| Cross-sectional case-control studies  

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

To determine the impact of MS disease-modifying therapies (DMTs) on the development of cellular and humoral immunity to SARS-CoV-2 infection.

MS patients aged 18-60 were evaluated for anti-nucleocapsid and anti-Spike 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 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. Between 1/6/2021 and 7/21/2021, 389 MS patients were recruited (mean age 40.3 years; 74% female; 62% non-White). Most common DMTs were ocrelizumab (OCR) – 40%; natalizumab – 17%, Sphingosine 1-phosphate receptor (S1P) modulators -12%; and 15% untreated. 177 patients (46%) had laboratory evidence of SARS-CoV-2 infection; 130 had symptomatic infection, 47 – asymptomatic. Antibody responses were markedly attenuated in OCR compared to 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. COVID-19 clinical course was mostly non-severe and similar across DMTs; 7% (9/130) were hospitalized. The authors concluded that 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 non-disabled group of MS patients.
Ilya Kister, Yury Patskovsky, Ryan Curtin, Jinglan Pei, Katherine Perdomo, Zoe Rimler, Iryna Voloshyna, Marie I. Samanovic, Amber R. Cornelius, Yogambigai Velmurugu, Samantha Nyovanie, Joseph Kim, Ethan Tardio, Tamar E. Bacon, Lana Zhovtis Ryerson, Pranil Raut, Pedotti Rosetta, Kathleen Hawker, Catarina Raposo, Jessica Priest, Mark Cabatingan, Ryan C. Winger, Mark J. Mulligan, Michelle Krogsgaard, Gregg J. Silverman. 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. Annals of Neurology. First published: 15 March 2022

https://doi.org/10.1002/ana.26346