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

  1. Ilya Kister
  2. Yury Patskovsky
  3. Ryan Curtin
  4. Jinglan Pei
  5. Katherine Perdomo
  6. Zoe Rimler
  7. Iryna Voloshyna
  8. Marie I. Samanovic
  9. Amber R. Cornelius
  10. Yogambigai Velmurugu
  11. Samantha Nyovanie
  12. Joseph Kim
  13. Ethan Tardio
  14. Tamar E. Bacon
  15. Lana Zhovtis Ryerson
  16. Pranil Raut
  17. Rosetta Pedotti
  18. Kathleen Hawker
  19. Catarina Raposo
  20. Jessica Priest
  21. Mark Cabatingan
  22. Ryan C. Winger
  23. Mark J. Mulligan
  24. Michelle Krogsgaard
  25. Gregg J. Silverman
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Abstract

Objective

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

Methods

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.

Results

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≤ 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.

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 non-disabled group of MS patients.

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