Distinct clinical symptom patterns in patients hospitalised with COVID-19 in an analysis of 59,011 patients in the ISARIC-4C study
Abstract 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 clu...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-08032-3 |
| _version_ | 1828839884664602624 |
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| author | 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 J. M. Openshaw Malcolm G. Semple J. Kenneth Baillie ISARIC-4C |
| author_facet | 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 J. M. Openshaw Malcolm G. Semple J. Kenneth Baillie ISARIC-4C |
| author_sort | Jonathan E. Millar |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-12T19:31:09Z |
| format | Article |
| id | doaj.art-dd82bb16bfa84fd290d8ce57abc1ca37 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-12T19:31:09Z |
| publishDate | 2022-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-dd82bb16bfa84fd290d8ce57abc1ca372022-12-22T00:14:25ZengNature PortfolioScientific Reports2045-23222022-04-0112111310.1038/s41598-022-08032-3Distinct clinical symptom patterns in patients hospitalised with COVID-19 in an analysis of 59,011 patients in the ISARIC-4C studyJonathan E. Millar0Lucile Neyton1Sohan Seth2Jake Dunning3Laura Merson4Srinivas Murthy5Clark D. Russell6Sean Keating7Maaike Swets8Carole H. Sudre9Timothy D. Spector10Sebastien Ourselin11Claire J. Steves12Jonathan Wolf13Annemarie B. Docherty14Ewen M. Harrison15Peter J. M. Openshaw16Malcolm G. Semple17J. Kenneth Baillie18ISARIC-4C Division of Functional Genetics and Development, Roslin Institute, University of EdinburghDivision of Functional Genetics and Development, Roslin Institute, University of EdinburghInstitute for Adaptive and Neural Computation, School of Informatics, University of EdinburghNational Infection Service, Public Health EnglandCentre for Tropical Medicine and Global Health, Nuffield Department of Medicine, ISARIC Global Support Centre, University of OxfordBC Children’s Hospital, University of British ColumbiaCentre for Inflammation Research, The Queen’s Medical Research Institute, University of EdinburghIntensive Care Unit, Royal Infirmary of EdinburghDivision of Functional Genetics and Development, Roslin Institute, University of EdinburghSchool of Biomedical and Imaging Sciences, King’s College LondonDepartment of Twin Research and Genetic Epidemiology, King’s College LondonSchool of Biomedical and Imaging Sciences, King’s College LondonDepartment of Twin Research and Genetic Epidemiology, King’s College LondonZOE Global LtdCentre for Medical Informatics, Usher Institute, University of EdinburghCentre for Medical Informatics, Usher Institute, University of EdinburghNational Heart and Lung Institute, Imperial College LondonNIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences, University of LiverpoolDivision of Functional Genetics and Development, Roslin Institute, University of EdinburghAbstract 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.https://doi.org/10.1038/s41598-022-08032-3 |
| spellingShingle | 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 J. M. Openshaw Malcolm G. Semple J. Kenneth Baillie ISARIC-4C Distinct clinical symptom patterns in patients hospitalised with COVID-19 in an analysis of 59,011 patients in the ISARIC-4C study Scientific Reports |
| title | Distinct clinical symptom patterns in patients hospitalised with COVID-19 in an analysis of 59,011 patients in the ISARIC-4C study |
| title_full | Distinct clinical symptom patterns in patients hospitalised with COVID-19 in an analysis of 59,011 patients in the ISARIC-4C study |
| title_fullStr | Distinct clinical symptom patterns in patients hospitalised with COVID-19 in an analysis of 59,011 patients in the ISARIC-4C study |
| title_full_unstemmed | Distinct clinical symptom patterns in patients hospitalised with COVID-19 in an analysis of 59,011 patients in the ISARIC-4C study |
| title_short | Distinct clinical symptom patterns in patients hospitalised with COVID-19 in an analysis of 59,011 patients in the ISARIC-4C study |
| title_sort | distinct clinical symptom patterns in patients hospitalised with covid 19 in an analysis of 59 011 patients in the isaric 4c study |
| url | https://doi.org/10.1038/s41598-022-08032-3 |
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