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
Eleanor Barnes (Co-Investigator)
Adam Finn (Co-Investigator)
Doreen Cantrell (Co-Investigator)
Massimo Palmarini (Co-Investigator)
V Ridger (Co-Investigator)
John Robert Grainger (Co-Investigator)
Paul Klenerman (Co-Investigator)
Malcolm Gracie Semple (Co-Investigator) orcid http://orcid.org/0000-0001-9700-0418
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
Pablo Ramiro Murcia (Co-Investigator) orcid http://orcid.org/0000-0002-4352-394X
Antonia Ho (Co-Investigator) orcid http://orcid.org/0000-0003-1465-3785
Awen Gallimore (Co-Investigator) orcid http://orcid.org/0000-0001-6675-7004
Paul Morgan (Co-Investigator) orcid http://orcid.org/0000-0003-4075-7676
Linda Wooldridge (Co-Investigator)
Andrew John Fisher (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)
Julian Leether Griffin (Co-Investigator)
Nicholas John Timpson (Co-Investigator)
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)
Ian Humphreys (Co-Investigator)
Kenny Baillie (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)
Omer Bayraktar (Co-Investigator)
Niharika Arora Duggal (Co-Investigator)
David Kavanagh (Co-Investigator) orcid http://orcid.org/0000-0003-4718-0072
Markus Ralser (Co-Investigator)
Tracy Hussell (Co-Investigator)
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)
Sarah Teichmann (Co-Investigator)
Jianmin Zuo (Co-Investigator)
Joby Cole (Co-Investigator)
Heather Margaret Long (Co-Investigator)
Ken Smith (Co-Investigator)
Thushan De Silva (Co-Investigator)
Matthew David Snape (Co-Investigator)
Brian James Willett (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

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