PT - JOURNAL ARTICLE AU - Navid Manouchehri AU - Lawrence Steinman AU - Olaf Stuve TI - Biological Significance of Anti–SARS-CoV-2 Antibodies AID - 10.1212/NXI.0000000000000935 DP - 2021 Mar 01 TA - Neurology - Neuroimmunology Neuroinflammation PG - e935 VI - 8 IP - 2 4099 - http://nn.neurology.org/content/8/2/e935.short 4100 - http://nn.neurology.org/content/8/2/e935.full SO - Neurol Neuroimmunol Neuroinflamm2021 Mar 01; 8 AB - Objective To discuss the pathogenic and diagnostic relevance of cellular and humoral immune responses against severe acute respiratory syndrome novel coronavirus (SARS-COV-2) and pertinent observations made in progressive multifocal leukoencephalopathy (PML).Methods Review of pertinent literature.Results There is at least 1 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 commonly occurs 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 defense 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.Conclusion Based on pathogenic lessons learned from PML under natalizumab therapy, we suggest the incorporation of functional assays that determine neutralizing properties of SARS-CoV-2–specific antibodies. In addition, we outline the potential role of T-cell detection assays in determining herd immunity in a given population or in studying therapeutic responses to vaccines.GMFR=geometric mean fold rise; GMT=geometric mean titer; Ig=immunoglobulin; IRIS=immune reconstitution inflammatory syndrome; JCV=JC virus; PML=progressive multifocal leukoencephalopathy