BACKGROUND: Clinical disability is among the risk factors of a more severe coronavirus disease of 2019 (COVID-19) course in patients with multiple sclerosis (PwMS), but might provide an insensitive reflection of actual tissue pathology. Brain volume loss has emerged as a magnetic resonance imaging (MRI) proxy of neurodegeneration in PwMS. Our main objective was to investigate whether brain volume predicts COVID-19 severity in PwMS. METHODS: Clinical data of PwMS followed at the Belgian National Multiple Sclerosis (MS) Center in Melsbroek are collected in a local database in case of COVID-19 diagnosis. One hundred ninety-eight unique PwMS with a suitable 3D brain MRI available, conducted maximally 24 months before their COVID-19 infection, were included. RESULTS: An unfavorable outcome due to COVID-19 was noted in fourteen PwMS (hospitalization: 7.1 %, death: 0.5 %). Neither global nor regional normalized brain volumes predicted COVID-19 severity. Similar results were obtained in patients fulfilling the criteria for benign MS. Being unprotected by vaccination was the only variable significantly associated with a poor COVID-19 outcome (OR 3.7; CI 1.2-10.2). We observed a significant worsening of Symbol Digit Modality Test performance in PwMS with the lowest (Q4) whole brain volume, as compared to those with the highest (Q1) (2.2 ± 8.5 versus -1.2 ± 9.1; P = 0.037). CONCLUSION: Brain volume does not predict COVID-19 outcome in PwMS, including those with benign MS. Unvaccinated individuals remain susceptible to developing a more severe infection. PwMS with the most profound pre-existing brain atrophy may be at risk for cognitive deterioration after COVID-19.

Department of Neurology and Center of Clinical Neuroscience 1st Faculty of Medicine Charles University Prague and General University Hospital Prague Czechia

Nationaal Multiple Sclerose Centrum Melsbroek Belgium

Nationaal Multiple Sclerose Centrum Melsbroek Belgium; Vrije Universiteit Brussel Center for Neurosciences NEUR and or AIMS Research Groups Brussels Belgium; Universitair Ziekenhuis Brussel Department of Neurology Brussels Belgium

Vrije Universiteit Brussel Center for Neurosciences NEUR and or AIMS Research Groups Brussels Belgium; Universitair Ziekenhuis Brussel Department of Neurology Brussels Belgium; Icometrix Leuven Belgium

Vrije Universiteit Brussel Center for Neurosciences NEUR and or AIMS Research Groups Brussels Belgium; Universitair Ziekenhuis Brussel Department of Physical Medicine and Rehabilitation Brussels Belgium

Vrije Universiteit Brussel Center for Neurosciences NEUR and or AIMS Research Groups Brussels Belgium; Vrije Universiteit Brussel ETRO Department Brussels Belgium

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