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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.
Kister, Ilya; Patskovsky, Yury; Curtin, Ryan; Pei, Jinglan; Perdomo, Katherine; Rimler, Zoe; Voloshyna, Iryna; Samanovic, Marie I; Cornelius, Amber R; Velmurugu, Yogambigai; Nyovanie, Samantha; Kim, Joseph J; Tardio, Ethan; Bacon, Tamar E; Zhovtis Ryerson, Lana; Raut, Pranil; Pedotti, Rosetta; Hawker, Kathleen; Raposo, Catarina; Priest, Jessica; Cabatingan, Mark; Winger, Ryan C; Mulligan, Mark J; Krogsgaard, Michelle; Silverman, Gregg J.
  • Kister I; Department of Neurology, NYU Multiple Sclerosis Comprehensive Care Center, New York University Grossman School of Medicine, New York, NY.
  • Patskovsky Y; Department of Pathology, Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY.
  • Curtin R; Department of Pathology, Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY.
  • Pei J; Genentech, Inc., South San Francisco, CA.
  • Perdomo K; Department of Neurology, NYU Multiple Sclerosis Comprehensive Care Center, New York University Grossman School of Medicine, New York, NY.
  • Rimler Z; Department of Neurology, NYU Multiple Sclerosis Comprehensive Care Center, New York University Grossman School of Medicine, New York, NY.
  • Voloshyna I; Department of Pathology, Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY.
  • Samanovic MI; Department of Medicine, NYU Langone Vaccine Center, NYU Grossman School of Medicine, New York, NY.
  • Cornelius AR; Department of Medicine, NYU Langone Vaccine Center, NYU Grossman School of Medicine, New York, NY.
  • Velmurugu Y; Department of Pathology, Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY.
  • Nyovanie S; Department of Pathology, Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY.
  • Kim JJ; Department of Pathology, Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY.
  • Tardio E; Department of Pathology, Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY.
  • Bacon TE; Department of Neurology, NYU Multiple Sclerosis Comprehensive Care Center, New York University Grossman School of Medicine, New York, NY.
  • Zhovtis Ryerson L; Department of Neurology, NYU Multiple Sclerosis Comprehensive Care Center, New York University Grossman School of Medicine, New York, NY.
  • Raut P; Genentech, Inc., South San Francisco, CA.
  • Pedotti R; F. Hoffmann-La Roche Ltd, Basel, Switzerland.
  • Hawker K; Genentech, Inc., South San Francisco, CA.
  • Raposo C; F. Hoffmann-La Roche Ltd, Basel, Switzerland.
  • Priest J; Genentech, Inc., South San Francisco, CA.
  • Cabatingan M; Genentech, Inc., South San Francisco, CA.
  • Winger RC; Genentech, Inc., South San Francisco, CA.
  • Mulligan MJ; Department of Medicine, NYU Langone Vaccine Center, NYU Grossman School of Medicine, New York, NY.
  • Krogsgaard M; Department of Pathology, Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY.
  • Silverman GJ; Division of Rheumatology, Department of Medicine, New York University Grossman School of Medicine, New York, NY.
Ann Neurol ; 91(6): 782-795, 2022 06.
Article in English | MEDLINE | ID: covidwho-1739116
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;91782-795.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 / Multiple Sclerosis Type of study: Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Topics: Variants Limits: Adult / Female / Humans / Male Language: English Journal: Ann Neurol Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 / Multiple Sclerosis Type of study: Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Topics: Variants Limits: Adult / Female / Humans / Male Language: English Journal: Ann Neurol Year: 2022 Document Type: Article