CHARACTERIZATION of the IMMUNE RESPONSE in PATIENTS with INFLAMMATORY IMMUNE-MEDIATED DISEASES on IMMUNOSUPPRESSIVE TREATMENT after ONE MONTH of SARS-COV-2 VACCINATION

ABSTRACT

Background: The relevance of studying immune response after SARS-CoV-2 vaccination in patients with infammatory immune-mediated diseases (IMIDs) represents a deep concern regarding the risk estimation and management of patients with these diseases on immunomodulatory drugs. It is well known that certain treatments as anti CD20 therapies results in a diminished immunogenicity against common vaccines but it is a scarce data regarding the cellular protection obtained upon vaccination between patients with different IMID and between different treatments. Objectives: To compare a potential detriment on cellular and antibody-mediated protection upon SARS-CoV-2 vaccination in patients with IMIDs treated with immunosuppressive drugs. Methods: We recruited 73 patients with rheumatoid arthritis-RA-(n=49), spondy-larthritis-SpA-(n=19), infammatory bowel disease-IBD-(n=5), idiopathic juvenile arthritis-IJA-(n=2) and heterogenous group composed of sclerodermia, lupus, uveitis(n=6). They were treated mainly with rituximab (n=27), TNFi (n=37) or JAKi (n=3). We collected data of age,sex, csDMARDs, previous SARS-CoV-2 infection, last RTX infusion and prednisone use. After one month of vaccination, we assessed the humoral response performing the Thermo Scientific EliA SARS-CoV-2-Sp1 IgG Test (positivity cut-off >0.70 IU/ml) which was also compared with the data with of 35 healthy controls. In addition, in 40 patients who had serum antibody levels under 100UI/ml, we analysed the cellular response by the use of the QuantiFERON SARS-CoV-2 Starter Pack (Quiagen). A cut-off value of 0.15 IU/ml discriminate between positive or negative cell-mediated immune responses. We compared differences among the different IMIDs and between the different immu-nosuppressive treatments through non-parametric test (p<0.05) Results: Regarding demographic characteristics of patients, older patients (>56 years) and female sex were factors which were associated with low titles of serum antibodies. Anti-spike IgG antibodies were present in an 86% of the IMIDs patients and in 100% healthy controls with signifcant different IgG titre (median [IQR]) 51[11-184] vs 700[440-940];p<0.0001. The differences between (median [IQR]) serum antibody levels were statistically different between IMID type 33[1-138] in RA vs 94[34-191] in SpA vs 204[187-204] in IBD vs 133[61-204] in IJA vs 13[1.5-31.8] in the rest;p=0.04. Remarkably, patients with IBD who had the highest antibodies titles were the youngest compared with the other patients. Target of the therapy played also an important role in serum antibody levels being these 3.6 [0.7-51] in RTX patients vs 156 [45-204] in TNFi vs 40 [18-58] in JAKi patients;p<0.0001. In those patients who the last infusion of rituximab was, at least, one year before vaccination presented CD19+ B cells detected by fow cytometry and anti-spike IgG antibodies as well. Cell-mediated responses to SARS-CoV-2 were positive in 33% of IMIDs patients, indeterminated in 3% and negative in 65% of the patients. Strikingly, out of the 33% positive patients, 85% were treated with RTX. A 61% of the RTX patients had inducible cell-mediated responses vs 14% of the patients treated with TNFi;p<0.01. On the other hand, there were not differences in cell-mediated responses between positive and negative antibody patients. Conclusion: Titres of serum antibodies against spike protein of SARS-CoV-2 were lower in IMIDs patients than in controls. Patients with RTX had lower rates of positivity humoral response as well as lower serum titles than patients treated with other therapies regardless the patients 'age. Neverthless, in those patients in whom RTX infusion was delayed because of vaccination they conserved a humoral response. On the other hand, more patients treated with RTX had inducible cell-mediated responses compared with patients with TNFi.