A couple of days ago I commented on that people without B cells and immunoglobulin (X-linked aggammaglobulinemia) making capacity were surviving COVID-19, which I feel is potential good news for people taking ocrelizumab.
However I got blasted from a wee timmerous beastie called Neurology101 saying that they had people struggling with COVID-19. Were they saying Duh MD, you are wrong because here we have people struggling….Remeber I am not giving advice on what to take, I am trying to understand the science.
I accepted that these people were being given immunoglobulin, but you couldn’t say this had any anti-COVID immunity as it was no doubt made before this mesh arrived. However, I hold my hands up as it would block the Fc receptors on macrophages and polymorphs and may block their function. However, it is not about the individual cases as I know some one in Italy has died who was taking rituximab. It is not a COVID-19 cure, but alot of people have died who are not taking rituximab, However the importance is to understand what is going on.
However, I was not the only person to think this is interesting
A possible role for B cells in COVID-19?: Lesson from patients with Agammaglobulinemia.Quinti I, Lougaris V, Milito C, Cinetto F, Pecoraro A, Mezzaroma I, Mastroianni CM, Turriziani O, Bondioni MP, Filippini M, Soresina A, Spadaro G, Agostini C, Carsetti R, Plebani A.J Allergy Clin Immunol. 2020 Apr 22:S0091-6749(20)30557-1. doi: 10.1016/j.jaci.2020.04.013
COVID-19 had a mild clinical course in patients with Agammaglobulinemia lacking B lymphocytes, whereas it developed aggressively in Common Variable Immune Deficiency. Our data offer mechanisms for possible therapeutic targets.
They (Italian Doctors 1010) say “To date, we have identified seven Primary Antibody Deficiencies (PAD) patient with COVID-19 infection: five affected with Common Variable Immune Deficiencies (CVIDs) and two affected with Agammaglobulinemia, one with X-linked Agammaglobulinemia (XLA) and one with Autosomal Recessive Agammaglobulinemia (ARA). All Primary Antibody Deficiency patients have defective antibody production. Patients with Agammaglobulinemia lack B lymphocytes whereas patients
with Common Variable Immune Deficiency have dysfunctional B lymphocytes. In patients affected with Agammaglobulinemias, the COVID-19 course was characterized by mild symptoms, short duration, with no
need of treatment with the immune-modulating drug blocking IL-6, and had a favorable outcome. In contrast, patients affected with Common Variable Immune Deficiencies presented with a severe form of the
disease requiring multiple drug treatment, including antiretrovirals agents and IL-6 blocking drugs, and mechanical ventilation”
Now to take Neurology101’s side of the argument you have to say people with ocreliziumab are not B cell deficient, but the antibody hanfs around to ensure that any B cell made that gets in the blood is killed, so it may not quite be the same as B cell deficiency.
However from the point of Immunology 101 the antibody response is at least blunted.
Therefore one implication could be this that making antibody to COVID-19 can be part of the problem. Why because it may mark the cells infected with the virus for destruction via the immune system. It warns that vaccinating people with existing infection could be the last thing you may want to do. Sure it will be the individual that suffers. They are also filling people with anti-COVID antisera and they have already made anti-COVID monoclonal antibodies. There will be idiots that make IgG1 variants because that’s what pharma does and shove them in people. I think they should be IgG4 (Non-depleting non complement fixing ) variants as these will block the virus and not stimulate the macrophages of better still Fab fragments (the bits that block the antigen binding) to stop them being the targets for macrophage destruction.
However Italian Doctors101 say “The strikingly different clinical course of COVID-19 in patients with agammaglobulinemia compared to CVIDs cannot be explained by the level of serum immunoglobulins, which were similarly low in all PAD patients at diagnosis, and were maintained at adequate and comparable levels in all patients by immunoglobulin substitutive therapy……All patients with primary antibody deficiencies are equally vulnerable to most bacterial infections since antibodies are important in blocking infectivity and preventing diseases……we speculate on a possible role of B lymphocytes in the SARS-CoV-2 induced inflammation“. However maybe on group could make some anti-SARS-Cov-2 antibody the other can’t. There was no mention if there antibodies were tested.
However, this would imply that depleting B cells would be a good thing. But Neurology101 will say look at my MS patient doing badly and if you look at the lungs reported there are no B cells…although I have heard in some cases their are plasma cells. So where will taking B cell depleting therapy leave you, in a better place, the same place or a worse place? The natural experiment is on-going and people with MS and arthritis, etc will give us the answer. Case reports although interesting will not give us the answer. I suspect we have not to wait too long as the registries will have this data…..At the end of the day it is Biology101 that needs to be explained as this helps give us Treatment101.