CLINICAL COURSE and OUTCOMES of COVID-19 INFECTION in PATIENTS with SJOGREN'S SYNDROME TREATED with RITUXIMAB

ABSTRACT

Background: Data from multiple rheumatological cohorts have shown that treatment with rituximab (RTM) is associated with higher COVID-19 morbidity and mortality. Information about the course of COVID-19 in patients (pts) with Sjogren's syndrome (SjS) is still lacking. Objectives: To compare clinical course of COVID-19 in pts with SjS treated with anti-CD20 monoclonal antibody (RTM) and treated with synthetic disease-modifying antirheumatic drugs and low doses of glucocorticoids. Methods: Single center observational study. Pts with SjS were screened for SARS-CoV-2 infection anamnesis via telephone interview. Diagnosis of SjS was based on ECR/EULAR 2016 criteria. COVID-19 diagnosis was based on positive PCR test and typical clinical features (CT signs, fever and anosmia). RTM was administered as two infusions of 1000 mg each 2 weeks apart, and then 500 mg every 6 months. Results: 387 pts with SjS were interviewed, 142 of them with confrmed SARS-CoV-2 were included in the study and divided into 2 groups. The frst group (gr) consisted of 86 pts (79 women and 7 men) receiving RTM (gr R), median age was 56 years (33-66,5 years), and median rituximab treatment duration was 36 months (12-42 months). Pts in the control gr (gr C), 56 pts did not receive RTM (55 women and 1 man), their median age was 50 years (35-69 years). Median time from last RTM administration to COVID-19 symptoms onset was 4 months (2-6 months). Ten pts had concomitant RA, 4 pts-SLE, 5 pts-Systemic sclerosis. Fifteen pts had MALT-lymphoma anamnesis. Additionally, 15 pts (10.5%) had pulmonary involvement secondary to rheumatic disease. In total 37 pts had chronic ischemic heart disease and/or severe arterial hypertension, diabetes mellitus type 2. In gr R 31 pts (36%), and in gr C 13 (23%) required hospitalization due to marked shortness of breath and long febrile period (p=0,1). Anti-IL6 treatment or/and Jak inhibitors were prescribed to 17 of 31 pts (54.8%) in gr R and to 5 of 13 (38%) in gr C (p=0,1). The risk of hospitalization was slightly higher in pts with comorbidity (p=0.06) and with a history of lymphoma (p=0.056) and didn't correlate with the following parameters age, the duration of RTM therapy, lung damage. A high rate of hospitalization correlated with a shorter period between the administration of the RTM and the development of COVID-19 (R=0,387, Spearmaǹs Rank Correlation). Anti-SARS-CoV-2 IgG were measured in 66 pts, 47 (71%) of them were positive. Positive Anti-SARS-CoV-2 IgG were signifcantly more often detected in gr C (84% vs. 57,6%). No correlation was found between the formation of antibodies and the duration of RTM therapy or the time from the last RTM administration. Conclusion: According to our data anti-CD20 therapy doesn't predispose SjS pts to severe course of COVID-19. Lymphoma anamnesis, cardiovascular diseases and diabetes have greater impact on COVID-19 severity. Obviously, anti-CD20 therapy negatively affected the formation of specifc anti-SARS-CoV-2 humoral immunity.