Impact of brain volume on coronavirus disease of 2019 severity and subsequent cognitive decline in patients with multiple sclerosis

J Neurol Sci. 2025 Aug 15:475:123552. doi: 10.1016/j.jns.2025.123552. Epub 2025 May 29.

Abstract

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.

Keywords: Brain volume loss; COVID-19; Multiple sclerosis; Outcome; SDMT.

MeSH terms

  • Adult
  • Belgium
  • Brain* / diagnostic imaging
  • Brain* / pathology
  • COVID-19* / complications
  • COVID-19* / diagnostic imaging
  • Cognitive Dysfunction* / diagnostic imaging
  • Cognitive Dysfunction* / etiology
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis* / complications
  • Multiple Sclerosis* / diagnostic imaging
  • Multiple Sclerosis* / pathology
  • Multiple Sclerosis* / psychology
  • Organ Size
  • SARS-CoV-2
  • Severity of Illness Index