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Published September 2, 2022 | Version v1
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Integrated plasma proteomic and single-cell immune signaling network signatures demarcate mild, moderate, and severe COVID-19

Description

The biological determinants underlying the range of COVID-19 clinical manifestations are not fully understood. Here, over 1400 plasma proteins and 2600 single-cell immune features comprising cell phenotype, endogenous signaling activity, and signaling responses to inflammatory ligands are cross-sectionally assessed in peripheral blood from 97 patients with mild, moderate, and severe COVID-19 and 40 uninfected patients. Using an integrated computational approach to analyze the combined plasma and single-cell proteomic data, we identify and independently validate a multivariate model classifying COVID-19 severity (multi-class AUCtraining = 0.799, p-value = 4.2e-6; multi-class AUCvalidation = 0.773, p-value = 7.7e-6). Examination of informative model features reveals novel biological signatures of COVID-19 severity, including the dysregulation of JAK/STAT, MAPK/mTOR, and NF-κB immune signaling networks in addition to recapitulating known hallmarks of COVID-19. These results provide a set of early determinants of COVID-19 severity that may point to therapeutic targets for prevention and/or treatment of COVID-19 progression.

Notes

The data files contain:
- FCS files of mass cytometry measurements
- PatientCharacteristics: file containing clinical information regarding the patients. Column "Cohort" indicates which samples were used for training and which for validation.
- Penalization matrix: penalization matrix used to penalize the mass cytometry data
- Olink_NPXvalues: data from the Olink plasma proteomic assay. Proteomic values are provided in the arbitrary unit NPX
- CyTOF_FrequencySignaling_preprocessed: Frequencies and processed phosphosignaling responses of the mass cytometry dataset
- Correlation_matrix: Absolute spearman correlation coefficients of the chord diagram depicted in Figure 3D.

Further information and requests for resources and reagents should be directed to an will be fulfilled by the lead contact, Brice Gaudillière (gbrice@stanford.edu)

Funding provided by: Bill and Melinda Gates Foundation
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000865
Award Number: COVID-19 Pilot Award OPP1113682

Funding provided by: Bill and Melinda Gates Foundation
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000865
Award Number: INV-002704

Funding provided by: Bill and Melinda Gates Foundation
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000865
Award Number: OPP1113682

Funding provided by: Bill and Melinda Gates Foundation
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000865
Award Number: Pilot Seed Grant

Funding provided by: Burroughs Wellcome Fund
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000861
Award Number:

Funding provided by: CEND*
Crossref Funder Registry ID:
Award Number: CEND Covid Catalyst Award

Funding provided by: Centers for Disease Control and Prevention
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000030
Award Number: 75D30120C08009

Funding provided by: Center for Health System Innovation, University of Southern California
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100012685
Award Number: Pilot Seed Grant

Funding provided by: Consejo Nacional de Ciencia y Tecnología
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100003141
Award Number: 289788

Funding provided by: Consejo Nacional de Ciencia y Tecnología
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100003141
Award Number: 311783

Funding provided by: Doris Duke Charitable Foundation
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000862
Award Number: 2018100A

Funding provided by: Mercatus Center, George Mason University
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100019004
Award Number: Fast Grants for COVID-19

Funding provided by: National Cancer Institute
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100021671
Award Number: Task Order No. HHSN261100039

Funding provided by: National Cancer Institute
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100021671
Award Number: Contract No. HHSN261201500003I

Funding provided by: National Institute of Allergy and Infectious Diseases
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000060
Award Number: K23 grant AI135037

Funding provided by: National Institutes of Health
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000002
Award Number: 5U19AI100627-09 Systems Approach to Immunity and Inflammation COVID supplement

Funding provided by: National Institutes of Health
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000002
Award Number: CCHI U19AI057229

Funding provided by: National Institutes of Health
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000002
Award Number: R35GM137936

Funding provided by: National Institutes of Health
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000002
Award Number: R35GM138353

Funding provided by: National Institutes of Health
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000002
Award Number: SeroNet 1U54CA260517

Funding provided by: National Institutes of Health
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000002
Award Number: T32GM089626

Funding provided by: Rachford and Carlota A. Harris Endowed Professorship*
Crossref Funder Registry ID:
Award Number:

Funding provided by: Sean N. Parker Center for Allergy and Asthma Research, Stanford University
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100016667
Award Number:

Funding provided by: Parker Institute for Cancer Immunotherapy
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100014547
Award Number:

Funding provided by: Sunshine Foundation*
Crossref Funder Registry ID:
Award Number:

Funding provided by: U.S. Food and Drug Administration
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000038
Award Number: 75F40120C00176

Funding provided by: U.S. Food and Drug Administration
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000038
Award Number: HHSF223201610018C

Funding provided by: Alfred E. Mann Institute for Biomedical Engineering, University of Southern California
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100013829
Award Number:

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Additional details

Related works

Is cited by
10.1101/2021.02.09.430269 (DOI)
10.1016/j.xcrm.2022.100680 (DOI)