Cellular and Humoral Immunity to SARS‐CoV‐2 Infection in Multiple Sclerosis Patients on Ocrelizumab and Other Disease‐Modifying Therapies: A Multi‐Ethnic Observational Study

Abstract

Objective The objective of this study was to determine the impact of multiple sclerosis (MS) disease‐modifying therapies (DMTs) on the development of cellular and humoral immunity to severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) infection. Methods Patients with MS aged 18 to 60 years were evaluated for anti‐nucleocapsid and anti‐Spike receptor‐binding domain (RBD) antibody with electro‐chemiluminescence immunoassay; antibody responses to Spike protein, RBD, N‐terminal domain with multiepitope bead‐based immunoassays (MBI); live virus immunofluorescence‐based microneutralization assay; T‐cell responses to SARS‐CoV‐2 Spike using TruCulture enzyme‐linked immunosorbent assay (ELISA); and IL‐2 and IFNγ ELISpot assays. Assay results were compared by DMT class. Spearman correlation and multivariate analyses were performed to examine associations between immunologic responses and infection severity. Results Between January 6, 2021, and July 21, 2021, 389 patients with MS were recruited (mean age 40.3 years; 74% women; 62% non‐White). Most common DMTs were ocrelizumab (OCR)—40%; natalizumab —17%, Sphingosine 1‐phosphate receptor (S1P) modulators −12%; and 15% untreated. One hundred seventy‐seven patients (46%) had laboratory evidence of SARS‐CoV‐2 infection; 130 had symptomatic infection, and 47 were asymptomatic. Antibody responses were markedly attenuated in OCR compared with other groups (p ≤0.0001). T‐cell responses (IFNγ) were decreased in S1P (p = 0.03), increased in natalizumab (p <0.001), and similar in other DMTs, including OCR. Cellular and humoral responses were moderately correlated in both OCR (r = 0.45, p = 0.0002) and non‐OCR (r = 0.64, p <0.0001). Immune responses did not differ by race/ethnicity. Coronavirus disease 2019 (COVID‐19) clinical course was mostly non‐severe and similar across DMTs; 7% (9/130) were hospitalized. Interpretation DMTs had differential effects on humoral and cellular immune responses to SARS‐CoV‐2 infection. Immune responses did not correlate with COVID‐19 clinical severity in this relatively young and nondisabled group of patients with MS. ANN NEUROL 2022;91:782–795

Hybrid and vaccine-induced immunity against SARS-CoV-2 in MS patients on different disease-modifying therapies

“…In our study, post-vaccine antibody or cellular responses were similar among Whites, African-Americans, and Hispanic Americans, regardless of whether they were treated with an aCD20 agent or not. This reassuring finding is consistent with what we observed with post-infection immune responses to SARS CoV-2 among unvaccinated patients 42 and reinforces the importance of vaccination across all race/ethnic groups.…”

“…A limitation of our study is the inability to definitively establish past infection in patients who did not undergo PCR testing at the time of symptoms or had an asymptomatic infection and did not have anti-spike antibody testing before vaccination. All of our patients were extensively queried about prior COVID-19 symptoms, exposures, and testing, and most patients had pre-vaccination antibody testing (including 90 patients who underwent such testing as part of our prior study 42 ). Nevertheless, there is a risk of misclassifying some PI patients as NPI exists - especially in aCD20 and S1P patients with attenuated post-infection humoral responses - and this could potentially skew the results towards the null hypothesis, i.e., artificially decrease the differences in immune responses between PI and NPI.…”

“…Patients’ serologic status was assessed using three different methods as described in our prior work 42 . Briefly, we carried out the following tests:…”

Multiple sclerosis disease-modifying therapies and COVID-19 vaccines: a practical review and meta-analysis

“…Evidence on T-cell responses among DMF-treated pwMS was limited to one study with a limited sample size17 (very-low-certainty evidence), which by using AIM assays, did not confirm any effect of DMF on the vaccine-induced responses of CD4+ (OR not measurable) and CD8+ (OR (95% CI): 3.78 (0.18 to 78.38), p=0.39) subpopulations of T-cells. Interferon-gamma release responses were sufficient in DMF-treated pwMS after SARS-CoV-2 infection , suggesting adequate T-cell response 18…”

“…Activation-induced marker (AIM) assay in one study with limited sample size17 (very low-certainty evidence) suggested that GA affects vaccine immunogenicity neither in CD4+ (OR not measurable) nor CD8+ (OR (95% CI): 0.62 (0.04 to 9.00), p=0.72) subpopulations of T-cells. Furthermore, it is worth mentioning that adequate interferon-gamma release responses were present after SARS-CoV-2 infection in GA-treated people,18 suggesting favourable T-cell responses.…”