In-depth blood proteome profiling analysis revealed distinct functional characteristics of plasma proteins between severe and non-severe COVID-19 patients

Park, Joonho; Kim, Hyeyoon; Kim, So Yeon; Kim, Yeonjae; Lee, Hyukmin; Dan, Kisoon; Seong, Moon Woo; Han, Dohyun

doi:10.1038/s41598-020-80120-8

Cited by 98 publications

(80 citation statements)

References 45 publications

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“…Given the central role of proteins in biological processes as a whole, and in particular in diseases, we applied mass spectrometry–based proteomics to identify protein biomarkers that could discriminate between the COVID-19 patients who recovered and those who did not survive. Several proteomic studies ( 2 , 3 , 4 , 5 ) or even multi-omics studies, including proteomics ( 6 , 7 ), have to date investigated the serum or plasma of COVID-19 patients for the most part comparing a cohort of COVID-19 patients with control subjects (no disease) ( 2 , 3 ). Of special relevance to our work, an extensive study by Demichev et al ( 8 ) has already investigated the temporal aspect of COVID-19 progression in individuals to predict outcome and future disease progression.…”

Section: Introductionmentioning

confidence: 99%

A serum proteome signature to predict mortality in severe COVID-19 patients

et al. 2021

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Here, we recorded serum proteome profiles of 33 severe COVID-19 patients admitted to respiratory and intensive care units because of respiratory failure. We received, for most patients, blood samples just after admission and at two more later time points. With the aim to predict treatment outcome, we focused on serum proteins different in abundance between the group of survivors and non-survivors. We observed that a small panel of about a dozen proteins were significantly different in abundance between these two groups. The four structurally and functionally related type-3 cystatins AHSG, FETUB, histidine-rich glycoprotein, and KNG1 were all more abundant in the survivors. The family of inter-α-trypsin inhibitors, ITIH1, ITIH2, ITIH3, and ITIH4, were all found to be differentially abundant in between survivors and non-survivors, whereby ITIH1 and ITIH2 were more abundant in the survivor group and ITIH3 and ITIH4 more abundant in the non-survivors. ITIH1/ITIH2 and ITIH3/ITIH4 also showed opposite trends in protein abundance during disease progression. We defined an optimal panel of nine proteins for mortality risk assessment. The prediction power of this mortality risk panel was evaluated against two recent COVID-19 serum proteomics studies on independent cohorts measured in other laboratories in different countries and observed to perform very well in predicting mortality also in these cohorts. This panel may not be unique for COVID-19 as some of the proteins in the panel have previously been annotated as mortality markers in aging and in other diseases caused by different pathogens, including bacteria.

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Section: Introductionmentioning

confidence: 99%

A serum proteome signature to predict mortality in severe COVID-19 patients

et al. 2021

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“…Several groups have analyzed the serum or plasma proteome of COVID-19 infected patients (D’Alessandro et al ., 2020; Messner et al ., 2020; Park et al ., 2020; Shen et al ., 2020; Shu et al ., 2020). These were generally small-scale studies with single or few time points.…”

Section: Introductionmentioning

confidence: 99%

High-resolution longitudinal serum proteome trajectories in COVID-19 reveal patients-specific seroconversion

Geyer

Arend

Doll

et al. 2021

Preprint

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Biomarkers for COVID-19 are urgently needed. Here we bring the powerful technology of mass spectrometry (MS)-based proteomics to bear on this challenge. We measured serum proteomes of COVID-19 patients and symptomatic, but PCR-negative controls, in a time-resolved manner. In 262 controls and 458 longitudinal samples (average of 31 days) of 31 patients, hospitalized for COVID-19, a remarkable 26% of proteins changed significantly. Bioinformatics analyses revealed co-regulated groups and shared biological functions. Proteins of the innate immune system such as CRP, SAA1, CD14, LBP and LGALS3BP decreased early in the time course. In contrast, regulators of coagulation (APOH, FN1, HRG, KNG1, PLG) and lipid homeostasis (APOA1, APOC1, APOC2, APOC3, PON1) increased over the course of the disease. A global correlation map provides a systems-wide functional association between proteins, biological processes and clinical chemistry parameters. Importantly, five SARS-CoV-2 immunoassays against antibodies revealed excellent correlations with an extensive range of immunoglobulin regions, which were quantified by MS-based proteomics. The high-resolution profile of all immunoglobulin regions showed individual-specific differences and commonalities of potential pathophysiological relevance.

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“…As a result, 27 potential prognostic biomarkers (including complement factors, coagulation proteins, inflammation modulators, and pro-inflammatory factors induced by IL-6) were identified. Another study on serum proteome of patients with the severe and mild infections revealed differential expression of 91 proteins, of which 77 proteins were associated with neutrophil degranulation, blood coagulation, and neutrophil mediated immunity, and were proposed as prognostic biomarkers [ 101 ].…”

Section: Main Textmentioning

confidence: 99%

Mass spectrometry-based proteomics in basic and translational research of SARS-CoV-2 coronavirus and its emerging mutants

Rais

Drabovich

2021

Clin Proteom

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Molecular diagnostics of the coronavirus disease of 2019 (COVID-19) now mainly relies on the measurements of viral RNA by RT-PCR, or detection of anti-viral antibodies by immunoassays. In this review, we discussed the perspectives of mass spectrometry-based proteomics as an analytical technique to identify and quantify proteins of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and to enable basic research and clinical studies on COVID-19. While RT-PCR and RNA sequencing are indisputably powerful techniques for the detection of SARS-CoV-2 and identification of the emerging mutations, proteomics may provide confirmatory diagnostic information and complimentary biological knowledge on protein abundance, post-translational modifications, protein–protein interactions, and the functional impact of the emerging mutations. Pending advances in sensitivity and throughput of mass spectrometry and liquid chromatography, shotgun and targeted proteomic assays may find their niche for the differential quantification of viral proteins in clinical and environmental samples. Targeted proteomic assays in combination with immunoaffinity enrichments also provide orthogonal tools to evaluate cross-reactivity of serology tests and facilitate development of tests with the nearly perfect diagnostic specificity, this enabling reliable testing of broader populations for the acquired immunity. The coronavirus pandemic of 2019–2021 is another reminder that the future global pandemics may be inevitable, but their impact could be mitigated with the novel tools and assays, such as mass spectrometry-based proteomics, to enable continuous monitoring of emerging viruses, and to facilitate rapid response to novel infectious diseases.

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In-depth blood proteome profiling analysis revealed distinct functional characteristics of plasma proteins between severe and non-severe COVID-19 patients

Cited by 98 publications

References 45 publications

A serum proteome signature to predict mortality in severe COVID-19 patients

A serum proteome signature to predict mortality in severe COVID-19 patients

High-resolution longitudinal serum proteome trajectories in COVID-19 reveal patients-specific seroconversion

Mass spectrometry-based proteomics in basic and translational research of SARS-CoV-2 coronavirus and its emerging mutants

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