The objective of this review was to discuss the pathogenic and diagnostic relevance of cellular and humoral immune responses against SARS-COV-2 and pertinent observations made in progressive multifocal leukoencephalopathy (PML). There is at least one precedent for an antibody response against a viral pathogen that fails to provide host protection in the absence of immune-competent CD4+ T cells. PML is an infection of the CNS caused by JC virus (JCV), which may occur during treatment with the therapeutic monoclonal antibody, natalizumab. In this context, the humoral immune response fails to prevent JCV reactivation, and elevated anti-JCV serum indices are associated with a higher PML incidence. The more relevant immune-competent cells in host defence against JCV appear to be T cells. T cell–mediated responses are also detectable in convalescing patients with SARS-COV-2 irrespective of the humoral immune response. Based on pathogenic lessons learned from PML undergoing natalizumab therapy, the authors suggest the incorporation of functional assays that determine the neutralising properties of SARS-CoV-2–specific antibodies. In addition, they outline the potential role of T-cell detection assays in determining herd immunity in a given population or in studying therapeutic responses to vaccines.
DOI: https://doi.org/10.1212/NXI.0000000000000935