The ongoing COVID-19 pandemic requires information that could stratify patient treatment and new treatment options for the minority that develop fatal lung injury of unclear pathogenesis. Very few studies have focused on defining SARS-CoV-2 viral interaction with the host immune system, natural history and the pathogenesis of severe disease. This project is designed to discover important pathogenesis principles that may guide triage and choice of therapy, allow an understanding if immune inhibition should play a role, facilitate two clinical trials and suggest novel biomarkers that can point to patients that risk developing life threatening lung disease.
We propose a multidisciplinary groundbreaking study of material from blood and bronchoalveolar space from lungs of COVID-19 patients that develop acute fatal lung injury. We will define the pathogenic disease course and biomarkers of fatal disease with single cell mass cytometry and RNA sequencing. Cells from two international clinical trial launched in accordance with the ?Proposed next steps? in the 2020 WHO Roadmap will be compared for inflammatory signature.
We ask what exact types and subsets of inflammatory cells that secrete pro-inflammatory cytokines, a cytokine storm and inflammation that destroys lung tissue. We ask if there is too weak or too strong immune responses in fatal COVID-19. We ask if convalescent patient serum with neutralizing antibodies can reduce the inflammatory cells that cause lung injury. We also ask if cell therapy with immune inhibitory decidua stroma cells (DSC) can negate the cellular inflammatory responses and fatal lung injury in COVID-19.
Results will suggest new biomarkers for risk stratification, and triage, test the effect of convalescent serum and immune inhibitory DSC, have importance for the use of cheap anti-inflammatory medication in low-income countries, and will be disseminated in a European lab network to allow improved laboratory prediction of severe lung disease.