Analyzing the biological mechanisms of CCL11 in cognitive impairments following COVID-19 infection and populations at greater risk

Abstract

 “Brain fog”, an informal term that encapsulates various neurological symptoms including impaired attention, concentration, speed of information processing, memory, and executive functions, is a persistent symptom common among a quarter of COVID-19 survivors. While severe COVID-19 causes multi-organ disease, even mild COVID-19 can result in neuroinflammatory responses and subsequent brain fog. SARS-CoV-2 infection has been shown to also increase the risks of later developing other neurodegenerative disorders such as Alzheimer’s disease. Considering the continued prevalence of COVID-19 around the globe and emerging variants such as Omicron, these neurological symptoms present a major public health concern. Recent studies have detected elevated levels of pro-inflammatory chemokine CCL11 only in those experiencing cognitive impairments after SARS-CoV-2 infection, establishing a strong link between CCL11 and the central nervous system (CNS). CCL11 plays a major role in eosinophilic inflammation, and has been shown to limit neurogenesis and contribute to other cognitive and psychiatric illnesses, such as multiple sclerosis, Alzheimer’s, major depression, bipolar disorder, and schizophrenia. However, the biological mechanisms of CCL11 over-expression as a result of SARS-CoV-2 infection remain poorly understood. This article will investigate the mechanism behind SARS-CoV-2-driven CCL11 upregulation from infection to CCL11 entry into the CNS across the blood-brain barrier, outlining the sources of CCL11 and targets within the plasma and CNS. Additionally, it will discuss the subsequent pathological effects of CCL11 on the CNS, including eosinophil degranulation, activation of microglia, inhibition of oligodendrocyte precursors, and production of reactive oxygen species. It will also investigate which demographics are more vulnerable to the adverse effects of CCL11 and risks of long COVID. These inquiries play a key role in understanding CCL11 functions within the brain and evaluating the potential of CCL11 as a new therapeutic target. If this therapeutic strategy is successful, it will improve health outcomes not only for post-COVID brain fog, but also for other neurological disorders related to inflammatory dysregulation.