COVID-19 Clinical Phenotypes: Presentation and Temporal Progression of Disease in a Cohort of Hospitalized Adults in Georgia, United States

Abstract

Background The epidemiological features and outcomes of hospitalized adults with coronavirus disease 2019 (COVID-19) have been described; however, the temporal progression and medical complications of disease among hospitalized patients require further study. Detailed descriptions of the natural history of COVID-19 among hospitalized patients are paramount to optimize health care resource utilization, and the detection of different clinical phenotypes may allow tailored clinical management strategies. Methods This was a retrospective cohort study of 305 adult patients hospitalized with COVID-19 in 8 academic and community hospitals. Patient characteristics included demographics, comorbidities, medication use, medical complications, intensive care utilization, and longitudinal vital sign and laboratory test values. We examined laboratory and vital sign trends by mortality status and length of stay. To identify clinical phenotypes, we calculated Gower’s dissimilarity matrix between each patient’s clinical characteristics and clustered similar patients using the partitioning around medoids algorithm. Results One phenotype of 6 identified was characterized by high mortality (49%), older age, male sex, elevated inflammatory markers, high prevalence of cardiovascular disease, and shock. Patients with this severe phenotype had significantly elevated peak C-reactive protein creatinine, D-dimer, and white blood cell count and lower minimum lymphocyte count compared with other phenotypes (P < .01, all comparisons). Conclusions Among a cohort of hospitalized adults, we identified a severe phenotype of COVID-19 based on the characteristics of its clinical course and poor prognosis. These findings need to be validated in other cohorts, as improved understanding of clinical phenotypes and risk factors for their development could help inform prognosis and tailored clinical management for COVID-19.

Identification of Endotypes of Hospitalized COVID-19 Patients

“…We hypothesize that COVID-19 endotypes identified based on observable characteristics of the entire hospitalization (age and a representation of laboratory values) will reveal unexpected clinical courses and outcomes that defy prediction using classic risk factors. This approach is in contrast to some initial reports of clustering COVID-19 patients including using initial laboratory values and clinical variables collected in the first 24 ( 22 ) and 72 h ( 23 ); clustering patients by demographics, comorbidity, and maximum laboratory value ( 24 ) and using principal component analysis (PCA) and k-means of 18 initial laboratory values resulting in six values used in final analysis ( 25 ). Additionally, clusters have been created from initial ICU clinical data for patients with COVID-19 ARDS ( 26 ) and from ICU patients using demographics, initial ICU labs, and other clinical variables ( 27 ).…”

The COVID HOME study research protocol: Prospective cohort study of non-hospitalised COVID-19 patients

“…The authors have declared that no competing interests exist. 21 This study has been approved by the Medical Ethical Review Committee of the UMCG (METc 2020/158) and follows international standards for the ethical conduct of research involving human subjects. All procedures employed in the clinical and related laboratory studies comply with national and European legislation in respect of research involving human subjects.…”

“…However, COVID-19 patients have diverse clinical presentations encompassing the number and duration of symptoms [20] as well as different alterations of laboratory parameters. Some of these clinical phenotypes could be linked to evolution to severe disease and/or to the development of long-term sequelae [21]. Several blood parameters including cytokines, have been identified as markers of COVID-19 disease severity [22, 23] while other studies have characterised blood parameters to predict COVID-19 diagnosis in patients presenting to hospital with symptoms [22, 24].…”

The COVID HOME study research protocol: Prospective cohort study of non-hospitalised COVID-19 patients

“…However, COVID-19 patients have diverse clinical presentations encompassing the number and duration of symptoms [18] as well as different alterations of laboratory parameters. Some of these clinical phenotypes could be linked to evolution to severe disease and/or to the development of long-term sequelae [19]. Several blood parameters including cytokines, have been identified as markers of COVID-19 disease severity [20,21] while other studies have characterised blood parameters to predict COVID- 19 patients presenting to hospital with symptoms [20,22].…”

“…Some of these clinical phenotypes could be linked to evolution to severe disease and/or to the development of long-term sequelae [19]. Several blood parameters including cytokines, have been identified as markers of COVID-19 disease severity [20,21] while other studies have characterised blood parameters to predict COVID- 19 patients presenting to hospital with symptoms [20,22]. However, data collected in a systematic and longitudinal manner soon after infection will better characterise the clinical features and laboratory parameters (haematological, biochemical, immunological) in outpatient individuals convalescing at home and their potential as early markers of disease progression.…”