SARS-CoV-2 Omicron Breakthrough Infectios in Patients with Multiple Sclerosis

SARS-COV-2 omicron breakthrough infections are more prevalent in patients with MS on anti-CD20 therapies and S1PR modulators compared with other patients with MS, correlating with decreased humoral responses after vaccination, suggests a new study from Amsterdam.

The COVID-19 pandemic is continuously changing due to ongoing mutations of SARS-CoV-2. Although omicron variants mostly induce less severe COVID-19 compared with the delta variant due to differences in pathogenesis, transmissibility of these variants is higher despite vaccination.

In patients with multiple sclerosis (MS), anti-CD20 therapies (eg, ocrelizumab, rituximab) and sphingosine-1 phosphate receptor (S1PR) modulators (eg, fingolimod and ozanimod) are associated with decreased humoral immune responses after SARS-CoV-2 vaccination. Patients with MS treated with anti-CD20 therapies also have increased risks of severe COVID-19, at least for SARS-CoV-2 variants up to delta. Despite both reduced humoral and cellular responses, treatment with S1PR modulators has not been associated with increased risks of severe COVID-19.

In this study by Kempen et al, omicron breakthrough infections were more prevalent in patients with MS on anti-CD20 therapies and S1PR modulators compared with patients on natalizumab or without DMTs. Lower antibody titres after vaccination was a risk factor for an omicron breakthrough infection. Most omicron breakthrough infections described in this cohort were mild confirming that omicron breakthrough infections are less severe compared with other variants, which is in agreement with other studies.

Interestingly, while most S1PR-treated patients had limited effect of the first booster vaccination on humoral responses, a clear increase in antibody titres was observed after infection. In anti-CD20-treated patients, humoral responses both after booster vaccination and infection were low. We speculate that this discrepancy may indicate that patients on S1PR modulators may benefit from repeated (vaccination or infection) exposures to develop a humoral response. This has also been observed in mycophenolate mofetil-treated patients who started to show higher humoral response only after three vaccinations. Alternatively, this discrepancy may indicate that the immunological pathways activated during infection are affected less by S1PR modulators compared with pathways activated after vaccination, which could also explain why patients on S1PR modulators do not have an increased risk for severe course of COVID-19.

The authors concluded that SARS-COV-2 omicron breakthrough infections were more prevalent in vaccinated patients with MS on anti-CD20 therapies and S1PR modulators compared with other patients with MS, which was likely due to decreased humoral responses after vaccination. Antibody titres after infection increased in S1PR modulator-treated patients but not in patients on anti-CD20 therapies suggesting either a benefit of repeated antigen exposure or that infection-induced responses are affected less in S1PR modulator-treated patients.

Reference

SARS-CoV-2 omicron breakthrough infections in patients with multiple sclerosis Zoé L E van Kempen, Eileen W Stalman, Maurice Steenhuis, et al Journal of Neurology, Neurosurgery and Psychiatry http://dx.doi.org/10.1136/jnnp-2022-330100