Detection of Respiratory Viruses for the Clinician

Podcast Transcript

Respiratory Exchange Podcast Series

Release Date: April 10, 2024

Expiration Date: April 9, 2026

Estimated Time of Completion: 30 minutes

Detection of Respiratory Viruses for the Clinician

Hannah Wang, MD

Christopher Attaway, MD

Description

Welcome to a special series by the Respiratory Exchange Addressing the Impact of RSV and Vaccine Hesitancy. In this series, we explore the efficacy of RSV vaccines and discuss preventive strategies aimed at reducing the occurrence of severe RSV respiratory illness in infants, children, and older adults.

This episode will focus on Detection of Respiratory Viruses for the Clinician, where we will explore emerging RSV testing as it pertains to understanding the capabilities and limitations of different diagnostic tests.

Learning Objectives

• Discuss the different types of RSV tests by explaining their specific applications and limitations.
• Evaluate the role and potential benefits of at-home testing, considering factors like accuracy, accessibility, and interpretation of results.

Target Audience

Geriatricians, infection disease physicians, intensivists, nurse practitioners, nurses, obstetricians/gynecologists, pediatricians, pharmacists, physician assistants, primary care physicians, pulmonologists, and other prescribing and non-prescribing providers.

Accreditation

In support of improving patient care, Cleveland Clinic Center for Continuing Education is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

Credit Designation

• American Medical Association (AMA)

Cleveland Clinic Center for Continuing Education designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Participants claiming CME credit from this activity may submit the credit hours to the American Osteopathic Association for Category 2 credit.

• American Nurses Credentialing Center (ANCC)

Cleveland Clinic Center for Continuing Education designates this enduring material for a maximum of 0.50 ANCC contact hours.

• American Academy of PAs (AAPA)

Cleveland Clinic Center for Continuing Education has been authorized by the American Academy of PAs (AAPA) to award AAPA Category 1 CME credit for activities planned in accordance with AAPA CME Criteria. This activity is designated for 0.50 AAPA Category 1 CME credits. PAs should only claim credit commensurate with the extent of their participation.

• Accreditation Council of Pharmacy Education (ACPE)

Cleveland Clinic Center for Continuing Education designates this knowledge-based activity for a maximum of 0.50 hours. Credit will be provided to NABP CPE Monitor within 60 days after the activity completion. Universal Activity Number List:

- Pharmacist UAN: JA0000192-0000-24-426-H06-P

• Certificate of Participation

A certificate of participation will be provided to other health care professionals for requesting credits in accordance with their professional boards and/or associations.

Cleveland Clinic Planning Committee for Addressing the Impact of RSV and Vaccine Hesitancy Series

Cecile Foshee, PhD
Co-Activity Director
Director, Office of Interprofessional Learning

Steven Gordon, MD
Co-Activity Director
Chairman, Infectious Disease Department

Kaitlyn Rivard, PharmD
Co-Activity Director
Department of Pharmacy

Nichole Brown, MSN, RN, CHSE-A, PhD(c )
Nursing Institute

Neal Chaisson, MD
Department of Critical Care Medicine
Department of Pulmonary Medicine

Frank Esper, MD
Pediatric Infectious Disease
Cleveland Clinic Children’s Hospital

Debra Kangisser, PA-C
Director of Education
Physician Assistant Services

Aanchal Kapoor, MD, Med
Department of Critical Care Medicine
Department of Pulmonary Medicine

Steven Kawczak, PhD, CHCP, FACEHP
Co-Medical Director, Center for Continuing Education

Neil Mehta, MBBS, MS
Center for Technology-Enhanced Knowledge and Instruction
Associate Dean of Curricular Affairs, Cleveland Clinic Lerner College of Medicine

Anne Vanderbilt, APRN
Senior Director, Advance Nursing Practices
Center for Geriatric Medicine

Hannah Wang, MD
Director, Molecular Microbiology & Virology

Faculty

Hannah Wang, MD
Director, Molecular Microbiology & Virology
Cleveland Clinic

Christopher Attaway, MD
Molecular Microbiology Fellow
Cleveland Clinic

Host

Steven Gordon, MD
Cleveland Clinic Chairman of Infectious Disease Department

Agenda

Detection of Respiratory Viruses for the Clinician

Hannah Wang, MD

Christopher Attaway, MD

Disclosures

In accordance with the Standards for Integrity and Independence issued by the Accreditation Council for Continuing Medical Education (ACCME), The Cleveland Clinic Center for Continuing Education mitigates all relevant conflicts of interest to ensure CME activities are free of commercial bias.

The following faculty have indicated that they may have a relationship, which in the context of their presentation(s), could be perceived as a potential conflict of interest:

The following faculty have indicated they have no relationship which, in the context of their presentation(s), could be perceived as a potential conflict of interest: Christopher Attaway, MD, Nichole Brown, MSN, BSN, Cecile M Foshee, PhD, Steven Mark Gordon, MD, Debra Kangisser, PA-C, Aanchal Kapoor, MD, Steven Kawczak, PhD, Neil Mehta, MD, and Anne Vanderbilt, APRN.

CME Disclaimer

The information in this educational activity is provided for general medical education purposes only and is not meant to substitute for the independent medical judgment of a physician relative to diagnostic and treatment options of a specific patient's medical condition. The viewpoints expressed in this CME activity are those of the authors/faculty. They do not represent an endorsement by The Cleveland Clinic Foundation. In no event will The Cleveland Clinic Foundation be liable for any decision made or action taken in reliance upon the information provided through this CME activity.

HOW TO OBTAIN AMA PRA Category 1 Credits™, ANCC, AAPA, ACPE Contact Hours, OR CERTIFICATE OF PARTICIPATION:

Go to: http://cce.ccf.org/ccecme/process?site_code=main&activity_session_code=EHCE05701

 to log into myCME and begin the activity evaluation and print your certificate. If you need assistance, contact the CME office at myCME@ccf.org

Acknowledgement:

The Cleveland Clinic Center for Continuing Education acknowledges an educational grant for support of this activity from ModernaTX, Inc.

Copyright © 2024 The Cleveland Clinic Foundation. All Rights Reserved.

PODCAST TRANSCRIPT

Dr. Dweik:

Hello and welcome to the Respiratory Exchange podcast. I'm Raed Dweik, Chairman of the Respiratory Institute at Cleveland Clinic. This podcast series of short, digestible episodes is intended for healthcare providers and covers topics related to respiratory health and disease. My colleagues and I will be interviewing experts about timely and timeless topics in the areas of pulmonary, critical care, sleep, infectious disease, and related disciplines. We will share information that will help you take better care of your patients today as well as the patients of tomorrow. I hope you enjoy today's episode.

Dr. Gordon:

I just want to say I'm very excited about this podcast that we're doing. My name is Steven Gordon. I'm Chairman of the Department of Infectious Disease, an infectious disease clinician. We have two young rising talented guests here, Dr. Hannah Wang and Dr. Chris Attaway. They represent a key component at least as an ID specialist our kind of three-legged stool here, and that's the microbiology lab. I think the goals of this podcast will focus on the micro lab in terms of respiratory viruses and RSV testing, but also the importance of what behind that black box is, and as I like to frame it, in a solutions business for clinicians to help us get a rapid diagnosis in certain things and initiate treatment when needed.

But before we get into the nitty-gritty, I first want to direct my first question to Dr. Hannah Wang. Hannah, welcome and can you just tell us a little bit about your journey and how you got here to the Cleveland Clinic?

Dr. Wang:

Yes, absolutely. Thank you so much for having me. So, my name is Hannah Wang. My journey at Cleveland started in medical school here. I came to Cleveland Clinic for medical school in 2012, and it was here, in the micro lab, that I developed a love for pathology, lab medicine and diagnostic testing. And I went out to Stanford to do my pathology residency and microbiology fellowship, and now, as of August 2022, I started here as the Medical Director of Molecular Microbiology and Virology, and I oversee a lot of the respiratory virus testing that's done for this hospital and for Northeast Ohio.

Dr. Steven Gordon:

Well, thank you, Hannah. We'll get back to your return, which was very prescient. You arrived into the medias of the COVID epidemic. Chris, I wonder if you could tell us about your journey.

Dr. Chris Attaway:

Yeah, absolutely. First of all, thank you for having us, Dr. Gordon. I always like to tell people I am just a humble boy from rural South Carolina. I went to undergrad there and then I worked in an entamoeba histolytica lab. I got my first exposure to infectious disease, back then even, and from there, I was contacted by somebody at the London School of Hygiene and Tropical Medicine, I did my master’s degree in medical Parasitology. So, then I was even more interested.

From there, I went to medical school at the Medical University of South Carolina in Charleston. Next, I made my way to every other microbiologist, did my anatomic and clinical pathology residencies at University of Pennsylvania. From there people told me that there's this really great place in Northeast Ohio where I should continue my training. I applied, and they were outstanding. I'm proud to join the group and I'm happy to learn from our amazing medical directors and infectious disease colleagues.

Dr. Gordon:

Wow, thank you, Chris. As you know, it's been a great two-way street in terms of the microlabs so are embedded in our practice. Pre-pandemic, many people did not have a good awareness of respiratory viral testing, and now we've evolved to one of the more successful platforms, I think, from the pandemic, and that was the availability of home testing point of care. I wonder if you can give us just an overview, as you look at respiratory virus testing in general, kind of the ABCs for our home audience?

Dr. Wang:

Yes, absolutely, and, you know, these days our home audience doesn't need the ABCs anymore. We went from a situation where really nobody really understood what lab testing was or how it's accomplished, maybe even what the most common respiratory viruses were. With COVID, we started with not having access to testing. Very few tests being developed, and now this sort of explosion and growth, so much that almost everybody and their mother knows what PCR is and knows what antigen testing is, can do their own antigen testing at home. So, I think the past few years has represented an incredible growth in public knowledge about respiratory viruses and the testing that we can do.

So, if I could just summarize this into sort of two big categories for our at-home audience, there are things called antigen tests where we're detecting a little piece of the viruses', let's say, shell or clothing, like their outside presenting pieces. Or there are nucleic acid amplification tests, a type of which is PCR, and these types of tests are looking for the sort of interior genomic material in the virus. These two types of tests have different pros and cons, but one of the major things I think for our at-home audience to think about is, in general, our nucleic acid tests or our PCRs are going to be more sensitive, so better at detecting the virus when it’s there in low quantities.

However, the problem with the nucleic acid tests is they tend to be less accessible. There are only a few options where you can do that at home or at the point of care, and these traditionally have been concentrated in the laboratory.

Dr. Gordon:

Well, Chris, I wonder if you can expound. What is the importance, in terms of respiratory viruses, from the clinical side, because the clinicians were always pushing you. What rationale do we use for turnaround time and in terms of understanding what may be causing this syndrome of either cough or influenza-like illness?

Dr. Attaway:

I think that's the hard part about being a clinician, getting this presentation of symptoms and then attempting to order the right test, that is the really hard part. We try to make the lab as easily accessible to help you make the right decision and so that’s our dividing point.

When someone comes to the clinic, to the emergency department, let's say your standard outpatient, they're a little sick. I think the best testing for an outpatient in that setting is a limited panel or a targeted test. So, you are going to want to get a nucleic acid-based test, something like PCR, and something for your heavy hitters, so influenza, COVID, and RSV right now. Those kinds of tests are really at the top the differential. If you're not thinking, bacterial pneumonia or something to that effect. If you're thinking upper respiratory, those types of testing will get you what you need.

You want to rule in the big things, rule out the big things, and send these patients on their way. Now that being said, you're seeing someone inpatient, it's a different scenario. You have somebody who is, very challenging to manage, someone who is really, really sick, they are inpatient. In that case, even as an outpatient, there's a lot of testing at your fingertips. Now that we are talking about an inpatient, a more exhaustive panel of testing might be warranted for these types of patients because this time you really need to know. It's not like, oh, they're going to get better, they're going to leave. We need to be very sure about what this is. Then you might want to explore the multi-targeted panel, something that has 15 targets, bacterial, fungal, and viral diseases on there as well to give you that peace of mind going forward with their treatment.

Dr. Gordon:

Wow. Well, thank you for that. I think, you know, from the clinical point of view, it's very humbling. There was an article written probably 20 years ago about how good are clinicians in diagnosing influenza. As you know, it's about a 50-50 shot. Now if there's widespread influenza out there, you are going to be more likely to be able to diagnose that.

As you stated, there are other respiratory viruses now that can mimic flu-like symptoms. I think from our point of view, what my mentor always taught me, Dr. Crawford, is if you're going to order a test, you should understand why you're ordering that test. Sometimes it's nice to have the diagnosis so the patient knows, maybe that's a stewardship thing. Other is we have treatment, at least for three of the big viruses you mentioned. Potential treatment could militate symptoms, especially in those at high risk for progression, whether it's SARS-CoV-2 or influenza. RSV, we don't.

Hannah, if this is a situation, how do you set the menu up to make your clinician succeed? Because as Chris said, behind the scenes, there are a plethora of things that we may be able to order ala carte. How did you make the decision with the clinicians in terms of what is the best panel to set up during what seasons, so I'm just curious, in 2024?

Dr. Wang:

Yes, this is a great question. I think you have to balance so many different factors. There are the things that Dr. Attaway mentioned in terms of the patient's severity, the urgency of care. But there are a few key factors with the COVID pandemic that are new to us. The first of which is actually, that there is a lot of growing interest and demand from the patients to know what respiratory virus is causing their illness. I think we see with all the research and development that's happened during COVID how powerful that is. Knowing what virus causes your symptoms means that treatments and vaccines can be developed for it.

If there's not a public awareness that a certain virus is causing disease, then we can't do anything about it. I think that's the piece that I really learned from the COVID pandemic. Other factors, this is completely a decision that has to be focused on who your providers are at the hospital, who your patients are at the hospital. In terms of the approach, we took to set the testing menu here, we involved our ID colleagues, our infection prevention colleagues, our ED colleagues, our primary care colleagues, and pediatrics colleagues. And all those people come together to make a decision about which patient population is going to get what type of testing?

And the last piece of this I want to say, is that its changing. The epidemiology is changing. So, I think this year, and last year, for the first time we're seeing this return to maybe some sort of seasonal trend or predictability that was absent during the COVID pandemic. The decision we made was that this year, we're going to offer flu, RSV and COVID testing to all patients as the default.

Now, clinicians can choose. Maybe they only want to do flu and COVID testing, or they only want to do COVID testing, but we made that COVID plus flu plus RSV available to outpatients this year for the first time. I think that's in recognition of the fact that we have these new vaccines available, and we want to promote sort of a better understanding of RSV among our population so that maybe people will seek out that vaccine next year.

I think there are so many factors that go into this decision, as you said, you have to make it with all of the stakeholders in the room. I don't think the lab alone can make a good decision by themselves, but I believe that decision also has to involve the lab. I'll tell you why with the RSV piece, which adding the RSV component, the reagents are a little bit more expensive, but the labor actually, we were able to bring on a new assay that made the labor the same. So, we were able to offer that value to patients without that incredible amount of added cost. And that sort of strategic thinking and planning, with all the people in the room, at the table, including lab, that's what made it so much better, that’s what makes it possible.

Dr. Gordon:

Thank you.

Dr. Gordon:

Chris, with RSV being the new kid on the block, I wonder if you can expound a little bit from the lab point of view, RSV is not a new virus. You know, we were like oh my God, this is just for little kids. Can you explain to our audience about the recognition of the kind of medically attended disease that it causes, not just in infants or the newborns or the small children, but adults.

Dr. Attaway:

Yeah, it's interesting because when I was in medical school, RSV is, that's for children and that is, you know, that's kind of it, it lurks around otherwise. Like, anybody of all ages can get them, but it's not a severe disease, it's sort of a cold, and that's kind of where we left it, but I don't know when we call post-pandemic, but we're going to say now in our post-pandemic world. RSV seems to have combined powers with COVID and influenza and we've seen these numbers rise and it's begun to mimic more, in more cases, especially older patients who are greater than 65. We're seeing flu-like illness in these and RSV being the culprit, which has always been a possibility, but we don't see it as we have in the past.

Dr. Gordon:

Yes, and…Go ahead.

Dr. Wang:

Well, I was just going to say, I think part of that is maybe our increased awareness around respiratory viruses. The fact that we have these multiplex panels that enable us to test for multiple viruses with a little less labor involved, and we are finding RSV in these patients who are really sick that we didn't previously have an explanation for.

Dr. Attaway:

Yes, the epidemiology, just to continue that, the epidemiology is interesting now that these nucleic acid tests are so commonplace. This is the baseline test you'll get at most laboratories because it has become so simple. Historically speaking, trying to get a viral diagnosis into the last 20 years has been a long, arduous process for select agents. So actually, getting a routine RSV diagnosis, it's the same as like once you start testing, ah, now we're actually seeing the full picture, which is really interesting. And now that we've got the vaccine in the market and again it's important now, we should add this testing on to see how that changes the epidemiology.

Dr. Wang:

I'm curious, Dr. Gordon, from your perspective, I saw a paper that was published earlier, I think it was last year, which showed that even though RSV is less common, the presentation actually was more severe in adults who are hospitalized compared to flu and even COVID. I'm curious if that's been your experience clinically as well.

Dr. Gordon:

So, it's a great question. I think that was a nice CDC study which looked at hospitalizations in adults. To your point, although less prevalent than influenza, those were that hospitalized. Now there's probably some bias there. And when we look at RSV in adults, immunosuppression which we have a bunch of at the clinic, especially those older than 75.

So, I think this goes full circle because the more we are testing for syndrome in viruses, we will likely uncover more cases that maybe previously weren't tested because of the collective decision now to make that standard for adults during this season. And then the hope is of course, we'd rather prevent the disease than diagnose it. I think we would all agree with that, and there are vaccine-preventable which we would now potentially include RSV in that genre, for the first time, at least for adults.

I do think we're in an interesting space as we move forward and I agree that the lab is so important now because we can be assured about a lot of things, but not necessarily be correct. And if we're not testing for it, we actually don’t know. Obviously, we care about the patient. I think this has been a great kind of interaction with the clinicians and the lab and what you all have done.

I want to re-pivot because, I get a lot of questions from patients. They ask, "Hey, Dr. Gordon, if I have a flu-like illness, won't it be a lot simpler for both of us if I had a COVID test that I'm doing at home, an antigen test, and had a flu and RSV test so that I can then call you after my testing and show you the results?" How far we away from that and what are the barriers for that, Hannah?

Dr. Wang:

Yes, so that's a really good question. I don't think there has been as much movement in the home testing arena for flu and RSV as there has been for COVID, at least I haven't really heard about it. I think part of the COVID at-home testing is largely driven by isolation guidance and how that diagnosis affects our social and our personal lives. So, I don't know, because there hasn't been that same level of guidance for flu and RSV, I don't know that there is the demand as much for at-home testing at the volume at which manufacturers would need to make that attractive.

I think the other problem is that we have seen with influenza, antigen testing specifically, that's an antigen test that's very challenging to develop with the rate at which it mutates and the lower sensitivity. I think there are challenges there, but we may see something like that one day. I will point that there is now a nucleic acid test that's available at home for COVID testing that uses a type of amplification that is very fast and can be done at home that doesn't require the type of machinery we need in a laboratory. So, I wonder if we might also see development of this sort of at-home testing as well.

And the last piece, I'm curious about your thoughts, Dr. Gordon, we're seeing with the COVID pandemic is that we really need to meet patients where they are in terms of access to testing. That could be in the form of home testing, and I think also home collection and sending that specimen to a lab to be tested. You can Amazon anything.

Dr. Gordon:

Yes.

Dr. Wang:

I don't know if I'm allowed to say Amazon.

Dr. Gordon:

Yes, yes.

Dr. Wang:

You can ship anything anywhere these days. One thing we'll have to keep an eye out for is the availability of at-home collection that could be convenient for the patient, that gets then sent out to a laboratory where the highest quality of testing can be done. So that may be a form of testing that meets all those criteria.

Dr. Gordon:

Wow. Thank you for that. Chris, what's implied in here is what you all would call the pre-analytics. I wonder if you can also explain to the audience that box that you all don't control, but can be so important for testing that Dr. Wang just kind of indirectly spoke about?

Dr. Attaway:

Right, this is one of the reasons why, for the at-home antigen tests, we really like those because they're at-home. The patient can collect the sample themselves; they drop a little drop on it, and they wait for a line. Now, with the astronomical convenience of it you sacrifice some sensitivity. They may not always be positive when you're actually positive.

But on the flip side, like Dr. Wang also mentioned, is that this self-collection, pop it in the mailbox, send it away, you can get a nucleic acid-based test, which has significantly higher sensitivity, but now you're adding in the complexities of this pre-analytic phase. Did the patient collect the sample correctly? Did they collect it from the right site? Did they pop it into the media correctly? Say you got a swab that comes with a media, you do that at home, did they do all this correctly? There are all sorts of variables that can occur between the swab, swabbing the location, and then making its way to the vial.

Then now it depends on where you live in this planet because you're going to put that in an envelope, put it in your mailbox. Is it 100 degrees outside? Is it -20 degrees outside? Then it goes through this cold chain of just circulating from the mail. Even with the fastest delivery it could still be eight or nine hours out and about under a certain circumstance that nucleic acids don't like to be in. So, there's a lot more complexity added even though we're ideally looking for a better test. So, navigating this aspect of the shipping, what's the best container, what's the best way to ship it, what's the fastest way to ship it, so that the lab can actually receive it and perform that test quickly, now that's the hard part.

Dr. Gordon:

I really appreciate that. The other side we think about, and I think there was a powerful message, and that was Test-to-Treat. So, if you're testing where the test is going to potentially the patient is a candidate for treatment, then there's the time aspect, and then you can get a test result. But if a tree falls and no one's around, does anyone hear it? So, there's that other piece of the effector arm, which raises another degree of complexity.

But I do think we're moving in this way. Obviously when we talk about pregnancy testing, there's other home tests that this space is exploding. As you said, it's probably not for everyone, but I do think, especially for those caregivers at home that have their kids in daycare where there's a fever, you know, is it strep, is it flu, is it COVID? You can see where this would be extremely important not just for Test-to-Treat but also for infection prevention purposes.

Dr. Attaway:

Yes, that's what the lab wants to get people, that's what clinicians want to get people, they want to give them more power. A lot of people can regulate themselves. Like you said, they know they were exposed, somebody has a diagnosis, they're like, "Ah, spent all day with that person."

"I was in the office with that person all day. I have the same symptoms." They want that peace of mind that's like, I want to know if I have blank. To provide them with this opportunity to just order a test that comes in the mail, send it off, they're like, "Ah, I knew it." So, it kind of gives patients a lot of access, which is what I think we all want, but navigating it in a way that provides them a meaningful result is the hard part.

Dr. Gordon:

I wonder if we can pivot to other things that the lab helped us with or helped us stay in our lanes about what a positive test means. Dr. Wang want to talk about cycle thresholds, and we were pushing. what is that cycle threshold? But of course, there was probably not a lot of data to support that this meant you had a lot of infection versus a little bit of infection.

And I wonder if you can also talk about the concept of, you can be infected, but not also have disease and that isn't necessarily a failure of say a vaccine, it actually might mitigate the infection, which a lot of people I think misinterpret it. "Oh, I got a vaccine. I had a positive COVID test. The vaccine doesn't work."

Dr. Wang:

So, this is a great question. And you mentioned that study that an ID doc can't necessarily tell based on the symptoms what respiratory virus it is. Well, also, the flip side is true. Just because you have a positive test, that doesn't tell you that you have a respiratory illness. We have to understand that the testing and the clinical signs and symptoms go hand in hand.

There is no sort of nucleic acid test for COVID, flu or RSV that is only positive in patients who are clinically presenting with illness. I'd argue that it's also important to be able to detect positives in asymptomatic individuals because those people may go on to transmit infection to other people. So, it can be really challenging to interpret nucleic acid tests and that's where I think the interaction between the clinical team and the lab is so important.

I'm sure Dr. Attaway can speak to his experience as a trainee during this time in answering those questions. That interaction is so important because we're tasked with taking what is not a quantitative test but there is information behind that yes-no answer that could be helpful in the right context to the right person to be able to help interpret that assay a little better. And we can't put out that result as if it were quantitative value because it's not a quantitative test, but it's that dialogue that ultimately helps provide that additional information for interpretation. I don't know if you want to add anything.

Dr. Attaway:

The only thing I thought that would be interesting is the interpretation is challenging. Even outside of CT values and things like that. I was thinking of the negative aspects of large multiplex panels. Which, Dr. Gordon mentioned earlier, it might provide peace of mind to the patient to get a result that is not actionable. That can be the hard part of having this expensive, big panel that gives you a result. Now, does that result provide meaning? Not necessarily.

And simultaneously, what if you have somebody who is very, very ill, inpatient. You get a big panel and the only thing that comes back positive is something like rhinovirus and you're like, "Hmm?" Now it's almost convoluted, the picture. This probably isn't what's causing the disease, but something is, and this might give you sort of false security that maybe it’s just something else. So, the testing can be very challenging to interpret sometimes. Not just from where it falls on the CT number, but what tests come back positive. Based on what they find, whether who’s carrying, who’s actually symptomatic at this kind of setting. It can be very challenging.

Dr. Gordon:

Thank you for that perspective. I know you could probably give the top 10 most interesting queries that you've received from clinicians over the COVID era from clinicians that I'm sure there were things that would make us …. and I was probably asked one of those questions. But I think it's important for the clinicians to ask a question. There's no such thing as a stupid question because a lot of clinicians are not trained in the black box behind the lab, and I think that support that we have is just amazing.

The other thing is, test of cure, which also came up. It's interesting to note, I think we're going to see some guidance now on return to either the workplace or workspace following a COVID infection. It's going to fall back into traditional other respiratory viruses where one would say, "Once your symptoms abate, the fever's gone, you can go back to wherever you want to go." But I wonder if you can tell us, where is the role for test of cure, if there is any, for any other respiratory viral pathogens?

Dr. Wang:

That's an amazing question, especially in light of the very recent change in terms of isolation guidance from the CDC. So, I think that's a great question. The question is why are we testing for cure? Are we trying to say this patient's symptoms have resolved and they no longer need a drug or a therapy? Very sick patient who's maybe immunocompromised and admitted, do they need convalescent plasma or not? These sorts of decisions.

Or is it to say, is this person capable of onward transmission? I can't really speak to this, but I think in the US, as a society, we've sort of decided that if you look at our public health guidance and whatnot, we've decided that we're not going to be able to prevent onward transmission using test of cure. Because that comes with a bunch of difficulties and challenges logistically that as a society, we need to all agree that we're willing to accept, and I don't think we're there. 

If you're not willing to do the arm that says we're going to isolate and we're going to do something different for patients who are positive after, let's say, five days of, initial test, then what's the point of testing? And I think those two arms have to go hand in hand. You can't test for a cure and then not do anything about it. You have to decide what you're going to do with that result. There is no test of cure necessarily. But what we basically do know is that as time goes on, patients can continue to be positive for respiratory viruses even if they're asymptomatic. So, what we do with that I think is a public health decision.

Dr. Gordon:

No, thank you for that. I think most of us have not adopted the test of cure for SARS-CoV-2 or other things, realizing that the test could remain positive, it's rendered until asymptomatic. Perhaps the only exception would be our very immunosuppressed patients, which we know have difficulty clearing all sorts of viruses. Our guidance to them has always been that you're going to have to try to protect yourselves. That is masking in public or avoiding those situations because the rest of the public is probably not going to do that at this point in time or is it an expectation. Chris, anything you want to add.

Dr. Attaway:

Yes, the only thing I was going to add is something that we already touched on is that the test for cure, there isn't one but, I'm sure you have patients come to you and they quote, "need" a negative test. Especially historically speaking, they needed a negative test to visit relatives, to travel, to do what have you. This is the hard part of working with humans is that everybody is different, and Dr. Wang mentioned there are patients who will be positive for a long time after they got sick, or they may be asymptomatic to begin with and will be positive for so long after.

So, even with the current methods we have, getting that negative test, if you want to even call that test before, it's just different for every person. So, I know there has to be listeners who have been like, "Oh, yeah, I had it, I had COVID and then two months later I still had a positive test," and there's just no right way to go about it.

Dr. Gordon:

Yes. Thank you. I wonder if we could pivot now to, I mean, we've talked about the individuals and all the great work and expertise that has been done and that you have provided us. I'm wondering, we talk about public health and the other thing that I think is fascinating that came out of COVID was the wastewater surveillance of sewage. I wonder if you could give us the ABCs there. I find that to be obviously a different sampling, a different way, but very interesting, and powerful.

Dr. Wang:

Yes, I agree with you. The data that I have seen and has shown in that wastewater sampling and surveillance is incredibly powerful, and pretty accurate. I'll give you an example. Earlier, last year, there was circulation of a new variant of SARS-CoV-2 that we detected in our population through genomic, screening that we do with ODH, or Ohio Department of Health. We detected this one patient who had this new variant of COVID, but at the very same time, basically the same day, that variant was also detected in wastewater.

So, it just shows the power of wastewater surveillance. I think the data I've seen have shown that done in the right way, it's challenging, you have to do right and can be very powerful and is increasingly important as patients move to non-laboratory-based testing. Because a lot of our public health reporting relies on data fed from the laboratory. So, I think this new stream of data is going to be increasingly useful and important as testing becomes decentralized.

Dr. Gordon:

I like that. Chris had brought up health equity in everything else. As Hannah, you mentioned, most of our surveillance today depends on someone's access to curating the test in wastewater sewage surveillance, which I know sounds gross.

But you obviously, if you're hooked up to the sewer, which most Americans are, you would then, contribute to the detection. And there's been some wonderful, interesting things, polio and other aspects.

Now I also heard in New York City of course there's other things that can contribute to the sewer that are non-human. So, whether it's rats or things of this nature, you’re measuring all sorts of potential things, some of these are zoonosis. But I find that to be fascinating and another piece of the tool. Chris, anything that you want to add about that or your reflections on WWS?

Dr. Attaway:

No, I think it is very interesting. I don't know how much the listeners know, but I think people are somewhat familiar with, influenza, a lot of diseases are reportable and that means they are sent to places like the CDC or state health. And some people are not always aware of how exhaustive that list may be. These things are tracked to within an inch of their life.

So, it is for the greater good of the public that if you have a positive test, it is reported to the state and the federal level. When things start to not add up, that's what's very helpful for infection control purposes. So, there's a new variant on the stage, oh, it's being detected in these locations, you can predict trends. It is very interesting as you said, it's also very gross, wastewater, but there is a silver lining to that being processed through a facility that is able to measure these types of things. They measure lots of things, it is very interesting all the things they do for us.

Dr. Gordon:

Well, in closing, this has been truly fascinating. Again, my deepest gratitude to you both and to the entire lab team. I think it was probably only the second or third time where you saw the CEO of the clinic go to the lab and that just reflects that you guys are the BASF, it’s the things behind making things work well. I think the lab got a lot of appropriate gratitude, as you mentioned, for not just developing the test volume in the pandemic, but also keeping the other service lines going. It is truly amazing, and we are very fortunate to have talent and all your hard work in your teams.

Again, I think this has been fascinating to see where the future holds, too, in terms of testing. in terms of, as you taught us, the right test for the right situation. But I wonder if we can end, and I can put you on the spot a little bit, is there anything you're reading, book, medical or not medical that you might recommend to the listening audience? So, Hannah, we'll start with you.

Dr. Wang:

Oh, man. That is an interesting question. My reading is generally not medical. I actually got a recommendation on a book from a colleague, Dr. Harrington, she directs our Acid-fast Bacilli Lab as well yourself, it's The Covenant of Water. It’s one of the most powerful books I have read in a long time, and I don't want to give away the ending for any listeners on the line, but it helps me reflect on the power of medicine and public health in terms of combating disease, and as a reminder of not just the impact we have medically for patients, but socially and on people's personal lives. I think renews my passion and drive for what I do.

Dr. Gordon:

Well, thank you for that.

Dr. Wang:

Yes.

Dr. Gordon:

That is written by your former colleague, Abraham Verghese, who's an ID clinician at Stanford.

Dr. Wang:

Yes.

Dr. Gordon:

Thank you for that. And Chris, I want to do a shout out for Chris, he runs a lot of our monthly or weekly clint micro and it is for me it’s like an off-Broadway. It's not only entertaining, but also very educational. So, I'm very curious to see what your book recommendation will be.

Dr. Attaway:

I try to bridge the gap, so you have the insider knowledge that I'm a history person, and so I only read things that are true as a rule.

Dr. Wang:

I'm the opposite.

Dr. Attaway:

I know. But I did just finish reading a very incredible book which is called The Warmth of Other Suns,
and it is incredible. It's of course all true. It follows three people who grew up in the South and then they moved to the west and the north, this follows the Great Migration. When Black or African American people left between basically between 1910 and 1970s, they left their homes for better opportunities elsewhere. But it is really incredible to follow their journey, because I've been to all the places they've been to. As I said, I'm a rural southern boy, I've been to all the places that they were from, so it's very interesting to see the places that they went and how they got there and what their lives were like, if they were different at all. It's very powerful that the things these people saw are still evident in our landscape, so I think that's the most interesting part about it.

Dr. Gordon:

Wow. Again, my name is Steve Gordon and, just gratitude to our guests, Dr. Wang, Dr. Attaway, for a great overview of microbiology testing with a focus on RSV and respiratory viruses. Thank you both and thank you for listening.

Dr. Dweik:

Thank you for listening to this episode of the Respiratory Exchange podcast. For more stories and information from the Cleveland Clinic Respiratory Institute, you can follow me on Twitter, @RaedDweikMD.