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

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Instituto de Salud Carlos-III (Spain).