COVID-19 Immunity - National Core Study (IMM-NCS)

Lead Research Organisation: University of Birmingham

Abstract

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Technical Summary

The ‘NCSi4P’ programme will determine how assessment and optimisation of immune function can accelerate control of the Covid-19 pandemic. NCSi4P will focus on the role of immunity in Prediction of outcome, Protection against infection and Prevention of re-infection. These will provide a legacy for future Preparation. Prediction research will define how immunogenetics and immune function, including memory to other coronaviruses, determines risk from SARS-CoV-2 infection. Comparisons will be made between ethnic groups and in patients with a cancer diagnosis to determine how optimisation of immune function may be supported. In Protection studies we will work with surveillance teams to study people with asymptomatic infection. The aim is to understand how the immune system can control infection and to contrast this with findings in severe disease. The potential role of the immune system in ‘long-covid’ syndromes will be studied. Prevention will determine how immune memory after infection is predictive of individualised risk of potential re-infection. The findings will be compared to data emerging from vaccine studies in order to guide optimal regimens. This will be complemented with studies to optimize laboratory assays of cellular immune function. The integration of these immune studies will support the UK in Preparation for future pandemics.

Publications

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publication icon
Moss P (2022) The T cell immune response against SARS-CoV-2. in Nature immunology

 
Description Asymptomatic COVID-19 in Education (ACE) Immunity Study 
Organisation Cardiff University
Country United Kingdom 
Sector Academic/University 
PI Contribution COVID-19 Immunity - National Core Study (IMM-NCS) has funded this study
Collaborator Contribution Establishment of a student cohort of 30,000 individuals completing asymptomatic SARS-COV2 screening with around 550 baseline samples collected. We have collected samples (PBMCs, plasma, dried blood spots and saliva) from over 500 individuals to enable us to comprehensively examine immune responses in asymptomatic vs symptomatic individuals. Levels of antibodies in these individuals is currently being determined. Deep phenotyping of SARS-CoV-2 T/NKT cell responses in a subset of stored PBMC samples are also being examined to answer the key question of how immune responses differ in asymptomatic and symptomatic infection.
Impact Plasma samples have been assayed for Wuhan Full length spike/nucleocapsid IgG levels showing no significant differences between asymptomatic infection and symptomatic infection (P=0.4899). Saliva samples have also been analysed for Wuhan Full length spike/nucleocapsid IgA levels. There is no correlation between plasma IgG and salivary IgA levels, although identified some interesting groupings that require further analysis (i.e. IgA positive but self-report no COVID, IgG positive but no IgA, IgG and IgA positive). Some PBMC samples have also been deep phenotyped using Spectral Flow Cytometry, to examine quality and quantity of SARS-CoV2 specific T cells, showing differences between symptomatic/asymptomatic infection.
Start Year 2021
 
Description Asymptomatic COVID-19 in Education (ACE) Immunity Study 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution COVID-19 Immunity - National Core Study (IMM-NCS) has funded this study
Collaborator Contribution Establishment of a student cohort of 30,000 individuals completing asymptomatic SARS-COV2 screening with around 550 baseline samples collected. We have collected samples (PBMCs, plasma, dried blood spots and saliva) from over 500 individuals to enable us to comprehensively examine immune responses in asymptomatic vs symptomatic individuals. Levels of antibodies in these individuals is currently being determined. Deep phenotyping of SARS-CoV-2 T/NKT cell responses in a subset of stored PBMC samples are also being examined to answer the key question of how immune responses differ in asymptomatic and symptomatic infection.
Impact Plasma samples have been assayed for Wuhan Full length spike/nucleocapsid IgG levels showing no significant differences between asymptomatic infection and symptomatic infection (P=0.4899). Saliva samples have also been analysed for Wuhan Full length spike/nucleocapsid IgA levels. There is no correlation between plasma IgG and salivary IgA levels, although identified some interesting groupings that require further analysis (i.e. IgA positive but self-report no COVID, IgG positive but no IgA, IgG and IgA positive). Some PBMC samples have also been deep phenotyped using Spectral Flow Cytometry, to examine quality and quantity of SARS-CoV2 specific T cells, showing differences between symptomatic/asymptomatic infection.
Start Year 2021
 
Description Asymptomatic COVID-19 in Education (ACE) Immunity Study 
Organisation University of Nottingham
Country United Kingdom 
Sector Academic/University 
PI Contribution COVID-19 Immunity - National Core Study (IMM-NCS) has funded this study
Collaborator Contribution Establishment of a student cohort of 30,000 individuals completing asymptomatic SARS-COV2 screening with around 550 baseline samples collected. We have collected samples (PBMCs, plasma, dried blood spots and saliva) from over 500 individuals to enable us to comprehensively examine immune responses in asymptomatic vs symptomatic individuals. Levels of antibodies in these individuals is currently being determined. Deep phenotyping of SARS-CoV-2 T/NKT cell responses in a subset of stored PBMC samples are also being examined to answer the key question of how immune responses differ in asymptomatic and symptomatic infection.
Impact Plasma samples have been assayed for Wuhan Full length spike/nucleocapsid IgG levels showing no significant differences between asymptomatic infection and symptomatic infection (P=0.4899). Saliva samples have also been analysed for Wuhan Full length spike/nucleocapsid IgA levels. There is no correlation between plasma IgG and salivary IgA levels, although identified some interesting groupings that require further analysis (i.e. IgA positive but self-report no COVID, IgG positive but no IgA, IgG and IgA positive). Some PBMC samples have also been deep phenotyped using Spectral Flow Cytometry, to examine quality and quantity of SARS-CoV2 specific T cells, showing differences between symptomatic/asymptomatic infection.
Start Year 2021
 
Description BE-DIRECT_Broadening our understanding of Early versus Late InfluEnza Vaccine Effectiveness - Determining the Immune Response in Ethnic minority healthcare workers to COVID-19 infecTion, (a sub-study of UK-REACH). 
Organisation University of Leicester
Country United Kingdom 
Sector Academic/University 
PI Contribution BE-DIRECT has been funded by the NCS Phase 0 award.
Collaborator Contribution BE-DIRECT is investigating the impact of ethnicity on outcome from COVID-19 in UK healthcare workers. The primary objectives are to determine if the immune response to COVID-19 infection and SARS-CoV-2 vaccination differ according to ethnicity in a population of healthcare workers (HCW) and to determine if co-administration of influenza and SARS-CoV-2 vaccination has an effect on immune responses to either vaccine. An extensive questionnaire collects information on a broad range of sociodemographic characteristics and SARS-CoV-2 exposure information to address secondary outcome measures pertaining to the effects of demographic characteristics. Participants have consented for linkage to healthcare records (including occupational health record) for a period of 25 years.
Impact BE-DIRECT has exceeded its recruitment target within 3 months. The cohort is unique in its ethnic diversity. - The majority of participants in BE-DIRECT have already been sampled at baseline (approximately 6 months pre-booster), immediately pre-booster and 3 weeks post-booster. - A large dataset has been curated containing data from over 800 participants in total (the combined cohorts of the DIRECT and BELIEVE studies). This currently contains baseline serology and ELISpot results as well as pre-boost and post-boost ELISpot results (for those who consented to participate in BE-DIRECT).
Start Year 2021
 
Description COVID-19 vaccine responses in follicular lymphoma 
Organisation University of Liverpool
Country United Kingdom 
Sector Academic/University 
PI Contribution COVID-19 Immunity - National Core Study (IMM-NCS) has funded this study
Collaborator Contribution The PETReA clinical trial provides an ideal context for studying antibody and T-cell responses to COVID-19 vaccines in people with follicular lymphoma (FL) and how such responses are affected by treatments that selectively deplete B cells (rituximab) or T cells (bendamustine), or which have an immunostimulatory effect (lenalidomide). Study participants are asked to provide blood samples at specified timepoints after COVID vaccination. The samples are sent to Liverpool or Oxford for measurement of antibodies and T cells that react to SARS-CoV-2 using the same assays that are used in the PITCH study of COVID vaccine responses in healthy individuals. As we learn more about which parts of the immune system are most important in protecting against COVID-19, the study should help people with FL to make better informed decisions about treatment options, while it should give those patients who have already completed treatment a better idea of how much protection to expect from vaccination and what additional precautions might be required.
Impact mple collection and analysis is ongoing, but the results so far can be summarized as follows: 1. There is wide variation in anti-spike antibody levels, with values significantly lower than in the PITCH study of healthy individuals 2-6 weeks after the first and second jabs (p<0.001) and below the threshold for positivity in a substantial proportion of patients: 4/5 (80%) 2-6 weeks after the first jab (T1); 25/44 (57%) 2-6 weeks after the second jab (T2); and 26/36 (72%) 6 months after the second jab (T3). 2. Measurement of anti-spike T-cell responses by ELISpot is so far available for timepoints T1, T2 and T3 in 2, 34 and 20 patients, respectively. Values for all three timepoints vary widely between patients but are relatively well preserved with only the T3 timepoint showing values significant lower than in healthy individuals (p=0.018). 3. 24/83 (29%) of ELISpot tests had unacceptably high background levels and are being re-run.
Start Year 2021
 
Description Collaboration across the NCS network 
Organisation Public Health Agency (PHA)
Country United Kingdom 
Sector Public 
PI Contribution The GoS/UKRI NCS award has facilitated a wide range of interactions both across the NCS specialist groups, and also within NCS immunology. The investment has supported 15+ groups who work independently but also meet regularly for virtual meetings and share reagents. We have also worked with the PHE/DHHSE team in preparation and delivery of the CONSENSUS study which assesses immunity in relation to the dose interval between first and second dose.
Collaborator Contribution We demonstrated that extended interval BNT162b2 vaccination was associated with increased antibody response in older people.
Impact Joint publications from the CONSENSUS study as shown
Start Year 2020
 
Description Cytokine Autoimmunity: Anti-interferon autoantibodies in COVID-20 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution COVID-19 Immunity - National Core Study (IMM-NCS) has funded this study
Collaborator Contribution This project is a true collaborative effort that will give a detailed overview of anti-cytokine autoimmunity in COVID-19 in a large population group. Covering seven cohorts from across the UK, we have performed anti-cytokine autoantibody screens on nearly 5,500 samples from 2,700 individuals. Our screens cover more cytokine targets and isotypes than previously reported, allowing for a better understanding of the nuances of anti-cytokine autoantibodies in COVID-19, other respiratory infections, and population controls.
Impact In this study, we screened over 5,000 patient samples for anti-cytokine autoantibodies using a Luminex multiplex bead system. Confirming previously reported findings, we find high-titre anti-type I interferon autoantibodies in around 10% of severe COVID-19 patients. Interestingly, an even larger subgroup develop lower levels of these antibodies over the course of disease. We are currently investigating the functional capacity of these autoantibodies in a cellular reporter assay and are integrating these findings with detailed clinical parameters as well as whole blood RNAseq data. This will allow us to investigate the correlation of these antibodies with clinical factors, ethnicity, reinfection rates, and symptoms of long COVID. Expanding our study to other infections, such as the flu, will help us determine whether these antibodies are specific to COVID. A better understanding of how these antibodies impact disease may help us predict the risk of COVID complications, and provide insight into how to prevent or treat them.
Start Year 2021
 
Description Effects of shielding for Vulnerable people during COVID-19 pandemic (EVITE Immunity) 
Organisation Swansea University
Country United Kingdom 
Sector Academic/University 
PI Contribution COVID-19 Immunity - National Core Study (IMM-NCS) has funded this study
Collaborator Contribution Shielding was introduced during the COVID-19 pandemic across the UK. It was intended to protect those thought to be at highest risk of serious harm should they catch COVID-19 because of preconditions such as cancer or medications that they were taking. EVITE Immunity will involve work with NHS partners to evaluate shielding in Wales, where records for people who were shielding have already been anonymously linked into other integrated data systems. We will identify records of patients who mirror those who were shielding and use the routinely available data to compare outcomes between both groups.
Impact The results of the data analysis carried out in Phase 1 of the EVITE Immunity study have shown that the implementation of the shielding policy in Wales did not result in a significant reduction in COVID-19 infections in the shielded population that had been hoped for. We will continue to analyse the data, and the work undertaken in Phase 2 will help to understand the effects of the shielding policy. Phase 2 of the study is now underway. Research permissions have now been granted. The ethics committee has approved the interview materials and participant questionnaire. Work has been undertaken to construct a cohort of people that matches the population asked to shield on age group, gender, and recent healthcare use (summarised by outpatient attendances, and length of stays in hospital) characteristics. Digital Health and Care Wales have created a sample of individuals matching these characteristics, the data for this group will be passed to SAIL. A subsample of this group will be passed to NHS Shared Services. We have worked with colleagues at Digital Health and Care Wales and NHS Shared Services to identify a mechanism to distribute the participant's questionnaires. Questionnaires will be posted to individuals to gather data on their experiences during the first wave of the COVID 19 pandemic. Returned questionnaires will be anonymously linked to their patient data within the SAIL databank. The questionnaires are ready for distribution by post. However, we are experiencing some delays to distribution as several key staff in the NHS Shared Services have been absent from work due to COVID 19. Several papers are currently being drafted for publication in the new year. The protocol has been submitted for publication to the BMJ Open. The project has had some slippage due to the delayed confirmation of the funding for Phase 2 and now risks not meeting the milestones set out in the proposal (manuscript ID: bmjopen-2021-059813).
Start Year 2021
 
Description OCTAVE DUO 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution COVID-19 Immunity - National Core Study (IMM-NCS) has funded this study
Collaborator Contribution Work from OCTAVE identified that many patients with immune suppression mounted either suboptimal or absent antibody response following dual COVID vaccination. This was particularly true for patients on immune suppression after allogeneic transplantation or patients with blood cancer. As such this indentifed a need for 'booster' vaccines in several patient subgroups. Following discussion between OCTAVE and the Deputy CMO, the OCTAVE-DUO clinical trial was initiated: a Phase III, multi-centre, multi-disease, open-label, randomised CTIMP to determine whether a 3rd dose of vaccine can induce an immune response in clinically vulnerable patients with proven inadequate response to 2 doses of SARS-CoV-2 vaccine.
Impact OCTAVE-DUO has successful recruited (~791 patients) across multiple diseases and multiple centres in the UK. Recruitment to 7 of the 9 disease sites has now stopped and most samples have been processed for initial serological and cellular characterization of the immunological response to vaccination. Interim analysis of the first 186 patients revealed that the 3rd dose was able to enhance a low antibody response to a level that was equivalent to healthy controls after 2 vaccine doses. However, the majority of patients who had no antibody responses after 2 doses, continued to have no antibody response after the 3rd dose.
Start Year 2021
 
Description OCTAVE DUO 
Organisation University of Glasgow
Country United Kingdom 
Sector Academic/University 
PI Contribution COVID-19 Immunity - National Core Study (IMM-NCS) has funded this study
Collaborator Contribution Work from OCTAVE identified that many patients with immune suppression mounted either suboptimal or absent antibody response following dual COVID vaccination. This was particularly true for patients on immune suppression after allogeneic transplantation or patients with blood cancer. As such this indentifed a need for 'booster' vaccines in several patient subgroups. Following discussion between OCTAVE and the Deputy CMO, the OCTAVE-DUO clinical trial was initiated: a Phase III, multi-centre, multi-disease, open-label, randomised CTIMP to determine whether a 3rd dose of vaccine can induce an immune response in clinically vulnerable patients with proven inadequate response to 2 doses of SARS-CoV-2 vaccine.
Impact OCTAVE-DUO has successful recruited (~791 patients) across multiple diseases and multiple centres in the UK. Recruitment to 7 of the 9 disease sites has now stopped and most samples have been processed for initial serological and cellular characterization of the immunological response to vaccination. Interim analysis of the first 186 patients revealed that the 3rd dose was able to enhance a low antibody response to a level that was equivalent to healthy controls after 2 vaccine doses. However, the majority of patients who had no antibody responses after 2 doses, continued to have no antibody response after the 3rd dose.
Start Year 2021
 
Description OCTAVE DUO 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution COVID-19 Immunity - National Core Study (IMM-NCS) has funded this study
Collaborator Contribution Work from OCTAVE identified that many patients with immune suppression mounted either suboptimal or absent antibody response following dual COVID vaccination. This was particularly true for patients on immune suppression after allogeneic transplantation or patients with blood cancer. As such this indentifed a need for 'booster' vaccines in several patient subgroups. Following discussion between OCTAVE and the Deputy CMO, the OCTAVE-DUO clinical trial was initiated: a Phase III, multi-centre, multi-disease, open-label, randomised CTIMP to determine whether a 3rd dose of vaccine can induce an immune response in clinically vulnerable patients with proven inadequate response to 2 doses of SARS-CoV-2 vaccine.
Impact OCTAVE-DUO has successful recruited (~791 patients) across multiple diseases and multiple centres in the UK. Recruitment to 7 of the 9 disease sites has now stopped and most samples have been processed for initial serological and cellular characterization of the immunological response to vaccination. Interim analysis of the first 186 patients revealed that the 3rd dose was able to enhance a low antibody response to a level that was equivalent to healthy controls after 2 vaccine doses. However, the majority of patients who had no antibody responses after 2 doses, continued to have no antibody response after the 3rd dose.
Start Year 2021
 
Description OCTAVE UK-Vaccine Immune Protection. 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution COVID-19 Immunity - National Core Study (IMM-NCS) has funded this study
Collaborator Contribution The OCTAVE study is a multi-centre, multi-disease, prospective observational cohort analysis of the effectiveness of SARS-CoV2 vaccination in clinically vulnerable groups across the UK. Disease phenotypes recruited include end-stage renal disease, hepatic disease, cancer (solid and haematologic), immune-mediated inflammatory diseases including rheumatoid arthritis psoriatic arthritis, ANCA-associated vasculitis, inflammatory bowel disease (IBD) and solid organ and blood transplant recipients. The primary aim of the study is to evaluate immunity (serological and cellular) arising from receipt of the AstraZeneca ChAdOx1 nCoV-19 (AZD1222) vaccine or Pfizer/BioNTech mRNA vaccine.
Impact It is too early for us to report formal insights, however, formal analysis is on-going and will report in January 2022. The most important initial observation from our informal analysis is that there are a proportion of patients in our cohort that do not mount a detectable serological response. These groups have been identified and enrolled in the OCTAVE-DUO follow-on study that is aimed at evaluating the capacity of a 3rd vaccine dose to drive and enhance serological response. Cellular responses will also be characterised in that setting. Combined these studies are already having an immediate impact at a policy level; identifying at risk groups with minimal vaccine responsiveness and supporting the roll out of 3rd doses to at risk individuals. We also anticipate that further findings in this study will inform policy around alternative therapies (e.g. monoclonal antibodies & anti-virals) for those at the greatest risk of COVID-19-related hospitalisation or mortality.
Start Year 2021
 
Description OCTAVE UK-Vaccine Immune Protection. 
Organisation University of Glasgow
Country United Kingdom 
Sector Academic/University 
PI Contribution COVID-19 Immunity - National Core Study (IMM-NCS) has funded this study
Collaborator Contribution The OCTAVE study is a multi-centre, multi-disease, prospective observational cohort analysis of the effectiveness of SARS-CoV2 vaccination in clinically vulnerable groups across the UK. Disease phenotypes recruited include end-stage renal disease, hepatic disease, cancer (solid and haematologic), immune-mediated inflammatory diseases including rheumatoid arthritis psoriatic arthritis, ANCA-associated vasculitis, inflammatory bowel disease (IBD) and solid organ and blood transplant recipients. The primary aim of the study is to evaluate immunity (serological and cellular) arising from receipt of the AstraZeneca ChAdOx1 nCoV-19 (AZD1222) vaccine or Pfizer/BioNTech mRNA vaccine.
Impact It is too early for us to report formal insights, however, formal analysis is on-going and will report in January 2022. The most important initial observation from our informal analysis is that there are a proportion of patients in our cohort that do not mount a detectable serological response. These groups have been identified and enrolled in the OCTAVE-DUO follow-on study that is aimed at evaluating the capacity of a 3rd vaccine dose to drive and enhance serological response. Cellular responses will also be characterised in that setting. Combined these studies are already having an immediate impact at a policy level; identifying at risk groups with minimal vaccine responsiveness and supporting the roll out of 3rd doses to at risk individuals. We also anticipate that further findings in this study will inform policy around alternative therapies (e.g. monoclonal antibodies & anti-virals) for those at the greatest risk of COVID-19-related hospitalisation or mortality.
Start Year 2021
 
Description OCTAVE UK-Vaccine Immune Protection. 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution COVID-19 Immunity - National Core Study (IMM-NCS) has funded this study
Collaborator Contribution The OCTAVE study is a multi-centre, multi-disease, prospective observational cohort analysis of the effectiveness of SARS-CoV2 vaccination in clinically vulnerable groups across the UK. Disease phenotypes recruited include end-stage renal disease, hepatic disease, cancer (solid and haematologic), immune-mediated inflammatory diseases including rheumatoid arthritis psoriatic arthritis, ANCA-associated vasculitis, inflammatory bowel disease (IBD) and solid organ and blood transplant recipients. The primary aim of the study is to evaluate immunity (serological and cellular) arising from receipt of the AstraZeneca ChAdOx1 nCoV-19 (AZD1222) vaccine or Pfizer/BioNTech mRNA vaccine.
Impact It is too early for us to report formal insights, however, formal analysis is on-going and will report in January 2022. The most important initial observation from our informal analysis is that there are a proportion of patients in our cohort that do not mount a detectable serological response. These groups have been identified and enrolled in the OCTAVE-DUO follow-on study that is aimed at evaluating the capacity of a 3rd vaccine dose to drive and enhance serological response. Cellular responses will also be characterised in that setting. Combined these studies are already having an immediate impact at a policy level; identifying at risk groups with minimal vaccine responsiveness and supporting the roll out of 3rd doses to at risk individuals. We also anticipate that further findings in this study will inform policy around alternative therapies (e.g. monoclonal antibodies & anti-virals) for those at the greatest risk of COVID-19-related hospitalisation or mortality.
Start Year 2021