Blunted Post-COVID-19 Humoral Immunity in Patients With CNS Demyelinating Disorders on Anti-CD20 Treatments

Abstract

With unclear characteristics of post-infection and post-vaccination immunity, the multiple sclerosis community lacks evidence to guide patients on their continued coronavirus disease 2019 (COVID-19) infection risk. As disease modifying treatments all modulate the immune system, we expect their use to alter acquired immunity to COVID-19, but the specific impact of individual treatments is unclear. To address this, we analyzed the patient and COVID-19 specific characteristics associated with post-infection humoral immunity in 58 patients with central nervous system (CNS) demyelinating disorders in the Boston metropolitan area. Univariate analysis of variance was performed using Mann Whitney U test for continuous variables, and Chi Square or Fisher Exact test for nominal variables. Univariate and stepwise multivariate nominal logistic regression identified clinical characteristics associated with COVID-19 specific nucleocapsid IgG antibody formation post-infection. Our cohort demonstrated a 42% post-infection seropositive rate with a significantly higher rate observed with shorter duration between infection and antibody collection and use of natalizumab over no/other treatment. Use of anti-CD20 treatments compared to no/other treatment was associated with a significantly lower rate of seropositivity. However, only shorter duration between infection and antibody collection as well as use of no/other treatment compared to anti-CD20 treatment were found to be independently associated with increased likelihood of post-infection seropositivity. Additionally, we demonstrate durability of antibody response up to 9 months in a small subset of patients. Thus, our data supports that patients with CNS demyelinating disorders regardless of DMT are able to form a measurable antibody response after COVID-19 infection, and that patients on anti-CD20 treatments form less robust immunity after COVID-19 infection.

Keywords: COVID-19 antibody; anti-CD20 monoclonal antibodies; disease modifying therapy; multiple sclerosis; natalizumab.

Figure 1

Post-infection COVID-19 IgG prevalence by DMT. Prevalence of post-infection COVID-19 IgG antibody positivity was grouped by DMT type. All DMTs were considered individual groups with the exception of the anti-CD20 monoclonal antibodies rituximab and ocrelizumab. DMT type is indicated on the X axis and COVID-19 IgG seroprevalence is on the Y axis. As shown in Table 1, there was a significantly lower rate of seroprevalence in patients on anti-CD20 treatments and significantly higher rate of seroprevalence in patients on natalizumab via Chi Square or Fisher Exact test compared to patients on no/other DMTs. The number of patients within the seropositive group on each treatment were none = 3, anti-CD20 = 5, natalizumab = 6, fingolimod = 1, dimethyl fumarate = 5, teriflunomide = 1, glatiramer acetate = 3, and interferon-beta = 0. The number of patients within the seronegative group on each treatment were none = 4, anti-CD20 = 19, natalizumab = 1, fingolimod = 2, dimethyl fumarate = 2, teriflunomide = 1, glatiramer acetate = 4, and interferon-beta = 1. Significance (p < 0.05) is indicated by *.

Figure 2

Univariate and multivariate analyses of factors impacting seropositivity. Univariate and multivariate nominal logistic regression analyses were performed on patient characteristics, prior COVID-19 infection severity, and selected lab values based upon COVID-19 IgG antibody values (n = 24 for seropositive, n = 34 for seronegative). (A) Univariate logistic regression was performed on characteristics of cohort. Odds ratios with 95% confidence intervals of all significant factors are listed in the table to the left. Significant correlations are indicated by bold font and *. Longer duration between COVID-19 infection and antibody collection as well as use of anti-CD20 treatment (rituximab or ocrelizumab) compared to no/other DMT were found to be predictive of negative post-infection COVID-19 IgG, whereas use of natalizumab vs. no/other DMT was found to be predictive of positive COVID-19 IgG. (B) Stepwise multivariate logistic regression utilizing Akaike information criteria was performed using significant factors in univariate analysis. Odds ratios with 95% confidence intervals of all factors evaluated are shown in the table (left) and figure (right). Only longer duration between COVID-19 infection and antibody collection and use of anti-CD20 treatment were found to independently decrease likelihood of seropositivity.