Haematology

Our research in Haematology is helping to understand the COVID-19 disease. Through understanding the immune response to COVID-19 infection, we can gain a detailed understanding of our body’s response to the virus. Our researchers are also working to understand the inflammatory and coagulation processes involved in disease progression which could not only allow clinicians to identify patients at risk of becoming severely ill, but also inform effective treatment options for patients.

• Professor Kikkeri Naresh’s lab has proposed the use of cytotoxic T cells from convalescent COVID‐19 patients as the ‘need of the hour’ therapy to treat patients with COVID-19. Whilst there are many ongoing clinical trials utilising donor serum or plasma (a source of antibodies), not many are investigating T cell donation. Antibodies are only effective against extracellular viruses, but once a virus has entered the host cell it is shielded from the antibody. Cytotoxic T cells are an important element because they can fight viruses that have already infiltrated cells.
• Professor Barbara Bain’s group have observed that lymphocytes with atypical morphology are seen in patients infected with SARS-CoV-2. They have indicated that this particular morphology may help in the clinical diagnosis of COVID-19. 
• Professor Mike Laffan, as part of a team with Dr Quentin Hill at St James's University Hospital in Leeds, has provided practical guidance for managing patients with thrombocytopenia during the COVID-19 pandemic. Recommendations have been made available to support clinicians on the management and treatment of immune thrombocytopenia. 
• In a new preprint, a team of researchers including Professor Frederick Tam have identified a drug which can be used in the management of COVID-19 patients with lung disease. Fostamatinib is already licensed as a tyrosine kinase inhibitor, but this work shows it may also be effective at reducing the presence of Mucin-1, a protein associated with poor clinical outcomes, on the lung surface.
• Dr Deepa Arachchillage and colleagues at the Royal Brompton Hospital have found a link between COVID-19 and blood clotting. Despite being given the standard dose of anti-thrombotic medication, almost half of patients demonstrated thrombosis induced by COVID-19 infection. The team have described alternative drugs which can successfully anticoagulated these patients.

Image credit: David Gregory & Debbie Marshall

Nephrology

The COVID-19 research activities in nephrology cover a wide range of topics to elucidate the link between renal disease and COVID-19, as well as developing preventative measures to improve clinical outcomes in patients with kidney disease. These patients are extremely vulnerable to COVID-19 so understanding the development of the disease in this patient population is crucial. Our research in this field addresses a public health knowledge gap and will inform policy regarding access to healthcare facilities, for vulnerable patients with chronic illness, during the pandemic.

• Dr Jimmy Peters, Dr David Thomas, Dr Michelle Willicombe and colleagues measured around 500 proteins in the blood of kidney failure patients with COVID-19 with repeat sampling throughout the illness. In a recent eLife paper, they showed that severe COVID-19 has a protein ‘signature’ indicating activation of the innate immune system, increased immune cell communication and movement, and lung and blood vessel injury.
• Dr Nicholas Medjeral-Thomas and colleagues have published a paper in Frontiers in Immunology describing changes in proteins of the complement lectin pathway during COVID-19 infection. The work, in collaboration with Dr Steffen Thiel (Aarhus University, Denmark) is the most comprehensive measurement of lectin pathway proteins in COVID-19 infection.
• Dr Maria Prendecki and colleagues from the Centre for Inflammatory Disease and the Imperial NHS Trust Renal and Transplant Centre have published a paper suggesting that activation of complement plays a role in the pathogenesis of COVID-19, leading to endothelial injury and lung damage. The data support the testing of complement inhibition as a therapeutic strategy for patients with severe COVID-19.
• Dr Candice Roufosse has been awarded funding from Imperial’s donor-backed COVID-19 Response Fund to lead a project using histological and molecular analysis of tissues from COVID-19 patients to better understand disease development, including the vascular injury and thrombosis observed in severe cases. 
• Dr Jimmy Peters and colleagues from the Centre for Inflammatory Disease and the Imperial NHS Trust Renal and Transplant Centre have received funding from the Community Jameel Imperial College COVID-19 Excellence Fund to support their longitudinal study of patients with End-Stage Kidney Disease, a group at high risk of severe COVID-19. The study will measure gene and protein expression signatures in immune cells to better understand the biological mechanisms underlying severe disease.
• Dr Candice Roufosse and Professor Terry Cook, working in collaboration with Dr Desley Neil from Queen Elizabeth Hospital Birmingham, are using electron microscopy to investigate the progression of kidney injury in patients with COVID-19. 
• Dr Michelle Willicombe, Dr David Thomas and Dr Stephen McAdoo have published a paper suggesting that calcineurin inhibitors, which are drugs given to transplant patients to stop the body rejecting the new organ, may be safe to use in COVID-19 disease and may even inhibit the replication of the virus. 

• A team of our researchers, including Dr Damien Ashby, have described effective strategies for controlling transmission of COVID-19 in dialysis centres and have shown that early adoption of these measures can help protect patients from infection. The authors used control measures, including universal protective equipment, a regular screening process and case isolation to contribute to a fall in infection rates. 

Image credit: Amadalvarez

Molecular Immunology

Working within national consortia and as part of international collaborations, Professor Danny Altmann has published a number of impactful papers which have provided a better understanding of COVID-19 protective immunity, including reinfection risk and the impact of coronavirus variants.

• Professor Altmann and collaborators from Queen Mary University of London and University College London published findings in Science demonstrating that a single dose of vaccine boosts protection against SARS-CoV-2 coronavirus variants, but only in those with previous COVID-19 infection.
• Working with colleagues at the University of Sergipe in Brazil, Professor Altmann co-led a study analysing 33 cases of recurrent COVID-19 in Brazil. The team found that recurrence was often more severe compared to initial infection with the SARS-CoV-2 virus and resulted in one death.
• Professor Altmann and collaborators published findings in Science Immunology indicating that the majority of individuals carry neutralizing antibodies 16-18 weeks after mild or asymptomatic SARS-CoV-2 infection, but antibody and T cell responses can "uncouple".

Clinical trials

The multi-disciplinary collaborations formed by our scientists is changing our understanding of COVID-19 and of how patients with the disease in intensive care can be treated safely but quickly. In addition to vaccines, which are important for long-term control of the outbreak, drugs which manipulate the immune response may be vital to preventing progression of the disease in affected patients. Through researching the immune-related pathology of COVID-19, and the process of protective immunity against the virus, our Department is helping to identify new therapeutic drug targets and repurpose existing drugs.

• Dr Nichola Cooper co-led the UK arm of the COVACTA clinical trial evaluating whether an existing drug, Tocilizumab, can be used to treat patients with severe COVID-19. The trial recently reported that tocilizumab does not significantly improve outcomes for patients with severe COVID-19 pneumonia. However, the team found that tocilizumab reduced the time the patients spent in hospital by an average of 8.4 days and reduced time spent in the ICU by an average of 6 days.
• Dr Nichola Cooper is the Chief Investigator of the MATIS trial, which is evaluating the use of the drugs fostamatinib and ruxolitinib in patients with COVID-19 pneumonia. The study is a collaboration with Rigel Pharmaceuticals and Novartis Pharmaceuticals.
• Dr Michelle Willicombe is co-leading the Imperial arm of the UK study, OCTAVE, which seek to understand the immune response to COVID-19 vaccinations in patients with certain immunosuppressed conditions.
• Dr Michelle Willicombe and Dr Steve McAdoo are working in partnership with researchers from the Francis Crick Institute to study how well COVID-19 vaccines protect dialysis patients from infection. The research, jointly funded by Kidney Research UK and the National Kidney Federation (NKF), will also establish how long vaccine-induced immunity lasts in these patients.

Policy and public engagement

Our laboratory-based research into the relationship between COVID-19 and its effect on the immune system, as well as our clinical work within the NHS, is informing both the local and national response to the pandemic. Members of our Department have also been working directly with policymakers and speaking in public-facing forums to offer vital insights into COVID-19 research. 

• Throughout the pandemic, Professor Danny Altmann has been working to synthesise the emerging body of COVID-19 research to support policymakers and to help improve understanding of the virus within both the wider science community and the general public. Professor Altmann spoke as an Expert Witness to the Commons Science and Technology Committee, contributed to an expert summary of COVID-19 immunology research published by the Academy of Medical Sciences and the British Society for Immunology and published a paper on 'What policy makers need to know about COVID-19 protective immunity' in The Lancet.
  
• Professor Altmann has also published reviews of current research on SARS-CoV-2 T cell immunity (Science Immunology) and adaptive immunity to SARS-CoV-2 (Oxford Open Immunology)
• Professor Altmann has also delivered two talks as part of the British Society for Immunology's 'Connecting on Coronavirus' webinar series, in addition to giving a lesson on 'The Immunological Response to COVID-19' as part of Imperial College's Lockdown Lessons series aimed at 16-18-year-olds.