Can immunological imprinting drive neurological dysfunction in long COVID?

Abstract

This scientific commentary refers to ‘Neurologic sequelae of COVID-19 are determined by immunologic imprinting from previous coronaviruses’ by Spatola et al. (https://doi.org/10.1093/brain/awad155).

Figure 1

Proposed contribution of coronavirus immunologic imprinting to the development of long COVID neurological dysfunction. Previous (ancestral) infection with common coronaviruses induces B cell immune responses, clonal expansion and production of antibodies against these viruses. Subsequent (years) infection with SARS-CoV-2 triggers enhanced production of these ancestral antibodies, and relatively limited production of anti-SARS-CoV-2 antibodies, in patients who go on to develop long COVID neurological dysfunction. Selective transfer of anti-SARS-CoV-2 IgG1 (and not other immune globulin classes) across the blood–brain barrier by the binding and transport functions of neonatal Fc receptors (FcRn) contributes to a limited immune response to SAR-CoV-2 in the CNS. It has also been proposed that the robust expression of ancestral coronavirus antibodies limits the ability of naïve B cells to generate antibody responses to SARS-CoV-2 (a phenomenon consistent with immunologic imprinting). This may result in decreased SARS-CoV-2 clearance and increased inflammation within the CNS compartment, leading to neurological dysfunction. Created with BioRender.com.