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

• Published in: EBioMedicine Vol. 60; p. 102999
• Main Authors: Masiá, Mar, Fernández-González, Marta, Padilla, Sergio, Ortega, Piedad, García, José A., Agulló, Vanesa, García-Abellán, Javier, Telenti, Guillermo, Guillén, Lucía, Gutiérrez, Félix
• Format: Journal Article Web Resource
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2020; Elsevier BV; Elsevier
• Subjects: Aged; Anti-cytokine therapy; Antibodies, Monoclonal, Humanized - immunology; Antibodies, Monoclonal, Humanized - therapeutic use; Antibodies, Viral - blood; Antibody Formation; Antibody responses; Betacoronavirus - isolation & purification; Betacoronavirus - physiology; Coronavirus Infections - drug therapy; Coronavirus Infections - pathology; Coronavirus Infections - virology; COVID-19; Female; Humans; Immunoglobulin G - blood; Immunosuppressive agents; Interleukin-6 - analysis; Interleukin-6 - immunology; Kinetics; Male; Middle Aged; N-IgG; Pandemics; Pneumonia, Viral - drug therapy; Pneumonia, Viral - pathology; Pneumonia, Viral - virology; Proportional Hazards Models; Prospective Studies; Research Paper; RNA, Viral - blood; S-IgG; SARS-CoV-2; Tocilizumab; Viral kinetics; Viral Load; COVID-19; SARS-CoV-2; Viral kinetics; Tocilizumab; S-IgG; Antibody responses; N-IgG; Anti-cytokine therapy
• ISSN: 2352-3964; 2352-3964
• DOI: 10.1016/j.ebiom.2020.102999

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. 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. 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. 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. Instituto de salud Carlos III (Spain).