COVID-19 and cognitive performance: a Mendelian randomization study

Abstract

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BackgroundA substantial proportion of individuals with COVID-19 experienced cognitive impairment after resolution of SARS-CoV-2 infection. We aimed to evaluate whether genetic liability to SARS-CoV-2 infection per se, or more severe COVID-19, is causally linked to cognitive deficit.MethodsWe firstly performed univariable Mendelian randomization (MR) analysis to examine whether genetic liability to SARS-CoV-2 infection, hospitalized and severe COVID-19 is causally associated with cognitive performance. To dissect the causal pathway, multivariable MR (MVMR) analysis was conducted by adjusting for five inflammatory markers [C-reactive protein, interleukin (IL)-1β, IL-6, IL-8, and tumour necrosis factor α, as proxies of systemic inflammation].ResultsIn univariable MR analysis, host genetic liability to SARS-CoV-2 infection was associated with lower cognitive performance [inverse variance weighted (IVW) analysis, estimate: −0.023; 95% Confidence Interval (CI): −0.038 to −0.009]. Such causal association was attenuated in MVMR analysis when we adjusted for the five correlated inflammatory markers in one analysis (IVW analysis, estimate: −0.022; 95% CI: −0.049 to 0.004). There was insufficient evidence of association for genetic liability to hospitalized and severe COVID-19 with cognitive performance.ConclusionThe causal effect of host genetic liability to SARS-CoV-2 infection on reduced cognitive performance may be mediated by systemic inflammation. Future studies examining whether anti-inflammatory agents could alleviate cognitive impairment in SARS-CoV-2-infected individuals are warranted.

Keywords

• SARS-CoV-2 infection
• COVID-19
• cognitive performance
• inflammatory markers
• Mendelian randomization