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Introduction: Transverse myelitis has previously been reported following administration of the Johnson and Johnson (J&J) vaccine against SARS-CoV-2. Brain and peripheral nervous system involvement is less well described. Aims/Methods: We report on a case series of 3 patients who developed neuro-inflammation following administration of the J&J vaccine (Ad26.COV2.S). Spinal cord was involved in all 3 patients, brain - in 2, and peripheral nervous system involvement (facial nerve enhancement, radiculitis) in 2. Result(s): Case 1: A 43F developed progressive gait difficulty and ascending paresthesias in bilateral lower extremities ~4 weeks after J&J COVID-19 vaccination. MRI revealed multiple enhancing cervical and thoracic cord lesions and 1 small enhancing subcortical brain lesion. Workup included extensive serum and CSF testing that was unremarkable, except for matching bands in CSF and serum. 3 months later she developed symptom recurrence with persistent enhancement and enlargement of one cord lesion. Case 2: A 39M developed bilateral ascending numbness, tingling, gait instability, urinary hesitancy/urgency and bilateral peripheral facial weakness 10 days after J&J COVID-19 vaccination. MRI revealed bilateral facial nerve enhancement, patchy cervical and thoracic cord and cauda equina enhancement. CSF revealed lymphocytic pleocytosis and elevated protein, with no oligoclonal bands. Extensive serum/CSF testing was otherwise unremarkable. Patient developed recurrent symptoms during steroid taper 3 months later;MRIs showed persistent enhancement and enlarging lesions. Case 3: A 34F developed blurred vision, body aches, paresthesias and urinary retention 2 weeks after J&J COVID-19 vaccination. MRI revealed large, mostly enhancing fluffy occipital/parietal lesions, cervical lesion, longitudinally extensive thoracic lesion and lumbar nerve root enhancement. CSF revealed neutrophilic pleocytosis and elevated protein. 3 months later she developed new enhancing brain lesions with persistent enhancement in the spine. Conclusion(s): Our case series highlights that central and peripheral nervous system inflammatory involvement without clear alternative explanation can rarely be seen in close temporal relationship to administration of the J&J COVID-19 vaccine. Unusual feature of our cases was clinical/radiographic worsening and persistent enhancement several months after initial presentation.Two patients required second-line immunotherapy for disease control.
ABSTRACT
Background: Patients on OCR have attenuated antibody, but largely intact T-cell responses to COVID-19 vaccination. Little is known about durability of post-vaccine responses in OCR-treated patients. Objective(s): To examine antibody and cellular responses to mRNA COVID-19 vaccines (Pfizer, BioNTech/Moderna) in Ocrelizumab (OCR)-treated MS patients over 24-week period. Method(s): MS patients on OCR were recruited from NYU (New York City) and Rocky Mountain at CU (Denver) MS Centers. Antibody responses to SARS-CoV-2 spike proteins were assessed with multiplex bead-based (MBI) immunoassays, and cellular responses to SARS-CoV-2 Spike protein with ELISpot and activation induced marker (AIM) panel in a Cytek Aurora full-spectrum flow cytometry platform. Data on samples collected pre-vaccine and 4-, 12-, 24-weeks post 2-doses and 4-, 12-weeks post-third dose will be presented. Result(s): 40/61 enrollees (age 38.3+/-10.9;77.5% female;57.5% non-white) had 24-week post-vaccination data and 9 patients had 4-week post 3rd dose data. Antibody response increased from prevaccine level of 972.0 U/mL to 6307.4 U/mL at week-4 (p=0.0002), then decreased to 4633.8 u/mL at week-12 (26% decrease from week-4, p=0.1377), and further to 2878.4 u/mL at week-24 (37% decrease from week-12, p value=0.109). Spikespecific IFNgamma T-cell responses by ELIspot were 125.7 SFU/106 cells pre-vaccine, increased to 362.9 SFU/106 cells at week-4 (p=0.009), then to 511.5 SFU/106 cells at week-12 (40.9% increase relative to 4-week time-point, p=0.8474), and remained elevated at 501.7 SFU/106 cells at week-24 (p=0.7393, 1.9% compared to week 12). 4-week post 3rd dose, Ab level increased to 5094.8 U/mL (189.9% compared to pre-3rd dose, p =0.076) and IFNgamma responses to 1253.3 SFU/106 cells (484.5% increase, p=0.037). Conclusion(s): Antibody responses to 2-series vaccine peaked at 4 weeks and trended downward thereafter, while cellular responses were sustained at 24 weeks. Third-dose resulted in marked increases in both antibody and T-cell responses 4-weeks. Expanded analyses, including in-depth immunophenotyping and 12-week post 3rd vaccination responses will be presented.
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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.
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Objective: To analyze rates of COVID vaccination in patients of different race/ethnicities receiving care at NYU Multiple Sclerosis Comprehensive Care Center (MSCCC) in NYC;and to identify factors associated with non-vaccination status. Background: SARS Cov2 Vaccines are the mainstay of protection against severe COVID-19. Vaccination is especially important in those at higher risk for COVID complications and death, such as minorities, older patients, patients with comorbidities and disability, and those on immunosuppressive therapies. Limited information is available on vaccination rates and reasons for vaccine hesitancy in patients with chronic neurologic conditions, such as MS. Design/Methods: From July 1 2021, COVID-19 vaccination status was systemically ascertained on consecutive patients with MS or related disorders seen at NYU MSCCC by the first author. Data was collected by standard questionnaire, including questions on reasons for nonvaccination and review of medical record. Results: Data from 168 patients were analyzed to 9.30.2021 (ages 8-82, mean 37, SD 16.8, 72% female, 38% white, 28% African American, 13% Hispanic). 132 (78.5%) were vaccinated and 36 (21.4%) were unvaccinated. Among the unvaccinated, 39% were planning to receive vaccine which were delayed because of timing of anti-CD20 therapies or other reasons, 38% indicated delay related to countervailing considerations ('deliberation'), 8.3% expressed disagreement with medical advice to vaccinate ('dissent') and 8.3% expressed concerns about vaccine safety ('distrust'). Vaccination rates were similar among Whites (83%), AA, (72%, p=0.244 compared to whites), and Hispanics (82%, p= 1.00). Conclusions: We observed very high COVID vaccination rates among all race/ethnic groups in our Center, which exceeded local vaccination rates (65% to date). Patients with chronic conditions who attend specialized centers where vaccine importance is emphasized may be more likely to be vaccinated. Reasons of deliberation were the most cited among non-vaccinated and represent a point of intervention. Additional strategies for improving vaccination rates will be discussed.
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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.
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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.
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Introduction: Disease-modifying therapies (DMTs), especially the highly-effective DMTs, improve both short-and long-term outcomes in relapsing MS (RR-MS). Most DMTs are approved for indefinite use, but it is unclear whether they should be used indefinitely, and, if not, what benchmarks are relevant to the decision to stop them. Objectives: 1. To review the studies of DMT discontinuation in RR-MS and to discuss the variables that may be relevant to the decision to discontinue therapy. 2. To discuss the 'pros' and 'cons' of therapy discontinuation in patients deemed to be 'low risk' of disease reactivation and to address the knowledge gaps in this area. Methods: Literature review Results: More than a dozen recent studies have been identified that directly address the question of DMT discontinuation. All of these studies are observational and many are retrospective. Various demographic (e.g. older age), clinical (prolonged disease stability, lower disability rank), radiologic (absence of MRI activity), and laboratory (low Neurofilament light chain) variables have been identified that may be relevant for assessing the risk of post-discontinuation relapse. However, even in the patients with low risk for relapses, it is unknown whether DMT discontinuation may impact PIRA (progression independent of relapse activity), subclinical disease activity, and brain atrophy. The potential negative impact of DMT discontinuation needs to be balanced against the risk of prolonged immunosuppression/immunomodulation in the aging and more disabled patients, especially in the era of COVID-19 as some of the therapies may increase the risk of COVID-19 complications and lower vaccine immune-responsiveness. Conclusions: The available literature does not allow for an unambiguous, evidence-based decision of whether/when it may be safe to stop DMT, but it provides a framework for a rational discussion of the pros and cons of DMT discontinuation. The three ongoing randomized trials of DMT discontinuation are expected to generate higher-level evidence for making this difficult decision.