HCA Data Explorer

Time-resolved systems immunology reveals a late juncture linked to fatal COVID-19.

Updated May 10, 2023

COVID-19 exhibits extensive patient-to-patient heterogeneity. To link immune response variation to disease severity and outcome over time, we longitudinally assessed circulating proteins as well as 188 surface protein markers, transcriptome, and T cell receptor sequence simultaneously in single peripheral immune cells from COVID-19 patients. Conditional-independence network analysis revealed primary correlates of disease severity, including gene expression signatures of apoptosis in plasmacytoid dendritic cells and attenuated inflammation but increased fatty acid metabolism in CD56dimCD16hi NK cells linked positively to circulating interleukin (IL)-15. CD8+ T cell activation was apparent without signs of exhaustion. Although cellular inflammation was depressed in severe patients early after hospitalization, it became elevated by days 17-23 post symptom onset, suggestive of a late wave of inflammatory responses. Furthermore, circulating protein trajectories at this time were divergent between and predictive of recovery versus fatal outcomes. Our findings stress the importance of timing in the analysis, clinical monitoring, and therapeutic intervention of COVID-19.

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Can Liu1
Andrew J Martins2
William W Lau3
Nicholas Rachmaninoff1
Jinguo Chen4
Luisa Imberti5
Darius Mostaghimi2
Danielle L Fink6
Peter D Burbelo7
Kerry Dobbs8
Ottavia M Delmonte8
Neha Bansal2
Laura Failla2
Alessandra Sottini5
Eugenia Quiros-Roldan9
Kyu Lee Han4
Brian A Sellers4
Foo Cheung4
Rachel Sparks2
Tae-Wook Chun10
Susan Moir10
Michail S Lionakis8
Camillo Rossi11
Helen C Su8
Douglas B Kuhns6
Jeffrey I Cohen12
Luigi D Notarangelo8
John S Tsang13
1Multiscale Systems Biology Section, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD 20892, USA; Graduate Program in Biological Sciences, University of Maryland, College Park, MD 20742, USA.
2Multiscale Systems Biology Section, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD 20892, USA.
3Multiscale Systems Biology Section, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD 20892, USA; Office of Intramural Research, CIT, NIH, Bethesda, MD 20892, USA.
4NIH Center for Human Immunology, NIAID, NIH, Bethesda, MD 20892, USA.
5CREA Laboratory, Diagnostic Department, ASST Spedali Civili di Brescia, Brescia 25123, Italy.
6Neutrophil Monitoring Laboratory, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD 20701, USA.
7National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD 20892, USA.
8Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD 20892, USA.
9Department of Infectious and Tropical Diseases, University of Brescia and ASST Spedali Civili di Brescia, Brescia 25123, Italy.
10Laboratory of Immunoregulation, NIAID, NIH, Bethesda, MD 20892, USA.
11ASST Spedali Civili di Brescia, Brescia 25123, Italy.
12Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, MD 20892, USA.
13Multiscale Systems Biology Section, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD 20892, USA; NIH Center for Human Immunology, NIAID, NIH, Bethesda, MD 20892, USA. Electronic address: john.tsang@nih.gov.
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To reference this project, please use the following link:

https://explore.data.humancellatlas.org/projects/ae62bb31-55ca-4127-b0fb-b1771a604645
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Analysis Portals

CZ CELLxGENECZ CELLxGENE
UCSC Cell BrowserUCSC Cell Browser

Project Label

covid19PBMCsTCRandCITEseq

Species

Homo sapiens

Sample Type

specimens

Anatomical Entity

blood

Organ Part

Unspecified

Selected Cell Types

peripheral blood mononuclear cell

Disease Status (Specimen)

2 disease statuses

Disease Status (Donor)

2 disease statuses

Development Stage

human adult stage

Library Construction Method

3 library construction methods

Nucleic Acid Source

single cell

Paired End

false

Analysis Protocol

analysis_protocol_1, analysis_protocol_2, analysis_protocol_3, analysis_protocol_4

File Format

6 file formats

Cell Count Estimate

411.9k

Donor Count

46
csv.gz4 file(s)fastq.gz3,950 file(s)rds.gz1 file(s)tar1 file(s)tar.gz1 file(s)xlsx1 file(s)