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BEHANDLING-God og treffsikker diagnostikk, behandling og rehabilitering

Defining the immune cells in COVID-19 that correlate with disease severity

Alternative title: Undersøkelse av immunceller ved alvorlig covid-19-sykdom

Awarded: NOK 3.2 mill.

The project uses advanced methodology to follow immunity and disease in COVID-19 and in vaccination, including severe adverse effects of vaccination published in NEJM and EHJ. The project has allowed us to initiate a range of activities and gain additional funding including the first grant from CEPI to a Norwegian group, an observational trial, an interventional vaccine trial (2021-003618-37) and further follow-up of patients with severe venous thrombosis after COVID-19 vaccination in Norway. We have several publications in pipeline that define the cellular responses towards corona vaccines in immunocompromised individuals, we monitor immune responses of third and fourth revaccination of high-risk groups. We are currently comparing immune responses to wild type, alpha and delta variant Covid-1. We are also analyzing cellular immune responses of family members participating in the Household Study where NIPH researchers recruit participants and collect blood from families where one or more have developed covid-19 disease. Further, we measure the levels of protective cellular immune responses in vaccinated health care workers and immunocompromised patients. Results have been reported to NIPH and the government and helped decision making. A RCN-Bia project and innovation projects have been started, a new RCN-Bia application and an application to CEPI have been submitted.

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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 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 COVID-19 patients that develop acute lung injury. We will define the pathogenic disease course and biomarkers of 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, but this study is currently on hold due to few relevant patients. 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.

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BEHANDLING-God og treffsikker diagnostikk, behandling og rehabilitering