A time-resolved proteomic and prognostic map of COVID-19

Demichev, Vadim; Tober‐Lau, Pinkus; Lemke, Oliver; Nazarenko, Tatiana; Thibeault, Charlotte; Whitwell, Harry J.; Röhl, Annika; Freiwald, Anja; Szyrwiel, Łukasz; Ludwig, Daniela; Correia‐Melo, Clara; Aulakh, Simran Kaur; Helbig, Elisa T; Stubbemann, Paula; Lippert, Lena J; Grüning, Nana‐Maria; Blyuss, Oleg; Vernardis, Spyros; White, Matthew; Messner, Christoph B.; Joannidis, Michael; Sonnweber, Thomas; Klein, Sebastian; Pizzini, Alex; Wohlfarter, Yvonne; Sahanic, Sabina; Hilbe, Richard; Schaefer, Benedikt; Wagner, Sonja; Mittermaier, Mirja; Machleidt, Felix; García, Carmen; Ruwwe‐Glösenkamp, Christoph; Lingscheid, Tilman; Jarcy, Laure Bosquillon de; Stegemann, Miriam; Pfeiffer, Moritz; Jürgens, Linda; Denker, Sophy; Zickler, Daniel; Enghard, Philipp; Zelezniak, Aleksej; Campbell, Archie; Hayward, Caroline; Porteous, David J.; Marioni, Riccardo E.; Uhrig, Alexander; Müller-Redetzky, Holger; Zoller, Heinz; Löffler‐Ragg, Judith

doi:10.1016/j.cels.2021.05.005

Cited by 154 publications

(185 citation statements)

References 106 publications

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“…In the last months, the research efforts on COVID-19 have expanded enormously. In this period, quite a few multi-omics and plasma proteomics studies have appeared studying COVID-19 patients, generating data comparable to ours, but with different research questions and thus also different study designs (2,5,6,7,8 Preprint, 31 Preprint). Still, the outcome of these studies and their conclusions can be compared with the data obtained in our cohort (further termed "Ferrara cohort").…”

Section: Comparison With Related Recent Covid-19 Plasma Proteome Studiessupporting

confidence: 62%

“…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. Although their cohort did comprise some patients who did not survive, for the most part, the subjects recovered and were discharged.…”

Section: Introductionmentioning

confidence: 99%

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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: Comparison With Related Recent Covid-19 Plasma Proteome Studiessupporting

confidence: 62%

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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“…Finally, a DIA-MS study was performed by Demichev et al [ 42 ] to characterize the time-dependent evolution of COVID-19 disease in 139 patients (classified with a variable grade). Analyzing the plasma proteomes at 687 sampling points, the authors describe a primary spike of the inflammation and systemic response, and then a gradual decrease in such response, suggestive of ongoing processes of immunomodulation, tissue repair, and metabolic recovery.…”

Section: Proteomics Of Covid-19mentioning

confidence: 99%

COVIDomics: The Proteomic and Metabolomic Signatures of COVID-19

Costanzo

Caterino

Fedele

et al. 2022

IJMS

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Omics-based technologies have been largely adopted during this unprecedented global COVID-19 pandemic, allowing the scientific community to perform research on a large scale to understand the pathobiology of the SARS-CoV-2 infection and its replication into human cells. The application of omics techniques has been addressed to every level of application, from the detection of mutations, methods of diagnosis or monitoring, drug target discovery, and vaccine generation, to the basic definition of the pathophysiological processes and the biochemical mechanisms behind the infection and spread of SARS-CoV-2. Thus, the term COVIDomics wants to include those efforts provided by omics-scale investigations with application to the current COVID-19 research. This review summarizes the diverse pieces of knowledge acquired with the application of COVIDomics techniques, with the main focus on proteomics and metabolomics studies, in order to capture a common signature in terms of proteins, metabolites, and pathways dysregulated in COVID-19 disease. Exploring the multiomics perspective and the concurrent data integration may provide new suitable therapeutic solutions to combat the COVID-19 pandemic.

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“…SAAs and SERPINAs are important for proper neutrophil functionality [56,[65][66][67], which might play an additional role in the impairment we observed. Moreover, recent reports linked plasma proteomic changes of COVID-19 patients to different degrees of disease severity, with special emphasis on tissue repair and coagulation proteins, such as the SERPINAs, inflammatory markers and regulators, like CRP and TSKU, macrophage trafficking markers, like SELENOP, as well as immune cell markers such as LBP and CD14 [68][69][70][71][72][73][74][75]. These findings in our cohort further strengthens our hypothesis on myeloid cell dysregulation and it is in line with the reported COVID-19 proteomic data [71,74,75].…”

Section: Plos Pathogensmentioning

confidence: 99%

Hyperinflammatory environment drives dysfunctional myeloid cell effector response to bacterial challenge in COVID-19

et al. 2022

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COVID-19 displays diverse disease severities and symptoms including acute systemic inflammation and hypercytokinemia, with subsequent dysregulation of immune cells. Bacterial superinfections in COVID-19 can further complicate the disease course and are associated with increased mortality. However, there is limited understanding of how SARS-CoV-2 pathogenesis and hypercytokinemia impede the innate immune function against bacterial superinfections. We assessed the influence of COVID-19 plasma hypercytokinemia on the functional responses of myeloid immune cells upon bacterial challenges from acute-phase COVID-19 patients and their corresponding recovery (rec)-phase. We show that a severe hypercytokinemia status in COVID-19 patients correlates with the development of bacterial superinfections. Neutrophils and monocytes derived from COVID-19 patients in their acute-phase showed an impaired intracellular microbicidal capacity upon bacterial challenges. The impaired microbicidal capacity was reflected by abrogated MPO and reduced NETs production in neutrophils along with reduced ROS production in both neutrophils and monocytes. Moreover, we observed a distinct pattern of cell surface receptor expression on both neutrophils and monocytes, in line with suppressed autocrine and paracrine cytokine signaling. This phenotype was characterized by a high expression of CD66b, CXCR4 and low expression of CXCR1, CXCR2 and CD15 in neutrophils and low expression of HLA-DR, CD86 and high expression of CD163 and CD11b in monocytes. Furthermore, the impaired antibacterial effector function was mediated by synergistic effect of the cytokines TNF-α, IFN-γ and IL-4. COVID-19 patients receiving dexamethasone showed a significant reduction of overall inflammatory markers in the plasma as well as exhibited an enhanced immune response towards bacterial challenge ex vivo. Finally, broad anti-inflammatory treatment was associated with a reduction in CRP, IL-6 levels as well as length of ICU and hospital stay in critically ill COVID-19 patients. Our data provides insights into the transient functional dysregulation of myeloid immune cells against subsequent bacterial infections in COVID-19 patients and describe a beneficial role for the use of dexamethasone in these patients.

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A time-resolved proteomic and prognostic map of COVID-19

Cited by 154 publications

References 106 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

COVIDomics: The Proteomic and Metabolomic Signatures of COVID-19

Hyperinflammatory environment drives dysfunctional myeloid cell effector response to bacterial challenge in COVID-19

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