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
Mar Masiá, Marta Fernández-González, Sergio Padilla, Piedad Ortega, José A García, Vanesa Agulló, Javier García-Abellán, Guillermo Telenti, Lucía Guillén, Félix Gutiérrez
EBioMedicine, doi:10.1016/j.ebiom.2020.102999
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 = 0016) and SARS-CoV-2 viral load (p<0001, 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 035 [95%CI] [015À081], log-rank p = 0014), but an adjusted propensity score matching model did not demonstrate a significant relationship of IL-6 blockade with viral clearance (HR 163 [035À77]). Cox regression showed an inverse association between SARS-CoV-2 RNA clearance and the initial viral load (HR 035 [011À089]). 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 31 [19À5] for and HR 30 [19À49] for N-IgG; log-rank p<0001 for both). However, no significant differences between groups were found in either S-IgG (HR 156 [041À60]) nor N-IgG (HR 096 [026À35]) 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.
Declaration of Competing Interests Dr. Guti errez reports personal fees from Janssen-Cilag and from ViiV Health Care, outside the submitted work. The other authors have nothing to disclose.
Supplementary materials Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.ebiom.2020.102999.
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