Impaired immunogenicity to COVID-19 vaccines in autoimmune systemic diseases. High prevalence of non-response in different patients’ subgroups

• Published in: Journal of autoimmunity Vol. 125; p. 102744
• Main Authors: Ferri, Clodoveo, Ursini, Francesco, Gragnani, Laura, Raimondo, Vincenzo, Giuggioli, Dilia, Foti, Rosario, Caminiti, Maurizio, Olivo, Domenico, Cuomo, Giovanna, Visentini, Marcella, Cacciapaglia, Fabio, Pellegrini, Roberta, Pigatto, Erika, Urraro, Teresa, Naclerio, Caterina, Tavoni, Antonio, Puccetti, Lorenzo, Varcasia, Giuseppe, Cavazzana, Ilaria, L'Andolina, Massimo, Ruscitti, Piero, Vadacca, Marta, Gigliotti, Pietro, La Gualana, Francesca, Cozzi, Franco, Spinella, Amelia, Visalli, Elisa, Dal Bosco, Ylenia, Amato, Giorgio, Masini, Francesco, Pagano Mariano, Giuseppa, Brittelli, Raffaele, Aiello, Vincenzo, Caminiti, Rodolfo, Scorpiniti, Daniela, Rechichi, Giovanni, Ferrari, Tommaso, Monti, Monica, Elia, Giusy, Franceschini, Franco, Meliconi, Riccardo, Casato, Milvia, Iannone, Florenzo, Giacomelli, Roberto, Fallahi, Poupak, Santini, Stefano Angelo, Zignego, Anna Linda, Antonelli, Alessandro
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2021
• Subjects: 2019-nCoV Vaccine mRNA-1273 - immunology; Antibodies, Neutralizing - blood; Antibodies, Viral - blood; Autoimmune Diseases - blood; Autoimmune Diseases - immunology; Autoimmune systemic diseases; BNT162 Vaccine - immunology; COVID-19 - prevention & control; COVID-19 vaccine; Cryoglobulinemic vasculitis; Female; Humans; Italy; Lupus Erythematosus, Systemic - immunology; Male; Middle Aged; Neutralizing antibodies; Prospective Studies; Rheumatoid arthritis; SARS-CoV-2 - immunology; Scleroderma, Systemic - immunology; Systemic lupus; Systemic sclerosis; Systemic vasculitis; Systemic Vasculitis - immunology; Vaccination; Vaccine Potency; Italy; World Health Organization; Neutralizing antibodies; Systemic lupus; Autoimmune systemic diseases; Neutralizing antibody; Rheumatoid factor; Anti-citrullinated protein antibodies; Systemic lupus erythematosus; Adverse events; Systemic sclerosis; Rheumatoid arthritis; Binding Antibody Units; COVID-19 vaccine; Systemic vasculitis; Cryoglobulinemic vasculitis
• ISSN: 0896-8411; 1095-9157; 1095-9157
• DOI: 10.1016/j.jaut.2021.102744

Autoimmune systemic diseases (ASD) may show impaired immunogenicity to COVID-19 vaccines. Our prospective observational multicenter study aimed to evaluate the seroconversion after the vaccination cycle and at 6-12-month follow-up, as well the safety and efficacy of vaccines in preventing COVID-19. The study included 478 unselected ASD patients (mean age 59 ± 15 years), namely 101 rheumatoid arthritis (RA), 38 systemic lupus erythematosus (SLE), 265 systemic sclerosis (SSc), 61 cryoglobulinemic vasculitis (CV), and a miscellanea of 13 systemic vasculitis. The control group included 502 individuals from the general population (mean age 59 ± 14SD years). The immunogenicity of mRNA COVID-19 vaccines (BNT162b2 and mRNA-1273) was evaluated by measuring serum IgG-neutralizing antibody (NAb) (SARS-CoV-2 IgG II Quant antibody test kit; Abbott Laboratories, Chicago, IL) on samples obtained within 3 weeks after vaccination cycle. The short-term results of our prospective study revealed significantly lower NAb levels in ASD series compared to controls [286 (53–1203) vs 825 (451–1542) BAU/mL, p < 0.0001], as well as between single ASD subgroups and controls. More interestingly, higher percentage of non-responders to vaccine was recorded in ASD patients compared to controls [13.2% (63/478), vs 2.8% (14/502); p < 0.0001]. Increased prevalence of non-response to vaccine was also observed in different ASD subgroups, in patients with ASD-related interstitial lung disease (p = 0.009), and in those treated with glucocorticoids (p = 0.002), mycophenolate-mofetil (p < 0.0001), or rituximab (p < 0.0001). Comparable percentages of vaccine-related adverse effects were recorded among responder and non-responder ASD patients. Patients with weak/absent seroconversion, believed to be immune to SARS-CoV-2 infection, are at high risk to develop COVID-19. Early determination of serum NAb after vaccination cycle may allow to identify three main groups of ASD patients: responders, subjects with suboptimal response, non-responders. Patients with suboptimal response should be prioritized for a booster-dose of vaccine, while a different type of vaccine could be administered to non-responder individuals. •Autoimmune systemic diseases (ASD) show impaired immunogenicity to Covid-19 vaccines.•ASD show significantly higher percentage of non-responder patients than controls.•Early neutralizing Ab post-vaccine detection is recommended in immunocompromised patients.•Patients with suboptimal response should be prioritized for a booster-dose of vaccine.•A different type of Covid-19 vaccine could be attempted in non-responder individuals.