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)

Abstract

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.

Determinants of SARS-CoV-2 IgG response and decay in Canadian healthcare workers: a prospective cohort study

“…Apostolidis et al [32] similarly demonstrated reduced anti-RBD IgG response to mRNA vaccines in a small group of patients with MS on anti-CD20 therapy. A recent registry study of patients with MS showed those treated with anti-CD20 therapies at the time of vaccination had “Abnormally Low” values [33]. In the current study, participants taking tumor necrosis factor-alpha inhibitors (TNFi) had significantly lower anti-RBD IgG as did the three participants prescribed calcineurin inhibitors.…”

Evaluation of SARS-CoV-2 Vaccine-Induced Antibody Responses in Patients with Neuroimmunological Disorders: A Real-World Experience

“…A Danish cohort study indicated an increased risk of COVID-19-related hospitalization and mortality in these patients [ 11 ]. The patients with MS receiving anti-CD20 therapies show severe breakthrough COVID-19 infection [ 12 , 13 ]. Myasthenia gravis (MG) patients also exhibit worse outcomes from COVID-19 infection [ 14 ].…”