COVID-19 vaccine immunogenicity in 16 patients with autoimmune systemic diseases. Lack of both humoral and cellular response to booster dose and ongoing disease modifying therapies.

Background: Patients with autoimmune systemic diseases (ASDs) represent a frail population during the ongoing COVID-19 pandemic. The vaccination is the major preventive measure; however, a significant number of ASD patients show an impaired production of anti-COVID-19 neutralizing antibodies (NAb), possibly counterbalanced by adequate T-cell response. The present study aimed at evaluating both humoral and cellular response to COVID-19 vaccine booster dose in this particular setting. Patients and methods: Serum NAb titer and T-cell response (measuring interferon gamma -IFN-γ- release) were evaluated 3 weeks after the COVID-19 vaccine booster dose, in 17 patients (12 F, mean age 68.8 ± 15.3 SD yrs) with different ASDs, compared to 17 healthy controls (HCs). Results: The analysis excluded one patient reporting symptoms of COVID-19 only after the immunogenicity tests had been performed.The NAb levels were significantly lower in ASD compared to HCs (p < 0.0001); moreover, patients showed a higher percentage of negative/sub-optimal humoral response (31% vs 0% of HCs; p = 0.0184).The study of cellular response showed lower levels of IFN-γ for both Ag1 (p = 0.0032) and Ag2 (p = 0.0136) in ASD patients compared to HCs, as well lower rate of adequate T-cell response compared to HCs (50% vs 94%; p = 0.0066).Disease modifying therapies (DMT) were administered in all patients with deficient NAb production (5/5, 100%), but in only 3/11 (27%) of responders (p = 0.025).Worthy to note, 3/16 (19%) ASD patients developed neither humoral nor cellular responses, all treated with DMT. Conclusions: The impaired immunogenicity to COVID-19 vaccine booster and even more the concomitant lack of both humoral and cellular response might represent a high risk for severe COVID-19, particularly in ASD patients undergoing DMT.These frail subjects should be tightly monitored for their immune protection and prioritized for the fourth dose of COVID-19 vaccine. Moreover, in the occurrence of SARS-CoV2 infection, treatments with specific monoclonal antibodies and/or antivirals may be highly recommendable.