Relationship of SARS-CoV-2 spike antibody response to lymphocyte subsets and timepoint of ocrelizumab dosing in multiple sclerosis patients

Introduction: B-cell depletion agents such as ocrelizumab (OCR) are highly effective treatment options for active multiple sclerosis (MS). However, it is known, that B-cell depletion can be associated with a lower antibody response after SARS-CoV-2 immunisation. The individual factors that contribute to the immune response are less understood. Objective, aims and method: Here, we retrospectively analysed single centre, structured clinical routine SARS-CoV-2 spike antibody response data after completion of basic immunization in 42 consecutive included MS patients under OCR therapy who are standardised investigated in our outpatient clinic. In particular, we examined treatment duration, previous immunotherapies, immunoglobulin levels, and lymphocyte subsets includingB-cell and lymphocyte countsas well as time interval between last OCR treatment and SARS-CoV-2 vaccination as influencing factors in patients with and without SARS-CoV-2 spike antibody response. All patients gave written ethical consent. Result(s): 42 MS patients were identified and included (38 RRMS, 4 PPMS patients, 28 females, median age: 42.0 years, median disease duration: 11.2 years), which are treated with OCR (median treatment duration: 2.0 years. 29 patients (69.1 %) and showed no SARS-CoV-2 spike antibody response. Median IgG and IgM levels and B-cell counts were marginally lower in patients without SARS-CoV-2 spike antibody response.The time interval between last OCR administration and first vaccination, however, was significantly longer (median = 2.8 [0.3;5.1] months vs median = 4.0 [2.9;5.7] months [min;max]) in patients with positive SARS-CoV-2 spike antibody response. Antibody response was not associated with age, sex, number of previous immunotherapies and duration of OCR therapy. Further data regarding lymphocyte subsets will be presented during the ECTRIMS congress. Conclusion(s): As an influencing factor the time interval between last OCR dosing and vaccination affects SARS-CoV-2 spike antibody response to vaccination. Our results support previous findings and help to advise patients for the best timepoint of vaccination under B-cell depleting therapies. We identified the time interval between OCR dosing and vaccination date as the main influencing factor after SARS-CoV-2 vaccination. Against expectation, the duration of ocrelizumab therapy and the number of previous therapies do not seem to be an influencing factor.

Is the clinical onset of demyelinating CNS disease after COVID-19 vaccination a denovo disease or the clinical manifestation of a preexisting condition?

Introduction: Within the last year, cases with multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) associated with SARS-CoV-2-vaccination have been published worldwide. It remains unclear, whether the clinical onset in these patients is either causal and denovo or, alternatively, the initial manifestation of a preexisting demyelinating disease and thus a coincidence in time. Objective(s): We therefore compared clinical, laboratory and neuroimaging data of MS patients with clinical onset after SARSCoV- 2-vaccination (MSpostvacc) with a MS cohort without association to the vaccination (MSreference), respectively, with a single case of MOGAD following SARS-CoV-2-vaccination (MOGADpostvacc). Aim(s): To determine whether there is evidence of a preexisting, chronic inflammatory disease at clinical onset in MSpostvacc and MOGADpostvacc patients. Method(s): We included patients with clinical manifestation of MS or MOGAD <=30 days following SARS-CoV-2-vaccination and analysed clinical, cerebrospinal fluid (CSF), magnetic resonance imaging (MRI) and optical coherence tomography (OCT) data. The MSpostvacc characteristics were compared to an age- and gender- matched MS cohort recruited at our neuroimmunological outpatient clinic. Result(s): In 5 patients (3 female) the initial diagnosis of MS was made in association to SARS-CoV-2-vaccination (4 after BNT162b2 vaccine;mean clinical onset after 8 days). CSFspecific oligoclonal bands and indications of a preexisting inflammatory process were detectable on MRI and OCT in all MSpostvacc patients. Their analysed parameters (clinical, CSF, MRI, OCT) were assimilable to those of the MSreference cohort. One woman with onset of MOGAD after ChAdOx1 nCoV-19 vaccination was identified. Here, CSF analysis revealed an acute inflammatory profile (106 cells per mul;no CSF-specific OCB). After treatment with high-dose corticosteroids, the initial cerebral and cerebellar lesions resolved on follow-up MRI. Conclusion(s): Since we found CSF-specific oligoclonal bands, chronic inflammatory lesions on MRI and retinal neuroaxonal damage on OCT a denovo disease seems unlikely for the MSpostvacc cohort. Our data point to the hypothesis that the MSpostvacc patients described had a subclinical disease that first manifested coincidentally with the SARS-CoV-2-vaccination. However, this cannot be assumed for the MOGADpostvacc patient.

Clinical onset of CNS demyelinating disease after COVID-19 vaccination: denovo disease?

BACKGROUND: Clinical onset of multiple sclerosis (MSpostvacc) and myelin-oligodendrocyte-glycoprotein-antibody-associated disease (MOGADpostvacc) has been reported in association with SARS-CoV-2-vaccination. There is uncertainty as to whether this is causality (denovo disease) or temporal coincidence (manifestation of a preexisting, subclinical neuroinflammation). OBJECTIVES: Comparing the clinical characteristics of MSpostvacc-patients versus patients with MS (PwMS) whose clinical onset occurred independently of vaccination (MSreference). METHODS: Consecutive patients with clinical onset ≤30 days after SARS-CoV-2-vaccination were included. Clinical data, cerebrospinal fluid (CSF) parameters and magnetic resonance imaging (MRI) as well as optical coherence tomography (OCT) data were compared to an age- and sex-matched MSreference-cohort. RESULTS: We identified 5 MSpostvacc and 1 MOGADpostvacc patients who developed their clinical onset ≤ 30 days after SARS-CoV-2-vaccination. Clinical characteristics, CSF, MRI and OCT parameters from MSpostvacc patients were comparable to the MSreference cohort and showed evidence of preexisting subclinical CNS disease. The single case with MOGADpostvacc clearly differed from PwMS in higher CSF cell counts, remission of MRI lesions during follow-up, and absence of oligoclonal bands. CONCLUSIONS: Our case series indicates that MSpostvacc patients showed a rather typical initial manifestation in temporal association with SARS-CoV-2-vaccination and harbored preexisting subclinical neuroinflammation. This argues against the denovo development of MS in this cohort.

Clinical onset of CNS demyelinating disease after COVID-19 vaccination: denovo disease?

Background Clinical onset of multiple sclerosis (MSpostvacc) and myelin-oligodendrocyte-glycoprotein-antibody-associated disease (MOGADpostvacc) has been reported in association with SARS-CoV-2-vaccination. There is uncertainty as to whether this is causality (denovo disease) or temporal coincidence (manifestation of a preexisting, subclinical neuroinflammation). Objectives Comparing the clinical characteristics of MSpostvacc-patients versus patients with MS (PwMS) whose clinical onset occurred independently of vaccination (MSreference). Methods Consecutive Patients with clinical onset ≤30 days after SARS-CoV-2-vaccination were included. Clinical data, cerebrospinal fluid (CSF) parameters and magnetic resonance imaging (MRI) as well as optical coherence tomography (OCT) data were compared to an age- and sex-matched MSreferencecohort. Results We identified 5 MSpostvacc and 1 MOGADpostvacc patients who developed their clinical onset ≤ 30 days after SARS-CoV-2-vaccination. Clinical characteristics, CSF, MRI and OCT parameters from MSpostvacc patients were comparable to the MSreference cohort and showed evidence of preexisting subclinical CNS disease. The single case with MOGADpostvacc clearly differed from PwMS in higher CSF cell counts, remission of MRI lesions during follow-up, and absence of oligoclonal bands. Conclusions Our case series indicates that MSpostvacc patients showed a rather typical initial manifestation in temporal association with SARS-CoV-2-vaccination and harbored preexisting subclinical neuroinflammation. This argues against the denovo development of MS in this cohort.