Biological Significance of Anti–SARS-CoV-2 AntibodiesLessons Learned From Progressive Multifocal Leukoencephalopathy Navid Manouchehri, Lawrence Steinman, Olaf Stuve. Neuology N2. DOI: https://doi.org/10.1212/NXI.0000000000000935
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.
So the three Amigos reporting here are occassional readers of the blog and like the “colourful language”. The senior authors are T cell immuologists and we know from them that the sun shines out of a T cell’s bum and B cells are bit part players to the T cell cause of MS.
They suggest that if we are thinking about SARS-CoV-2 we have to think about T cells and B cell responses may not be enough…You have to think about T cells based on the suggestion that T cells are important immunity against the JC virus that causes progressive multi-focal leukoencephalopathy (PML). “In summary, the humoral acquired immune response against JCV is a reliable diagnostic and prognostic biomarker, but it fails to correlate with host defense in the absence of Ag-specific cellular immune response”
I would agree, but perhaps would say NSS (No**** sherlock). To make these conclusions perhaps you don’t need to think about PML just have to read the COVID-19 literature to see that T cells are important in removing the SARS-CoV-2 virus. Indeed it is suggested that Monkeys make anti-SARS-Cov2 antibodies but that should not be seen as causal part of the immunity…I would go further and say these experiments showed that the virus was removed before signficiant IgG responses were formed. Likewise people recover from COVID-19 in people with ocrelizumab who have not seroconverted to make antibodies. Therefore studying JC virus is not going to give us the answer.
PML is a brain disease and as antibodies dont really enter the CNS is it not surprising that T cells are useful in getting rid of the virus. Ocrelizumab and rituximab studies will be most informative
The question we need to know ASAP are whether/How many people with ocrelizumab serocovnert? Whether they make CD4 and CD8 T cells responses and whether people are protected from SAR-CoV-2 infection/COVID-19