Inflammation in Covid-19: Exploration of Critical Aspects of Pathogenesis (ICECAP)

The current coronavirus pandemic is causing significant illness and death. Severe coronavirus disease 2019 (Covid-19) leads to acute lung damage and organ injury, often requiring intensive care admission and prolonged periods of time on a ventilator. As this disease is new, the way that the virus causes organ injury is not understood. It is therefore urgent and vital that the effects of severe Covid-19 are described to rapidly inform clinical management and identify new treatment approaches.

The ICECAP consortium was established as a rapid response to the Covid-19 pandemic. By assembling a team of expert clinicians and scientists we are studying key features of fatal Covid-19. Authorised hospital post-mortem examinations of those who have died from Covid-19 provides a unique opportunity to study the whole body in a level of detail that is not possible during life. By collecting and analysing tissue samples collected during post-mortem examinations this will yield crucial information on the presence of the coronavirus in multiple organs in the body and also understand in greater depth how the body's immune system is responding. This allows us to rapidly answer important clinical questions and help to rapidly inform the evaluation and development of therapeutic interventions for Covid-19.

The morbidity and mortality of patients with severe Covid-19 is high: understanding disease pathogenesis is critical to prioritise therapeutic targets. To achieve this, ICECAP has established a unique programme of rapid and detailed tissue sampling at autopsy of fatal Covid-19, integrated with optimised pipelines for downstream scientific analyses. By combining clinical and scientific expertise ICECAP are uniquely placed to address critical knowledge gaps.

Core project deliverables:
1.Ongoing recruitment to ICECAP research autopsies, performing detailed tissue retrieval within hours of death to ensure key cellular and biological information is preserved. This activity complements and expands our established COVID-19 tissue bank.
2.Mapping SARS-CoV-2 organotropism and cellular distribution. Expanding our preliminary findings, viral presence at an organ and cellular level will be described in multiple tissues, with evidence of viral replication sought. The organ-specific consequences of viral presence will be investigated, with immediate implications for clinical management, treatment with antivirals and healthcare services.
3.Delineation of Pulmonary Immunopathology is critical to understand in terms of viral elimination, immune-mediated organ dysfunction and cytokine production. Building upon established pathways, quantification and phenotyping of immunopathology will be achieved by complementary approaches of flow cytometry, single cell RNA sequencing, spatial RNA analysis and proteomics.

Our multi-disciplinary approach harnesses national and international expertise to incisively and rapidly deliver new disease-specific insights. These deliverables will drive the understanding of organ-specific viral presence, tolerance and mechanisms of immunopathology with clear benefits on prioritising potential therapeutic targets and patient management.