Op-Ed: Are the Immunosuppressed Responding to Two Doses?

[Celerity]

— Our new study on transplant patients suggests it's not yet safe for them to relax restrictions

https://www.medpagetoday.com/infectiousdisease/covid19vaccine/92439

Back in March, we published in JAMA and reported here in MedPage Today that only 17% of immunosuppressed transplant patients -- in stark contrast to 100% of immunocompetent people -- mounted detectable antibodies to SARS-CoV-2 after the first dose of mRNA vaccine. Our report was among the top five most read articles in JAMA, and generated substantial -- and understandable -- concern among communities of immunosuppressed people. As a transplant surgeon, I was frustrated and frightened for my patients, and my Johns Hopkins colleagues and I eagerly awaited the results looking at antibody response after full two-dose vaccination. The moment many transplant patients and physicians have been waiting for has finally arrived, but unfortunately the news is not great. We have now published in JAMA second-dose data from our national study of vaccine immune responses in immunosuppressed solid organ transplant recipients.

Among 658 COVID-19-naïve participants who received the full two-dose series of mRNA vaccines, 46% (compared to 83% after just one dose) still had no detectable antibodies, and even among those with detectable antibodies, the levels were still somewhat low. The situation is worse among those taking anti-metabolites: for this group, 57% had no antibodies after full vaccination, compared to 32% with no antibodies among those not taking anti-metabolites. Unfortunately, this blunted antibody response seems to correlate with diminished protective immunity. We are seeing in our own patients, and hearing from around the country, many cases of transplant patients receiving a full vaccine series, thinking they are immune, believing that the CDC guidelines for vaccinated people apply to them, relaxing the masking and distancing behaviours that have protected them for over a year, and sadly finding themselves hospitalized with a new COVID-19 infection. Some have even died. This is highly problematic.

We need more effort and action to spread the word that vaccination does not necessarily mean immunity in this vulnerable population. So, what should our transplant patients do in light of these findings? First and foremost, they should continue to practice all the protective behaviours they have thus far practiced. While the rest of the world is celebrating the new freedoms that come with vaccination, unfortunately the time is not yet right for transplant patients to do so. Eventually we will understand the immune response to vaccines in our patients enough to relax these restrictions, but right now we only know the impact on antibody response (with very little understanding of memory B cell and T cell response, which are both important), and what we know is not encouraging. Transplant patients should also make sure that everyone around them gets vaccinated, so at least their environments are safer. And, of course, this is yet another reason that everyone should want to get vaccinated -- to protect the vulnerable who cannot achieve immunity for themselves, and ultimately help reach herd immunity.

So, what is next? Will other platforms perform better? If someone had no, or limited, immune response to two doses, will a third dose help? Should the third dose be of the sample platform or a different platform? Is it reasonable for some patients to reduce immunosuppression, risking rejection, just to achieve an immune response? How do B cell and T cell responses look in immunosuppressed people? In the meantime, should people with no vaccine response receive pre-exposure exogenous antibody preparations for interim protection? We continue to strive to answer these questions, and enrolment in our study remains open and ongoing.

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[Sympthsical]

1. And that's why I'll keep my mask on

I'm young and vaccinated. I'll be fine. But I don't know who's around me, who's vulnerable.

It's not only about me. It's about protecting others. Always has been.

[Celerity]

2. List of Antimetabolites

https://www.drugs.com/drug-class/antimetabolites.html?condition_id=0&generic=0&sort=reviews&order=desc

Xeloda
Generic name: capecitabine

Hydrea
Generic name: hydroxyurea

Gemzar
Generic name: gemcitabine

Otrexup
Generic name: methotrexate

Rheumatrex Dose Pack
Generic name: methotrexate

Purinethol
Generic name: mercaptopurine

Leustatin
Generic name: cladribine

Folotyn
Generic name: pralatrexate

Fludara
Generic name: fludarabine

Alimta
Generic name: pemetrexed

Xatmep
Generic name: methotrexate

Trexall
Generic name: methotrexate

Tabloid
Generic name: thioguanine

Siklos
Generic name: hydroxyurea

Rasuvo
Generic name: methotrexate

Pemfexy
Generic name: pemetrexed

Oforta
Generic name: fludarabine

Mylocel
Generic name: hydroxyurea

Mavenclad
Generic name: cladribine

Infugem
Generic name: gemcitabine

FUDR
Generic name: floxuridine

Droxia
Generic name: hydroxyurea

DepoCyt
Generic name: cytarabine liposomal

Dacogen
Generic name: decitabine

Clolar
Generic name: clofarabine

Arranon
Generic name: nelarabine

Adrucil
Generic name: fluorouracil