Host danger signals in determining the severity of Covid19: Blocking damage associated molecular patterns (DAMPs) as a new stratified treatment approach in STOPCOVID

Many patients with Covid19 infection have mild symptoms and recover quickly. However, 1 in 10 patients become desperately unwell with rapidly declining lung function, followed by multi-organ failure and death. We do not understand why this happens. Following entry, the Sars-Cov2 virus takes over the cell to make many more new viruses. The new Sars- Cov2 viruses then weaken and make ‘holes’ in the cell to allow them to escape and infect other nearby cells. We think that these ‘holes’ also result in the leak of ‘damage-associated molecular patterns (DAMPs), otherwise known as ‘danger signals’ from the cells that are infected and damaged by Sars-Cov2. These danger signals serve as ‘alarms’ that immediately activates the immune system to contain the viral damage. However, very high levels of DAMPs can also provoke an overwhelming but indiscriminate immune response, resulting in catastrophic collateral tissue damage to the lungs, circulation and heart. Our lab has an expertise in measuring DAMPs in human diseases. In this study, we aim to measure the blood levels of DAMPs in Covid19 patients and investigate if high levels of DAMPs identify Covid19 patients who are more unwell. We think that this signal will be present in unwell Covid19 patients who will need intensive care support. Our data will allow us to develop a blood test that can serve as an early warning system and also new clinical trials to test drugs that can block DAMPs and improve the recovery of Covid19 patients.