0:00

This. Week Enviro a g

0:02

the podcast about viruses the

0:04

kind that make you sick.

0:10

From microbe T V this is

0:12

to with. This. Weekend Virology.

0:15

Episode. Eleven Ten recorded on

0:18

May second. Twenty Twenty Four.

0:21

I'm. Vincent Rak and Yellow and you're

0:23

listening to the podcast All About Viruses.

0:26

Joining. Me today from New

0:28

York, Daniel Griffin Hello everyone.

0:31

And. Now we have a bow tie. It's

0:33

been a few weeks it and I

0:35

think I only missed one bow tie.

0:37

but I'm not sure. I'm yeah. I'd

0:39

say this is my ebola. Bow.

0:41

Tie. So.

0:44

That's good. I like the color purple yeah

0:46

it's a this is a i this a

0:48

crowd pleaser so people usually like that to

0:50

her time out have a these acts actually

0:52

out who he is that once a little

0:54

bit thicker this the one that I like

0:56

them right. Yeah. How many? how

0:58

many men out there have to Ebola

1:00

bow ties to choose from? So you

1:02

may be the only in the world.

1:04

Atm a lucky man. Or

1:07

us as jump right into it and

1:09

I'm gonna start with a of Ralph

1:11

Waldo Emerson quotation I met your Eyes

1:14

people may know last week I was

1:16

I was out in nature as out

1:18

in Yosemite which are currently have spent

1:20

a lot of time in my life

1:22

in Yosemite. was younger at the games

1:24

there for like about a month in

1:26

the park climbing. Up in the Meadows

1:28

try to climb half dome and you know,

1:31

just basically coming up with stories rather than

1:33

as successful as that is. make it. You

1:36

know, it was a really. Was we were?

1:38

I think the term was sandbagged, right? So

1:40

we're We're climbing up in the Meadows to

1:42

Army Meadows, work there for a few weeks

1:44

and I think hours with my body Erik

1:46

Johnson We were nicknamed the Boulder Boys because

1:49

we had had it out. from bolder and

1:51

knowing oh you guys, you don't want to

1:53

take the trail you see there are four

1:55

thousand feet of these five nine slabs. Any

1:57

you guys should just throw your backpacks on

1:59

So. Those flags and then we'll buy

2:01

Tommy. Got like done with that and

2:04

a few hundred feet up the actual

2:06

proper stays. We were down to about

2:08

a quarter water who's August and were

2:11

like, you know what, we're going to

2:13

die. Season Six Six Yeah, so then.

2:16

Not. Knowing that we could decide to the

2:18

trail we then down climbed in a four

2:20

thousand feet of five nine with salt backpack

2:22

sought So yeah we did we did not

2:24

Actually gets the top of half dome that

2:26

you were young so was I was immortal

2:28

back that's a yes. Or

2:33

itself. Man is what he thinks about

2:35

all day locked. And. So

2:37

I have as thick as I say

2:39

when I read that was thinking actually

2:42

united that defiance in our lot of

2:44

a lot of people. I certainly defines

2:46

a scientist. Scientists are always thinking about

2:48

you know, questions and puzzles and skill

2:50

and what do we not know and

2:52

what can we learn going forward? So

2:54

think about. Viruses

2:56

mostly all day on. Yeah

2:59

so I am a virus by definition that

3:01

by rote Ralph Waldo Emerson really at we

3:03

are. He has some people say you are

3:05

which you eat Well this is you are

3:07

which you think about So. I

3:11

as a you know as A was

3:13

a clinician. Scientists I think about you

3:15

know, my patients. I think about people

3:17

all day long so I'm a pimple.

3:20

Rs. So let us start

3:22

with an article. I see you know I

3:24

was stuck in the hallway by I just.

3:26

Random Lab for a family member

3:28

yesterday army he had some questions

3:30

about this article In and Vincent,

3:33

you set of my way. So

3:35

let's let's talk about the article:

3:37

intranasal near mice and evokes broad

3:39

spectrum anti viral immunity in the

3:41

upper respiratory tract published in P.

3:43

Any yes I'm so let's walk

3:45

through this paper to see see

3:47

what these researchers dad and thence

3:49

and try to make some sense

3:51

of it. So they start by

3:53

taking mice and squirting near my

3:55

son into their. nostrils to what what

3:57

his knee and my son of the We're

4:00

probably familiar with this. It's

4:02

a generic immunoglycoside antibiotic that

4:04

has been shown to turn

4:06

on interferon-stimulated genes. They

4:09

then euthanize different mice on days 1,

4:11

3, 5, and 7 after this administration.

4:15

I say different mice because you

4:17

can't kill the same mouse, right? So you've got

4:19

some mice that are, you know, sprayed

4:21

and then some of them are going to be

4:23

euthanized, killed on day 1, day 3, 5, 7.

4:28

And then what they're going to do is they're going to collect

4:30

the nasal turbinate tissues. I'm kind of

4:32

hoping they collaborate with someone else because there's

4:34

a lot of rest of the mouse to

4:36

look at. And

4:38

what are the nasal turbinates? These are actually

4:41

these areas inside the nose.

4:45

Now similar to studies squirting

4:47

neomycin into the vagina and

4:49

the lower respiratory mucosa, they

4:52

detect upregulation of interferon-stimulated genes.

4:55

So far, I think we know this

4:58

and prior work has suggested that this

5:00

is dependent upon TLR3 and

5:03

the downstream signaling. We

5:05

can even leave a link into that

5:08

study from 2013. Actually Akiko,

5:11

who's on this paper, is part of that group

5:13

as well, some of the common authors there. So

5:17

then these investigators take these K18Hase2

5:19

mice. Our

5:23

listeners are familiar with those and

5:26

show that much like earlier experiments with

5:28

herpes simplex viruses, influenza A,

5:30

Zika virus, this application of

5:32

neomycin to a mucosal surface

5:34

is associated with the antiviral

5:37

effect. Also

5:39

works for the flu in their experiments

5:41

in a different mouse model. Now

5:44

this is where it gets to be a little bit is it

5:47

appears in their experiments that

5:49

one must either apply this

5:52

before exposure or

5:54

within four hours after

5:57

exposure to the virus. So

6:02

then, I'm just going

6:05

to make a note there. So then they

6:07

got a bunch of people, right? Because we all

6:09

know about mice and monkeys and ferrets. So now

6:11

they've got some people. And

6:14

they have the people self-apply

6:17

this up their noses

6:21

twice daily for seven days. And no one

6:24

gets deaf. And then they see about 44%

6:26

of the folks have

6:28

a five-fold or higher induction in

6:30

at least two of the interferon-stimulated

6:33

genes. About 19% of the

6:35

folks have a good 10-fold or

6:37

higher induction of greater than two

6:39

ISGs. They don't

6:41

then go and expose those people to SARS-CoV-2.

6:44

So the person who stops me in

6:46

the hall is like, so doctor, should

6:49

I start squirting this stuff up my

6:52

nose? A little bit of a

6:54

discussion about it. I don't know. He's like, well, maybe

6:56

I can do it every time before I get on

6:58

an airplane. I'm

7:00

not sure that this is ready for

7:02

prime time. I'm actually a little concerned,

7:04

actually, that people are going to start

7:06

doing what this gentleman suggests. They're going

7:08

to start squirting neomycin in different places.

7:14

We have a regulated immune system. It doesn't

7:17

stay on all the time. So

7:19

we're not really sure about the

7:21

safety and the long-term issues about

7:23

constantly triggering TLR3 and

7:25

turning this on. So I just

7:27

wanted to share this. And maybe, Vincent,

7:29

you and I can have a discussion

7:31

about it. What are your thoughts about

7:34

this? Well, yeah. So

7:36

this is only useful as a

7:39

pre-exposure prophylaxis,

7:41

right? Because four hours after

7:43

exposure, nobody is going to know when they

7:46

got exposed, right? So I don't

7:48

think that's terribly useful. And then

7:51

you have to apply it continuously in places

7:53

where you think you might be at risk.

7:56

I'm concerned that you're

7:58

going to select for some reason. antimicrobial resistance

8:00

by keeping everybody suddenly is using

8:02

this and we're going to have

8:06

bacteria resistant to neomycin.

8:10

But they, you know, I don't know that this

8:13

will provide much protection in people.

8:15

How do we know? You need to do

8:17

a clinical trial and I doubt anyone

8:20

would pay the money for this because

8:24

it's not clear that it would have such a broad effect,

8:26

right? And here's my main thing.

8:29

We have toyed with inducers of

8:32

interferon-stimulated genes before. For

8:36

many viruses, people have tried to make

8:38

agonists and it

8:41

has not gotten far because

8:43

interferon makes you really sick, right?

8:47

And that's because the interferon-stimulated genes are

8:49

made and they have a variety of

8:51

effects. You remember, Daniel, when you treat patients

8:53

for hep C with interferon in the old days, they don't

8:55

like it. They used to do that. They

8:57

feel like you've got the flu for weeks and

8:59

weeks and it's miserable, yeah. So I

9:02

don't think this is viable. I don't know why

9:04

they would even do this experiment. I

9:06

don't know what the point is. And the

9:08

press is taking it wrong. They're saying, oh,

9:10

antibiotics can prevent virus infections.

9:13

No, no, they don't. Yeah, so yeah,

9:15

that's one of the many things I

9:17

worry about is, yeah, so this is

9:19

not an antibiotic preventing

9:22

a virus. This is an antibiotic

9:25

that, as a side effect, stimulates

9:27

interferon-stimulated genes. Yeah, and as you

9:29

bring up, this is an issue.

9:32

So what if we

9:34

lose this antibiotic? What if we keep doing this

9:36

and now, for whatever minimal

9:38

effect you may or may not see? And

9:40

we don't know. We have yet to actually

9:43

see, is this safe? Is it effective? It

9:46

was clear that some people are going to start doing this.

9:49

Sure, yeah. I mean, if you

9:51

really are interested, you take the active

9:54

compound and you give

9:56

different amounts intranasally to mice

9:58

and see if you have a dose-free. response and

10:00

what's the maximal dose. I mean, what's in

10:02

an ointment? Neomycin comes as an ointment, right?

10:05

It's not necessarily formulated for your

10:07

nasal tract. So

10:10

it makes no sense. This is

10:12

like garage biology, right?

10:14

It makes no sense to do that. Come

10:16

on, go get the active chemical and do

10:18

the experiment properly. And this

10:20

is in PNAS of all places, which doesn't

10:23

make any sense either. This is not a stunning finding. As

10:25

you said, much of this has been done before. I'm

10:28

very unhappy with this paper. Yeah, and I'm

10:31

not sure. I don't know if our listeners

10:33

know much about PNAS, but it's one of

10:35

those where there's sort of two avenues to

10:37

publication. One is like you're a member of

10:40

this August group and you

10:42

sort of, or someone is and sponsors the

10:44

paper and it sort of doesn't necessarily require

10:46

kind of editorial peer review to get in

10:48

there. It sort of gets slotted in. Or

10:52

the other is the normal. You send it in

10:54

and the editor looks at it in peer review

10:56

and should we publish this? So

10:58

sometimes stuff can kind of end up in here. The

11:01

other is I worry about too, is yeah, the media

11:03

loves this. This is like great media stuff, but I

11:06

worry about the potential negative impact.

11:08

Is this really good science that

11:10

should be in PNAS and all

11:12

through the media and people having

11:15

these ideas, they're going to start

11:17

taking some Neosporin ointment, sticking it

11:19

up their nose when it's really

11:21

not what they studied here. They

11:23

studied this, basically spraying this

11:25

liquid. Yeah,

11:28

little worries. But now

11:30

that we've discussed it, we've given it more air

11:32

and everyone's going to start sticking Neomycin up their

11:34

noses before they fly Vincenzo. Yeah, I'll notice

11:37

them. They'll have the ones with the greasy nose. Okay.

11:43

All right, let's jump right into

11:45

COVID. So,

11:47

you know, things are going in the right direction. We're

11:49

just going to see these posts like, oh, we're about

11:51

to have another horrible surgery. I'm not seeing that, right?

11:53

We're down to 5,000, 6,000 folks in hospitals.

12:00

in the entire country. Unfortunately, we just had

12:02

a gentleman come in last night in the

12:05

ICU down to about 1,000 deaths.

12:07

New deaths this last

12:10

week, we actually finally got

12:12

under 100 deaths per day.

12:15

Kind of crazy that we're all excited

12:17

about that at this rate, but

12:21

36,000 a year at that rate if you do the math. But

12:25

we are going in the right direction. And if you

12:27

look across the country, I'm not seeing any hot spots.

12:29

Everyone's got a 2% or less, 1%

12:32

or less of deaths across the

12:34

country. And then if you

12:36

look at the wastewater, we're really about as

12:38

low as we've ever been over

12:40

the last year. We're kind of at June

12:43

levels from last year, really come down

12:45

pretty nicely here. So we'll

12:47

keep track and see. One of the

12:49

tough things is that the

12:51

gentleman that I was just talking to

12:53

today who got admitted, he

12:56

went to a big concert.

12:58

This is actually his third time

13:00

getting COVID. Went to the

13:02

big concert. It was Sunday night,

13:04

enjoyed it. It was sort of

13:07

an Irish classic rock band. So

13:09

we chatted about that. And

13:12

then it was like three days later, starting

13:14

to feel sick, starting to feel crummy, you

13:17

know, goes to one of our local

13:20

hospitals, maybe not

13:22

the best of our local hospitals.

13:25

And, you know, they basically because he feels crummy and

13:27

falls down, they do a CT of his head or

13:29

they want to do CT of his head. And he's

13:31

like, Listen, I'm here because I feel crummy. And I'm

13:33

having trouble breathing. And I have a cough if you

13:35

want to do a CT, you should do it in

13:37

my lungs. Anyway, he leaves there.

13:39

He leaves there without the

13:41

proper diagnosis ends up at one

13:43

of our urgent cares, sends

13:46

them to the hospital where I spend a

13:48

bit of my day after Columbia this morning,

13:50

I was at this other hospital, where

13:52

finally, someone actually did a test, he's

13:54

got COVID. He relates that the last

13:56

time he got COVID, he got started

13:58

on some medicine. Apparently Pax Loved, he

14:01

tells me, started that within a day or

14:03

two of symptoms, said it was a breeze,

14:05

he felt better, felt great. Now

14:07

he's actually in the hospital on oxygen

14:09

and not doing so well this time.

14:11

So it's still out there, you

14:14

know, and maybe part of the numbers is

14:16

that people are missing diagnosis. Like this guy

14:18

could have easily been missed. But

14:22

let's talk about testing. This

14:24

is the MMWR SARS-CoV-2

14:26

Viral Shedding and Rapid

14:28

Antigen Test Performance Respiratory

14:31

Virus Transmission Network, November 2022 through May

14:33

2023. So

14:37

this study looked at 354 participants in 129 households. Participants

14:45

who were enrolled in this household

14:48

transmission study completed daily symptom diaries

14:50

and collected two nasal swabs. They're

14:53

going to do SARS-CoV-2 RT-PCR. They're going

14:55

to do culture antigen tests. They're going

14:57

to do this each day for 10

15:00

days after enrollment. And

15:03

I'm going to give you some numbers and we're going to look

15:05

a little closely at those numbers. So

15:07

antigen test sensitivity was calculated using

15:10

the RT-PCR and viral culture as

15:12

the references. The

15:14

peak percentage of positive antigen, 59

15:16

percent, RT-PCR, 83 percent. And

15:22

those are going to occur three days after

15:24

onset and the peak percentage of positive culture

15:26

results. Only 52 percent occurred

15:28

two days after onset. Now

15:31

they're going to tell us, and this is of course

15:33

what's going to end up in the media, they're going

15:35

to say the sensitivity of antigen tests was 47 percent

15:37

and 80 percent using RT-PCR

15:41

and culture respectively as the

15:43

references. Now

15:46

a couple things that I think if we

15:48

look closely at the figures. A

15:51

big thing, and this is something we've

15:53

talked about over time, this is not

15:55

new, is that there's a big issue

15:57

if you're asking about symptomatic Versus

15:59

ACE. Symptomatic cried. So when you

16:01

look at the folks in the

16:03

there's this nice figure. We've got

16:05

panels like a the and see

16:07

so I'm. Panel V, which

16:10

is great is okay, so it's

16:12

about two to three days you

16:14

are symptomatic and we're talking about

16:16

a. Percent positivity

16:19

rates If we're talking about

16:21

symptomatic and actually ends up

16:23

with a fever then were

16:25

actually I'm or sensitivity is

16:27

up there at about eighty

16:29

percent plus. right? So

16:31

it's not so bad in the context

16:33

of i've got a fever of got

16:35

symptoms and vs I'm just trying to

16:37

pick up many symptomatic person who may

16:40

not have a lot going on. A

16:42

crew striking difference between the symptomatic and

16:45

asymptomatic or get into a really is

16:47

really it's and I. I think that's

16:49

important so we know you've seen as

16:51

forty seven percent oh my gosh antigen

16:53

test at work anymore Well as we

16:55

most accurate they work in someone who's

16:57

fab rile and symptomatic. The not a

16:59

great test for oh you've been exposed

17:01

unless try to catch a positive Id

17:03

low level so. And.

17:06

This is probably that is because viral

17:08

load is lower in and asymptomatic person

17:10

you think I would have loved if

17:12

they had you know a another figure

17:14

we just said what's the sensitivity as

17:16

we've talked about our times relative to

17:19

com in of this this viral get

17:21

so. Happy numbers,

17:23

etc. So states who have foreseen

17:25

panel A they have culture positivity

17:27

only which is not really useful.

17:30

For. Would like them to do a plaque essay. why

17:32

can't we do that? Give

17:34

me a tighter. I want to see how much

17:36

viruses present a different days after. Onset

17:39

right? That would be very useful. Yep. Yep.

17:42

Yep! And even yeah,

17:44

as we mentioned, surf grew couldn't quantification of

17:46

all these things such as this? this binary.

17:49

Say. All

17:51

right, so covered as active Saxony? Sudden? Yeah.

17:53

We we talked about for a while. That

17:55

does. Cdc has recommended for folks sixty five

17:58

and older get another get shot. That

18:00

was recommended February twenty eighth and

18:02

for this section we have these

18:04

short communication published in the Journal

18:07

Vaccine Covered nineteen booster vaccine up

18:09

the it and reduced risk for

18:11

long covert a cross sectional study

18:13

of the Us adult population so.

18:16

The. Study examined association between booster

18:18

uptake and long covered prevalence among

18:21

eight thousand seven or fifty seven

18:23

Us adults aged eighteen years or

18:25

older with a history of Covered

18:28

nineteen infection from the Twenty Twenty

18:30

Two National Health Interview Survey. right?

18:32

So with and indeed, and they're

18:35

a little that way to prevalence.

18:37

A logistic regression models examined relationships

18:40

between self reported Covered Nineteen Booster

18:42

vaccine status and long coded adjusting

18:44

for social demographics, health factors. Individuals

18:47

receiving the covered nineteen booster vaccines

18:49

had a twenty five percent lower

18:51

adjusted odds of Long Cove. It.

18:54

Compared to the on vaccinated folks are

18:56

this. Carson said the Under the Stairs

18:58

is really the the proper. This.

19:01

Is the. Seventies does

19:04

not the boosters the new vaccine the on

19:06

the crime related vaccine correct. Some.

19:08

If you look at the dates, yeah,

19:10

it was basically getting that. yeah, getting

19:12

that vaccination. Spirit.

19:15

Does a language is confusing right when you

19:18

think about boosters, right? Because now we don't

19:20

call it a booster. We got the new

19:22

vaccine. Yeah, but it's the new new vaccine.

19:24

So. I guess. I don't

19:26

know how much this is going to translate, right? You.

19:28

Know there there may be a diminishing returns

19:30

and you know. And I know. We talked

19:33

about a study last week about you know,

19:35

with kids right? So the kids had got

19:37

a vaccine or then certain period out from

19:39

the vaccine. was that a vaccine of fact?

19:42

Was that a new variants of fact right?

19:44

And so. He added

19:46

this is it has always important sort of throw

19:48

the said in there because a lot of people

19:50

at this point like why are they even getting

19:52

a booster it's because they're are think that are

19:54

going to die right like you know many of

19:56

us are are still as immortal as I was

19:58

when I try to climb half. I'm

20:00

a we don't want long cove it right?

20:03

I want to be alive and you know,

20:05

chronically city in cognitively impaired and so. Tight.

20:08

And passes actually so waiting for a

20:10

little more information on family card us

20:12

a that's the sort of the new

20:14

abuse shelves and so have you know

20:16

will give people updates from we actually

20:18

start seeing this sub be used in

20:20

accessing the rest. Are

20:23

a covert early viral say is.

20:25

Unfortunately as a gentleman that I

20:27

I saw today it's sort of

20:29

this dad at at first Seven

20:31

Day window and the we have

20:34

an Aids treatment guidelines with idea

20:36

say guidelines feel free to share

20:38

those and then he knows his

20:40

your providers not familiar Yeah I

20:42

just. Sort. Of Ceo ask

20:44

that you get you know and

20:46

I each idea say Id Society

20:48

of America Guideline Therapy So couple

20:51

couple things I want to comment

20:53

about and maybe this relates to

20:55

are opening Observe the late Show

20:57

reports major over use of antibiotics

20:59

for treatment of covered nineteen. And

21:02

so there was that presentation at E

21:04

S C M Id Global crisis that

21:07

this used to be Akhmed. For those

21:09

people that that? this is the Annual

21:11

Meeting of the European Society of Clinical.

21:13

Microbiology, an Infectious Diseases and and

21:15

we get a i just sort

21:17

of a quote from one of

21:19

the presentations. when a patient requires

21:21

antibiotics, the benefits outweigh the risks

21:23

associated with side effects or antibiotic

21:25

resistance. Is Sylvia for tag no

21:27

lo M D W H O

21:30

unit had for surveillance to the

21:32

the Switzerland's However when they are

21:34

unnecessary they offered no benefit while

21:36

posing risks and these contributes to

21:38

the emergence and spread of anti

21:40

microbial resistance. In on A I

21:42

think this is important. it

21:44

is always this you know people are

21:46

are ready to criticize you know how

21:49

our how come you are withholding those

21:51

lifesaving antibiotics are much less likely to

21:53

realize that that and about issues in

21:55

appropriately can be associate with harm hands

21:58

at the same conference we have The

22:00

antibiotics have no beneficial effect on

22:02

clinical outcomes in patients hospitalized with

22:04

moderate COVID-19. Actually,

22:07

let's read what they found and then maybe we

22:09

want to redo that title. At this

22:11

meeting, they presented an analysis of over 1,300 adults from

22:14

Germany who are hospitalized

22:17

with moderate COVID-19 where they found

22:19

that treatment with antibiotics was associated

22:21

with a five times greater likelihood

22:24

of COVID-19 deterioration to bear with

22:26

patients who did not receive antibiotics.

22:29

So maybe that should be antibiotics are

22:32

harmful. Right? Because

22:35

that's not just like innocuous. That's not just

22:37

failing to have a beneficial effect. Five

22:40

times greater likelihood of deterioration. That's not good.

22:44

Still many physicians give Z-PACs

22:46

right all the time for

22:48

COVID. All the time. Unfortunately,

22:50

I think the data we've talked about, the

22:53

majority of people with COVID are still getting

22:55

antibiotics. People are still throwing antibiotics at them.

22:57

I mean, it's crazy, right? We

23:00

may need some sort of revision

23:02

about who's allowed to use antibiotics

23:04

because they're being misused, right? You

23:07

wouldn't let people just give out chemotherapy

23:09

without having gone through the training to

23:11

understand the risks and benefits. Maybe

23:14

your primary care doctor shouldn't be just giving

23:16

out antibiotics when we keep sharing

23:19

evidence of greater harm

23:21

when you do this. Actually, you're harming your

23:23

patients. Think about that. They

23:26

may demand them, but you wouldn't do

23:28

something harmful to your patients knowingly. Well,

23:30

hopefully we're educating people. What

23:34

do you do? Number one,

23:36

Paxilovid. Number two, Remdesivir. Malnipiribir.

23:39

Convalescent plasma in certain circumstances.

23:42

Then of course, isolation guidance so that we

23:44

don't get everyone else sick. Then

23:48

Week two, this is sort of interesting.

23:50

I Was seeing this patient today with

23:53

a colleague of mine, Alex Shalshen. They've

23:55

sort of weathered the storm of COVID

23:57

together for the last few years. And

24:00

you know and I I see the spatial

24:02

when I go in the groove, the pieces

24:04

not on oxygen but the charred has some

24:06

you know on two years of auction by

24:08

saturation sermon nineties so I I. I

24:11

see these but started on steroids so

24:13

I asked the nurse is he on

24:15

us? Is he not on our sin?

24:17

Currently he's not a lawsuit but he's

24:19

been started as on oxygen So we

24:21

go ahead. makes your is not an

24:23

oxygen I say listen unlikely given steroids

24:26

unless he really is hypoxic. We get

24:28

it, oxygen saturation of ninety percent on

24:30

rumors. So yeah he actually that oxen

24:32

should actually be turned on. And so

24:34

as we say during that second early

24:36

inflammatory week, steroids at the right time

24:38

in the rotation, at the right dose.

24:41

This is after the first week

24:43

and in patients with roomier oxygen

24:45

saturation less and ninety four percent

24:47

a guard gentleman here so I

24:49

and I cry. Gleason guidelines, pulmonary

24:51

supports and remnants of you're Still

24:53

has a role in the first

24:55

ten days from symptom onset not

24:57

on a ventilator on and immune

25:00

modulation with talked about this in

25:02

a while we talked a bit

25:04

about socialism as but now we

25:06

have the article coded nineteen Immunologic

25:08

Antiviral Therapy with all now lives

25:10

do. Math a randomized controlled

25:13

clinical trial. So.

25:15

What What is this up? Oh

25:17

my resume. Mab is a the

25:19

anti and be to god bulent

25:22

he monoclonal antibodies you're trying us

25:24

neutralize Get rid of that am

25:26

I G E This is used

25:29

to treat moderate to severe chronic

25:31

idiopathic hereditary africa size as money's

25:34

polyps and here they're investigating the

25:36

idea that this on the list

25:38

man it's may enhance the in

25:41

each anti viral response and have

25:43

anti inflammatory properties so. These results

25:45

of a cease to randomized double

25:47

blind placebo controlled trial where they

25:50

compare our treatment with placebo or

25:52

been hospitalized patients with covert nineteen

25:54

the primary endpoint with the composite

25:56

of mechanical ventilation and or death

25:58

a date fourteen. How many

26:01

are also secondary endpoints included: all

26:03

cause mortality as a twenty eight,

26:05

time to clinical improvement, duration of

26:07

hospitalization, and ultimately this is is

26:09

a small study. with only forty

26:11

patients, he gets twenty getting drugs

26:13

when he a placebo. I'm on

26:16

day fourteen. Three

26:18

fifty percent of patients from the

26:20

treatment group, but double that. Six

26:22

or thirty percent from the placebo

26:25

group have died or received mechanical

26:27

ventilation. Numerically fewer adverse events were

26:29

reported. Actually in the treatment groups are

26:32

no drug related serious adverse events am

26:34

and they have one of these nice

26:36

survival probability kaplan meier curves where it's

26:38

really sort of interested in a you

26:40

can see when the deaths kind of

26:43

occur but it's not as impressive as

26:45

the numbers right? because it's or to

26:47

see like they see get out to

26:49

the first few days and then there

26:52

are a number of people that that

26:54

die rights in the placebo group with

26:56

any get out of like dates wells.

26:59

Same. Number. right? So

27:01

that people just. Side. A little

27:03

bit later the got student and then you

27:05

go out to day like twenty two twenty

27:08

four kind comes together. Since then it's about

27:10

the twenty five twenty six. When you actually

27:12

see a few more people in the placebo

27:14

group die which is really interesting right? This

27:16

will get out to about the twenty eighth.

27:18

A lot of us, you know, lot of

27:21

people out there is no you survive the

27:23

get Ready at Clap You Out or something

27:25

and actually you're you're seeing sort of this

27:27

late hub. Mortality. That

27:31

we some. That not

27:33

impress is it or not. Impressive. small

27:35

study but you know probably something that

27:37

and go. Be. Interesting to know more

27:39

about Bmc see if they move forward with

27:41

more trials. Be. A bigger study would be.

27:44

With good at it. so

27:46

we also have the articles he

27:48

back to sept pharmacogenetics exposure response

27:50

and pieces has fights with covered

27:53

nineteen a secondary analysis of the

27:55

axes up one i am randomized

27:57

clinical trial published in jama network

28:00

open. So what is this

28:02

drug? So a trade name,

28:04

Orancia, is a recombinant fusion

28:07

protein that inhibits T cell

28:09

activation, thereby reducing

28:11

multiple inflammatory cytokines, including

28:14

interleukin 6, tumor necrosis

28:16

factor alpha, that

28:18

are part of the COVID-19 cytokine storm.

28:21

I probably should mention, like we call it the cytokine

28:23

storm, and I like that name. Is

28:25

interleukin 6 higher than we see in

28:27

bacterial sepsis? No, but I think it

28:30

still helps to keep people thinking

28:32

this is not the second rebound

28:34

week. This is the second inflammatory

28:36

cytokine storm week. So

28:38

here these investigators conducted a planned

28:41

secondary analysis of this trial with

28:43

the goals to, one, look at

28:45

the pharmacokinetics of this agent, relate

28:48

exposure with clinical outcomes, determine the need

28:50

for dosage adjustments. Are they even really

28:53

getting to the target they want? In

28:56

the secondary analysis of the

28:58

pharmacokinetics and exposure response data for

29:00

395 hospitalized patients

29:04

who achieved this higher projected

29:06

e-batycep exposure, they noticed significantly

29:08

reduced mortality, a higher probability

29:11

of recover, and fewer

29:13

composite safety events. The

29:15

clearance and exposure is related to total

29:17

body weight, baseline disease severity. But

29:20

again, if you actually look at the data, a

29:23

statistician is going to tell us it's different.

29:26

But there's really big overlaps

29:28

here. The two

29:30

means are about the same. But

29:32

statistically, a statistician is going to, yeah,

29:35

that's always what sort of is a

29:37

problem as a clinician. Is

29:39

it clinically significant? Is it

29:41

statistically significant? Is there really a difference

29:44

if we'd done a trial with a really

29:46

high dose? So maybe this

29:48

will be something that fuels further investigations.

29:50

All right. And we're

29:52

going to spend most of our time, I

29:54

think, today on late phase past long COVID.

29:57

And I was actually just watching a new Netflix

30:00

Last night some new Netflix gut

30:02

microbiome show by the way, so for

30:05

listeners if they're interested The

30:07

article the gut microbiome associates with

30:10

phenotypic manifestations of post acute covet

30:12

19 syndrome recently published in cell

30:14

host and microbe You

30:17

know and so I must admit I'm

30:19

still trying to wrap my head around the

30:21

evidence and the reports from my patients about

30:23

the profound impacts of modification of the gut

30:26

microbiome on Symptoms and even

30:28

biochemical abnormalities associated with past

30:31

So here a total of

30:34

one thousand two hundred and seven Hong Kong

30:36

Chinese With post acute covet

30:38

sequelis. So they call it packs instead of

30:40

past We're recruited in

30:42

two cross-sectional cohorts. So we've got you

30:44

know, a thousand and eleven and we've

30:47

got this longitudinal cohort of 196 And

30:50

then they performed this metagenomic sequencing

30:52

on the collected fecal samples Sort

30:56

of reminds me Vincent of our conversation at

30:58

that That New

31:00

York Yacht Club dinner, you

31:02

know about this sequencing exploring the microbiome

31:04

in these folks now They use this

31:07

information to develop a mid-covidous Microbiome

31:10

in these folks And then they perform

31:12

this Metagenomic sequencing

31:14

on the collected fecal samples Now

31:17

they use this information to develop

31:20

a machine learning model for using

31:22

the microbiome to predict specific symptoms

31:25

They looked at five hundred

31:27

eighty five bacterial species and

31:29

five hundred microbiome microbial pathways

31:32

Which they report explained twelve point

31:34

seven percent of the inter individual

31:36

variability in the symptom

31:39

post acute COVID symptoms three

31:41

gut microbiome based intro

31:43

types were identified in

31:45

subjects with Post-acute COVID

31:47

symptoms and associated different

31:49

phenotypic manifestations The

31:52

trained model showed an accuracy of

31:54

zero point eight nine and predicting

31:56

individual symptoms of

31:58

post-acute COVID symptoms symptoms in the test

32:01

set and they actually had a sensitivity of 86%

32:03

specificity of 82% in

32:06

predicting upcoming symptoms in this

32:08

independent longitudinal cohort. Now

32:11

this is one of those like I see this

32:13

and I'm so excited but I

32:15

can't get access because it doesn't get updated

32:18

on the Columbia access until two days later

32:20

and I'm all excited to dig even deeper

32:22

into this because I want to know like

32:24

what are the microbes, what are we

32:26

seeing here, right? And so, you know, I sort

32:28

of had in my head like am I going

32:30

to see like that the bipyto bacterium is depleted

32:32

because that's what we're trying to put

32:34

back in our therapeutics and yes,

32:37

the top ranked gut microbiome

32:39

features included depletion of bipyto

32:42

bacterium, Adelis centis

32:44

and Rose burea hominis

32:47

and enrichment of Clostridium

32:49

voltaea and flavano

32:51

fractor platii and

32:54

the urea cycle. So there's not only,

32:56

you know, gut microbes, we're actually seeing

32:59

some other biochemical features as well.

33:03

Not clear if it's association or

33:05

causation, right? That's

33:07

clearly true. Yeah, clearly true. You

33:10

know, ideally what we want to do, right,

33:12

you know, and we're going to have the

33:14

opportunity to do this, people who are listening,

33:16

you know, of looking at people's microbiome and

33:18

then they get COVID and then you look

33:21

afterwards and you see like, you know, was

33:23

this change and then, you know,

33:25

even better, then you restore sort of that

33:27

pre-infectious microbiome. Yeah, because I hate just shooting

33:29

in there, like, hey, take 10 billion twice

33:32

a day to bipyto bacterium. I mean, I

33:34

left it then like, are we achieving anything?

33:36

Are we restoring the microbiome? Is that the

33:39

right dose for you? And

33:41

then correlating our interventions with

33:43

restoration of microbiome and actually

33:45

resolution of symptoms. All

33:50

right, and we have the article

33:52

Characteristic Determinants of Pulmonary Long COVID,

33:54

it was published in JCI Insight.

33:56

You know, I'm always searching for

33:59

objective abnormalities. that both validate, explain

34:01

the symptoms and abnormalities seen in people

34:04

with PASK. Here,

34:06

the author shared the results of a single

34:09

center retrospective study that included 1,097 patients with

34:12

clinically defined long COVID characterized for

34:15

persistent pulmonary symptoms. So, trouble

34:17

breathing, cough, chest discomfort had to last

34:19

at least one month or longer after

34:22

resolution of the primary COVID infection. They

34:24

ultimately end up with 929 patients with

34:28

post-COVID pulmonary symptoms. They

34:30

measure pulmonary function tests, stratified diffusion

34:32

impairment and restriction as

34:35

measured by predicted diffusion capacity

34:37

for carbon monoxide and total

34:39

lung capacity. This

34:42

mea was the predominant symptom in the cohort, 78%

34:46

had similar prevalence regardless of degree

34:48

of diffusion impairment or restriction. So,

34:50

don't worry, I'm gonna explain what does all

34:52

that terminology mean? What did I just say?

34:56

So, what are we talking about

34:58

here? So, let's just go through.

35:00

So, the DLCO,

35:02

so diffusion capacity for carbon

35:04

monoxide. So, this

35:07

is a way of really measuring

35:10

is there good gas exchange in the

35:12

lung? So, you're looking at the diffusion

35:15

here. And then pulmonary restriction is, you

35:18

know, you have a total lung capacity, a predicted

35:20

total lung capacity. So, you take a big deep

35:22

breath, how much can you fill those lungs? And

35:24

if your total lung capacity is less than 80%

35:27

of what you'd expect, you would call this

35:29

a restricted, right, so we can have restrictive

35:32

patterns, we can have normal patterns. Obstructive is

35:34

you can fill those lungs, but it really

35:36

takes you a long time to get it

35:38

back out because the flow is obstructed. And

35:41

then a sub-analysis of CAT

35:43

scan imaging identified radiographic evidence

35:46

of fibrosis in this patient population.

35:48

So, you know, what are we

35:50

seeing here? You know, in

35:52

some cases, right, you're actually seeing

35:55

fibrosis, you're seeing objective CT imaging

35:57

evidence basically scarring fibrosis, but

35:59

also... So in some patients, I will

36:01

say not all patients, but some patients,

36:04

you're actually seeing there's impaired gas

36:06

exchange, and you're also seeing that the

36:08

lungs are not able to expand to

36:10

that pre-infection capacity. All

36:13

right. And I think we're coming

36:15

down to the home stretch with the last article.

36:18

Long COVID plasma levels of neurofilament

36:21

light chain in mild COVID-19 patients

36:23

with neurocognitive symptoms published in Molecular

36:25

Psychiatry. It's a good one to

36:28

wrap things up this week. It

36:30

made me think of one of the last this

36:32

week in neuroscience, right, where

36:34

you guys were talking about these

36:37

organoids, right, and exposing them to

36:39

virus. And I'm

36:41

on the same page with the events,

36:43

and I'm not sure it's exposure to

36:45

the virus, but exposure to some sort

36:47

of inflammatory milieu that gets triggered. But

36:49

the most frequent symptoms,

36:52

this spectrum of cognitive

36:54

issues, chronic fatigue, neuropsychiatric

36:56

complaints, nuanced depression, anxiety,

36:59

headaches, dizziness, disorders

37:02

of smell and taste. So

37:05

several mechanisms have been proposed

37:07

to explain the neuropathogenesis of

37:09

long COVID, including active viral

37:11

replication in the CNS, immune

37:13

activation, secondary to systemic inflammatory responses.

37:16

Maybe the data is most supportive

37:18

of that. Spike

37:20

protein damage to the endothelium

37:22

and perivascular inflammation, microvascular

37:25

injury, hypoxic consequences of severe

37:27

disease, certainly see that in

37:29

some cases. And what

37:31

is this neurofilament light chain?

37:34

So plasma neurofilament light chain

37:36

is a highly specific structural

37:38

proteins of neurons, and it's

37:40

been validated as a biomarker for

37:42

neuroexonal damage, right? So not going to

37:44

tell us how, but it is going

37:47

to tell us if there is neurooxonal

37:49

damage, right? So neurons,

37:51

axons, are these long projections that

37:53

are part of the transmission of

37:55

signaling. Are those being damaged?

37:57

Are we seeing evidence with this plasma?

38:00

neurofilament light chain. So

38:02

in this as

38:04

a biomarker of brain injury in

38:07

non-hospitalized long COVID patients. So

38:09

they get a group of 63 long

38:11

COVID patients ranging from 18

38:14

to 59 years old, submitted

38:16

to this neurocognitive battery assessment,

38:18

then subdivided into different groups

38:21

according to results. Plasma

38:23

samples are collected during the long COVID

38:25

assessment and used for the measurements. Long

38:28

COVID patients with cognitive impairment and

38:31

fatigue symptoms presented higher

38:34

levels of this marker when compared to

38:36

long COVID patients without these symptoms. You

38:39

know, again, they get some nice

38:41

p-values and correlation analysis showed that

38:43

levels of cognition loss and exacerbation

38:46

of fatigue had a significant correlation

38:48

with the higher levels. You

38:50

know, there is some degree

38:53

of overlap, but there really are a number

38:55

of long COVID patients with really high levels

38:58

compared. So, all

39:00

right. So lots of overlap here. Interesting, but

39:02

kind of adding to our story. All right.

39:04

Well, I will close this. Yeah, Vincent, you

39:06

want to jump in there? I mean, these

39:09

are all very small

39:11

differences between groups

39:13

and it's just highlighting, I think

39:15

there's a great heterogeneity in

39:17

this condition. It's going to be very hard to

39:19

pin down. I

39:21

think that's really true. Like there's no cutoff

39:24

here where you can say, okay, you

39:26

have some cognitive issues, you had COVID. Oh,

39:28

the test is above here. We only

39:30

see that in folks with, you know, post

39:32

COVID neurological issues. So yeah, it's not going

39:35

to be that biomarker, that definitive test

39:37

we're looking at. It's not like these serotonin

39:39

of 12 that we're seeing, right? All

39:42

right. No one is safe until everyone is safe.

39:45

We're in a new fundraiser, Vincent.

39:48

We just entered the Floating Doctors

39:50

fundraiser, Where for May,

39:52

June and July, we're going to double

39:54

your donations up to a potential maximum

39:56

donation of $20,000. These

40:00

funds are going go to trial, know

40:02

not to travel words, they're all gonna

40:04

go to help excluding doctors with their

40:07

tremendous work that they do down in

40:09

Panama. Time

40:11

for your questions for Daniel, you can

40:14

send yours to Daniel at Microbe.t V.

40:16

David. Rides. You. To

40:19

suggested. You.

40:22

Know when people talk like that it's kind of like.

40:25

You. Know know, That. Nice right thigh

40:27

highs. You know it's hard it's

40:29

hard to now right? Like idea

40:31

Pulled Toad success This so I

40:33

don't know you know says so

40:35

you have suggested you to assist

40:37

you to.dot.com matter Us attorney's use

40:39

of people yelling at me when

40:42

they say you've You've suggested you

40:44

to suggest that the apparent persistence

40:46

of source cause you to is

40:48

detected by Pcr could either be

40:50

viral remnants were ongoing replication to

40:52

these be distinguished by sequencing the

40:54

Pc our products over time. Continued.

40:57

Replication should result in a progression

40:59

of and accumulate mutations Well with

41:01

viral remnants, Sequences would be unchanged.

41:04

Since I've been dated, this is at

41:06

this a reasonable question. I think what

41:08

we've basically said is to we don't

41:10

know right I'm so you know if

41:12

you you find antigen it's you can

41:14

replicate Some you know are in a

41:16

okay see you know that you know

41:18

that and that's what you know but

41:20

is a reputation competent virus so you

41:22

know how or how you gonna do

41:24

that So one is as I think

41:26

this is interesting if you could do

41:28

periodic sequencing over time and you actually

41:30

see that there are changes in that

41:32

sequence overtime. Okay, that's. that's that would

41:34

be interesting i'm and that would sort of

41:36

support more that there is ongoing replication of

41:39

the sequences changing i said changing over time

41:41

and we would suggest it but doesn't nestle

41:43

tell us if that's true it may just

41:45

be that you're picking up different ones over

41:47

types really the sexier and it's been years

41:50

of people trying to do this is you

41:52

do a biopsy you know in some of

41:54

these aren't that simple she do a biopsy

41:56

and then you grow up the virus right

41:58

we're getting better better growing up the

42:00

virus. So if there's replication-confident

42:03

virus there, which would be important to

42:05

know, right? So, you know, this is

42:07

we don't know, not we know not,

42:10

then that would be great. Vincent, thoughts

42:12

on that? Yeah, I think we, this is

42:14

an interesting approach, but it would just be

42:16

better to culture the virus to quantify

42:18

it, right? Because if it's replicating,

42:21

you should see it and you

42:23

should be able to see how many PFO are there. And

42:26

it's very few people are doing that. Sharon

42:29

writes, Dr. Griffin, the latest COVID vaccine

42:31

guidance from the CDC seems to focus

42:33

on older folks and the

42:35

immune compromise continuing to be vaccinated with

42:37

the most updated shots. There are some

42:39

circumstances where younger people should get the

42:41

latest COVID vaccine. My nephew and his

42:43

wife, 36 and 40, are traveling

42:45

to Peru for vacation this June.

42:48

Both have had COVID twice, have

42:50

had three previous vaccines. My

42:52

nephew's wife takes a biologic for rheumatoid arthritis,

42:55

but other than that, no major health issues.

42:57

Would you recommend they receive an updated COVID

42:59

vaccine before traveling or should they ride the

43:01

wave of hybrid immunity?

43:05

I like the vision of riding the wave. You

43:08

know, it is interesting. We will often recommend

43:10

certain vaccines for travelers kind of out of

43:12

season, right? Like so influenza, sometimes we'll, you

43:14

know, someone's like, hey, it's June, I'm traveling

43:16

to, you know, the southern hemisphere. We're like,

43:19

well, so right there, you might be moving

43:21

yourself into the flu. So we might give

43:23

them a flu shot then. So when they get back,

43:25

they'll get their flu shot in November. So there

43:27

is a little subtlety here to think about. Now, you

43:31

know, I say this in the context, it's

43:33

a licensed vaccine. So you know, individual may

43:36

make, you know, sort of a risk benefit

43:38

decision part, but also is your, your interest

43:40

and, you know, willingness to take vaccines. You

43:42

know, if you look and you say, hey, it

43:45

looks like they're really starting to have a not

43:47

a wave of hybrid immunity, but a wave of

43:49

COVID infections in the area I'm heading to someone's

43:52

immunocompromised, you may start thinking about that.

43:55

But yeah, as we've talked about the

43:57

last CDC guidance was a little bit soft, right?

44:00

of people have gone with that.

44:02

So just sort of, you know, all the complexities there.

44:05

Dr. Patrick Seeler Lisa

44:07

writes, I'm hoping you will take my questions. I've had

44:09

it for a long time. 47-year-old

44:11

healthy healthcare worker knows risk factors

44:13

for severe COVID. I had original

44:15

two vaccine series with Moderna in

44:17

2021. One booster later

44:20

that year, original strain. I work in

44:22

an outpatient setting and see

44:24

mostly well patients. I'm confident I've

44:26

not had COVID. I'm still masking

44:28

in public almost all the time. I've only

44:31

been ill once with a cold in 2020.

44:33

All household cold

44:35

did negative at the time with repeated testing

44:37

through day five. My question

44:39

is, is three doses of the

44:42

original strain mRNA vaccine still effective against

44:44

severe COVID, is specifically for people who

44:46

have not had COVID infection? Do we

44:48

have data on this? What about effectiveness

44:50

against COVID related effects

44:53

like myocarditis, VTE, et

44:55

cetera? Because all vaccines and

44:57

medications have potential side effects, although rare,

44:59

I prefer not to vaccinate for COVID

45:02

again without proof that it is needed for me.

45:04

I'm trying to weigh benefits versus

45:06

risks, and I don't know what the benefit

45:08

is. I do know that my personal risk

45:10

from COVID was low, at least after my

45:13

three doses. I don't personally feel the benefit

45:15

of avoiding infection for a few months is

45:17

sufficient alone to get me more boosters. I

45:19

will, however, get another dose if there are

45:22

data that the protection of the original three

45:24

doses against severe disease has waned significantly. I've

45:27

been unable to find these data. It

45:29

seems it's assumed everyone has been exposed

45:31

to post-Omicron strains, while the vast majority,

45:34

with the vast majority of the population

45:36

having probably been infected by now, it

45:38

seems that whole population data on vaccine

45:40

effectiveness may not apply to

45:42

novids necessarily for me to weigh my

45:44

own personal risk here. I feel I

45:46

really need data on those who have

45:49

neither had COVID nor updated vaccine doses.

45:51

Does it exist? Didn't

45:53

we talk about such a study last time,

45:55

Daniel, the waning of the

45:58

original vaccine? Yeah, so

46:00

it is a challenge. Like, I think, you

46:02

know, the original idea was you get your

46:04

three shots, that's going to give us you

46:06

know, your your ongoing 90%. So

46:09

then when you compare like getting back

46:11

getting a boost or not, you're really

46:13

comparing it to protection kind of on

46:15

top of prior infection on top of

46:17

prior, you know, vaccination. So yeah,

46:20

so what can I say to you?

46:22

So, you know, we're right now, as

46:24

I mentioned, lowest levels of COVID and

46:27

wastewater and diagnoses and hospitalizations and deaths

46:29

that we've seen since like last summer. So

46:31

right now, you don't have to worry about

46:33

this in certain ways, or I should say,

46:35

right now, your risk is very low. But

46:38

really, I think the question is going to be

46:40

what are you going to do next October, November,

46:42

when rates are going to go back up? Are

46:44

you going to keep masking? Are you going

46:47

to think about doing a vaccine at that

46:49

level? I'm sort of getting

46:51

from this, the fact that you've done

46:53

three doses, you're not exactly particularly bullish

46:55

on vaccines, so you prefer to avoid

46:57

if possible. You know,

46:59

a lot of the data you're asking for, I think,

47:01

you know, we've talked about some of it. But

47:04

yeah, there are still some novids out there

47:07

like you. And

47:09

then you've got to sort of weigh, you

47:11

know, what are what are my risks of

47:13

getting COVID? And you'll sort of be able

47:15

to kind of assess that next fall, versus

47:17

really the low risk of an adverse issue

47:19

with the vaccine. Alan

47:22

writes, Dear Daniel, you and others have

47:24

cautioned against consuming raw milk, due

47:26

to the presence of H5N1 in dairy

47:28

cows. However, not many Americans have

47:30

access to raw milk, while many

47:33

are consuming raw cheeses. Should

47:35

the same caution apply? All

47:38

right, Alan, this is actually a good

47:40

question, right? So it actually it reminded

47:42

me of the last this week in

47:44

microbiology, Vincent, that you missed. So Michael

47:47

Schmidt and the crew did it without you, but

47:49

they had your nice intro in the beginning. So

47:51

it's almost like you were there. But, you know,

47:55

so, you know, what happens here, right? So,

47:57

you know, raw milk, that sort of straightforward,

48:00

right? And I will admit, you know, I mean, I have

48:03

consumed raw milk in my lifetime, you

48:05

know, up in the mountains of West

48:07

Virginia, right? It's a little farm. But

48:10

yeah, and 1% of Americans, you believe that 1% of

48:12

Americans, millions of Americans consume raw

48:14

milk on a regular basis. Right now, maybe

48:16

not the best time to be doing that.

48:18

But what about raw cheese? What about making

48:20

cheese from that raw milk? You

48:23

know, never putting it through any pasteurizing

48:25

option? I would have the same

48:27

concern, right? I mean, my initial thought was, Oh,

48:29

well, you know, you see cheese, it goes

48:31

through this whole process. And sort of why

48:33

we make cheese, because it's a way of

48:35

preserving. But but, you know, until sort of

48:37

we find out otherwise, maybe not so great

48:40

for the moment. How

48:42

much of that milk from those cows has entered

48:44

the cheese chain yet, you know, that's? Yeah, yeah,

48:46

because it takes time to make cheese. I mean,

48:48

other than like a cottage or those sort of

48:50

quick cheeses, but most cheeses take quite a while.

48:52

So but I think that the

48:54

farms should be aware

48:57

of whether they have H5 or not and

48:59

take that into consideration. Yeah, and it may

49:01

be more prevalent, right, as we've talked about

49:03

maybe under diagnosed, right? So All

49:05

right. And Nikki writes, our point of

49:07

care cepheid PCR machines are set up

49:09

to detect influenza A, B, RSV

49:12

and COVID. They do not reveal the

49:14

subtype. If a patient walks in with H5N1, would

49:18

we have any way of knowing? Also,

49:20

we don't swab patients who present

49:22

solely with conjunctivitis. How is avian

49:24

influenza diagnosed in the Texas rancher?

49:28

Yes, so you bring up a you

49:30

bring up a good thing. We probably have missed and I think

49:32

there was a there was a recent study, I don't know what

49:34

to make of it yet, sort of trying to mold this over,

49:36

like, you know, it was where they had a one or 2%

49:39

positive serology in a sample, you know,

49:41

saying, Oh, we're missing H5N1 and look,

49:43

one to 2% of this population had

49:46

it. You know, if H5N1 is something

49:48

that we see is affecting a herd,

49:50

and then we've got, you know, one

49:52

of the workers comes in with conjunctivitis,

49:54

okay, you sort of think about it,

49:56

and then you go down this road.

50:00

But no, I think that we probably

50:02

have missed some H5N1. The

50:04

fortunate thing, if you're not a cat, and I

50:07

actually really like cats, even though I'm maybe a dog

50:09

person, I'm also a cat person. The

50:11

cats are dying, right? So we

50:13

are fortunate so far in that we're

50:16

not actually seeing severe disease in humans.

50:18

We're just seeing this conjunctivitis. And Vincent

50:20

mentioned on one of our prior episodes

50:22

that had actually to do with the

50:24

different receptor binding of H5N1 in avian

50:29

versus the

50:31

H1N1, the sort of

50:33

typical human influences. So

50:36

how was it diagnosed in the Texas rancher?

50:39

It's a good question. I

50:41

assume they do oropharyngeal swabs, right? So

50:44

you can do oropharyngeal. You

50:47

can actually take a swab because when they've

50:49

got this conjunctivitis against all this fluid, so

50:51

the fluid you can actually, with a soft

50:53

swab, you can actually collect that fluid. When

50:56

they do that, sometimes they've got a patient

50:58

in the hospital now with a herpes infection,

51:00

right? And it just ends up with all

51:02

this stuff. And also sometimes bacterial will end

51:04

up getting a swab as well. So

51:07

what do you do for influenza nasal

51:09

or oropharyngeal? So normally for our influenza,

51:11

particularly the cepheid, we're going to do

51:13

a nasal, right? Sometimes it can be

51:16

a deep nasopharyngeal or it can just

51:18

be doing sort of anterior aneurysm

51:20

which is probably just fine. And

51:22

then here, you know, with the Texas rancher, you

51:25

just get a little bit of that conjunctival fluid

51:27

on that swab. You can send it off for

51:29

a molecular test for the H5N1. That's

51:32

Twiv weekly clinical update with Dr. Daniel

51:34

Griffin. Thank you, Daniel. Oh, thank you.