2021-02-10 - 'Integrated immune dynamics define correlates of COVID-19 severity and antibody responses' published
Check out our latest paper: Integrated immune dynamics define correlates of COVID-19 severity and antibody responses. 2021. M Koutsakos, LC Rowntree, L Hensen, et al. Cell Reports Medicine.
Abstract: SARS-CoV-2 causes a spectrum of COVID-19 disease, the immunological basis of which remains ill-defined. We analysed 85 SARS-CoV-2-infected individuals at acute and/or convalescent timepoints, up to 102 days post-symptom onset, quantifying 184 immunological parameters. Acute COVID-19 presented with high levels of IL-6, IL-18 and IL-10 and broad activation marked by upregulation of CD38 on innate and adaptive lymphocytes and myeloid cells. Importantly, activated CXCR3+cTFH1 cells in acute COVID-19 significantly correlate with and predict antibody levels and their avidity at convalescence as well as acute neutralisation activity. Strikingly, intensive care unit (ICU) patients with severe COVID-19 display higher levels of soluble IL-6, IL-6R, IL-18, and hyperactivation of innate, adaptive and myeloid compartments than patients with moderate disease. Our analyses provide a comprehensive map of longitudinal immunological responses in COVID-19 patients and integrate key cellular pathways of complex immune networks underpinning severe COVID-19, providing important insights into potential biomarkers and immunotherapies.
Summary: the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused >101 million infections and 2.18 million deaths worldwide (as of January 28, 2021). Infection with SARS-CoV-2 results in a spectrum of clinical presentations, called coronavirus disease 2019 (COVID-19), ranging from asymptomatic to fatal disease. Through a collaboration with the Doherty Institute and the University of Melbourne, we comprehensively profiled the immune response to SARS-CoV-2 in a cohort of COVID-19 patients. Our work demonstrated that patients with severe disease exhibited an excessive and hyper-activated immune response (Koutsakos et al. 2021). To study the kinetics of this immune response, we used our Spectre analysis toolkit, and also developed and applied a novel time-series analysis approach called TrackSOM.
- Our webinar from 2020 (Mapping Immunity Across Time, Space and Disease State) is featured on the Fluidigim ‘COVID-19 resources’ page.
- Our mass cytometry protocols have been cited in a number of COVID-19 studies, including Rodriguez et al. 2020 and Koutsakos et al. 2021.
- Panel design and analysis protocols that may be helpful in COVID-19 research can be found on the resources page.