We are a new national network to establish partnerships that facilitate new research collaborations in co-infections and to provide seed-corn funding for new project colloborations across the UK
Humans are continuously exposed to multiple pathogens yet, with the exception of a few well defined coinfection scenarios (HIV and tuberculosis for example), relatively little is known about the impact of co-infections on morbidity and mortality. There is growing evidence indicating that co-infections are common, exacerbate disease severity and can considerably worsen outcome (Influenza or COVID-19 associated Aspergillus infection, for example). Co-infections with drug-resistant pathogens have shown to add another layer of complexity with high case-fatality rates.
Our aim is to integrate and exploit the expertise of four Centres involved in this new Network that are tackling the major pathogen groups [viruses, bacteria, fungi and parasites] to promote UK-wide research on the pathophysiological impact and mechanistic basis of disease in co-infections. Our overall objective is to strengthen UK-based research in the area of co-morbidities, particularly around co-infections, that are understudied and often occur in complex disease settings. While the scientific priorities will be informed by the national workshop we will hold, we anticipate that at least some activities will focus on important emerging and understudied co-infections. Examples include: Aspergillus and influenza or COVID-19 – also both viruses cause secondary bacterial pneumonia; COVID and Malaria; HTLV1 and Schistosomiasis; mycobacterial co-infections with helminths or fungi. The partnerships that are being created through this award will stimulate and empower innovative research programmes focussed on relevant co-infections, establish infection models in which to address common challenges in diagnoses and therapy, provide access to relevant patient cohorts, and the sharing of relevant tools, data, technologies and methods. Moreover, this award helps catalyse new cross-disciplinary research activities across the UK that will have scientific and translational impact, promote a culture of collaboration and resource sharing between Centres and other UK-based groups, and enhance the positioning of all Centres as outward facing national assets. As each seed-corn project will be designed to lay a foundation for long term interactions, the ambition of this proposal will extend well beyond the lifetime of this award.
Four seed-corn projects tackling co-infections have been funded. Each seed-corn project must:
Need to demonstrate how this funding will support new collaborative ventures to tackle the key priorities;
Involve principal investigators from at least two of the four Centres and may include (or be led by) one or more investigators from other UK institutions;
Demonstrate a route to long term collaboration and further funding; and
Involve an element of engagement, which will be supported through the resources already available in our Centres.
AWARDED PROJECTS 2022-2023
Aran Singanayagam (Project Lead, CMBI, Imperial College London) - Rhys Farrer & Peter Cook (CMM, University of Exeter)
Asthma is a lung condition characterised by flare-ups (or ‘exacerbations’) which are commonly triggered by viruses and responsible for >1000 UK deaths every year. Recent evidence suggests that the lungs of even healthy individuals can contain low levels of fungi (or ‘moulds’) and that these can influence disease and viral infection. We want to understand how these newly discovered fungi interact with common respiratory viruses in patients to promote severe asthma flare-ups. Our research will inform the development of new therapies that target airway fungi to enhance the ability of the immune system to fight off viral infection in asthma.
Elaine Bignell (Project Lead, CMM, University of Exeter) - Massimo Palmarini & Vanessa Herder (CVR, University of Glasgow) - Peter Cook (CMM, University of Exeter) - Darius Armstrong-James (CMBI, Imperial College London) - Simon Funnell (UK Health Security Agency)
Infections caused by influenza and coronaviruses are often complicated by life-threatening fungal pneumonias that are difficult to detect and treat. Understanding of such co-infections is critically limited. Urgent questions are: How does viral infection weaken antifungal immune defence? Is fungal growth limited to the airway surface or involve invasion of the tissue and bloodstream? Do anti-inflammatory drugs increase risk for fungal disease? Our diversely multiskilled team will establish rodent models of two increasingly common post-viral fungal pneumonias and identify common and distinct pathological features and underlying mechanisms. Our work will enable improved diagnosis and therapy of current and future co-infectious threats.
Sara Gago (Project Lead, University of Manchester) - Kieran Dee (CVR, University of Glasgow) - Peter Cook (CMM, University of Exeter)
Patients with chronic respiratory diseases do often have worse disease outcomes due to infections caused by microorganisms e.g., respiratory syncytial virus (RSV) and the fungus Aspergillus. In some cases, patients are coinfected by these organisms and we do not know why this interaction occur and why that leads to poor disease outcome. The cells which line the respiratory airways are called epithelial cells and are the first point of contact of inhaled pathogens with our body. Here we will investigate the fungal factors that support RSV replication in lung epithelial cells from healthy patients and those with lung disease.
Georgia Perona-Wright (Project Lead, WCIP, University of Glasgow) - Suzannah Rihn (CVR, University of Glasgow) - Simon Babayan (Institute of Biodiversity, Animal Health and Comparative Medicine (BAHCM), University of Glasgow)
Troubles rarely come alone, and infections are no different. People often suffer multiple infections at once. Our immune systems respond to different infections in different ways, and simultaneous infections mean the immune system must decide which one to prioritise. Data suggests that each of us make this decision differently, and we want to understand why. We think one decision factor is nutrition: some immune responses may be luxuries, only possible when our bodies have energy to spare. Our work will identify ways to optimise the impact of drugs that boost immunity, enabling people to avoid the dangers of multiple infections.