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. 2020 Oct:60:102999.
doi: 10.1016/j.ebiom.2020.102999. Epub 2020 Sep 16.

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  1 , Marta Fernández-González  2 , Sergio Padilla  2 , Piedad Ortega  2 , José A García  3 , Vanesa Agulló  2 , Javier García-Abellán  2 , Guillermo Telenti  2 , Lucía Guillén  2 , Félix Gutiérrez  4
Affiliations

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 et al. EBioMedicine. 2020 Oct.

Abstract

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).

Keywords: Anti-cytokine therapy; Antibody responses; COVID-19; N-IgG; S-IgG; SARS-CoV-2; Tocilizumab; Viral kinetics.

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Conflict of interest statement

Declaration of Competing Interests Dr. Gutiérrez reports personal fees from Janssen-Cilag and from ViiV Health Care, outside the submitted work. The other authors have nothing to disclose.

Figures

Fig. 1
Fig. 1
Kaplan Meier curve to estimate the cumulative proportion of patients with detectable viral RNA according to therapy with tocilizumab. (a) Unadjusted. (b) Adjusted (Wald test).
Fig. 2
Fig. 2
Median time from the onset of symptoms to seropositivity according to therapy with tocilizumab (Mann-Whitney-Wilcoxon test). (a) S-IgG. (b) N-IgG.
Fig. 3
Fig. 3
IgG titers according to therapy with tocilizumab (Mann-Whitney-Wilcoxon test). (a) Peak S-IgG. (b) Peak N-IgG. (c) Peak S-IgG after excluding non seroconverters. (d) Peak N-IgG after excluding non seroconverters.
Fig. 4
Fig. 4
Kaplan Meier curve to estimate the cumulative proportion of patients with negative titers of IgG according to therapy with tocilizumab. (a) S-IgG (unadjusted). (b) N-IgG (unadjusted). (c) S-IgG (adjusted) (log-rank test). (d) N-IgG (adjusted) (log-rank test).
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