key: cord-0764181-oeq0sejn
authors: nan
title: Differences in clinical deterioration among three sub-phenotypes of COVID-19 patients at the time of first positive test: results from a clustering analysis
date: 2020-10-19
journal: Intensive Care Med
DOI: 10.1007/s00134-020-06236-7
sha: d991e4cf2385c0eed611d0ec27c4378c4d8be894
doc_id: 764181
cord_uid: oeq0sejn

nan

applied an unsupervised consensus clustering method and determined the optimal number of clusters, which we also refer to as sub-phenotypes (Supplementary File) [4, 5] . We evaluated the association between the sub-phenotypes and with clinical deterioration defined as ICU admission and/or death within 28 days. Eight hundred and ninety-three patients were enrolled (Supplementary file), 50% required hospital admission, 104 (11.6%) patients were treated in the ICU, and 100 (11.2%) patients died.

We identified three distinct sub-phenotypes of patients seen at the hospitals participating in this study. Major sub-phenotype determinants are illustrated in Fig. 1 and Supplementary Fig. 2 . Biological results within each subphenotype are presented in Supplementary Table 2 .

Sub-phenotype #1 (n = 179) included mostly younger (median age 44 [IQR = 23.4]) women (74.9%), with no or few comorbidities (on average 0.5 comorbidity per patient) that were rarely on renin-angiotensin-aldosterone system inhibitors (RAASi) (8%), presenting with fever (56%), dyspnea (42%) or cough (78%) and numerous non-respiratory symptoms (mean 3.2/patient), including myalgia (82%), headaches (71%), and gastrointestinal symptoms (54%).

Sub-phenotype #2 (n = 279) included both men (54.1%) and women, with a median age of 53 [IQR = 26.4] years, with few or no comorbidities (mean 0.66/patient). Patients were rarely on RAASi (97%). While some had respiratory symptoms (dyspnea 35%, cough 57%), few had non-respiratory symptoms (mean 0.8/patient, i.e., myalgia 15%, headaches 15%, gastrointestinal symptoms 13%).

Sub-phenotype #3 (n = 150) included mostly male (70.7%) older patients (median age 73 [IQR = 19.3]) with more comorbidities (mean 2.2/patient), pervasive chronic hypertension (94%), and frequent treatment with RAASi (67%). A minority of patients in sub-phenotype #3 presented with fever (23%) or pulmonary symptoms (dyspnea 45%, cough 42%), and rarely other systemic symptoms (mean 0.65/patient, i.e., myalgia 13%, headaches 7%, gastrointestinal symptoms 19%). ICU admission and/or death occurred in 8%, 18%, and 43% of the patients in sub-phenotypes #1, #2, and #3, respectively (supplementary Fig. 1) . 7%, 13%, and 29% of patients required ICU admission in sub-phenotype #1, #2, and #3, respectively. In each respective sub-phenotype, 3%, 9%, and 22% of patients died.

In conclusion, we identified three sub-phenotypes, mostly determined by a history of chronic hypertension, the presence of fever, respiratory and non-respiratory symptoms, and age. These sub-phenotypes were strongly associated with clinical deterioration. The results of this clustering analysis should be now validated in other cohorts.

The online version of this article (https ://doi.org/10.1007/s0013 4-020-06236 -7) contains supplementary material, which is available to authorized users.

Facing COVID-19 in the ICU: vascular dysfunction, thrombosis, and dysregulated inflammation

Development and validation of a clinical risk score to predict the occurrence of critical illness in hospitalized patients with COVID-19

Clinical phenotypes of SARS-CoV-2: Implications for clinicians and researchers

ConsensusClusterPlus: a class discovery tool with confidence assessments and item tracking

Unbiased recursive partitioning: a conditional inference framework

Acknowledgements The authors declare that they have no conflict of interest.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Accepted: 31 August 2020