HCA Data Explorer

Human SARS-CoV-2 challenge resolves local and systemic response dynamics

Updated June 17, 2024

The COVID-19 pandemic is an ongoing global health threat, yet our understanding of the cellular disease dynamics remains limited. In our unique COVID-19 human challenge study we used single cell genomics of nasopharyngeal swabs and blood to temporally resolve abortive, transient and sustained infections in 16 seronegative individuals challenged with preAlpha-SARS-CoV-2. Our analyses revealed rapid changes in cell type proportions and dozens of highly dynamic cellular response states in epithelial and immune cells associated with specific timepoints or infection status. We observed that the interferon response in blood precedes the nasopharynx, and that nasopharyngeal immune infiltration occurred early in transient but later in sustained infection, and thus correlated with preventing sustained infection. Ciliated cells showed an acute response phase, upregulated MHC class II while infected, and were most permissive for viral replication, whilst nasal T cells and macrophages were infected non-productively. We resolve 54 T cell states, including acutely activated T cells that clonally expanded while carrying convergent SARS-CoV-2 motifs. Our novel computational pipeline (Cell2TCR) identifies activated antigen-responding clonotype groups and motifs in any dataset. Together, we show that our detailed time series data ( covid19cellatlas.org ) can serve as a “Rosetta stone” for the epithelial and immune cell responses, and reveals early dynamic responses associated with protection from infection.

Rik G.H. LindeboomWellcome Sanger Instituter.lindeboom@nki.nl
Marko NikolićUniversity College Londonm.nikolic@ucl.ac.uk
Sarah TeichmannWellcome Sanger Institutet9@sanger.ac.uk
Rik G.H. Lindeboom1
Kaylee Worlock2
Lisa Dratva1
Masahiro Yoshida2
David Scobie2
Helen Wagstaffe3
Laura Richardson1
Anna Wilbrey-Clark1
Josephine Barnes2
Krzysztof Polanski1
Jessica Allen-Hyttinen2
Puja Mehta2
Dinithi Sumanaweera1
Jacqueline Boccacino1
Waradon Sungnak1
Ni Huang1
Lira Mamanova1
Rakesh Kapuge1
Liam Bolt1
Elena Prigmore1
Ben Killingley2
Mariya Kalinova4
Maria Mayer4
Alison Boyers4
Alex Mann4
Vitor Teixeira2
Sam Janes2
Rachel Chambers2
Muzlifah Haniffa1
Andrew Catchpole4
Robert Heyderman2
Mahdad Noursadeghi2
Benny Chain2
Andreas Mayer2
Kerstin Meyer1
Christopher Chiu3
Marko Nikolić2
Sarah Teichmann1
1Wellcome Sanger Institute
2University College London
3Imperial College London
4hVIVO
Ida Zucchi

To reference this project, please use the following link:

https://explore.data.humancellatlas.dev.clevercanary.com/projects/16dc40f9-2c13-42e3-8cdf-251e95bfc043

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://www.covid19cellatlas.org/challenge_nasal/2.https://www.covid19cellatlas.org/challenge_pbmc/
None

Atlas

None

Analysis Portals

None

Project Label

SARSCoV2ResponseDynamics

Species

Homo sapiens

Sample Type

specimens

Anatomical Entity

2 anatomical entities

Organ Part

Unspecified

Selected Cell Types

Unspecified

Disease Status (Specimen)

COVID-19

Disease Status (Donor)

COVID-19

Development Stage

human adult stage

Library Construction Method

2 library construction methods

Nucleic Acid Source

2 nucleic acid sources

Paired End

false

Analysis Protocol

processed_matrix_generation, raw_matrix_generation_PBMC, raw_matrix_generation_alfa_beta, raw_matrix_generation_gamma_delta, raw_matrix_generation_nasal

File Format

2 file formats

Cell Count Estimate

606.1k

Donor Count

16
h5ad2 file(s)xlsx1 file(s)