AUTHOR=Räuber Saskia , Willison Alice , Korsen Melanie , Kölsche Tristan , Golombeck Kristin S. , Plaack Benedikt , Schüller Julia , Huntemann Niklas , Rolfes Leoni , Schroeter Christina B. , Nelke Christopher , Regner-Nelke Liesa , Förster Moritz , Ringelstein Marius , Barnett Michael Harry , Hartung Hans-Peter , Aktas Orhan , Albrecht Philipp , Ruck Tobias , Melzer Nico , Meuth Sven G. , Kremer David TITLE=Vaccine-based clinical protection against SARS-CoV-2 infection and the humoral immune response: A 1-year follow-up study of patients with multiple sclerosis receiving ocrelizumab JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1037214 DOI=10.3389/fimmu.2022.1037214 ISSN=1664-3224 ABSTRACT=Introduction

Given the varying severity of coronavirus disease 2019 (COVID-19) and the rapid spread of Severe-Acute-Respiratory-Syndrome-Corona-Virus-2 (SARS-CoV-2), vaccine-mediated protection of particularly vulnerable individuals has gained increasing attention during the course of the pandemic.

Methods

We performed a 1-year follow-up study of 51 ocrelizumab-treated patients with multiple sclerosis (OCR-pwMS) who received COVID-19 vaccination in 2021. We retrospectively identified 37 additional OCR-pwMS, 42 pwMS receiving natalizumab, 27 pwMS receiving sphingosine 1-phosphate receptor modulators, 59 pwMS without a disease-modifying therapy, and 61 controls without MS (HC). In OCR-pwMS, anti-SARS-CoV-2(S)-antibody titers were measured prior to the first and after the second, third, and fourth vaccine doses (pv2/3/4). The SARS-CoV-2-specific T cell response was analyzed pv2. SARS-CoV-2 infection status, COVID-19 disease severity, and vaccination-related adverse events were assessed in all pwMS and HC.

Results

We found a pronounced and increasing anti-SARS-CoV-2(S)-antibody response after COVID-19 booster vaccinations in OCR-pwMS (pv2: 30.4%, pv3: 56.5%, and pv4 90.0% were antibody positive). More than one third of OCR-pwMS without detectable antibodies pv2 developed positive antibodies pv3. 23.5% of OCR-pwMS had a confirmed SARS-CoV-2 infection, of which 84.2% were symptomatic. Infection rates were comparable between OCR-pwMS and control groups. None of the pwMS had severe COVID-19. An attenuated humoral immune response was not associated with a higher risk of SARS-CoV-2 infection.

Discussion

Additional COVID-19 vaccinations can boost the humoral immune response in OCR-pwMS and improve clinical protection against COVID-19. Vaccines effectively protect even OCR-pwMS without a detectable COVID-19 specific humoral immune response, indicating compensatory, e.g., T cell-mediated immunological mechanisms.