Understanding SARS-Cov-2 evolution in haemato-oncology patients
Piers Patten
PhDKing's College London
Project Term: September 1, 2021 - August 31, 2024
Through phenotypic and functional studies of immune cells, proteomic mapping of immune responses and genomic studies of variant strains, this project will assess the evolution of natural SARS-CoV-2 infection and COVID-19 vaccine responses in hemato-oncology patients. Integration of immunological profiles and genomic outcomes with clinical characteristics will inform future best patient management, especially for those patients at risk of prolonged infection with long term viral shedding.
Many (but not all) patients with blood cancers are unable to clear or have delayed clearance of SARS-CoV-2, the virus that causes COVID-19, following infection. Such patients may continue to shed the virus for long periods. The consequences of this may include a more severe infection or increased viral infectivity. A proportion of patients show changes in their immune cells, which becomes more pronounced over time, indicating an abnormal immune response and may explain their inability to eradicate the infection. Finally, development of viral variants has been described in those patients with a prolonged infection. All of these phenomena may contribute to the worse outcome of blood cancer patients with COVID-19. Our study will explore in more depth the underlying immune system of patients. Through evaluation of blood obtained at time of initial infection or before vaccination and at time points thereafter, our studies will aim to explain which patients may not be able to clear SARS-CoV-2 virus or may not be able to mount an appropriate immune response following vaccination. We also wish to understand whether naturally infected patients may develop new viral variants which may be both resistant to therapies and to vaccinations. We will correlate our findings with underlying patient characteristics including the type of blood cancer and treatment they are receiving. We will look for characteristics that will predict for those patients at risk at longer infections and/or inadequate vaccine responses. Comparing such patients to others who have cleared the infection may reveal possible strategies that could be developed in the future to both treat blood cancer patients who are infected with SAR-CoV-2 (for example boosting the immune system or using preventative drugs) and also to suggest the best vaccination strategies in those patients at risk of not mounting a normal response to COVID-19 vaccines.