Omicron breakthrough disease activity in the Swiss multiple sclerosis cohort study

ABSTRACT

Introduction: In patients with Multiple Sclerosis (pwMS), specific disease modifying treatments (DMTs) may compromise immune response following SARS-CoV-2 vaccination. Limited information is available, whether levels of anti-SARS-CoV-2 antibodies are linked to the risk of breakthrough infections in pwMS. Objective(s) To determine the rate of Omicron breakthrough infection and severity of COVID-19 in a cohort of MS patients treated with different DMTs and to estimate the impact of SARSCoV- 2-specific antibody level on breakthrough infection risk. Method(s) This study is nested within the Swiss MS Cohort, a nationwide multicenter study that has recruited 1585 pwMS. Patients who received two doses of SARS-CoV-2 vaccines before Omicron became the dominant variant in Switzerland on Dec-15, 2021 and had a follow-up thereafter were included. Data on SARS-CoV-2 infections, severity of COVID-19 according to the WHO scale and SARS-CoV-2 vaccines were collected by questionnaires. Anti-SARS-CoV-2-S antibody levels were measured after the second vaccine dose. Incidence of infections grouped by antibody level after second vaccination was visualized using Kaplan-Meier curves. Cox regression models were used to estimate the impact of antibody levels on the hazard of breakthrough infection during follow-up. Result(s) 242 pwMS (median age 49y [39,58], 162 (67%) female, 36 (15%) with progressive disease, median EDSS 2.5 [1.5,4.0]) were included. 22 (9%) had SARS-CoV-2 infection and 137 (57%) at least one additional vaccine dose prior to Omicron start. Since then, 57 breakthrough infections were reported. Severity of breakthrough disease on WHO scale ranged from 1-10 7 were asymptomatic, 46 were symptomatic as outpatients, 3 were hospitalized and 1 died. Patients with antibody levels >150U/ml (n = 95, 39%) after second vaccination had a 64% reduced risk for Omicron breakthrough-infection compared to patients with antibody levels <0.7U/ml (n = 81, 33%) (HR 0.36, 95%CI=0.18- 0.71, p<0.01). This effect was maintained after adjustment for DMT at vaccination and time since second vaccination Conclusion(s) Humoral immune response after second SARSCoV- 2 vaccination is associated with Omicron breakthrough infection rate, a finding contrasting general populations, where antibody levels seem to have little impact on protecting from Omicron infection. Most breakthrough infections in our cohort were mild. Analyses on the effect of booster vaccinations on serology and infection rates will follow.