Ocvrelizumab can blunt the anti-COVID19 antibody response.

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We have recently reported on the the possibility that taking ocrelizumab may reduce your chance of producing protective antibody against COVID-19-related virus.

COVID-19 vaccine-readiness for anti-CD20-depleting therapy in autoimmune diseases.Baker D, Roberts CAK, Pryce G, Kang AS, Marta M, Reyes S, Schmierer K, Giovannoni G, Amor S.Clin Exp Immunol. 2020 Jul 16. doi: 10.1111/cei.13495. Online ahead of print.

Here is one example to show that this hypothectical idea appears to be a clinical reality.

Mild clinical manifestations of SARS-CoV-2 related pneumonia in two patients with multiple sclerosis under treatment with ocrelizumab

Marco Iannetta, Novella Cesta, Christof Stingone, Vincenzo Malagnino, Elisabetta Teti, Pietro Vitale, Giuseppe De Simone, Benedetta Rossi, Lorenzo Ansaldo, Mirko Compagno, Ilaria Spalliera, Andrea Di Lorenzo, Doriana Landi, Carolina Gabri Nicoletti, Girolama Alessandra Marfia, Massimo Andreoni, Loredana SarmatiPublication stage: In Press Journal Pre-Proof

Highlights

  • Ocrelizumab is not associated to increased severity in MS patients with COVID-19
  • B-cell depleting treatment could impact on virus-specific antibody production
  • B-cell depleting therapies can reduce IL-6 production, thus modulating inflammation

Background: Recently SARS-CoV-2 has spread worldwide causing a pandemic. Little is known about disease severity in immunocompromised hosts and people receiving disease modifying therapies (DMTs). In the last decades DMTs have been widely employed, and ocrelizumab represents one of the newest therapies for the relapsing remitting and progressive forms of multiple sclerosis (MS).Objectives: to describe SARS-CoV-2 related pneumonia in two MS patients under ocrelizumab treatment.Methods: Case series.Results: Patients showed a mild clinical course of SARS-CoV-2 related pneumonia without complications or sequelae.Conclusion: Ocrelizumab treatment is not necessarily associated to increased severity in MS patients with SARS-CoV-2 infection.

However, this re-affirms the view that the antibody response is not critical to removing the virus as we suggested a number of months ago.

The underpinning biology relating to multiple sclerosis disease modifying treatments during the COVID-19 pandemic.Baker D, Amor S, Kang AS, Schmierer K, Giovannoni G.Mult Scler Relat Disord. 2020 Aug;43:102174. doi: 10.1016/j.msard.2020.102174.

Are we showing off our immunological knowledge to get a paper, as suggested by one of the readers, or were we attempting to give insight to what we thought may happen in COVID-19?

I can assure you it was not about getting papers and immportantly I will point out that this is essentially what was found to happen and therefore I think we did a pretty good job and we did not predict the Doom and Gloom that was the concern at the time the paper was written. We worked hard to write try and get the paper out fast. This paper also had a view on vaccination and if you want it repeated you can have a look at a new paper….which is already out of date. Because we know the clinical consequnce of infection to the DMT and in many cases the antibody-generating response and importantly we do know the effect of some vaccines including RNA vaccines on COVID-19.

Effects of MS disease-modifying therapies on responses to vaccinations: a review. John Robert Ciotti, Manouela V. Valtcheva, Anne Haney CrossPublication stage: In Press Journal Pre-Proof. Mult scler Rel Disord DOI: https://doi.org/10.1016/j.msard.2020.102439

Background.: Development of long-term immunologic memory relies upon humoral and cellular immune responses. Vaccinations aim to stimulate these responses against pathogens. Several studies have evaluated the impact of multiple sclerosis disease-modifying therapies on immune response to vaccines. Findings from these studies have important implications for people with multiple sclerosis who require vaccination and are using disease-modifying therapies.

Methods: Searches using PubMed and other engines were conducted in May 2020 to collect studies evaluating the impact of various disease-modifying therapies on immune responses to vaccination.

Results: Several studies demonstrated preserved immune responses in people treated with beta-interferons to multiple vaccine types. Limited data suggest vaccine responses to be preserved with dimethyl fumarate treatment, as well. Vaccine responses were reduced to varying degrees in those treated with glatiramer acetate, teriflunomide, sphingosine-1-phosphate receptor modulators, and natalizumab. The timing of vaccination played an important role in those treated with alemtuzumab. Humoral vaccine responses were significantly impaired by B cell depleting anti-CD20 monoclonal antibody therapies, particularly to a neoantigen. Data are lacking on vaccine responses in patients with multiple sclerosis taking cladribine and high-dose corticosteroids. Notably, the majority of these studies have focused on humoral responses, with few examining cellular immune responses to vaccination.

Conclusions : Prior investigations into the effects of individual disease-modifying therapies on immune responses to existing vaccines can serve as a guide to expected responses to a SARS-CoV-2 vaccine. Responses to any vaccination depend on the vaccine type, the type of response (recall versus response to a novel antigen), and the impact of the individual disease-modifying therapy on humoral and cellular immunity in response to that vaccine type. When considering a given therapy, clinicians should weigh its efficacy against MS for the individual patient versus potential impact on responses to vaccinations that may be needed in the future.

Are you getting bored with COVID-19 stuff?….I know I am….I can’t even be bothered to try make a joke out papers looking at out of date face masks or how long-sleeved gowns influence on hand washing. I spent alot of effort getting up to speed to try and understand the disease. There are now over 35,000-40,000 papers on the subject and it is gone way past diminishing returns to keep up….Even “Medcram” has run out of steam.

Dr Love has another paper in the mix

Sandra Amor, Laura Fernandez Blanco, David Baker. Innate immunity during SARS-CoV-2: evasion strategies and activation trigger hypoxia and vascular damage. Authorea. August 04, 2020.
DOI: 10.22541/au.159656134.40877628

We will have more to say on this and we will have some research to report in due course. However, the bureaucracy we have had to deal with is unbelievable. Hopefully ProfG has his MoJo topped up to see if we can resource our plans for MS studies and MS service.

We know what has happened from case-reports, and soon we will have a raft of registry data surfacing it is all sounding relatively uninteresting, but ocrelizumab may increase your risk of a symptomatic infection according to sublished Iranian and Italian studies, Ocrelizumab accounts for about 1/3 (106/337. Salter iWiMS July 15/16) of the COVID cases in the USA is that because it is a risk factor a a best seller?

About the author

MouseDoctor

6 comments

  • All very interesting and fascinating to see predictions based on science becoming reflected in the real life data.

    I am sick of covid as in I wish it would get lost (!) but I will never be tired of learning crucial information relating to covid risk and my DMT so thank you for bringing it to us.

    Did the surfacing registry data show anti CD20 risk of severe disease again, or simply more ‘symptomatic’ disease as you said (which may be one way of interpreting severity).

    Thanks!

    • What he said /\ …also alemtuzumab zaps cd 20 (along with various T cells) sooooooo….even though it’s ocrevus is it the same for alemtuzumab? I did a third round of it in February of this year.

    • To fight off COVID-19 you may not absolutely require T and B cells so alemtuzumab and ocrelizumab may not give you too much extra risk from COVID-19
      However if you take ocrelizumab you will not be able to make a good antibody response if you get infected with COVID-19 and you may not make a good vaccine response if you take ocrelizumab and rituxuimab. However, the T cell response may be enough to protect you from re infection

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