Tocilizumab in COVID-19: Factors Associated With Mortality Before and After Treatment.

Luis Sarabia De Ardanaz,Victor Ruíz Del Valle,Rafael Cáliz-Cáliz,Inmaculada Salcedo-Bellido,Miguel Ángel Ferrer-González,Pilar Requena,Jose M Andreu-Ubero,Rocío Barrios-Rodríguez,Miriam Navidad-Fuentes

doi:10.3389/fphar.2021.620187

Abstract

Tocilizumab (TCZ) has been administered in SARS-CoV-2 pneumonia but the factors associated with mortality before and after treatment remain unclear. Cox regression models were used to estimate the predictors of time to death in a cohort of hospitalized patients with COVID-19 receiving TCZ. In addition, the mean differences between discharged and deceased patients in laboratory parameters measured before and 3, 6 and 9 days after TCZ administration were estimated with weighted generalized estimation equations. The variables associated with time to death were immunosuppression (Hazard Ratio-HR 3.15; 95% confidence interval-CI 1.17, 8.51), diabetes mellitus (HR 2.63; 95% CI 1.23–5.64), age (HR 1.05; 95% CI 1.02–1.09), days since diagnosis until TCZ administration (HR 1.05, 95% CI 1.00–1.09), and platelets (HR 0.27; 95% CI: 0.11, 0.69). In the post-TCZ analysis and compared to discharged patients, deceased patients had more lactate dehydrogenase (p = 0.013), troponin I (p = 0.013), C-reactive protein (p = 0.013), neutrophils (p = 0.024), and fewer platelets (p = 0.013) and lymphocytes (p = 0.013) as well as a lower average PaO2/FiO2 ratio. In conclusion, in COVID-19 diagnosed patients receiving TCZ, early treatment decreased the risk of death, while age, some comorbidities and baseline lower platelet counts increased that risk. After TCZ administration, lower platelet levels were again associated with mortality, together with other laboratory parameters.

Highlights

More than one year after the identification in December 2019 of a cluster of atypical pneumonia cases in Wuhan (China) caused by a new type of Coronavirus (SARS-CoV-2), the so called Coronavirus disease 2019 (COVID-19) pandemic is not under control despite the efforts of massive vaccination protocols
This was a retrospective observational evaluation of all patients diagnosed with COVID-19 who received TCZ and were 18 years of age or older, admitted at Hospital Universitario Virgen de las Nieves (HUVN) in the city of Granada between 13 March and November 5, 2020, coinciding with the peak of the second COVID-19 wave
In March, TCZ was prescribed to patients with a severe hyperinflammatory syndrome, defined by severe bilateral pneumonia with criteria for acute respiratory distress syndrome (ARDS), or by the presence of two of the following criteria, fever >38.4°C, respiratory rate >24/ min and Pa02/Fi02 40 ng/L, D-dimer >1 mg/L and ferritin>300 μg/L

Summary

Introduction

More than one year after the identification in December 2019 of a cluster of atypical pneumonia cases in Wuhan (China) caused by a new type of Coronavirus (SARS-CoV-2), the so called Coronavirus disease 2019 (COVID-19) pandemic is not under control despite the efforts of massive vaccination protocols. In the severe stage of COVID-19 (Siddiqi and Mehra, 2020), shock, and respiratory and systemic organ failure may manifest secondary to a surge of proinflammatory cytokines (cytokine storm) which include IL-6, IL-1β, IL-2, granulocyte colony stimulating factor, macrophage inflammatory protein 1-α and tumor necrosis factor (Huang et al, 2020a; Siddiqi and Mehra, 2020; Wu et al, 2020) These cytokines increase vascular permeability facilitating the entrance of a large amount of fluid into the alveoli, causing dyspnea and respiratory failure (Zhang C. et al, 2020). The use of IL-6R antagonists has been suggested as a potential therapy for severe COVID-19related pneumonia cases

Objectives

Methods

Results