A multiplex protein panel assay for severity prediction and outcome prognosis in patients with COVID-19: An observational multi-cohort study

Wang, Ziyue; Cryar, Adam; Lemke, Oliver; Tober‐Lau, Pinkus; Ludwig, Daniela; Helbig, Elisa T; Hippenstiel, Stefan; Sander, Leif E.; Blake, Daniel M.; Lane, Catherine; Sayers, Rebekah; Mueller, Christoph; Zeiser, Johannes; Townsend, StJohn; Demichev, Vadim; Mülleder, Michael; Kurth, Florian; Sirka, Ernestas; Hartl, Johannes; Ralser, Markus

doi:10.1016/j.eclinm.2022.101495

Cited by 27 publications

(53 citation statements)

References 53 publications

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“…To our knowledge, the repurposing of panel assays for assessing disease severity, for clinical trial monitoring, or for predicting future disease courses has not been explored previously but could prove a helpful tool in mounting a rapid response to emerging diseases. [28]) in parallel to a targeted proteomic assay that quantifies COVID-19 severity biomarkers ( [22]) to characterize the plasma proteome in an MPX case series, and comparison the proteomes to those of healthy volunteers and COVID-19 patients. b) Volcano plot of contrast MPX vs healthy controls; α <= 0.015 and |logFC| >= 1.35 were used for selection of regulated proteins.…”

Section: Discussionmentioning

confidence: 99%

“…2 µl of diluted PQ500 stock solution were spiked into 18 µl of the 200 ng/µl sample before transfer to vials for injection. For targeted proteomics, 15 µl of pre-digested heavy labeled standards (details in [22]) were spiked into 10 µl samples (QCs, monkeypox, COVID-19, and healthy controls) and 20 µl were injected into the LC-MS system.…”

Section: Sample Preparationmentioning

confidence: 99%

“…We recently demonstrated the translational potential of plasma proteomics for applicability in clinical practice through the transfer of protein marker candidates which had been identified by discovery proteomics in COVID-19 into a routinely applicable targeted protein panel assay. The assay absolutely quantifies up to 50 peptides derived from 30 COVID-19-related plasma biomarker proteins and captured hallmarks of COVID-19 in a multi-cohort observational study conducted using routine-lab-compatible high-flow chromatography and LC-MRM acquisition [22]. The LC-MRM assay consistently quantifies 32 of the peptides in plasma samples from MPX cases, controls, and in COVID-19 patient samples.…”

Section: Potential To Repurpose Proteomic Assays To Rapidly Respond T...mentioning

confidence: 99%

“…Furthermore, proteomic signatures turned out to accurately classify disease severity in COVID-19 and allow for outcome prediction weeks in advance [19–21]. Recently, we were able to show the strength of mass-spectrometry-based proteomics for rapid translation to medical care by generating a routine-applicable proteomic biomarker panel which predicted COVID-19 severity and outcome in a multi cohort study [22]. While such proteomic assays are currently primarily used to monitor clinical trials, they are increasingly being considered for their potential to optimize treatment and resource allocation, as well as to aid navigation of difficult triaging situations in the event of a pandemic.…”

Section: Introductionmentioning

confidence: 99%

“…Because we detected a partial overlap between the MPX and COVID-19 host response proteome, we were able to explore the possibility of repurposing a COVID-19 biomarker panel for classifying MPX. We report successful classification of the MPX cases based on the proteomic biomarkers initially designed to assess severity and outcome in COVID-19 [22]. Hence, our case series study provides a biochemical characterization of the MPX host response and reveals correlation of host proteins with MPX disease severity.…”

Section: Introductionmentioning

confidence: 99%

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The human host response to monkeypox infection: a proteomic case series study

Wang

Tober‐Lau

Farztdinov

et al. 2022

Preprint

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Monkeypox (MPX) is caused by the homonymous orthopoxvirus (MPXV) known since the 1970s to occur at low frequency in West and Central Africa. Recently, the disease has been spreading quickly in Europe and the US. The rapid rise of MPX cases outside previously endemic areas and the different clinical presentation prompt for a better understanding of the disease, including the development of clinical tests for rapid diagnosis and monitoring. Here, using Zeno SWATH MS - a latest-generation proteomic technology - we studied the plasma proteome of a group of MPX patients with a similar infection history and clinical severity typical for the current outbreak. Moreover, we compared their proteomes to those of healthy volunteers and COVID-19 patients. We report that MPX is associated with a strong and characteristic plasma proteomic response and describe MPXV infection biomarkers among nutritional and acute phase response proteins. Moreover, we report a correlation between plasma protein markers and disease severity, approximated by the degree of skin manifestation. Contrasting the MPX host response with that of COVID-19, we find a range of similarities, but also important differences. For instance, Complement factor H-related protein 1 (CFHR1) is induced in COVID-19, but suppressed in MPX, reflecting the different role of the complement system in the two infectious diseases. However, the partial overlap between MPX and COVID-19 host response proteins allowed us to explore the repurposing of a clinically applicable COVID-19 biomarker panel assay, resulting in the successful classification of MPX patients. Hence, our results provide a first proteomic characterization of the MPX human host response based on a case series. The results obtained highlight that proteomics is a promising technology for the timely identification of disease biomarkers in studies with moderate cohorts, and we reveal a thus far untapped potential for accelerating the response to disease outbreaks through the repurposing of multiplex biomarker assays.

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Section: Discussionmentioning

confidence: 99%

Section: Sample Preparationmentioning

confidence: 99%

Section: Potential To Repurpose Proteomic Assays To Rapidly Respond T...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The human host response to monkeypox infection: a proteomic case series study

Wang

Tober‐Lau

Farztdinov

et al. 2022

Preprint

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Mass spectrometry‐based high‐throughput proteomics and its role in biomedical studies and systems biology

et al. 2022

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There are multiple reasons why the next generation of biological and medical studies require increasing numbers of samples. Biological systems are dynamic, and the effect of a perturbation depends on the genetic background and environment. As a consequence, many conditions need to be considered to reach generalizable conclusions. Moreover, human population and clinical studies only reach sufficient statistical power if conducted at scale and with precise measurement methods. Finally, many proteins remain without sufficient functional annotations, because they have not been systematically studied under a broad range of conditions. In this review, we discuss the latest technical developments in mass spectrometry (MS)-based proteomics that facilitate large-scale studies by fast and efficient chromatography, fast scanning mass spectrometers, data-independent acquisition (DIA), and new software. We further highlight recent studies which demonstrate how high-throughput (HT) proteomics can be applied to capture biological diversity, to annotate gene functions or to generate predictive and prognostic models for human diseases.

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