Use of tocilizumab in COVID-19 pneumonia hospitalized patients. Cohort study

Abstract

Introduction

In COVID 19, an aggressive inflammatory response called cytokine release storm has been described. It is mainly mediated by the activation of Interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α), mainly observed in critically ill patients. Among the multiple treatments proposed throughout these two years of pandemic, we highlight the use of Tocilizumab (TCZ).

Objectives

To evaluate in-hospital mortality, transfer to critical care unit (CCU), invasive mechanical ventilation requirement (IMV), and hospital stay in patients treated with TCZ versus conventional treatments (CT).

Methods

Retrospective, descriptive, and analytical cohort study. Hospitalized patients, May to July 2021. Branches: treated with TCZ versus CT. Statistical analysis: Epi Info 7.2.

Results

Ninety patients, 51 TCZ branch and 39 CT branch. Age 48.2 years (± 11.7), males 74 (82.2%). Comorbidities 66 (73.3%): High blood pressure (HBP) 32 (35.6%), Diabetes mellitus 13 (14.4%), BMI > 30, 51 (56.7%). Medical Clinic Admission (MC) 85 (94.4%). Days post-symptom onset 7.9 (± 2.6). Severity of COVID 19: severe 61 (67.8%), critical 26 (28.9%). CCU admission 26 (29.9%). IMV 16 (17.8%). Deaths 7 (7.9%). Hospital stay 12.9 (± 6.6) days. Comparative analysis TCZ versus CT: MC admission 50 (98%) versus 35 (89.7%) p .08. CCU admission 12 (23.5%) versus 14 (38.9%) p .1. IMV 4 (7.8%) versus 12 (30.8%) p .005. Death 1 (2.0%) versus 6 (15.8%) p .02. Mortality in univariate analysis (p < .05): APACHE II, BMI > 30, TCZ, IMV, and CCU admission. TCZ was a protective factor against RR of death .86 (.74–.99). The IMV requirement was a RR factor for death 2.0 (1.23–3.42). Cox logistic regression, independent survival factors: use of TCZ, absence of obesity, and no IMV, p .0000.

Conclusions

IMV was found to be a risk factor for mortality. TCZ did not show a decrease in CCU requirement, but it did prove to be a protective factor against mortality. However, this is a non-randomized study so it should be interpreted with caution.

Resumen

Introducción

En COVID-19 se ha descrito una respuesta inflamatoria agresiva denominada tormenta de liberación de citocinas. Está mediado principalmente por la activación de la interleucina-6 (IL-6) y el factor de necrosis tumoral alfa (TNF-α), observado principalmente en pacientes críticos. Entre los múltiples tratamientos propuestos a lo largo de estos 2 años de pandemia, destacamos el uso de tocilizumab (TCZ).

Objetivos

Evaluar la mortalidad hospitalaria, el pase a una unidad de cuidados críticos (UCI), la necesidad de ventilación mecánica invasiva (VMI) y la estancia hospitalaria entre pacientes tratados con TCZ vs. tratamientos convencionales (TC).

Material y métodos

Estudio de cohorte retrospectivo, descriptivo y analítico. Pacientes internados de mayo a julio de 2021. Ramas: tratados TCZ vs. TC. Análisis estadístico: Epi Info® 7.2.

Resultados

Noventa pacientes, 51 en la rama TCZ y 39 en la rama TC. Edad 48,2 años (±11,7), masculinos 74 (82,2%). Comorbilidades 66 (73,3%): HTA 32 (35,6%), diabetes mellitus 13 (14,4%), IMC > 30 51 (56,7%). Ingreso en clínica médica (CM) 85 (94,4%). Días desde el inicio de los síntomas 7,9 (±2,6). Grado COVID-19: severo 61 (67,8%), críticos 26 (28,9%). Pase a la UCI 26 (29,9%). VMI 16 (17,8%). Óbitos 7 (7,9%). Estancia hospitalaria 12,9 (±6,6) días. Análisis comparativo TCZ vs. TC: Ingreso en CM 50 (98%) vs. 35 (89,7%) p 0,08. Pase a la UCI 12 (23,5%) vs. 14 (38,9%) p 0,1. VMI 4 (7,8%) vs. 12 (30,8%) p 0,005. Óbito 1 (2,0%) vs. 6 (15,8%) p 0,02. Análisis univariado mortalidad (p < 0,05): APACHE II, IMC > 30, TCZ, VMI y pase a la UCI. TCZ resultó factor protector ante óbito RR 0,86 (0,74-0,99). La necesidad de VMI resultó factor de riesgo de morir RR 2,0 (1,23-3,42). Regresión logística de Cox factores independientes sobrevida: uso TCZ, ausencia obesidad y no VMI, p 0,0000.

Conclusiones

La VMI resultó ser un factor de riesgo de mortalidad. TCZ no demostró disminuir requerimiento de la UCI, pero sí ser factor protector ante mortalidad. No obstante, es un estudio no aleatorizado por lo que debe interpretarse con precaución.