Tocilizumab reduces COVID-19 mortality and pathology in a dose and timing-dependent fashion: a multi-centric study

Tocilizumab reduces COVID-19 mortality and pathology in a dose and timing-dependent fashion: a multi-centric study

Abstract Life-threatening COVID-19 is associated with strong inflammation, where an IL-6-driven cytokine storm appears to be a cornerstone for enhanced pathology. Nonetheless, the specific inhibition of such pathway has shown mixed outcomes. This could be due to variations in the dose of tocilizumab...

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Autores principales: Alejandro Durán-Méndez, Alma Delia Aguilar-Arroyo, Emiliano Vivanco-Gómez, Eduardo Nieto-Ortega, Daniela Pérez-Ortega, Cristian Jiménez-Pérez, Karla Y. Hernández-Skewes, Guillermo Montiel-Bravo, Oscar J. Roque-Reyes, Fernanda Romero-Lechuga, Diana Medina-Santos, Perla Oriana-Román, Jorge Rafael Flores-Hernández, Juan Daniel Méndez-Coca, Daniela Montaño-Olmos, Karla Cecilia Farfán-Lazos, Miranda Tobón-Cubillos, América Viveros-Hernández, Fernando Sevilla-Castillo, Ángel Raúl Hernández-Romero, Shannat Ortega-Rodríguez, Aldo Christiaan Jardínez-Vera, María Antonieta Solís-González, Antonio Ramos de la Medina, Laura Martínez Pérez-Maldonado, Elizabeth Lagunes-Lara, Miguel Cova-Bonilla, Alberto N. Peón
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
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Medicine
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Science
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Acceso en línea:https://doaj.org/article/b632d86dac4740a59ca6312d3f6f933f
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Sumario:Abstract Life-threatening COVID-19 is associated with strong inflammation, where an IL-6-driven cytokine storm appears to be a cornerstone for enhanced pathology. Nonetheless, the specific inhibition of such pathway has shown mixed outcomes. This could be due to variations in the dose of tocilizumab used, the stage in which the drug is administered or the severity of disease presentation. Thus, we performed a retrospective multicentric study in 140 patients with moderate to critical COVID-19, 79 of which received tocilizumab in variable standard doses (< 400 mg, 400–800 mg or > 800 mg), either at the viral (1–7 days post-symptom onset), early inflammatory (8–15) or late inflammatory (16 or more) stages, and compared it with standard treated patients. Mortality, reduced respiratory support requirements and pathology markers were measured. Tocilizumab significantly reduced the respiratory support requirements (OR 2.71, CI 1.37–4.85 at 95%) and inflammatory markers (OR 4.82, CI 1.4–15.8) of all patients, but mortality was only reduced (4.1% vs 25.7%, p = 0.03) when the drug was administered at the early inflammatory stage and in doses ranging 400–800 mg in severely-ill patients. Despite the apparent inability of Tocilizumab to prevent the progression of COVID-19 into a critical presentation, severely-ill patients may be benefited by its use in the early inflammatory stage and moderate doses.

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