ABSTRACT
Background: Information about humoral and cellular responses to SARS-CoV-2 vaccination in patients with Multiple Sclerosis (PwMS) and other autoimmune diseases (AID) is scarce. Objective: To determine humoral and cellular responses after SARS-CoV-2 vaccination in PwMS and anti-CD20-treated patients with other AID. Methods: Ongoing prospective study performed in two Catalan MS centres from February 2021. Unvaccinated adult pwMS and other anti-CD20-treated AID were recruited. Demographic, clinical and laboratory data were obtained. Whole blood samples were obtained before and 30-90 days after vaccination. The humoral response to SARS-CoV-2 was qualitatively and quantitatively measured before and after vaccination with commercial chemiluminescence immunoassays targeting SARS-CoV-2 antibodies against spike (TrimericS, IgG anti-S) and nucleocasid proteins (Elecsys, Ig anti-N). In 150 selected patients according to diseasemodifying therapy (DMT), the SARS-CoV-2 specific T-cell response was assessed after vaccination by a whole blood Interferon-Gamma Release immuno Assay (IGRA) that uses two Qiagen proprietary mixes of SARS-CoV-2 S protein (Ag.1 and Ag.2) selected to activate both CD4 and CD8 T cells. Results: 457 patients have been enrolled in the study (anti-CD20 therapy n=164, S1P DMTs n=37, natalizumab n=32, cladribine n=29, alemtuzumab n=31, other DMTs n=129, no DMT n=35). Participants characteristics are: mean age 48.1 years (SD 12.0), 69% female, 422 pwMS (29.4% progressive forms) and 35 with other AID, disease duration 13.9 years (IQR 14.1), median EDSS 3.0 (IQR 3.0). 450 have been fully vaccinated (94.2% mRNA vaccine). Pre-vaccination samples were collected 0.33 days (SD 0.5) before the first vaccine dose of which 12 (3.35%) had positive anti S/N immunoglobulin (Ig). As of June 30th, 42 post-vaccination samples have been obtained (1.3 months [SD 0.42] after the 2nd vaccination dose). Positive IgG rates were 44.8% (n=13/29) for CD20s, 100% (8/8) for other DMTs and 100% (4/4) for no DMT. No anti-N Ig were detected. Media titres of anti-S IgG were lower in anti-CD20-treated patients (7.8 [IQR 50.1]) compared to untreated patients (800 [0], p<0.01) or other DMTs (755 [228], p<0.01). Conclusions: Initial results of the study suggest blunted anti-S/N Ig response under anti-CD20 therapy. Knowledge of the cellular response in these patients will be crucial. Data from the cellular study and the completed humoral study will be presented at the meeting.
ABSTRACT
Background: Coronavirus disease 2019 (COVID-19) is a pandemic-spread systemic infectious disease with prominent respiratory manifestations and significant associated morbidity and mortality. Elderly people are most significantly affected with mortality ranging from 2.4% (age 60-69) to 19.6% (age≥80) in European Countries. The prevalence of COVID-19 and of its complications in patients with immune-mediated disorders, remains unclear. The frequency and impact of COVID-19 on patients with IgG4-related diease (IgG4-RD), many of whom are on concurrent immunosuppression has not been addressed. Objectives: To assess the epidemiological and clinical relevance of COVID-19 in patients with IgG4-RD. Methods: This is a multi-centre retrospective observational study of IgG4-RD patients from France, Italy, Spain and the United Kingdom. Demographics, comorbidities, IgG4-RD features, current and past treatment along with COVID-19-suggestive symptoms and COVID-19 diagnoses from February 2020 to January 2021 were recorded by means of direct or phone interviews. Patients with reverse-transcriptase polymerase chain reaction-confirmed (cCOVID) or presumed COVID-19 based on clinical, serological or imaging features (pCOVID) were pooled for analysis (totCOVID) and compared to patients who were not diagnosed with COVID-19. Inter-group comparison of categorical and quantitative variables were performed by using the chi-square test with Fisher's correction and the Mann-Whitney's test respectively. Data are expressed as median (interquartile range) unless otherwise specified. Results: A total of 305 patients [71% males, median age 64 (54-74) years] were studied. Pancreato-biliary disease was the most frequently observed IgG4-RD phenotype (39%). Fifty-one percent of patients were taking corticosteroids at time of interview and 30% were on biological or conventional immunosuppressants. Thirty-two totCOVID cases (23 cCOVID, nine pCOVID) were identified: 11/32 were hospitalised, two needed intensive care and four (13%;3/4 aged ≥80 years) died. Having one or more infected family members was a risk factor for COVID-19 in patients with IgG4-RD (OR=19.9;p<0.001). No other demographic, clinical or treatment features associated with COVID-19. In particular there was no association between adverse outcomes with COVID-19 and higher doses of steroids (≥20mg) or rituximab administration. Conclusion: The prevalence and course of COVID-19 in IgG4-RD patients are similar to those of the general population of the same age, with no evident impact of disease-or treatment-related factors to the basal infectious risk. Effective public health countermeasures might be beneficial for patients with IgG4RD.