ABSTRACT
Background: SARS-CoV-2 influenced all aspects of healthcare and will do so in the future. Early pre-vaccination studies, including our first NYCNIC cohort, demonstrated favorable COVID-19 outcomes in people with MS, though anti-CD20 therapies were associated with increased hospitalization. While SARS-CoV-2 vaccines reduce incidence and severity of infections in the general population, anti-CD20 and S1P modulating agents blunt humoral vaccination response. T cell responses are preserved in anti- CD20-treated-patients, suggesting at least partially intact vaccinemediated protection. Therefore, data on COVID-19 incidence and severity in vaccinated MS patients is necessary. Objective(s): To identify risk factors of severity of breakthrough COVID-19 infection in vaccinated MS patients before and during the Omicron wave. Aim(s): To characterize COVID -19 infection in vaccinated MS patients. Method(s): Demographics, MS, clinical variables (time from last vaccination to infection, vaccine type, booster receipt, antibody presence, ambulatory status, comorbidities) and COVID-19 outcomes were collected on vaccinated MS patients followed at 5 MS Centers through January 31st, 2022. Infections were labeled as 'pre-Omicron (prior to Dec 1st 2021) and "During Omicron". Infection severity was measured by a 4-point ordinal scale (home care, hospitalization, ICU, death). Univariate and multivariate regression models were used to assess risk factors for hospitalization. Result(s): Our cohort included 209 patients with 211 breakthrough infections (45 pre and 166 during Omicron) with median age 42 (range 19-78), 71% female, 65% Caucasian. Anti-CD20 agents were used by 67% of patients pre- and 62% during Omicron, substantially higher than in first (pre-vaccination) NYCNIC cohort (35%). In a multivariate model including the entire cohort, adjusting for age, use of anti-CD20 or S1P agents during infection increased risk of hospitalization or worse (p= 0.0454, OR 3.815, 95% CI: 1.028-14.161). In a multivariate model including only patients during the Omicron wave, adjusting for comorbidity, use of anti-CD20 therapies during vaccination increased risk of hospitalization or worse (p=0.0462, OR 3.565, 95% CI: 1.022-12.436). Conclusion(s): Anti-CD20 and S1P modulating agents were associated with higher severity of COVID-19 infections in vaccinated MS patients. Compared to the first NYCNIC cohort, use of anti- CD20 was more prevalent, suggesting potential negative impact on vaccine efficacy.
ABSTRACT
Objective: To compare humoral and cellular responses to COVID-19 vaccines in 400 consecutive MS patients who were on Ocrelizumab ('OCR') and other disease-modifying therapies ('nonOCR') at the time of vaccination. Background: Peripheral B-cell depletion with anti-CD20 therapies, attenuates humoral responses to vaccines, but less is known about cellular responses. Design/Methods: Consecutive MS patients from NYU MS Care Center were invited to participate if they completed COVID-19 vaccination ≥6 weeks previously. Immune testing included anti-spike RBD antibody (Elecsys Anti-SARS-CoV-2) (Roche Diagnostics);multiepitope bead-based immunoassays (MBI) of antibody-responses to SARS-COV-2 spike proteins (threshold of 'positivity'was chosen as 2 SD below non-OCR mean);T-cell responses to SARSCoV-2 Spike protein using IFNγ enzyme-linked immune-absorbent spot (Invitrogen) and TruCulture (Myriad RBM) assays;high dimensional immunophenotyping;live virus immunofluorescence-based microneutralization assay. Results: Antibody and T cell data was available on 145/355 patients enrolled to date (mean age: 40.0 years;75% female;48% non-white;39% on OCR;12% with prior COVID-19 infection;vaccines: 58% Pfizer/BioNTech, 36% Moderna and 6% Johnson&Johnson;median vaccine-tosample time: 93 (+/-32) days). In OCR, Elecsys Anti-SARS-CoV-2 Ab titers were detected in 30/63 (48%;mean antibody titer in log scale: 1.63) and in non-OCR - in 78/81 (96%, mean Ab titer in log scale: 2.83;p<0.0001). In OCR, antibody response by MBI were detected in 41/57 (72%, mean level in log scale: 3.09) and in non OCR - in 68/72 (94%, mean level in log scale: 4.08;p<0.001). Neutralizing antibodies were detected in 10/42 (38%) of OCR and 24/43 (56%) of non-OCR (p=0.1). T-cell activation based on induced IFNg secretion (TruCulture) was observed in 50/64 (78%) OCR and 43/81 (53%) non-OCR (p=0.002). Conclusions: Preliminary results suggest robust vaccine-specific T-cell immune response to SARS-CoV2 vaccines in B-cell depleted patients, but markedly attenuated antibody responses. Final results of pre-planned multivariable analyses stratified by DMT class and high-dimensional immunophenotyping will be presented.
ABSTRACT
Objective: To examine antibody and T-cell responses to mRNAplatform COVID-19 vaccines in Ocrelizumab-treated MS patients over a 12-month period. Introduction: B-cell depletion with Ocrelizumab attenuates humoral responses to vaccines. The kinetics of humoral and cellular immune responses to COVID-19 vaccines in B-cell depleted MS patients has not been reported. Methods: VIOLA (NCT04843774) is an open-label, observational study enrolling 60 MS patients on Ocrelizumab from NYU and Rocky Mountain at the University of Colorado MS Centers. First vaccine dose occurred ≥2 weeks after ocrelizumab infusion;second-dose ≥8 weeks before the next infusion. Antibody responses to SARS-COV-2 spike proteins were assessed with Elecsys Anti-SARS-CoV-2 (Roche Diagnostics) and multiplex bead-based immunoassays. T-cell responses to SARS-CoV-2 Spike protein were assessed with IFNγ ELISpot (Invitrogen) and TruCulture (Myriad RBM) and high-dimensional immunophenotyping. Samples are collected pre-vaccination and at 4, 12, 24, and 48-weeks post-vaccination. Results: As of 7/15/2021, 52 subjects have been enrolled (39.7±10.0 years;73% female;47% non-white), of whom 47 were fully vaccinated (85% Pfizer, 15% Moderna). Anti-spike RBD antibody (Elecsys Anti-SARS-CoV-2) were available for pre- and post-vaccine timepoints for 15 patients. Pre-vaccine, 1/15 (7%) patients had detectable titers, while at 4-weeks postvaccine, 10/15 (66%) patients had detectible titers (mean for positives: 1189 U/ml;5 patients had positive titers <25 U/ml). T-cell activation based on induced IFNγ secretion (TruCulture) at baseline and 4-week post-vaccine timepoints were available for 13 patients, of whom 12 (92%) were increased (mean pre-vaccine: 24 pg/ml;mean post-vaccine: 366 pg/ml, two-tailed t-test, p=0.0032). Conclusions: This prospective study of humoral and cellular immune responses to COVID-19 vaccines in Ocrelizumab-treated patients will generate data to help guide management of MS patients on anti-CD20 therapies. Early results suggest that 4-weeks post-vaccination nearly all Ocrelizumab-treated MS patients develop T-cell immunity and two-thirds showed evidence of humoral response. Additional 4-week and 12-week post-vaccination data will be presented.
ABSTRACT
Objective: To compare humoral and T-cell responses to COVID- 19 vaccines in 400 MS patients who were on Ocrelizumab ('OCR') v. other disease-modifying therapies ('non-OCR') at the time of vaccination. Introduction: Peripheral B-cell depletion with anti-CD20 therapies attenuates humoral responses to vaccines. Whether immune responses to COVID-19 vaccines differ between B-cell depleted and non-B cell depleted MS patients is not known. Methods: Consecutive MS patients from NYU MS Care Center were invited to participate if they completed COVID-19 vaccination ≥6 weeks previously. Immune testing included anti-spike RBD antibody (Elecsys Anti-SARS-CoV-2) (Roche Diagnostics);multiplex bead-based immunoassays of antibody-responses to SARS-COV-2 spike proteins;T-cell responses to SARS-CoV-2 Spike protein using IFNγ enzyme-linked immune-absorbent spot (Invitrogen) and TruCulture (Myriad RBM) assays;high dimensional immunophenotyping;and live virus immunofluorescencebased microneutralization assay. Results: As of 7/15/2021, 105 MS subjects were enrolled (mean age: 40.5 years;76% female;41% non-white;38% on OCR;12% with prior COVID-19 infection). 95% were fully vaccinated with mRNA vaccines (Pfizer/Moderna);5% - with adenovirus-based vaccine (Johnson&Johnson). Median time from sample collection to last vaccine was 79 days. Positive Elecsys Anti-SARS-CoV-2 Ab titers post-vaccine were detected in 11/37 (30%) in OCR (mean level: 702 U/mL among seropositives) and 54/54 (100%) patients in non-OCR (mean level: 2310 U/mL;p<0.0001). Positive response by multiplex assay (threshold of 'positive' defined as 2 SD below the mean for the non-OCR) were detected in 10/27 (37%) OCR and 29/31 (94%) non-OCR (p<0.00001). T-cell activation based on induced IFNγ secretion (TruCulture) was detected in 20/25 (80%) OCR and 16/19 (84%) non-OCR patients (p=0.71). Conclusions: Preliminary results suggest robust T-cell immune response to SARS-CoV2 vaccines in approximately 80% of both OCR and non-OCR MS patients. Antibody responses were markedly attenuated in OCR compared to non-OCR group. Updated results will be presented.
ABSTRACT
Introduction: Patients with MS and related conditions may be at higher risk for COVID-19 complications due to disease or medication- related factors. Elucidating those factors is imperative for appropriate counseling of patients. Objective: To determine outcomes of COVID-19 in patients with MS and related conditions, and to determine predictors of these outcomes. Aims: To assess impact of COVID-19 in MS patients. Methods: This was a multicenter, observational cohort study of patients with MS or related CNS autoimmune disorders who developed confirmed or highly suspected COVID-19 infection from 2/1/2020 to 12/31/2020. Patients from 5 MS centers in New York City and tri-state area were identified by the treating neurologist. The primary outcome measure was hospitalization status due to COVID-19. Data relating to COVID-19 symptoms, diagnostic testing including SARS-CoV-2 nasopharyngeal swab results (NAAT or antigen testing) and SARS-CoV-2 serologic status as well as data regarding potential risk factors and comorbidities was obtained. Results: Of 474 patients in the study, 63.3% had confirmed COVID-19 infection and 93.9% were diagnosed with an MS phenotype. Mean age was 45±13 (mean±SD) years, 72% were female, and 86% were treated with a DMT at the time of infection. 58 patients (12.2%) were hospitalized. 24 patients (5.1%) were critically ill (requiring ICU care or outcome of death), of which 15 patients (3.2%) died. Higher neurological disability and older age independently predicted hospitalization. There was no association between specific DMTs or DMT classes and COVID-19 severity. 85% (102/120) of patients with known antibody results who were not treated with anti-CD20 therapies were seropositive while only 39.5% (17/43) of patients being treated with anti-CD20 demonstrated seropositivity (p<0.0001). Only 25% (2/8) of patients with PCR-confirmed COVID-19 being treated with anti-CD20 therapies demonstrated seropositivity. Conclusions and relevance: In this multicenter study, neurological disability and older age were independent predictors of hospitalization due to COVID-19. These findings will improve counseling of patients regarding risk from COVID-19. Additionally, the results demonstrate that anti-CD20 therapies significantly blunt humoral responses post-infection, a finding that carries potential implications with regards to natural or vaccine- mediated immunity.