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Persistent COVID Symptoms; Spit vs Nasal Swab: It’s TTHealthWatch!

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.

0:48 Persistent symptoms following hospitalization for COVID

1:48 Lung problems seen

2:48 Give us the opportunity to continue follow up

3:11 Saliva versus nasopharyngeal swab for COVID

4:15 Almost eight percentage points lower with saliva

5:15 Could be a false negative

6:18 Bring up secretions from respiratory tract

7:15 Antibodies to variant of SARS-CoV2 from vaccination

8:17 Laboratory generated variant

9:15 mRNA technology can be rapidly adjusted

9:36 Methamphetamine use disorder

10:36 First stage half treated

11:36 Stimulant-like medicine

12:27 It’s a 12-week study

13:08 End

Elizabeth Tracey: Can we start using saliva instead of nasopharyngeal swabs for SARS-CoV-2?

Rick Lange: Do people that have recovered from COVID infection have antibodies against the new variant COVID virus?

Elizabeth: Can we effectively treat methamphetamine use disorder?

Rick: And how do individuals fare six months after being hospitalized for COVID 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: 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, why don’t we turn to one of yours first that’s in The Lancet? That’s taking a look at what are the persistent symptoms of people who’ve been hospitalized with COVID-19 infection six months down the road?

Rick: The aim of this particular study was to describe the long-term health consequences in people that have been discharged from the hospital with COVID-19 infection, and then investigate the various risk factors, and in particular, does the disease severity affect long-term consequences? They looked at over 1,700 individuals that had been discharged with COVID-19 infection from a hospital in Wuhan, China. The mean age was about 57. About half were men and half were women, six months of follow-up, and here’s what they discovered.

A large number of these individuals continued to have persistent symptoms six months after they had been discharged from the hospital. The most common symptom was fatigue or muscle weakness, which occurred in 63% of individuals. 26% had sleep difficulties. 23% had anxiety or depression. A significant number of individuals had persistent lung problems. The more severe the disease in the hospital, the more likely they were to have any of these symptoms six months after hospitalizations.

Elizabeth: I would like to see a compare and contrast with people who are not hospitalized with COVID-19 but other diseases and conditions and what happens down the road. The other thing I would really like to know is what were their pre-existing conditions before they were hospitalized.

Rick: Many of these people had pre-existing conditions, but not the conditions that would cause these types of symptoms. The most common were hypertension, diabetes, and those occurred in 29% and 12% of individuals respectively, and less than 10% had cardiovascular disease or cerebrovascular disease. These conditions wouldn’t normally cause fatigue, muscle weakness, sleep disorders, or the anxiety or depression that are reported six months after COVID infection.

Elizabeth: Clearly, then, they call for the need for follow-up.

Rick: Absolutely, and we’ve now had over 23,000,000 people infected in the United States alone. Unfortunately, this will give us the opportunity to examine people even 6 to 12 months to years afterwards. What’s most concerning to me is not only these symptoms, but the persistent difficulty with exercise, the lung problems, and the CT abnormalities of the chest that indicate there will be ongoing pulmonary problems in the future.

Elizabeth: Let’s turn to Annals of Internal Medicine. This is a meta-analysis taking a look at sensitivity and costs of testing for SARS-CoV-2 infection with saliva versus the nasopharyngeal swab. They searched all these databases, and interestingly, I noted they searched Embase, Medline, medRxiv, and bioRxiv, and I think this tells us just how important these preprint servers are starting to become. They were able to identify 37 studies, over 7,300 paired samples were included, and they had a reference standard of a positive result on either a saliva test or a nasopharyngeal swab. Basically, the sensitivity of the saliva test was 3.4 percentage points lower than the nasopharyngeal swab overall.

Among those who had previously confirmed SARS-CoV-2 infection, though, the sensitivity of the saliva was 1.5 percentage points higher. In those without a previous diagnosis, saliva fell almost 8 percentage points lower than the nasopharyngeal test.

From a cost standpoint, however, if you tested 100,000 people with a SARS-CoV-2 prevalence of 1% in the population, the nasopharyngeal swabs would detect 79 more cases, but with an additional cost of $8,000-plus per additional case.

To me, this really makes the case — sorry to use that again — for really largely switching to saliva testing, not to mention the fact that it reduces the need for specially-trained personnel who have to be all hanging out in PPE and it’s so uncomfortable for the person who has to undergo testing.

Rick: I’m going to be a little bit of a naysayer here, Elizabeth. Where the saliva test is mostly done is not in people that have confirmed COVID, but in people that you’re doing COVID testing to see whether they have it or not. Well, the sensitivity was only 85%, 8 percentage points less than nasopharyngeal.

If it’s a negative test with a very low prevalence, there’s a high likelihood that it could be a false negative test and so in that particular situation, I’m thinking, “Well, that’s not really helpful.” Because if you tell someone they’re negative and you let them go around and infect a bunch of other people, the $8,000 you would have spent on the positive test, that gets magnified by exposing a bunch of other people. I actually think that an 85% sensitivity and being 8% lower than nasopharyngeal testing isn’t adequate in the individuals that we would want to apply this to.

Elizabeth: I would ask you, then, to just reflect on the idea that I understand that with regard to this predicted prevalence of 1%, but what about in populations where the prevalence is much higher?

Rick: It ranges from about 1% at the highest level to about 15%. But at any particular point in time, it’s less than that. The other thing about saliva testing — and by the way, your point’s well-taken — you can do it at home. It doesn’t require special personnel. It doesn’t require PPE, but it ought to be supervised or instructed because you’re not testing the saliva in the mouth.

You’re trying to bring up the secretions from the respiratory tract, so you want to do it early in the morning. You want to make sure that people are coughing vigorously to try to bring it up. If you don’t do that, the sensitivity goes down even further, so this is the best sensitivity in studies. We know that real-world practices it’s often less. Those are my concerns.

Elizabeth: I guess right now I’m thinking about the UK and where the prevalence is just so high. I wonder if switching to something like this… I mean, it would be significantly less expensive and it probably would result in quicker turnaround.

Rick: Yeah. There’s value. The more often you could do testing, the more likely you are to review where cases are that are otherwise asymptomatic, so there’s always a trade-off. There’s no question about it. The storage and transportation in this is extremely important. You don’t face that issue with nasopharyngeal swabbing because the professional puts it directly into a viral medium, so these are all considerations before we adopt this particular practice.

Elizabeth: Okay. Speaking of preprint servers, let’s turn to bioRxiv, looking at Pfizer’s vaccine and whether it’s likely to still protect us against this new variant of SARS-CoV-2.

Rick: Elizabeth, we have very little data about whether previous infection will protect against this new variant and this variant is associated with increased contagiousness, but it’s not more likely to cause severe disease and it’s not more likely to cause mortality. But the change in the spike protein makes it bind more avidly and makes it much more contagious.

Well, what these authors did with data that we have available was they took the previous study that had been done with the Pfizer vaccine. They had blood from people that had received the Pfizer vaccine. They collected the sera two weeks after they received the vaccine and four weeks after the vaccine. These antibodies that were generated from this blood were effective in neutralizing the regular virus.

They took those same 20 samples. They made a version of the variant that looks very similar to what’s been going on in England and South Africa, and they used the sera as well to see if it would neutralize this virus. They found in these 20 individuals that it did, both the two-week sera and the four-week serum.

Keep in mind, this was a virus generated in the lab — it’s not the one that we see — there’ll be additional variations of the virus coming over the next several years and months, and this was a small sample. But it’s the first data we have that suggests that antibodies to the previous virus, especially those generated by the vaccine, may be helpful.

Elizabeth: Clearly, this is everybody’s nightmare, that this virus is going to gain enough traction with regard to mutations that something is going to elude these numerous vaccines that are out there, almost all of which are targeted against the spike protein. My understanding is that the J&J vaccine is shortly going to report data and that’s one that’s got the advantage of being targeted against more than the spike protein and also a single dose.

Rick: Right. That will be helpful in situations like this. The other thing about the Pfizer vaccine and the Moderna vaccine is it’s an mRNA technology that can be very rapidly adjusted. The most important thing is that we continually monitor for the virus changes to be flexible to address these situations.

Elizabeth: Exactly. Finally, let’s turn to the New England Journal of Medicine. I picked this study that’s looking at bupropion and naltrexone in methamphetamine use disorder because one of my colleagues and friends, Eric Strain, who is a specialist in the drugs of abuse at Hopkins, has talked to me throughout this whole pandemic about these parallel pandemics that we’re experiencing. Not necessarily related to methamphetamine use disorder, but also opioid use, and there’s a good deal more concomitant use that’s going on nationally, and I suspect probably also internationally, a lot more death relative to these disorders also.

This is a double-blind, two-stage, placebo-controlled trial in what they call a sequential parallel comparison design to look at efficacy and safety of extended-release injectable naltrexone plus oral extended-release bupropion in adults with moderate or severe methamphetamine use disorder.

They had a total of 403 participants enrolled in stage 1 and 225 in stage 2, and they had in this one group, in the first stage, some of whom got this naltrexone-bupropion and some of whom didn’t, and then in the second stage, they had more people doing the treatment.

The results are not incredible. Basically what they show is that they are able to get more people to stay off of the methamphetamine by using this combination. It’s incremental, but it does help. I think it’s incumbent upon us to attempt these kinds of things because we are having such a big societal problem with this right now.

Rick: As you mentioned, this is an important issue. This came from UT Southwestern, my old stomping grounds, but majorly because there has been a rise in methamphetamine use disorder across the United States, particularly in the Midwest and the West, where now it is a leading cause of overdose deaths.

To date, there’s no medications that have been approved by the FDA for the treatment of methamphetamine use disorder. So these two drugs, bupropion, it’s a stimulant-like antidepressant and it was meant to address the dysphoria that people experience when they come off of methamphetamine. Then naltrexone, it’s an opioid receptor antagonist and it has been used for opioid use disorders, so there’s some rationale for combining these two medications.

But as you suggest, when you’re trying to get people off of methamphetamines, in this particular study, the placebo group, the rate of disuse was 2.5% with placebo. With this combination of medications prescribed over 12 weeks it only went to 13.6%, so again, it’s low in terms of its efficacy. It is incremental. It will not get us to where we need to go in terms of addressing this disorder.

Elizabeth: Right, but I think it’s a step in the right direction. It’s both recognition of it and an attempt to try to develop something. My hope is at least this gets people thinking about it.

Rick: Elizabeth, it does. The caveats about this, it’s a 12-week study, there was a very low attrition, people stayed in this study, they were motivated to be in this study, so these are the best results we can expect from these medications.

In a real-world experience, it’s not likely to be quite as good. It’s better than placebo, but we’ve still got a lot of work to do, so hopefully this will shine a light and say, “Okay, this was a starting point. What can we do to make this significantly better?”

Elizabeth: On that note, that’s a look at this week’s medical headlines from Texas Tech. I’m Elizabeth Tracey.

Rick: I’m Rick Lange. Y’all listen up and make healthy choices.

Source: MedicalNewsToday.com