UCL Great Ormond Street Institute of Child Health researchers are working across disciplines, to help find a cure, improve diagnosis, and advise Government in the UK and globally.
Overview of current Covid-19 research projects led by our Institute researchers:
- Developmental Biology and Cancer
COVID-19: Assessing the vulnerability of the fetus to SARS-CoV2 infection across development
While the SARS-CoV-2 (CoVID-19) virus has generated a pandemic, little is known about its impact on pregnant women and their fetuses. With this study, we plan to analyse fetal, placental and postnatal tissues for the expression of gene and proteins associated with SARS-CoV-2 infection, to investigate the risk of mother/child transmission. Our study will on investigating the presence of the ACE2 receptor as well as the protease TMPRSS2. These two proteins are felt to be necessary to allow viral entry into the cell. We plan to analyse a library of fetal tissues already obtained at the UCL Great Ormond Street Institute of Child Health and through the Human Developmental Biology Resource. In addition, we will study placenta and amniotic membrane at various gestational stages as well as cells isolated from donated amniotic fluid, obtained via the UCLH Fetal Medicine Unit / UCL EGA Institute for Women’s Health. We will then compare our results with postnatal tissues acquired through the UCLH and Great Ormond Steet Hospital pathology biobanks. Our research will involve the use of real time PCR, to assess gene expression, immunostaining and western blot for protein expression and localisation. Finally, RNA sequencing, will be used to analyse the global gene expression profile of our samples. This study will not only allow us to investigate ACE2, and other SARS-CoV-2 related genes, but will also provide insights into the mechanisms of fetal protection against COVID-19. Our results will help guiding clinicians, in implementing effective procedures to protect the child, to prevent SARS-CoV-2 vertical transmission.
Led by: Dr Mattia Gerli
The global COVID-19 observatory and resource centre for childhood cancer
This project is a collaboration between St. Jude Global programme and the International Society of Paediatric Oncology (SIOP) for which Professor Kathy Pritchard-Jones is president. This initiative has three components: a registry for gathering data on infected childhood cancer patients worldwide, educational resources, including weekly webinars, and a community space for news, the sharing of experiences and information and discussion. For more details: https://global.stjude.org/en-us/global-covid-19-observatory-and-resource-center-for-childhood-cancer.html
Led by: Professor Kathy Pritchard-Jones
- Developmental Neurosciences
Attitudes About COVID-19 and Health (ATTACH) study
COVID-19 has caused monumental shifts in all aspects of daily life. Everyone is experiencing challenges; however, some vulnerable communities (BAME, those with medical conditions, older adults) have been more affected by COVID-19. Sadly, there is currently little research to address the potential mental health crisis unfolding with vulnerable communities.
This study offers an easy to use smartphone app (Air My Opinion) to capture daily attitudes and beliefs and longitudinally assesses mental and physical health through a short REDCap survey. Through participant involvement from feedback about questions, advice about website resources, and guidance from charities and groups that include vulnerable communities, our findings will offer a real-time insight into the immediate effects of COVID-19 on our communities. Aggregated, anonymous poll responses will be posted on the study website https://bit.ly/attachstudy
- Genetics and Genomic Medicine
Development of a rapid, specific and high throughput method for the testing of the presence of Severe Acute Respiratory Syndrome Coronavirus-2 Antibodies in Human Sera
We are developing a more specific and accurate mass spectrometry based test that is capable of determining the presence and level of circulating antibodies to Severe Acute Respiratory Syndrome Coronavirus-2 in patient blood. Using a combination of both hypothesis generating- and targeted-proteomics assays, we have identified not only extra immunoglobulins that bind to the virus but also several other additional proteins involved in the immune response. These proteins have been developed into a rapid, multiplexed and targeted mass spectrometry based test capable of measuring ~ 20 immune and anti-viral proteins circulating in the bloodstream. The current antibody based test used in the NHS predominantly measures one type of antibody, we believe our test will provide significant more specificity and accuracy. Our assay has also been developed on a platform and in collaboration with industry, so it allows the test to be rolled out to all large hospitals throughout the NHS.
- Infection, Immunity and Inflammation
COG-UK HOCI clinical study
Evaluation of impact of rapid genome sequencing of COVID-19 patient SARS-CoV-2 virus samples on IPC (Infection Prevention and Control) team efforts to reduce nosocomial spread in UK hospital settings.
Led by: Professor Judith Breuer
Identification of repurposed , new and combination therapies for treatment of Covid 19
The project will make use of a CL3 housed hollow fibre infection model to measure invitro drug pharmacometrics required to achieve optimal dosing, and efficacy while minimising toxicity. The use of genomic methods to identify genetic signatures of drug action and to model the evolution of resistance mutations. deep sequencing of samples from patients treated with drugs will provide insights into whether biomarkers that predict he success and failure of new, repurposed and combination therapies in vivo can be developed.
Led by: Professor Judith Breuer
Covid 10 genomics (COG) UK
Sequencing of covid 19 genomes from around the UK for public health
Led by: Professor Judith Breuer
A patient-level meta-analysis on SARS-CoV-2 viral dynamics to model response to antiviral therapies
A key strategy in the battle against SARS-CoV-2 is antiviral drug therapy. Significant efforts are currently under way to establish whether currently available drugs may be re-purposed to treat SARS-CoV-2, in addition to development of novel therapies. To judge whether a drug can significantly disrupt viral levels, it is important to understand the natural timeline of the infection and patient factors which may influence this. In addition, since data are now being published on re-purposed clinical drug activity, it is possible to begin to assess the effectiveness of these treatments. The aim of this study is therefore to undertake a systematic literature review to examine individual patient-level data on viral load over time and develop a viral kinetic model. This model will be primarily used to understand the predicted effects of antiviral medications.
Led by: Dr Joe Standing
A survey to understand the feelings towards and impact of COVID-19 on the households of JDM patients from a parent or carer perspective
The worldwide COVID-19 pandemic and associated ‘lock down’ is a worrying time for everyone. It is important that the opinions and experiences of families who are caring for a young person with chronic disease are heard and appropriately addressed. Professor Wedderburn is leading a study working with families of young patients with the auto-immune disease Juvenile Dermatomyositis (JDM). The aim of this study is to gain a better understanding of how they feel about the effects and impact of the COVID-19 lock down on both them and the young person with JDM. Parents or carers of JDM patients are asked to complete a questionnaire and add comments regarding their experiences during this pandemic.
Led by: Professor Lucy Wedderburn
Sex-bias in COVID-19: a meta-analysis and review of sex differences in disease and immunity
Some early reports suggest that men are more likely to suffer from severe disease caused by COVID-19. This study investigates this theory using compiled data from 28 countries concerning the sex of COVID-19 patients and their disease outcomes. The analysis shows an important trend that whilst men and women seem equally likely to be infected by COVID-19, men with COVID-19 are more at risk of requiring intensive care and more at risk of dying from the disease. Although the reasons for this remain unclear, previous reports have shown that women generally have stronger responses to other viral infections. This may help them to clear the infection earlier in the disease course and perhaps prevent more serious respiratory complications. This study shows that sex should be considered an important biological factor when designing therapies and vaccination strategies for COVID-19.
Determining age-dependent factors driving COVID-19 disease severity using experimental human paediatric and adult models of SARS-CoV-2 infection
An important barrier to developing effective treatments for COVID-19 is our lack of understanding of how the virus interacts with the human airways. So far, we do know that COVID-19 disease severity increases with age, with very few severe cases among children. Our research group has extensive experience in studying the lining of the human airways called the ciliated epithelium, and how it interacts with viral pathogens. This project aims to determine the key factors responsible for the age-dependent differences in disease severity. This will be done by culturing human ciliated epithelium from samples donated by young children and the elderly, and comparing how these cells are infected by the SARS-CoV-2 virus.
Led by: Dr Claire Smith
Investigating mucosal immunity as a correlate of protection against SARS-CoV-2
As with the previous SARS pandemic strain, SARS-CoV-2 has been shown to target the various cells that line the airway (the epithelium), the first line of host defence against inhaled viruses. Survivors of COVID-19 who then have an antibody response directed to this site can block the virus from interacting with epithelial cells, which should be effective at preventing re-infection. This project aims to determine whether SARS-CoV-2 infection causes a protective mucosal immunity by testing for secreted antibodies (sIgA) in the saliva of GOSH staff who have previously tested positive for COVID-19. Using saliva raises the possibility of a future non-invasive, regular test for functional immunity against COVID-19 with practical advantages compared to testing blood or nose and throat swabs.
Led by: Dr Claire Smith
Synthetic immunity against COVID19
Identification and application of T cell receptors specific for COVID19 antigens.
The National Institute of Health Research (NIHR) is supporting our work to develop new immune cell therapies, including ‘universal’ T cells against leukaemia using cutting edge genome editing technologies. Through these projects we have accumulated expertise in understanding how T cells code their genes against viruses and developed techniques for reprogramming T cells to be used as cellular medicines. The immune response to COVID-19 relies heavily on T cell immunity, and so as patients and staff recover from the infection, we will collect blood samples to try and decode genes carrying information on T cell receptors. This is a difficult undertaking because of the high degree of variation between unrelated individuals, but we have access to specialised labs and advanced high throughput DNA sequencing technology. Once the codes are unravelled, we can copy the information to regenerate anti-COVID-19 T cells in large numbers and these could ultimately be used as therapies. The information gathered should also be useful for working out which parts of the virus are important for generating vaccine responses and whether any virus proteins are triggering cross-reactive responses against healthy tissues.
Led by: Professor Waseem Qasim
Pan European Paediatric Health Care Worker SARS-CoV-2 Antibody Prevalence and COVID-19 Staff Testing of Antibody Responses Study (CO-STARS EU)
This project will study the prevalence of anti-SARS-CoV-2 antibodies in healthcare workers employed in Paediatric Facilities in Europe and South Africa. It is linked to a large study of Health Care Workers being undertaken at Great Ormond Street Children’s Hospital NHS Trust that has approval by the Health Research Authority (HRA). The latter study consists of both cross sectional (that is, at a specific time point) and longitudinal (that is, over a period of time) analysis of antibody.
Led by: Professor David Goldblatt
The Coronavirus infection in primary or secondary immunosuppressed children (ImmunoCOVID-19)
The Coronavirus infection in immunosuppressed children (ImmunoCOVID-19) study hosted by University Hospital Southampton, aims to describe the clinical spectrum of COVID-19 infection in children who have a condition that make them more vulnerable to infections. This study will help inform clinical policy and enhance the quality of information given to patients and parents. Eligible participants are children for whom the annual influenza vaccination is indicated. Participants are identified through their respective hospitals and clinics, and are provided information regarding the study, prior to their enrolment onto the study. Relevant information is collected through weekly questionnaires sent to the participants, and the collected data is analysed weekly by the team at University Hospital Southampton. Specific markers or trends identified within this data will be reported back to participating consultants and Public Health England.
Led by: Dr Winnie Ip and Professor Lucy Wedderburn
Development of a rapid and quantitative method for SARS-CoV-2 diagnostic
The most current and widespread testing method available for COVID-19 is a semi-quantitative test, known as reverse transcription polymerase chain reaction (qRT-PCR). However, this diagnostic test is limited by sensitivity, and also the time required for sample processing and read-out. This has important health and economic implications for population screening, contact tracing, and diagnosis. This study aims to develop a rapid and quantitative test for detection of the SARS-CoV-2 virus, using the CRISPR/Cas technology. This system would allow for detection of the virus, even at very low levels, within a few minutes.
Led by: Dr Giandomenico Turchiano
The thymus and SARS-CoV2
This project aims to investigate the role of the thymus in the response to SARS-CoV2 infection in children in order to increase understanding of Covid-19 and Paediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-CoV-2 (PIMS-TS). We will test the hypothesis that PIMS-TS is caused by rare SARS-CoV2 infection of the thymus. PIMS-TS is associated with lymphopenia. We postulate that SARS-CoV2 infection might kill thymic epithelial cells (TEC), reducing T-cell output and recovery of the peripheral T-cell pool after its depletion by viral infection. Death of the medullary TEC population, which is required for tolerance induction and Treg production, could result in a failure of tolerance in new T-cells produced in response to lymphopenia, around or after an infection in some children, resulting in unregulated inflammation. In support of this, SARS-CoV2 infects cells by binding its spike protein (S) to cell surface ACE2 and also requires the protease TMPRSS29 and we found high expression of ACE2 and TMPRSS2 in TEC in public transcriptome databases, whereas their expression was low/undetectable in developing T-cells.
Led by: Professor Tessa Crompton
- Population, Policy and Practice
Downs Syndrome and COVID -19: An international study to determine whether the risk and course of COVID-19 in people with Down Syndrome (DS) are associated with their pre- existing conditions
People with Down syndrome (DS), caused by trisomy 21, have many co-occurring conditions beyond intellectual disability, that may increase their risk for COVID-19 or its progression. For example, their immune system compromises their ability to fight respiratory infections. This might also be true for viral infections, but there is no literature that addresses this question. Our international survey study proposes to collect anonymous data from families and clinicians who are caring for people with DS affected with COVID-19 to identify specific risk factors based on co-occurring conditions and to determine whether disease progression is associated with these pre-existing conditions. This study will be done at an international level and is undertaken in association with the Trisomy 21 Research Society (T21RS).
Led by: Trisomy 21 Research Society Taskforce. Child Health UK Key investigator Professor Monica Lakhanpaul
Parent’s help seeking for, and care of, a sick or injured child during Covid-19 pandemic Stay Home period.
The aim of the study is to find out what impact the Stay Home period (lock down) is having or has had on parent’s actions and decision when caring for, or seeking help for, a sick or injured child. The findings aim to help us learn from parents’ experiences and direct the development of support for parents with a sick or injured child in the future. This survey has now been further extended to Rotterdam.
Led by: Chief Investigator Sarah Neill Plymouth, and Rachel Carter Co-I Professor Monica Lakhanpaul on behalf of the ASK SNIFF consortium
Mental health and wellbeing in context of COVID-19 and beyond
National data show that COVID-19 is causing high levels of anxiety and impacting wellbeing in nearly half of the population (ONS Survey). Such figures are likely to be significantly higher for patients at GOSH and their families, as well as staff at the hospital. In response, GOSH has put wellbeing at the heart of its COVID response. This project aims to build upon a previous grant funded project evaluating a drop-in mental health booth at GOSH. Specifically it aims to evaluate the impact of a stepped-care approach to the provision of evidence-based interventions for mental health and wellbeing of GOSH patients and their families during COVID-19. Patients and family members will be made aware of mental health and wellbeing provision that is accessible via the existing mental health drop-in centre (‘Lucy Booth’) that can provide remote support. Standardised assessments and evidence-based stepped care interventions will be provided. The data collected will be compared to existing data from a three-year GOSH CC funded project (‘The Lucy Project’) that evaluated a self-referral mental health and wellbeing drop-in centre from January – December 2019. This will allow us to benchmark mental health and wellbeing provision during COVID-19 against provision of such input prior to the crisis. We will also be able to benchmark the mental health of our patients against national data. Information collected will allow for a sustainable, effective mental health and wellbeing provision for the duration of the COVID-19 and recovery period.
Led by: Professor Roz Shafran
The ‘Lucy Project’: https://www.ucl.ac.uk/psychological-medicine/
You-COPE: Youth COVID Response Personal Experience: Tracking health and wellbeing amongst 16-24 year olds in the UK during and after the COVID-19 pandemic
You-COPE is a longitudinal cohort study tracking health and wellbeing amongst 16-24 year olds in the UK during and after the COVID-19 pandemic. We are aiming to understand the specific impacts on this age group of the national response to COVID-19. We are capturing disruptions to various domains including housing, training and income and tracking physical and mental health through the ‘lockdown’ and thereafter in order to inform national health and education policy. Question topics include mental health and wellbeing, mental health disorders and treatments, social connectedness and loneliness, sleep, sexual health, eating behaviours, substance use and alcohol, physical health, COVID-19 symptoms and anxiety, demographics, socioeconomic status, education and employment and housing. We are recruited young people through multiple channels, including word of mouth, personal contacts and professional networks; anyone aged 16-24 years old in the UK is eligible to take part if they can access the internet to do so. We are following up with a smaller subset of measures every 2 weeks at first, and then, later, monthly until after the end of the main pandemic public health response period in the UK.
Led by: Professor Russell Viner
Short and long term impacts of school closures, or other isolation measures in childhood, on physical and mental health
The UK has implemented school closures (for most children) as part of national social distancing efforts to reduce the transmission of COVID-19. The potential benefits of school closures need to be considered alongside any potential harms, both economically and directly for children and families over the short- and long-term, as well as the broader political context. In a recent systematic review, we demonstrated that the evidence is currently limited and unclear as to the effectiveness of school closures for containing corona virus outbreaks (Viner et al, 2020; DOI:https://doi.org/10.1016/S2352-4642(20)30095-X). There are suggestions of potential wide reaching harms for children from school closures, especially if school closures persist over a prolonged period. This includes impacts on physical and mental health, wellbeing and health-related behaviours (especially physical activity, diet, use of tobacco, alcohol, other drugs, perpetration or victimisation of violence). It is also likely that children will be differentially affected, with some children (likely vulnerable children and those from more deprived backgrounds) particularly at risk. Therefore, in this systematic review, we will examine the impact of school closures on a range of child outcomes, over both the short and longer term, and whether these impacts are moderated by child/ school/ country characteristics.
Led by: Professor Russell Viner
Assessing the impact of the COVID-19 pandemic on vulnerable children
During the C-19 Lockdown, the limited access to support from health, social care and education services, and the effects of household confinement are challenging for everyone, but particularly for children and young people who are already vulnerable, due to social welfare or chronic health needs. Our study will assess the impact of the pandemic on these vulnerable children, firstly by identifying different groups of vulnerability, and then by quantifying the risks of acute health outcomes for these groups. This could be due to missed appointments for chronic health conditions, loss of education support or threats to safety. Our results will inform local services of the key characteristics, and estimated numbers, of children who may need extra support to recover from the long term effects of the pandemic.
Led by: Professor Ruth Gilbert
COVID-19 New Mum Study
In any circumstances, mothers face many challenges around infant feeding. Important issues include whether they can afford to take time off work, and what kinds of support are available from professional sources and other family members within and beyond the immediate household. The COVID-19 pandemic and resulting lockdown policies have profoundly impacted these dynamics. Mothers may be experiencing changed family circumstances within the household, reduced financial income, and reduced access to wider family and professional help. Our anonymous online survey aims to improve understanding of mothers' experience during this difficult time. We aim to identify how COVID-19 is impacting infant feeding practices, which groups are most affected, and which are least able to access relevant support. We will share this information with relevant organisations that provide support for maternal health, wellbeing and breast-feeding. Find out more about the study. Professor Mary Fewtrell discusses the study in Episode 29 of UCL's Podcast series - Coronavirus The Whole Story.
Led by: Professor Jonathan Wells, Professor Mary Fewtrell
Coronavirus Experiences Study: Understanding the experiences of coronavirus in Imagine-ID families
In England, there are over a million people with learning disabilities, a quarter of whom are children of school age. The IMAGINE-ID programme of research, funded by the Medical Research Council from 2015 until 2024, has recruited 3,402 UK children aged 5 to 18 years old with ID due to a genetic cause. We discovered that IMAGINE-ID children have a far greater risk of physical, behavioural and emotional problems than typically developing children. Approximately half the cohort meet criteria for a mental health disorder, and 40% have an Autism Spectrum Disorder. The Coronavirus pandemic poses unique challenges to this group, as families are shielding vulnerable children. Media reports have suggested the pandemic is more unsettling for children with autism than typically developing children. However, anecdotal reports speak of unexpected benefits for some autistic children during lockdown, such as reduced pressure on having to socialise. We aim to understand the experiences of IMAGINE-ID families during the pandemic using online questionnaires and interviews with a subset of families. We will recruit equally sized sample of families with and without an autistic child. We aim to interview families at two time points. First, during the extended period of shielding for families of vulnerable children (August 2020). Second, approximately 6 months later. This approach will be used to identify areas of difficulty and resilience during the pandemic and de-confinement. We will also compare the experiences of children who have autism with those who do not, in order to understand the unique challenges experienced by the families of children with autism.
Led by: Dr Jeanne Wolstencroft