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

EBioMedicine

Marta Fernández-González¹  Mar Masiá²  Sergio Padilla³  Piedad Ortega³  Lucía Guillén³  Guillermo Telenti³  José A. García³  Javier García-Abellán³  Félix Gutiérrez³  Vanesa Agulló⁴ 

[1] Corresponding author.;Hospital General Universitario de Elche and Universidad Miguel Hernández, Camí de la Almazara 11, Elche, Alicante 03203, Spain;Hospital General Universitario de Elche, Camí de la Almazara 11, Elche, Alicante 03203, Spain;Operational Research Center, Universidad Miguel Hernández, Elche, Alicante, Spain;

关键词: Tocilizumab;    SARS-CoV-2;    COVID-19;    Viral kinetics;    Antibody responses;    Anti-cytokine therapy;   

DOI  :  

来源: DOAJ

【 摘 要 】

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).

【 授权许可】

Unknown