Distinct clinical phenotypes of critically ill COVID-19 patients: a cohort observational study

ABSTRACT

Introduction: COVID-19 presents a complex pathophysiology and evidence collected points towards an intricated interaction of viraldependent and individual immunological mechanisms. The identification of phenotypes, through clinical and biological markers, may provide a better understanding of the subjacent mechanisms and an early patient-tailored characterization of illness severity. Method(s) Multicenter prospective cohort study performed in 5 hospitals of Portugal and Brazil, during one year, between 2020-2021. All adult patients with an Intensive Care Unit admission with SARS-CoV-2 pneumonia were eligible. COVID-19 was diagnosed using clinical and radiologic criteria with a SARS-CoV-2 positive RT-PCR test. A two-step hierarchical cluster analysis was made using several class-defining variables. Result(s) 814 patients were included. The cluster analysis revealed a three-class model, allowing for the definition of three distinct COVID- 19 phenotypes 244 patients in phenotype A, 163 patients in phenotype B, and 407 patients in phenotype C. Patients included in the phenotype C were significantly older, with higher baseline inflammatory biomarkers profile, and significantly higher requirement of organ support and mortality rate (Table 1 ( P062)). Phenotypes A and B demonstrated some overlapping clinical characteristics but different outcomes. Phenotype B patients presented a lower mortality rate, with consistently lower C-reactive protein, but higher procalcitonin and interleukin-6 serum levels, describing an immunological profile significantly different from phenotype A (Table 1). Conclusion(s) Severe COVID-19 patients exhibit three different clinical phenotypes with distinct profiles and outcomes. Their identification could have an impact in patients' care, justifying different therapy responses and inconsistencies identified across different randomized control trials results.