ABSTRACT
Introduction: Information about how SARS-CoV-2 specific humoral and cellular response is modified by disease-modifying therapies (DMTs) is scarce. Objective: To investigate humoral and cellular responses to SARS-CoV-2 and factors for presenting them in a Barcelona cohort of pwMS. Methods: Retrospective cohort study of adult unvaccinated PwMS with confirmed COVID-19 with at least one SARS-CoV-2 antibody (Ab) determination included from February 2020 to May 2021 and followed until May 2021. Demographic, clinical and laboratory data were obtained. Humoral SARS-CoV-2 response was measured with commercial chemiluminescence immunoassays targeting specific Ab against spike (IgG-S) and nucleocapsid proteins (Ig-N), as per clinical practice. SARS-CoV-2 specific T-cell response was studied in 42 selected pwMS according to DMT by a whole blood Interferon-Gamma (IFN-y) Release Immunoassay. Humoral and cellular response was assesed using a logistic regression model corrected for age, sex, comorbidities, MS form, expanded disability status scale, DMT, COVID-19 severity and PCR result. Results: 145 pwMS were enrolled (mean age 46.8 years;64.1% female;18.6% progressive forms, 20.7% untreated, 22.8% on anti-CD20s therapies and 56.6% on other DMTs). Humoral and cellular tests were performed from 0.3 to 13.1 months after COVID-19. 121(83.5%) presented positive Ab (57.6% anti-CD20 therapy, 90.2% other DMTs, 93.3% untreated). Untreated patients presented higher Ig-N titres (34.3[128.8]) compared to those with anti-CD20s (0.08[0.13], p<0.01), and other DMTs (19.55[42.92], p<0.01). Humoral response persisted over 6 months in 12/12 untreated, 9/22 with anti-CD20s and 22/28 with other DMTs (p=0.068). 31/42(73.8%) presented cellular response (81.0% anti- CD20, 62.5% other DMTs, 80.0% untreated), with similar levels of IFN-y levels among DMTs. 5/12(41.7%) anti-CD20-treated PwMS with negative Ab presented cellular response. In the multivariate analysis, humoral response decreased in anti-CD20 therapy (OR 0.08[95% CI,0.01-0.55]) and was associated with male sex (OR 3.59[1.02-12.68]). Cellular response was associated with seropositivity (OR13.0[1.29-130.4]), but can be present even in the absence of Ab. Conclusions: Humoral response is altered by DMTs, specially in anti-CD20-treated PwMS. Cellular response is associated with seropositivity but can be present in anti-CD20-treated PwMS even in the absence of Ab. Both can be detected up to 13.1 months after COVID-19.
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.