Growing clamour for booster shots in immunocompromised patients

6 minute read

FDA tick imminent for covid vax third dose in vulnerable patients as more immunogenicity data emerges.

Emerging data on immunosuppressed patients reinforces the importance of a timely second vaccine dose and suggests boosters may be beneficial.

Two European studies on covid vaccine responses in patients receiving immunosuppressive therapies for autoimmune and rheumatic diseases, as well as a successful booster trial in immunosuppressed organ transplant recipients, have added to growing clamour for booster shots to protect people with weakened immune systems.

Indeed, as Rheumatology Republic went to press it was announced that the FDA was expected to authorise a third dose of the Moderna and Pfizer vaccines for certain immunocompromised people. Reported to be a response to the resurgence of covid cases due to the Delta variant, the FDA will amend emergency-use authorisations to help people who may not get adequate protection from two doses.

Early reports from a Boston healthcare network have also indicated that breakthrough infections are occurring in a small fraction of fully vaccinated patients with autoimmune rheumatic diseases on immunomodulatory therapies, which were expected to blunt immune responses to vaccines.

Put together, the data suggests a third vaccine dose may be necessary to enhance immune responses in immunocompromised patients.

Commenting on the two European studies of rheumatology patients, Associate Professor Peter Wong, a rheumatologist at Sydney’s Westmead Hospital, said it was still “too early to recommend a booster in immunosuppressed patients” considering current vaccine supplies in Australia.

But it is “reasonable to think we will all need a booster at some stage, especially if [people are] immunosuppressed – and especially if more covid variants develop, which they will,” he said.

One study, published in Annals of the Rheumatic Diseases, found patients on immunosuppressive drugs had an impaired immune responses to covid vaccines compared to healthy healthcare workers.

Both T-cell and B-cell responses were assessed, and although less than 30% of immunosuppressed patients had detectable immune responses after one vaccine dose, response rates improved among the 91 patients who had received a second dose of either a Pfizer or AstraZeneca vaccine.

“Reassuringly, only 8.7% of infection-naïve patients had neither antibody nor T-cell responses detected following second-dose vaccine,” the UK study authors wrote.

“B-cell depletion following rituximab impairs serological responses, but T-cell responses are preserved in this group,” they added.    

The second study, a retrospective analysis comparing seroconversion rates (but not T-cell responses) after first and second covid vaccinations, published in The Lancet Rheumatology, has suggested patients receiving immunosuppressive drugs should not delay their second dose of a COVID-19 vaccine.

In a group of 432 infection-naïve patients with rheumatoid arthritis, ankylosing spondylitis and other rheumatic diseases, those treated with methotrexate and anti-CD20 therapies – but not prednisone or TNF inhibitor – had significantly lower seroconversion rates after their first vaccination compared to patients off treatment and healthy controls, the Dutch study found.

“After the second vaccination, seroconversion exceeded 80% in all patient treatment subgroups [without previous COVID-19 infection], except among those treated with anti-CD20 therapies,” the study authors wrote.

“The bottom line is [these patients] really need that second vaccine dose,” Professor Wong told Rheumatology Republic.

In July, Professor Wong published an update for rheumatologists summarising the limited but growing evidence on vaccinating patients with autoimmune inflammatory rheumatic diseases against covid, as well as influenza and herpes zoster, in the Asia-Pacific region.

He said the two new European studies add to this evidence base, although each study had its limitations. The UK study had very few rheumatology-type patients as most participants were diagnosed with rare autoimmune disorders such as anti-GBM disease and ANCA-associated vasculitis.

Professor Wong also said while B-cell depleting rituximab “wipes out” vaccination responses, it was reassuring that most other modes of immunosuppression were associated with reasonable post-vaccination T and B-cell responses – although only handful of patients in the UK study were on conventional therapies, such as methotrexate, or biologics.

Also, despite good antibody levels in immunosuppressed patients, no cell-based assays were done in either study to test whether detected antibodies neutralised SARS-CoV-2, Professor Wong noted on Tuesday.

Meanwhile, new data just released in the New England Journal of Medicine has reported on the impacts of a booster shot in a small placebo-controlled clinical trial involving 120 solid organ transplant recipients on immunosuppressive therapy.

Half received a third dose of the Moderna vaccine two months after their second dose, with the other half getting a saline placebo. Those receiving the booster had substantially higher immunogenicity than the placebo group, as determined by levels of antibodies, neutralising activity and T-cell response. However, the follow-up was short and the study wasn’t powered to detect differences in clinical outcomes.

The Canadian team concluded that the “third dose was safe when risk versus benefit was considered” and that “a third-dose booster Covid-19 vaccine should be considered, in conjunction with regulatory approval, for transplant recipients who have received two doses of mRNA-1273 [Moderna vaccine]”.

Also published in NEJM, a French study of 101 immunosuppressed solid-organ transplant recipients who received a third dose of the BNT162b2 (Pfizer-BioNTech) vaccine has found the booster shot “significantly improved the immunogenicity of the vaccine” when antibody levels were measured a month later.

“Among the 59 patients who had been seronegative before the third dose, 26 (44%) were seropositive at 4 weeks after the third dose,” the French authors reported.   

The French National Authority for Health had already recommended the use of a third dose in immunosuppressed patients, based on earlier reports. 

The results of these studies coincide with a small, retrospective case series, published on medRxiv but not yet peer reviewed, examining clinical characteristics of autoimmune rheumatic disease patients who contracted covid after vaccination.

All but one of the 16 Boston-based patients with breakthrough infections after two vaccine doses were symptomatic. Most cases were not severe and managed as outpatients, but six required hospitalisation and two deaths resulted. Both those patients had previously received rituximab and had severe interstitial lung disease.

“Additional studies are urgently needed to estimate the risk of breakthrough infections among systemic autoimmune rheumatic disease patients and to evaluate the efficacy of booster vaccines and other strategies for DMARD users with poor immunologic response to COVID-19 vaccination,” the authors concluded.


Ann Rheum Dis 2021, 6 Aug

Lancet Rheumatol 2021, 6 Aug

NEJM 2021, 11 Aug

NEJM 2021, 12 Aug

medRxiv 2021, 5 Aug

End of content

No more pages to load

Log In Register ×