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Distinct clinical symptom patterns in patients hospitalised with COVID-19 in an analysis of 59,011 patients in the ISARIC-4C.pdf (1.42 MB)

Distinct clinical symptom patterns in patients hospitalised with COVID-19 in an analysis of 59,011 patients in the ISARIC-4C study.

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posted on 2023-06-10, 05:21 authored by Jonathan E Millar, Lucile Neyton, Sohan Seth, Jake Dunning, Laura Merson, Srinivas Murthy, Clark D Russell, Sean Keating, Maaike Swets, Carole H Sudre, Timothy D Spector, Sebastien Ourselin, Claire J Steves, Jonathan Wolf, Annemarie B Docherty, Ewen M Harrison, Peter JM Openshaw, Malcolm G Semple, J Kenneth Baillie, Chi EziefulaChi Eziefula, ISARIC-4C
COVID-19 is clinically characterised by fever, cough, and dyspnoea. Symptoms affecting other organ systems have been reported. However, it is the clinical associations of different patterns of symptoms which influence diagnostic and therapeutic decision-making. In this study, we applied clustering techniques to a large prospective cohort of hospitalised patients with COVID-19 to identify clinically meaningful sub-phenotypes. We obtained structured clinical data on 59,011 patients in the UK (the ISARIC Coronavirus Clinical Characterisation Consortium, 4C) and used a principled, unsupervised clustering approach to partition the first 25,477 cases according to symptoms reported at recruitment. We validated our findings in a second group of 33,534 cases recruited to ISARIC-4C, and in 4,445 cases recruited to a separate study of community cases. Unsupervised clustering identified distinct sub-phenotypes. First, a core symptom set of fever, cough, and dyspnoea, which co-occurred with additional symptoms in three further patterns: fatigue and confusion, diarrhoea and vomiting, or productive cough. Presentations with a single reported symptom of dyspnoea or confusion were also identified, alongside a sub-phenotype of patients reporting few or no symptoms. Patients presenting with gastrointestinal symptoms were more commonly female, had a longer duration of symptoms before presentation, and had lower 30-day mortality. Patients presenting with confusion, with or without core symptoms, were older and had a higher unadjusted mortality. Symptom sub-phenotypes were highly consistent in replication analysis within the ISARIC-4C study. Similar patterns were externally verified in patients from a study of self-reported symptoms of mild disease. The large scale of the ISARIC-4C study enabled robust, granular discovery and replication. Clinical interpretation is necessary to determine which of these observations have practical utility. We propose that four sub-phenotypes are usefully distinct from the core symptom group: gastro-intestinal disease, productive cough, confusion, and pauci-symptomatic presentations. Importantly, each is associated with an in-hospital mortality which differs from that of patients with core symptoms.

History

Publication status

  • Published

File Version

  • Published version

Journal

Sci Rep

ISSN

2045-2322

Publisher

Springer Science and Business Media LLC

Volume

12

Page range

6843-

Event location

England

Department affiliated with

  • Global Health and Infection Publications

Full text available

  • Yes

Legacy Posted Date

2022-11-04

First Open Access (FOA) Date

2022-11-04

First Compliant Deposit (FCD) Date

2022-11-04

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