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

Clodoveo Ferri, Francesco Ursini, Laura Gragnani, Vincenzo Raimondo, Dilia Giuggioli, Rosario Foti, Maurizio Caminiti, Domenico Olivo, Giovanna Cuomo, Marcella Visentini, Fabio Cacciapaglia, Roberta Pellegrini, Erika Pigatto, Teresa Urraro, Caterina Naclerio, Antonio Tavoni, Lorenzo Puccetti, Giuseppe Varcasia, Ilaria Cavazzana, Massimo L'AndolinaPiero Ruscitti, Marta Vadacca, Pietro Gigliotti, Francesca La Gualana, Franco Cozzi, Amelia Spinella, Elisa Visalli, Ylenia Dal Bosco, Giorgio Amato, Francesco Masini, Giuseppa Pagano Mariano, Raffaele Brittelli, Vincenzo Aiello, Rodolfo Caminiti, Daniela Scorpiniti, Giovanni Rechichi, Tommaso Ferrari, Monica Monti, Giusy Elia, Franco Franceschini, Riccardo Meliconi, Milvia Casato, Florenzo Iannone, Roberto Giacomelli, Poupak Fallahi, Stefano Angelo Santini, Anna Linda Zignego, Alessandro Antonelli

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1-8
JournalJournal of Autoimmunity
Early online dateNov 10 2021
Publication statusPublished - Dec 2021


  • Autoimmune systemic diseases
  • COVID-19 vaccine
  • Cryoglobulinemic vasculitis
  • Neutralizing antibodies
  • Rheumatoid arthritis
  • Systemic lupus
  • Systemic sclerosis
  • Systemic vasculitis


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