Clinical clustering with prognostic implications in Japanese COVID-19 patients: report from Japan COVID-19 Task Force, a nation-wide consortium to investigate COVID-19 host genetics

Abstract

Background The clinical course of coronavirus disease (COVID-19) is diverse, and the usefulness of phenotyping in predicting the severity or prognosis of the disease has been demonstrated overseas. This study aimed to investigate clinically meaningful phenotypes in Japanese COVID-19 patients using cluster analysis. Methods From April 2020 to May 2021, data from inpatients aged ≥ 18 years diagnosed with COVID-19 and who agreed to participate in the study were collected. A total of 1322 Japanese patients were included. Hierarchical cluster analysis was performed using variables reported to be associated with COVID-19 severity or prognosis, namely, age, sex, obesity, smoking history, hypertension, diabetes mellitus, malignancy, chronic obstructive pulmonary disease, hyperuricemia, cardiovascular disease, chronic liver disease, and chronic kidney disease. Results Participants were divided into four clusters: Cluster 1, young healthy (n = 266, 20.1%); Cluster 2, middle-aged (n = 245, 18.5%); Cluster 3, middle-aged obese (n = 435, 32.9%); and Cluster 4, elderly (n = 376, 28.4%). In Clusters 3 and 4, sore throat, dysosmia, and dysgeusia tended to be less frequent, while shortness of breath was more frequent. Serum lactate dehydrogenase, ferritin, KL-6, d-dimer, and C-reactive protein levels tended to be higher in Clusters 3 and 4. Although Cluster 3 had a similar age as Cluster 2, it tended to have poorer outcomes. Both Clusters 3 and 4 tended to exhibit higher rates of oxygen supplementation, intensive care unit admission, and mechanical ventilation, but the mortality rate tended to be lower in Cluster 3. Conclusions We have successfully performed the first phenotyping of COVID-19 patients in Japan, which is clinically useful in predicting important outcomes, despite the simplicity of the cluster analysis method that does not use complex variables.

Serum KL-6 levels predict clinical outcomes and are associated withMUC1polymorphism in Japanese patients with COVID-19

“…Since February 2020, more than 100 institutions across Japan have contributed clinical data and specimens from patients with COVID-19 to improve knowledge of this disease. [26][27][28][29][30][31] Using this large pool of available data, the present study aimed to (1) determine whether serum KL-6 is associated with important clinical outcomes, such as mortality, extracorporeal membrane oxygenation (ECMO) and invasive positive pressure ventilation (IPPV), that more directly reflect COVID-19 prognosis than its severity; and (2) clarify the association among serum KL-6 levels, important critical outcomes and KL-6-associated genetic polymorphisms.…”