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
Introduction: Some MS DMTs, such as anti-CD20 antibodies and sphingosine-1-phosphate (S1P) receptor modulators, decrease post-infection and post-vaccination SARS-Cov-2 humoral responses. However, humoral immunity is only one component of the adaptive response, and T cell responses, which may be preserved in anti-CD20 treated patients, play an important role. Objective(s): To characterize SARS-Cov-2 spike specific memory T-cell receptor repertoires in patients with MS and related conditions post-vaccination with mRNA vaccines. Aim(s): To characterize SARS-Cov-2 vaccine-mediated responses for people using MS DMTs. Method(s): Patients without prior COVID-19 infection provided a whole blood sample >3 weeks and <6 months after vaccination with two doses of Pfizer-BioNTech or Moderna mRNA vaccines. Sequencing of the complementary determining region within T-cell receptors (TCRs) was performed. Antigen recognition activates unique TCRs and results in expansion of antigen-specific T-cell clones. Sample TCR sequences were cross-matched with sequences known to react to SARS-CoV-2 using "Multiplex Identification of T-cell Receptor Antigen Specificity (MIRA)", allowing for characterization of SARS-CoV-2-spike-specific TCR frequency (clonal depth) and diversity (clonal breadth). Humoral responses were compared. Result(s): 39 patients were recruited: age 25-77;27 female;37 with MS, 2 with NMO, and 1 with another neuroimmune condition. DMTs included anti-CD20 (N=13), natalizumab (N=9), fumarates (N=8), S1P receptor modulators (N=3), and controls (2 glatiramer acetate, 4 no DMT). Mean time interval between 2nd vaccination dose and TCR testing was 13.3+6.0 weeks. Humoral responses (Roche) were absent in all anti-CD20 and S1P treated patients but preserved in all others. SARS-CoV-2-spikespecific clonal depth and breadth did not differ across all treatment classes except S1P modulators. Despite lack of antibody production, patients treated with anti-CD20 therapies demonstrated comparable TCR depth and breadth to all other groups in univariable assessment. No spike-specific TCRs were found in patients treated with S1P modulators. TCR breadth and depth did not vary with time since vaccination even up to 24 weeks following vaccination. Conclusion(s): TCR repertoires were preserved except for in those treated with S1P receptor modulators.Humoral responses were diminished with both anti-CD20 and S1P DMTs. These findings may help guide counseling of patients with regards to DMT choice.
ABSTRACT
Objective: To present a single-health system retrospective analysis of post-mRNA-based COVID-19 vaccination CNS autoimmunity conducted in the greater New York City area. Background: There have been rare reports associating mRNA-based COVID-19 vaccines with central nervous system (CNS) inflammation. We report a case series of five patients with newonset neurological disorders of immunological origin temporally associated with these vaccines. Design/Methods: Case-series. Results: Five cases of post-vaccination CNS disorders of immune origin were observed within two weeks of inoculation with either the first or second dose of mRNA-based COVID-19 vaccines (Moderna = 3, Pfizer = 2). This includes: Fatal ADEM (n = 1), new-onset NMO (n = 2), new-onset fulminant MS (n = 1), and meningoencephalitis (n = 1). The age of our patients ranged from 27 to 81, and three were female. None of the patients had pre-existing neurological illnesses and one had a pre-existing autoimmune condition (immune thrombocytopenia purpura). New-onset focal neurological symptoms were present in all five patients, including quadriparesis, numbness, diplopia, and encephalopathy. CSF pleocytosis was present in all patients, and three had elevated protein. All but one patient (meningoencephalitis) had contrastenhancing lesions involving either the cerebrum or spinal cord. Both NMO patients had longitudinally extensive transverse lesions involving the central thoracic cord. Aquaporin-4 serum antibody was present in one NMO patients and aquaporin-4 CSF antibody present in the other. All but one patient (fatal ADEM) clinically improved with pulse steroids or plasmapheresis. Conclusions: These are among the emerging cases of CNS immunological events temporally associated with mRNA-based COVID-19 vaccines. These findings should be interpreted with great caution as they neither prove a link nor imply a potential long-term increased risk in postvaccination CNS autoimmunity. Larger prospective studies are needed. The mRNA-based SARS-CoV-2 vaccines should continue to be strongly encouraged given their high efficacy in overcoming this pandemic.
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.