COVID-19 and Monkeypox: What Transplant and CAR T-cell Recipients Need to Know

COVID  19 and Monkey Pox: What Transplant and CAR T-cell Recipients Need to Know.

Wednesday, November 16, 2022

Presenter: Dr. Shivan Shah MD, Houston Methodist Hospital

Presentation is 26 minutes long with 23 minutes of Q & A.

Summary: The COVID 19 pandemic has become an endemic disease that requires ongoing vigilance from stem cell transplant recipients. This presentation reviews current guidelines for when to test for COVID and the varieties of treatments that have become available since the onset of the virus.

Highlights:

• COVID is here to stay, and yearly vaccinations are likely to become routine.  Immunosuppressed patients should maintain reasonable precautions like masking in large crowds and  “cocoon vaccination” by encouraging family members and close friends to also become vaccinated. 
• There are several effective antiviral medications for treating COVID-19 including Remdesivir, Paxlovid and Marabavir. Since they can interact with other medications to prevent graft-versus-host-disease in transplant recipients, patients should consult with their oncologist before receiving these medications.
• Multiple studies have conclusively shown that ivermectin, azithromycin and hydroxycholoquine are not effective against COVID and should be avoided. Studies have also shown that vaccines consistently reduce the severity of COVID infections and there is no evidence that vaccines do more harm than good.

Key Points:

(02:09): COVID is a rapidly mutating virus, but effective treatments are becoming available.

(02:50): People should test for COVID if they have respiratory symptoms or close contact exposures.

(05:08): Antibody testing is not a good measure of immunity because it is only one form of immunity.

(07:38): Monoclonal antibodies are a one-time infusion that can prevent severe COVID. However, the virus is now mutating so fast that monoclonal antibodies quickly lose effectiveness and new ones must be developed.

(08:44): Several anti-inflammatories are used for severe COVID, but steroids are the mainstay of these treatments.

(11:12): COVID can be prevented for many people by staying up to date with vaccinations including the newest bivalent vaccine.

(12:44): Vaccines may not prevent getting the virus, but they can decrease shedding to others and catching it from others.

(14:17): Monkeypox is not a new virus; it originated with African rodents in the 1950s.

(15:37): Monkey pox is a rare, self-limiting disease with relatively low mortality.

(20:55): There are two vaccines for monkeypox; only one of them can be given to immunosuppressed patients. Vaccination for monkeypox should occur after exposure to prevent the virus from causing infection and sexual partners of people diagnosed with monkeypox should also be vaccinated.

Transcript of Presentation:

(00:01) [Susan Stewart ]       Introduction. Good evening and welcome to Webinar COVID 19 and Monkey Pox : What Transplant and CAR T-cell Recipients Need to Know. My name is Susan Stewart and I'm the founder and the executive director of BMT InfoNet, also known as Blood and Marrow Transplant Information Network, and I will be your host this evening.

(00:22): Without further ado, I would like to introduce to you our guest speaker for this evening, Dr. Shivan Shah. Dr. Shah is an Onco-Transplant Infectious Disease Specialist at Houston Methodist Hospital where he works with the oncology team and the stem cell transplant team to treat patients who have various oncology or transplant related infections. He previously trained at MD Anderson Cancer Center in Houston where he helped develop protocols to treat opportunistic infections. Dr. Shah's clinical interest and specialties include onco transplant infections, infections in leukemia and lymphoma patients, respiratory infections and travel medicine. Please join me in welcoming Dr. Shah.

(01:15): [Dr. Shivan Shah]     Overview of Talk. Hello everyone and good evening. So, we'll begin the presentation, just some brief introduction about COVID 19 and monkeypox. In the past few years, we've dealt with multiple viruses. Currently, we're having a surge of influenza and RSV, but we've learned a lot since the start of the COVID-19 pandemic. So, we're going to have an update on that and then we're going to touch a little bit on Monkeypox and see what risk factors there are for our immunosuppressed population.

(01:57): So, today's objectives, we're going to learn about COVID 19, the diagnostics, treatments, prevention and whatever is in the future. And then we'll have a quick discussion on monkeypox.

(02:09): COVID is a rapidly mutating virus, but effective treatments are becoming available. So, I wanted to first show you this slide on the different COVID variants. As you can see from May 11th, 2020, when we first started doing analysis of the variants in the genotypes, we found that it mutated fairly quickly. As you can see, every time we came up with a monoclonal antibody or some form of treatment, it mutated, and then we pop to another one. Luckily, we've gotten ahead of this curve and we're developing more and more different things which I'll get to shortly.

(02:50): People should test for COVID if they have respiratory symptoms or close contact exposures. Diagnostics in our stem cell patients. So, when to test? That's always a question I get in my clinic. Basically, at this point we have an endemic virus. This virus lives in our environment. So, pretty much [you should test] anytime you have a symptom of upper respiratory infection, or if you had close contact exposures or were at large gatherings, and you feel like you might have got caught it. Just test. We have at-home tests. We'll go over the different type of tests too, But we have different varieties of tests and we'll see which one is the best one and which one you shouldn't do.

(03:32): Retesting is not recommended once people are negative for COVID. Again, another question is when to retest after an episode. Retesting is not recommended for patients who are immunosuppressed to see if the disease is gone because, unfortunately, our immunosuppressed patients might not have active clinical disease but could test positive with the PCR test, and they may not be infectious.

(03:53): We don't actually recommend patients continue to retest when they're negative. That unfortunately was developed by a lot of work-based elements without any scientific background to it, so we don't recommend it.

(04:15): The PCR test is the gold standard, but rapid antigen tests are becoming more common. The types of tests, the gold standard is the nasopharyngeal PCR, the one that they swab all the way back in your nose, touch your brain essentially. We always say if it doesn't tickle your brain and you're not crying, it wasn't a good sample.

(04:30): The rapid antigen is the one that we've seen being used a lot more. Those are the ones you can get over-the -counter at the store, more like a nasal swab. The antibody tests that people have been using, which we will go over. and certain other blood tests. To clarify blood test, there is no good blood test to determine if you have active COVID or viral infection from COVID. And we do not recommend getting any sort of blood test for this. And if you hear about it, it probably isn't a good test.

(05:08): Antibody testing is not a good measure of immunity because it is only one form of immunity. Antibody testing, I just wanted to quickly go over that. I always get asked, "Can I see what my level of immunity is?" It's actually not that simple. You could have a negative antibody test in the blood and you could still actually have some sort of immunity. There are different cells in your body. Some of them produce antibodies, other ones work differently. Instead of using antibodies, they fight viruses by their own cell, the T-cell.

(05:39): There's no actual number or level that I can tell you you're immune or you're not immune. Some people can have a low level and be immune. Other people can have a high level and not be. It's hard to say, there's no standard care. We highly recommend against getting antibody testing to determine if you're immune or not.

(05:58): Now, some people just want to know if they've ever been exposed to it. You can use antibody testing to determine if you've been exposed to it.

(06:10): There are now several effective inpatient and outpatient antiviral medications .Going into treatment. Luckily, since the May 2021, when we were first battling this pandemic, we've developed a lot of treatments. I'll start with the antiviral first because they are the ones that we can technically use outpatient. The one that is only used inpatient is Remdesivir because it's only IV. But Paxlovid and Marabavir, both are antivirals as well and they're available outpatient.

(06:44): Antiviral agents could interact with other medications so always consult with your oncologist before starting them. The problem with those two are they interact with many medications. And if a patient has GVHD, they could be on a medication to prevent the GVHD that interacts with the Paxlovid or Marabavir and that can cause toxicity on medication. So, we always don't want to just give Paxlovid outpatient to anybody. You need to clarify with your oncology doctor or infectious disease doctor if it's okay for you to take it.

(07:16): The Remdesivir, unfortunately, is IV only, so you'd have to be in the hospital and get it. Typically, these treatments, all of them are about five to 10 days, but more and more are being developed. They're trying to find an oral formulation of Remdesivir eventually. Hopefully, we get to that point.

(07:38): Monoclonal antibodies are a one-time infusion that can prevent severe COVID. Monoclonal antibodies. The most famous one was Regeneron. It's a concentrated amount of antibodies against COVID. They give a very high dose and basically it's a one-time infusion. It's used to pretty much prevent progression into severe COVID.

(08:02): The job of these medications is not to prevent you from getting COVID, of course, it's to help prevent you from getting severe COVID. So, all these medications will do that.

(08:16): However, the virus is now mutating so fast that monoclonal antibodies quickly lose effectiveness and new ones must be developed. Regeneron, actually you won't be able to find anymore because of the variant mutations that we're getting with COVID. We've had to come up with new different monoclonal antibodies. And honestly, even the ones we have today won't work next year because the virus will mutate. We'll have to come up with different ones. That's why I didn't list them all because there's 20 or 30 different ones. So, I've only listed most...ones

(08:44): Several anti-inflammatories are used for severe COVID, but steroids are the mainstay of these treatments. Anti-inflammatories. Now, this is used for when somebody develops severe COVID or they're hypoxic - have decreased oxygen, inflammation of the lungs. Tocilizumab is actually used in a lot of our oncology patients and CAR-T patients. We used it before to prevent CRS [cytokine release syndromes] and then during COVID, it was used as an anti-inflammatory for COVID, pneumonia. It works fairly well at decreasing mortality.

(09:23): But the mainstay one that we use is steroids, still. High dose steroids for about 10 days was shown to decrease mortality in patients getting into it.

(09:35): Another one that we use is Baricitanib. That was recently published as well. That worked fairly well. The tocilizumab or baricitanib both have side effects that could lead to bleeding and potentially increased infections, but steroids as we know can lead to increased infections as well. There are certain contraindications for each of these [and is why] the physician might choose one or the other. But all of these can only be given inpatient. You should not be given this as an outpatient because you'll be on oxygen and you'll need more radical treatment.

(10:16): Studies have conclusively shown that ivermectin, azithromycin and hydroxycholoquine are  not effective against COVID. And then what's not recommended is ivermectin, azithromycin and hydroxycholoquine. Multiple, multiple, multiple studies have shown that these are ineffective against the COVID virus. They do not have any activity against it. Earlier studies were very faulty, and of course, there's a lot of panic, so people wanted something to help treat [COVID]. But we've learned that [these] just don't work.

(10:50): So, antivirals, as I said, the Paxlovid and Marabavir have interactions so just make sure you discuss them with your physician before you take any because they're available over the counter. Some people will end up taking them from one physician but should discuss with their oncologist if it's okay. We just want to make sure that that point is made.

(11:12): COVID can be prevented for many people by staying up to date with vaccinations including the newest bivalent vaccine. So, prevention. Basically, what we found, there' are new guidelines for transplant and CAR-T vaccination schedules. And as you can see the Janssen, J&J, that's one of the newer ones. The additional dose, if you got the two doses, then they recommend a booster dose two months after the additional dose. I'll go into a little bit about what the plan is in the future in a couple of slides.

(11:47): But for all patients, it is highly recommended that new bivalent vaccination, done recently for all our immunosuppressed patients, should be given. And getting the booster dose at three months for the Pfizer and Moderna, is recommended.

(12:11): The bivalent one is not listed here because that came out after these new guidelines came out and we still recommend that because they're targeted to the specific more recent variants.

(12:26): Masking is still recommended for immunosuppressed patients in large crowds. Additional prevention. Again, masking is still recommended in large crowds, especially for immunosuppressed patients. Holidays are coming up. So smaller crowds, small visits during the holidays are recommended. Again, I know it's hard and if you are in a large crowd, mask up.

(12:44): Vaccines may not prevent getting the virus, but they can decrease shedding to others and catching it from others. Cocoon vaccination, meaning, try to convince any family or friends that come over for the holidays to be vaccinated before they come. Vaccines don't prevent you from getting the virus but they can decrease shedding. They can decrease you catching it from someone else. And if the entire family has it, you got a very good herd humidity essentially from the vaccination.

(13:07): And again, hand washing, and sanitizing are always recommended. That's just a normal thing for any infection you should be doing.

(13:20): The COVID pandemic is now an endemic that is here to stay and yearly vaccinations are likely to become routine.  Future of COVID. So the pandemic has become endemic, which just means that this virus is here to stay. We're going to live with it. The vaccination is gearing towards a yearly vaccine like influenza, maybe even twice a year. We have to see the trends, but I could see it definitely happening yearly.

(13:42): We're always getting newer antivirals being developed for this. Currently, the only three antivirals that work against COVID are the ones I mentioned. No other antiviral really has any efficacy against it. So, that's where the future is leaning towards with COVID, and hopefully, we can see less and less cases. I know at my hospital I'm seeing less and less, so it's good.

(14:17): Monkeypox is not a new virus; it originated with African rodents in the 1950s. Now, I'm going to switch gears and go to monkeypox. We'll discuss a little bit about the history of it. Not a new virus. It's something that we've seen before. So, just because it's an exotic virus, a lot of people didn't hear about until recently. It was discovered in 1958. There were two outbreaks in colonies of monkeys kept for research. That's why they named it the monkeypox. But the source actually isn't from monkeys. It's from African rodents and non-human primates, but usually in African rodents is where we see it.

(14:57): The first human case was in 1970. We've had multiple outbreaks even in the US before, but it's usually from animals coming from out of the country.

(15:10): Last summer monkeypox turned into a transmissible disease. What kind of change during this little outbreak during the summer was it turned into a transmissible disease, like sexual transmission. And that was a new finding of monkey pox that we hadn't seen. So, that's where the concern was.

(15:37): Monkey pox is a rare, self-limiting disease with relatively low mortality. It's a rare disease, the same family of smallpox. Rarely, you'll see any fatalities. It's not a high mortality type virus. It is self-limiting. And usually it's all from international travel or imported animals. But we've had it multiple times in the US before.

(16:04): Monkeypox is often transmitted through sexual contact and presents as rash along with other symptoms. Signs and symptoms. So, the rash may occur before or after some of these symptoms. We see a rash on extremities of the skin if you touched an animal and all that. But recently, it's been more sexual transmission. We've seen genitals and the anal area having it, hands, feet, mouth. face or chest. Symptoms can be fevers, chills, swollen lymph nodes, exhaustion, muscle aches, backache, headache. Respiratory symptoms are more like nasal congestion versus pneumonia, which I mean COVID was like more of a pneumonia. This will be more just sore throat, nasal congestion.

(16:44): Symptoms can occasionally become more severe with necrotic lesions. Severe symptoms can happen where you can get necrotic lesions that are pretty severe. Lymphadenopathy that can obstruct airways and multiple organ system involvement, meaning nodular lesions that can cause septic-like syndromes, encephalitis causing maybe altered mental status, myocarditis, even affecting the eye and around the eye so it can get severe. These are the lesions you see. It's usually a single area unless you have immunosuppressed patients or a high inoculum. So, if somebody touched one of the rashes and it was all over their hands, they touched it all over, it could spread to multiple areas. Typically, it's a single lesion. And then it eventually becomes necrotic and scabs.

(17:45): The duration of symptoms. Some people get flu-like before the rash, other people get the rash and then symptoms. It usually starts within three weeks of exposure, and they develop the rash one-to-four days later. Symptom timelines vary, especially with this new one, but usually, two-to-three weeks, patients can continue with symptoms until the rash scabs over.

(18:15): Monkeypox can be transmitted from the onset of symptoms until any rash has fully healed. Transmission. So, first thing with monkeypox, you can spread it to others at the time symptoms start until the rash has fully healed and a fresh layer of skin has formed. So, it's very important to avoid any random rashes on somebody.

(18:30): We've seen patients having exposure because they touch somebody with rash. But luckily, it turned out not monkeypox positive but still something you need to worry about. It could be other types of diseases. So anytime you see rash, try to avoid it.

(18:52): If there are no symptoms and there was an exposure, somebody had an exposure, can you get it from that person who had an exposure? There are those cases that we've seen. As long as a patient, the person who was exposed doesn't have any symptoms. Contact with monkeypox with saliva, upper respiratory secretions can cause it too.

(19:13):   Testing. Currently, testing is only recommended if you have the rash consistent with monkeypox, just because we don't have enough tests to test for every single person with sore throat and things like that. You need to contact your physician who will have to contact the health department and they'll test you for it. Swabbing the area of the vesicles is usually where you test so that way you can see if viral replication occurs.

(19:52): Treatment should occur for symptomatic, high risk patients like stem cell transplant recipients. The treatments for immunosuppressed individuals. So, basically, treatments should be considered for patients who are high risk, meaning stem cell patients, cancer patients - anytime you've gotten a stem cell [transplant], even if it's an auto, you're still consider [a stem cell patient]. [Treatment should also be considered for patient who had a] solid organ transplant or HIV disease.

(20:11): Several medications are currently used for monkeypox. There's no treatment approved for monkeypox. However, tecovirimat, brincidofovir, and vaccinia immune globulin are all used for it. Tecovirimat is the one that you could get from your physician, from the CDC. They'll order it. If you have exposure, they'll ship it over pretty fast. It's an effective treatment against i. And typically you'll want to give it to immunosuppressed patients just because they have higher chance to developing severe monkeypox symptoms.

(20:55): There are two vaccines for monkeypox; only one of them can be given to immunosuppressed patients. There are two vaccines that are approved for monkeypox in the US. Only one can be given to our immunosuppressed population. The JYNNEOS, it's made with a virus that has been crippled essentially, it cannot replicate. So, it's used as the mainstay for immunosuppressed individuals. We have given it to patients that have been transplanted. It's fine. There have been no reported cases that the patient developed monkeypox from the vaccine itself. As I said, it's a crippled virus so it cannot replicate.

(21:40): Vaccination for monkeypox should occur after exposure to prevent the virus from causing infection and sexual partners of people diagnosed with monkeypox should also be vaccinated. And then, who should be vaccinated? This is one of the rare instances where you give a vaccine after you've been exposed to very quickly prevent the virus from causing any infection. The other people that should be vaccinated, especially if [they had] close contact with someone with monkey pox is if one of your sexual partners in the past two weeks has been diagnosed with monkeypox. So, a two-week period, the incubation period can be that long. And then, they've recommended recently vaccination for men who have sex with men or transgender, nonbinary people , if in the past two weeks you've had sex with multiple partners, group sex, commercial sex workers, sex at a commercial event venue, an area where monkeypox remission is occurring.

(22:30): Monkeypox cases in the U. S. have been rapidly declining since the summer. We have good news now about the rates of monkey pox. So, this is the best part, as you can see, monkeypox cases on a seven-day daily average have almost gone down to zero. And this is just because the US has actually been pretty decent about vaccinating individuals, trying to curb it. And also, the transmission is not as contagious as COVID or influenza because it's sexually transmitted. So, again, in the summertime, yes, we were seeing a lot and then it was eventually going to taper itself off. Now, is this the last we'll ever see of it? Probably not. There are always outbreaks. There's viral spillover from other areas of the world and I expect in the future we may have this. But again, we have effective vaccines and treatments against it.

(23:32): Vaccination for COVID is crucial in preventing severe cases of the virus. So, in conclusion, COVID is likely here to stay. We have major advancements in reducing severe disease. Vaccinations are never to prevent you from getting it for COVID, but they will curb you from getting severe COVID. The treatments that we have, too, will help prevent you from getting severe COVID. That's the main aspect to these treatments and vaccinations, and that's what we want to avoid - severe COVID.

(24:05): Test for COVID only under specific conditions. So next, avoid unnecessary testing and swabbing. Again, be very low threshold to swab and test if you've been exposed, large crowds, if you're going to a gathering. But don't test yourself to see if you're immune constantly. Don't test yourself with blood tests.

(24:28): The antigen test is fine to do, especially if you're high risk that you may have been exposed by somebody during the holidays. Children are high risk because they've been in school, and they become very symptomatic. They might spread the virus. So, it's always better to be safe and sorry at that point. But again, avoid the unnecessary tests.

(24:51): Monkey pox. What we've seen is, likely, it's not a major cause of infection in immunosuppressed individuals just because the rates are going down now, and we are not as concerned that it'll be an issue. But you want to know the patients that's in that category that may need to get the vaccine. It is reasonable to go get it before maybe another outbreak happens. And just, I always want to say that there will always be new viruses popping up and it's our job as infectious disease doctors to help put down the fear a little bit of it. There's always going to be concern, but again, there's always going to be ways to find treatment.

(25:32): Just an advice, make sure you follow the recommendations that we have for you. Listen to your oncology physician and your ID doctor and we'll be able to get through any type of infection in the future hopefully. All right. So, questions I guess. Thank you.

Question and Answer Session

(25:54): [Susan Stewart]     Thank you Dr. Shah. That was a very good overview of where we're at with COVID and with monkeypox. We have a number of questions. We'll try to get to them as many as possible. And again, if you would like to submit a question, please type it into the chat.

(26:16): The first questions: "Is Evusheld still effective in resisting the latest Omicron subvariant or is it no longer being recommended for people who are immunocompromised?"

(26:30): [Dr. Shivan Shah] Evusheld is one of those monoclonal antibody situation, unfortunately it is not as effective. Like I said, every time there's a mutation we have to come up with a new one. There will be other ones, but the problem is as it's endemic now, there might be random variants popping up. It is still recommended at this time that people are getting Evusheld, but I will say the efficacy is much lower. There are some variants that Evusheld does work for, but again, it's just going to keep mutating and then there are some of the monoclonal antibodies that will work and some that won't work, unfortunately.

(27:18): [Susan Stewart] All right. The next question: is, "Is there any sense in how to protect the person from COVID who fits my husband's profile: six-month post-transplant, has only had bivalent booster since transplant per doctor's instructions. Should his immunity be tested at some point and should he receive further COVID testing?"

(27:37): [Dr. Shivan Shah] No, like I said, it's going to be hard to judge with the immunity. I do not recommend testing immunity again and again and again. So the vaccines, they don't necessarily need to boost your antibody level, which is the immunity test that they test for. Vaccines can also work on your T-cells, which you can't really test for. And T-cells help fight off virus too. So, it's still recommended. He's gotten the bivalent vaccine. The next vaccine will likely be next year. And I would recommend getting it at that point just to help curb any potential severe COVID because the vaccine helps with that. But I do not recommend getting tested for immunity over and over again.

(28:25): [Susan Stewart]  All right. The next question is, "I have an allergy to the Pfizer and Moderna vaccine. I've had two J&J vaccines, but I haven't had anything since November 2021. What do you recommend for people with this allergy? I've called multiple doctors and pharmacists but never get any help. I would appreciate any advice. Several pharmacies have told me J&J does not cover any of the new variants of COVID."

(28:52): [Dr. Shivan Shah] It's necessarily not true. So, the J&J, I would recommend still getting the booster for it. Partially, it can cover and still curb it and I do recommend it. And I would also clarify your allergy with Pfizer and Moderna vaccines with your physician to make sure it's a true allergy it. But if the J&J works for you, then I still recommend getting the booster. It still will help. There's still some efficacy against it. Because again, there are multiple variants out there. It's still useful to get it.

(29:34): [Susan Stewart] All right. Our next question is, "How effective is acyclovir as an antiviral?"

(29:38): [Dr. Shivan Shah] It is not effective at all. Only three are, as I discussed - Paxlovid, Remdesivir, and Maribavir.

(29:48): [Susan Stewart] All right, and I think you answered this, but we'll ask this again. "Will we have to get vaccinated every year moving forward? A COVID 19 shot every year like a flu shot?"

(30:01): [Dr. Shivan Shah] Yes. So, I again recommend getting it every year like the flu shot. It'd probably go that route. It works in preventing severe disease. That's what vaccination is for. We're not trying to prevent you from [getting] it completely. It's hard to prevent you from catching it, but it works against you getting severe disease. So, definitely, it'll probably become a yearly thing, maybe twice a year.

(30:36): [Susan Stewart]  All right. "I have an anti-vax friend and family. Would it be sufficient if they took an antigen test before seeing me or should I still avoid seeing them indoors?"

(30:49): [Dr. Shivan Shah] So yeah, just ask them to do that. I don't want anybody to be restricting family during holidays. I think, you can ask them to take an antigen test. I would advise you to wear a mask around them, especially if they're having any symptoms. If they're having symptoms, maybe maintain a little bit of a distance. But again, holidays are coming up. I understand family wants to see family, friends will see friends, it makes complete sense. I think it's okay. It's reasonable for getting these antigen tests before. And currently, COVID rates are much lower, luckily, but the flu and RSV rates are very high. So, you can catch other viruses. That's why we still recommend wearing a mask. And for immunosuppressed individuals, it's a problem. If you get RSV, you can have severe RSV or severe flu. So that's why we still say mask.

(31:53): [Susan Stewart] Well, actually that leads into another question. Someone would like you to speak a bit about RSV. "How does it impact transplant and CAR T-cell recipients? How serious is it and what should you do to prevent it?"

(32:08): [Dr. Shivan Shah] Unfortunately there's no great antiviral against it. The best way is trying to avoid any symptomatic person, wearing a mask, especially in close quarters, especially if you're very immunosuppressed. Children carry it a lot. It's the winter cold, it's children along with influenza. So, again, hand washing and wearing masks are crucial during those times, especially if you're immunosuppressed.

(32:40): [Susan Stewart] This individual had CAR-T cell therapy three months ago and was instructed to get COVID and flu shots at this point. He wants to know whether you start with the same COVID vaccination again or do you get COVID and flu together or separately?

(33:00): [Dr. Shivan Shah]  You can get the same COVID vaccination. You could start with the same COVID vaccination. You could get the COVID and flu together. That's fine. But speaking from personal experience, I developed muscle pains and things like that when I got the COVID booster. So, I separated mine out by two days. Some people, I have some patients that say, "Give me all of them at once." So, it's up to you how comfortable you are from your previous interactions with the virus too. If you feel like you I want to space them out, that's fine, but it is okay to get them at the same time.

(33:43): [Susan Stewart] The next question is, "Have there been any changes in the recommended type of mask to wear indoors? Is N95 still the best to use or is a regular medical mask okay?"

(33:56): [Dr. Shivan Shah] So, N95 is the more filtered one is used. So, surgical masks are useful for patients who have symptoms. So, they can't expel any fluid or droplets from their mouth. That's why it's called surgical mask. When a surgeon has surgery, they put a surgical mask on, not really an N95 because the mask won't be able to prevent any droplet scanning onto the patient. The N95 is filtered, so when you breathe in there's some pathogen around, it's very difficult for it to get inside. So, N95 is recommended in the large crowds. However, I understand it is very uncomfortable. And if it's hard for you to do that, a surgical mask does have some efficacy against preventing spread. It's like if someone decided to go without pants on, all the fluid's going to get out. But if they put pants on, none of the fluid or some of the fluid will at least not get out there of course. So, the surgical mask will help, but N95 is better.

(35:18): [Susan Stewart] Okay, this person is a 17-year survivor post-transplant and wants to know how strong her immune system is. How does she know?

(35:29): [Dr. Shivan Shah] That is a very difficult question just because it depends on your transplant type. If it's a haplo, if it's an allo, if it's an auto. As we know, haplo or umbilical cord too, there's many different types. If there's GVHD involvement, it's a very complicated question. Every patient is different. So, it would have to be somebody, you'd have to talk to your oncologist, you'd have to talk to your infectious disease doctor too if you have one. But it's hard to determine what level of immunity you have. And there are different types of immunity in your body too. It might be hard for you to fight against fungal diseases, but you might be okay against viral disease. It's a very complicated question, but I would talk to your oncologist. And there's also immunologists out there if there's a specific reason for your immunity, if you're catching colds constantly, they might help out with that.

(36:34): [Susan Stewart] All right. This person wants to know if you have any thoughts on the Novavax vaccine.

(36:40): [Dr. Shivan Shah] Yeah, so the Novavax vaccine has fallen out of favor. It wasn't as effective. It's hard to get nowadays. I don't have a lot of usage for it personally. So unfortunately, I know there's not a lot of data anymore on it and it's moved away.

(37:08): [Susan Stewart] All right, the next person wants to know if there'll be any kind of update to Evusheld upcoming.

(37:13): [Dr. Shivan Shah] Yeah, so constantly we're getting these monoclonal antibody updates. Now, there's going to be an update. There were many companies that were developing these monoclonal antibodies. Now, they're trying to target it a little more specifically because they're trying to find a monoclonal antibody that might house multiple variants instead of just one. So, a combination situation because now we're in a post monoclonal antibody era. Meaning, there's no more emergency use for it. It's going to be more, we're going to try to figure out a good cocktail to give patients to have handy in case they do get COVID at post-transplant. Something, we can give it to them. So that's in the works. It's still being studied. There's no good timeline yet on it, but we're getting more and more information as days go on.

(38:15): [Susan Stewart] The next question is, "How soon after CAR T-cell therapy can one gets a COVID booster?"

(38:23): [Dr. Shivan Shah] Typically, the booster, we say it's about three months. That's what we've had in our dockets. Now, if it's more important, if it's two months, it should be fine. Again, you're allowed to do two months. Say, holidays are coming up and you want to get earlier, it'd be okay,

(38:48): [Susan Stewart] This woman is a nurse and she worked up until July 2021. She's a year post transplant and has been vaccinated for COVID. And she's wondering if it will ever be safe for her to work with patients again with PPE. She's being treated right now for GVHD.

(39:09): [Dr. Shivan Shah] Very good question. So again, what I would say is definitely you need to wear N95 with PPE. I would just wear an N95 in the hospital if you're working with patients. Like I said, COVID numbers are actually pretty low right now. So, if you want to go back to work, it should be fine, but you can pick up other viruses. So, it's very crucial you wear the N95. And what we found in hospital studies was the biggest outbreaks were in nursing lunchrooms because everyone took off their masks during eating lunch and they spread and then it spread to patients.

(39:49): So, if you know a patient has COVID and you're wearing PPE and you just ask them wear a mask in the hospital as long as they're not on oxygen, everything should be fine, way less spread. But the biggest thing you need to be careful about is your colleagues if you're in a lunchroom and make sure they don't spread it to you.

(40:08): [Susan Stewart] All right. This individual wants to know what studies have shown that vaccine really reduces the severity of disease. So, he's aware of some studies that say the vaccine is potentially more harmful than it helps.

(40:25): [Dr. Shivan Shah] I'm not aware of any studies that show it's more harmful that have been validated or actually randomized controlled studies. There's a lot of misinformation out there. You got to remember there are multiple studies that show vaccine actually reduces severity, coming from multiple centers, in the New England Journal of Medicine. It's going to be hard to go over all them of course in this small segment, but feel free to email and I can send studies over to Susan and it can be up for discussion. But again, the vaccine has not been shown to be more harmful than helpful. Again, a lot of misinformation out there to this day and it is beneficial.

(41:14): [Susan Stewart] All right. This woman had a transplant and developed COVID from her granddaughter and has since tested negative. She wants to know whether she still needs to take the vaccine.

(41:26): [Dr. Shivan Shah ] Yes. So, they found that natural immunity after three months wanes. I tell patients that if they want to wait a little bit after they get COVID to get it, meaning two months or so, that is fine. But again, the virus can mutate, and you can catch it again and again, especially if you're a stem cell patient. The last thing you want is to continuously get recurrent COVID infections. I've had patients, I've had it five times unfortunately and they've developed complications. So, I do recommend getting the vaccination, especially around the holiday time.

(42:11): [Susan Stewart] All right. This individual had a stem cell transplant in December of 2021, received Evusheld in March of 2022 and wonders if she should still be re immunized for COVID. She had three immunizations before her stem cell transplant.

(42:29): [Dr. Shivan Shah] Yeah, unfortunately after you got the stem cell transplant, it wiped out your immune system, meaning, your B cells and antibodies. So yes, you should get it. Evusheld only lasts for 90 days. I would recommend getting the vaccination again.

(42:47): [Susan Stewart] Okay. This individual wants to know what is the J&J booster because he has an allergy. His allergy is anaphylaxis, severe. He had an allergy to testing, to test the tolerance to the vaccine. It's not an option for him.

(43:06): [Dr. Shivan Shah] So, you could ask for the J&J itself booster at the pharmacies. Again, they've fallen out favor so that there only might be specific pharmacies that will have it, but you just tell them that you have anaphylactic allergy to the Pfizer vaccine. And they should be able to find out one of the other pharmacies. Just say the J&J vaccines, Johnson and Johnson.

(43:36): [Susan Stewart] All right. This woman wants to know that if COVID is an endemic, are we going to still need to continue wearing masks and avoiding crowds forever?

(43:46): [Dr. Shivan Shah] Again, like I said, I would hate for people to avoid their family and crowds on the holidays. No. No one should be asking you to avoid crowds but try to limit your exposure as much as you can to droplets. So again, toddlers who just went to school, high risk for infection. People who just were at a large concert and they're developing sniffles, try to avoid them. But no one is asking you to completely avoid family and friends. There's a mental health aspect to it and I think it's reasonable. But the most crucial time for patients is, say they're six months post-transplant. That would be the time to avoid is that's where you're the most immunosuppressed. And I'm pretty sure most patients would understand that it's no.

(44:51): Or say you're just getting your CAR-T, three months. Those are the times that we should be a little more careful and avoid. But if you're 15 years post-transplant or auto transplant, it's fine. Your immunity's less likely to be a factor in play, but you can still catch it. Try to tell your other loved ones, you could have older family members, so be smart. That's what we usually ask and it's something we want to make sure, yeah.

(45:26): [Susan Stewart] All right. The next question is, "Are immunosuppressed patients at increased risk of getting long COVID?"

(45:34): [Dr. Shivan Shah] So yes, they are because of potential active viral shedding and long COVID symptoms. It could be a lot of different things, brain fog, joint pain, chronic headaches, but it's a yes. It definitely can happen and that's why we try to tell our immunosuppressed to just try to be careful around people. And again, this is especially in the first six months to one-year post transplant is higher risk for you guys.

(46:12): [Susan Stewart] All right. I think this is a similar to a question you answered before, but maybe you can clarify this. This person wants to know whether people are considered immunocompromised 15 years post any GVHD or GVHD therapy or is just having had an allo transplant, meaning that you'll always be immunocompromised.

(46:33): [Dr. Shivan Shah] So, having an allo transplant, yes, you're considered immunocompromised just because your cells don't, they weren't your cells, and they don't work as effective as your own cells could have before you getting any sort of cancer. It's hard to say what level of immunity, especially after 15 years and now you're post GVHD therapy, and you haven't been on any treatment for that. You definitely have a better immune system than you did when you were on GVHD therapy. But yes, you would still be considered immunocompromised at that point because you have a higher risk of catching it than a person who's never had a transplant and never been on GVHD therapy.

(47:26): [Susan Stewart] All right. The next person said she had her booster in September. Coming up on three months, she wanted to know is there a new vaccination coming up or should she wait and be fine until six months.

(47:41): [Dr. Shivan Shah] Your last booster was September. The bivalent is the newest one, which was targeting the two most common variants. That was the newest one. If you haven't gotten that, we still do recommend getting it. But if you got that one, then there's nothing more for you to do at this moment. Luckily, as I said, COVID rates are low. I do anticipate once Thanksgiving rolls around next week and Christmas, there'll probably be some spikes going on, but I don't think it will be as dramatic as it was in the past two years.

(48:21): [Susan Stewart] All right. And the last question we have right now in the queue is, "Do you know of any changes that might be in the vaccinations to come, the new vaccines? Any change in approach?"

(48:33): [Dr. Shivan Shah] Yes. Actually, they're trying to go based off more, instead of even the mRNA, they want to try to do a protein based one, which is more related to our older vaccines, which have a longer efficacy. The mRNA, what we found was the reason why we keep on having the vaccine is mutations, but also the lasting effects dropped after some time. They're trying to find a more long-term solution to it. But again, it's still in the works, still waiting on trials and such.

(49:08): [Susan Stewart]     Closing. Okay, well with that, I think we are ready to close this session. I want to thank you Dr. Shah for wonderful presentation, and I also want to thank everyone who submitted their questions. They were great questions and I think it helped all of us.