Intentional COVID Infection Study; Anxiety and Depression Screening

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 intentional infection of people with COVID to study transmission; screening for anxiety; screening for depression; and whether post-COVID condition (PCC) differs from sequelae of other infectious disease acute illnesses.

Program notes:

0:40 Intentional infection of volunteers with COVID

1:40 Collected lots of samples and data

2:40 Only two individuals responsible for vast majority of virus

3:40 Thought it was largely respiratory

4:25 Differences between sequelae after acute infectious disease hospitalization

5:25 All adults hospitalized with flu, COVID, or sepsis

6:25 PCC, post-COVID condition

7:16 Screening for anxiety?

8:16 Screening postpartum or pregnant persons

9:16 What can we do?

10:00 Screening for depression

11:00 Referrals and a benefit

12:01 Onus on primary care docs

13:06 End

Transcript:

Elizabeth: What can a bunch of brave people who got infected with COVID teach us about transmission?

Rick: Should we be screening for depression and suicide risk in adults?

Elizabeth: And should we be screening for anxiety?

Rick: And COVID long symptoms, are they really unique?

Elizabeth: That’s what we’re talking about this week on TTHealthWatch, 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: We have two COVID things this week, Rick. Which of those would you like to start with?

Rick: Let’s start with yours.

Elizabeth: Okay. This [is why] I said, “Oh, those brave souls.” I do have huge admiration for people who step into the space of these kinds of challenge studies. This is from The Lancet and this is taking a look at a cohort of young people, let me call them, who allowed themselves to be infected with SARS-CoV-2 in order to study transmission. That would be airborne transmission, transmission on fomites, inanimate objects, and then what they expired in their breath, what’s the relationship with symptoms, and all that sort of thing.

Okay. These brave folks, as I said, stepped forward. They were screened to make sure that they had never had COVID previously. They were 18 to 30 years of age. They were unvaccinated. They got infected with a previously calculated inoculum of SARS-CoV-2, the wild type, pre-alpha, by intranasal drops and they were in isolation. Everything about those folks was studied pretty intensively. They collected all the air and everything that they touched. They also had symptom scores that were assessed three times daily.

At the end, they had 36 participants, sort of unsurprisingly 10 female and 26 male. Of that number, 18, or 53% of them became infected with this inoculum that was put into their nose. They took a look at these mask samples, breath, the viral load, and all that sort of thing. They did it in the nose and the mouth and they came up with some pretty interesting conclusions — almost no correlation with how severe your symptoms are and how much virus you shed. They clearly identified what … or gave support to this notion of super spreaders, people who seem to be extraordinarily good at producing virus and releasing it into the environment. I’m going to step out on a limb and say thank you to these folks for participating in this study.

Rick: You said even though half of the people that were exposed became infected, only two of those individuals were responsible for almost 90% of the airborne virus detected. As you mentioned, that suggests there are some that are super spreaders. Furthermore, it looked like the nasal mucosa, not the respiratory mucosa, had the highest titer of virus.

Here is what I find interesting. We oftentimes see people wear masks and they wear them over their mouth, and they’re not over their nose, but the super spreaders actually had more coming from the nose than they did from the mouth. Also, the fact that they could detect it on most of the surfaces suggests again how important it is not only for hand hygiene, but for cleaning surfaces as well. I think this was a very well-done study in infecting individuals in a very controlled environment that allowed us to assess precisely how the virus transmits from one individual to another.

Elizabeth: I was frankly a little bit surprised by the fomites and they specifically identified the remote control of the television as having viable virus on it when they sampled it. We had previously kind of disparaged that, thinking that it was largely respiratory and if you didn’t get sneezed on or fall into that sidestream you weren’t really at risk.

Rick: Even when it’s detectable as fomites, that is, on surfaces, it doesn’t get into the body through the skin. It’s after you’ve touched that surface and then brought your fingers to your face. That’s when it’s infective.

Elizabeth: Finally, I think one important conclusion of this study in identifying that it’s the nasal mucosa that’s shedding most of the virus is that they postulate that antiviral nasal sprays really have a role in ultimately preventing or in treating infection.

Rick: That’s why this particular study, I think, is incredibly important. I think it not only drives our non-pharmacologic measures, but it can actually drive future therapies as well.

Elizabeth: Okay. Let’s turn to JAMA Internal Medicine. Now we’re taking a look and we’re going to switch over to this mental health issue and medical issues. What about the comparison of medical and mental health sequelae following hospitalization for either COVID, the flu, or sepsis?

Rick: This particular study was directed at looking at post-COVID-19 condition, PCC, also called long COVID. That’s known as people that have a persistence of symptoms or sequelae occurring 1 to 3 months after they’ve had a COVID infection. We’ve attributed this to the COVID infection and the virus in thinking it’s somewhat unique.

But what these authors did is they said, listen, we’re talking about people who survived a hospitalization and they are at risk for having post-COVID symptoms: cardiovascular, neurologic, mental health, and inflammatory autoimmune conditions. They really postulated that maybe it wasn’t the COVID, any infection that results in a hospitalization could also cause similar symptoms.

To see whether that was the case or not, they looked at a population of all adults that were hospitalized with COVID-19 between April 2020 and October 2021. They said, “Let’s compare them to individuals that had the flu beforehand; do they have post-sequelae symptoms?” and the people that had sepsis as a bacterial infection. It looked at 13 different pre-specified conditions, cardiovascular, neurologic, mental health conditions, and even inflammatory conditions like rheumatoid arthritis, all of those within 1 year of hospitalization for any of these symptoms.

What they discovered when they looked at almost 400,000 individuals was that the only symptom that was associated with an increased risk that was attributable to COVID was actually venous thromboembolic disease, compared to influenza. There was no increased risk of developing cerebrovascular, cardiovascular, neurologic disease, rheumatoid arthritis, or mental health conditions compared with either the flu or with the sepsis cohorts.

Elizabeth: Now you introduced a new acronym. You said PCC. I thought we were talking about this as PASC, post-acute sequela of COVID. Is this a new one? Educate me.

Rick: It’s also a very similar term and that’s why I introduced it to our listeners as PCC, post-COVID condition. But there are other terms for it as well.

Elizabeth: Eh, we need to standardize this so we all know what we’re talking about. Are you surprised by these results?

Rick: Elizabeth, I am. I mean, I always thought that all of these sequelae were a result of the COVID infection, but this suggests that many of the post-acute consequences are related actually to the severity of the infectious illness itself and that results in hospitalization. It’s the severity of the illness, regardless of whether it’s flu, or sepsis, or COVID that results in the post-sequelae.

Elizabeth: I guess I’m not surprised. I spend so much time on the MICU and certainly I’m very familiar with the post-ICU syndromes that have been well described for quite a while now.

Rick: Anything that’s severe enough to get you into the hospital may have long-lasting sequelae.

Elizabeth: Let’s turn to JAMA. The USPSTF has been at it again; in this case, we’re talking about what I’m going to serve up, the anxiety disorders in adults — should we screen for those? And ultimately what the panel decided that there is moderate certainty that screening for anxiety disorder in adults should be done. That should include pregnant and postpartum persons, with a moderate net benefit.

Let’s give a little background. Anxiety disorders are the second most influential contributor to mental disorders worldwide. Of course, we’ve been reporting for quite some time that these things are on the increase.

It turns out that anxiety disorders typically have onset early in life. So this recommendation that all adults aged 18 to 64 be screened for anxiety should really start at that earlier end of the spectrum and then clearly this need to screen persons who are pregnant or postpartum is also something we’ve become a good deal more aware of.

Rick: We’re going to talk about another behavioral condition shortly. This affects primarily younger individuals. The recommendations are particularly centered towards this population. It implies that you can detect it. You can detect it with some precision and then more importantly is, once you do that, you can do something about it that can favorably affect its outcome. The data in older individuals, those over 65, is really not there. What they comment is there is really not any good evidence that screening in these older individuals is helpful. Were you surprised by that?

Elizabeth: I guess I thought it was a hopeful message honestly that somehow these anxiety disorders, we kind of age out of them and maybe that’s the result of experience, which we have certainly talked about in the past. The editorialist points out that the USPSTF’s recommendation is screening for anxiety, which is a symptom, but not a disorder. That’s a really important distinction and clinicians need to be aware of that. Per your notion of what are we going to do about it if we find it, there are quite a large number of potential therapies that can be employed, including pharmacologic and behavioral interventions. They seem to be fairly efficacious.

Rick: Elizabeth, as you mentioned, it’s a symptom. There are many different disorders: generalized, social anxiety, specific phobias, substance abuse, medication-induced anxiety, other medical conditions, and even agoraphobia. So again, the screening detects anxiety and then it requires additional testing or additional assessment to find out which particular anxiety disorder the individual manifests, and as you mentioned, how best to treat it.

Elizabeth: Let us move on, then, to screening for depression.

Rick: You kind of set the stage for anxiety. Regarding depression, in 2019 almost 8% of adults in the U.S. experienced at least one major depressive episode — that’s over 19 million individuals — and 13 million experienced a major depressive episode with severe impairment. Depression is a condition that’s oftentimes associated with remission and recurrence. Suicide is the 10th leading cause of death in U.S. adults — again, in that same year, over 45,000 deaths — and unfortunately we’ve talked about from 2001 to 2017 there was a 31% increase in suicide deaths.

Now fortunately, over the last year, it looks like it may have decreased slightly, but nevertheless it remains a significant issue. Again, the U.S. Preventive Services Task Force makes recommendations based upon evidence. They conclude that there is again moderate certainty that screening for major depressive disorder in adults, including pregnant and postpartum persons and older adults, has a moderate net benefit.

We have good screening tools. The screening tools result in referrals in which there is a benefit to the individual. However, unfortunately, they concluded that the evidence is insufficient on the benefits and harms of screening for suicide risk in adults. This also includes pregnant and postpartum persons and older adults.

I was surprised by the latter. I’m not saying that it can’t be useful. It’s just that there is insufficient data and especially when you’re using it as a general screening tool. They weren’t able to show any harm that is screening for it increases the risk of suicide, nor were they able to demonstrate any benefit.

Elizabeth: Clearly, older people are also subject to the development of depression. I would specifically point to older men and then their choice of guns as their means of dispatch, which we know are highly lethal.

Rick: Even though women have twice the risk of depression compared with men, the older men are the more likely to have severe consequences and to act on it as you mentioned.

Elizabeth: The other concern I have about both of these sets of recommendations is that the onus is really on primary care docs once again to step into this fray and employ screening, and then also to either manage therapy themselves or to make appropriate referrals. We have a dearth of primary care physicians and a dearth of mental health workers. It’s unclear to me how we’re going to satisfy this need.

Rick: You’re right. We don’t have enough professionals that have expertise in this area. Having said that, what the data clearly show is even in the current situation, the screening is accurate, and despite the fact that we don’t have adequate services, the services we have do provide some net benefit. I think, as you mentioned, it does bring light to the fact that we need to have better training for our primary care professionals and a better referral system for those individuals in whom they can’t handle.

Elizabeth: An ongoing story I’m sure. On that note then, 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.