Longitudinal Cluster Analysis of Hemodialysis Patients with COVID-19 in the Pre-Vaccination Era

Abstract

Coronavirus disease 2019 (COVID-19) in hemodialysis patients (HD) is characterized by heterogeneity of clinical presentation and outcomes. To stratify patients, we collected clinical and laboratory data in two cohorts of HD patients at COVID-19 diagnosis and during the following 4 weeks. Baseline and longitudinal values were used to build a linear mixed effect model (LME) and define different clusters. The development of the LME model in the derivation cohort of 17 HD patients (66.7 ± 12.3 years, eight males) allowed the characterization of two clusters (cl1 and cl2). Patients in cl1 presented a prevalence of females, higher lymphocyte count, and lower levels of lactate dehydrogenase, C-reactive protein, and CD8 + T memory stem cells as a possible result of a milder inflammation. Then, this model was tested in an independent validation cohort of 30 HD patients (73.3 ± 16.3 years, 16 males) assigned to cl1 or cl2 (16 and 14 patients, respectively). The cluster comparison confirmed that cl1 presented a milder form of COVID-19 associated with reduced disease activity, hospitalization, mortality rate, and oxygen requirement. Clustering analysis on longitudinal data allowed patient stratification and identification of the patients at high risk of complications. This strategy could be suitable in different clinical settings.

Keywords: COVID-19; cluster analysis; cytokines; hemodialysis.

Figure 1

Cluster analysis of longitudinal data performed on the derivation cohort. Top panel (A): result of cluster analysis. Bottom panel (B): centroid profiles of Clusters 1 and 2. Abbreviations: white blood cell count, WBC; C-reactive protein, CRP; interleukin, IL; tumor necrosis factor-alfa, TNF-α; intercept, i; slope, s.