TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine in Baltimore, and Rick Lange, MD, president of the Texas Tech University Health Sciences Center in El Paso, look at the top medical stories of the week.
This week’s topics include excess mortality relative to COVID, brain changes secondary to COVID infection, a gene therapy for hemophilia A, and screening for eating disorders.
1: 30 Estimate 18.2 million deaths
2: 31 Increase again?
3: 00 Brain changes and COVID
4: 00 Greater reduction in grey matter thickness
5: 01 Largest brain imaging study we have
6: 01 Relatively modest changes
7: 01 Follow up a year and two years
8: 01 Hepatitis treated with steroids
10: 00 Screening in primary care nonexistent
11: 06 No studies to show benefit
12: 18 End
Elizabeth Tracey: Should we be screening for eating disorders?
Rick Lange, MD: Gene therapy for bleeding disorder.
Elizabeth: Brain changes secondary to COVID.
Rick: And we have severely underestimated the mortality associated with COVID-19 infection.
Elizabeth: That’s what we’re talking about this week on TT HealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a Baltimore-based medical journalist.
Rick: And I’m Rick Lange, president of Texas Tech University Health Sciences Center in El Paso, where I’m also dean of the Paul L. Foster School of Medicine.
Elizabeth: Rick, how about we turn right to the Lancet — this issue of excess mortality, the numbers, and how much more COVID-19 related death there has actually been?
Rick: Elizabeth, if you look at reports, it appears that there has been about 6 million people that have died of COVID. But what this study suggests is that may underestimate things substantially. In fact, that number is probably closer to 18 million.
These authors did an all-cause mortality report — not just what was COVID-related, but all-cause mortality during the COVID period, and they compared it to previous periods. That way they could assess what the excess mortality was. They did this for 74 countries and 226 sub-national locations. They corrected for things like excessive heat waves that may occur or any other natural disasters. Here is what they discovered.
When they looked from January 20 through December of 2021, reports were that there were about 6 million worldwide deaths due to COVID. They estimate the number is actually 18.2 million.
They also did some statistical modeling to say, “Well, how accurate are our numbers?” They felt that their numbers were + or – 15%, so it’s nowhere near 6 million. It’s much closer to about 18 million. Then they looked at certain areas, what countries had the highest number of cumulative excess deaths: India – 4 million, USA – 1.1 million, Russia – 1 million, Mexico about 800,000, and Brazil about 800,000 as well. This indicates the full impact of COVID is really much greater than we previously estimated.
Elizabeth: I don’t think either one of us is terribly surprised by this analysis. I would suggest that if we included all the other conditions that were unquestionably exacerbated by COVID and hung them under that umbrella, it would be a staggering number.
Rick: Essentially, there were some deaths that were higher, but some were lower. For example, we know that there was less travelling, so there were lower accidents, but that was balanced by other excess deaths in other areas as well.
Elizabeth: I must say that I’m a little concerned that we are going to see this number increase even more now that we’re seeing this Omicron variant starting to take hold in Europe.
Rick: It appears that we are still going to have these cycles, Elizabeth. The more people that either have natural immunity or get immunity, or the more that we’re able to use preventive measures and/or provide treatments, obviously, we’ll be able to lower that. But I agree with you, I think we are still going to be cycling for several years to come.
Elizabeth: Sort of sobering. Let’s turn to Nature. This, my favorite database — as you’re well aware, we’ve mentioned it, I can’t tell you when, in the last 6 weeks I think at least 3 times — at the U.K. Biobank.
This is a study taking a look at SARS-CoV-2-associated brain changes in people who have had COVID with a comparator group of people who did not. Once again, the elegance of these big databases that look at people over time, this U.K. Biobank in this case looked at brain changes in 785 participants between the ages of 51 and 81, who had all been imaged twice. There were 401 cases who tested positive for SARS-CoV-2 between their 2 scans with 141 days on average separating their diagnosis and second scan, and 384 controls.
This is pretty amazing that they were able to have this preexisting brain scan and then be able to do a second scan in a group of people who ended up getting infected, compared to those who weren’t infected.
They found a greater reduction in grey matter thickness and in tissue contrast in the orbitofrontal cortex and parahippocampal gyrus. These are both areas that are associated with that whole olfactory pathway. Then they also saw — in that primary olfactory cortex — changes there and then a greater reduction in total brain size. They also assessed these people’s cognition, and sure enough, they found out that those who had been COVID-infected did have prolonged time to do a tracking problem. They took out the people who had been hospitalized from COVID and still saw that these same trends were in place.
Rick: In the past they had done studies where they examined people that had had COVID with brain scans and those that hadn’t and tried to compare them. But this longitudinal study, the way it was done, people were getting scans regardless of whether they were exposed to COVID or not. We have a group of individuals who had a baseline scan. About half of them developed COVID and half did not; then they got re-scanned.
It’s really the largest COVID-19 brain imaging study we have. They actually had automated objective quantitative methods for looking at these areas of the brain. The areas that they identify correlate with some of the clinical findings — the cognitive deficits that are prolonged in the areas of the brain that they identified decrease with COVID, were involved, and then obviously, the areas associated with both smell and with taste. It’s a very robust study.
Elizabeth: In some respects, it’s not really surprising. Of course, we are seeing a lot of followup studies looking at long COVID. I’m not sure that there is anything actionable here, however.
Rick: That’s the next question. What’s causing the brain to be affected? Is it the fact that the virus is actually infecting the brain tissue itself? Is it causing an inflammatory response that’s doing this? The next step would be identifying what the underlying mechanism is and then see if we can address those.
Elizabeth: Yeah. They do make a suggestion that they think there could be resolution largely of these particular deficits over time, and that would be a good thing for all concerned.
Rick: These changes we’re seeing are really relatively modest. We are talking about a 2% change in the volume, but they were able to detect it because they were using these automated objective methods. Otherwise, we wouldn’t have even been able to see it.
Elizabeth: Let us turn to your next one. That’s in the New England Journal of Medicine: gene therapy for Hemophilia A.
Rick: These individuals that have hemophilia A in severe form have very low levels of factor VIII and they are predisposed to bleeding. It can be very debilitating.
Currently, the treatment is you have to give regular doses of factor VIII to get the level up to prevent some of the bleeding, but there is a lot of breakthrough. There’s even another monoclonal antibody that simulates factor VIII.
They used gene therapy. This is a mouthful, so it’s valoctocogene roxaparvovec. This gene is attached to a viral vector. These individuals received a single intravenous infusion of this. This gene is inserted into the genetic components in the liver — the liver is responsible for making factor VIII — and then they examined these people a year and 2 years later.
Hemophilia A, 134 people with severe hemophilia A that received a single intravenous dose and a year later, what they discovered was that, in fact, the vast majority did have elevations in factor VIII that were sufficient to prevent bleeding or the need for infusion therapy. They decreased that bleeding episode by 99% and decreased necessary infusions by 84%. This was sustained for a year and in some individuals up to 2 years, although the factor VIII level had decreased somewhat.
Elizabeth: Clearly, a very, very significant advance in something that has been moving in this direction for quite a while. We have talked a lot about gene therapy for not just this, but for other disorders as well. Let’s talk about the downside of this.
Rick: The upside are there were zero bleeds and it prevented 150 infusions that people would otherwise need. The downside is almost all individuals developed a mild form of hepatitis, but they were able to treat that with steroids. There really weren’t any serious side effects. But, obviously, you had to pay attention to what was going on.
Elizabeth: I am wondering about how that particular side effect might be exacerbated if subsequent treatments were needed.
Rick: Great question, Elizabeth. This didn’t look at durability. They did have some exclusion criteria, people that had underlying liver disease or people that had HIV infection, or people that have antibodies to this thing. I failed to mention, by the way, is that there were some other side effects, nausea and headache, in about 35% to 40% of individuals. This particular therapy seems to be effective out to 2 years. Whether it’s more durable or whether we need to have repeated infusions are subjects of future studies.
Elizabeth: Since we are also wrestling with a gene therapy for sickle cell that’s ferociously expensive, let’s talk about the expense of this particular treatment.
Rick: I wish I could tell you how much it cost. I don’t know the answer to that. Usually it’s quite expensive, but the current therapy for hemophilia is not cheap either.
Elizabeth: More to come. Let’s turn to JAMA. The USPSTF took a look at all the literature relative to should we be screening adolescents and adults with normal or above-normal BMI for eating disorders.
What they concluded is an “I” recommendation — the evidence is “insufficient” to assess the balance of benefits and harms regarding screening these folks, this particular group, for eating disorders.
Let’s take a look just a little bit at some of the background of this. Anorexia nervosa, bulimia nervosa, and binge eating disorder impact — affect — an estimated 4.9% of women and 2.2% of men in the U.S. These disorders commonly begin during adolescence and young adulthood, and lots of folks avoid or delay seeking specialized care because they feel embarrassed, there is a stigma associated with it, they’re ambivalent toward the treatment, and the screening for these disorders in primary care settings is nonexistent, especially if you’re of normal or above-normal BMI.
This review is limited to general studies, rather than that high-risk population that we do know may already have a particular eating disorder — those who have low weights or are symptomatic in other ways, like they are not getting a period, or they have another psychiatric or anxiety disorder. So this excluded those folks.
They did find that there was one screening instrument that’s called a SCOFF that might be helpful, but basically it really points to the need for us to be doing a whole lot more research on this.
Rick: I think what our listeners need to be aware of is, for example, if you’re talking about anorexia nervosa, the excess deaths associated with that condition is about 5 per 1,000, or it increases the risk of death about 6-fold. They are usually relatively young individuals.
There are people that fall in high-risk categories, and screening these individuals is helpful. We don’t have enough data about screening in the general population. The gap is we don’t have any studies that show that identifying these people and treating them actually improves their outcome.
You may say, “Why would you publish a paper that says we just don’t know?” Well, it’s actually to spur these studies. That’s exactly what it’s about. The implications of this are pretty large. There is a lot of things we screen for. If this is another thing we are screening for, but we don’t have any data that is effective in terms of identifying individuals or aids in their treatment, then it shouldn’t be done. We need more studies on this particular subject.
Elizabeth: There is also a couple other issues that I think are worth mentioning. One is that underrepresented populations are even more underrepresented with regard to these particular issues. The other is that there is some discussion that the prevalence may have increased during COVID.
Rick: Yeah, and specifically Black, Latinx, and transgender youth have higher reports of self-reporting eating disorders. As you mentioned, it looks like things have increased during the pandemic. So I think we will be hearing more about this.
Elizabeth: More to come. On that note, that’s a look at this week’s medical headlines for Texas Tech. I’m Elizabeth Tracey.
Rick: And I’m Rick Lange. Y’all listen up and make healthy choices.