What level of antibodies should you have to feel safe?
There are not enough studies yet that explain that, the experts said. There are also dozens of commercial assays available, and each has its own curve in its numbers, Pereira said.
“And some of them are difficult to interpret, and definitely they’re very difficult to compare across the board. So it’s highly dependent on the assay. And you can see that even in the studies that are available out there, that, some studies, for example, they’re all using different spike antibody assays. If I had a test and if I were to look at whether I had the adequate response or not, I would look at that particular test characteristics and speak with their provider about whether the number that you get is related to a good response or not a good response.”
“I am immunocompromised due to Rituxan maintenance therapy for non-Hodgkin’s lymphoma,” another audience member said. “I’ve heard about gamma globulin being infused with COVID antibodies and then given to patients who are on monthly infusions of gamma globulin. What can you tell me?”
Gamma globulin replaces what a patient is missing. Over time, as vaccination numbers increase, gamma globulin — which is basically a pool of antibodies from healthy donors — will start to contain antibodies to COVID-19. So it’s possible that it will become an effective strategy to help boost immunity for those who can’t generate it themselves, Wherry said.
Monoclonal antibodies have been used as a treatment for COVID-19 patients to prevent severe disease. Now, researchers are studying whether monoclonal antibodies can be used to prevent people from contracting the virus in the first place.
“So we have asserted that there’s some debate now about, for these immunocompromised individuals who we don’t think are responding to the vaccine, whether they should get periodic monoclonal antibodies, whether it’s once a month or once every three months, it really depends,” Pereira said.
But that option is not yet available for most patients, the experts said.
An Eli Lilly researcher tests possible COVID-19 antibodies in a laboratory in Indianapolis. (David Morrison/AP Photo)
Drugs and vaccine effectiveness
“I have Bordetella bronchiseptica [a common pathogen in the respiratory tract of many wild and domestic animals, rarely found in humans], on regimen Tobramycin inhalation 28 days on, 28 off. Have rheumatoid arthritis, [and am on a] monthly infusion Orencia. Now diagnosed with CLL, awaiting what stage of disease. Do the above drugs affect B & T Cells?”
Wherry recommended that this individual talk in detail with his or her physician.
The antibiotics for Bordetella are unlikely to affect the immune response, he said, but the bordetella infection itself may.
The experts said autoimmune diseases somewhat affect vaccine response, but not to the degree cancers that affect the blood, bone marrow, and lymph nodes, or solid-organ transplants do. It is possible medication for rheumatoid arthritis could affect vaccine response, but more needs to be known.
“We don’t yet know a lot about how immunosuppression for RA and other diseases affect vaccination,” Wherry said. “There’s some data starting to emerge, and most people seem to make at least some immune response to the vaccine. We don’t yet know how protective those responses will be, but people do respond to the vaccines.”
The treatment for CLL may be more immunosuppressive, however. So this person should be sure to get vaccinated before starting that treatment, Wherry said.
“I suffer from psoriasis and am currently taking Otezla orally to control my outbreaks. I recently learned that folks who take immunosuppressive medications may not produce any or sufficient numbers of antibodies against the COVID-19 virus. I am curious if you have learned if PDE4 medications (i.e. Otezla) present similar issues as TNF [a medication for autoimmune conditions that block a substance in the body that can cause inflammation and lead to immune-system diseases].”
There are many different flavors of immunosuppressant drugs, and they treat a variety of different manifestations of autoimmunity or other diseases, Wherry said. The metaphor he uses is getting work done on your car.
“The ones that we have looked at so far are the equivalent of taking the engine out of the car. They hit the big parts of the immune system so that you block lots of activities of the immune system, especially those making antibodies,” Wherry said. “These would be things like rituximab [which in addition to treating cancer, is used to treat autoimmune conditions like rheumatoid arthritis].”
“Then you have things like removing the muffler, or taking away a couple of doors in the car, things that are much more specific to certain functions of the immune system. And they tend to allow some aspects of the immune system to continue to work, but key pathways that are important in very specific disease processes do not work. This is the case for some of the newer drugs for psoriasis,” he said. “So the level of impact on the vaccine response may be a lot less in those cases because you’re not taking out sort of the main engine of the immune system. You’re taking out an optional component that you would need for one activity, but not others.”
There are no specific studies yet that look at what Wherry calls “more specific immunosuppression regimens.” But there’s some data emerging on the medications that are predicted to have the most broad and dramatic impact on vaccines, he said.
“So right now, I think those more specific things like TNF blockers and some of the other pathways mentioned are less likely to have an all-or-not effect on vaccine responses,” Wherry said. “But the data is emerging very quickly. We’re seeing reports almost daily as we move forward. So, I would stay tuned. I would stay in touch with your physician. But with those drugs, I would be less concerned than some of the other broader immunosuppression situations that we talked about earlier.”
Overall vaccine effectiveness
“How many vaccinated immunocompromised people have become ill with COVID. Is there any data on this?”
There have been a couple of studies about breakthrough COVID-19 cases among vaccinated transplant recipients.
Columbia University studied 904 kidney and pancreas transplant patients who got the vaccine. Thirteen of them contracted COVID-19, and seven of those cases met the CDC definition of a breakthrough infection. A similar study from Yale studied solid-organ transplant recipients, and found breakthrough infections occurred in three of 459 fully vaccinated patients.
“Living with an immune deficiency is terrifying. I took the first vaccination, Moderna, and had an awful reaction that took weeks to recover from. I am conflicted when it comes to deciding to take the second shot. What does science tell us about this?”
Side effects like fever, chills, and muscle aches are common, and can be a sign that your immune system is responding. They usually resolve after a day or two, but some people can experience persistent side effects. Adverse events like blood clots, on the other hand, are unexpected reactions to a vaccine.
Wherry said it’s important for this individual to get a second dose. Vaccine clinical trials show people get reasonably good protection after one dose. But the clinical trials do not explain how long that protection after one dose lasts, because everybody in the clinical trials got second doses.
“So it is worth considering getting the second dose at some point down the road. It’s worth talking to your physician,” Wherry said. “It’s possible to get antibody testing in some places, and that might help make that decision about whether or not to get the second dose.”
Most of the side effects pale in comparison to the symptoms of COVID-19, Pereira added.
“So for this particular individual, it really depends on the kind of side effects that they had. But in general, they should proceed with the second scheduled dose,” he said. “Whether they want to delay it for a week or two, they can talk to their provider and discuss some strategies. Certainly after the second dose they can get ibuprofen or acetaminophen to perhaps reduce some of the side effects, but it really depends on the kind of symptoms this person is having.”
I have fibromyalgia and IBS [irritated bowel syndrome]. I don’t take any medication for these. Since the second Pfizer shot, I’ve been having lots of leg, back and overall pain. My joints hurt all over too. Can this be related to the shot?
It could be, or it might not be, both experts said.
“As we’ve vaccinated hundreds of millions of people, everybody is more aware of things that happen at a similar time as getting the vaccine. And so we call this observation bias, or whatever you want to say, that if you watch 100 million people very carefully for a month, you will find events happening even if you don’t vaccinate them,” Wherry said.
“And I’m not saying that that’s the case for this individual. But the temporal link may not be sufficient to infer causality. It may not be unrelated either. It’s hard to know, and especially in individual cases, it’s very hard to ever know causality.”
Pereira said when it’s difficult to tease out the side effects from the vaccine versus symptoms from other chronic illnesses, it might help to note the timing of the symptoms. Side effects usually occur within a few hours to a few days after the vaccine.
“I have several autoimmune conditions, and I am unsure if it will trigger them into flares doing the vaccine.”
Pereira and Wherry said they have not seen any detailed reports showing that autoimmune symptoms worsen following vaccinations. In fact, since many patients with other immune diseases are on some form of immunosuppression, that likely blunts the vaccine responses slightly and may counteract any potential exacerbation that may occur, Wherry said.
“I’m on medication for MS [multiple sclerosis]. My research study team told me for years to stay away from any vaccines. They just don’t know how it might affect my body while on this drug. Can there be adverse vaccine effects for people like me on Kesimpta for MS?”
There are at least 16 different treatments for MS, Wherry said, and their effects on vaccines can vary. Most should only make the vaccine response suboptimal, he said, and it’s unlikely to complicate MS.
The University of Pennsylvania has begun studying which MS medications reduce vaccine effectiveness, and at least one of the drugs does.
Most physicians recommend either getting vaccinated before you start your cycle of treatment for MS or doing it in between cycles, Wherry said.
The National MS Society recommends that if you are about to start Kesimpta, consider getting fully vaccinated two to four weeks or more prior to starting the treatment. There’s no data to guide timing for those already taking Kesimpta. When possible, resume Kesimpta injections two to four weeks after getting fully vaccinated.
Pereira said this individual should probably get the vaccine, without having any expectations of a strong antibody response.
“But again, the immune system is a complex set of cells. And it may be that this person’s T cells will maybe pick up the slack and form some sort of response. So it certainly seems safe. And to get these vaccines, and whether it’s going to be effective or not, it will be a little bit up in the air,” he said.
Saba Tedla, owner of Booker’s restaurant in West Philadelphia, said she’d like to keep their outdoor seating permanently. (Kimberly Paynter/WHYY)
What is safe to do?
“My husband is 71 and has taken Humira for psoriatic arthritis for 30 years. His daughter and her family are not getting vaccinated. We canceled our trip to visit her. We were planning a three-week stay at her house. Can we ever go there safely?”
Pereira said the public health initiative should focus on understanding why some people don’t want to or are not getting vaccinated. If the husband’s family got vaccinated, they would not only protect themselves against the virus, but also their immunocompromised family member. Until they get vaccinated, they could harbor the virus without knowing it, and transmit the virus to him.
Pereira added that he doesn’t believe Humira affects the immune system that much, but that this individual’s husband should wear a mask, social distance, and avoid being exposed to unvaccinated individuals.
Wherry said these situations will arise more and more.
“I think the real goals here are to get to a high enough level of nationwide vaccine coverage that we eliminate pockets of continued spread or even increases. We’re now starting to see variant virus numbers increase in some places in the U.S., and it correlates very, very well with lower vaccine rates. And so there is a direct correlation between the safety of people at risk visiting with relatives and friends and the coverage rate of vaccination,” he said.
“So as much as there’s, in some parts of the country, a debate about whether they should get vaccinated or not, the data is super clear: When the vaccination rates are lower, the risk of virus spreading is higher.”
A person from Monmouth County asks: I did not develop COVID antibodies, likely because I am taking Rituxan for RA. I am also on IVIG [intravenous immunoglobulin] every three weeks. Can I be around my 11-year-old twin granddaughters whose parents are vaccinated in the house?
These questions come down to risk assessment, both experts said: Consider COVID-19 cases in your location, including the Delta variant of the virus, as well as your grandchildren’s school’s policies around preventing the spread of the coronavirus.
“So we should see vaccination become available for younger kids, or when these 11-year-olds turn 12, they can get vaccinated. These are things that will be changing rapidly over the next four to six months,” Wherry said.
“Locally in the Philadelphia area right now, COVID cases are pretty low, our hospitalization rate is the lowest it’s been in a long time, the rates of local spread are pretty low. The risk may be on the relatively low side. Other parts of the country where you’re seeing continued increase in the rate of spread and new infections, that equation makes it a little bit different.”
“I am immune-compromised from cancer, and have been fully vaccinated. Can I safely be around people who had mild COVID and are not vaccinated?”
“I would say don’t tempt fate,” Pereira said. “The vaccines are not 100% effective. I think if there is an opportunity to avoid that exposure, I would by all means avoid it until they are no longer considered contagious.”
If it’s necessary to be around those with COVID-19 diagnoses, such is the case for health care providers, wear a mask and maintain a physician distance.
Spending time with people who aren’t vaccinated but who don’t have known COVID-19 takes a risk assessment evaluating COVID-19 rates in the area, and whether the unvaccinated people could potentially have the virus due to their daily interactions, Wherry said.
A person from eastern Montgomery County wrote in: “I’m immunocompromised and vaccinated but concerned about going back to the office where there are maskless and unvaccinated people. My company has a mask requirement, however not fully following through on that. How do I cope with this moving forward?”
Wearing a mask yourself, and maintaining a physical distance from others, goes a long way, the experts said. But Pereira added that if you feel comfortable, talk to human resources about your situation. Perhaps they will allow you to work remotely or have your own office space. If comfortable, you can also explain to coworkers that you’re not as protected as other people.
“It’s going to be a tricky situation because on the one hand, you might not want to divulge your medical history, but this is a situation where it is better to be safe than sorry and avoid transmission,” Pereira said. “I think that we’re in a good situation right now that cases are very low and the risk is low overall. But I think it’s probably a good idea to discuss this in advance with the company and figure out ways to avoid that risk.”