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.
ABSTRACT
Background: there are some concerns among patients (pts) with rheumatic diseases regarding the tolerability and efficacy of SARS-CoV-2 vaccination. The impact effect of vaccination on the course of Sjogreǹs syndrome (SjS) is not entirely clear. Objectives: to evaluate the efficacy and tolerability of the heterologous recombinant adenovirus (rAd)-based vaccine Sputnik in pts with SjS receiving various types of therapy. Methods: single center observational retrospective study. Diagnosis of SjS was based on ACR/EULAR 2016 criteria. Rituximab (RTM) was administered in two 1000 mg infusions 14 days apart for the 1 st course, then 500 mg every 6 months. Results: 70 pts with a defnite diagnosis of SjS were included in the study. Four out of 70 were women. The mean age was 52.5±14.6 years, the average duration of the SjS was 72 (36-120) months. Three pts had concomitant RA, 3 pts-SLE, 2 pts-Systemic sclerosis. Extraglandular manifestations of SjS were detected in 35 cases. Five pts received single-dose rAd26 vector-based COVID-19 vaccine 'Sputnik Light', other 65 pts received 2 doses of Gam-COVID-Vac (Sputnik V). Eighteen pts did not receive any immunosuppressive therapy and were vaccinated before RTM therapy. One patient of them just diagnosed with lymphoma, 8 pts had extraglandular manifestations of the SjS (hypergam-maglobulinemic purpura, cryoglobulinemic vasculitis with polyneuropathy, interstitial lung disease). 20 pts at the time of vaccination received various immunosuppressive drugs: 1-cyclophosphamide (CYC), 1-lefunomide, 1-Azathioprine, 3-methotrexate, 2-mycophenolate mofetil (MMF), 10-hydroxychloroquine, 13-low doses of methylprednisolone. Thirty-two pts received anti B-cells therapy with RTM. The duration of RTM therapy before vaccination was 18 (12-36) months, the period of time between the last injection of the RTM and the vaccine was on average 6 (5-8) months. B-cells level was determined in 18 pts immediately before vaccination and it was normal only in 10 pts. The level of neutralizing antibodies after vaccination was monitored in 44 pts. The level of IgG antibodies against SARS-CoV-2 was positive in 15 of 22 pts who did not receive RTM and in 10 of 22 pts who received the RTM (p>0.05). Neutralizing antibodies did not develop in 4 pts despite complete recovery of B cells. It is important that none of the vaccinated pts was infected COVID-19 within at least 6 months after vaccination. Various types of adverse reactions were observed in 8 pts. The most common was fu-like syndrome. In one case this syndrome required the prescription of dexameth-asone. In 3 cases disease exacerbation occurred after vaccination. These pts had extraglandular manifestations of SjS and received immunosuppressants (CYC, MMF or RTM), 2 of them required treatment intensifcation, in one case the exacerbation was self-limiting. Conclusion: vaccination against SARS-CoV-2 infection was well tolerated by pts with SjS even in the absence of immunosuppressive therapy. In most cases, there were no exacerbation of the SjS and pts could continue immunosuppres-sive therapy without becoming infected COVID-19.
ABSTRACT
Background: The severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) disease 2019 (COVID-19) raised concern for the outcomes in people with different rheumatic diseases and management of these patients. There was an anxiety that biologic therapies, especially anti-B-cell depletion strategies, could lead to more severe disease course and lack of protective antibodies formation. Information about the course of COVID-19 in patients with certain rheumatic diseases is still lacking. Objectives: To examine clinical course of COVID-19 in patients with Sjogren's syndrome treated with anti-CD20 monoclonal antibody (rituximab). Methods: Single center observational study. Diagnosis of SjS was based on ECR/EULAR 2016 criteria. COVID-19 diagnosis was based on positive PCR test even without clinical symptoms and/or typical clinical features (CT signs, fever and anosmia). Rituximab was administrated in two 1000 mg infusions 14 days apart for the 1st course, then 500 mg every 6 months. Results: 19 patients were included, 18 women and 1 man. Median age was 55 years (29-70 years), and median rituximab treatment duration was 24 months (1-48 months). Five patients had concomitant RA (2 patients), SLAE (1 pt), Systemic sclerosis (2 patients). Patients with RA took baricitinib and methotrexate as well. 3 patients had MALT-lymphoma anamnesis (24, 38 and 24 months before the diagnosis of COVID-19). Only 3 patients had chronic ischemic heart disease and/or arterial hypertension. 12 patients were PCR positive, 6 negative and in 1 the test was not done. 11 patients had full and 4 partial B-cell depletion in peripheral blood. Five patients had <20% lung involvement on CT, 2 patients -20-40% and 4 patients -40-60%. Three patients with 40-60% lung involvement required hospitalization due to marked shortness of breath and long febrile period, 2 of them received anti-IL6 treatment and neither of them required mechanical lung ventilation (either non-invasive or invasive). Seventeen patients were treated at home and recovered in 10-24 days. Anti-SARS-CoV-2 IgG were measured in 9 patients, 6 (66.7%) of them were positive. Conclusion: It seems that neither SjS itself nor anti-CD20 therapy predisposes patients to severe course of COVID-19. Presumably risk factors such as age, diabetes or anamnesis of cardiovascular diseases have far more significant impact on COVID-19 severity. Data hints that anti-CD20 therapy might negatively affect the formation of specific anti-SARS-CoV-2 humoral immunity, but further investigation is required to determine that with any degree of certainty.