INCREASED ANTIBODY RESPONSE AFTER SARS-COV-2 MRNA-BASED VACCINATION IN RITUXIMAB-TREATED PATIENTS WITH PREVIOUS COVID-19 INFECTION

BackgroundRituximab (RTX) is associated with reduced humoral response to SARS-CoV-2 mRNA-based vaccine (1, 2). A recent study has shown that, despite their immunosuppression burden, kidney transplant recipients with previous exposure to SARS-CoV-2 showed a marked increase in antibody titer, even after a single dose of vaccine (3).ObjectivesTo describe the results of immunization after 1 to 3 doses of mRNA SARS-CoV-2 vaccine in RTX-treated patients with previous symptomatic COVID-19 infection.MethodsObservational prospective usual care study including consecutive patients with inflammatory rheumatic diseases in maintenance therapy with RTX. All patients received a 1 to 3-dose regimen of mRNA-based COVID-19 vaccination (BNT162b2 Pfizer/BioNTech or mRNA-1273, Moderna). Serum IgG antibody levels against SARS-CoV-2 spike proteins were measured at the time of the new RTX infusion. The SARS-CoV-2 S1/S2 IgG immunoassay (DiaSorin) was used for the quantitative determination of antibodies to the receptor-binding domain of the viral spike (S) protein. Seropositivity was defined by anti-S antibodies >15 UA/mL.ResultsWe included 69 patients (60 females, mean age 60±13 years) on maintenance therapy with RTX including 13 with previous symptomatic COVID-19, all proven by RT-PCR (10 females, mean age 58±12 years) (Table 1). SymptomaticCOVID-19 occurred between March 2020 and May 2021. The mean interval between the infection and vaccination was 8±3 months and the serological response was assessed after a mean of 74±58 days from the last dose of vaccination (3rd dose for 3 patients, 2nd dose for 6 patients and 1st dose for 4 patients). The 56 patients with no history of symptomatic COVID-19 infection all received 3 doses of vaccine and the serological response was assessed after a mean of 63±27 days from the 3rd dose of vaccination. The seropositivity rate was significantly higher in RTX-treated patients with previous symptomatic COVID-19 infection (11/13, 85% vs.15/56, 27%, p<0.001). Anti-S antibody titles were also markedly increased in patients with previous symptomatic COVID-19 infection (median 119 AU/mL, 95% CI 16-400 AU/mL vs. 3.80 AU/mL, 95% CI 3.80-4.81 AU/mL p<0.0001) (Figure 1). Antibody titles were not different according to the severity of previous COVID-19, the number of doses of vaccine, the underlying disease, and B-cell counts.Table 1.Study populationPatients with previous symptomatic COVID-19 (n=13)Patients without symptomatic COVID-19 (n=56)Age (years), mean ± SD58±1260±11Females, n (%)10 (77)50 (89)Underlying disease: Rheumatoid arthritis10 (77)45 (80) Systemic sclerosis2 (15)5 (9) Systemic lupus erythematosus1 (8)1 (2) Sjögren syndrome0 (0)3 (5) Mixed connective tissue disease0 (0)2 (4)Disease duration (years), mean ± SD17±920±10Associated Methotrexate, n (%)9 (69)36 (64)Current treatment with corticosteroids, n (%)5 (38)21 (38)Corticosteroid dose >10 mg/day, n (%)0 (0)0 (0)CD19+ (/µL) (100-600), mean ± SD65±10645±51CD19 <18/µL, n (%)7 (54)33 (58)Figure 1.Distribution of SARS-CoV-2 spike antibody levels according to the history of proven symptomatic COVID-19. **** p<0.0001 by Mann Whitney test. Dotted red line corresponds to the seropositivity thresholdConclusionRTX-treated patients with previous proven COVID-19 showed increased seropositivity and antibody titers after SARS-CoV-2 vaccination, even after a single-dose of vaccine. This response is strikingly different from that observed for SARS-CoV-2-naïve RTX treated patients who received 3 doses of SARS-CoV-2 mRNA-based vaccination. An “antigen dose phenomenon” may account for these discrepancies. A potential clinical implication might be to increase antibody response with an additional dose of vaccine following an exposure to SARS-CoV-2 in RTX-treated patients with absent or insufficient postvaccination antibody response.References[1]Avouac et al, Rheumatology 2021[2]Jyssum et al, Lancet Rheumatol 2021[3]Benotmane et al, Am J Transplant 2021Disclosure of InterestsNone declared