The CD20 onslaught continues at a pace and there is no refuting it, anti-CD20 depletion blocks the formation of vaccine response. I have seen this occur irrespective of the vaccine that was used. I am sorry to say if you are on anti-CD20 you are going to see this over and over again…it will be like-water torture, drip, drip, drip.
Yep and I control the tap (faucet for our American readers:-)….The water will continue to flow until our work surfaces and is done
CD20-depletion is used all over the place because it is good at stopping many disease responses…but in this context it is also good at stopping the formation of new antibody responses. We can see this in arthritis and MS and lupus etc etc etc.
There are about 200,000 people taking ocrelizumab (Ker Ching) and they should be vaccinated. We have only seen case reports from about 150 people so far and these are all for the Pfizer vaccinees, so stay turned for a lot of papers, and be prepared for the Astrazeneca vaccine data.
I predict it will be worse news antibody-wise. Why?
Because it is becoming very clear that the AZ vaccine induces a much lower antibody response than the RNA vaccines. You could always see this signal based on trial data but now that head to head studies have arrived it is obvious in my mind. Maybe this is because you spend your effort also making adenoviral antibodies or maybe because the vaccine makes a floppy Spike as the others are engineered to have a more rigid Spike (Furin cleavage sites removed). Moderna probably induces the strongest antibody response based on the trial and some real-life data.
The Americans have dodged this AZ bullet as this vaccine was never made available, and it is now being avoided in MS-endemic areas (Norther Europe) because of the blood clot issues. As booster season arrives in my mind, immunosuppressed people should be offered something else and the JCVI need a bit of a shake.
Fear-not if you had the AZ vaccine before, it is perfectly safe to get an RNA-vaccine as a booster and if may work better. There are plenty of papers surfacing on that one.
Can you say how much antibody you need to be protected? and I say “I don’t know”, but if you start with a very high level you will be protected for longer.
So what does this mean?
At the moment we have made the case that macrophages and T cells are pretty good at getting rid of the virus and you don’t need antibodies for this to occur because you can get rid of the virus before you make an antibody response and most B cell depleted individuals recover. However high levels of antibodies are probably going to stop infection,
However as the antibody levels drop you may get infected and show some signs of COVID-19 and then the T and antibody immune response will kick in. It means you may get disease but deal with it. Antibody levels often wane over time and this is why boosters are being considered. This will give your antibody levels a kick in the tush. It seems in immunosuppressed people with low antibody responses after two rounds, a third dose can make the difference. I think however that CD20-depletion is a different beast and the immunosuppressed people making a response are not taking anti-CD20 depletion. This is a special case and I hope the JVCI understand this.
If you are on immunomodulating treatment even if you make an antibody response it is probably at a lower level. This will wane quicker and if you are on an adenoviral vaccine the starting point for the waning response is lower, it will be quicker still….so I can see the Astrazeneca vaccine becoming a thing of the past for people taking immunosuppressive agents.
The next problem with a low antibody response are variants. We can see that antibodies against the Wuhan-variants work against alpha (UK variant) or delta (Indian variant) but to work effectively you need more antibody maybe three to ten times more antibody and so as the level of antibody drops you become more susceptible to the variants of interest e.g. delta. Given that BoJo and his chronies are inviting us in the England to a COVID-19 fest….free-for-all…with cases still massively increasing remember to be cautious, as you have been, if you are taking anti-CD20, you are likely to have a weak or non-existent antibody response.
However, what is becoming increasingly clear is that you make a T cell response after vaccination and so this should give protection. Will it stop you showing an infection maybe yes but for some I think not because you will not have the sufficient immunity. Will it inhibit hospitalization let’s hope so and if you end up in hospital let’s hope it stops you going to ICU. I have heard of double-vaccinated dosed ocrelizumabers getting infected. However, the only way to understand if the vaccine is making a difference is to look at big numbers and the only people to be able to do this in my mind, will be people with big registries like the Scandies have. The Aussies have MSbase but as they have been locking- themselves-in the infection rate is going to be so low, I will have retired by the time they get the data:-).
So the one big hope is …yes you’ve guess it…….Pharma.
The manufacturers have their pharmacovigilance process and so they can collect the data. They also have thousands of people in trials…..I know the makers of ocrelizumab are doing this and are best place to get the big picture. Sure some academics will do it, to ensure it is reported properly.
Can we optimize an antibody response for people on ocrelizumab, I think to some extent yes, but it will not be straight forward given the variability between people in their response to CD20 depletion. Remeber keeping MS at bay is a good protection against COVID as disability is an enemy. The manufactures will probably not investigate optimization if it strays away from the label recommendations. At the moment we do not have the information how best to do this and do not know if it is worthwhile and so the more CD20-antibody response data that we get, the better we can assess this. Also remember vaccination may be a regular occurence
So the new challenge for the global initiative and the MS Societies..Collect CD data
Note this is arthritis but it doesnt matter
Simon D, Tascilar K, Schmidt K, Manger B, Weckwerth L, Sokolova M, Bucci L, Fagni F, Manger K, Schuch F, Ronneberger M, Hueber A, Steffen U, Mielenz D, Herrmann M, Harrer T, Kleyer A, Krönke G, Schett G. Brief Report: Humoral and cellular immune responses to SARS-CoV-2 infection and vaccination in B cell depleted autoimmune patients.Arthritis Rheumatol. 2021 Jul 1. doi: 10.1002/art.41914. Online ahead of print.
Objective: B cell depletion is an established therapeutic principle in a wide range of autoimmune disease. However, B cells are also critical for inducing protective immunity after infection and vaccination. We therefore assessed humoral and cellular immune responses after infection with or vaccination against severe acute respiratory syndrome coronavirus -2 (SARS-CoV-2) in B cell depleted patients and B cell competent healthy controls.
Methods: Antibody (ELISA) and T cell (IFNγ ELISPOT) responses against the SARS-CoV-2 spike S1 and nucleocapsid proteins were assessed in a limited number of infected (N=6) and vaccinated (N=8) B cell depleted autoimmune patients as well as infected (N=30) and vaccinated (N=30) healthy controls.
Results: As expected, B and T cell responses to the nucleocapsid were observed only after infection, while respective responses to spike S1 were found both after infection and vaccination. A SARS-CoV-2 antibody response was observed in all vaccinated controls (30/30, 100%) but in none (0/8) of the vaccinated B-cell-depleted patients. In contrast, after SARS-CoV-2 infection, both B-cell-depleted patients (spike S: 5/6, 83%; nucleocapsid 3/6, 50%) and healthy controls (spike S: 28/30, 94%; nucleocapsid 28/30, 93%) developed antibodies. T cell responses against the spike S1 and nucleocapsid proteins were found in both infected and vaccinated B cell depleted subjects and in the controls.
Conclusion: These data show that B cell depletion completely blocks humoral but not T cell SARS-CoV-2 vaccination response. Furthermore, limited humoral immune responses are found in B cell depleted patients after SARS-CoV-2 infection.
However rememebr to stay safe, being vaccinated does not mean you are bullet-proof man and if you have been taking CD20-depleting antibodies and other treatment you have a more limited protection.
You can be vaccinated and get COVID-19.
Nissimov et al. BNT162b2 vaccine breakthrough: clinical characteristics of 152 fully-vaccinated hospitalized COVID-19 patients in Israel Clin DOI:https://doi.org/10.1016/j.cmi.2021.06.036. Microbiol infecthttps://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(21)00367-0/fulltext
A total of 152 patients who received the BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine and developed COVID-19, requiring hospitalisation, more than 7 days after receiving the second vaccine dose. The median time elapsed from the second-dose vaccination to admission was 39.5 days (range 8-97), and the majority (82%) of patients were admitted 21 days or more after vaccination, which, noted the researchers, supported the assumption that the patients were not infected before vaccination. The median age was 71.1 (range 22-98) and most (70%) were males. The cohort was characterised by a high prevalence of comorbidities including hypertension (71%), diabetes (48%), congestive heart failure (CHF; 27%), chronic kidney diseases (24%) and chronic lung diseases (24%), dementia (19%), and cancer (24%), with only 6 (4%) patients having no comorbidities. Additionally, immunosuppression was present in 60 (40%) patients. Common causes of immunosuppression were chronic corticosteroid treatment, chemotherapy or anti-metabolite treatment and anti-CD20 treatment.
Good news from India
Clinical outcomes in vaccinated individuals hospitalized with Delta variant of SARS-CoV-2V, J. K., Sowpati, D. T., Munigela, A., Banu, S., Siva, A. B., Sasikala, M., Nutalapati, C., Kulkarni, A., Mukherjee, P., Zaveri, L., CCMB COVID-19 Team, , AIG Hospitals COVID-19 Vaccine study Team, , Tallapaka, K. B., D, N. R.10.1101/2021.07.13.21260417
Emerging variants of SARS-CoV-2 with increased transmissibility or immune escape have been causing large outbreaks of COVID-19 infections across the world. As most of the vaccines currently in use have been derived from viral strains circulating in the early part of the pandemic, it becomes imperative to constantly assess the efficacy of these vaccines against emerging variants. In this hospital-based cohort study, we analysed clinical profiles and outcomes of 1161 COVID-19 hospitalized patients (vaccinated with COVISHIELD (ChAdOx1) or COVAXIN (BBV-152), n = 495 and unvaccinated n = 666) in Hyderabad, India between April 24th and May 31st 2021. Viral genome sequencing revealed that >90% of patients in both groups were harbouring the Delta variant (Pango lineage B.1.617.2) of SARS-CoV-2. Vaccinated individuals showed higher neutralizing antibodies (545+-1256 AU/ml Vs 51.1+-296 AU/ml; p<0.001) when compared to the unvaccinated group. Severity of the disease (3.2% Vs 7.2%; p=0.0039) and requirement of ventilatory support (2.8% Vs 5.9%; p=0.0154) were significantly low in the vaccinated group despite the fact that these individuals had significantly higher age and risk factors. The rate of mortality was about 50% lower (2/132=1.51%) in the completely vaccinated breakthrough infections although mortality in individuals who had received a single dose was similar to the unvaccinated group (9/269=3.35% vs 23/666= 3.45%). Our results demonstrate that both COVISHIELD and COVAXIN are effective in preventing disease severity and mortality against the Delta variant in completely vaccinated hospitalized patients.