Impact of interleukin-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and antibody responses in patients with COVID-19: A prospective cohort study
Background: The virological and immunological effects of the immunomodulatory drugs used for COVID-19 remain unknown. We evaluated the impact of interleukin (IL)-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and the antibody response in patients with COVID-19. Methods: Prospective cohort...
| Autores: | , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2020 |
| País: | España |
| Institución: | Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO) |
| Repositorio: | r-FISABIO. Repositorio Institucional de Producción Científica |
| OAI Identifier: | oai:fisabio.fundanetsuite.com:p9059 |
| Acceso en línea: | https://fisabio.portalinvestigacion.com/publicaciones/9059 |
| Access Level: | acceso abierto |
| Palabra clave: | Tocilizumab SARS-CoV-2 COVID-19 Viral kinetics Antibody responses Anti-cytokine therapy S-IgG N-IgG |
| Sumario: | Background: The virological and immunological effects of the immunomodulatory drugs used for COVID-19 remain unknown. We evaluated the impact of interleukin (IL)-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and the antibody response in patients with COVID-19. Methods: Prospective cohort study in patients admitted with COVID-19. Serial nasopharyngeal and plasma samples were measured for SARS-CoV-2 RNA and S-IgG/N-IgG titers, respectively. Findings: 138 patients with confirmed infection were included; 76 (55%) underwent IL-6 blockade. Median initial SOFA (p = 0.016) and SARS-CoV-2 viral load (p<0.001, Mann-Whitney-Wilcoxon test) were significantly higher among anti-IL-6 users. Patients under IL-6 blockade showed delayed viral clearance in the Kaplan-Meier curves (HR 0.35 [95%CI] [0.15.0.81], log-rank p = 0.014), but an adjusted propensity score matching model did not demonstrate a significant relationship of IL-6 blockade with viral clearance (HR 1.63 [0.35.7.7]). Cox regression showed an inverse association between SARS-CoV-2 RNA clearance and the initial viral load (HR 0.35 [0 .11.0.89]). Patients under the IL-6 blocker showed shorter median time to seropositivity, higher peak antibody titers, and higher cumulative proportion of seropositivity in the Kaplan Meier curves (HR 3.1 [1.9.5] for S-IgG; and HR 3.0 [1.9.4.9] for N-IgG; log-rank p<0.001 for both). However, no significant differences between groups were found in either S-IgG (HR 1.56 [0.41.6.0]) nor N-IgG (HR 0.96 [0.26.3.5]) responses in an adjusted propensity score analysis. Interpretation: Our results suggest that in patients infected with SARS-CoV-2, IL-6 blockade does not impair the viral specific antibody responses. Although a delayed viral clearance was observed, it was driven by a higher initial viral load. The study supports the safety of this therapy in patients with COVID-19. Funding: Instituto de salud Carlos III (Spain). (c) 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
|---|