TWiV 642: Bringin’ in 50 keys of spike mRNA

This Week in Virology

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

Guests: Daniel Griffin, Chuck Knirsch

Aired 19 July 2020

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

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VR: From MicrobeTV, this is TWiV, This Week in Virology, Episode 642, recorded on July 16, 2020. I’m Vincent Racaniello and you’re listening to the podcast all about viruses. Joining me today from New York State, Daniel Griffin.

Daniel Griffin: Hello, everyone.

VR: Also from New York State, Chuck Knirsch.

Chuck Knirsch: Hi, Daniel. Hi, Vincent.

VR: Welcome back. It’s been another week, and SARS-CoV-2 and COVID-19 is still in the news.

DG: If you can imagine that. I don’t know if you’ll splice in that line about viruses, the kind that make you sick, but I’m going to make sure I remind people that COVID-19 actually is one of those viruses that makes you sick.

Let me start off with a couple of quotations. There was one I prepared but then I was listening to one of the other TWiVs so I had to add a second. The first is from Lin-Manuel Miranda from Hamilton. I hope everyone’s had a chance to enjoy that on Disney+. If you don’t Disney+, well, I don’t know if you can safely go over someone else’s house and watch it there. [laughs] “In the eye of a hurricane, there is quiet for just a moment.”

When I put that in earlier this week, that’s the way I was feeling like things were in New York. The storm clouds are starting to gather and move in. I’ve got a patient in the ICU right now on high-flow oxygen who’s not doing well. I’ve got another patient in a negative pressure room who probably could use the close observation of the ICU. The cases are starting to climb here in the New York area. The calm is not looking it’s going to last for us in the area.

The second was, and this is a quote from Dr. Evazan in Mos Eisley, this is the Star Wars in that den of iniquity and he’s speaking about COVID-19, I don’t know if you remember this where he says “He doesn’t like you, I don’t like you,”-

VR: I remember that.

DG: –Right before someone gets an arm chopped off with a lightsaber. I want to remind people about how bad COVID-19 is. I feel like people have forgotten. We were talking just before. We went on about people want to do a challenge study. A couple of things just to remind people about, here in the US alone, we have over 70,000 new cases per day. My birthday was yesterday. I’m older. You get older all of a sudden.

VR: Happy birthday.

CK: Happy birthday.

DG: On my birthday, over a thousand people in United States died of COVID-19. I got an email actually the same day from a friend of mine in the UK. He’s actually a physician that I’ve worked with in Uganda. He was basically saying, “Hey, this is really difficult,” and expressing concern for me. Sharing a personal story, he said that “A friend of mine, a work colleague was recently woken up from four weeks of intubation only to be told that she had had both lower legs amputated and all her fingers. She’s 52, she’s Caucasian, no underlying health issues.”

I know people have started talking about these challenge studies, “Oh, we’ll give them to younger people.” Maybe this person wouldn’t be young enough to be in a challenge study. This is a scary virus and the whole idea that you’re going to expose people to this on purpose, you got to be willing to live with these potential outcomes. I really want to remind people that this virus, it’s bad.

VR: Chuck and Daniel, remind me. If you only test the vaccine in 30, 40-year-olds, you can’t use it in 60, 70, 80-year-olds. Is that correct?

CK: The concern is with immunosenescence and that’s why either higher doses of, say, the flu vaccine or adjuvanted vaccines in the elderly are really important as you get older. Unfortunately, we start losing both our B and our T-cell health when you start hitting about 30 years of age. It’s a slow decline. Immunosenescence starts quite early but really it has an impact in, say, people over 60. Absolutely true, Vincent.

DG: We’ll wind up with a vaccine for 20 and 30-year-olds but that’s really not the target population. We want to be able to give it to people in their 50s, 60s, 70s, all the way on up.

CK: The other thing with challenge studies, there’s enough viral transmission in clinical disease that we can do proper studies right now with COVID. There is a role for challenge studies when you can safely abort the infection. I put an exclamation point on that. It’s good, for instance, in predicting the drift that you get with influenza. A challenge study would help you choose the correct strain. When you think you have a vaccine that’s 80% effective for influenza and because of drift, you actually turn out to have a 20% of it. You could predict that earlier with a challenge study. There is a role for it. I don’t see the role right now with COVID to be honest with you.

DG: I’m going to get back to this, but another quote, this is a teaser, this will be, “Wear a mask now or a wig later.” I’m going to get back to why I say that. As I started to mention, the case numbers are rising. I said last time on TWiV, I think that it takes time for people to die. The number of deaths per day is twice what it was when we recorded TWiP a week ago. It’s about 500 a day. As mentioned yesterday, on my birthday, it was over a thousand in a single day. The numbers are going up, and this is not great.

The next thing, here I am appearing on this TWiV but I’m going to tell everyone to stop, turn off this TWiV and listen to TWiV 640. It’s a fantastic treatment of testing. It’s actually interesting, I’ve been working with the UnitedHealth Group on the whole concept that frequency is more important than sensitivity. We’ve got to start doing more testing, and we can’t be handling all these result delays, and I think that episode does a great job.

I was just on the phone, mere moments ago, speaking with the head of our ProHEALTH New York Urgent Cares Adam Fiterstein, and he was like, “Dan, you don’t know how embarrassing it was. I was just on the phone calling people back about their testing that was done on July 2nd.” That’s embarrassing. I was like, “Adam, I don’t want to be the one making those phone calls.”

I was saying it’s really tough because ProHEALTH, we were the leaders early on in March. We were the only ones who prepared and had capacity. Part of the way we did that was by partnering with the private labs. The private labs just don’t have the turnaround time anymore for various reasons. There are our ProHEALTH private patients where we’ve set up the ability to do it internally within a day but that capacity is only so much.

Calling someone, I might hate if one of those phone calls was, two weeks later, “By the way, two weeks ago you were positive,” the resulting delay is a disaster. I’ll say, I won’t go too much into the details of testing, listen to 640. When that paper came out by Michael Mina’s group, we were working on a similar paper which we’d already submitted but we don’t do the preprints. Maybe I need to do preprints, get scooped if you don’t, but he does a great job. If we don’t start employing the technology, if we don’t start using tests with rapid resulting without these resulting delays, we are missing the ability to intervene.

CK: Our children might be able to go back to school for daily saliva dipstick. It seems like the technology is there, we just need to scale it up. I think this can be fixed. I’m optimistic after listening to that. It was a great interview, Vincent, that you did. I am optimistic that this can be brought online for this fall even. Let’s keep our fingers crossed and maybe talk offline about how we can help them.

DG: I listened to episode 640 and it’s reinforcing all the things I’m pushing for. I’m hoping the audience of TWiV is going to really push this forward, but the technology is there. The first rapid COVID-19 antigen test, it was a Quidel. Lateral flow assay, got FDA approval in May 8th. Here we are. We’re in July. We’re two months later.

VR: I’ve had already several emails from people who said they’re writing their senators and congressmen and telling them to listen to that and get these rapid tests developed.

DG: We need them. I know Anthony Fauci was on 641, and Vincent, I asked you to have him weigh on school opening so I’ll talk about that. That’s interesting. As a doctor, you think you take care of people and they call you because they have a disease, but a lot of the questions now is people are saying, “Well, I would like to know if it’s safe for us to get our kids back in school. What are the pros and cons? Can we do this safely?”

Some of the issues, I’ve focused on, is this is a place where kids get meals, a lot of kids get meals. If anything, food insecurity is become more of a problem in the United States in the last several months, child abuse and neglect is a problem. There’s the alcohol stores were essential services. We’re seeing a lot more alcohol-related admissions. We know that that’s increased in the community. Kids lost a lot by missing school, but there’s also a regression, if you’re not continuing to learn. Non-traditional learners, which I have a couple those, even my traditional learner is struggling with staying motivated in this context. Social interactions, for most people not for me, I like this, I don’t have to shake hands, but no, this is really tough for most people.

CK: Me too. That is fine with me.

DG: Also, it’s interesting, too, for a lot of parents, school is the ability for someone to look after your kids while you go out and earn a living. For some parents it’s – I’m going to shift even more to – they really need to earn a living and get food on the table, and pay the rent. Are they going to bring in the elderly grandparents to serve that role? There’s really two sides to this. If you don’t give those kids the opportunity to go to school and they’re being taken care of by the grandparents, that may end up being the case anyway. There’s a lot of issues dealing with how do the kids eat at school? How do you handle transportation? if it’s a sleep-away, how do you deal with the dorm rooms?

My oldest daughter is looking at going back to William & Mary maybe, but their idea is one person in their room, no one else can go in that room. I worry about her mental health being in that room. She suffers from pretty severe migraines. If she’s in that room and no one can go in there and maybe help her out, that puts a lot of strains on individuals.

It’s very hard, our schools were not designed for COVID-19. They were not designed with the physical distance or even the space to create the physical distance, and a lot of the equipment, the putting up of the plexiglasses, shortages of plexiglass, the ventilation systems were not, again, designed for respiratory viral pandemic. This is going to be huge, but again, what would be one thing that would really be a game changer, Vincent? Testing.

VR: Daily test the kid. Before you go to school, the kid takes it, “Mom, it’s positive.” Stay home for two weeks. It’s perfect. I didn’t think it was possible and $1 is really the point. When it’s $1, it’s nothing. Everyone can do it, right?

DG: The technology is there and I think it’s a paradigm shift. People have to stop saying, “I need a test that’s so sensitive that’s going to pick up just the tiny –“ I care about people that have virus at a level where they’re going to spread it to others. That’s what we care about.

VR: That’s exactly Mina’s point yesterday, that we don’t care about people who have so little that they’re not going to transmit, right?

DG: Yes, it’s difficult.

VR: By the way, we talked about the school issue with Dr. Fauci, and one of the things he mentioned is we’re concerned about the kids, but also the teachers, they’re older and we have to protect them as well.

DG: It’s interesting because so much in our society has become divisive and a lot of people, “Oh, the teacher unions, they’re–” well, the teacher unions are looking out for the teachers. A third of all the teachers in the US are over the age of 50. They’re high-risk and they’re looking at this and saying, “Hey, can you provide me the appropriate personal protective equipment or situation?”

As a physician, would I go into the ICU without proper protection and expose myself, and potentially wake up missing some limbs and fingers? Is it OK to ask teachers to do that? I don’t think. I think opening schools is a great idea, but you’ve got to do it safely, safely for the children, safely for the parents, safely for the teachers.

VR: Testing has to be part of it. I see so many people are sending us plans on TWiV in their local schools, and so many of them do not have testing as part of it. It’s just wrong. Now, of course, if you’re in a part of the country where there are no cases, then maybe that will work, right?

DG: Yes. We just got guidance on Monday from the Governor, and it was reasonable guidance, I’ll say, where he basically said, if the seven-day moving average is below a certain threshold, he picked 5%, that might be a little high in my mind and then another threshold if it rises, you have to shut back down. That’s one way. Think about a pooled approach. You’re saying, “What’s the prevalence in my community?” As long as we stay below that, that helps us. You got to do that. You got to constantly monitor what’s going on in your community.

If you’re in Houston, like one of our friends, then maybe starting the schools up is not so great, if you’re in Jacksonville, Miami. There’s certain parts of our country when it’s different. I think you want a unified approach, but that unified approach needs to take into account regional situations and local situations, and respond.

VR: Daniel, the increase in cases we’re seeing in New York, what is that due to? Is that travel importations or people getting relaxed?

DG: I was entertained, Vincent. I was in the ICU and they have the TVs on. A couple things I always comment when I’m rounding is that, please don’t. If I’m unconscious and intubated, don’t put on cartoons. Put on PBS or something or some British drama, make it appear that I’m intelligent. One of the news channels was on and the individual was actually not responsive, they were ventilated. I’m not sure they were watching it or who had it on, but it was the head of the CDC, Redfield, and he was explaining why we’re seeing all these cases in the South.

I think, Chuck, you probably know, it’s because all the New Yorkers are going there on vacation and spreading it. He said this, he wasn’t completely straight-faced. There was a little bit of a smile, but he wasn’t joking. Come on, that’s not what’s going on. Part of it as we’re seeing in our area is we don’t have closed borders, If there’s lots of it in the country, we started seeing people coming from other states. That was part of it. I think I mentioned a woman from Pakistan who flew in with it, but another of the women I’m taking care of right now actually is a nursing assistant in the OR at one of our hospitals. Maybe people are coming in for surgeries with it.

We’re seeing various different routes, all little things. We saw a little bit coming out of the beach parties. I don’t know if it’s actually so much the beach party as the after-beach party when everyone gets together in the air-conditioned places. As we’ve mentioned, it’s mostly younger people, so it’s a different pattern of spread.

CK: You’re seeing the loosening-up. The park behind my house, on Wednesdays they play kickball, the 20-somethings. I can’t blame them. Everybody’s going crazy. One of the 30 people out there was wearing a mask.

DG: I think people have lost their fear of the virus. Our attention span can only last for so long. I keep repeating to people, “I know that you’re done with the virus, but the virus is not done with us. Please take it seriously, be careful.”

New data on treatment; I came out with this PPI versus the H2 blocker. Remember when everyone in the world bought Pepcid and it was going to save the world? It was based on this observation that if you compared people who took the more expensive antacids, the protein pump inhibitors seem to have outcomes that were not as good as the people who took the cheap stuff.

Actually, this study basically showed that there was no protective effect to the H2 blockers, but there was a negative effect to the proton pump inhibitors. A few more publications are coming out supporting Tocilizumab, that we’ve talked about. I quote my ICU colleague, Mina Makaryus, “You do not have science until you have the results of a randomized controlled trial.” Waiting for those UK folks with the recovery trial.

Airborne transmission has been in the press quite a bit. I’m not sure that anything has really changed there. I think that predominantly this is a droplet spread, but there are certain situations that I think we acknowledge where airborne transmission, the small particles can occur. The WHO continues to recommend droplet and contact precautions, and airborne precautions when you’re in a situation where aerosol generating procedures are performed. Similar, this is in the press. I’m not sure why, but it sells newspapers I guess.

VR: I asked Dr. Fauci, he said, “Maybe a little bit, but still it’s mostly droplet.”

DG: I think that’s what we’ve been saying for a really long time and we’ll just keep saying that. True.

VR: I just don’t understand why WHO had to come out and say, “Yes, it’s aerosol. We now admit it.” We always said that and it’s minor. It’s a minor contribution.

DG: It’s interesting when you go through the exact wording where they look at certain places and they say, “Outside of medical facilities-” I copied this down as I prepared, “-some outbreak reports related to indoor crowded spaces have suggested the possibility of aerosol transmission.” They say, “However, the detailed investigations of these clusters suggest that droplet and phloemite transmission could also explain human-to-human transmission within these clusters.”

Maybe in certain circumstances it’s an exception but the main thing is, stand within six feet of someone who’s talking, singing, breathing, coughing, sneezing, and you’re getting sprayed in the face or the eyeballs.

VR: Did you see the wonderful report MMWR where the two infected hairdressers treated 139 patients– They’re not patients.

DG: [laughs] You can call them patients, people that had long hair, the hippies.

VR: They all wore face masks. No one got infected. Isn’t that great?

DG: I hate to say it but, you know what, masks may work.

VR: [laughs] Why do you hate to say it tough? Don’t hate to say it.

DG: I jokingly said that. Now, there’s this whole thing that we get hit with people want mask exceptions. The other day, there’s a surgeon and he was like, “I would like a mask exception so that when I operate I can just– Because I feel like the hypoxemia drops my surgical performance.” I’m like, “I’m just joking.” That was the analogy I used. That was like, “If you want to mask exception, then when you go and get surgery, are you OK with the surgeon having a mask exception?” I think it’s gotten a little bit out of control.

Come on, masks, we expect our surgeons and our doctors to wear when they are doing surgery because we don’t really want them to infect our insides. Well, I don’t want people to infect my face, my eyeballs, my mouth. Let’s all be good citizens here and try to make this work.

The other, and I’m going to put these two together because I’m trying to understand, but this is the concept of people who are sick with COVID and it takes a really long time to get better. I’ve talked to this about a long time. A lot of these people have started to refer to themselves as the long haulers. Vincent, you’ve asked many times like, “Well, what percent?” I’m beginning to think, at least the studies seem to be that this is much more common than an exception.

There was a JAMA paper, “Persistent Symptoms in Patients After Acute COVID-19.” They looked at, folks two months out and they asked these people, “It’s two months since you got sick with COVID-19. How many of you are 100% better? How many feel like it’s all over?” It was only 12.6% that said, they were all better. I’m seeing a growing number of people in the clinic who had COVID-19 and now it’s two months, it’s three months later and they still have the fatigue, they still have trouble breathing, they still have joint pain, they still have chest pain. Some of these were athletes, and they’re like, “Dan, I can’t go up a flight of stairs without taking a break. This is not OK.”

I think people look at the case numbers, and they look at the deaths, but those case numbers, a lot of people who get COVID-19, they may not die but there’s a lot of disability and suffering associated with this.

VR: We also see long-term effects after influenza, serious influenza.

DG: Yes, you do actually, and particularly really severe cases, you see the long-term effects. This is not out of the box. This is just, “Boy, what a large number of people have had this,” and now we’re seeing a significant number.

As far as doctors that manage this, because I know a lot of the ProHEALTH doctors, and actually you’ll like this Vincent, I was on a call with a group down in Kentucky, there are a lot of medical groups that actually listen to this. They listen to TWiV. They have someone designated to take notes, and then they use that. Thank you for setting up this forum where we can share all this knowledge. I get emails back from clinicians, too, sharing experiences, so this has been a nice two-way street.

A couple of things that we’ve noticed about these patients is, it seems to be a biphasic pattern to this illness. This may, even in my mind, explain some of these concerns people have about reinfection. I’m not sure. I’m hoping. I’m an optimist here that maybe it’s part of the biphasic where people, they get sick initially, they get better, and then they feel worse, and then eventually they seem to get better. At least that’s what I’m seeing.

Maybe that biphasic is really just part of a have-a-long-reaction to this virus and that second peak when sometimes they’ve been PCR negative and now PCR positive. Maybe that’s just part of this biphasic long haul and not necessarily anything beyond that. I always ask people to remember the names of the four common coronaviruses, and when they look at me blankly I’m like, “Yes, I’m not sure our immune system is as good at remembering those as you are, but hopefully, we’ll see what that means.”

One of the most frightening things I was talking to several people about this week and my wife is like, “Yes, that’s just not true,” is the women described where they were sick, better for about a month, and then they start to notice that their hair is thinning. I do a lot of these visits through telemedicine, and the woman leaned forward, I was like, “What’s up with your hair?” It’s not that the hair is falling out. We always lose a certain amount of hair each day but it’s that the hair is not growing back in.

We’re starting to see something called telogen effluvium. It’s something that we’ve seen in other situations, when someone’s been quite ill, the stress of being quite ill can actually put your hair follicles into a state of arrest that can last for a few months. It’s quite disturbing for these women. I think that’s what it is. I hope there’s anything special about COVID, but a growing number of women are noticing this when they were sick with COVID, a month later they started to notice that their hair is getting thinning and over a period of the next two, three months, the hair not growing in and the hair loss we experience, they’re starting to get bald.

That was my, “Wear your mask now or wear your wig later,” ladies. Men, I don’t know, most of my hair is already gone. I haven’t seen this in men. There might be a slightly different dynamic in hair growth.

Now, I’m just going to finish with last little things and I’m going to go race sailboats while you guys chat more. The new dogma; early on, we were given a whole bunch of dogma. and I’m going to replace that with what I call the new dogma. These are optimistic things. One is it looks you can bend the curve of a respiratory pandemic. Two is travel restrictions may actually help in certain situations.

Face masks do work. Intubate only if you need to. We don’t want to rush into that. We now are saying consider steroids in certain COVID patients. Look at anticoagulation. We now know that’s a big thing. Don’t give everyone hydroxychloroquine. Most importantly, listen to Anthony Fauci and the other scientists and physicians.

CK: Exclamation point on that one.

DG: [laughs] Yes. Thank you to everyone who’s continuing to help us support in Bududa, Uganda. We are actually very close to reaching our goal. We’re only about $2,000 away. Head to parasiteswithoutborders.com and donate. Thank you for all the support because as tough a time as we’re having here in the States, talking to my friends in Sub-Saharan Africa, things there are really tough.

VR: You have time for a couple of questions?

DG: Oh, I certainly do.

VR: OK, don’t want to hold you from your boat.

DG: [laughs] That’s OK.

VR: We have a letter from Dominic, who is a hospital internist who wants to know about testing, “I think a couple of months ago you mentioned work suggesting the oral pharyngeal or saliva samples could be just as sensitive and specific. What do you think of studies to date? Should we change our practice? The work I’ve seen does not include huge numbers, but the results seem encouraging.”

DG: Again, we’re in a pandemic. We can’t just continue with business as usual. All these different assays out there are the “gold standards” that we compare things against, were all given approval as nasal pharyngeal swabs. We’ve already started to gravitate. In young children, I tell our urgent care, “Don’t shove that all the way back to the middle of the turbinate. The child will never come back for another test, and you basically lose the ability to ever check that child. You have to be reasonable here.”

Back quite a while ago, UnitedHealth Group, the organization that I’m also chief of ID for, did a study out in Seattle, looking at over 500 people. You’re picking these people up by even just doing anterior nares, the stuff on oral I think, is looking really good. Again, we do not need to pick up every single person who has just a very small amount of SARS-CoV-2 RNA. We need to pick up people that are contagious that are transmitting for the public health perspective.

If we’re clinicians, and we’re trying to understand a case and we’re trying to decide whether or not to give steroids or Tocilizumab or anticoagulation, OK, that’s the setting where you need that more sensitive test, but the screening, the public health we’ve got to step back and say, “Let’s start using tests where we have a lack of resulting delays, where we get that information quickly.” A beautiful test is not a Q-tip shoved into your brain. A beautiful test is you spit in the tube and they tell you if you have COVID.

VR: Dominic says he loves your concise, erudite review of evidence-based medicine some weeks ago. It should be required listening for all medical students and politicians. Quality medical care has been advanced greatly by rigorous science. Sadly, the federal government’s premature imposition of comprehensive electronic data management systems has set us back years in other ways such as through interference with a doctor-patient relationship, decreased consideration of differential diagnosis of clinical symptoms and findings, production of a great deal of garbage in health records and physician burnout.

DG: Thank you.

VR: Would you agree with all that?

DG: Well, the compliment, yes. Now, a lot of it is a challenge. We do this as part of the academics like, “OK, that’s great. Now, what do you actually think it is?” These did a five-page H&Ps. It’s like, “Yes, that’s great, but what do you actually think it is? What should we be testing for?” There’s a tremendous amount of noise that has been introduced. I try actually to give these reviews up front because I think we’re currently in the middle of an info-pandemic, where there’s so much and I’ll call it a misinfo-pandemic where there’s so much just stuff out there that may or may not be true.

I try to do my part and Vincent, Chuck, and the rest of the TWiV team, you guys do a great job. I listen all to TWiV episodes myself. It helps me cut through just all the noise that’s going on, and unfortunately, the patient record has become so full of noise. It’s a challenge for us.

VR: Diane is a retired RN and mother of a virologist, who has a question for Daniel. “I have a good friend who’s an RN on an OB unit in a small rural hospital. She was recently exposed to SARS-CoV-2 at work because a traveling nurse who also works on the unit flew home to Houston to visit her boyfriend. When the traveling nurse returned to work, she was asymptomatic, but voluntarily tested, went to work and then a day later, received her positive test results.

She spent the day, although with a mask on, in close quarters with a few other nurses staff and a handful of OB patients and newborns. On top of all this, my RN friend received a phone call from a contact tracer who said that she, my friend, was not required to have a test for COVID before returning to work since she had been wearing a mask on the day she was exposed. I’d love to hear your thoughts on how this could have been handled differently. To me, the traveling nurse should have been required to quarantine and test before returning to work having visited a known hot zone.

I understand it is not easy with limited staff. It seems more prudent than allowing her to potentially infect and sicken patients and co-workers. With testing readily available in our community, shouldn’t contacts of a positive case be required to test? Thanks for all you do.”

DG: All right. Diane from Steamboat Springs. I listened to this and it’s frustrating to hear. There’s all the problems in what you write about. One is the resulting delay. If this person had been tested and we knew right away that they had a level of virus that was potentially going to be spread to others, then all this could have been avoided. Testing, testing, testing. Testing is so key. It’s great to then have a more sensitive test that you hear about a day later after you’ve already cleared the first hurdle.

The other which is interesting is here’s someone who’s traveled from a high-risk state. The problem is the whole incubation period. You leave that high-risk state, you may be PCR negative now, you may not be shedding virus now, but any time in the next 14 days, you may start to get sick, you may start to shed virus. Coming from one of these places either really, you have to quarantine for that period of time and then get a negative test where testing has to be something that lets us know if you’re safe.

Particularly, you listen to this, she’s working with children, with newborns, with OB patients, a lot of these are pregnant. We now have some signals suggesting that there might be concern in that population. This is difficult.

Now, the other, which is again, we’re still in this paradigm of limited access to testing, where you’re exposed to someone and they run through basically a scenario where they say, “Were you within six feet of this person for more than 15 minutes without a mask and glasses?” They’re setting a bar for testing which reminds me back of how frustrated I was back in February. The bar then was you have to have come from Wuhan, you have to have a fever, you have to have trouble breathing, “Oh, no test for you.” Even when we identified that guy in Westchester, we were like, “This guy was not in Wuhan.” They’re like, “Well, you must have gotten it from someone in the temple.” Here we still have barriers to testing. People got to get tested.

VR: Bob in Philadelphia says, “Lots of buzz, but very little science regarding giving inhaled steroids early in the course of COVID. Any thoughts?”

DG: Bob, we don’t know. Early on, and I still say I’ll approach it this way now, I try to think about what’s going on and what I’m trying to do. The first seven days is viral replication. I don’t see a role for steroids in the viral replication phase. The second week, that’s when we start getting our inflammatory, our cytokine storm, people start to get hypoxic. That’s when it made sense to me to start targeting the immune response. We don’t know about inhaled versus systemic steroids. I’ll leave it there.

I would say the thinking and understanding, the pathophysiology, would still say avoid steroids during that first week, data now on systemic steroids during that second week. Again, this is something that would be great to study because so much of that inflammation we think is coming from a pulmonary source. This, in my mind, would make a lot of sense to look at.

VR: One last one from a septuagenarian mouse immunologist at the University of Massachusetts Medical School in Worcester, “Is it possible that older individuals are more sensitive to infection because more of us have had our tonsils removed?”

DG: That’s one of those questions that one of these large medical centers, maybe one of our listeners, could very quickly do a medical search, and just look at, “OK, all the people who had tonsils out who didn’t–” This is a project for one of those sidelined medical students or a resident, or a fellow, talk to your medical informatics team and say, “Hey, can I look at people who had tonsils removed, people who didn’t?” and look at COVID-19 outcomes.

VR: “We don’t know,” is the answer.

DG: We don’t know, but it’s a question you can ask.

VR: We think the disease in older people is an immune response-based disease.

DG: I don’t think that tonsils are going to play a role, in all honesty.

VR: Those are just two and you have more other lymph nodes throughout your body, right?

[laughter]

DG: Yes, it’s like Carl Sagan, “There’s dozens. There’s lymph nodes galore.” If you remove two stars from the sky, unless they were special ones, most of us wouldn’t notice. These are special ones.

VR: There are billions and billions of lymphocytes for sure, right?

DG: Yes, there are actually.

VR: OK. Daniel, thank you again for joining us. Enjoy your sail.

DG: My pleasure. Everyone, take care and be safe. Thank you for listening.

VR: Chuck, thank you.

[00:38:00] [END OF AUDIO]

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