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A patient-centric modeling framework captures recovery from SARS-CoV-2 infection.

Published version
Peer-reviewed

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Authors

Hanson, Aimee L 
Lodge, Samantha 
Whiley, Luke 

Abstract

The biology driving individual patient responses to severe acute respiratory syndrome coronavirus 2 infection remains ill understood. Here, we developed a patient-centric framework leveraging detailed longitudinal phenotyping data and covering a year after disease onset, from 215 infected individuals with differing disease severities. Our analyses revealed distinct 'systemic recovery' profiles, with specific progression and resolution of the inflammatory, immune cell, metabolic and clinical responses. In particular, we found a strong inter-patient and intra-patient temporal covariation of innate immune cell numbers, kynurenine metabolites and lipid metabolites, which highlighted candidate immunologic and metabolic pathways influencing the restoration of homeostasis, the risk of death and that of long COVID. Based on these data, we identified a composite signature predictive of systemic recovery, using a joint model on cellular and molecular parameters measured soon after disease onset. New predictions can be generated using the online tool http://shiny.mrc-bsu.cam.ac.uk/apps/covid-19-systemic-recovery-prediction-app , designed to test our findings prospectively.

Description

Funder: Lopez-Loreta Foundation


Funder: Australian Federal Government’s Medical Research Future Fund (MRFF-ARAPC ARG76435); Western Australian Department of Health; Spinnaker Health Research Foundation; McCusker Charitable Foundation


Funder: Medical Research Council Programme Grant (MR/L019027)


Funder: Botnar Research Centre for Child Health (BRCCH)


Funder: COVID-19 Rapid Response DCF (RG93172/HESS/40558); Botnar Research Centre for Child Health (BRCCH)

Keywords

Resource, /692/699/255, /631/250/255, resource

Journal Title

Nat Immunol

Conference Name

Journal ISSN

1529-2908
1529-2916

Volume Title

24

Publisher

Springer Science and Business Media LLC
Sponsorship
Medical Research Council (MR/L019027/1)
Wellcome Trust (200871/Z/16/Z)
Wellcome Trust (219506/Z/19/Z)