You don’t need B cells to fight #MSCOVID19

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In light of todays discussion, we have this paper today. I told you the review (below) was out of date already, but this supports what we have suggested.

Two X-linked agammaglobulinemia patients develop pneumonia as COVID-19 manifestation but recover.Soresina A, Moratto D, Chiarini M, Paolillo C, Baresi G, Focà E, Bezzi M, Baronio B, Giacomelli M, Badolato R.Pediatr Allergy Immunol. 2020 Apr 22. doi: 10.1111/pai.13263. [Epub ahead of print]

What’s this got to do with MS?

Well here is a genetic condition where the affected individual does not make B cells. They got COVID-19 and recovered therefore B cells and probably antibody are not essential for immune protection against SARS-CoV2. Therefore, if you are taking ocrelizumab and rituximab, you can deal with the infection

ABSTRACT

Therefore, we evaluated the outcome of SARS-Cov2 infection in patients with inborn errors of immunity (IEI) such as X linked agammaglobulinemia (XLA).

METHODS:When the SARS-Cov2 epidemic has reached Italy, we have activated a surveillance protocol of patients with IEI, to perform SARS-Cov2 search by nasopharyngeal swab in patients presenting with symptoms which could be a manifestations of COVID-19, such as fever, cough, diarrhea or vomiting.

RESULTS:We describe two patients with X-linked agammaglobulinemia (XLA) of 34 and 26 years of age with complete absence of B cells from peripheral blood who developed COVID-19, as diagnosed by SARS-Cov-2 detection by nasopharyngeal swab, while receiving immunoglobulin infusions. Both patients developed interstitial pneumonia characterized by fever, cough and anorexia and associated with elevation of CRP and ferritin, but have never required oxygen ventilation or intensive care.

CONCLUSION:Our report suggests that XLA patients might present high risk to develop pneumonia after SARS-Cov2 infection, but can recover from infection, suggesting that B cell response might be important, but not strictly required to overcome the disease. However, there is need of larger observational studies to extend these conclusions to other patients with similar genetic immune defects.

Now to clarify this further someone has indicated that the people were being treated with immunoglobulin, this would not give neutralising protection from COVID-19, however it could block macrophages and neutrophils and natural killer cell activity and this could be beneficial which is not being done with anti-CD20 therapy, but does not change the argument that B cells are not essential for anti-COVID immunity, which is the point of the post

Successful treatment of plasma exchange followed by intravenous immunogloblin in a critically ill patient with 2019 novel coronavirus infection.Shi H, Zhou C, He P, Huang S, Duan Y, Wang X, Lin K, Zhou C, Zhang X, Zha Y.Int J Antimicrob Agents. 2020 Apr 13:105974. doi: 10.1016/j.ijantimicag.2020.105974

High-Dose Intravenous Immunoglobulin as a Therapeutic Option for Deteriorating Patients With Coronavirus Disease 2019.
Cao W, Liu X, Bai T, Fan H, Hong K, Song H, Han Y, Lin L, Ruan L, Li T.Open Forum Infect Dis. 2020 Mar 21;7(3):ofaa102. doi: 10.1093/ofid/ofaa102. eCollection 2020 Mar.

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MouseDoctor

9 comments

  • One question i have ask myself manny times

    Does X linked agammaglobulinemia (XLA) patients (without b cells) develop MS?

    Obrigado

    • Well not quite Ms

      But severe neurodegeneration Cd8+ t cell infiltration gait and speech abnormalites

      And guess what ?

      No b cell no antibodies no macrophages, to go around

      Last but no least no viral infection to be detected

      CD8+ lymphocyte infiltration in the
      cerebral cortex and leptomeninges
      (Fig. 1). Cortical neurons were surrounded
      by lymphocytes but not
      neutrophils and showed the features of
      both neuronal injury and areas of
      astrogliosis. The majority of infiltrating
      lymphocytes expressed granzyme B,
      which may have mediated T-celldependent
      brain injury. The patient
      has become cachectic, immobile and
      unable to drink and eat and died at
      age 7.
      PCR-based assays (serum and cerebrospinal
      fluid) failed to unveil potential
      causal agents for the disease. Unbiased
      pyrosequencing (4) used in Patient 2
      failed to define virus-specific genetic
      markers in brain biopsy material. These
      findings provide further evidence that
      cytotoxic T cells play a critical role in
      the pathogenesis of PNG in patients
      with XLA (5). Viral sequences could not
      be identified in brain biopsy by metagenomic
      analysis, suggesting that causative
      agents other than astrovirus are to be
      defined. We propose that prospective,
      multicenter analysis by using standard
      high-throughput assays is needed to
      define the role of astroviruses or other
      potential agents that may cause this
      formidable neurological complication of
      patients with XLA.

      DOI: 10.1111/j.1398-9995.2011.02713.x

      Progressive Neurodegenerative Syndrome in a Patient
      with X-Linked Agammaglobulinemia Receiving
      Intravenous Immunoglobulin Therapy

      https://www.ncbi.nlm.nih.gov/pubmed/25237746

      A case of X-linked agammaglobulinemia with progressive encephalitis

      https://www.pedneur.com/article/S0887-8994(04)00283-8/fulltext

      Obrigado

      Cytotoxic T lymphocytes mediate neuronal injury in patients with X‐linked agammaglobulinemia and progressive neurodegenerative disease

  • Hi gavin
    I think this report does not necessarily mean patients can deal with covid infection because both cases reported were receiving immunoglobulin infusions so it is not the same situation of antiCD20 users.
    Thank you !!!

    • I am biased as I know a lot of real-life data that has not been published yet. In particular the Italian and French data sets.

    • IF they were getting immunoglobulin, this would not be specific for SARS-CoV-2. So the only value would be blocking macrophages

      Successful treatment of plasma exchange followed by intravenous immunogloblin in a critically ill patient with 2019 novel coronavirus infection.Shi H, Zhou C, He P, Huang S, Duan Y, Wang X, Lin K, Zhou C, Zhang X, Zha Y.Int J Antimicrob Agents. 2020 Apr 13:105974. doi: 10.1016/j.ijantimicag.2020.105974

      High-Dose Intravenous Immunoglobulin as a Therapeutic Option for Deteriorating Patients With Coronavirus Disease 2019.
      Cao W, Liu X, Bai T, Fan H, Hong K, Song H, Han Y, Lin L, Ruan L, Li T.Open Forum Infect Dis. 2020 Mar 21;7(3):ofaa102. doi: 10.1093/ofid/ofaa102. eCollection 2020 Mar.

  • We believe that an autoimmune
    mechanism mediated by CD8 T cells may have caused this
    severe complication with X-linked agammaglobulinemia.
    Hence, to establish diagnostic and treatment strategies for
    this unidentified disease, multicenter studies will be required.

    A Case of X-Linked
    Agammaglobulinemia
    With Progressive
    Encephalitis

    Its not only the B side

    🙂

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