Understanding the long-term neurological effects of SARS-CoV-2 infection

Post-COVID-19 condition (PCC), also known as long COVID, is a heterogeneous condition marked by persistent symptoms following acute SARS-CoV-2 infection. As approximately 6% of people who have experienced acute COVID-19 are estimated to develop PCC, the potential population is vast. Many of the key symptoms of PCC reflect involvement of the nervous system, ranging from cognitive impairment ('brain fog'), headaches and fatigue to anxiety and depression. This Review summarizes the spectrum of neurological and psychological symptoms that occur following acute SARS-CoV-2 infection, with a particular focus on the international consensus-based core outcome set for PCC. We also explore the proposed underlying mechanisms, including evidence for immune system dysregulation, microvascular dysfunction and volumetric changes on neuroimaging. In addition, we review ongoing and completed large-scale treatment trials. Growing evidence suggests a bidirectional interaction between symptoms traditionally considered neurobiological in origin, such as cognitive deficits and headache, and those within the purview of psychiatry, such as anxiety and depression. PCC represents an opportunity to better understand the long-term consequences of acute infection and improve management strategies and outcomes, not only for people with the condition but also for those with other post-viral syndromes that affect brain health.