We are reporting frequently on the lack of an antibody response in people treated with anti-CD20 and whilst we think about how we manipulate the biology to encourage B cell responses in B cell depleted individuals, there is another solution and that is to supply people with an antibody response. This can be in the form of convalescent sera (antibodies from people recovered from covid) or SARS-CoV-2 antibody cocktail. These could be selected to defend against the variants circulating. We know they work as they can be shown to prevent infection in animals
Some of these have been approved as a prophylactic against infections in homes for the unifected from the infected. This should have been tested in health care workers/high risk individuals as prohylactics against infection months ago, but perhaps in the post-vacination era it is too late. They can give antibody responses to people who don’t have them.
However, it in addition to protecting against infection in immunosuppressed individuals they may protect against escape mutants occuring in immunosupressed people that could stop the vaccines working, as we would not want the next delta, omega or andromeda strain to come from immunosupressed pwMS
Copin R et al. The monoclonal antibody combination REGEN-COV protects against SARS-CoV-2 mutational escape in preclinical and human studies. Cell. 2021;184(15):3949-3961.e11.
Remember the UK alpha variant is thought to come from someone immunosuppressed as it had serial mutations
Pan D et al. The new UK SARS-CoV-2 variant and lockdown – causes and consequences. Clin Med (Lond). 2021; 21:e295-e299.
and this can virus evolution has been seen
Avanzato VA et al. Case Study: Prolonged Infectious SARS-CoV-2 Shedding from an Asymptomatic Immunocompromised Individual with Cancer. Cell. 2020;183(7):1901-1912.e9.
Other alternatives possible outcomes
Kemp SA et al. SARS-CoV-2 evolution during treatment of chronic infection. Nature. 2021;592:277-282.
Would they work and be useful in CD20-depleted individuals? I don’t know but should be tested in a trial.
On the whole treating people after they have the virus and the results have been indifferent and when used late in hospitalisation they often don’t work. However here is an example of a study…it is clearly too small to be truely informative.
Successful treatment of COVID–19 infection with convalescent plasma in B cell-depleted patients may promote cellular immunity.Kremer AE, Kremer AN, Willam C, Völkl S, Verhagen J, Achenbach S, van der Meijden ED, Lang V, Aigner M, Maier C, Tenbusch M, Korn K, Lutzny-Geier G, Spoerl S, Strauß R, Vetter M, Überla K, Neurath MF, Mackensen A, Schiffer M, Hackstein H.Eur J Immunol. 2021 Aug 4. doi: 10.1002/eji.202149277. Online ahead of print.
Treatment with convalescent plasma has been shown to be safe in COVID-19 infection, although efficacy reported in immunocompetent patients varies (Yep often it doen’t work). Nevertheless, neutralizing antibodies are a key requisite in the fight against viral infections. Patients depleted of antibody-producing B cells, such as those treated with rituximab (anti-CD20) for haematological malignancies (and MS), lack a fundamental part of their adaptive immunity. Treatment with convalescent plasma appears to be of general benefit in this particularly vulnerable cohort. We analysed clinical course and inflammation markers of three B-cell depleted patients suffering from COVID-19 that were treated with convalescent plasma. In addition, we measured serum antibody levels as well as peripheral blood CD38/HLA-DR positive T-cells ex vivo and CD137 positive T-cells after in vitro stimulation with SARS-CoV-2 derived peptides in these patients. We observed that therapy with convalescent plasma was effective in all three patients and analysis of CD137 positive T-cells after stimulation with SARS-CoV-2 peptides showed an increase in peptide-specific T-cells after application of convalescent plasma. In conclusion, we here demonstrate efficacy of convalescent plasma therapy in three B cell-depleted patients and present data that suggests that while application of convalescent plasma elevates systemic antibody levels only transiently, it may also boost specific T cell responses.
I reiterate that this should be done as a trial and not self experiment.
I am rehearsing these arguments in public for a review paper. What do you think?
Would it give you more confidence in going out if you knew you have an protective antibody response? Having seen my own vaccination response on our blood spot test, I felt better for it? I would have been happier with the levels we found in a STORMCHASER (Had anti SARS-COV2 Ig) participant that we measured.
Disclaimer: Please note that the opinions expressed here are those of the author and do not reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust or Queen Mary Univeristy of London.