Early stimulated immune responses predict clinical disease severity in hospitalized COVID-19 patients

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 diseas...

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Published in:Communications medicine Vol. 2; no. 1; p. 114
Main Authors: 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
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 12.09.2022
Springer Nature B.V
Nature Portfolio
Subjects:
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631/250/255/2514
631/250/262
96/21
Biomarkers
Coronaviruses
COVID-19
Cytokines
Flow cytometry
Hospitalization
Immune response
Infections
Intensive care
Medicine
Medicine & Public Health
Pandemics
Patients
Severe acute respiratory syndrome coronavirus 2
T cell receptors
Tumor necrosis factor-TNF
Ventilators
Denmark
Innate immunity
Viral infection
ISSN:2730-664X, 2730-664X
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Summary: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. Plain language summary The manifestation of COVID-19 varies from asymptomatic to severe pneumonia requiring ventilator support or multi-organ failure. It is still poorly understood how the immune response to SARS-CoV-2 affects the development of severe disease. There is also a lack of clinical tools to identify patients early with high risk of poor outcome. Here, we looked for potential markers of disease severity in hospitalized COVID-19 patients using method to measure individual immune reactions. We found associations between impaired immune response pathways at time of hospitalization and development of severe and critical COVID-19 disease, and we identified a number of immune markers that could be used to predict poor outcome. Our findings could help identify at-risk patients upon hospitalization, enabling closer monitoring and earlier interventions. Svanberg et al. longitudinally assess the immune response in patients with COVID-19. The authors report specific immune parameters associated with the development of severe disease.
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ISSN:2730-664X
2730-664X
DOI:10.1038/s43856-022-00178-5