Robust long-term immunity to SARS-CoV-2 in patients recovered from severe COVID-19 after interleukin-6 blockade

• Published in: EBioMedicine Vol. 82; p. 104153
• Main Authors: Masiá, Mar, Fernández-González, Marta, García, José Alberto, Padilla, Sergio, García-Abellán, Javier, Botella, Ángela, Mascarell, Paula, Agulló, Vanesa, Gutiérrez, Félix
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.08.2022; Elsevier
• Subjects: Antibody responses; COVID-19; Immunity; Interleukin-6 blockade; Reinfection; SARS-CoV-2; T-cell responses; Tocilizumab; COVID-19; SARS-CoV-2; Tocilizumab; T-cell responses; Interleukin-6 blockade; Antibody responses; Reinfection; Immunity
• ISSN: 2352-3964; 2352-3964
• DOI: 10.1016/j.ebiom.2022.104153

Whether interleukin-6 (IL-6) blockade in patients with COVID-19 will affect the protective immunity against SARS-CoV-2 has become an important concern for anti-IL-6 therapy. We aimed to investigate the effects of IL-6 blockade on long-term immunity to SARS-CoV-2. Prospective, longitudinal cohort study conducted in patients hospitalized for severe or critical COVID-19 with laboratory confirmed SARS-CoV-2 infection. We assessed humoral (anti-S1 domain of the spike [S], anti-nucleocapsid [N], anti-trimeric spike [TrimericS] IgG, and neutralizing antibodies [Nab]) and T-cell (interferon-γ release assay [IGRA]) responses and evaluated the incidence of reinfections over one year after infection in patients undergoing IL-6 blockade with tocilizumab and compared them with untreated subjects. From 150 adults admitted with confirmed SARS-CoV-2 infection, 78 were 1:1 propensity score-matched. Patients receiving anti-IL6 therapy showed a shorter time to S-IgG seropositivity and stronger S-IgG and N-IgG antibody responses. Among unvaccinated subjects one year after infection, median (Q1-Q3) levels of TrimericS-IgG (295 vs 121 BAU/mL; p = 0.011) and Nab (74.7 vs 41.0 %IH; p = 0.012) were higher in those undergoing anti-IL6 therapy, and a greater proportion of them had Nab (80.6% vs 57.7%; p = 0.028). T-cell immunity was also better in those treated with anti-IL6, with higher median (Q1-Q3) interferon-γ responses (1760 [702–3992] vs 542 [35–1716] mIU/mL; p = 0.013) and more patients showing positive T-cell responses in the IGRA one year after infection. Patients treated with anti-IL6 had fewer reinfections during follow-up and responded to vaccination with robust increase in both antibody and T-cell immunity. IL-6 blockade in patients with severe COVID-19 does not have deleterious effects on long-term immunity to SARS-CoV-2. The magnitude of both antibody and T-cell responses was stronger than the observed in non-anti-cytokine-treated patients with no increase in the risk of reinfections. Instituto de Salud Carlos-III (Spain).