QUESTION: I suffer from an autoimmune disease and need to take medications to suppress my immune system. I’ve had two doses of a coronavirus vaccine. But I’m worried that my medications might reduce the effectiveness of the inoculations. Am I protected from COVID-19?
ANSWER: You certainly have good reason to be concerned. Several studies indicate that the vaccines may not work as well in some patients who are on immune-suppressing drugs. But fortunately, preliminary research suggests that additional shots, or other strategies, may be able to boost vaccine efficacy.
It’s important to keep in mind that patients with autoimmune diseases weren’t included in the original trials for the vaccines. So there was always some uncertainty about how they would respond to the shots.
In people with autoimmune disorders – which include rheumatoid arthritis, lupus and Crohn’s disease – the immune system becomes confused, or imbalanced, and attacks the body’s own tissues. To keep the disease in check, an assortment of medications are usually prescribed to dampen down the immune system.
It is now becoming increasingly clear that these powerful medications can also suppress the immune system’s reaction to the vaccines.
And it’s not just those with autoimmune diseases who are affected. The same drugs are also used to prevent organ rejection in transplant recipients and to treat certain cancers such as B-cell chronic lymphocytic leukemia.
In fact, transplant recipients – who are on fairly high levels of immune-suppressing medications – appear to be at greatest risk of not responding to the vaccines, says Deepali Kumar, director of transplant infectious diseases at the University Health Network (UHN) in Toronto.
Even after receiving the complete two doses of an mRNA coronavirus vaccine, less than half of the transplant patients make antibodies to guard against COVID-19, she adds.
“The challenge right now is to identify those who are at risk of not responding to the vaccines so we can develop strategies to help them,” says Paul Fortin, a professor of medicine at Laval University in Quebec City.
Two recent studies suggest that an additional shot might be able to generate a more robust immune reaction.
Researchers at Johns Hopkins University in Baltimore assessed the immune responses of 30 transplant recipients.
Although all the patients were fully vaccinated, 24 of them had no sign of antibodies against the coronavirus and six had only low levels.
After receiving an extra shot, eight of the patients who initially had no antibodies began to produce some. And the additional jab led to more antibodies in the six patients who originally had low levels.
A study in France found similar results in a group of 101 transplant patients. French health authorities are now calling for a third shot in immune-compromised individuals.
But Canadian doctors say it’s not possible to draw firm conclusions about the effectiveness of additional shots based on these two studies alone.
For one thing, doctors still don’t know how many antibodies are required to guard against COVID-19, says Glen Hazlewood, a rheumatologist and associate professor at the University of Calgary.
Furthermore, the immune system is made up of a host of other specialized cells that are harder to measure than antibodies. “So there is some uncertainty about the level of response that’s needed to protect you,” he adds.
Canadian medical experts generally agree that more research is needed before they can recommend the best course of action for patients on immune-suppressing drugs. Some of those studies are already underway.
Vaccines may not work as well in some patients who are on immune-suppressing drugs, but there may be ways to boost vaccine efficacy.
For instance, Fortin and his colleague Inés Colmegna at McGill University launched a study to document the response to two doses of the Moderna mRNA vaccine in a group of 165 volunteers with rheumatoid arthritis or lupus and 55 healthy people. Those who have poor responses to the standard vaccine protocol will then be eligible for an extra shot.
Not only will the study help determine who is most likely to benefit from a third dose, but it will also investigate whether this is a safe approach in patients with autoimmune disorders.
Fortin says there has been some worry that an extra shot might stimulate the immune system in a way that leads to a “flare” in a patient’s underlying disease.
“At this point, there’s no evidence of flare-ups – and that’s reassuring,” says Fortin, who holds a Canada Research Chair in systemic autoimmune rheumatic diseases.
Meanwhile, Kumar at UHN is leading a study that will examine a third shot in a group of 120 transplant recipients. Half of them will be injected with the Moderna vaccine, while the other half will get an inactive placebo shot.
Vaccine safety is also a key component of this study. “We are looking for any off-target effects of the third dose – like whether organ rejection might occur,” she explains. “So far, we haven’t seen that happen with the first two doses. So that is good news.”
Kumar and her fellow researchers will begin analyzing their data over the next few weeks. “I think our study will significantly add to the growing body of literature about third doses.”
But she also believes other approaches may need to be considered for patients who do not respond to additional shots. (As a case in point, 16 of the 30 subjects in the Johns Hopkins study did not produce more antibodies after a third inoculation.)
One option might involve patients temporarily stopping or lowering the doses of their immune-suppressing medications. “They could modify their drug treatment for two weeks, giving the vaccine time to take effect, and then resume the medications at the regular levels,” she explains.
“It is a bit of a risky strategy,” Kumar acknowledges. By altering their drug therapy, it might trigger organ rejection in transplant recipients or a disease flare-up in people with autoimmune diseases.
Even so, she believes this approach should at least be studied so that vaccine recommendations are based on actual evidence, not just speculation.
She points out that some of these patients – especially the transplant recipients – are extremely susceptible to COVID-19. “They can’t effectively fight off the virus because of their immune suppression,” she explains. “In our transplantation program, more than half of the patients who got COVID were admitted to hospital.”
To make matters worse, their protracted battle with COVID means that they shed the virus much longer than people who are able to bring the infection quickly under control.
And that could be bad for everyone. Prolonged shedding increases the chance the virus will mutate into a new and more infectious variant that’s capable of evading the vaccines.
Researchers are hoping to release their recommendations for immune-compromised individuals sometime this summer.
However, until the recommendations can be implemented, these vulnerable patients are being urged to adhere to safety measures even if they have been fully vaccinated, says Hazlewood. This means they should wear a mask in indoor public places and keep physically distanced from people outside their household.
“I understand it can be frustrating for people who have to continue with precautions,” says Kumar. “But we are working as fast as possible to find ways to ensure that the vaccines work and whether a booster dose is necessary.”