Early stimulated immune responses predict clinical disease severity in hospitalized COVID-19 patients
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Early stimulated immune responses predict clinical disease severity in hospitalized COVID-19 patients. / Svanberg, Rebecka; MacPherson, Cameron; Zucco, Adrian; Agius, Rudi; Faitova, Tereza; Andersen, Michael Asger; da Cunha-Bang, Caspar; Gjærde, Lars Klingen; Møller, Maria Elizabeth Engel; Brooks, Patrick Terrence; Lindegaard, Birgitte; Sejdic, Adin; Harboe, Zitta Barrella; Gang, Anne Ortved; Hersby, Ditte Stampe; Brieghel, Christian; Nielsen, Susanne Dam; Podlekareva, Daria; Hald, Annemette; Bay, Jakob Thaning; Marquart, Hanne; Lundgren, Jens; Lebech, Anne-Mette; Helleberg, Marie; Niemann, Carsten Utoft; Ostrowski, Sisse Rye.
In: Communications Medicine, Vol. 2, 114, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Early stimulated immune responses predict clinical disease severity in hospitalized COVID-19 patients
AU - Svanberg, Rebecka
AU - MacPherson, Cameron
AU - Zucco, Adrian
AU - Agius, Rudi
AU - Faitova, Tereza
AU - Andersen, Michael Asger
AU - da Cunha-Bang, Caspar
AU - Gjærde, Lars Klingen
AU - Møller, Maria Elizabeth Engel
AU - Brooks, Patrick Terrence
AU - Lindegaard, Birgitte
AU - Sejdic, Adin
AU - Harboe, Zitta Barrella
AU - Gang, Anne Ortved
AU - Hersby, Ditte Stampe
AU - Brieghel, Christian
AU - Nielsen, Susanne Dam
AU - Podlekareva, Daria
AU - Hald, Annemette
AU - Bay, Jakob Thaning
AU - Marquart, Hanne
AU - Lundgren, Jens
AU - Lebech, Anne-Mette
AU - Helleberg, Marie
AU - Niemann, Carsten Utoft
AU - Ostrowski, Sisse Rye
N1 - © 2022. The Author(s).
PY - 2022
Y1 - 2022
N2 - BACKGROUND: The immune pathogenesis underlying the diverse clinical course of COVID-19 is poorly understood. Currently, there is an unmet need in daily clinical practice for early biomarkers and improved risk stratification tools to help identify and monitor COVID-19 patients at risk of severe disease.METHODS: We performed longitudinal assessment of stimulated immune responses in 30 patients hospitalized with COVID-19. We used the TruCulture whole-blood ligand-stimulation assay applying standardized stimuli to activate distinct immune pathways, allowing quantification of cytokine responses. We further characterized immune cell subsets by flow cytometry and used this deep immunophenotyping data to map the course of clinical disease within and between patients.RESULTS: Here we demonstrate impairments in innate immune response pathways at time of COVID-19 hospitalization that are associated with the development of severe disease. We show that these impairments are transient in those discharged from hospital, as illustrated by functional and cellular immune reconstitution. Specifically, we identify lower levels of LPS-stimulated IL-1β, and R848-stimulated IL-12 and IL-17A, at hospital admission to be significantly associated with increasing COVID-19 disease severity during hospitalization. Furthermore, we propose a stimulated immune response signature for predicting risk of developing severe or critical COVID-19 disease at time of hospitalization, to validate in larger cohorts.CONCLUSIONS: We identify early impairments in innate immune responses that are associated with subsequent COVID-19 disease severity. Our findings provide basis for early identification of patients at risk of severe disease which may have significant implications for the early management of patients hospitalized with COVID-19.
AB - BACKGROUND: The immune pathogenesis underlying the diverse clinical course of COVID-19 is poorly understood. Currently, there is an unmet need in daily clinical practice for early biomarkers and improved risk stratification tools to help identify and monitor COVID-19 patients at risk of severe disease.METHODS: We performed longitudinal assessment of stimulated immune responses in 30 patients hospitalized with COVID-19. We used the TruCulture whole-blood ligand-stimulation assay applying standardized stimuli to activate distinct immune pathways, allowing quantification of cytokine responses. We further characterized immune cell subsets by flow cytometry and used this deep immunophenotyping data to map the course of clinical disease within and between patients.RESULTS: Here we demonstrate impairments in innate immune response pathways at time of COVID-19 hospitalization that are associated with the development of severe disease. We show that these impairments are transient in those discharged from hospital, as illustrated by functional and cellular immune reconstitution. Specifically, we identify lower levels of LPS-stimulated IL-1β, and R848-stimulated IL-12 and IL-17A, at hospital admission to be significantly associated with increasing COVID-19 disease severity during hospitalization. Furthermore, we propose a stimulated immune response signature for predicting risk of developing severe or critical COVID-19 disease at time of hospitalization, to validate in larger cohorts.CONCLUSIONS: We identify early impairments in innate immune responses that are associated with subsequent COVID-19 disease severity. Our findings provide basis for early identification of patients at risk of severe disease which may have significant implications for the early management of patients hospitalized with COVID-19.
U2 - 10.1038/s43856-022-00178-5
DO - 10.1038/s43856-022-00178-5
M3 - Journal article
C2 - 36101705
VL - 2
JO - Communications Medicine
JF - Communications Medicine
SN - 2730-664X
M1 - 114
ER -
ID: 346258949