HCA Data Explorer

Local and systemic responses to SARS-CoV-2 infection in children and adults

Access Granted
Updated June 19, 2024

While a substantial proportion of adults infected with SARS-CoV-2 progress to develop severe disease, children rarely manifest respiratory complications. Therefore, understanding differences in the local and systemic response to SARS-CoV-2 infection between children and adults may provide important clues about the pathogenesis of SARS-CoV-2 infection. To address this, we first generated a healthy reference multi-omics single cell data set from children (n=30) in whom we have profiled triple matched samples: nasal and tracheal brushings and PBMCs, where we track the developmental changes for 42 airway and 31 blood cell populations from infancy, through childhood to adolescence. This has revealed the presence of naive B and T lymphocytes in neonates and infants with a unique gene expression signature bearing hallmarks of innate immunity. We then contrast the healthy reference with equivalent data from severe paediatric and adult COVID-19 patients (total n=27), from the same three types of samples: upper and lower airways and blood. We found striking differences: children with COVID-19 as opposed to adults had a higher proportion of innate lymphoid and non-clonally expanded naive T cells in peripheral blood, and a limited interferon-response signature. In the airway epithelium, we found the highest viral load in goblet and ciliated cells and describe a novel inflammatory epithelial cell population. These cells represent a transitional regenerative state between secretory and ciliated cells; they were found in healthy children and were enriched in paediatric and adult COVID-19 patients. Epithelial cells display an antiviral and neutrophil-recruiting gene signature that is weaker in severe paediatric versus adult COVID-19. Our matched blood and airway samples allowed us to study the spatial dynamics of infection. Lastly, we provide a user-friendly interface for this data 1 as a highly granular reference for the study of immune responses in airways and blood in children.

Marko NikolićUniversity College Londonm.nikolic@ucl.ac.uk
Kerstin MeyerWellcome Sanger Institutekm16@sanger.ac.uk
Masahiro Yoshida1
Kaylee Worlock1
Ni Huang2
Rik G.H. Lindeboom2
Colin Butler3
Natsuhiko Kumasaka2
Cecilia Dominguez Conde2
Lira Mamanova2
Liam Bolt2
Laura Richardson2
Krzysztof Polanski2
Elo Madissoon2
Josephine Barnes1
Jessica Allen-Hyttinen1
Eliz Kilich4
Brendan Jones3
Angus de Wilton4
Anna Wilbrey-Clark2
Waradon Sungnak2
Patrick Pett2
Elena Prigmore2
Henry Yung1
Puja Mehta1
Aarash Saleh5
Anita Saigal5
Vivian Chu5
Jonathan Cohen4
Clare Cane5
Aikaterini Iordanidou5
Soichi Shibuya3
Ann-Kathrin Reuschl1
Christine Argento6
Richard Wunderink6
Sean Smith6
Taylor Poor6
Catherine Gao6
Jane Dematte6
Gary Reynolds7
Muzlifah Haniffa7
Georgina Bowyer8
Matthew Coates8
Menna Clatworthy8
Fernando Calero-Nieto8
Berthold Göttgens8
Christopher O’Callaghan3
Neil Sebire3
Clare Jolly1
Paolo de Coppi3
Claire Smith3
Alexander Misharin6
Sam Janes1
Sarah Teichmann2
Marko Nikolić1
Kerstin Meyer2
NU SCRIPT Study Investigators6
1University College London
2Wellcome Sanger Institute
3NIHR Great Ormond Street BRC and UCL Institute of Child Health
4University College London Hospitals NHS Foundation Trust
5Royal Free Hospital NHS Foundation Trust
6Northwestern University Feinberg School of Medicine
7Newcastle University
8University of Cambridge
Ida Zucchi

To reference this project, please use the following link:

https://explore.data.humancellatlas.org/projects/1538d572-bcb7-426b-8d2c-84f3a7f87bb0

Supplementary links are provided by contributors and represent items such as additional data which can’t be hosted here; code that was used to analyze this data; or tools and visualizations associated with this specific dataset.

1.https://covid19cellatlas.org/2.https://github.com/Teichlab/COVID-19paed
EGA Accessions:GEO Series Accessions:

Analysis Portals

CZ CELLxGENECZ CELLxGENE
UCSC Cell BrowserUCSC Cell Browser

Project Label

SARSCov2ChildrenAdults

Species

Homo sapiens

Sample Type

specimens

Anatomical Entity

3 anatomical entities

Organ Part

7 organ parts

Selected Cell Types

peripheral blood mononuclear cell

Disease Status (Specimen)

3 disease statuses

Disease Status (Donor)

3 disease statuses

Development Stage

6 development stages

Library Construction Method

2 library construction methods

Nucleic Acid Source

single cell

Paired End

false

Analysis Protocol

UK_expression_matrix_generation, chicago_expression_matrix_protocol, clustering

File Format

3 file formats

Cell Count Estimate

659.2k

Donor Count

97
h59 file(s)h5ad2 file(s)xlsx1 file(s)