Emerging Therapies in the Management of Sickle Cell Disease - Episode 4
Biree Andemariam, MD: Wally, that’s a perfect pivot to something we’re all dealing with: the coronavirus pandemic. Exactly how has COVID-19 [coronavirus disease 2019] impacted individuals with sickle cell disease? What do we know about their risk of serious manifestations of disease and mortality?
Wally Smith, MD: It’s safe to say that we were very afraid at the outset of COVID-19 that it was going to wipe our population out. Patients with sickle cell disease have impaired immunity. Now it is impaired opsonization and B-cell immunity and encapsulated organisms, but we all were quite afraid that even that immune compromise would make people with sickle cell disease more susceptible to getting COVID-19 and die more quickly if they got it.
I just looked up the stats to see where we are on this. Patients with sickle cell disease—according to the SECURE-SCD Registry, which is a worldwide registry, now has 482 reported cases. There are 19 deaths in that registry, which is a 3.9% mortality rate, and that does compare unfavorably with the source I looked at for worldwide and US COVID-19 [fatalities]. Worldwide, as of December 21, 2020, there are 76.9 million patients and 4.7 million deaths. In the United States, there are 18 million patients and 319,000 deaths. That’s 2.2% and 1.7%, respectively.
Numerically, sickle cell patients are faring worse. But subjectively, those who care for many patients with sickle cell disease are relieved. Most of us in our centers would say we are in the single digits—maybe double digits if you have large populations—with regard to the prevalence of sickle cell disease patients with COVID-19, and certainly in the single digits with regard to patients who have died.
It manifests in the way that it manifests in others, but it can also manifest as a crisis. Patients who have a crisis, that might be their COVID-19 manifestation, but you can get COVID-19 pneumonia. You can get all the other things we do now. It’s still appropriate, and we can hypothesize why these patients haven’t died more often. Maybe they’re staying in. We certainly saw that. Many patients were staying in and not coming to the hospital. The people coming to the hospital with crises dropped dramatically at the beginning of the pandemic.
We started doing telemedicine. We started trying to keep people from coming in. So far, we have escaped a huge scourge of patients with sickle cell disease with COVID-19. Larger cities are having lots of numbers, but in general we are not finding a huge scourge from sickle cell disease with COVID.
Biree Andemariam, MD: Thank you. What about the rest of you on the panel? Are you seeing what Wally is describing and what the large global registry has shown us to date?
Michael DeBaun, MD, MPH: We took a very proactive approach in early March. We shut down. We actually said we’re moving to telemedicine. We were early adapters of that strategy. We had a donor provide funds to purchase tablets for our families who didn’t have the discretionary income to do telemedicine, and we shipped them through FedEx. We set up town hall meetings weekly for 10 weeks to make sure that they understood the ever-changing landscape of how to protect yourself with COVID-19, because there was a significant amount of misinformation about how to manage COVID-19, and multiple myths that could have actually put our patients at risk.
We have continued the telemedicine. We worked closely with our legislature in Tennessee, and they agreed to extend telemedicine through March 2022 with the same reimbursement rate that we get from the face-to-face appointments. This was a concerted effort to keep our families safe and to inform them so that they could be their best advocates.
Julie Kanter, MD: That was something we did as well. We certainly have embraced, and continue to embrace, telemedicine. But I wonder about 2 things. One is that we are very proactive, so when 1 of our individuals with sickle cell disease gets sick, we’re on top of them. “How are you? What’s going on? Do we need to see you right away?” We often get labs before someone’s ever hypoxic or bring them in, even when they tell us that they’re not feeling short of breath, because we want to get a look at them.
I wonder if our aggressiveness to treat them quickly, to transfuse them very quickly even at the slightest amount of hypoxia, has made a difference in our outcomes and if, in some ways, we’re more proactive than the general population. When you look at bad cases of COVID-19, it becomes a microvascular disease, much like sickle cell, and it’s just interesting.
I’ve even had people wonder if people with sickle cell disease used up all their inflammation or if transfusion is making a huge difference. I don’t think we know these things, but I do wonder about all them.
Elliott Vichinsky, MD: I studied sickle cell in young adults and reported some cases when they had the other epidemics of flu-like infections, and we did see a lot of seriously ill kids. But what I was concerned about in follow-up of those kids was how they developed more reactive and restrictive lung disease problems. It’s important, because sickle has underlying injuries, to follow up and see what the long-term effects are in their organ function. Though I am encouraged by what you’re talking about.
Julie Kanter, MD: You’re right. I’ve been trying to figure out if we should preemptively schedule postcoronavirus PFTs [pulmonary function tests] and echocardiograms because we’ve also seen some postcoronavirus echocardiographic abnormalities in people without sickle cell disease. Could we catch some things earlier if we look? I don’t think we know yet.
Michael DeBaun, MD, MPH: Yes, not to mention kidney disease and brain.
Julie Kanter, MD: Thankfully, like Wally, we have not seen many individuals die as a result of COVID-19, but I have seen a lot of worsening of kidney disease. You mentioned it earlier, Michael, how kidney disease is the underspoken problem in sickle cell, especially because many of the adults with severe kidney disease don’t have as much pain. I’ve often found they’re not referred to the specialist when they need to be. I’m flabbergasted at people I see in my clinic who’ve never seen a sickle cell specialist, and they’re 50 years of age with kidney failure.
Michael DeBaun, MD, MPH: It turns out that when we did the regression analysis, the 1 modifiable factor for death was referral to a nephrologist within 6 months of the onset of dialysis. If they saw a nephrologist, their rate of mortality was significantly lower than if they had never seen a nephrologist in previous 6 months. You’re absolutely right, but this gets back to the broader picture that we talked about: access to care and who’s going to help? Remember, 50% of the adults with SS [sickle cell anemia] have silent infarcts, so the minute you start adding multiple care appointments—the nephrologist, the pulmonologist, the hematologist, the primary care doctor—we would be remiss if we didn’t mention the importance of the primary care doctor in a population that has 30% depression. The hematologist is not the expert on how to manage depression. No matter how many drugs we give, no matter how well we think we’re versed in depression, we’re not the experts. That’s the primary care doctor’s domain of expertise. You can see why this becomes very complicated extremely fast.
Transcript Edited for Clarity