TWiV 648 Life is for learning

This Week in Virology

Host: Vincent Racaniello, Dickson Despommier, Alan Dove, Rich Condit, and Brianne Barker

Guests: Daniel Griffin, Chuck Knirsch

Aired 1 August 2020

Vincent Racaniello: This Week in Virology, the podcast about viruses, the kind that make you sick.


Vincent: From MicrobeTV, this is TWiV, This Week in Virology, Episode 648, recorded on July 31st, 2020. I’m Vincent Racaniello. You’re listening to the podcast all about viruses. Joining me today from New York State, Daniel Griffin.

Daniel Griffin: Hello, everybody.

VR: Also from New York State, Chuck Knirsch.

Chuck Knirsch: Hi, Vincent. Hi, Daniel.

VR: Welcome back, everyone. Time for our weekly update. The weeks seem to shoot by, July is almost over. How about that?

DG: This is true. I was just thinking, Chuck, when I go sailing tonight, I can probably see your house. [chuckles]

CK: It’s dark outside. You’re going to maybe have some rough weather out there.

VR: Do you go on the Sound or something? Is that how–

DG: We do. We go out into the Sound and sometimes it can get a little exciting out there.

VR: I’m sure. That’s a good way to get away from COVID for a while, right?

DG: [chuckles] It’s important. I have a couple of quotations here. I heard people enjoyed the quotation last week. Apparently, we’re going to be making a T-shirt, “Masks are cool.” The doctor. Some people got the reference there. Here are my quotations this week, “Headlines, in a way, are what mislead you because bad news is a headline and gradual improvement is not.”

VR: It’s so right.

DG: That’s from Bill Gates.

VR: It’s true. I often ask journalists, “Why don’t you report this or that?” They say, “It’s not news.”


DG: The other is, “I’d rather get bad news from an honest man than lies from a flatterer.” That is Ursula K. Le Guin.

VR: The writer.

DG: Yes.

VR: Nice.

DG: Big fan of her stuff. I put those out there because I was having a conversation in the intensive care unit yesterday and it was with one of the emergency room physicians. His comment after we talked for a while was, “Dan, that is the first good news you’ve given me since February.” [laughs] Apparently, I have a reputation for lots of bad news. We’ll start off with bad news, case numbers, deaths, morbidity, we’re not doing well as a country. We’re not doing well as a world actually. We’re back up to over 1,400 COVID deaths per day. That’s more than a death every single minute. Just think about how many minutes you listen to this podcast. Every minute, another person in the United States is dying. This is a disaster. People talk about things plateauing. That’s not an OK plateau in my mind.

How are we going to get on top of this? The last TWiV just before was testing our way out of the crisis. I’m going to talk quite a bit about testing actually. This has been a challenge actually. I got a call yesterday from Lawrence Shulman. He’s the head of our COVID core team at ProHEALTH New York. We’re now ramping up our ability to do testing. One of the things we’re running into is even though maybe the public has lost their fear of COVID, healthcare workers haven’t.

Now, that we can do more testing, there’s a lot of offices that really– basically the signage is, “We don’t want COVID patients here.” As soon as you say, “Hey, we’re going to start doing these rapid tests. We want to be able to find out who has this or not.” A lot of the people in the office are scared. They’re basically like, “Can’t we do that, can’t we keep them outside? Can’t we just leave them in their cars?” Et cetera. I’m going to talk a little bit about the transmission and testing and how this works.

I’d think repetition is important. We know that those people who show symptoms that they actually start to become RNA positive two to three days prior to the onset of symptoms. Two to three days, 2.4 is actually the number out there. They are RNA positive actually at higher levels than when you test them the day they come in with symptoms. These are some studies that we’ve got now. That’s going on. Are they transmitting as much? I think this is an interesting issue for case-control studies. If the nose isn’t running, if they’re not coughing and sneezing, they may have a lot of RNA in their nasopharynx but there’s a question, “How much they’re spraying out into the environment?”

Once there’s an onset of symptoms in the large percentage of people with normal immune systems who are able to stay out of the hospital, we say it’s five to nine days after onset of symptoms that they’re remaining PCR-positive at a rate high enough that we think that they’re infectious. I’m going to hit on what is that RNA level that correlates with infectiousness. This gives us a window as we’re talking about from seven, shortest seven days. I think Michael Mina hit a seven, but maybe out as far as 12 in some of those individuals. We’ve actually cultured it out to nine days. Contact tracing I think goes along with that. The WHO and CDC, they actually push back and they start looking at people that you were exposed to four days prior to the onset of symptoms. Let’s say, you’ve got this 7 to 12-day infectiousness window.

Now, we think the same period of infectiousness applies to asymptomatic individuals because we know a certain number of individuals become PCR positive at high levels but never ever show any symptoms that we would attribute to COVID-19 to the SARS-CoV-2 virus but there’s a little bit more uncertainty there. We just don’t have the same amount of data that we have in the symptomatic.

Now, in severe cases, people with immunosuppression, people are hospitalized. Those treated with immunomodulators, those are the steroids, the IL-6 receptor inhibitors we talk about, the infectiousness may extend out to 20 days or even longer past the onset of symptoms. That’s where the CDC guidance is, that’s where you need to start considering test-based approaches to address those people, the involvement of an infectious disease specialist or an infection control specialist.

Let’s talk a little bit about RNA levels and infectiousness. I’ve created a little table here. I was glad I created this table because I keep getting asked this question. In my table, I have one, two, three, four, five levels. The very low level is an RNA load or an RNA piece number of about 100 or less. That’s that sensitivity of our nucleic acid amplification test, our RT-PCR. We get up to an RNA load of about 1000. That’s CT values of about 36. Maybe people are getting a little familiar with the CT values.

Then, an RNA load of about 4,000 or 5,000 and that’s when we have a CT number of 34, if we can ever get access to those CT numbers which we’ve talked about. That’s where our Abbott ID NOW picks them up. 4,000, you’re not even infectious yet. I know we talk a lot about sensitivity of tests but in that seminal publication at NYU, if you had more than 4,000 pieces of RNA, the Abbott ID NOW was 100% sensitive.

I think when we talk about these quick, inexpensive, cheap tests that lack sensitivity, I’m going to challenge the concept of sensitivity. Sensitivity for someone who had virus two weeks ago when we’re just picking up the tail, that’s different than sensitivity for infectiousness. You get up to an RNA load of 50,000 or a CT value of about 30 on our RT-PCR. These would be all those rapid antigen tests that Michael Mina’s talking about that the Broad Institute is hopefully going to be helping the Boston schools use to get everyone tested.

The rapid antigen tests such as BD, Quidel, or Assure, all these ones that at this point, we’re not down to the dollar-a-test price point but we’re moving rapidly there. If you have an RNA load of 50,000 or more, these tests are picking it up. You don’t really become infectious until a CT value of about 24, that’s 3 million, that’s a lot. The sensitivity of these cheap rapid tests for picking up someone who is infectious, they’re great. They’re not really inferior tests. I just want to make that out there.

What does it take to get sick with COVID-19? This is, I know, a concern that our nurses, our office staff. If you bring a person into an exam room, they sit down, they’re wearing a mask, you put a Q-tip in the nose, you pop that in the vial, they walk right back out. Minimal contact time, you’re wearing a mask and eye protection. We don’t consider that a significant exposure. That’s not where we’re seeing transmission. We’re seeing transmission when you’re sitting within six feet of someone. They don’t have a mask, you don’t have a mask. No one’s got eye protection and you’re talking for 15 or more minutes. This is not radiation.

CK: Probably especially indoors, right, Daniel?

DG: Yes, exactly. Outdoors, it seems like it takes even more exposure. In an ideal world, we’re doing this in the cars, rapid, people are swabbing themselves, et cetera. We’re all going to benefit by testing, tracing, identifying these people. Just a reassure that this is not measles, where someone walks through on the way to the exam room and well, we’re all sick. This actually takes a certain exposure and I think we’ve learned more and more about how much exposure that really is. I like to use my slide analogy when I tell people about this whole infectious thing. Think about going up the slide, like when you’re standing there and you get onto the first rung, even if you slip, you’re going to be okay because that’s such low level of virus that you’re not contagious.

When you’re getting there up about halfway to up the top of the slide, that’s when you’re getting into the millions, when people are at risk. If you’re the mom or the dad, stand there, don’t let the child fall off the slide. That’s also the time when you don’t want this person going to work. We don’t want the person out there spreading virus. When they start coming down the slide still they’re up there. You don’t want it falling off either side. Once they get to the bottom of the slide, we’re okay again. Think about that as far as exposure and the infectiousness. We–

VR: Daniel, sorry, these numbers, does it make a difference if you’re symptomatic or asymptomatic throughout the entire course of infection?

DG: It doesn’t seem to, when you look at– I know Anthony Fauci made the point of, “Hey, if you’re above 35, the chance of spreading disease is minuscule.” That was based on one study where they actually were able to culture virus from someone who was at 35. In general, if you look at the transmission studies and the other studies, unless you’re above, unless you’re more virus, unless you’re coming up before 24, you’re not spreading. This, we know a lot more, I think about people who are contagious, but now as we get more and more data, I think this probably is the same for people who are asymptomatic as well.

VR: It must be because we know a lot of transmissions occur from asymptomatic people.

DG: Yes. Unfortunately, they would make this disease a lot easier if you could eyeball people with symptoms. I was doing a talk today on fever and only a quarter of people with COVID-19 who are spreading we think ever even get a fever. The people who get symptomatic, it’s not everyone. Then the asymptomatic people, they don’t get fevers by definition.

VR: Yes, a lot of schools want to do fever checks and I’m like, I’m not sure it’s worth it. A lot of them are going to buy equipment and it’s not going to pick up and it’s even less penetrant in children, I think the fever, compared with adults.

DG: Yes, you’re correct. I think that we’ve seen that children are seemingly less likely to show symptoms. If you’re going to be looking at schools, if you’re going to be opening things up, testing is how you know. I remember early on, it was actually the early days of March and it was the chief of medicine in Plainview. He was asking like, “Oh, what about the procalcitonin? What about this test?” I was like, “Oh, actually, you know what test seems to correlate with COVID? The PCR.”


It’s like we actually have a test. That’s how you tell if someone is shedding virus, you do a COVID test. I was on a call Tuesday night with one of the large media production companies and they basically were saying, “We want to open, then if we want to open how often do we have to test and who do we have to test?” I said, “Well, if you really want this to work, you’re going to test everyone every morning before they go to work.”

I even laid out and I said, “This is how much it’s going to cost.” Basically, they said, “Okay, that’s what we’re going to do.” I love those conversations where people get it. If you want to do this, yes, it’s going to cost a certain amount of money. Maybe right now that’ll be $30 a day, but very soon that’ll be 10 and before we know it, we know we can get that down to a dollar or two and a dollar or two to open up the economy per person, that’s not even a cup of coffee at Starbucks. Maybe people are listening in other parts of the world and they don’t know how much we pay for a cup of coffee at Starbucks, but we can do this. We can test ourselves out of this crisis. We can safely open schools, but yes, as I think we’re hammering in here, testing is how we–

VR: Unfortunately many schools–

CK: We can safely open when there’s low transmission, I think in the areas and our friend, Peter Hotez wrote to The Wall Street Journal, probably more drastic measures, I don’t know about full shutdown. You were debating that, I think in the last TWiV a bit, but some measures you need to bring the level of viral transmission down before testing and tracing contact will be helpful. I think it could open the schools, especially in New England, New York, New Jersey, Connecticut right now where we have flattened the curve, so to speak.

VR: I think many schools do not have the ability to test, Daniel, and so they’re not, and it’s unfortunate because they should. It should be cheap enough that they could do it because that’s really the key as we’ve been saying.

DG: Yes. Interestingly enough, you say that, but it is basically no cost to get a COVID test. That was that conversation is it is supposed to be the deal that with all the federal government support, which is now seems like there’s a little bit of a waffle here. When you go get a COVID test, it’s not supposed to be a cost to you. This is something that the insurers, et cetera, are supposed to cover. No copays, you’re supposed to be able to go get tested without a cost to you. It isn’t even a dollar a day, this is what our government is supposedly providing for us.

I think a lot of us– there was actually, I think I mentioned on the last TWiV where it was Quest or Labcorp had said on email, not only will we partner with you to do testing but by the way, we’ll also do sexually transmitted infection testing at the same time. Which I thought was interesting.

CK: Public health campaign.

DG: Let’s not just give up. Let’s demand that if we’re going to say let’s open the schools, let’s demand that we do it in a way that’s safe for our children and for our teachers, and for our communities. Vincent and I, we were talking right before, another study coming out, maybe kids are not less likely to transmit than adults. Maybe they’re even more. This is concerning. I know I did a Tri-State Urgent Care talk the other day, I talked about the urgent care centers and I talked about what tests we need in those settings. Really similar to just echo what I just said. If someone comes in and they’re sick and they don’t feel well, and they’re thinking it might be COVID-19, one of these rapid tests will tell you if it is or not because during the acute onset of illness, you’re going to have very high levels.

If the person says, I’m going to be in a situation where I might expose someone at risk, the rapid tests are going to tell you if you’re infectious. If you were sick two weeks ago or 10 days ago, and now you’re having shortness of breath and we’re worried that you’re getting into that cytokine storm phase, OK, that’s where you need the RT-PCR, that’s where you need a more sensitive test, because now you’re not suffering from a high viral load, you’re suffering from this immunological issue. Different tests, but you know what? The expensive ones are not the ones we need in most circumstances. Masks, so there’s actually some more stuff coming out about masks, so where do masks play a role.

The nice thing I thought about this recent article I saw was, so we’ve been telling people wear masks to protect your neighbors. I’m not sure how altruistic we all are, so it was really nice to see a study. Masks do more than protect others during COVID-19. This was actually an article looking at mask reducing your risk of getting COVID-19. I think it’s nice, maybe there’s a little evidence that not only are you doing the right thing by your neighbor, but you yourself might benefit from wearing a mask. Not only are masks cool, but they might be something that helps you as well as helping others.

I was going to talk a little bit about the public health perspective we as physicians are being pushed into. We are role models now. I was at a meeting a couple of weeks ago and there were a lot of clinicians in this room. Actually, it was only a couple of us that were actually wearing masks, I was one of them. That’s an issue. You got to think about that. I’m going to say, let’s not mask-shame each other. Let’s think about how to wear masks properly because this is not a sprint, this is a marathon.

When you’re with your wife, when you’re with your social cohort, that you might be sitting together in the home limiting your exposures, watching TV. If you’re now sitting on the back deck or you go for a walk and it’s just you and you’re able to avoid others, it’s the same outdoors. Maybe it’s even safer outdoors than it was sitting in the living room watching Doctor Who on the BBC. When you’re not able to maintain that social distance and you’re going to be within six feet of others, then you’ve got to wear the mask.

One of the things I’ve been pushing for a while is this concept of these social cohorts. Some people use the term social bubble. I don’t like the baggage of a social bubble. I think it carries some interesting social connotations that maybe emails will write about, but the idea of it looks now about 50% of Americans have adopted this, where two families might decide we’re going to be a social cohort or form this bubble as they say. A lot of times it’s based around the children because it is really important to have those social interactions. I do want to remind people that it’s not like Kevin Bacon and Six Degrees of Separation.

That social cohort has to be of a certain size. You can’t then have a social cohort that becomes your entire town because then it ceases to be a social cohort. These are important and interesting enough, that is a nonpartisan issue. They actually looked at people of different political affiliations and it’s 47%, 50% independent of who you might support in the 2020 upcoming election. This is being embraced by about half of Americans and I think there’s a big mental health advantage to these social cohorts.

Understanding the clinical phases, I’m going to very quickly go through this but I want to– the pre-symptomatic, the viral phase, the cytokine storm, the hypercoagulable, and a little later I’m going to talk about the late hyperinflammatory phase. This multi-system inflammatory phase that we don’t just see in children but we see in adults. Then the long phase or the tail phase. A couple of articles came out and I think a lot of this is helpful for reinforcing the validity of these symptoms. I see a lot of individuals, they call me and they say, “I’ve been suffering and just discounted.”

There was a MMWR publication that came out, “Symptom Duration and Risk Factors for Delayed Return to Usual Health Among Outpatients,” which is a neglected COVID population, we focused a lot on hospitalized. They actually looked at about a third of the individuals were over 50 which meant two-thirds were under the age of 50. We’re looking at younger individuals who still think that they’re immortal and immune to all these maladies and they actually looked at, in this study, individuals aged 18 to 34.

Then they called them two to three weeks after disease onset saying, “Hey are you back to all better? Are you feeling fine.” Actually one in five said “No, I am not back to all better” I like to say with influenza, if you check about a month out about 10% of people say they have residual symptoms. People sick enough to get hospitalized with COVID, it’s only about 10% that say they’re all better, so it’s a reverse, 90 are still struggling. What we’re seeing is not just hospitalized patients but even people that didn’t end up in the hospital, there’s a tail to COVID.

An interesting thing about that tail is it can have this second peak where they feel crummy, they get better and then some people it’s this week four they feel worse again. I know Vincent you would ask me like when we do blood tests what do we see? We actually often see the neutrophils go back up, the lymphocytes drop back down, we see inflammatory markers start to go up. There was a study looking at cardiovascular issues in patients who were out a little bit and they actually were– we looked at 100 patients that had recovered.

These people that were supposed to be better. When they looked at them, 78% of these people post-COVID had ongoing myocardial inflammation. There seems to be a late inflammatoryresurge and I don’t know what drives this. We’ll get John Udall, he’s going to help us and tell us why this is happening. We often think of COVID as some animal that no one has ever seen before but that’s not true. There’s a lot of immunology, there’s a lot of virology that we know fortunately, we don’t know as much as we would like to.

We spent too much money on aircraft carriers and not enough on basic science. This may be something that we can learn from other illnesses. We got some good news and some bad news on therapeutics. Was an interesting inhaled treatment with interferon beta that came out, a very small number so we’ll see where that goes. We continue to have our evidence for pulmonary support. We had another trial, the Montefiore trial on steroids, but then we have a bit of negative news on tocilizumab or Actemra and I think it’s reasonable to discuss that here.

This was looking at using IL-6 receptor blockade without steroids and I’ve talked about this for a little while. We were talking about this in the ICU today. In many ways I was not surprised what we were seeing and actually, there was a trial at Columbia where Justin Aaron was involved. When you seem to give tocilizumab when you seem to do IL-6 receptor blockade on individuals without a steroid first, people seem to get better and then get worse.

In this study, they did not show a mortality benefit, they didn’t show an improvement benefit, that was the primary outcome. Interesting enough there was an eight-day shorter hospital duration with a p-value of 0.03 but that was not their primary endpoint, so we won’t mention that. That’s a little more impressive than the three day with Remdesivir but another reassuring thing out of that study was there was no significant increase in bacterial infections which I know I was quite concerned with tocilizumab because once you put them on it, you’ve suppressed the immune system for a month so it was nice not to see negative but maybe a little trend towards shortened hospital stay, but Chuck do you want to jump in on that?

CK: It’s not published yet so I think that what I’d like to do is look at each component of the seven ordinal scale to see what’s going on because composite endpoints when they don’t all go in the same direction, and with this one, you can’t go in the same direction you can get better, you get worse. I want to see what’s going on because overall, it was about 450 patients if you look at and the p values but not the absolute numbers are in the press release. Let’s wait for the publication. I think with IL-6 therapies like this, the choice of a patient population be critical for benefit.

I suspect the steroid situation with dexamethasone that maybe the sicker patients will have more benefit than this population that really just had oxygenation deficits at the beginning of the study. That’s, I’m guessing, I haven’t seen the publication but we should look at that carefully when it comes out.

DG: Yes I’m curious to see also about these therapies you used in the context of they got steroids and then progressed and then got tocilizumab because yes I think our experience when this came out we’re, “Yes, that’s what we would have expected” I don’t view this as a negative for tocilizumab as much as yes, I don’t think this is something you want to use monotherapy or at least that this confirms that impression we had early. I don’t know Vincent if you had a comment?

VR: There were two previous studies on anti-IL-6 receptor antibodies before and they didn’t do well. There was an Italian study and another one with a different antibody so is it the case that none of these they’re using steroids, you think that’s the issue?

DG: Yes, so most of them are not using steroids. There was an article I should probably share this with you guys. It was by Ramiro and it was where they basically– a lot of the challenges a lot of these are historically controlled where we did this and then we did this and then people did better but when people weren’t doing well we didn’t really know about proning and anticoagulation and where they actually did the steroids with and without tocilizumab so it was tocilizumab within this context.

There they showed a pretty significant reduction in people going on to require ventilatory support. I’m still curious to see where tocilizumab fits in the context background of steroids first because what we see is when we give the tocilizumab without steroids that IL-6 just shoots up and it might go from being in the 40s to maybe over 3,000. It really goes up if you haven’t done something because you’re blocking the receptor which is going to create this feedback. It seems to me a problem if you don’t somehow shut down that feedback loop.

VR: OK, so you still have —

CK: We were emailing earlier today just that the factorial design of the recovery study, the Oxford study, has a primary randomization to the therapeutics followed by if you meet certain criteria either tocilizumab or placebo. I think that might help because to Dan, you were saying months ago that the pre-treatment of steroids and then IL-6 treatment seem to be working anecdotally at the bedside better. We should get that answer and the primary endpoint of that study is mortality.

DG: Yes, and that’s really ultimately what we care about I would say. It’s great to go to the hospital a few days early but the big thing is to get out of the hospital.

CK: Yes.

VR: All right. The message here is unlike hydroxychloroquine anti-IL-6 antibodies not over yet?

DG: Yes, there’s still more to go. There’s other stuff where I think the story should be over but it won’t die. [laughs] All right. I think that’s it for me. Do we have some emails that we want to have before–

VR: Yes, there is a couple here. The first one is just a nice story of Stephen who was turned on to TWiV by his brother virologist. Over the weekend his wife’s aunt had got sick she went to the hospital with a 105 fever, difficulty breathing, appears to have phase 2 COVID. She was rushed to the same hospital where Daniel Griffin works and it turns out that looks, like he’s going to take care of her and Stephen, is very grateful because having heard Daniel on TWiV, Stephen is confident that the aunt will be getting the best care.

DG: Actually, this is an interesting case. This reminds me to get back to what I was going to talk about. This was a woman who people did not know that she had COVID. She came with this very interesting story of bilateral pulmonary changes. Initially, the impression was, “Oh, this looks like a bilateral pneumonia.” Sounds familiar maybe to our listeners. Then they also noticed she was in heart failure. Normally, when the heart fills, it’ll eject about 60%, 70%, but her ejection fraction was cut in half. It was down like 35%.

Here’s this woman previously without any cardiac issues, now she’s in heart failure. She’s got this bilateral pneumonia. What’s going on? She’s got elevated inflammatory markers. She’s got the elevated neutrophil, the low lymphocytes, but the COVID PCR is negative. We went ahead and we did COVID IgG. A positive in this lab would be greater than one. Her IgG was up at 100. We then actually had her daughters get tested. They also had high serology, so they also were positive. At some point, it looks like there may have been an exposure, but no symptoms.

My impression is that this woman was suffering this multi inflammatory phase. We actually gave her steroids. Today, she was sitting up in a chair chatting. She had a number of interesting features when I first saw her. I looked at her hair, this has become a telltale thing, and I was like, “What happened to your hair?” The nurse is like, “Her hair is all over the pillow.” I’m like, “Your hair’s falling out.” She’s like, “Oh, it’s okay. It’s really thick. I’ll be fine.”

Then she said, “Oh, did you speak to my brother?” I said, “What’s your brother’s name?” She said, “Oh, I can’t remember it actually.” I was like, “You can’t remember your brother’s name?” This is a teaching assistant, and she had the encephalopathy, she had the hair loss, she had the cardiac manifestations. It was really amazing. We gave her steroids, dexamethasone. We gave her IVIg. The response was, as mentioned, pretty dramatic.

VR: Landy writes, “I heard Dr. Griffin make a reference to aerosol generation by nebulizers. I’m aware that CDC considers it an aerosol generating procedure. The UK National Health Service, however, states that nebulized medication administration is not an aerosolizing procedure because the aerosol generated is not from the patient, but from the machine. They don’t provide a reference though. I’m curious, what you think about their argument, especially as we have more pediatric patients with the disease that may be hard to get cooperation with an MDI/spacer?”

DG: This is a good point that’s being made here. Different recommendations in different areas. Let’s talk a little bit about why we say what we say, why everyone isn’t saying the same thing. We should all be saying the same thing. When you’re using a nebulizer, you’re actually creating particles that are in that critical 1-to-5 micron level, so that they can get deep into the lungs, supposedly that can deliver the medicine properly. In all honesty, I have to say, we really don’t want them that small. You want them a little larger so they deposit in the upper airways and give you your bronchial dilation.

They’re too small. They should fix their product design. I think the UK idea is these are being inhaled into the lungs, so what’s the problem? We’re not blowing them back out. The force of these jet nebulizers actually will create a little bit of a spray. Then as the person breathes in, it often triggers coughing. They’ve breathed in these small particles into their virally infected lungs, upper airways, and then cough them back out.

This is great. That’s a mechanical article, but where’s the science? Where’s the evidence that this is an issue? There were a couple studies actually go back 17 years. There was another outbreak, SARS-1. In actually a study in the Toronto nurses, they looked at different activities that the nurses were involved in. Those that were involved in the nebulizing of patients were 3.24 times more likely to get SARS. That was one of the words of caution. We’re erring on the caution.

There was another study where they did not show an increased risk in nurses or health care workers that were involved in nebulizers. We’re not sure, but we, at least in the US, this is a second tier per the CDC, where the CDC says, “These top numbers. These are clearly aerosol-producing.” There’s less evidence to support nebulizer, but there is concern. We’ve as much as possible switched over to MDIs, the metered-dose inhalers. Chuck, did you want to weigh in on that?

CK: No, just the biology of SARS-1 and SARS-2 is a little bit different. SARS-1 maybe more infectious with more active disease, so an open issue. I actually agree with erring on the side of caution, which you said, Daniel.

DG: I think it’s also timing, if you think about it. They come to an urgent care and they’re in that peak viral level. That may be the time when they are potentially going to have the most spread if you give them a nebulizer. By the time they’re in an ICU, or they’re in a hospital during the cytokine storm, their viral level may be low enough. We’re trying as much as we can in our hospitals here to create negative fresher rooms so that we can nebulize, if we need to. This may be a way to keep them from ending up on a ventilator, which as we know is not great.

VR: Last one for you, Daniel, from Sanjita, who is a pediatrician in private practice in Texas, and writes that, “If there’s one podcast every scientist and physician should listen to, then it’s TWiV.” Question. “Dr. Griffin mentioned they’ve started testing for COVID in the patient exam room. So far, we have been testing everyone in our parking lot, but as you can expect, parking lot is less than perfect for a clinical exam. Pulse oximetry doesn’t work outdoors. Neither does the touchless infrared thermometer. If we were to bring these kits to the exam room and do the test wearing PPE, do we need a negative pressure room? We don’t have one, but a good heap of filter helper. Should we just clean the room thoroughly after the patient leaves?”

DG: Actually, this is great, Sanjita, and actually thank you. This lets me hit on this topic again. I mentioned this early on. This was the No. 1 question when I was giving this talk to the urgent care providers in the Tri-State area. That always makes me think of Phineas and Ferb when I say the Tri-State area. There were hundreds of physicians on, and this was their top question is, “We’re trying to increase access to COVID-19 testing. How do we do it safely?” Because outdoors has a lot of limitations, as mentioned.

The big thing is just to embrace the science. This is not March anymore. We now have millions of infections. We have months of information, very well studied. The main way that this spread is through droplet. The risk for you is you go into the room with the patient, you’re within six feet. They are talking, singing, sneezing, coughing into your face. We have ways to protect ourselves, wearing a mask, wearing eye protection, wearing all the personal protective equipment that we’re used to now doing.

You don’t have to be in a negative pressure room unless there’s an aerosol-producing procedure. As we talked, if anything, we’re erring on the side of caution when we talk about nebulizers. If the person vomits, if the person needs to be intubated, or suction, there’s very few aerosol-producing procedures that are going to occur in this setting. You bring the person in, they wear a mask. They push it down a little so the nose is accessible, and you do your testing. The mask comes up and then we’re good to go.

If you limit your exposure, not only can it be safely done, but I think that this is a great thing for people to start introducing into their practice. The person leaves the room and we wipe off the surfaces. We still think that that’s a minor way of transmission. You looked at some of these studies and people claim you had to have 100 people cough onto the table before it really got to that infectious level.

The big thing is protect yourself, get them in and out. We have approved products with certain dwell times where you can clean that surface. If the person, let’s say, they do vomit, this is going to happen, then what we do is we close the door. We give it 30 minutes, a normal room without negative pressure will take about 30 minutes for things to settle down. Then you do your 10-minute dwell time and cleaning and you can move on. No, I think this can very safely be done in patient exam rooms without creating exposures for the staff or the providers.

VR: Finally, any recommendations in stopping estrogen-containing birth control in teens with risk factors for COVID? Estrogen creates a hypercoagulable state, but so does pregnancy.

DG: This has actually come up a few times. I guess I’ll fix my bow tie to bring back bad memories. This is where I was on CNN and I was supposed to be talking about Trump and testing. They said, “Dan, let’s talk about pregnancy and COVID.” This is early March. I’m like, “Nobody knows anything about that.” Thanks for asking. This is one of those theoretical risks. We haven’t actually seen significant issues with hypercoagulation in young women on estrogen-containing birth control. We fortunately have not seen significant issues in pregnancy.

There was one paper that came up suggesting a little bit of a signal of more hospitalization. Then I think we may be just more likely to hospitalize pregnant women because they’re pregnant. Fortunately, this is not panned out as a significant concern. There are lots and lots of young women on estrogen-containing birth control. We’re not seeing a signal there. There are lots of women who still get pregnant, I think maybe more during the pandemic because we’re sheltering at home. We seem to be doing OK so far. I think we’re gone be OK with this. I would not recommend stopping estrogen-containing birth control or doing anything special as far as pregnancy.

VR: All right, that’ll do it for this week’s COVID-19 report with Dr. Daniel Griffin. Thanks, Daniel.

DG: Oh, thank you so much. Everyone, take care.

VR: Chuck Knirsch, thank you for joining us.

CK: Good seeing you both.

[00:40:48] [END OF AUDIO]

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