A UK underpinning platform to study immunology and immunopathology of COVID-19:The UK Coronavirus Immunology Consortium

Lead Research Organisation: University of Birmingham
Department Name: Institute of Immunology & Immunotherapy

Abstract

The immune response to SARS-CoV-2 infection is the critical determinant of clinical outcome for patients but although this can suppress virus replication (immunity) it can also cause damage to tissues such as the lung (immunopathology).
It is unclear how effective immunity is established or why it damages tissues. Many UK research groups have initiated research and UK-CIC will bring together a consortium of 17 UK centres to coordinate coronavirus immunology research.

We will work on 5 questions:
-the features of immunity during initial infection and how this relates to clinical outcome of individual patients.
SARS-CoV-2 infection triggers an immediate (innate: interferon and white cell) and delayed (adaptive: antibody and cellular) immune response. How these develop and interact is currently unclear but will determine how quickly the infection is cleared. We will study this in patients with mild and severe infection. A number of risk factors for severe Covid-19 infection have been identified including age, gender, obesity and ethnicity. These will be studied in relation to the features of the initial immune response.

-how effective immunity is established and maintained to prevent re-infection
After infection the immune response develops some 'memory' of the infection and this helps to prevent reinfection. For some infections (e.g. measles) this protection is virtually complete; for others (such as the common cold) this protection is brief. We do not know what the situation will be for SARS-CoV-2.
This work will take samples from people in the first year after infection and measure the virus-specific immune response. We will examine the fine details of how the immune system kills the virus and the longevity of this response. We will examine a broad representation of population groups to do this work effectively and compare groups of different ages and backgrounds.

-the mechanisms by which the immune system can damage tissue and how this can be stopped
In severe or fatal infection the problems arise due to two mechanisms:
(1) The virus infects and damages tissue
(2) The immune response to the virus can itself damage tissue
In this research theme we will investigate the relative importance of these two problems and try to find ways to prevent them. This will involve taking blood and tissue samples from patients with severe disease and also using post mortem tissue.

-if immunity to mild 'seasonal' coronaviruses alters the outcome of SARS-CoV-2 infection
The term coronavirus was first used in 1965 to describe identification of a common cold virus and these viruses circulate widely in the community. It is thought that the immune response to these viruses may potentially 'cross-react' with the new SARS-CoV-2 coronavirus, perhaps giving some people relative protection against infection. We will investigate this possibility and assess how it might happen.
Here we will use blood samples in the laboratory to assess their recognition of both viruses and also see if blood samples frozen down before the Covid-19 pandemic make any response to the new virus.

-the details by which the virus 'evades' the immune system and how this could be targeted by new treatments.
Viruses can only grow, spread and cause disease if they are able to evade being killed by the immune system. If we can understand how this happens we might be able to develop new drugs that can block this response and allow the virus to take control and eliminate the virus. This work takes place in the laboratory using viral infection studies of cells.

UK-CIC will work with other major recent UK investments in Covid-19 biology and represents an essential additional pillar of UK research infrastructure to hasten the control of the pandemic.

Technical Summary

Incomplete understanding of mechanisms of protective immunity and immunopathology following SARS-CoV-2 infection limits development of diagnostics, treatments and vaccination.
The UK coronavirus immunology consortium (UK-CIC) will link the UK immunology community to deliver, at pace, a coordinated and agile national research programme.

This will focus around 17 centres of excellence and address five key research themes:

-The primary immune response and clinical outcome
Here we will integrate immune datasets from patients at the time of primary infection to assess how this relates to clinical risk factors such as gender, ethnicity and age. We will compare and contrast patients with mild and severe disease

-long term protective immunity
This theme will focus on mechanisms of cellular immunity, how these responses are maintained over time, and how they relate to the severity of initial infection. The consortium incorporates intensive deep phenotyping of an ISARIC 4C follow up cohort.

-mechanisms and prevention of immunopathology
Using primary tissue samples and post-mortem material we will utilise start of the art technology to assess how viral replication and immune mechanisms mediate pathology, and how these can be prevented.

-cross reactivity with seasonal coronaviruses
Here we will focus on T cell cross-reactivity between SARS-CoV-2 and seasonal coronaviruses, using fresh and historical samples

-viral immune evasion
The virus mediates disease by evading host immunity. Here we will use molecular, proteomic and cellular approaches to define new, and potentially reversible, mechanisms of viral evasion.

Research outcomes will be translated rapidly to policy makers, academic & industrial collaborators, and the public.

The UK has one of the strongest immunology communities in the world and UK-CIC will bring this together to hasten pandemic control and serve as an exemplar for potential future challenges.

People

ORCID iD

Paul Moss (Principal Investigator)
Endre Kiss-Toth (Co-Investigator) orcid http://orcid.org/0000-0003-4406-4017
Adam Finn (Co-Investigator)
Eleanor Barnes (Co-Investigator)
Doreen Cantrell (Co-Investigator)
Massimo Palmarini (Co-Investigator)
V Ridger (Co-Investigator)
John Robert Grainger (Co-Investigator)
Malcolm Gracie Semple (Co-Investigator) orcid http://orcid.org/0000-0001-9700-0418
Paul Klenerman (Co-Investigator)
Paul Martin Kaye (Co-Investigator) orcid http://orcid.org/0000-0002-8796-4755
Marc-Emmanuel Dumas (Co-Investigator) orcid http://orcid.org/0000-0001-9523-7024
Antonia Ho (Co-Investigator) orcid http://orcid.org/0000-0003-1465-3785
Pablo Ramiro Murcia (Co-Investigator) orcid http://orcid.org/0000-0002-4352-394X
Awen Gallimore (Co-Investigator) orcid http://orcid.org/0000-0001-6675-7004
Paul Morgan (Co-Investigator) orcid http://orcid.org/0000-0003-4075-7676
Andrew John Fisher (Co-Investigator)
Linda Wooldridge (Co-Investigator)
Marina Botto (Co-Investigator)
Nathalie Yvonne Signoret (Co-Investigator)
David Cameron Wraith (Co-Investigator) orcid http://orcid.org/0000-0003-2147-5614
Michelle Willicombe (Co-Investigator)
Muzlifah Haniffa (Co-Investigator)
Munitta Muthana (Co-Investigator) orcid http://orcid.org/0000-0003-2497-8903
Julie Wilson (Co-Investigator) orcid http://orcid.org/0000-0002-5171-8480
Zoltan Takats (Co-Investigator)
Paul J Lehner (Co-Investigator)
Sophie Hambleton (Co-Investigator)
Hans Stauss (Co-Investigator)
Nicholas John Timpson (Co-Investigator) orcid http://orcid.org/0000-0002-7141-9189
Laura Rivino (Co-Investigator) orcid http://orcid.org/0000-0001-6213-9794
Benny Chain (Co-Investigator)
Sam John Wilson (Co-Investigator)
Claire Elizabeth Lewis (Co-Investigator)
John Kenneth Baillie (Co-Investigator) orcid http://orcid.org/0000-0001-5258-793X
Ian Humphreys (Co-Investigator)
Peter J Openshaw (Co-Investigator) orcid http://orcid.org/0000-0002-7220-2555
Richard Stanton (Co-Investigator)
Sarah Louise Rowland-Jones (Co-Investigator) orcid http://orcid.org/0000-0001-5788-6998
Adrian Hayday (Co-Investigator)
Sarah R Walmsley (Co-Investigator)
Mala Kunti Maini (Co-Investigator)
Jo Spencer (Co-Investigator)
Peter John O'Toole (Co-Investigator)
David Anthony Price (Co-Investigator)
Paul John Collini (Co-Investigator)
Magnus Rattray (Co-Investigator) orcid http://orcid.org/0000-0001-8196-5565
Lance Turtle (Co-Investigator) orcid http://orcid.org/0000-0002-0778-1693
Emma Thomson (Co-Investigator) orcid http://orcid.org/0000-0003-1482-0889
Omer Bayraktar (Co-Investigator)
David Kavanagh (Co-Investigator) orcid http://orcid.org/0000-0003-4718-0072
Markus Ralser (Co-Investigator)
Niharika Arora Duggal (Co-Investigator)
Tracy Hussell (Co-Investigator) orcid http://orcid.org/0000-0001-7186-6141
Christopher James Duncan (Co-Investigator) orcid http://orcid.org/0000-0003-4181-2315
Claire Harris (Co-Investigator) orcid http://orcid.org/0000-0003-0845-1730
Andrew Filby (Co-Investigator) orcid http://orcid.org/0000-0001-9078-4360
Dimitris Lagos (Co-Investigator) orcid http://orcid.org/0000-0003-0637-281X
Sarah Teichmann (Co-Investigator)
Jianmin Zuo (Co-Investigator)
Julian L Griffin (Co-Investigator) orcid http://orcid.org/0000-0003-1336-7744
Joby Cole (Co-Investigator)
Heather Margaret Long (Co-Investigator)
Thushan De Silva (Co-Investigator)
Matthew David Snape (Co-Investigator)
Brian James Willett (Co-Investigator)
Kenneth George Smith (Co-Investigator)
Susan Margaret Ring (Co-Investigator) orcid http://orcid.org/0000-0003-3103-9330
Graham Taylor (Co-Investigator)
Janet Lord (Co-Investigator)
John Wright (Co-Investigator)
Eddie Chung Wang (Co-Investigator) orcid http://orcid.org/0000-0002-2243-4964
Susanna Jane Dunachie (Co-Investigator) orcid http://orcid.org/0000-0001-5665-6293
Suzannah Rihn (Co-Investigator) orcid http://orcid.org/0000-0001-9495-4056

Publications

10 25 50
 
Description Paul Morgan (Cardiff University) sits as UK-CIC representative on the UK Coronavirus Treatment Acceleration Program committee
Geographic Reach National 
Policy Influence Type Gave evidence to a government review
 
Description Professor Moss is a member of the Vaccine Task Force Expert Advisory Group on Vaccine Variants
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
 
Description Professors Moss (University of Birmingham) and Hussell (University of Manchester) have been invited to join the WHO Technical Advisory Group on immune modulation for novel therapeutics in Covid-19
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
 
Title Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID- 19. Sekine et al 
Description Supplementary Items -Table S1. Correlative analyses of immune activation phenotypes versus soluble factor measurements in acute COVID-19. Related to Figure 1. 
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? Yes  
Impact To be completed 
URL https://data.mendeley.com/datasets/phgv35zpxm
 
Description UK-CIC collaboration with Bradford Teaching Hospitals NHS Trust 
Organisation Bradford Teaching Hospitals NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution The University of Birmingham provides central coordination of the UK-CIC funding; operational support of Consortium events including fortnightly meetings for all collaborators and quarterly individual Centre meetings; management of reporting to the funder of all Centre's progress; engagement with the British Society for Immunology regarding all communications, and preparation for the UK-CIC virtual conference. Professor Paul Moss, as Consortium Lead, brings collaborators together to share scientific findings, encouraging sharing of methodology, data and expertise. He takes responsibility for feeding into the Oversight Committee the achievements and challenges of UK-CIC. The University provides expertise on contracts and finance, ensuring the smooth running of this project.
Collaborator Contribution This Centre contributes to Theme 2, with broad milestones as follows: Theme 2 - Define sampling frame and identification of cases through case identification from primary care records, questionnaire survey with COVID19 symptoms, LFIA serology using 2000 Fortress POCT kits. Submit Ethics and MHRA applications. Update primary care data with Pillar 1 and 2 results from TPP and linkage to Born in Bradford (BiB) participants to identify test positive cases. Post 2000 questionnaires to BiB families with COVID19 symptom questions. Undertake feasibility and acceptability of home based POCT kits. Home visits with suitable IPC to deliver 2000 LFIA kits and obtain results for parents and their children. Identify 200 cases and 200 potential controls with an aim of 50% response rate to recall at clinic. The monthly reports submitted to the MRC and NIHR provide ongoing updates of milestone progress.
Impact Papers attributable to this project are listed under the relevant section of this form. This collaboration is part of a wider 19-Centre Consortium, with multi-disciplinary working throughout the various institutions.
Start Year 2020
 
Description UK-CIC collaboration with British Society for Immunology 
Organisation British Society For Immunology
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution The University of Birmingham provides central coordination of the UK-CIC funding, including a grant to the British Society for Immunology for provision of the services outlined below
Collaborator Contribution BSI President, Professor Arne Akbar, is chair of the UK-CIC Scientific Advisory Board, which delivers independent oversight of the consortium, and input to its strategic priorities. The BSI also provides secretarial services to this Board. Ensuring that the views of patients and the public influence the direction of research through running the patient public involvement programme for UK-CIC. Running communications for UK-CIC including internal and external communications, media engagement, and the website and social media presence. This includes providing communications to engage with all key audiences from researchers to policy makers to the public. Management of the UK-CIC virtual conference on SARS-CoV-2 immunology in April 2021
Impact This collaboration is part of a wider 19-Centre Consortium, with multi-disciplinary working throughout the various institutions. A major output will be the UK-CIC virtual conference in April 2021.
Start Year 2020
 
Description UK-CIC collaboration with Cardiff University 
Organisation Cardiff University
Country United Kingdom 
Sector Academic/University 
PI Contribution The University of Birmingham provides central coordination of the UK-CIC funding; operational support of Consortium events including fortnightly meetings for all collaborators and quarterly individual Centre meetings; management of reporting to the funder of all Centre's progress; engagement with the British Society for Immunology regarding all communications, and preparation for the UK-CIC virtual conference. Professor Paul Moss, as Consortium Lead, brings collaborators together to share scientific findings, encouraging sharing of methodology, data and expertise. He takes responsibility for feeding into the Oversight Committee the achievements and challenges of UK-CIC. The University provides expertise on contracts and finance, ensuring the smooth running of this project.
Collaborator Contribution This Centre contributes to Themes 1, 3 and 5 with broad milestones as follows: Theme 1 - Publish initial T cell datasets for severe disease, asymptomatic and mildly symptomatic cases (https://www.cell.com/cell/fulltext/S0092-8674(20)31008-4), making available for central aggregation. Initiate longitudinal studies for these cases. Complete phenotypic analyses of acute T cell responses and integrate data with other centres. Theme 3 - Organise division of Complement studies with HICC, arranging sample transfer. Prepare tools/reagents for all assays to be undertaken. Optimise all assays, subjecting them to QC. Measure levels in 25 normal control samples to establish normal ranges. Receive samples from ISARIC. Commence measurements of all analytes in in local sample sets and those from Newcastle and Cambridge. Collaborate with Newcastle and Cambridge to identify key markers for analysis in samples from national consortia. Theme 5 - Develop analytical plan for experiments co-ordinated between the three centres (Cardiff, Cambridge and Glasgow). Share Information and resources to facilitate development of cell lines that allow high level infection by SARS-CoV-2 for use in NK and T-cell assays. : Suppression of targets of cellular immune recognition Test ACE2+ TMPRSS2+ target cell lines for levels of infection and functional experiments. Clone predicted SARS-CoV-2 genes, growing for titre. Generation of standardised effector cells/cell lines. The monthly reports submitted to the MRC and NIHR provide ongoing updates of milestone progress.
Impact Papers attributable to this project are listed under the relevant section of this form. This collaboration is part of a wider 19-Centre Consortium, with multi-disciplinary working throughout the various institutions.
Start Year 2020
 
Description UK-CIC collaboration with Francis Crick Institute 
Organisation Francis Crick Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution The University of Birmingham provides central coordination of the UK-CIC funding; operational support of Consortium events including fortnightly meetings for all collaborators and quarterly individual Centre meetings; management of reporting to the funder of all Centre's progress; engagement with the British Society for Immunology regarding all communications, and preparation for the UK-CIC virtual conference. Professor Paul Moss, as Consortium Lead, brings collaborators together to share scientific findings, encouraging sharing of methodology, data and expertise. He takes responsibility for feeding into the Oversight Committee the achievements and challenges of UK-CIC. The University provides expertise on contracts and finance, ensuring the smooth running of this project.
Collaborator Contribution This Centre contributes to Theme 2, with broad milestones as follows: Theme 2 - Obtain, quality check, and plate >1,000 patient serum and plasma samples from the ISARIC cohort. Design a proteomic experiment that captures the COVID19 patient response. Measure the proteome of the ISARIC samples, identify protein signatures that respond to COVID19. Generate prognostic computational models that a) classify patients, b) predict their outcome on the basis if i) the proteome data and Ii) upon incorporation of clinical and peripheral omic data generated by the UK-CIC consortium. Design proteomic marker panel assays for patient stratification, and to be uses as part of clinical routine. The monthly reports submitted to the MRC and NIHR provide ongoing updates of milestone progress.
Impact Papers attributable to this project are listed under the relevant section of this form. This collaboration is part of a wider 19-Centre Consortium, with multi-disciplinary working throughout the various institutions.
Start Year 2020
 
Description UK-CIC collaboration with Imperial College 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution The University of Birmingham provides central coordination of the UK-CIC funding; operational support of Consortium events including fortnightly meetings for all collaborators and quarterly individual Centre meetings; management of reporting to the funder of all Centre's progress; engagement with the British Society for Immunology regarding all communications, and preparation for the UK-CIC virtual conference. Professor Paul Moss, as Consortium Lead, brings collaborators together to share scientific findings, encouraging sharing of methodology, data and expertise. He takes responsibility for feeding into the Oversight Committee the achievements and challenges of UK-CIC. The University provides expertise on contracts and finance, ensuring the smooth running of this project.
Collaborator Contribution This Centre contributes to Themes 1, 2 and 3, with broad milestones as follows: Theme 1 - Transfer samples to Sanger/Cambridge for the scRNA-Seq and CITE-Seq, which has been performed on the majority of the samples or is in progress. Theme 2 - Plan the ISARIC 4C Follow Up study in detail, with Centres prepared for sample analysis. First samples from the ISARIC 4C Follow Up study are delivered to research centres and deep phenotyping of the acute immune response is underway in each centre. Data analytics are sourced. Nasal and cell mediated immunity analyses are underway in all centres and include follow samples. Theme 3 - ISARIC4 Tier 2 urine samples shipped to Imperial for aliquoting. Initiation of metabolomics on plasma/serum samples. Data freeze, first-pass multivariate and univariate statistical analysis. The monthly reports submitted to the MRC and NIHR provide ongoing updates of milestone progress.
Impact Papers attributable to this project are listed under the relevant section of this form. This collaboration is part of a wider 19-Centre Consortium, with multi-disciplinary working throughout the various institutions.
Start Year 2020
 
Description UK-CIC collaboration with King's College London 
Organisation King's College London
Country United Kingdom 
Sector Academic/University 
PI Contribution The University of Birmingham provides central coordination of the UK-CIC funding; operational support of Consortium events including fortnightly meetings for all collaborators and quarterly individual Centre meetings; management of reporting to the funder of all Centre's progress; engagement with the British Society for Immunology regarding all communications, and preparation for the UK-CIC virtual conference. Professor Paul Moss, as Consortium Lead, brings collaborators together to share scientific findings, encouraging sharing of methodology, data and expertise. He takes responsibility for feeding into the Oversight Committee the achievements and challenges of UK-CIC. The University provides expertise on contracts and finance, ensuring the smooth running of this project.
Collaborator Contribution This Centre contributes to Themes 1 and 2, with broad milestones as follows: Theme 1 - Establish and implement pipeline for the SOAP study, of the impact of COVID-19 on solid and haematological malignancies and the management thereof. Establish and implement pipeline for the analysis of antigen receptor sequencing (TCRb; TCRd; IgH) from longitudinal samples of COVID-19 patients and controls with age-stratification above and below 50. Will be contextualised with extensive phenotypic, functional, and clinical data. Establish and implement pipeline for CiTE-Seq analyses of SARS-CoV-2-responsive T cells from severely affected versus mildly affected COVID-19 patients. Put in place applications to identify and study asymptomatic SARS-CoV-2 infection via the STD clinic network and innovative contact-tracing. Plan analysis of gamma delta T cell responses to live SARS-CoV-2 infected cells. Theme 2 - Designed panel for imaging mass cytometry (IMC) analysis of FFPE gut tissues; commence testing and validation. Commence process of acquiring FFPE post mortem samples from patients who died from SARS-CoV-2 and controls, initially from Italy. Initiate appropriate collaborations and planned acquisition of fresh colonic biopsies from hospitalised SARS-CoV-2 infected patients. Plan for single cell analysis of single cells isolated from biopsies using BD Rhapsody system. The monthly reports submitted to the MRC and NIHR provide ongoing updates of milestone progress.
Impact Papers attributable to this project are listed under the relevant section of this form. This collaboration is part of a wider 19-Centre Consortium, with multi-disciplinary working throughout the various institutions.
Start Year 2020
 
Description UK-CIC collaboration with Newcastle University 
Organisation Newcastle University
Country United Kingdom 
Sector Academic/University 
PI Contribution The University of Birmingham provides central coordination of the UK-CIC funding; operational support of Consortium events including fortnightly meetings for all collaborators and quarterly individual Centre meetings; management of reporting to the funder of all Centre's progress; engagement with the British Society for Immunology regarding all communications, and preparation for the UK-CIC virtual conference. Professor Paul Moss, as Consortium Lead, brings collaborators together to share scientific findings, encouraging sharing of methodology, data and expertise. He takes responsibility for feeding into the Oversight Committee the achievements and challenges of UK-CIC. The University provides expertise on contracts and finance, ensuring the smooth running of this project.
Collaborator Contribution This Centre contributes to Themes 1, and 3, with broad milestones as follows: Theme 1 - Provision of anonymised clinical metadata and associated lymphocyte subset analysis for central aggregation in n=60 COVID-19 patients. Optimised protocol for CITE-seq data generation and analysis. Partnership agreement between Imperial, Newcastle and Sanger for BAME renal failure cohort CITE-seq analysis. T cell memory and multiparametric flow phenotyping (PBMC samples from COVID-19 inpatients) initiated. Theme 3 - Collate PM tissue blocks (kidney, lung, heart from n=10 Newcastle patients) and robust anonymised clinical metadata. Optimise viral Ag detection by IHC. Characterise histopathological changes of interest, marking up key ROIs (e.g. focal areas of inflammation and immune cell recruitment, regions of vascular abnormality). Prepare and distribute serial sections to York and Sanger for parallel mRNA expression analysis. Optimise 34-plex IMC panel including viral Ag detection (spike/nucleo-capsid). The monthly reports submitted to the MRC and NIHR provide ongoing updates of milestone progress.
Impact Papers attributable to this project are listed under the relevant section of this form. This collaboration is part of a wider 19-Centre Consortium, with multi-disciplinary working throughout the various institutions.
Start Year 2020
 
Description UK-CIC collaboration with University College London 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution The University of Birmingham provides central coordination of the UK-CIC funding; operational support of Consortium events including fortnightly meetings for all collaborators and quarterly individual Centre meetings; management of reporting to the funder of all Centre's progress; engagement with the British Society for Immunology regarding all communications, and preparation for the UK-CIC virtual conference. Professor Paul Moss, as Consortium Lead, brings collaborators together to share scientific findings, encouraging sharing of methodology, data and expertise. He takes responsibility for feeding into the Oversight Committee the achievements and challenges of UK-CIC. The University provides expertise on contracts and finance, ensuring the smooth running of this project.
Collaborator Contribution This Centre contributes to Themes 2 and 4, with broad milestones as follows: Theme 4 - Initial comparison of SARS-CoV-2 reactive T cells in pre-pandemic samples, exposed uninfected and infected HCW from Barts HCW Covidsortium. Design of peptide pools that allow delineation of SARS-CoV-2 versus pre-existing/cross-reactive CoV T cell responses. Selection of peptide regions from HCoV to be ordered jointly by Theme 4 centres. Monitor fate of pre-existing SARS-CoV-2-reactive T cells following in vivo COVID-19 using Barts Covidsortium and other cohorts with pre-infection samples including ALSPAC. Define specific HLA-restricted epitopes to focus on for cross-reactivity with HCoV (with other Theme 2/4 centres). Optimise sorting SARS-CoV-2 cross-reactive T cells for TCR analysis. Theme 2 - Detail the number of PBMC samples available for the TCR repertoire studies at UCL (access to PBMC collected by the Barts Covidsortium study and to PBMC collected at the Royal Free Hospital from patients admitted to the hospital with COVID-19. Collate initial data from bulk TCR repertoire. Create SOP for sorting Sars-Cov-2 specific T cells. The monthly reports submitted to the MRC and NIHR provide ongoing updates of milestone progress.
Impact Papers attributable to this project are listed under the relevant section of this form. This collaboration is part of a wider 19-Centre Consortium, with multi-disciplinary working throughout the various institutions.
Start Year 2020
 
Description UK-CIC collaboration with University of Bristol 
Organisation University of Bristol
Country United Kingdom 
Sector Academic/University 
PI Contribution The University of Birmingham provides central coordination of the UK-CIC funding; operational support of Consortium events including fortnightly meetings for all collaborators and quarterly individual Centre meetings; management of reporting to the funder of all Centre's progress; engagement with the British Society for Immunology regarding all communications, and preparation for the UK-CIC virtual conference. Professor Paul Moss, as Consortium Lead, brings collaborators together to share scientific findings, encouraging sharing of methodology, data and expertise. He takes responsibility for feeding into the Oversight Committee the achievements and challenges of UK-CIC. The University provides expertise on contracts and finance, ensuring the smooth running of this project.
Collaborator Contribution This Centre contributes to Theme 2, with broad milestones as follows: Screen 5000 participants (antibody home kits), combine these data with questionnaire and pillar testing/eHR linkage data to gain maximal case assignment. Develop protocol and obtain ethical approval for recruitment of participants, collection of samples and analysis of samples (with storage). Recruitment (participant consenting and visits for sample and data collection). Implement two sampling phases: PHASE1 - Initial cross-section sampling of all cases reported in ALSPAC and a maximum of 1:4 controls for initial sample collection and phenotypic assessment (including questionnaire) - a minimum of 50 cases, and up to 4n controls and a PHASE2 sample of a minimum of 50 cases and 10 controls. Implement a specific, secure, sample storage facility for UKCiC in Bristol within our ISO accredited facility and to ultimately make samples available through existing managed access routes. The monthly reports submitted to the MRC and NIHR provide ongoing updates of milestone progress.
Impact Papers attributable to this project are listed under the relevant section of this form. This collaboration is part of a wider 19-Centre Consortium, with multi-disciplinary working throughout the various institutions.
Start Year 2020
 
Description UK-CIC collaboration with University of Cambridge 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution The University of Birmingham provides central coordination of the UK-CIC funding; operational support of Consortium events including fortnightly meetings for all collaborators and quarterly individual Centre meetings; management of reporting to the funder of all Centre's progress; engagement with the British Society for Immunology regarding all communications, and preparation for the UK-CIC virtual conference. Professor Paul Moss, as Consortium Lead, brings collaborators together to share scientific findings, encouraging sharing of methodology, data and expertise. He takes responsibility for feeding into the Oversight Committee the achievements and challenges of UK-CIC. The University provides expertise on contracts and finance, ensuring the smooth running of this project.
Collaborator Contribution This Centre contributes to Themes 1 and 5, with broad milestones as follows: Theme 1 - Curate patient samples. Make flow phenotyping and inflammatory marker data available for transfer. Recruit staff with expertise in B cell repertoire analysis. Detailed immunophenotypic analysis of immunomes. B cell analysis, initially with flow (and Cytof) immunophenotypic data. B cell repertoire data generation. Complete datasets and B cell analysis, comparing mild and hospitalised cases, including repertoire. Cambridge flow data on severe and mild patients. Theme 5 - Establish infectivity of ACE2-expressing human cell lines, and time course of infection. Establish growth characteristics of virus in human primary epithelial cells. Establish infection characteristics and time course of infection for cancer cell lines, primary human epithelial cell lines (upper and lower airway) and alveolar epithelial cells. Complete proteomics time course in cells as outlined above. Full mass spec data available and processed and initiation of proteomic analysis. Discuss with Glasgow CVR about generation of viral mutants. The monthly reports submitted to the MRC and NIHR provide ongoing updates of milestone progress.
Impact Papers attributable to this project are listed under the relevant section of this form. This collaboration is part of a wider 19-Centre Consortium, with multi-disciplinary working throughout the various institutions.
Start Year 2020
 
Description UK-CIC collaboration with University of Dundee 
Organisation University of Dundee
Country United Kingdom 
Sector Academic/University 
PI Contribution The University of Birmingham provides central coordination of the UK-CIC funding; operational support of Consortium events including fortnightly meetings for all collaborators and quarterly individual Centre meetings; management of reporting to the funder of all Centre's progress; engagement with the British Society for Immunology regarding all communications, and preparation for the UK-CIC virtual conference. Professor Paul Moss, as Consortium Lead, brings collaborators together to share scientific findings, encouraging sharing of methodology, data and expertise. He takes responsibility for feeding into the Oversight Committee the achievements and challenges of UK-CIC. The University provides expertise on contracts and finance, ensuring the smooth running of this project.
Collaborator Contribution This Centre contributes to Theme 1, with broad milestones as follows: Mass spectrometry analysis of neutrophil samples from Edinburgh from healthy controls, patients with ARDS (acute respiratory distress syndrome) and patients with COVID and ARDS, with samples run in single-shot DIA mode. Mass spectrometry analysis of neutrophil samples from Dundee from controls and patients with COVID, with samples being run in single-shot DIA mode. Mass spectrometry analysis of PBMC samples from Dundee from controls and patients with COVID, with samples being run in single-shot DDA mode. Experiments to optimise preparation of cells from frozen blood samples for mass spectrometry analysis. Preparation and proteomic analysis of leucocyte populations from healthy donors as controls. Mass spectrometry analysis of leucocyte populations from patients with COVID collected by. the Consortium. Proteomic analysis of leucocytes from patients with COVID and patients recovering from COVID. Data analysis of this dataset. Proteomic analysis of cells from whole blood samples from healthy controls and patients with COVID. The monthly reports submitted to the MRC and NIHR provide ongoing updates of milestone progress.
Impact Papers attributable to this project are listed under the relevant section of this form. This collaboration is part of a wider 19-Centre Consortium, with multi-disciplinary working throughout the various institutions.
Start Year 2020
 
Description UK-CIC collaboration with University of Edinburgh 
Organisation University of Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution The University of Birmingham provides central coordination of the UK-CIC funding; operational support of Consortium events including fortnightly meetings for all collaborators and quarterly individual Centre meetings; management of reporting to the funder of all Centre's progress; engagement with the British Society for Immunology regarding all communications, and preparation for the UK-CIC virtual conference. Professor Paul Moss, as Consortium Lead, brings collaborators together to share scientific findings, encouraging sharing of methodology, data and expertise. He takes responsibility for feeding into the Oversight Committee the achievements and challenges of UK-CIC. The University provides expertise on contracts and finance, ensuring the smooth running of this project.
Collaborator Contribution This Centre contributes to Themes 1 and 2, with broad milestones as follows: Theme 1 - Proteomic analysis of normal and low-density neutrophils, COVID and non-COVID ARDS, for initial acute cohort. Paired metabolite analysis of early acute cohort. Lipidomics: initial samples phenotyped, further acute samples required. Recruitment of 6 month follow up patients to replicate assays and undertake epigenetic analysis. Theme 2 - The ISARIC 4C Follow Up study is planned in detail and Centres prepared for sample analysis. Protocol for follow-up sampling of T-cells, neutrophils, monocytes and plasma from post-Covid cases written, tested and agreed. Established analysis platform, with 25 internal users routinely using the data analysis platform and data linkage across the whole ISARIC 4C data set is at an advanced stage. External access system has been built with secure access through customisable virtual machines to enable external users to browse and analyse data freely and securely. Clinical and biological data have been cleaned and de-identified for delivery to external users. The monthly reports submitted to the MRC and NIHR provide ongoing updates of milestone progress.
Impact Papers attributable to this project are listed under the relevant section of this form. This collaboration is part of a wider 19-Centre Consortium, with multi-disciplinary working throughout the various institutions.
Start Year 2020
 
Description UK-CIC collaboration with University of Glasgow 
Organisation University of Glasgow
Country United Kingdom 
Sector Academic/University 
PI Contribution The University of Birmingham provides central coordination of the UK-CIC funding; operational support of Consortium events including fortnightly meetings for all collaborators and quarterly individual Centre meetings; management of reporting to the funder of all Centre's progress; engagement with the British Society for Immunology regarding all communications, and preparation for the UK-CIC virtual conference. Professor Paul Moss, as Consortium Lead, brings collaborators together to share scientific findings, encouraging sharing of methodology, data and expertise. He takes responsibility for feeding into the Oversight Committee the achievements and challenges of UK-CIC. The University provides expertise on contracts and finance, ensuring the smooth running of this project.
Collaborator Contribution This Centre contributes to Themes 2 and 5, with broad milestones as follows: Theme 2 - Undertake patient recruitment/PBMC isolation. Commence ddPCR analysis. Design and construction of oligonucleotide panels 1 and 2. Construction of phage library and immunoprecipitation experiments. Analysis of NGS data and sequencing. Theme 5 - Investigate ISGs and SARS-CoV-2 pathogenesis through ISG screen, miniscreen of candidate anti-SARS-CoV-2 ISGs, loss of function and mechanistic studies, synthesis and assessment of allelic variants and examine candidate factors in patient data. The monthly reports submitted to the MRC and NIHR provide ongoing updates of milestone progress.
Impact Papers attributable to this project are listed under the relevant section of this form. This collaboration is part of a wider 19-Centre Consortium, with multi-disciplinary working throughout the various institutions.
Start Year 2020
 
Description UK-CIC collaboration with University of Liverpool 
Organisation University of Liverpool
Country United Kingdom 
Sector Academic/University 
PI Contribution The University of Birmingham provides central coordination of the UK-CIC funding; operational support of Consortium events including fortnightly meetings for all collaborators and quarterly individual Centre meetings; management of reporting to the funder of all Centre's progress; engagement with the British Society for Immunology regarding all communications, and preparation for the UK-CIC virtual conference. Professor Paul Moss, as Consortium Lead, brings collaborators together to share scientific findings, encouraging sharing of methodology, data and expertise. He takes responsibility for feeding into the Oversight Committee the achievements and challenges of UK-CIC. The University provides expertise on contracts and finance, ensuring the smooth running of this project.
Collaborator Contribution This Centre contributes to Theme 2, with broad milestones as follows: Theme 2 - Recruitment of ISARIC tier 2 patients at follow up. Integration of recruitment into PHOSP for reducing patient burden, agree common SOP, submit documents to PHOSP for ethics amendment. Generate phenotyping data on acute cytodelics samples. 67 patients recruited to follow up (Liverpool target). Recruitment at other sites near complete. ELISpot harmonised between sites and underway. The monthly reports submitted to the MRC and NIHR provide ongoing updates of milestone progress.
Impact Papers attributable to this project are listed under the relevant section of this form. This collaboration is part of a wider 19-Centre Consortium, with multi-disciplinary working throughout the various institutions.
Start Year 2020
 
Description UK-CIC collaboration with University of Manchester 
Organisation University of Manchester
Country United Kingdom 
Sector Academic/University 
PI Contribution The University of Birmingham provides central coordination of the UK-CIC funding; operational support of Consortium events including fortnightly meetings for all collaborators and quarterly individual Centre meetings; management of reporting to the funder of all Centre's progress; engagement with the British Society for Immunology regarding all communications, and preparation for the UK-CIC virtual conference. Professor Paul Moss, as Consortium Lead, brings collaborators together to share scientific findings, encouraging sharing of methodology, data and expertise. He takes responsibility for feeding into the Oversight Committee the achievements and challenges of UK-CIC. The University provides expertise on contracts and finance, ensuring the smooth running of this project.
Collaborator Contribution This Centre contributes to Theme 1, with broad milestones as follows: Theme 1 - Collection of data for central aggregation. Appointment of two bio-informaticians. Data from different analytic platforms rendered in format for comparative study. Distribution of longitudinal plasma/serum to York, Birmingham and Sheffield for analyses including autoantibodies. Provision of plasma and cells to Dundee for proteomics. Implementation of MTAs between Manchester and others receiving samples. Protocol sharing platform (protocols.io) implemented and shared with consortium. Design of experiments to address the problem of PBMC analysis that omits study of innate immunity. Integration of data sets, leading to a manuscript on BAME/age/comorbidities. Draft manuscript for Nature Methods comparing whole blood analysis versus samples stored in Cytodelics versus PBMC preparations on healthy volunteers and COVID patients. Significant recruitment into the community study. The monthly reports submitted to the MRC and NIHR provide ongoing updates of milestone progress.
Impact Papers attributable to this project are listed under the relevant section of this form. This collaboration is part of a wider 19-Centre Consortium, with multi-disciplinary working throughout the various institutions.
Start Year 2020
 
Description UK-CIC collaboration with University of Oxford 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution The University of Birmingham provides central coordination of the UK-CIC funding; operational support of Consortium events including fortnightly meetings for all collaborators and quarterly individual Centre meetings; management of reporting to the funder of all Centre's progress; engagement with the British Society for Immunology regarding all communications, and preparation for the UK-CIC virtual conference. Professor Paul Moss, as Consortium Lead, brings collaborators together to share scientific findings, encouraging sharing of methodology, data and expertise. He takes responsibility for feeding into the Oversight Committee the achievements and challenges of UK-CIC. The University provides expertise on contracts and finance, ensuring the smooth running of this project.
Collaborator Contribution This Centre contributes to Themes 2 and 4, with broad milestones as follows: Theme 2 - Establishment of core T cell assays to allow evaluation of durability and relationship to ongoing infection risk. Publication on Medrxiv.org of cross-sectional characterisation of functional T cell immunity to SARS-CoV-2 following infection. Create a SOP for optimal T cell assay. Analysis of magnitude and phenotype of SARS-specific CD4+ responses defined in >50 donors. Theme 4 - Design peptide pools to allow delineation of SARS-CoV-2 and pre-existing/cross-reactive CoV T cell responses. In the STORY study, analysis of paediatric PBMC to evaluate cross-reactive immunity in children. The monthly reports submitted to the MRC and NIHR provide ongoing updates of milestone progress.
Impact Papers attributable to this project are listed under the relevant section of this form. This collaboration is part of a wider 19-Centre Consortium, with multi-disciplinary working throughout the various institutions.
Start Year 2020
 
Description UK-CIC collaboration with University of Sheffield 
Organisation University of Sheffield
Country United Kingdom 
Sector Academic/University 
PI Contribution The University of Birmingham provides central coordination of the UK-CIC funding; operational support of Consortium events including fortnightly meetings for all collaborators and quarterly individual Centre meetings; management of reporting to the funder of all Centre's progress; engagement with the British Society for Immunology regarding all communications, and preparation for the UK-CIC virtual conference. Professor Paul Moss, as Consortium Lead, brings collaborators together to share scientific findings, encouraging sharing of methodology, data and expertise. He takes responsibility for feeding into the Oversight Committee the achievements and challenges of UK-CIC. The University provides expertise on contracts and finance, ensuring the smooth running of this project.
Collaborator Contribution This Centre contributes to Themes 1, 2 and 4, with broad milestones as follows: Theme 1 - Recruiting/training researchers to comply with HTA and CL3 working requirements; SOP development. Piloting myeloid cell and microvesicle analysis. Initial functional experiments on the action of microvesicles on endothelial cells. Theme 2 - The ISARIC 4C Follow Up study is planned in detail, with Centres prepared for sample analysis. Samples are delivered from Sheffield to other relevant research centres, with cell mediated immunity analyses underway in Sheffield. Theme 4 - Generation of peptide pools containing viral escape mutations. T cell analyses performed in seropositive and seronegative donors. Cellular recognition of viral mutations is undertaken. Comparative studies undertaken in banked samples from CIC cohort studies. Potential importance of immune escape based on common viral variants is defined. The monthly reports submitted to the MRC and NIHR provide ongoing updates of milestone progress.
Impact Papers attributable to this project are listed under the relevant section of this form. This collaboration is part of a wider 19-Centre Consortium, with multi-disciplinary working throughout the various institutions.
Start Year 2020
 
Description UK-CIC collaboration with University of York 
Organisation University of York
Country United Kingdom 
Sector Academic/University 
PI Contribution The University of Birmingham provides central coordination of the UK-CIC funding; operational support of Consortium events including fortnightly meetings for all collaborators and quarterly individual Centre meetings; management of reporting to the funder of all Centre's progress; engagement with the British Society for Immunology regarding all communications, and preparation for the UK-CIC virtual conference. Professor Paul Moss, as Consortium Lead, brings collaborators together to share scientific findings, encouraging sharing of methodology, data and expertise. He takes responsibility for feeding into the Oversight Committee the achievements and challenges of UK-CIC. The University provides expertise on contracts and finance, ensuring the smooth running of this project.
Collaborator Contribution This Centre contributes to Themes 1 and 3, with broad milestones as follows: - Theme 1: Scoping and identification of potential sample cohorts that would benefit by high-resolution analysis of systemic correlates of infection (focussing on those that cyto/chemokine profiling has left unanswered questions and/or emerging cohorts). Complete analysis and integrate with other analyses within Theme 1. - Theme 3: Identification of available samples within the consortium. Complete MTA, ERC and HTA documentation. Scoping and identification of experimental hypotheses that could be tested through available post-mortem samples. Initial segmentation analysis based on morphology and / or potential therapeutic targets. Markers defined from published or in house studies. Initial data integration across Theme 3. The monthly reports submitted to the MRC and NIHR provide ongoing updates of milestone progress.
Impact Papers attributable to this project are listed under the relevant section of this form. This collaboration is part of a wider 19-Centre Consortium, with multi-disciplinary working throughout the various institutions.
Start Year 2020
 
Description UK-CIC collaboration with Wellcome Sanger Institute 
Organisation The Wellcome Trust Sanger Institute
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution The University of Birmingham provides central coordination of the UK-CIC funding; operational support of Consortium events including fortnightly meetings for all collaborators and quarterly individual Centre meetings; management of reporting to the funder of all Centre's progress; engagement with the British Society for Immunology regarding all communications, and preparation for the UK-CIC virtual conference. Professor Paul Moss, as Consortium Lead, brings collaborators together to share scientific findings, encouraging sharing of methodology, data and expertise. He takes responsibility for feeding into the Oversight Committee the achievements and challenges of UK-CIC. The University provides expertise on contracts and finance, ensuring the smooth running of this project.
Collaborator Contribution This Centre contributes to Themes 1 and 3, with broad milestones as follows: Theme 1 - Generation of sequencing data from CITE-seq samples. Analysis and interrogation of CITE-seq data to identify unique features of SARS-CoV-2 infected patients' immune subsets. Preparation of manuscript detailing findings in collaboration with consortium. Theme 3 - Generation of molecular histology data from post-mortem samples sections using Nanostring WTA analysis. Analysis and interrogation of nanostring and hyperion technology data to across different tissue sections. Assessment of relationship between viral replication and immunopathology. Preparation of manuscript detailing findings in collaboration with consortium. The monthly reports submitted to the MRC and NIHR provide ongoing updates of milestone progress.
Impact Papers attributable to this project are listed under the relevant section of this form. This collaboration is part of a wider 19-Centre Consortium, with multi-disciplinary working throughout the various institutions.
Start Year 2020
 
Description UK-CIC Patient and Public Involvement (PPI) panel 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact The panel works with the UK-CIC Scientific Advisory Board by providing advice, guidance, and feedback on the progress of UK-CIC and their unique perspectives on the wider implications of its research. Members were recruited based on the UK-CIC research priorities. It is important that we consider the impact of UK-CIC research on patients and the general public throughout, and the PPI panel are an integral part of the consortium.
Year(s) Of Engagement Activity 2020,2021
URL https://www.uk-cic.org/about-us/patient-and-public-involvement-panel
 
Description UK-CIC Scientific Advisory Board 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The Scientific Advisory Board is responsible for providing independent advice to the Principal Investigator and the Management Team of UK-CIC. It will act as a 'sounding board' for the Management Team as research progresses and results emerge, and will discuss the relevance of emerging global research to the consortium. Its members include world-leading immunologists (independent from the consortium) and two representatives of the Public Patient Involvement (PPI) Panel; this will ensure that the priorities for and impact of research on patients and the wider public is considered at all stages of the project. The Board includes representatives from the British Society for Immunology.
Year(s) Of Engagement Activity 2020,2021
URL https://www.uk-cic.org/about-us/scientific-advisory-board