EVALUATION of the HUMORAL IMMUNE RESPONSE SECONDARY to VACCINATION AGAINST SARS-COV2 in PATIENTS with AUTOIMMUNE RHEUMATIC DISEASES

ABSTRACT

Background: Several trials have reported lower seroconversion rates in patients with autoimmune rheumatic diseases than in healthy patients. In Argentina, the vaccines that were available during the development of this study were Sputnik V (Gam-COVID-Vac), AstraZeneca (ChAdOx1 nCov-19), Sinopharm (BBIBP-CorV) and Moderna (mRNA-1273). Limited information is available about vaccines against SARS-CoV2 with inactivated virus or viral vector in autoimmune patients. Objectives: To evaluate the humoral immune response to vaccines against SARS-CoV2 in patients with autoimmune rheumatic diseases;to compare the humoral response among patients with Systemic Lupus Erythematosus (SLE) and other autoimmune diseases and to analyse the variables associated. Methods: We included patients with autoimmune rheumatic diseases (Rheumatology Unit of Padilla Hospital, Tucumán, Argentina), who received vaccination against SARS-CoV2 from June 2021. Sociodemographic, comorbidities, related to rheumatic disease, vaccination and SARS-CoV2 infection were the variables recorded. To evaluate the humoral immune response, the neutralizing anti-S-RBD IgG antibody titres were determined by ELISA 'In House' test with a cut-off titre of 200 (IMMCA). The times established for the serological determinations were T0 or baseline 1st vaccine dose, T1 14 ± 2 days after the 1st dose, T2 2nd dose, T3 21-45 days after the 2nd dose, T4 30 days after the 3rd dose, T5 6 months and T6 12 months after the 3rd dose. Results: 66 patients were included, 91% women and 92.4% Amerindians. The mean age was 40.7 ± 11.4 years;53% with SLE, 15.2% Rheumatoid Arthritis, 7.6% Systemic Sclerosis, 7.6% Juvenile Idiopathic Arthritis, 7.6% Systemic Vasculitis and 9% other diagnoses;mean disease duration was 12.05 ± 7. 5 years;63.6% had at least one comorbidity (57% HBP, 31% overweight or obesity). At baseline, the treatments received were corticoster-oids (37.9%, prednisone mean dose 4.12 ± 8 mg/day), cDMARDs (75.7%), bDMARDs (18.2%) Rituximab (58.3%) and anti TNF (25%). Sixteen patients (24.2%) had previous COVID19 (75% mild symptoms). The vaccines applied were AstraZeneca 38.2%, Sinopharm 31.7%, Sputnik V 19%, and combined schedule Sputnik V/Moderna in 11%. At baseline, 28.8% had detectable anti-S-RBD IgG antibodies. This frequency increased to 48.4% at 1st dose and 70.2% at 2nd dose. The variables that were associated with lower sero-conversion rates and lower antibody titre were vaccination with Sinopharm (p 0.028) and treatment with bDMARDs (p 0.02), none of the 5 patients with Rituximab showed seroconversion. There were no significant differences in the levels of anti-S-RBD IgG antibodies between patients with SLE and the other rheumatic diseases. Patients who had SARS-CoV2 infection prior to vaccination had higher antibody titres in both T1 (p 0.006) and T2 (p 0.002) but after the two doses this difference was not significant (p 0.67). In the regression analysis, the variables that were independently associated with seroconversion were the type of vaccine applied at the 1st dose and the hypertensive disease. The chance of responding to vaccination was 13 and 9 times higher for those who received Sputnik V (OR 12.78;95% CI 1.46-315.9) or AstraZeneca (OR 8.61;95% CI 1.63-72.5) respectively, than Sinopharm in the 1st dose. The chance of being a responder was 88% lower for hypertensive patients (OR 0.12;95% CI 0.02-0.58). Conclusion: In this preliminary analysis, a seroconversion rate of 70.2% was associated with two-dose vaccination for SARS-CoV2 in patients with autoimmune rheumatic diseases. There were no differences in the serological response between patients with SLE and other rheumatic diseases. The humoral immune response was lower in patients with bDMARDs and null in those who received Rituximab. Seroconversion and antibody titres levels were associated with the type of vaccine applied, being Sinopharm who presented the lowest response. The follow-up will provide more knowledge about the behaviour of the humoral response in our patients.