COVID-19 progression with longitudinal peripheral blood mononuclear cell proteomics: Changes in the cellular proteome over time

Figueirêdo Leite, Giuseppe Gianini; Colo Brunialti, Milena Karina; Peçanha-Pietrobom, Paula M.; Abrão Ferreira, Paulo R.; Ota-Arakaki, Jaquelina Sonoe; Cunha-Neto, Edecio; Ferreira, Bianca Lima; Ronsein, Graziella E.; Tashima, Alexandre Keiji; Salomão, Reinaldo

doi:10.1016/j.isci.2023.107824

Cited by 6 publications

(4 citation statements)

References 63 publications

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“…Recently, Figueirêdo Leite et al . published their proteomics data from PBMC in hospitalised COVID-19 subjects, including both patients treated at the ICU (n=9) and those treated at the hospital ward (n=8) ( 29 ). To assess whether the transcriptional changes in PBMC from the present study were representative of changes at the protein level, we next accessed this proteomics dataset to investigate changes in the ECM remodelling process.…”

Section: Resultsmentioning

confidence: 99%

“…Pre-processed PBMC proteomics data from COVID-19 patients (n=17), collected on day 7 of hospitalisation, was obtained through a recent publications GitHub repository ( https://github.com/GiuseppeLeite/COVID19_Proteomic ) ( 29 ). Before differential protein abundance analysis, data were normalised, log2FC transformed, filtered, imputed and batch effect corrected as described in the original article ( 29 ). Sample clustering was inspected with a multidimensional scaling (MDS) plot ( Supplementary Figure S3 ).…”

Section: Methodsmentioning

confidence: 99%

“…Gene sets were derived from the Molecular signature database (MSigDB, version 7.5.1). Pearson correlation analysis of ECM remodelling gene expression and clinical-and circulating variables was performed in R, with the cor() function and presented with the corrplot package (v.0.92) (28).…”

Section: Statistical Analyses 281 Analyses Of Rna Sequencing Of Pbmcmentioning

confidence: 99%

“…Protein expression of PBMC in severe COVID-19 patients. GSEA analysis of PBMC protein levels from publicly available proteome analyses [28] shows that ECM regulators are significantly enriched in ICU patients (n=9) compared to Ward patients (n=8) (A). Significantly differentially abundant ECM regulator proteins in severe COVID-19 patients (p-value < 0.05, ICU vs Ward) (B).…”

Section: B Amentioning

confidence: 99%

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Extracellular matrix remodelling pathway in peripheral blood mononuclear cells from severe COVID-19 patients: an explorative study

Murphy,

Balzer,

Ranheim

et al. 2024

Front. Immunol.

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There is a reciprocal relationship between extracellular matrix (ECM) remodelling and inflammation that could be operating in the progression of severe COVID-19. To explore the immune-driven ECM remodelling in COVID-19, we in this explorative study analysed these interactions in hospitalised COVID-19 patients. RNA sequencing and flow analysis were performed on peripheral blood mononuclear cells. Inflammatory mediators in plasma were measured by ELISA and MSD, and clinical information from hospitalised COVID-19 patients (N=15) at admission was included in the analysis. Further, we reanalysed two publicly available datasets: (1) lung tissue RNA-sequencing dataset (N=5) and (2) proteomics dataset from PBCM. ECM remodelling pathways were enriched in PBMC from COVID-19 patients compared to healthy controls. Patients treated at the intensive care unit (ICU) expressed distinct ECM remodelling gene profiles compared to patients in the hospital ward. Several markers were strongly correlated to immune cell subsets, and the dysregulation in the ICU patients was positively associated with plasma levels of inflammatory cytokines and negatively associated with B-cell activating factors. Finally, our analysis of publicly accessible datasets revealed (i) an augmented ECM remodelling signature in inflamed lung tissue compared to non-inflamed tissue and (ii) proteomics analysis of PBMC from severe COVID-19 patients demonstrated an up-regulation in an ECM remodelling pathway. Our results may suggest the presence of an interaction between ECM remodelling, inflammation, and immune cells, potentially initiating or perpetuating pulmonary pathology in severe COVID-19.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Statistical Analyses 281 Analyses Of Rna Sequencing Of Pbmcmentioning

confidence: 99%

Section: B Amentioning

confidence: 99%

See 2 more Smart Citations

Extracellular matrix remodelling pathway in peripheral blood mononuclear cells from severe COVID-19 patients: an explorative study

Murphy,

Balzer,

Ranheim

et al. 2024

Front. Immunol.

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Blood proteomics of COVID-19 infection: An update

Alexovič,

Bondarchuk,

Uličná

et al. 2024

Clinica Chimica Acta

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Proteomic profiling of peripheral blood mononuclear cells reveals immune dysregulation and metabolic alterations in kidney transplant recipients with COVID-19

Leite,

Sousa,

Rodrigues

et al. 2024

Preprint

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The emergence of the Coronavirus disease 2019 (COVID-19) pandemic in 2020 has profoundly impacted global health systems, particularly affecting vulnerable populations like kidney transplant recipients (KTRs).We prospectively collected blood samples from 17 PCR-confirmed COVID-19 KTR patients and 10 non-COVID-19 KTRs between May and September 2020. Using tandem mass tag-based quantitative proteomics, we characterized peripheral blood mononuclear cells (PBMCs) from KTRs alongside plasma protein biomarkers and lymphocyte counts, followed by bioinformatics analyses. Our study revealed significant proteomic alterations within PBMCs of SARS-CoV-2 infected KTRs, particularly in pathways associated with glycolysis, glucose metabolism, and neutrophil degranulation. Additionally, we observed an altered immune response marked by elevated cytokines and inflammatory mediators, coupled with decreased lymphocyte counts. Notably, patients with acute kidney injury (AKI) exhibited worse outcomes, including higher rates of ICU transfer and mechanical ventilation. Comparison of PBMC proteomic profiles between AKI and non-AKI patients highlighted distinct immune-related pathways, with AKI patients showing pronounced alterations in innate immune responses, particularly in neutrophil degranulation. Moreover, our analysis unveiled a negative correlation between T cell counts and neutrophil degranulation, suggesting potential implications for immune dysregulation in COVID-19. Our findings shed light on the complex proteomic landscape and immune responses in COVID-19-infected KTRs, emphasizing the critical need for studies focused on this population, especially in individuals with AKI. Furthermore, our observations provide valuable insights for further exploration of therapeutic interventions targeting immune dysregulation pathways in this vulnerable population.

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Understanding COVID-19 progression with longitudinal peripheral blood mononuclear cell proteomics: Changes in the cellular proteome over time

Cited by 6 publications

References 63 publications

Extracellular matrix remodelling pathway in peripheral blood mononuclear cells from severe COVID-19 patients: an explorative study

Extracellular matrix remodelling pathway in peripheral blood mononuclear cells from severe COVID-19 patients: an explorative study

Blood proteomics of COVID-19 infection: An update

Proteomic profiling of peripheral blood mononuclear cells reveals immune dysregulation and metabolic alterations in kidney transplant recipients with COVID-19

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