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

0:12

is to with this weekend

0:15

virology. Episode Ten Eighty

0:17

Two. Recorded. On

0:20

January Twenty Five Twenty

0:22

Twenty Four. I'm. Vincent

0:24

Rak and Yellow and you're listening

0:26

to the podcast All About Viruses.

0:29

Joining. Me today here. In.

0:31

New York at the incubator

0:33

Daniel Griffin. Hello! Everyone.

0:36

I Daniel or what's with tuxedo?

0:38

We said we're going to be

0:40

casual here. needed you didn't get

0:42

the memo at? well tonight is

0:45

is burned tonight. Though. For

0:47

any of the Scots in

0:49

the audience this is a

0:51

celebration of Robbie Burns famous

0:53

for Old Legs I, the

0:55

Nobel laureate poet who have

0:57

a of Scotland and after

0:59

I record I will be

1:01

going with my daughter Daisy

1:03

to celebrate Burns night. We

1:05

will be will be enjoying

1:08

some we drafts of scotch,

1:10

will be reciting palms, singing

1:12

Rabbie Birds songs and I

1:14

will be enjoying some Hargis.

1:16

So you need you have to wear a

1:19

tuxedo this particular that I'm in the subvert

1:21

I formal okay about how many people are

1:23

going to this event I think it'll be

1:25

about one hundred or so. Yeah and had

1:28

of these people get selected you just you

1:30

sign up you sign how they look at

1:32

it sir and know be a mix of

1:34

you can wear a a standard western tuxedo

1:37

which Tuxedo Park New York City right Marina

1:39

home of the Tuxedo or their you're allowed

1:41

to wear a Kilt. So.

1:43

What you have is a standard western today. And

1:45

are you Western and you tie the bow tie

1:48

yourself? I see, I just learned to do that.

1:51

A Very good. Or well,

1:53

we're here to do a clinical update. All

1:55

right, Well. Let's.

1:58

start off with our quote a Good

2:01

advice is always certain to be ignored,

2:03

but that's no reason not to give

2:05

it. That's pretty sad that

2:08

it's always certain to be ignored, right?

2:11

Well, you know, I think people need to

2:13

unfortunately learn their own lessons. But

2:16

no, that's a quote from Agatha Christie and

2:19

sure, we have a lot of fans

2:21

in the audience. I particularly enjoy her

2:23

Foireau stories with

2:26

the Belgian detective. But

2:29

let's get right into RSV. You

2:32

know, we warned a little bit about this, that things

2:34

were starting to come down and sometimes we see that

2:36

double hump. It looks like we saw that double hump.

2:39

So RSV is still up there. We're

2:41

still seeing a significant amount of RSV

2:44

activity. And, you know,

2:46

just just a reminder, we're going to actually

2:48

talk next week about just all the updated

2:50

safety information. But we've really moved from, you

2:53

know, this shared decision making. Most of us

2:55

are just saying, you know, if you haven't

2:57

gotten your RSV vaccine and you're 60, you're

2:59

over. Go ahead and get it. If

3:02

you're pregnant last trimester, go ahead and get

3:04

it. Let's really

3:06

let's really reduce these these numbers.

3:09

Daniel, I can't read the X

3:11

axis on either of these. So

3:14

like on the right, you have a big peak. When

3:16

was that last two years ago? No,

3:18

no. So yeah. So that's yeah. Actually, we

3:20

should I should pull out my glasses because

3:23

the numbers are tiny on the X axis.

3:25

So the Y axis is huge. But let

3:28

me just get this close so I can

3:30

see it. Yeah, that was actually to November

3:32

of 2022. So

3:34

there was do you remember this big outbreak back then?

3:37

Yes. Yes. I mean, one of the tough things

3:40

and I know I was listening to the listening

3:42

to a toy of like two back. Actually, I

3:44

missed one of the deep dives. And,

3:46

you know, one of the challenges we've had over

3:48

time with with data is

3:51

if you don't test for something, you're not going to

3:53

see it. So when we went

3:55

into early days of 2020, all

3:58

of our resources went. went into SARS-CoV-2

4:01

viral testing. And so we weren't testing

4:03

for flu. We weren't testing for RSV.

4:06

So it was a bit of a data vacuum. And

4:09

actually it got people confused because they were saying things

4:11

like, oh, you can't get two things at the same

4:13

time. Well, you can't diagnose two things at the

4:15

same time if you're only testing for one of them. So

4:18

yeah, we had quite a lot of RSV

4:20

last year. And you can see

4:22

the peak's a little bit lower this year if you

4:24

look at the data that we'll leave links in. Well,

4:27

2022 big peak, right? And then it

4:29

looks to me like not a lot

4:31

throughout 23. And

4:33

now at the end of 23, and now

4:36

it's gone up again, right? Yeah. And

4:38

the 2022, that's like end of November going

4:40

into December. So the peak was a little

4:42

bit earlier. And in

4:44

a lot of ways, that is good from

4:47

an epidemiological standpoint. Because when

4:49

you have your peak going into the

4:51

December holiday, that peak can

4:53

start to stretch. People return to school. You

4:55

get kind of this little resurgence that we're

4:57

seeing. And I am hoping

4:59

next year we can compare this and see a

5:02

nice drop, a much lower level. Okay,

5:05

let's move into influenza.

5:09

And levels are still high here. We're

5:12

still above the 10% positive. We're

5:14

still seeing lots and lots

5:17

of cases. What I find

5:19

interesting there, Daniel, is you

5:21

see a peak and we're declining. And you said last time,

5:23

we'll see if it goes up again. Yeah.

5:26

It's still declining, but it could still go up.

5:28

Because if you look at previous years, it

5:31

does go up in middle to late

5:34

January, early February. Yeah, sometimes we

5:36

see this sort of double peak. And you can see it went

5:38

down, but we're kind of sitting on a plateau the last little

5:40

bit here. And we'll see, does

5:42

it drop? Does it rise back up with

5:44

people returning to schools? Some of the, well,

5:46

a lot of the kids, they're back in

5:48

the elementary and all those schools. But

5:51

universities, some of those are firing back up.

5:54

So we will see. And it's

5:56

mostly H1N1. It's over 80%. It's

5:59

H1N1. reassuring

6:01

the the cases that we're

6:03

seeing that are actually influenza

6:05

B it's about 17.5 percent

6:08

it is all Victoria lineage remember we

6:10

had that confusion where someone dumped some

6:12

Yamagata lineage sequences in from like a

6:14

few years back but no

6:16

we may be done with Yamagata lineage

6:18

influenza B all

6:21

right and across the country right we're

6:24

we're still seeing a lot of activity but we're starting

6:26

to see a little bit of sunlight

6:29

or should I say green a little

6:31

bit of a few areas where the

6:33

activities starting to drop down New York

6:35

it's getting a little bit better Minnesota

6:38

I'm still not sure what's do it why

6:40

they do such a great job out there

6:42

so someone asked me last night on the

6:44

stream why some states are higher than others

6:47

before the other states it seems like it

6:50

doesn't make sense epidemiologically that a border

6:52

would do that right is it a

6:54

matter of testing sometimes it

6:57

part of its testing but part of it actually

6:59

is the way the respiratory viruses come into the

7:01

country and the way they spread so RSV

7:04

influenza it's not like

7:07

there's a border between you know Georgia and

7:09

Florida but what happens is we often see the

7:11

the increased respiratory

7:14

activity in the southeast and

7:16

then we see it spread through the

7:18

country but yeah it doesn't respect state

7:20

you know borderlines because

7:22

you see there Texas is it

7:25

is very high right and

7:27

just above it Oklahoma is

7:29

moderate yeah so it's an

7:31

average but if you're right on the border it's

7:33

not like you can move north 10 miles and

7:35

be safe yeah but I also think that Texas

7:37

reports it and that's Texas and

7:40

then Oklahoma reports their own and that's Oklahoma

7:42

so they're separate and that's right that's why

7:44

you end up with you you see the

7:46

distinct borders but yeah it's a it's a

7:49

reporting artifact all

7:51

right and moving into covet can you believe we're

7:53

still talking about kovat in 2024 oh

7:56

we will forever Daniel right it's

7:59

here it is here to stay. And I

8:01

think because it's here to stay, it's

8:03

the big winter, it's a

8:06

big respiratory pathogen. So it's

8:09

important that clinicians, that those of

8:11

us that are not clinicians, potential patients,

8:13

even clinicians are up to date.

8:16

And where are we? So deaths,

8:18

we're still up at

8:20

2,381 new deaths just this last

8:22

week. And I mentioned I get

8:24

this data from BNO. That's

8:27

up 149 higher than

8:29

it was a week

8:31

before. So deaths are still on

8:33

the way up. But we are starting to see

8:35

a little bit of a decline in the in hospital numbers,

8:37

a little bit of a decline

8:40

in the ICU. And if

8:42

you look at wastewater, things look like

8:44

they're on the way down. So we're

8:46

probably probably going to see a drop

8:48

in RC, probably going to see a drop in

8:51

influenza. Probably going to see a decline

8:53

in COVID cases. So

8:57

Daniel, the 2,381 deaths, why are those people dying? We're

9:02

going to talk a little bit more about this

9:04

next week. But at

9:06

this point, immunity is

9:08

a fairly universal phenomenon. People have

9:10

had repeated infections, people have been

9:13

vaccinated. The biggest thing is we have

9:15

individuals who are at high risk of

9:18

progression, and they're not being offered early

9:20

treatment. And we'll talk a

9:22

little bit about a about a veteran study that

9:24

just came across my desk

9:26

today. But what's happening is people are

9:28

saying, oh, I think you'll

9:30

be okay, waiting until it's too

9:32

late. Oh, it seems mild. Let's

9:35

wait and see if you get sick. And

9:37

by the time people get sick and go

9:39

for mild and moderate, it's too

9:41

late and they end up in the hospital. And

9:43

unfortunately, we still see these deaths. So most of

9:45

these are elderly, you would say? They

9:47

really are. The majority are elderly. The

9:49

majority are people with medical

9:52

problems, right? And some of the

9:54

medical problems, to be honest, hypertension,

9:56

obesity, high cholesterol, maybe a heart

9:58

problem. Yeah. We have a

10:00

lot of that in the US. We certainly do.

10:03

We certainly do. And

10:05

I'm going to move right into

10:07

an article, which I think hopefully

10:09

will get a lot of thinking

10:11

from our listeners. How

10:14

is SARS-CoV-2 transmitted? How has this

10:17

virus transmitted? And what can we

10:19

do to decrease the

10:21

amount of SARS-CoV-2 transmission in

10:23

healthcare settings? Now, this is

10:26

an article, Integrated Genomic and

10:28

Social Network Analyses of

10:30

Severe Acute Respiratory Syndrome Covid-1 and

10:32

Rv2 Transmission in the

10:34

Healthcare Setting, recently published in CID,

10:38

Clinical Infectious Disease. So

10:40

these are the results of

10:43

a retrospective cross-sectional analysis of

10:45

viral genomics from all available

10:48

SARS-CoV-2 viral samples collected at

10:50

UC San Diego Health and

10:53

Social Network analysis

10:56

using the electronic medical record

10:58

to derive temporal spatial overlap.

11:02

So that's time and space. Overlap

11:04

of infections among related viromes and

11:06

supplemented with contract tracing data, right?

11:08

So we've got all these viral

11:10

samples from UC San Diego Health.

11:13

And we're going to look at who

11:15

was where, who was where

11:18

when. We're going to look at the genomes.

11:20

We're going to follow transmission. And

11:23

we're going to try to figure out what

11:25

was going on. Were we doing things

11:27

to mitigate transmission? Were we doing things

11:30

that resulted in transmission? So

11:32

the outcome measure for any

11:34

instance of healthcare transmission defined

11:36

as cases with closely related

11:39

viral genomes and epidemiological

11:41

connection within the healthcare setting

11:43

during this infection period between

11:46

November 2020 and January 2022. We're

11:51

going to look at 12,933 viral genomes obtained from 35,666 patients and healthcare

11:59

workers. So a

12:01

big thing about this study, which actually is

12:03

really I think helpful is UC

12:05

San Diego Health has two campuses All

12:08

right. There's the the older Hillcrest

12:10

campus This was built

12:12

back in established back in 1966 381

12:17

bed hospital with multiple shared patient

12:20

rooms and they're going to compare

12:22

this to the newer 418

12:24

bed La Jolla campus built between 1993 and 2016

12:30

Where they have a majority of modern

12:33

single occupancy rooms better

12:36

ventilation systems And

12:39

during the study period November 2020 through

12:41

January 2022 There

12:45

are 1000 well 15,000 333 adult admissions at the Hillcrest

12:47

campus 20,765

12:54

at the La Jolla campus Where

12:56

do you think most of the transmissions

12:58

occurred? Can you guess I would guess

13:00

at the older facility The

13:02

older facility with with poor ventilation and ventilation

13:04

all the people Yes,

13:08

actually During

13:12

the second and third 75% during amacron

13:16

Yeah, the majority of the transmission was

13:18

was actually happening in Hillcrest where only

13:20

about 21% with the La Jolla campus

13:24

the rate of SARS-CoV-2

13:26

transmissions for a thousand admissions

13:29

was 2.54 at

13:31

Hillcrest compared to zero point six three

13:33

at the La Jolla campus So

13:36

that that's quite a so basically they can

13:38

use the date the genomic data to imply

13:41

Transmission. Yeah, we can see here's your

13:43

index. We've got the genetics. Here's who

13:45

gets it. Ooh, it's the same Six-fold

13:48

higher, you know transmission when you stick

13:50

a whole bunch of people together in

13:53

crowded rooms with poor ventilation Okay,

13:56

So we're not surprised. but there are some

13:58

some more interesting things. So. Most.

14:00

Patients who either acquired are transmitted. Sars

14:02

can be to in the hospital where

14:04

in a shared room. during part

14:06

of their stay. Now. This.

14:09

Is interesting they did not identify

14:11

a single transmission events from exposures

14:13

the in the open doors as

14:16

covered nineteen Patience. Or.

14:18

From patients been placed in non

14:20

negative pressure room's. Right?

14:23

Unless you're in the same room with a person

14:25

and in this is a big thing. Because.

14:29

There's this whole. Terminology. Around

14:31

airborne. And. Recently there's these

14:33

measles issues with are like would you even

14:35

in the building right? or measles is a

14:37

beer. Even in the building like ninety percent

14:39

of people are getting measles and. And.

14:42

There's really this people love to use that like

14:44

okay, how can be transmitted through the air but

14:46

not be airborne. Of and this is

14:48

one of the things that we're seeing from

14:50

the Study and this is not Beatles is

14:53

is not tuberculosis up If you have an

14:55

individual in a well ventilated room. It's.

14:57

A private room, Even. If the door

15:00

is opened it's not like it's coming out

15:02

and just I'm selling the hallways. So to

15:04

back from a long time ago you could

15:06

have sat in the hallway of the hospital

15:08

and than to his clinical up. So

15:11

I didn't need to worry as much as I

15:13

went to a car to as I wasn't sure

15:15

and guess, sneak under the door aca know the

15:17

door when I was the it out. Yeah, yeah

15:19

and actually that's also I think it's interesting there

15:21

were no. Transmissions. From Covered

15:23

nineteen Patience of the health care workers

15:25

in the icy. And. I

15:28

make sense to. Because. We've talked about

15:30

time in ranked first five seven days

15:32

as we see other transmissions near second

15:34

week. That's when you get the the

15:36

inflammatory, the cytokine storm. That's when people

15:38

end up in the I Cu. so

15:40

most of those folks who end up

15:42

near see you know their Pc or

15:44

positive. There. Are no longer contagious. Oh hey.

15:46

sort of was safer for me to be in the I

15:48

see so I see you the of the beds or. Open

15:51

to each other Essentially right depends on the unit.

15:54

a lot of them. They're they're separated. but we're

15:56

We're done during the height of it systems such

15:58

a large volume that we kind of. First

16:00

things we we made the entire i see

16:02

You at Negative pressure. And

16:04

so he would enter with an and ninety

16:07

five and everything was open because was just

16:09

and out the ability to give each person

16:11

protected space. So. Summarize, The

16:13

majority of healthcare associated transmission events

16:15

happen either between health care workers

16:18

when they were breaks in massive

16:20

protocol of or in the setting

16:22

up a shared patient rooms in

16:24

a hospital with older infrastructure. They

16:28

suggest that airborne infectious isolation rooms

16:30

with negative pressure differentials are not

16:32

indispensable to safely managing. patience and

16:35

factor with Sars could be to

16:37

they sound that masking for source

16:39

control was effective in the study.

16:43

However, given that there are

16:45

inevitable lapses and adherence to

16:47

infection prevention protocols, health care

16:50

facilities could further benefit by

16:52

expanding mitigation measures including enhancing

16:54

ventilation and their changes to

16:56

clean as older facilities in

16:59

all spaces. And

17:01

making more single occupancy rooms. but that's

17:03

tough race financially stuff Sam yeah because

17:06

you you lose capacity or at were

17:08

already having issues now tickly this time

17:10

year with capacity Ab yeah and what

17:12

he what he did Well this is

17:15

one hospital the the new one is

17:17

four hundred and sixteen. Beds.

17:19

Is this is four hundred? So you're limited to

17:21

four hundred sixty patients deaths, Not a lot during

17:23

an outbreak or know. It's not.

17:27

An icy you capacities even lower, right?

17:29

Yeah, buckley. Yeah. Yeah,

17:32

most hospitals it's ten percent or less of the

17:34

total better I see bets. Know

17:36

so that that. Total. Includes I

17:38

see you get ah okay. All

17:42

Right Vaccine. So this week

17:44

Peter Hotez is perhaps celebrating

17:46

as quarterbacks the Coven eighteen

17:49

vaccine developed by. yeah, Well.

17:51

Children's Children's Hospital down there in

17:53

Texas. It's developed by

17:56

Bio He India based on the Rb

17:58

D protein engine technology from. Texas

18:00

Children's Hospital Center for

18:02

Vaccine Development or they

18:04

received W H O

18:06

Emergency Use Listing approval.

18:09

So this is where they use the

18:12

recombinant death pitch. yeah, Pastorius I yeast

18:14

strain that expresses the Rpd protein of

18:16

Sars cubby two Am and then they

18:18

formulate these with optimize damn adjutant to

18:21

develop this. The sexy services like any

18:23

in the Us as it is, it's

18:25

kind of like that. I you know

18:27

if the one thing I have to.

18:30

Say and Peter know hum hum if you're listening

18:32

to or updates all temps or let's see some

18:34

peer reviewed data on the efficacy. I was just

18:36

and I had a you that we have any

18:38

sets and I mean I don't either and I

18:40

was looking through this because I've gotta figure like

18:42

the Wh show is gotta have some kind of

18:44

the earth they're gonna if they're gonna. Give

18:47

this emergencies listing I'm and I know know

18:50

you know there there are am I was

18:52

reading a little bit through there's there's modification

18:54

So this is not just the original. Are.

18:57

B D protein is modified updates amp

18:59

or yeah, I'd love to see that

19:01

actual efficacy data is. The

19:03

other vaccines are not are be d me know

19:06

their day I mean I was actually decision hurley

19:08

aren't via do we do just rb deed we

19:10

do the whole abs by a members advisor was

19:12

doing our B d and whole spike and they

19:14

decided on our be the and a whole source

19:16

by i am. So I

19:18

don't know. I'd loved loved to see the data. But.

19:21

Yeah, a torrent. Poor Peter he always gets.

19:23

You know this, You know you're you're out.

19:25

What is it? a industry shawl and you're

19:27

just these like given the stuff out for

19:30

free So. I'll. Write

19:32

this my home for free work sets his exit

19:34

the I believe whatever works to give it out

19:36

for free at our. Our

19:38

cove it early I will say it's

19:40

made me Peter all right in Spanish

19:43

Think Peter ever listened to? Get it

19:45

all right Cove early viral says i

19:47

this is interest the guy I ran

19:49

across his articles several times because it

19:51

it seems of beta assume blast in

19:53

the press of and then it keeps

19:55

bringing me back to the dark on

19:57

like okay it's that article that the.

20:00

Oral Sim know trolls year for

20:02

adult patients with mild to moderate

20:04

covered in eighteen was published in

20:06

the New England Journal of Medicine.

20:09

So seven a trouser year is

20:11

an oral three time oh trips,

20:13

and like proteus inhibitor or that's

20:15

been sound. To add in vitro

20:17

activity against Sars Covey to. Been

20:20

be true means in cells and culture Her

20:23

you got is something I did in cells

20:25

in culture. Now.

20:27

They're just to get people little background

20:30

right? So in vitro and cells and

20:32

culture in vivo as you can actually

20:34

put it and living systems and we

20:36

we mention this this protease will. there's

20:39

there's to viral produce is right. There

20:41

is the main protease and that's the

20:43

that's the. Climate. Trips and

20:45

like produce or the. Am. Pro

20:47

the main proteus the other sep

20:50

happy and like protease to really

20:52

similar to paxil of it for

20:55

know protease inhibitor hear these results

20:57

of a phase two three double

20:59

blind randomized placebo controlled trial or

21:02

with a side patients with mild

21:04

to moderate covered nineteen. Onset

21:07

of symptoms within the past three

21:09

days in a one to one

21:11

ratio to get the sim the

21:13

trolls years with seven hundred fifty

21:16

milligrams plus one hundred milligrams of

21:18

return a beer or placebo you

21:20

my town of year for this

21:22

one. Also yeah, can't keep those

21:24

levels up of anything causes all

21:26

this drug drug interactions. The primary

21:29

advocacy and point was time to

21:31

sustained resolution of symptoms. A defined

21:33

as the absence of eleven covered

21:35

nineteen related symptoms. For two

21:37

consecutive days. and then we supplicants.

21:41

As as a safety and changes

21:43

in viral load were also assessed.

21:46

Am. So sure they look at a total

21:48

of one thousand two hundred eight patients enrolled at.

21:50

Thirty. Five sites in China. Six.

21:53

Hundred and Three get The Sims.

21:55

Twelve Years, Six o' Five, get

21:57

Placebo among pieces in the. The

22:00

Fight intend to treat population

22:02

who received the that the

22:04

drug war placebo within seventy

22:06

two hours after symptom onset.

22:08

The time to sustain resolution

22:10

of symptoms was significantly shorter

22:13

in the treatment group then

22:15

in placebo. So hundred and

22:17

eighty hours versus two hundred

22:19

sixteen hours. So.

22:21

That's our sorry try to do the math.

22:23

I'm about thirty six hours sooner. About a

22:25

day and a half, Since sooner you feel

22:27

better. So yeah, median difference. I

22:29

said thirty five point. It's about a day and

22:32

a half. I'm. On day

22:34

five, the decrease in viral load from

22:36

baseline was greater in treated than placebo

22:38

am. Now. The the incidence

22:40

of adverse events during treatment was

22:42

a little higher in treated so

22:45

twenty nine. Percent. Versus twenty

22:47

one point six percent of the most of

22:49

the adverse events were mile to or manners.

22:52

So. How would this compared to Pax? Love

22:54

it and turned to the day trial in

22:56

a similar way. Time to resolution. You know

22:58

it's I had to head. I'm here. There

23:00

was the the epic standard risk which was

23:02

trying to find this kind of a difference

23:04

I I I suspect is pretty similar as

23:06

far as the the impact on symptoms for

23:09

the only look for two days. Yeah, so

23:11

they look for two days and they don't

23:13

sort of ask. what about Day Eight nine?

23:15

The I'm followed a little bit longer which

23:17

would be helpful. but am I think one

23:19

of the big arguments that they've talked about

23:21

here is. Yeah. Most people when

23:23

they're make a decision about the Madison I am

23:25

not going into for the hospital I'm not going

23:27

to die So my dad their conversations this medicine

23:30

will make you feel better. More quickly,

23:32

you'll feel better a day and a half

23:34

sooner. A lot of people. That's gonna be

23:36

what motivates them to want to go and

23:38

take the medicine. Maybe clinicians to go ahead.

23:40

Naturally prescribed them as. A

23:42

present. this is not going to be license

23:44

in the Us. You wonder where it would

23:47

fit in when you've already got paglia of

23:49

it. So. It's very

23:51

interesting is for pages with mild to

23:53

moderate coffee respects love It is for

23:55

people who might have serious yes referred

23:58

mild to moderate but with. The

24:00

risk of progression right? right? Yes! A Pax!

24:02

Love it isn't really you know. F D

24:04

A approved for make you feel better quicker.

24:06

Sprites F the A proof or keep you

24:09

from progressing to severe disease says it. Is

24:12

it just hurts people? Packs loaded

24:14

with. Who are Who

24:16

are. Potentially. Going to have

24:18

severe disease with co morbidities are older and

24:20

so forth that's really the Ft approval of.

24:22

are starting to see a little bit of

24:25

a slide right and will talk a little

24:27

bit about I'm a the discussion about long

24:29

covered and and it is that really an

24:31

evidence based place for back home. Or

24:34

right last week I promised I would talk

24:36

about this Pre prince. And persistence

24:38

of an infectious form. Sars can

24:40

to. Post. Protease inhibitor treatment

24:43

of permissive cells in vitro posted

24:45

on bio archives and you're going

24:47

to recognize some of these authors.

24:51

Are the author's are been knows as

24:53

the Air. Maria. Luck.

24:56

He. Out Sheng Hou on. Ios.

24:58

Is say bow. And. Die

25:01

and David de Ho.

25:04

And all working up at Columbia University in

25:06

the house science know the moon I know

25:08

it well and says you have set the

25:10

Us has very well acts like. This

25:13

was posted on December Twenty First

25:15

Twenty twenty three. But yes, is

25:17

every getting a lot of questions

25:19

and there's good science? Yeah, I

25:21

went to spend some time going

25:23

over the results and and in

25:25

what what are the actual implicates

25:27

insects And in this investigation the

25:29

authors look at persistence of infectious

25:31

sars covey to in several permissive

25:33

cell lines. After treatment with

25:36

high doses of. Your. Mattel

25:38

Veer work and Citro the year of. They're

25:40

also get a look at rimmed as severe

25:42

by the way, in vitro. Am.

25:44

So as everyone knows, right? Number

25:46

Twelve Year That's that protease inhibitor

25:49

in packs loathe it up. And

25:51

M C Trial Zero? That's the

25:53

Japanese Price inhibitor known as. Zo.

25:56

Cover. Their

25:58

also gonna as I mentioned be. Growing Ram

26:00

Dass severe in these assets that

26:03

that glory i guess the that

26:05

the Viking drug that the three

26:07

different permissive cell lines are good

26:09

vn each wait seventies two and

26:11

a site a five forty nine

26:14

his to at a bureau compress

26:16

to. And and

26:18

will go through the figures a little

26:20

bit and jump in Vinson at any

26:22

point of So to start with figure

26:24

one. Of. The examined the persistence

26:26

of they say infectious virus in

26:29

h you eight seven is to

26:31

for three consecutive days after treatment

26:33

with each of these drugs So

26:35

and twelve year as the trolls

26:37

year war rubbed a severe. Said.

26:40

The decay half lives of the

26:42

infectivity were measured to be sorry.

26:44

Twenty Three Point Nine. For. Never

26:47

trump year. Twenty. Six point,

26:49

Seven, Four, and Sutra here.

26:51

Now indistinct contrast. Ramdas severe

26:53

treated cells had no measurable

26:56

infectivity at all the time.

26:58

Points assessed. Abs. They

27:00

say that this initial findings suggested

27:02

that while you're betrayal V or

27:04

or as a trophy or could

27:06

block the main viral produce a

27:09

replication competent former. The virus can

27:11

actually persist post treatment intercellular of

27:13

so similar results with other cell

27:15

types, more time points am and

27:17

even with a different. Variants.

27:20

What it would seem. Protocol. They

27:22

infect and then add the drug so

27:24

day the at the exact how many

27:26

hours later. And

27:29

what is? it? was about eight hours or something, so

27:31

I'm pretty pretty short period of time. In fact, jump

27:33

in. Case.

27:36

We gotta have to remember that the we

27:38

did the paper on know packs love it

27:40

a long time ago and with yeah and.

27:43

I. There was substantial inhibition of.

27:46

Virus. Reproduction? Yeah, and this is slightly

27:48

different, so I don't know what accounts

27:51

for that. Amount. Of think you're

27:53

still seeing. You know this a large scale and

27:55

you're still seeing. you know you still see this

27:57

pretty significant reduction that's interesting. their room and desert.

28:00

Really, On the graph, there's nothing. There's

28:02

no infectivity. It's pretty impressive. Inslee, right?

28:05

You want only wonders if from their severe

28:07

had been orally available right? Yeah. What

28:10

Was done? Yep Yep! And

28:12

even if they're been have better access right? I mean

28:14

right now we still we still do it. But

28:17

it's like zero point five percent of

28:19

treatment courses out there are remnants of

28:21

you. Really, oral is just

28:23

such an easy or less than telling somebody

28:25

sec. you've gotta go somewhere and get an

28:28

Ib infusion for, you know? Three.

28:30

Days and around. but despite the the.

28:32

You. Know. Non zero.

28:35

Effect of near my trousers. It's still very

28:37

effective in patients with, so I think that's

28:39

an interesting thing even before we get onto

28:42

the next figures. So this is interesting. This

28:44

is great, but if you look at the

28:46

Pine tree data which is getting it in

28:48

in the first, you know, never days. Yeah,

28:51

you look at the abd epic high risk

28:53

data getting packs. Love it in in the

28:55

first five this year he got about equivalent

28:58

clinical outcomes and yeah, about eighty eight percent

29:00

reduction in progress. So how meaning solicitous and

29:02

will will make come back to that. Like

29:04

how how clinically. Relic loves his cell

29:06

culture also right said so herself. A

29:08

series of cameras Very different from a whole

29:11

animal. whether it's an animal and and nonhuman

29:13

or human, right? Yep. Yep. So.

29:15

Them were gone to Sigur Do.

29:18

So They're going to look further

29:20

into this phenomenon by examining levels

29:22

of sars covey to genomic or

29:24

nay you to caps of protein

29:27

infected cells again treated. With

29:29

neutral. The Or or Ram des severe.

29:32

And so you know here we've got that

29:34

he to eight seven is to infect with

29:37

sars covey to ah yes sir x he

29:39

says six hours so it's infected at zero

29:41

point five And the why. For

29:43

six hours after which the viruses

29:46

removed and replaced with growth media

29:48

supplemented with either the their number

29:50

child the Euro, the Ram Dass

29:52

severe. And then we've

29:54

got the infectivity decay post removal of

29:56

the nerve or trolled the Or or

29:58

Rem disappear. And.

30:01

They'll sort of. you know again. you know,

30:03

if you're If you're I bet on rammed

30:05

ecevit, right? Seems a little bit better here

30:07

again when terms of genomic are ne. yeah,

30:09

I don't know. What? That

30:11

means because this is Pcr essay rights,

30:14

you know, It

30:17

it. Doesn't. Necessarily mean infectivity. So

30:19

I think the previous experiments

30:21

were more useful. Yeah. I

30:24

think what they're trying to go here as

30:26

with the idea that maybe this is what's

30:28

going to persist and allow for you know

30:31

they I was gonna say they use the.

30:34

The the inflammatory I'm.

30:36

Saying. As like you know we initiated

30:38

now nearing back up or something like

30:41

that. But yeah that's that's what kind

30:43

of a lot of is what their

30:45

with are suggesting here. So they're suggesting

30:47

that are studies on service kirby to

30:49

infected cells in vitro. Suggest

30:51

there is an intermediary form of

30:53

the virus that is blocked at

30:56

the stage of polypeptide cleavage by

30:58

the price. Inhibitors know trophy or

31:00

Or and twelve year and the

31:02

nature the spiral intermediates yanked out

31:04

Unclear but it's place slowly with

31:06

a half. Life of approximately one

31:08

day and maybe it can allow

31:10

for a sort of a of

31:12

reigniting of viral replication. Once

31:15

you stop the drug which you have

31:17

this intermediate form stoicism sub level that

31:19

there is. No. One is no

31:21

evidence for that is the the south

31:23

had virtually no I said and that

31:26

was if reigniting it out his yeah.

31:28

Yeah so. A I do you know

31:30

it in I think an idiot to be

31:32

careful in Socal to there's no immune response

31:34

to the to take care of things in addition

31:36

right? So it but what's interesting to me years

31:39

that even if it with all these drugs.

31:42

The. Nuclear captured protein

31:44

still. Remains. High

31:46

at all time points. and after treatment?

31:48

Yeah, so that protein is quite stable.

31:51

And. even though you're inhibiting a lot of

31:53

viral replication the pretty and that may

31:55

be why this antigen tests remain positive

31:57

for a long time i think that

32:00

I think that's actually really important

32:02

and insightful, right? Because people, how can

32:04

you test positive and no longer transmit?

32:06

But as we're seeing here, you've got

32:08

the stable protein, it's in cells, that

32:11

secondary phase of the

32:13

disease, that inflammatory phase kicks

32:15

in, you're shedding these epithelial,

32:17

these mucosal cells. They're

32:20

full of the protein. They don't necessarily have

32:22

a virus that can infect or get anyone

32:24

sick. And that is the amazing thing, right?

32:27

We spend all this time, right? And everyone

32:29

talks about rebound and they publish papers left

32:31

and right. Are

32:33

we seeing transmission after day 10? No, there's

32:35

no evidence. In fact, some of the papers

32:37

where we discussed, they said there's no evidence

32:39

that this is a transmission issue. Yeah. So

32:42

this is a very interesting figure because

32:44

even with remdesivir, there's persistence of nucleocapsid

32:46

protein up to 72 hours, right? Yeah.

32:50

In the presence of the drug. So that is

32:52

really important. Yeah. So

32:55

the protein sticks around. Yeah.

32:57

So I'm not sure this is, well,

32:59

you know, people keep asking, but I'm not sure

33:01

it's really clinically relevant. And so I don't, I

33:04

want people to like quote this article and be

33:06

like, oh, see, rebound really is a thing. And

33:08

now I understand the mechanism. And we've been over

33:10

this many times. And as per the CDC, not

33:13

a thing. So number one

33:15

person gets infected, they're

33:17

at high risk of progression, pexalovit,

33:21

get it within the first five days. And I'm not

33:23

sure there's a cliff here, right? I mean, the FDA

33:25

is, you know, out to five days. But if

33:27

it's like right past day five, and we were still

33:29

seeing, you know, 88% in the first

33:32

three, 86% in the first five, if

33:34

it's day six, have you really suddenly

33:36

zero efficacy in a high risk person?

33:38

Right. You know, it's

33:40

your, you do better erring on the side

33:42

of treating rather than withholding. What people, as

33:44

you have said many times, what people are

33:47

calling rebound is in fact the inflammatory phase.

33:49

Yes. Yeah. Yeah.

33:52

You got a little bit of a reprieve, you know, you feel better because

33:54

you took this and then you get hit with the early inflammatory

33:56

cytokine storm, you feel crummy for a

33:59

few days, not quite as crummy as you

34:01

would have felt if you had not gotten that reprieve

34:03

and that quick shutdown of the

34:05

viral replicat. And people are having positive rats

34:07

again and they say, see, the virus

34:10

has come back, but no, actually it

34:12

hasn't. It's just been persisting. Yeah. It's

34:14

just got this persistent stable protein in the

34:17

cells in your nose. I got an email

34:19

from someone who said, why are you guys

34:21

so against rebound? It clearly is a thing.

34:25

We're not against it. We just don't

34:27

see the evidence that there's something called

34:29

rebound. Yeah. No, it's, you

34:31

know, and, you know, I always show this link

34:33

to this article, you know, the timing of

34:35

interventions. You know, we

34:37

wrote this before Paxilovid was even a

34:39

thing. So we were already seeing people

34:41

get a little better and then they

34:44

get this cytokine storm during week two.

34:46

So how can it be caused by

34:48

Paxilovid unless someone went back into the

34:50

past, you know, in a time machine?

34:52

So, all right.

34:54

So let's stop withholding treatment because

34:57

of this mythology. All right.

34:59

There are two remdesivir, right? We're talking a

35:01

bit about remdesivir today. The

35:03

article, remdesivir reduced mortality in

35:06

immunocompromised patients hospitalized for COVID-19

35:08

across variant waves, finding from

35:10

routine clinical practice recently

35:13

published in CID. So this

35:15

really, I think this is really important because I still, you know,

35:17

the other day we had a wife,

35:19

you know, I just want to make sure my husband

35:21

isn't getting that remdesivir. So they're still

35:23

out there on the social media, you

35:25

know, misguiding people. Yeah, you know,

35:28

we learned it took us a while to figure

35:30

out, you know, when should we give remdesivir, what's

35:32

the right patient? I mean, once it's past day

35:34

10, you know, it's useless. But if

35:36

you can get it in the first 10 days, as

35:38

we see here, data from

35:40

immunocompromised patients hospitalized for COVID-19 during

35:43

December 2020 and April 2022 were

35:45

extracted from

35:48

the US PNC healthcare

35:51

database. Patients

35:53

who received remdesivir within two days of hospitalization

35:56

were matched one to one using

35:59

propensity score mapping. matching to

36:01

what a match them to sort of equally sick folks. They

36:05

matched them to people who did and did

36:07

not receive, you know, so the folks that

36:09

got match the people who did not receive

36:11

remdesivir. They looked at

36:13

admission month, age group,

36:15

which hospital. They

36:18

did the hazards models to determine the

36:20

effect of remdesivir on risk of 14

36:22

and 28 day

36:24

mortality. Looking at the

36:26

different variants of concerned periods. A

36:29

total of 19,184 remdesivir patients were matched

36:31

to 11,213 non remdesivir patients. Overall

36:38

11.1% and 17.7% of the remdesivir patients died within 14 and

36:41

28 days compared to

36:47

15.4 and 22.4 of the patients that were not treated.

36:53

So a reduction in mortality at 14 days of

36:56

about 30% and 28 days of reduction of about

37:03

So not as impressive as Paxilovid

37:05

or remdesivir in the first week,

37:08

but still a survival benefit

37:11

that was significant during pre-delta,

37:13

delta and amacron periods. Next

37:17

after remdesivir, because as I mentioned very hard

37:19

to get it in that first week, is

37:22

a s and

37:25

a nice go to. There's no

37:27

renal issues. There's no drug-drug interactions.

37:29

It's over the counter. Well, not

37:31

over the counter, but it's oral. Should

37:34

almost be over the counter. No, the

37:36

reason it should be over the counter as

37:39

we've talked about, not something recommended in children,

37:41

right? Not something recommended

37:44

in a woman of childbearing

37:46

age who might get pregnant. You

37:49

know, if you have that discussion, you

37:51

can use it there, but again, with that

37:53

caution with a negative pregnancy test. But

37:56

yeah, a great go to. Let's say you've got someone in their

37:58

80s or 90s. They're on a whole mess. of medicines,

38:01

you know, Eliquis, maybe

38:03

Meota Road, maybe other medicines that really

38:05

don't want to stop. Okay,

38:07

then you can go ahead with Myelinopirvir. We

38:10

still have convalescent plasma but really only

38:13

in a selected small group. And

38:16

week two, the cytokine storm week, right?

38:18

Person either gets a little bit of

38:20

a reprieve or not. Week two, they

38:23

get that cytokine storm, that inflammatory phase.

38:26

Remember, steroids, not for everyone, only at the

38:28

right time in the right patient, right? So

38:30

not in the first seven days, maybe

38:32

during the second week in folks

38:34

who have oxygen saturations less than 94%. Dexamethasone,

38:37

six milligrams

38:39

a day times six days. I

38:42

don't care if your EHR still has

38:44

ten days. Let's follow the science. Number

38:48

two, anticoagulation. We have guidelines in

38:50

American Society of Hematology. Despite

38:52

most people, it's a prophylactic dose.

38:56

But there are certain situations when you may go

38:58

up to a full therapeutic dose. Pulmonary

39:01

support, remdesivir.

39:03

Again, remember, if we're still in the first ten

39:05

days, within a couple days of admission, we

39:07

can still get some benefit here in the right

39:09

patients. Immune modulations with

39:12

tosylizumab in certain circumstances. And

39:14

let's not throw those harmful,

39:17

unnecessary antibiotics and other

39:19

things that folks, unless they're warranted. Alright,

39:22

an exciting week for long COVID.

39:24

I don't know if you spent

39:26

last Thursday listening to the Senate

39:29

hearing on long COVID, but

39:31

the committee chair was Senator

39:33

Bernie Sanders from Vermont. It

39:36

was indoors, so much of the day Bernie

39:38

had his mittens off, so to speak, literally

39:41

and figuratively. He was

39:44

keeping his mask on except for

39:46

the photo ops, right? Pulls it off for the photo

39:48

ops, breathes in the virus. They had a patient

39:51

testimony, testimony from researchers.

39:55

The discussion actually sounded very

39:57

bipartisan, you know, calling for

39:59

a moon. shot initiative with the

40:01

speeding up of long COVID

40:04

drug development trials, expanding capacity

40:07

and education among primary care physicians. I

40:09

think that's huge. Always, always gets kind

40:11

of left out the education component. You

40:13

need funding for that. You need to,

40:16

you know, people are going to have to not do their day

40:18

job or take time out

40:20

of their day job to do this education.

40:23

And they want to establish a new Institute

40:26

at the NIH for addressing long COVID, ME

40:29

CFS and other infection

40:31

associated chronic diseases. That

40:33

would be good to have such an Institute. I would

40:35

like that actually. Yeah. Yeah. Otherwise I

40:37

think, you know, you always worry when everyone

40:39

gets all excited. And then how

40:42

long does that attention span stay? Sure. And

40:44

I worry about that with long COVID. I mean,

40:47

a lot of the people that were all excited

40:49

and sort of. What would you call this Institute,

40:51

Daniel? Uh,

40:53

the post-infectious sequelae

40:55

Institute. Okay. Institute

40:58

of post-infectious sequelae.

41:01

Yeah. The IPIS.

41:05

Yeah. IPIS. Okay. All

41:08

right. Good. Let's work on that. All

41:11

right. Now, uh, in, in SidRAP, uh, that

41:14

comes out of University of Minnesota. There was

41:16

a nice piece. I'm going to leave a

41:18

link here. Does PaxLovid

41:20

prevent long COVID? Maybe

41:23

experts suggest. Um,

41:25

and, uh, nice discussion of the different

41:28

studies. Uh, you know, not

41:30

every study demonstrates a reduction in the risk

41:32

of long COVID with PaxLovid, um, and

41:34

really a call to study further, whether

41:36

the benefit of early antiviral therapy

41:39

is also seen, uh, passes acute

41:42

period, right? So, uh, you know,

41:44

mixed stuff on PaxLovid, um, not

41:46

particularly compelling for convalescent plasma or

41:49

our monoclonal therapies. Um, but

41:51

yeah, I think it would be important to know because as

41:53

we've discussed many times, a lot of folks think like, well, I'm

41:55

not going to die. I'm not going to end up in the

41:58

hospital, but I am really worried about long COVID. And

42:00

is this, you know, can this be

42:02

an evidence-based therapy in that space? We

42:04

don't know. And I think that's

42:06

the honest answer from this. All

42:09

right. So maybe some

42:11

more clues into mechanisms driving

42:13

long COVID with

42:15

the article Persistent Compliment

42:18

Disregulation with Signs of

42:20

Thrombo-Inflammation in Acute Long COVID,

42:22

published in Science. So

42:24

always challenged to go through a

42:26

science paper. And here the investigators

42:28

followed 39 healthy

42:30

controls and 113 COVID-19 patients for up to

42:34

one year after initial

42:36

confirmation of acute SARS-CoV-2

42:38

infection to identify biomarkers

42:40

associated with long COVID.

42:43

So at six months follow-up, 40 patients

42:46

had long COVID symptoms.

42:48

Initially, they say 39, but I'm seeing 40

42:50

here. These

42:53

clinical assessments were paired with blood draws,

42:55

resulting in a total of 268 longitudinal

42:58

blood samples. They measure

43:00

6,500 proteins in serum by proteomics. The

43:05

top candidate biomarkers were identified

43:08

using computational tools, further

43:11

evaluated experimentally. And

43:13

a few key findings, because this is, you

43:15

know, this is a science paper. It's really

43:18

a lot in here. They

43:20

found that long COVID

43:22

patients exhibited increased complement

43:24

activation during acute disease,

43:26

which persisted at six

43:28

months follow-up. You

43:31

know, and they have some nice figures

43:33

to get sort of, you know, if

43:35

you don't remember your classic and alternative

43:37

pathway, you can get a refresh there.

43:40

You know, again, it's that same issue

43:43

that we've talked about before. They don't

43:45

really separate into two groups, right? It's

43:47

more of the median shift, standard error

43:49

of the mean. We get statistical difference.

43:52

They looked at anti-thrombin 3. Their

43:55

data suggests that in general, there was

43:58

more cleavage and found... serum

44:00

levels of von Willebrand factor were

44:02

increased with a decrease in atoms

44:04

13, which regulates von

44:06

Willebrand factor, increased monocyte platelet

44:09

aggregations were also found, also

44:12

elevated levels of CD41

44:14

high monocytes. And

44:16

this, I have to say, this is what I really

44:18

found interesting. They

44:21

started this exploration of antibodies

44:23

that might activate this classical

44:25

complement pathway, right? Yeah.

44:29

One of the things that we do know,

44:31

sort of connect the dots here, is that

44:33

antibodies to the herpes virus

44:35

family, viruses can do this.

44:38

So herpes viridae, these are B

44:40

viruses like EBV or CMV, right?

44:42

And we know that there's a

44:45

connection there with really high EBV

44:47

or CMV IgG levels.

44:50

So while overall serum positivity

44:52

for CMV and EBV specific

44:55

IgG, and thus

44:57

prevalence of CMV or EBV

45:00

infection did not differ, we

45:03

do see these really increased antibody

45:05

titers. And this almost actually

45:07

starts to separate when you

45:10

start to look at the antibody

45:12

titers, particularly for CMV IgG. You

45:15

start to see this really high group. Now

45:18

the people with the EBV, you can actually, if

45:20

you look at the IgG, they're all

45:22

right at the above upper

45:24

limit of normal. I

45:26

think this is what I was looking

45:29

at when you showed the initial

45:31

results about complement that

45:34

doesn't have to be SARS-CoV-2 doing that. It

45:36

could be something else, and here's a candidate

45:38

for that. Yeah, so maybe the SARS-CoV-2, and

45:40

this is sort of this growing hypothesis,

45:43

is that you get

45:46

the latent viruses reactivated.

45:49

You get this just really

45:52

incredibly robust, too robust exuberant

45:55

response, incredibly high persistent

45:57

IgG. IgG

46:00

to your EBV, maybe even other viruses that

46:02

we're not measuring here, are continuing

46:04

to drive this complement activation. I

46:06

think that it's important to realize

46:09

this idea because many

46:12

people feel it's a persisting replication

46:14

of SARS-CoV-2, but it doesn't

46:16

have to be. Yeah, we don't have

46:18

evidence, right? We keep

46:20

looking, and we're looking desperately, right? And

46:23

everyone wants to find that. That

46:25

may not be the answer, and that's what science

46:27

is about. We want to know what the

46:29

answer is. We don't just want confirmation of our

46:32

hypothesis from early on. And this, I think

46:34

this is really an interesting connection that we have

46:36

here, the elevated IgG

46:39

knowledge that drives complement activation, here

46:41

evidence of ongoing complement activation. But

46:45

again, not in every patient.

46:47

If you look at the whisker

46:50

plots, right, the long

46:52

COVID patients, they

46:57

overlap substantially if you go back to

46:59

the original graph where you're

47:01

looking at... Yeah, no, there's even a big

47:03

overlap here. Big overlap, yeah. Like that one

47:05

that you showed, the red. See, there's a

47:07

huge overlap with the other two groups. They're

47:10

recovered, and they're no long. The

47:13

long is hugely overlapping, right? Yeah,

47:15

it really is. So this is not a

47:18

homogeneous patient population? And that's true,

47:20

too. The mechanisms may differ, so we say... It's

47:22

all X. Well, it's X in maybe one individual,

47:24

but it might be Y in the other person.

47:28

All right, so I will... As I've been saying

47:30

now for quite a while, no one is safe

47:32

until everyone is safe. Well, we've talked about the

47:35

number of people that are still at high risk.

47:39

I do want everyone to pause

47:41

the recording. I think this might

47:43

be our last recording that drops

47:45

during the Microbe TV fundraiser. So

47:47

go to parasites.org.com, click on the

47:49

Donate button. We are

47:51

going to continue. I think we're going to get

47:53

there, Vincent. I expect that we'll be writing you

47:55

a check. We'll

47:57

double donations up to potential maximum donations.

48:00

of $20,000. So only a little time

48:02

left in for this fundraiser. Yeah, when

48:06

you hear this it

48:08

will just be a few days till the 31st.

48:10

So please send in

48:13

your money. parasiteswithoutborders.com. It's

48:16

time for your questions for Daniel.

48:18

You can send them to danielatmicrobe.tv.

48:20

Laurie writes, I'm

48:23

an avid masquer using KN95s

48:26

and I cringe when I hear things such

48:28

as the virus is so small that the

48:30

mask provides no protection since it easily passes

48:32

through the pores or the material. It

48:34

occurs to me that while the virus itself

48:36

is indeed minuscule when an infected person expels

48:38

viral particles via a cough or sneeze, the

48:41

viral particles are likely contained in moisture

48:43

droplets that would be large enough for

48:46

a good quality mask to offer protection.

48:48

Am I right? Yes, you

48:50

are right. Very good. Barbara

48:54

writes, regular

48:57

listener, thank you for all of your advice.

48:59

Our family has not had COVID in our

49:01

household. We test quite regularly at least

49:04

once a week. We're vaccinated, boosted, recent

49:06

shot in November. I had a temperature ranging

49:08

from 101.5 to 102.5 for eight days with

49:11

no other symptoms except for some vomiting

49:15

day two. I've taken three rapid antigen

49:18

COVID tests, 48 hours apart, negative

49:21

all three. My husband, no symptoms,

49:23

no fever, also tested two small

49:25

children, no other symptoms.

49:27

Several hours after yesterday's negative

49:30

test, I noticed that a

49:32

second faint line appeared. This

49:34

did not happen with my husband's

49:36

test. I repeated this morning again

49:38

negative, remained negative at the

49:41

30 minute, one hour, 90 minute, and two hour

49:43

marks and then at the two and a half

49:45

hour mark a second line appeared again. What

49:48

does this mean? Okay, stop

49:51

testing. Now, you

49:53

know, as we've talked about this over time,

49:55

there's this issue with with positive

49:57

predictive values and the fact that no matter

49:59

what what test you've got out there. There's

50:02

a certain amount of false positives. So when you

50:04

give me the scenario and all these loads of

50:06

negative tests, and then you say, ooh, I see

50:08

a faint line, that

50:10

is probably not a true

50:12

positive. So stop testing, take

50:14

a deep breath, take some

50:16

antipyrrhetics, and rest assured. Take

50:19

the test to tell you not to look beyond

50:21

a certain amount of time, because funny

50:23

artifacts can happen. Well, even if you

50:25

look super close, there is a line

50:27

there, which is where the reagents are.

50:30

And I see people taking photos, and then

50:32

they use their iPhone to adjust the contrast.

50:35

No, I mean a positive line is

50:37

clear. Very clear. Nancy

50:41

writes, will we be permitted to get

50:43

another COVID vaccine this spring? You

50:46

know, they're licensed. So if

50:48

you have a discussion with your physician, you

50:50

say, boy, that three to four months, we've

50:52

talked about this. If

50:55

you have that discussion, you wanna do it, but

50:57

your physician can certainly go ahead and facilitate

51:00

that. In January, Eric

51:02

writes, in January, California changed its COVID-19

51:04

guidelines to focus on the

51:06

mildness of symptoms in order

51:09

to end isolation rather than the number

51:11

of days since an infection was first

51:13

recognized. This is reportedly a move toward

51:15

normalizing COVID-19 as just one

51:17

of any number of respiratory viruses, which I

51:19

know is something Vincent has wondered about relative

51:21

to flu or common colds in the past.

51:24

What is your opinion on this shift by

51:27

California as the person in charge of COVID

51:29

mitigation for my company and an avid listener

51:32

of your twiv? I'm not entirely convinced

51:34

that symptom severity or fever

51:36

is a great proxy for contagiousness.

51:40

It's not. I

51:44

understand the motivation here. And this is one of

51:46

the things you can actually even ask yourself in

51:48

a capitalist society, right? Do you want your

51:51

workers coming to work sick, making

51:53

other people sick, Triggering

51:56

them to miss work, in

51:58

impacting the productivity, In

52:00

the well being of your employees. I'm you

52:02

know. So the sciences. The science science didn't

52:04

change because we're all gotten tired of cove

52:06

it and so you know. and it's the

52:08

same with the flu. You. Know if you're

52:11

sick, let's say it's you know, forty eight

52:13

hours later and you like going to work

52:15

as you got that wonderful work ethic year

52:17

put in your coworkers at risk. So you

52:19

really need to balance this sort of the

52:21

American as thick with some with the science

52:23

of I had to keep people safe and

52:25

how to keep people from you know, being

52:27

sick and not being able to work. and

52:29

unfortunately some of those folks getting really quite

52:31

sick. Didn't. We just do a

52:33

paper where most of the transmissions occurred. Early

52:36

in the I accept most the transmission is

52:38

right like in that before you feel terrible

52:40

so if it's like days. The. Saints

52:42

Day. Sex? Nearly All. Man, I'm really. I'm

52:44

coming. Will. Europe. Less

52:47

likely transmit near then they wanted to

52:49

when you're just starting right? Okay, Are

52:52

you finally I? Denise Rights? I'm.

52:54

A pediatric anesthesiologists and have enjoyed listening

52:57

to your program for the last several

52:59

years. Many times during the pandemic, I

53:01

felt like a lone wolf was touting

53:03

the benefits of masking. To.

53:06

Have made me feel sane and reminded me

53:08

I was not alone. Anyway, my husband contract

53:10

covert over Christmas took a course of packs.

53:12

Love it! He. Had covered

53:14

two or three times before, but did not

53:16

take packs louvered for any of those. He

53:19

recently noted that his memory was sharper and

53:21

he was finally out of the covert brain

53:23

fog that he believes he has been experiencing

53:25

since his first and second in March. Twenty

53:27

Twenty. Are

53:30

there any data unpack? Slovak providing

53:32

relief. Relief. From long

53:34

covert. So. No, no evidence

53:36

based studies yet, but they are ongoing,

53:38

right? We've talked a little bit about

53:40

the so that the first one that

53:42

got rolled out was Stanford. and

53:45

that was that you know give a

53:47

courses packs living longer than the five

53:49

days and and that that study was

53:51

was ended our understanding is for futility

53:53

results haven't come out i think we

53:55

know what that means there are several

53:58

other studies so going on did got

54:00

one going up at Yale. I

54:02

think NYU has another. So we're

54:04

still waiting for the data to come out.

54:06

Okay. That's Twiv weekly

54:09

clinical update with Dr. Daniel Griffin.

54:11

Thank you, Daniel. Oh, thank you.

54:13

And everyone, be safe.