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Targeted proteomics identifies circulating biomarkers associated with active COVID-19 and post-COVID-19.

ABSTRACT: The ongoing Coronavirus Disease 2019 (COVID-19) pandemic is caused by the highly infectious Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). There is an urgent need for biomarkers that will help in better stratification of patients and contribute to personalized treatments. We performed targeted proteomics using the Olink platform and systematically investigated protein concentrations in 350 hospitalized COVID-19 patients, 186 post-COVID-19 individuals, and 61 healthy individuals from 3 independent cohorts. Results revealed a signature of acute SARS-CoV-2 infection, which is represented by inflammatory biomarkers, chemokines and complement-related factors. Furthermore, the circulating proteome is still significantly affected in post-COVID-19 samples several weeks after infection. Post-COVID-19 individuals are characterized by upregulation of mediators of the tumor necrosis (TNF)-α signaling pathways and proteins related to transforming growth factor (TGF)-ß. In addition, the circulating proteome is able to differentiate between patients with different COVID-19 disease severities, and is associated with the time after infection. These results provide important insights into changes induced by SARS-CoV-2 infection at the proteomic level by integrating several cohorts to obtain a large disease spectrum, including variation in disease severity and time after infection. These findings could guide the development of host-directed therapy in COVID-19.

SUBMITTER: Zoodsma M

PROVIDER: S-EPMC9670186 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Targeted proteomics identifies circulating biomarkers associated with active COVID-19 and post-COVID-19.

Zoodsma Martijn M de Nooijer Aline H AH Grondman Inge I Gupta Manoj Kumar MK Bonifacius Agnes A Koeken Valerie A C M VACM Kooistra Emma E Kilic Gizem G Bulut Ozlem O Gödecke Nina N Janssen Nico N Kox Matthijs M Domínguez-Andrés Jorge J van Gammeren Adriaan J AJ Ermens Anton A M AAM van der Ven Andre J A M AJAM Pickkers Peter P Blasczyk Rainer R Behrens Georg M N GMN van de Veerdonk Frank L FL Joosten Leo A B LAB Xu Cheng-Jian CJ Eiz-Vesper Britta B Netea Mihai G MG Li Yang Y

Frontiers in immunology 20221103

The ongoing Coronavirus Disease 2019 (COVID-19) pandemic is caused by the highly infectious Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). There is an urgent need for biomarkers that will help in better stratification of patients and contribute to personalized treatments. We performed targeted proteomics using the Olink platform and systematically investigated protein concentrations in 350 hospitalized COVID-19 patients, 186 post-COVID-19 individuals, and 61 healthy individuals fr ...[more]

PMID: 36405747

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Project description:PurposeCoronavirus disease 2019 (COVID-19) continues to threaten public health globally. Severe acute respiratory coronavirus type 2 (SARS-CoV-2) infection-dependent alterations in the host cell signaling network may unveil potential target proteins and pathways for therapeutic strategies. In this study, we aim to define early severity biomarkers and monitor altered pathways in the course of SARS-CoV-2 infection.Experimental designWe systematically analyzed plasma proteomes of COVID-19 patients from Turkey by using mass spectrometry. Different severity grades (moderate, severe, and critical) and periods of disease (early, inflammatory, and recovery) are monitored. Significant alterations in protein expressions are used to reconstruct the COVID-19 associated network that was further extended to connect viral and host proteins.ResultsAcross all COVID-19 patients, 111 differentially expressed proteins were found, of which 28 proteins were unique to our study mainly enriching in immunoglobulin production. By monitoring different severity grades and periods of disease, CLEC3B, MST1, and ITIH2 were identified as potential early predictors of COVID-19 severity. Most importantly, we extended the COVID-19 associated network with viral proteins and showed the connectedness of viral proteins with human proteins. The most connected viral protein ORF8, which has a role in immune evasion, targets many host proteins tightly connected to the deregulated human plasma proteins.Conclusions and clinical relevancePlasma proteomes from critical patients are intrinsically clustered in a distinct group than severe and moderate patients. Importantly, we did not recover any grouping based on the infection period, suggesting their distinct proteome even in the recovery phase. The new potential early severity markers can be further studied for their value in the clinics to monitor COVID-19 prognosis. Beyond the list of plasma proteins, our disease-associated network unravels altered pathways, and the possible therapeutic targets in SARS-CoV-2 infection by connecting human and viral proteins. Follow-up studies on the disease associated network that we propose here will be useful to determine molecular details of viral perturbation and to address how the infection affects human physiology.

Dataset Information

Targeted proteomics identifies circulating biomarkers associated with active COVID-19 and post-COVID-19.

Publications

Targeted proteomics identifies circulating biomarkers associated with active COVID-19 and post-COVID-19.

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