COVID Vaccine Boosters in Immuno-compromised People – Could They Also Help Curb Development of New Variants ?

This article is the second in a three-part series on COVID-19 booster vaccines, which is an evolving discussion as more evidence emerges about the performance of vaccines against variants.

Immunocompromised people are twice as likely to die from COVID-19 compared to healthy people and could benefit from receiving a third booster shot.

Despite heated debates about doling out booster jabs in healthy people who are already fully vaccinated against SARS-CoV-2, there seems to be consensus that at least one group could benefit from a third booster shot – immunocompromised people.

Immunocompromised groups, like those with solid organ transplants, are roughly twice as likely to die from COVID-19 compared to healthy people. And even after receiving two vaccine shots, their antibody responses are woefully inadequate.

But a third booster shot has potential to offer those patients stronger protection against  disease and death from SARS-CoV-2, Eyal Leshem, the Director of Israel’s Center for Travel Medicine and Tropical Diseases, told Health Policy Watch – referring to people with organ transplants, cancer patients, and others who are severely immunocompromised.

“There is some evidence that seroconversion rates [antibody responses] are lower in immunocompromised people like people with organ transplants, compared with people with healthy immune systems,” said Leshem, who is also a researcher for the United States Centers for Diseases Control and Prevention (CDC). 

“But there’s also encouraging evidence that a third booster shot in organ transplant patients increases the rate of seroconversion [antibody responses] in those patients.”

Based on this evidence, as well as new data suggesting that vaccines are becoming less effective overall in preventing disease, Israel and France approved a third jab in severely immunocompromised patients earlier this month. 

The United Kingdom and the United States, appear ready to follow suit very soon. Israel has since gone on to announce last week a controversial third jab for all people over age 60 – whose immune systems are generally weaker than their younger counterparts – with other countries likely to follow that move for older, healthy adults.  

“We see a drop in the vaccine effectiveness for those vaccinated early on, and we see it for those elderly people over the age of 60,” said Sharon Alroy-Preis, a top Israeli Ministry of Health expert in a weekend interview with the US television programme “Face the Nation.” 

While protection from disease remains high, protection against infection has dropped precipitously, she added:  “Previously we thought that fully vaccinated individuals are protected [from infection], but we now see that vaccine effectiveness is roughly 40 percent.”

Antibody counts in immunocompromised people rise dramatically following a third vaccine jab, suggesting they could benefit from a booster shot

Third jab among immunocompromised may also help curb some variant mutations 

Although rich countries that offer a third jab already before poorer nations have even been able to get one into the arms of older people leave themselves open to further charges of vaccine nationalism, in the case of immunocompromised groups, the argument may be somewhat different. 

Some researchers have suggested that offering immunocompromised groups an extra jab could also help prevent the virus from replicating in their bodies for long periods of time, and thus mutating into new variants.

To date, a handful of large-scale studies around boosters in immunocompromised people are ongoing or set to begin, including an NIH-led study in 400 people; a double-blind randomized controlled trial by Moderna in 120 people; and a non-randomized Phase 2 trial in 360 people that includes 180 children.

Booster is not magic bullet either 

A third shot may not guarantee potent antibody responses in all immunocompromised patients.

However, a third booster shot won’t always guarantee potent antibody responses in all immunocompromised patients, one report of a retrospective study of 101 patients, published in the New England Journal of Medicine (NEJM) has revealed. In the NEJM correspondence, researchers reported on a retrospective analysis of solid organ transplant patients who had received three jabs of the Pfizer/BioNTech vaccine. 

Strikingly, the NEJM study found that about half of patients who didn’t respond to a second jab also failed to respond to a third one (33 out of 56 patients). Those patients tended to be older and to have weaker immune systems, the study authors said.

Still, the study concluded that a third dose of the Pfizer/BioNTech vaccine “significantly improved the immunogenicity [immune response] of the vaccine, with no cases of Covid-19 reported in any of the patients”.

The lead author of the NEJM letter, Nassim Kamar, has proposed that the families of immunocompromised groups should also be vaccinated – insofar as a third jab is useful, but not always sufficient to protect immunocompromised groups.

“A weak humoral [antibody] response is observed in immunocompromised patients after SARS-Cov-2 vaccination,” Kamar told Health Policy Watch. “This means that most of them are not protected against COVID despite vaccination.”

“Hence, in order to limit the risk of infection, it is required that their relatives be vaccinated,” said Kamar, who is the Head of Nephrology and Organ Transplantation at the Toulouse University Hospital in France.

Second in a three-part series on COVID boosters. See the third article in this series, Boosters: Laboratory Evidence Needs to be Balanced with Field-based Data.

Image Credits: Rhoda Baer/National Cancer Institute, PAHO/Sebastian Oliel, NEJM, International Monetary Fund/Ernesto Benavides.

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