TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine, 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. A transcript of the podcast is below the summary.
This week’s topics include a reinfection with SARS-CoV2, excess death data on the pandemic, the benefits of bariatric surgery, and new strategies for rheumatoid arthritis.
0:44 Rheumatoid arthritis management
1:45 Looked after 12 weeks, 28 joints
2:45 Look at different pathways
2:55 Life expectancy after bariatric surgery
3:55 Three years longer life with surgery
4:56 Very large study
5:55 Deaths observed in other studies
6:10 Excess deaths relative to COVID-19
7:10 A 20% increase compared with expected deaths
8:10 Adopt best practices
9:10 Reinfection in the US
10:11 Isn’t the first case of reinfection
11:10 If you were asymptomatic you could spread
12:10 Could more severe disease be reinfection?
Elizabeth Tracey: Does bariatric surgery improve lifespan?
Rick Lange: Treatment of refractory rheumatoid arthritis.
Elizabeth: A case of frank reinfection with SARS-CoV-2.
Rick: And excess deaths associated with the pandemic of 2020.
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 the Texas Tech University Health Sciences Center in El Paso, where I’m also Dean of the Paul L. Foster School of Medicine.
Elizabeth: Rick, I’m going to let you decide. Do you want to start with the COVID stuff or would you rather do the other stuff first?
Rick: Let’s talk about the other stuff first. How about rheumatoid arthritis?
Elizabeth: Okay. That’s in the New England Journal of Medicine.
Rick: As you’re aware, and most of our listeners aware, rheumatoid arthritis is an inflammatory disease, a process that attacks the joints, and multiple joints throughout the body. The mainstay of treatment was what is known as DMARDS, or disease-modifying antirheumatic drugs. But despite these, some individuals continue to have a debilitating rheumatoid arthritis.
What investigators have done is try to identify different pathways that can affect the immune system, either to suppress it or modulate it. Two such pathways are called the Janus kinase pathway — and we now have access to an oral Janus kinase inhibitor called upadacitinib — and a separate pathway that affects T cells, called T-cell costimulator, and that’s abatacept. Is one better than the other? That’s what these authors attempted to examine.
They took over 600 patients that had been on a biologic DMARD, but it wasn’t successful, so they kept them on this synthetic DMARD and then added either the oral inhibitor or the IV abatacept. They evaluated them after 12 weeks and used what was known as the disease activity score. They looked at 28 different joints, and self-rated by the individuals.
What they discovered was that the percentage of patients that had remission of their rheumatoid arthritis was higher on the Janus kinase inhibitor, 30% had remission, versus those that took the T cell modulator, only 13% had remission.
The downside was there were more side effects, serious side effects, when people used the Janus kinase inhibitor, things like death, a stroke, and two venous thromboembolic events. They also had a higher incidence of having elevated liver enzymes. It tells us that by looking at different immune pathways we can affect rheumatoid arthritis. We have to balance that with the risk.
Elizabeth: Also, clearly we need to take a look at other pathways that might be involved in this disease that might be more amenable to modification.
Rick: Yep. You know, what was so attractive about this Janus kinase inhibitor was it’s an oral drug and many of the medications that we give, the biologics, require either an IV infusion or a subcutaneous injection. Investigators are looking at different pathways to modulate the immune system that can allow remission in some individuals with rheumatoid arthritis.
Elizabeth: Let’s stay in the New England Journal of Medicine and take a look at this issue of life expectancy after bariatric surgery. This is part of what’s called the Swedish Obese Subjects study that’s abbreviated SOS.
This cohort either had bariatric surgery or didn’t, and then they were also compared with 1,000-plus reference participants. In the surgery group, there were 2,007 patients. In the non-surgery or the conservative management group, there were 2,040 patients.
What was amazing was the median duration of follow-up for mortality was 24 years — that was in the surgery group — and then 22 years in the control group. And they were able to find the data on mortality for 99.9% of patients. I want to know where that 0.1% came from. But in any case, that’s really the power of Swedish studies, I would suggest, where they follow people really closely.
In this period of follow-up, they had 22.8% of folks in the surgery group and 26.4% of those patients in the control group who died. They were able to determine that the median life expectancy in the surgery group was 3 years longer than in the control group, but for both of these groups it was 5.5 years shorter than in the general population. So obesity is still a really big risk factor for death.
Some of the stuff that was also interesting about this study is that they utilized either banding, vertical banded gastroplasty, or a gastric bypass, in order to manage obesity in these patients. They note that despite the beneficial effects of bariatric surgery that have previously been identified, even in Sweden, only a minority of eligible patients actually choose to have the surgery, which I think is really kind of curious, particularly since mortality perioperatively has declined a lot.
It sounds like, “Hey, folks! We really should entertain the notion of having bariatric surgery in cases of morbid obesity.”
Rick: The virtues of this particular study is this large number of patients. Individuals that were obese and didn’t have surgery lived on average, 8 years shorter. The individual with surgery lived, on average, five and a half years shorter. There was a benefit with surgery compared to just usual care, but clearly just obesity by itself increases mortality.
These were old surgeries. But even the old surgeries, they were still done pretty well. The post-op mortality was 0.2% and only about 3% of the individuals underwent repeat surgery. Even though our surgical techniques have improved, the surgery back then really didn’t have very many side effects associated with it. I agree; hopefully this will spur individuals to have bariatric surgery that are unable to obtain normal weight by other mechanisms.
Elizabeth: I would note that in their discussion they also admit that they found a higher risk of alcohol abuse, suicide, and self-harm, and serious fall-related injuries among patients with obesity who did have the surgery.
Rick: There are obviously complications with it and the deaths that you mentioned have been also observed in other studies as well. But overall, looking at total mortality, to decrease cardiovascular deaths and it also decreased cancer-related deaths, both of those obviously related to obesity.
Elizabeth: Since we’re talking about deaths then, why don’t we turn to yours? Those are in JAMA. These are two research letters, as well as an editorial that take a look at this concept of excess deaths related to COVID-19.
Rick: I think everybody is aware the U.S. has experienced more deaths from coronavirus disease than any other country and we actually have one of the highest cumulative per-capita death rates. How is that death rate assessed? Obviously, if someone has lab-confirmed COVID and they die, you say, “Well, that’s pretty easy to count that.”
That doesn’t account for other deaths that may be COVID-related. Either the patient didn’t have testing or maybe it wasn’t directly due to a COVID infection, but for some other reason. Individuals have serious conditions, like heart attack or stroke, but don’t come to the hospital because of COVID, so those are all COVID-related deaths.
What these investigators did was they looked at deaths between March and July of 2020 and compared that to the same time period in previous years. Those previous years in the absence of a pandemic give fairly consistent death numbers.
What they discovered is that, over that 5-month period, there were a total of 1,336,000 deaths, an estimated 20% increase compared with the number of expected deaths. That means there were over 225,000 excess deaths related to COVID. Only about two-thirds of these were actually directly attributed to COVID.
Now, how does that compare with other countries? There are some that fall in the moderate excess deaths and some that fall in the high. We’re in the high excess deaths. In fact, we’re #3 among overall countries and actually, from May onwards, we have more excess deaths than any other developed country. Why is that in a country that has such a well-developed healthcare system? Well, obviously, there are things that we’re not doing very well.
Elizabeth: To me, a lot of this data really is not surprising. We have talked before about another study that also took a look at excess death. What is the utility of this particular metric as far as you’re concerned?
Rick: First of all, I think it gives a better idea and actually frames it. In fact, we’re approaching the number of excess deaths associated with World War II and also it should allow us to look at how we compare to other countries to see if we can adopt best practices to decrease those number of deaths and/or to improve reporting associated with COVID excess mortality.
Elizabeth: I think the reporting thing is absolutely an important aspect of this. Do you think that this kind of crunching of the numbers is actually going to take place more broadly?
Rick: We’re already doing it. We looked at excess deaths in our country. We compared it to excess deaths at other places as well. That’s an easier number to get than testing when testing is really not readily available.
There were other accompanying articles that looked at things like, “How does this affect other individuals?” Because for every death, it affects 9 individuals, so those people have mental health, behavioral issues, and post-traumatic stress disorder.
Another article looked at what the economic cost was, and it’s estimated to be a $16 trillion loss in the United States as a result of this. That’s about 90% of the GDP. In terms of excess death and in terms of mental health, the economy, this is pretty serious.
Elizabeth: On that note of pretty serious then, let’s turn to our final one for this week. That’s in the Lancet Infectious Diseases. This is a single case study of a young guy, 25 years old, who appears to have been — and it appears pretty persuasively — to have been infected twice with SARS-CoV-2. He is a resident of Washoe County in the U.S. state of Nevada. He had nasopharyngeal swabs taken during both of his infections, the first in April, April 18th, 2020, and the second, June 5th, 2020. That was separated by two negative tests that were done during May of 2020. They did a genomic analysis of this SARS-CoV-2 that was retrieved and showed genetically significant differences between each variant with each instance of infection.
And I would note that his second infection was symptomatically more severe than the first. He did have hypoxia and he did go to the hospital, so this is kind of a little worrisome. Isn’t it?
Rick: It is. A couple things about this. This isn’t the only person in the world that’s been reported to be reinfected. There have been other reports as well: Ecuador, Hong Kong, and one in Belgium.
They were all relatively young individuals. They were age 51 and younger. The four cases: one with reinfection was asymptomatic, one had mild disease, and two had worse disease. In this particular case, in the Nevada patient, he had mild symptoms at first and then was hospitalized with serious pneumonia the second time around.
None of these patients had a suppressed immune system. None of them were on immunosuppressive drugs at all, but they all appeared to be reinfected and as this particular individual, as you noted, with a genetically different strain. This shows that some individuals can become reinfected. It is that you aren’t necessarily immune once you’ve gotten it.
You say, “Well, there’s only four cases worldwide.” I suspect we’re really not testing very many individuals. The other thing is we’re only testing primarily those that are symptomatic. If you developed a second infection and were asymptomatic, you still might be a spreader, but you wouldn’t necessarily develop symptoms. There’s still a lot more that we need to learn about reinfection with the COVID virus.
Elizabeth: Yeah. The one place that you didn’t add in your list was the Netherlands where that fourth patient was. One of the things that I thought was really interesting about this — or that they self-describe as a limitation of the study — is they didn’t really take a look at any potential immune reactions that he had after the first infection. It would be really interesting to have that piece of data.
Rick: Right. There is no reason to suspect that he had a defective immune system. The reason why I say that, Elizabeth, is because after he tested the second time they did test for antibodies and he clearly had antibodies.
With the first time he developed antibodies, were they neutralized antibodies? Were there sufficient titer? Did they go down? Or were they just not effective against this second virus? These are things that we won’t know.
Elizabeth: Still, one of those things. I guess the other point I would make is that sometimes I just wonder if people who come to the hospital and present with more severe disease, hypoxia, and the whole thing that indicates that they’re having a problem, what number of those had been previously exposed or infected by another strain?
Rick: Right. I mean, you could make the case that the reason they had this serious infection is because they weren’t able to fight the infection. Their immune system was suppressed. Alternatively, they may have an immune system that causes severe inflammation and we’ve seen that with vaccines, for example, with the SARS and MERS vaccine. So whether this is inflammatory or whether this is a lack of response to an infection, we don’t really know at this particular point, so your question remains unanswered.
Elizabeth: No doubt time will tell. On that note, that’s a look at this week’s medical headlines from Texas Tech. I’m Elizabeth Tracey.
Rick: And I’m Rick Lange. Y’all listen up and make healthy choices.