Robust long-term immunity to SARS-CoV-2 in patients recovered from severe COVID-19 after interleukin-6 blockade
Mar Masiá,
Marta Fernández-González,
José Alberto García,
Sergio Padilla,
Javier García-Abellán,
Ángela Botella,
Paula Mascarell,
Vanesa Agulló,
Félix Gutiérrez
Affiliations
Mar Masiá
Infectious Diseases Unit, Hospital General Universitario de Elche, Alicante, Spain; CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain; Clinical Medicine Department, Universidad Miguel Hernández de Elche, Alicante, Spain; Corresponding authors at: Infectious Diseases Unit, Hospital General Universitario de Elche and Universidad Miguel Hernández, Camí de la Almazara 11, Elche 03203, Alicante, Spain.
Marta Fernández-González
Infectious Diseases Unit, Hospital General Universitario de Elche, Alicante, Spain; CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain
José Alberto García
Infectious Diseases Unit, Hospital General Universitario de Elche, Alicante, Spain; CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain
Sergio Padilla
Infectious Diseases Unit, Hospital General Universitario de Elche, Alicante, Spain; CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain; Clinical Medicine Department, Universidad Miguel Hernández de Elche, Alicante, Spain
Javier García-Abellán
Infectious Diseases Unit, Hospital General Universitario de Elche, Alicante, Spain; CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain
Ángela Botella
Infectious Diseases Unit, Hospital General Universitario de Elche, Alicante, Spain
Paula Mascarell
Infectious Diseases Unit, Hospital General Universitario de Elche, Alicante, Spain
Vanesa Agulló
Infectious Diseases Unit, Hospital General Universitario de Elche, Alicante, Spain; CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain
Félix Gutiérrez
Infectious Diseases Unit, Hospital General Universitario de Elche, Alicante, Spain; CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain; Clinical Medicine Department, Universidad Miguel Hernández de Elche, Alicante, Spain; Corresponding authors at: Infectious Diseases Unit, Hospital General Universitario de Elche and Universidad Miguel Hernández, Camí de la Almazara 11, Elche 03203, Alicante, Spain.
Summary: 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).
