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 an enzyme and risk of COVID infection, transmission among childcare centers, rates of antibodies to COVID in healthcare workers, and stimulating new white blood cells and COVID.
0:46 An enzyme and COVID infection
1:43 Nasal brushings examined
2:47 Works with spike protein and ACE receptor
3:45 Also associated with prostate cancer
4:37 Immune stimulation in COVID
5:35 Stimulates white cells
6:35 Usual care versus stimulation
7:37 Death rate of 0.2% in younger people
7:54 Three outbreaks in childcare facilities
8:54 Graphical presentation
9:54 Since kids were asymptomatic
10:54 Might mitigate spread from children
11:10 COVID among healthcare workers
12:10 40% went on to develop symptoms
13:49 End
Transcript:
Elizabeth Tracey: Do we have another clue in why people of color are disproportionately affected by COVID-19?
Rick Lange: Stimulating the immune system in people with COVID infection.
Elizabeth: What do transmission dynamics among childcare facility workers and denizens tell us about the risk imposed by children of COVID-19 infection?
Rick: And the rates of asymptomatic and previous COVID infection in healthcare workers.
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 Foster School of Medicine.
Elizabeth: Rick, how about if we turn to the Journal of the American Medical Association? This is a research letter. We've all been observing for this entire pandemic that people of color are disproportionately impacted by COVID-19, both infection and death. This is a look at, "Is there something else besides the ACE2 receptor that the virus is in contact with that might help to explain this disproportion?" Because even after we correct for all the socio-demographic factors, there's still this persistent difference.
So, this is a single-site study from the Mount Sinai Health System in New York. They collected nasal epithelium samples between 2015 and 2018 from people who were having nasal brushing for research on asthma biomarkers. These folks were pretty young. They were aged 4 to 60 years. They isolated RNA from these brushings, then that was followed by sequencing of RNA, alignment and normalization.
Among their cohort, which was 305 people, they had about 8% Asian, 15% Black, 26% to 27% Latino, some mixed, and 40% or so white individuals. They took a look at a receptor that's called -- it's abbreviated TMPRSS2 -- this is transmembrane serine protease 2, an enzyme that helps to facilitate the viral entry and spread.
What they found was that, sure enough, the expression of this enzyme was significantly higher in Black individuals compared with the Asian, Latino, and mixed, and white individuals. So the hypothesis clearly is that maybe it's the presence of this thing that's helping to explain some of the disproportion in susceptibility. They also suggest that there is an inhibitor of this enzyme that's called camostat mesylate, that's undergoing clinical trials right now to see whether it can help.
Rick: For individuals that may not be familiar with this, the spike protein on the virus binds to the ACE inhibitor on the cells in the nasal epithelium and the lungs, and then the virus is internalized into the cell and it's replicated. That requires this particular enzyme to activate the protein on the virus and also to cleave the receptor so they can get entry into the cell.
The hypothesis is if you have more of this enzyme, you have more entry of the virus into the cell, which makes it more infective and more severe disease. In fact, as you've suggested, African Americans have a disproportionate higher incidence of severe disease and of death compared to Latinos and to whites as well. And this may be one of the factors responsible.
Now, in fairness, there are other social, environmental, and geographic factors, but this obviously has some biologic plausibility. It's interesting -- this particular enzyme's also associated with prostate cancer and we know that African Americans have a higher incidence of prostate cancer as well.
It's an interesting hypothesis. It's a relatively small number of patients they've studied. It does look like it's a significant issue and the question is how, among all these factors, does this play into the higher incidence and severity of COVID disease in Blacks?
Elizabeth: Well, clearly, because they're trying inhibition of this already in clinical trials, there are lots of folks who think there may be something to it.
Rick: There are. There was some hypothesis that this ACE receptor, and using hypertensive medication, they somehow influence the disease process and we've shown that's not the particular case. It will be interesting to see whether this molecule that you mentioned that inhibits this enzyme actually affects the disease or not. We need to look at every particular pathway because we really don't have very many effective treatments for COVID.
Elizabeth: Exactly. Which of yours would you like to turn to, Sir?
Rick: Speaking of possible treatments, let's talk about immune stimulation. One of the things that's been particularly interesting about COVID infection is a significant number of people end up with lymphopenia -- that is, a decreased number of white cells. We know the white cells help fight infection.
Now, that's not uncommon in people that have bacterial or viral diseases, but what's particularly noted for COVID-19-infected patients is the magnitude and the duration of the lymphopenia is longer than in other infections.
It's been shown, by the way -- we talk about risk factors -- we can identify who is going to have more severe disease or likely to experience death. People with low white counts, lymphopenia, experience more severe disease and a higher instance of death.
This particular study looked at 200 individuals that had low white counts, no comorbidities, weren't on a ventilator, so they weren't severely sick at the particular time. But they randomize them to just usual care or administered what's called human granulocyte colony-stimulating factor, or hGCSF, and it stimulates white cells.
In the individuals who received this compound, compared to those that received usual care, there was no significant difference in time to clinical improvement. However, those that received this immune-stimulating compound were less likely to experience severe disease and they were less likely to die.
Patients progressing to acute respiratory distress, sepsis, or septic shock, 2% in the treated patients versus 15% in those that received usual care. At 21 days, only 2% of those treated had died, compared with 10% in the usual care group. This suggests that possibly in a relatively small subset, those with severe lymphopenia and no comorbidities, that stimulating the immune system may actually improve their overall outcome.
Elizabeth: Let's mention that this is in JAMA Internal Medicine. I would like to know was this within the environment, also, of the use of remdesivir and of dexamethasone?
Rick: These individuals were not severely diseased -- they weren't on a ventilator -- so they were less likely to receive steroids, but the usual care could have been anything that the physicians thought was indicated in this particular patient. That was not controlled for. Those that had severe lymphopenia are the ones who benefited. Then, as you described, there is the confounding issue which is they didn't control for the other potential treatments, so I'm glad you brought that up.
Elizabeth: Once again, though -- great that people are looking for additional things to add to the armamentarium with regard to trying to ameliorate or attenuate the severity of this disease.
Rick: Right, and this narrow population of patients that may benefit. We need to do additional studies with more patients to confirm.
Elizabeth: Okay. I'm going to say that within the light of that, a study that we're not talking about this week that I just saw today in MMWR -- Morbidity and Mortality Weekly Report, which I'm going to talk about next with regard to childcare facilities. But this one from today was looking at death in younger people from COVID-19 and many of those people, of course, don't have comorbidities, although the ones who died typically do.
Rick: Right. Again, the death rate in the younger population is extremely low. Here in the El Paso region, for example, it's about 0.2%. But having said that, you would segue into another MMWR report about the transmission in childcare facilities. Why don't you tell us about that?
Elizabeth: Clearly this is something, again, that we've all been wringing our hands about and that's, "How much of a risk do children present to others when they contract COVID-19?" This is a study that takes a look at three outbreaks in childcare facilities in Salt Lake County, Utah between April and July 10 of this year. They were retrospectively reviewed to explore this attack rate and then transmission patterns.
In total, they had 184 persons, including 110 children, who had a known epidemiologic link to one of these facilities. Thirty-one confirmed COVID-19 cases occurred, 42% among the children. Among pediatric patients with confirmed COVID-19, all had mild or no symptoms. Transmission was documented from these kids to at least 26% percent of non-facility contacts and those were either confirmed or probable.
They examined each one of these separately. Some of these were small childcare facilities and some of them were larger. I think they did a really great graph, so I would direct listeners to take a look at that. I really like it because it shows this -- it looks like a starburst pattern of who got what and when all of that stuff happened.
I think the things to note here were that interestingly to me, all of the original COVID-19 cases originated among staff members in all three facilities, not among the children. They had disparate mask use among these three facilities, with the largest of them not requiring staff members to use masks, but the other ones did require their staff members to use masks.
What they ultimately come to is that sure, no surprise, we know that kids can definitely transmit this to their parents and to other people. The same old thing -- use face masks, be vigilant about hygiene. If you suspect that you have a problem, stay away, and get tested more often.
Rick: This originated from the thought that, well, since kids were perhaps asymptomatic, they had a smaller or a lower viral load and they were less likely to infect other individuals they come in contact with, either at the childcare facility, in this particular instance, or even outside the facility. What this study shows is that asymptomatic individuals can pass the infection.
As you did mention though, this study originated in the early part of the COVID pandemic. Then many people, as you said, weren't following the CDC guidelines. It's clear that wearing face masks ... You can't social distance from kids, but you can wash your hands, disinfect surfaces, and make sure that if an individual is sick, that they remain at home. And as you highlighted, most of the infections were associated with childcare facilities that did not do that.
Elizabeth: The kids can give it to you. I will note that a pediatric infectious disease expert at Hopkins has made the point that there are two things about children that are worth remembering. One is that they're short -- when they cough, they don't usually cough into your face. And the other one is that they also frequently do not cough with the force that an adult does. And so those might mitigate spread from children.
Rick: Clearly, if people are wearing masks, that obviously dramatically decreases the risk as well, and washing down surfaces. Then when a kid has a cough or a sneeze or a flu-like illness, then they should remain at home. There is no question about it.
Elizabeth: Finally, let's turn to the British Medical Journal, once again taking a look at healthcare workers.
Rick: This is of interest to me because it looks at the seroprevalence -- that is, how many people have developed antibodies to COVID infection -- and asymptomatic viral infections in healthcare workers. This is a cross-sectional study in the United Kingdom at the University Hospitals in Birmingham. It's one of the largest hospital trusts in the United Kingdom with over 20,000 employees delivering care to about 2.5 million individuals. They said, "Gosh, we wonder how many of these individuals have been infected and may or may not have known about it -- and we'll detect that with antibodies -- and how many are asymptomatic and actively infected?"
They put out a survey that says, "We'd be happy to test you," and they opened it up to anybody that wanted to do so. There were 554 asymptomatic healthcare workers who were recruited while they were at work. What they discovered was that the asymptomatic active infection rate was 2.4%.
Some of these were pre-symptomatic and about 40% went on to develop symptoms in the next several days, but still about 2% to 2.5%. About 24% of individuals actually tested positive for the antibody. Some of those had symptoms, they just didn't recognize it, but about 17% of all individuals had no symptoms, but still tested positive for the antibody.
Then they did a really interesting thing. They said, "Which healthcare workers are more likely to have been infected?" The group that was more likely to be infected was, in fact, housekeeping, 35%, followed by people doing acute medicine or general internal medicine, and the lowest rates were those that were actually working in the intensive care unit. They had about 70% lower prevalence of having antibodies than those in the other areas. Not surprisingly, the Black, Asian, and minority ethnic groups had a seropositivity rate two times more likely than other groups.
Elizabeth: Good information and it lends credence to the idea that we really need to protect everybody in the hospital. It's not just a matter of providing all that stuff to people in the ICU.
Rick: Exactly, and so I think healthcare workers oftentimes put their guard down. They are most worried about the ICU and the emergency department, but that's where people are more likely to follow protocols, wear their PPE, and wash their hands. But what this was suggested is you can't let your guard down. You can't become complacent. You can get it anywhere, inside of a hospital or outside of the hospital, and you just need to follow the guidelines.
Elizabeth: Something to live by. 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.