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

Abstract

IntroductionGiven 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.MethodsWe 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.ResultsWe 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.DiscussionAdditional 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.

Long-Term Observation of SARS-CoV-2 Vaccination Response upon High Efficacy Treatment in Multiple Sclerosis—A Real-World Scenario

“…In our study, repetitive vaccination or infection with SARS-CoV-2 upon anti-CD20 treatment resulted in only a slight increase in the anti-spike protein response. This is controversially discussed among a few reports, with some reporting improved and some describing sustained low antibody levels in pwMS under anti-CD20 therapy [ 34 , 35 , 41 , 42 , 43 , 44 ]. The minor increase in the number of pwMS who seroconvert under anti-CD20, and the greater proportion of those who do the same under ns-S1P, mirrors the vaccination response.…”

Drugs Targeting CD20 in Multiple Sclerosis: Pharmacology, Efficacy, Safety, and Tolerability

“…In one study, only 25% of patients treated with ocrelizumab (25%) generated detectable protective IgG levels 8 weeks following COVID-19 mRNA vaccination, and this response was not maintained 24 or 36 weeks post vaccination [ 64 ]. However, in another study, a sequential increase in the proportion of patients with antibody response after each booster dose was found, and, after booster vaccinations with four doses, 90% of patients treated with ocrelizumab developed an antibody response [ 65 ]. In a study comparing antibody response on rituximab and ocrelizumab, both groups demonstrated reduced antibody levels compared to untreated patients (ocrelizumab 201-fold decrease and rituximab 20-fold decrease) [ 66 ].…”

Risk of COVID-19 in people with multiple sclerosis who are seronegative following vaccination

“…10 However, these studies did not measure serology in all participants, instead focussing on clinical infection. Lack of seroconversion after initial vaccination, especially in the context of anti-CD20 and S1P treatments, has been reported to be associated with increased rates of COVID-19 by some, [11][12][13][14] but not all, 15 groups. The differential protective effect of vaccination against severe infections in those exposed to DMT associated with lower seroconversion is less clear, given the relative rarity of severe infection in the post-vaccination era.…”