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: Prior studies in multiple sclerosis (MS) suggest the potential for reduced humoral response to vaccines among patients on disease modifying therapies (DMTs). Reduced antibody responses to SARS-CoV2 vaccination have been reported in other immunosuppressed populations such as organ transplant recipients. Limited data are available in people with MS. Objectives:To evaluate antibody responses to SARS-CoV2 vaccination in MS patients. Aims: Determine differential response by DMT, and identify other factors predictive of antibody response in people with MS. Methods: MS clinicians obtained commercially available SARSCoV2 antibody testing after a completed vaccine series beginning March 2021. Deidentified data were retrospectively abstracted from clinical charts with IRB exemption. All statistical analyses were performed using SAS. Results: We present 155 individuals with MS who received a SARS-CoV2 vaccine (58% Pfizer, 39% Moderna, and 3% Johnson & Johnson). 71% had a positive antibody response postvaccination. The median time from final vaccine date to antibody test was 34 days (8-106 days), this was not significantly different across antibody result. 10.3% (n=16) were not on any DMT at the time of vaccination, 100% of whom had positive antibodies. 5.8% (n=9) were on sphingosine-1 phosphate (S1P) modulators, of whom 89%(n=8) had positive antibodies. 41.9% (n=65) were on anti-CD20 therapies, of whom 33%(n=22) had positive antibodies. Anti-CD20 therapy was significantly associated with lower odds of antibody positivity (OR=.009, 95% CI .002-.042). Prior documented Covid-19 infection was significantly associated with higher odds of antibody positivity (OR=2.94 95% CI 1.446-4.147) in individuals on anti-CD20 therapies. Additionally, longer duration of anti-CD20 therapy was associated with lower odds of antibody positivity. Sex and age were not significant predictors of antibody positivity. Conclusions: All MS patients not on DMT had positive antibodies after SARS-CoV2 vaccine. The majority of individuals on S1P modulators developed a humoral response to the vaccine, while the majority of individuals on anti-CD20 therapies did not. Prior history of Covid-19 and shorter duration of therapy were predictive of humoral response among patients on anti-CD20 therapies. Further immunologic studies to determine the consequences of these observations are needed.
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.