Validation of FEN-COVID phenotypes in hospitalised COVID-19 patients across the first four waves of the pandemic

Abstract

Introduction

The FEN-COVID study identified 3 clinical phenotypes (PhA, PhB and PhC) in hospital-admitted patients with COVID-19, which were associated with mortality. The aim of this study is to validate the assignment to phenotypes and their association with mortality in two hospitals in Spain across the first 4 waves of the pandemic, including the impact of corticosteroids and anticoagulant drugs.

Methods

A prospective cohort study of patients admitted for COVID-19 in the first 4 waves in two hospitals was performed. Phenotypes were assigned using the FEN-COVID calculator. The primary outcome was 30-day all-cause mortality. Kaplan–Meier (KM) curves were compared using the log-rank test. Multivariate analysis was performed using Cox regression analysis to assess the association of phenotypes with mortality.

Results

1839 patients were included. Of these, 257 patients were identified as PhA, 1451 as PhB and 130 as PhC; their 30-day mortality was 1.9%, 15.4% and 45.4%, respectively. In multivariate analysis and controlling for wave effect, belonging to phenotype B and phenotype C was associated with progressive increased hazards of death. In addition, appropriate treatment with corticosteroids was significantly associated with lower mortality in PhB, while low-molecular weight heparin use was significantly associated with lower mortality in PhB and PhC.

Conclusions

Our results confirmed that the clinical phenotypes identified in the FEN-COVID study were predictive of mortality across all waves studied. Furthermore, we confirmed the importance of identifying the phenotype to which a patient belongs on admission when considering appropriate treatment with corticosteroids and/or anticoagulants.

Resumen

Introducción

El estudio FEN-COVID identificó tres fenotipos clínicos (PhA, PhB y PhC) en pacientes hospitalizados con COVID-19, asociados con la mortalidad. El objetivo del estudio es validar los fenotipos y su asociación con la mortalidad en dos hospitales de España durante las cuatro primeras oleadas de la pandemia, incluyendo el impacto de los corticosteroides y los anticoagulantes.

Métodos

Estudio prospectivo de cohorte de pacientes ingresados por COVID-19 en las cuatro primeras oleadas en dos hospitales. El resultado principal fue la mortalidad por todas las causas a los 30 días. Las curvas de Kaplan-Meier (KM) se compararon utilizando la prueba de log-rank. Se realizó un análisis de regresión de Cox para evaluar la asociación de los fenotipos con la mortalidad.

Resultados

Se incluyeron 1.839 pacientes. De ellos, 257 fueron identificados como PhA, 1.451 como PhB y 130 como PhC; su mortalidad a los 30 días fue del 1,9%, 15,4% y 45,4%, respectivamente. En el análisis multivariante, controlando el efecto de la ola, los fenotipos B y fenotipos C se asociaron con un aumento progresivo del riesgo de muerte. Además, el tratamiento adecuado con corticosteroides se asoció significativamente con una menor mortalidad en PhB, mientras que el uso de heparina de bajo peso molecular se asoció significativamente con una menor mortalidad en PhB y PhC.

Conclusiones

Los fenotipos clínicos se han confirmado predictivos de mortalidad. Además, confirmamos la importancia de identificar el fenotipo en el momento del ingreso al momento de considerar el tratamiento adecuado con corticosteroides y/o anticoagulantes.