Shared genetics and causal associations between COVID-19 and multiple sclerosis.

Area of Science:

• Neuroimmunology
• Genetics
• Infectious Diseases

Background:

• COVID-19 (Coronavirus disease 2019) neuroinflammation impacts brain function.
• Pre-existing neurological conditions like multiple sclerosis (MS) may increase COVID-19 severity.
• Understanding the bidirectional relationship between MS and COVID-19 is crucial for patient care.

Purpose of the Study:

• To investigate the potential causal associations between multiple sclerosis and COVID-19 outcomes using Mendelian randomization.
• To identify shared genetic risk factors and molecular pathways connecting MS and COVID-19 hospitalization.

Main Methods:

• Mendelian randomization (MR) analysis utilizing summary statistics from genome-wide association studies (GWAS).
• Comparison of genome-wide risk genes between MS and hospitalized COVID-19 GWAS datasets.
• Literature-based pathway analysis to elucidate molecular connections.

Main Results:

• Genetic liability to MS causally increases the risk of COVID-19 hospitalization (OR: 1.09).
• Genetic liability to hospitalized COVID-19 causally increases the risk of MS (OR: 1.15).
• Five shared risk genes (TNFAIP8, HSD17B4, CDC37, PDE4A, KEAP1) and immunity-related pathways were identified.

Conclusions:

• Multiple sclerosis is associated with an increased risk of COVID-19 hospitalization.
• Hospitalized COVID-19 is associated with an increased risk of developing multiple sclerosis.
• Immunity-related pathways likely mediate the observed bidirectional relationship between MS and COVID-19.