Vaccine-breakthrough SARS-CoV-2 infections in people with multiple sclerosis and related conditions: An observational study by the New York COVID-19 Neuro-Immunology Consortium (NYCNIC-2).

BACKGROUND: People with MS (PwMS) and related conditions treated with anti-CD20 and S1P modulating therapies exhibit attenuated immune responses to SARS-CoV-2 vaccines. It remains unclear whether humoral/T-cell responses are valid surrogates for postvaccine immunity. OBJECTIVE: To characterize COVID-19 vaccine-breakthrough infections in this population. METHODS: We conducted a prospective multicenter cohort study of PwMS and related CNS autoimmune conditions with confirmed breakthrough infections. Postvaccination antibody response, disease-modifying therapies (DMTs) at the time of vaccination, and DMT at the time of infection were assessed. RESULTS: Two hundred nine patients had 211 breakthrough infections. Use of anti-CD20 agents at time of infection was associated with increased infection severity (p = 0.0474, odds ratio (OR) = 5.923) for infections during the Omicron surge and demonstrated a trend among the total cohort (p = 0.0533). However, neither use of anti-CD20 agents at the time of vaccination nor postvaccination antibody response was associated with hospitalization risk. Anti-CD20 therapies were relatively overrepresented compared to a similar prevaccination-era COVID-19 cohort. CONCLUSION: Use of anti-CD20 therapies during vaccine breakthrough COVID-19 infection is associated with higher severity. However, the attenuated postvaccination humoral response associated with anti-CD20 therapy use during vaccination may not drive increased infection severity. Further studies are necessary to determine if this attenuated vaccine response may be associated with an increased likelihood of breakthrough infection.

Outcomes of COVID-19 infection in multiple sclerosis and related conditions: One-year pandemic experience of the multicenter New York COVID-19 Neuroimmunology Consortium (NYCNIC).

OBJECTIVE: To determine outcomes of COVID-19 in patients with Multiple Sclerosis (MS) and related conditions, and to determine predictors of these outcomes. 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. MAIN OUTCOME AND MEASURE: The primary outcome measure was hospitalization status due to COVID-19. Severity of infection was measured using a 4-point ordinal scale: 1. home care; 2. hospitalization without mechanical ventilation; 3. hospitalization and mechanical ventilation, and 4. death. 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. 85% (102/120) of patients with known antibody results not treated with anti-CD20 therapies were seropositive while only 39.5% (17/43) of patients 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: Neurological disability and older age independently predicted hospitalization due to COVID-19. Additionally, the results demonstrate that anti-CD20 therapies significantly blunt humoral responses post-infection, a finding that carries implications with regards to natural or vaccine-mediated immunity.