Expecting the Unexpected: Host response-based detection of respiratory viruses and applications to COVID-19

June 16, 2020

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Yale Cancer Center Grand Rounds | June 9, 2020

Ellen Foxman, MD, PhD

ID5332

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00:00But if you have additional questions,
00:03so let's now turn to our second Speaker.
00:07Doctor Ellen foxman is assistant professor
00:09of Laboratory Medison Ann Immunobiology and
00:12Ellen received her MD and PhD at Stanford.
00:16Her residency training in clinical
00:18pathology at Brigham and Women's
00:21Hospital before coming to yell and
00:24joining the faculty and Ellen is done.
00:27Extensive work now really understanding
00:29the immune responses and natural
00:31responses to respiratory viruses.
00:33Which is certainly a very
00:35timely topic of research.
00:36Uh, in 2020?
00:37So we were really pleased that Alan could
00:39take the time to share her research with us.
00:42So Ellen, thank you.
00:43Thank you. I'm
00:44happy to be here.
00:46And now I'm going to hopefully
00:48share the screen and it will.
00:49All will go well. Um?
00:55All right?
00:58Uh. So can you see the slides? Yes,
01:02OK, great. OK, well everyone,
01:04I'm very happy to be here even though it's
01:06by zoom an be able to participate in my
01:09first Yale Cancer Center Grand rounds.
01:11This actually is not going
01:13to be a talk about cancer.
01:15It's going to be a talk about COVID-19,
01:17which is also a topic on everyone's.
01:20Uh, mind these days,
01:22so I'll tell you about some of
01:25the work our lab has been doing.
01:27Looking at host response based
01:29detection of respiratory virus an
01:32specifically applications to COVID-19.
01:34OK, so uh,
01:36this is just a disclosure that I'm
01:39going to inventor on to patent applications.
01:44So today I'll be talking about why are
01:46we interested in studying the early host
01:49responses against respiratory viruses,
01:51or in this case in particular.
01:53SARS coronavirus two,
01:54the virus that causes cobra 19.
01:57I'll give a brief overview
01:58on the basics of Cobra 19
02:01diagnostics an I'll talk about,
02:03then a project that we've been doing
02:05since March on screening using host
02:07biomarkers for this disease and then
02:10future directions of the project.
02:14So as I was preparing this talk,
02:16I looked back at some of my previous
02:19talks and this is actually an intro slide
02:21I had from a talk I gave at the end of
02:24November to the virology faculty group,
02:26and I thought it was kind of.
02:28It looks so different in the lens
02:30of our current environment that
02:32I thought I would show it.
02:34So I I used to start my talk by
02:36convincing everyone of the importance
02:38of respiratory virus infections,
02:39which is a much easier sell now,
02:41but actually,
02:42even before this pandemic,
02:43these infections cause.
02:44Over 500 million infections
02:46per year in the US,
02:47so that's more than one per person and
02:50granted a lot of those are common colds,
02:52but some of those are
02:54serious illnesses such as.
02:55Influenza with hospitalization or
02:57hospitalization for asthma attack or
02:59CEO PD Exacerbation which are very
03:01often caused by viruses and also
03:04there has been this emerging this
03:06lingering concern about emerging
03:07infections with good reason.
03:09As we know now and I usually put
03:11up this photo to describe that
03:13that's actually a picture of
03:15the SARS coronavirus from 2003.
03:18But now when we see these pictures
03:21it definitely conjures up something
03:23else in all of our minds,
03:25which is the 2nd SARS Coronavirus SARS Co V2.
03:28Uh, which causes the disease cobra,
03:3019 and I just checked on the Johns
03:33Hopkins Portal an at the moment
03:35there's over 7 million cases and
03:37over 400,000 deaths described
03:38globally from Cobra 19,
03:40so this is definitely having a high impact.
03:43It's impacting our seminar that
03:44were having if I zoom today,
03:47it's impacting our work.
03:48It's impacting our economy and of
03:50course our health and there's still
03:52a lot of unanswered challenges
03:54were right in the middle of it.
03:56Trying to figure out how to deal with it.
03:59Um, and even when this acute phase is over,
04:02there will be long-term impacts,
04:03both on the health of the respiratory
04:05system in the patients who are recovering.
04:08Or have recovered and we also
04:10have to think what lessons can we
04:12learn from this that are going to
04:14help us with the next pandemic.
04:16So this is sort of a just a screenshot
04:19of my labs homepage to remind me to
04:22tell you a little bit about what
04:24we do a little bit more broadly,
04:26we really focus on the lining
04:28of the respiratory tract,
04:30the airway mucosa as you see in this picture.
04:33This is actually what the epithelial
04:35layer in the upper airway looks like,
04:37and these are these cells.
04:39The epithelial cells are the target
04:41cells of viral infection and viruses
04:43replicate all the various respiratory
04:45viruses replicate in these cells.
04:46And these cells also are the first
04:49line of defense that recognizes
04:51the infection and sends out signals
04:53to the immune system to come to
04:56the area and also sends out turns
04:58on affecter mechanisms to try to
05:00stop the virus from replicating.
05:02So there are very.
05:04It's a very highly active tissue.
05:06The airway mucosa.
05:07Our lab is focused on these
05:09early steps of host defense,
05:11and we're also interested in repair.
05:13Actually, because after the.
05:14Their way isn't like the skin.
05:17It doesn't constantly regenerate,
05:18but rather only when damage
05:19does it then regenerate,
05:20but it has the potential for these
05:22stem cells that you see here at
05:24the base of the epithelium to
05:26proliferate and recreate that issue.
05:28And one thing we're interested in
05:30is how come that sometimes goes
05:31right and sometimes goes wrong,
05:33and sometimes when it goes wrong
05:35that leads to cancer and that I
05:37hopefully I'll be able to come back
05:39for a different grounds and talk
05:41about that project at some point.
05:43But for today I'm going to focus
05:44on the upper respiratory tract.
05:46As the gatekeeper against infection,
05:48so most of the pathogens that
05:50come into our airway come in
05:52through the nose and mouth throat,
05:55and this includes viruses and bacteria.
05:57And often if that infection can
05:59be nipped in the Bud in the upper
06:01respiratory tract that protects
06:03the rest of the respiratory
06:05system from that that infectious
06:07agent getting down to the lungs.
06:09So when these offense defenses are
06:11effective in the upper respiratory tract,
06:14it can really be the difference
06:16between miles or asymptomatic illness.
06:18Versus a serious illness.
06:19And we know that that's happening
06:21all the time, not just with SARS,
06:23Co V2,
06:24but other viruses that often there
06:26cleared from the become their
06:27detectable in a way for a time.
06:29A short time.
06:30They and they are cleared without the
06:32patient knowing that they were there.
06:34That can happen,
06:35or you can have the opposite,
06:37where the patients in the ICU.
06:39So we're interested in factors
06:41that modulate those defenses,
06:42and we like to think of it as like
06:44a marble sitting on a mountain
06:46where this is the very beginning
06:47of the immune response.
06:49That's going to recruit certain
06:50activate certain immune cells in
06:52the respiratory system and sort of
06:53nudging that marble in One Direction.
06:55It will roll down the Hill one way,
06:57and you'll get one type of response,
06:59whereas if you nudge it in
07:01the other direction,
07:02it can have a very different outcome.
07:04So we're very interested in understanding
07:06the molecular basis of that.
07:09So, uhm,
07:09this is a another picture of this as an
07:12upper respiratory tract from a child,
07:15and so what's something that's kind
07:17of interesting about this anatomy
07:19is I actually just myself today.
07:22Had a swab for this surveillance
07:24for the stars,
07:25Kobe 2 and we all notice swab goes
07:28right in here in the nasopharynx,
07:30and that swab also collect some of the
07:33patients own cells and some of the
07:36proteins made by the patient's own cells.
07:39And in a study with Marie Landry
07:41of the director of the clinical
07:43virology lab back in 2018,
07:45we showed that you can actually
07:47detect the patterns of jeans and
07:50proteins being made in the respiratory
07:52tract and the huge changes that
07:54occur in the rapid response to
07:56viral infection. And if you think
07:58about the progression of SARS,
08:00Co V2, there's you probably have all
08:03seen a figure something like this.
08:05And of course this will be refined overtime,
08:07but the basic idea seems to be that
08:09at this early stage of infection
08:12we have upper respiratory tract
08:14replication and those kinds of symptoms.
08:16Then it moves to the long and
08:18then in severe cases there's
08:19a host inflammatory response.
08:21It causes a lot of damage.
08:24Um so.
08:25At this early stage,
08:27what we can find out using these
08:30respiratory swabs is what can we think
08:32about alternatives and additional things
08:34we can do for the best diagnosis an even,
08:37can we understand the difference
08:39is an inflammatory response is the
08:41very beginning that dictate the way
08:43the illness is going to progress?
08:46So today I'm not.
08:47I'm not gonna talk about bullet .2,
08:49I'm gonna talk about bullet .1 today.
08:52The diagnosis end.
08:54So I'll just start with giving a brief
08:56overview on diagnostics for a SARS Co V2.
08:59I know we have a diverse audience
09:01here an I gave a full length,
09:04uh,
09:04detailed description of this stuff for one of
09:06the Deans workshops that's available online.
09:08That this is everything in a nutshell,
09:11so I'm going to describe the test
09:13that we are currently doing at Yale.
09:15New Haven for this virus.
09:17The first Test answers a question.
09:19Does the patient have the
09:20infection right now?
09:21And basically what you do for that?
09:24Is you do the swab isolate are an RNA.
09:27Do RT PCR and ask?
09:29Can you detect viral jeans from
09:31the viral genome in this patient
09:34sample an if the answer is yes,
09:36it means a patient has the virus or
09:39the viral RNA and their nasopharynx
09:41right now and and that test is
09:44very specific because we're just
09:46looking at the genome of this
09:48virus and very specific regions.
09:50Sensitivity depends on when your
09:52sampling and sample collection
09:54and a few things like that,
09:56but it's a highly specific test.
09:58The other question,
09:59of course,
10:00is did the patient had the infection?
10:02Is there evidence of past infection
10:04and that's serology?
10:05So that's asking has the patient formed
10:08antibodies against the virus because
10:09they've already had the infection?
10:11Usually for a minimum of two weeks
10:13to have an adaptive immune response.
10:15And kudos to our clinical lab for having
10:18both of these up and running for awhile now.
10:21Marie Landry in the virology lab,
10:23and, uh, Rick Tourism.
10:24The clinical immunology lab
10:26have set these up and they're
10:28available to order on the patients,
10:30and this is this is our go to test to know.
10:33The server balance you know
10:36someone is infected right now.
10:38But there are still challenges.
10:40Are there still a lot of challenges
10:42that we're facing right now?
10:44One is how to expand testing capacity,
10:46and there's many different
10:47avenues this can go down.
10:49There is a group with Nate groove on an
10:52Wiley doing great stuff with saliva.
10:54Testing is one way,
10:56but there are there other ways
10:58we can be screening or expanding
11:00testing capacity to help make sure
11:02we're not spreading this virus.
11:04Further, as we restart the economy.
11:07Another challenge is that some people
11:09who test positive by the PCR tests
11:11don't actually seem to be infectious
11:13based on a study from South Korea and
11:15a few other observations elsewhere of
11:17people who recovered and still test
11:19positive for a long time but don't seem
11:21to spread the virus to their Contacts.
11:23So how can we tell the difference there
11:26and then finally also very important
11:28is how do we find new viruses that
11:30are going to be the next pandemic
11:32that are going around and causing
11:34Ellis in our patient under our radar?
11:37And so this is one.
11:39These kind of questions are why we got
11:41into looking at the host response.
11:44In addition to understanding pathogenesis.
11:46But sort of on the practical side
11:48of how can it help us an once is
11:52to die for diagnosis.
11:53We're all familiar with them.
11:55I mean the basic one for infection is fever.
11:58Fever is a host response
12:00to infection and fever.
12:02Is fever elevated?
12:03Leukocyte count?
12:03Those are signs that the patient
12:06has an infection.
12:07They're not terribly specific,
12:08but they are a host response
12:10has been used for, you know,
12:12long time, hundreds of years,
12:14even the the fever.
12:15But now we can get more granular
12:17about it that we have much
12:20better techniques to look at.
12:22Patterns of gene expression,
12:23patterns of protein expression using Multi
12:25Plex Technologies like transcriptomics an.
12:27The idea is if a patient comes
12:29in and is coughing,
12:31you don't know what's causing that,
12:33but if the if that's being caused by a
12:35respiratory virus that's replicating.
12:37That's activated,
12:38the immune system turned
12:39on antiviral defense is,
12:40which are different then defenses
12:42against an irritant or a bacteria or
12:44other things that cause coughing.
12:45And if you look at the patterns of Gene
12:48and proteins that the body is making,
12:50you can sort of interrogate the bodies own
12:53diagnosis and and know what's going on.
12:56And so,
12:57uh, again,
12:57this is based on the study from 2018.
13:01A very simple question was,
13:03are there common patterns to all respiratory
13:06viruses that we can look at to say?
13:08Is this patient experiencing a respiratory
13:11virus infection right now or not?
13:13Because you may not know this,
13:15but in the winter seasons I'm not
13:18talking about this year but in
13:20in past years between December,
13:22March redo thousands of panels
13:25of symptomatic patients testing
13:26them for 15 viruses to see.
13:28Uh,
13:29which virus might be causing their
13:31respiratory symptoms and only about 1/3
13:33of them actually have a viral infection,
13:35so 2/3 of them may have some
13:38other process going on.
13:39So we asked whether we can look
13:41at Biomarkers of the antiviral
13:43response to identify who those
13:45patients with viral infection R.
13:47And this is to this is
13:50published something to sum
13:51it up very quickly,
13:53but the idea is that we found that jeans
13:55and proteins that are highly induced
13:58during the antiviral interferon response.
14:00If you detect those in the nasopharynx,
14:03it's a very good good indicator that
14:05there's a viral infection there,
14:07and this colored graph just shows kcil 10.
14:10This is actually one of these
14:12interference stimulated jeans.
14:14It's a cytokine.
14:14And it goes up many orders of
14:16magnitude during viral infection and
14:18the level of it highly correlated
14:20to the presence of the virus.
14:22So this is like the level on a log scale,
14:25and then these bars indicate
14:27that there's a virus present.
14:28And we did two different studies at
14:31two different times of year with two
14:33different viruses circulating an in both
14:35of those are represented on these pie charts,
14:38which viruses were amongst the
14:39virus positives and it's basically
14:41any virus that we test for.
14:43We could pick up in this way and So what
14:46are the potential applications for Koba 19?
14:49Well,
14:49the first one is we want to know do these
14:52pan viral biomarkers pickup COVID-19.
14:54It's possible it could be different,
14:56and if so,
14:57how can this help us fight the pandemic,
14:59so there's a lot of more ideas
15:01than answers that I have since
15:03this is a relatively new project,
15:05but I'll just share some of our early
15:07data and this project so far has
15:09been spearheaded by ready chi Marla,
15:11a postdoc in my lab who's been like
15:13side by side with me in the lab
15:16every day since this pandemic hit.
15:18Trying to do the studies I'm going to.
15:20Tell you about and get them down the
15:22road and I also wanted knowledge.
15:24The lab working group.
15:26I'll talk about them again at the end.
15:28Organized by Albert Cohen,
15:29the School of public health who
15:31helped us at the beginning all
15:33get organised together to get the
15:35PCR testing going for research.
15:36You sent a support clinical use too.
15:39And so this is a graph of Cobra 19 Indiana,
15:43the country in our region.
15:45Green is the country.
15:46The first case was in January.
15:49But in our region of Connecticut,
15:51in New York,
15:52the first case was shown in
15:54the blue on March 2nd,
15:55Connecticut first case it was in
15:58Fairfield County on March 6th.
16:00And our testing began on March 13th,
16:02which is actually very fast.
16:04You may recall there is some
16:06snafus with the CDC test and they
16:08allowed high complexity in clinical
16:10labs like ours to do their own
16:13test starting on February 29th.
16:14Anna Marie Landry and the folks
16:17in the clinical virology lab had
16:19it up and running by March 13th.
16:21So very fast, but nonetheless,
16:23given the patterns that we see here,
16:25we wondered,
16:26did we miss any cases in those
16:28weeks before our testing started?
16:30So we performed a screen of the
16:32about the two weeks before testing
16:34started as shown on this Gray bar.
16:37And, uh, first,
16:38so during this time period a lot
16:41of people have been tested on that
16:43complete panel for 15 viruses and
16:46376 patients who are symptomatic
16:48and had suspected viral infection
16:50were negative for other viruses.
16:52So we thought, well,
16:53maybe some of those might have had SARS,
16:56Kobe 2 and we screened with
16:59the button marker.
17:00I mentioned CL 10 and out of
17:02all those negative patients,
17:04only about a tenth of them were
17:07positive for the biomarker.
17:09So it seems a good setup like these are
17:11people who tested negative for other viruses,
17:13but there's symptomatic.
17:14It may have a biomarker
17:16that a viral infection,
17:18their bodies fighting a viral infection.
17:20So then we tested all these
17:21people for with the PCR test,
17:23and it turns out that among these
17:26biomarker positive people were four
17:27patients who had actually did have SARS,
17:29Co V2, including some surprises like an
17:32infant that was seen as an outpatient,
17:34that that that was a bit of
17:36a surprise to find that.
17:39And unfortunately,
17:39being here at Yale,
17:41we have so many great collaborators
17:43with different expertise,
17:44we were able to ask Nate Grubaugh
17:46slab in the school of public health
17:49to sequence those for isolates.
17:51This was a paper earlier published by
17:53the group lab showing using sequencing
17:55of the virus that a lot of the early
17:58cases coming to Connecticut were
18:00from transmission that were domestic
18:02rather than international an the four cases.
18:05I hope you can see this,
18:07but the four cases that.
18:09Uh,
18:09we had picked up in those early weeks.
18:12Kind of fit this pattern.
18:13Three of the case is shown
18:16with the sort of red lines.
18:18They do a track most closely with North
18:20American other isolates from North
18:22America as opposed to other countries.
18:24And then there was one that tracked most
18:27closest to strains from Western Europe.
18:29So this kind of fit the pattern will
18:32also is really interesting to me.
18:34Is that all these for patients that came
18:37within a couple of days the hospital
18:39none of their viruses were directly
18:41related were the same as the other,
18:44so this is independent
18:45introductions coming in,
18:46which was also probably says something about
18:48travel back and forth and things like that.
18:51So that was quite an interesting
18:53bonus of being a in collaboration
18:55with other folks at Yale.
18:57To find more information
18:59about those patients.
19:00Uhm,
19:00but we also had an idea just looking at this.
19:04Well this is interesting.
19:05Like here we used up,
19:07you know 376 PCR test to
19:09test all these patients.
19:10But really if we had only tested the 33
19:13that were positive for the biomarker,
19:16we still would have found all the cases.
19:18And so it suggested maybe this
19:20is a way of expanding,
19:22like conserving,
19:23testing capacity or directing
19:25it towards people who really are
19:27high suspicion to be positive
19:28and so we tried that so far just.
19:31Piloted one day.
19:32We picked one day in March
19:34where we were able to get all
19:36the residual samples from
19:38testing went 144 patients were
19:39tested that day for SARS, Co V2.
19:42And did the biomarker test an what you
19:45can see is again as a smaller proportion
19:48of people were positive than negative.
19:51And then we compared this to the
19:53results from the PCR testing and it
19:56turned out that 17 people were PCR
19:58positive for SARS Kobe to that day.
20:01And 16 of them were among
20:03the biomarker positive,
20:04but one wasn't one was did not
20:06have the biomarker expressed,
20:07and that patient also happened
20:09to have a very low viral load,
20:11which is kind of something
20:13we're following up on.
20:14So if we had had all 17 up here,
20:17we could have said are
20:19negative predictive value.
20:20If you're negative on this biomarker,
20:22you don't have the virus is 100%,
20:24but we can't say that we
20:26have to say 99% because of.
20:28This this one patient out of out of
20:32the 144 that were screened and tested.
20:35Um, so we that got us interested in
20:38biological variables and how they
20:40impact this biomarker that's induces
20:43approaching that's induced by viral
20:45replication within the epithelial
20:47cells and possibly infiltrating cells.
20:49And we looked at all the positive
20:52patients in our initial study,
20:53which was 59 patients.
20:54If you look at their age distribution
20:56there mostly in the older age groups,
20:58and if you look at the symptoms by age group,
21:01the people in the older age
21:03groups had more serious illness.
21:04As you might expect much more likely
21:06to be hospitalised and have things
21:08like pneumonia and hypoxemia.
21:10So, uhm,
21:11So what about the correlation
21:12with the biomarker?
21:13Well, if you look at, uh,
21:15if you look at viral load
21:17versus the biomarker,
21:18there's a positive correlation.
21:20As you might expect.
21:21Because, as I mentioned,
21:23the trigger for production of this
21:25biomarker is viral replication.
21:27Um,
21:27interesting if you look at
21:29age versus the biomarker,
21:30there's a negative correlation
21:32where this biomarker is lower and
21:34the people with the older age is.
21:36But there doesn't seem to be a
21:38clear correlation between agent
21:39viral load in this same group,
21:41so we're still investigating this.
21:43So we actually struck up a collaboration
21:45with the Pediatrics Department,
21:47including Tom Murray and Danielle
21:49Pediatrics to delve into this further
21:51and see if we can figure out what's
21:54going on with this age correlation.
21:56I so finally I just want to mention um,
22:00what's ahead for this project?
22:03I mentioned from these headlines
22:04some of the challenges and we would
22:07like to know Kenneth biomarker
22:08help us to the question of who has
22:11live infectious virus versus is a
22:13persistent PCR positive but not infectious.
22:15Anna question everyone always asked me.
22:17I'm just going to preempt it.
22:19It would be great to know what this
22:21this type of biomarker an in general,
22:24what the host response to infection,
22:26how it's changing overtime during the
22:28course of what can be a long illness.
22:31And so we're actively looking at that
22:33right now. And I just want to finish.
22:36I just want to nod my head to a
22:39project that actually was going
22:40on a lab before the pandemic hit.
22:43Briefly got pause.
22:44Dan is getting restarted now of trying
22:47to find the next pandemic virus
22:49before it hits using this strategy.
22:51And this was spearheaded by Amelia
22:53Hammer in a Yale School of Public
22:55Health Masters student who is
22:57in my lab but graduated in 2019.
23:00And our idea there was the same
23:02idea of let's look at people who
23:05their doctors suspected viral
23:06infection sent the test.
23:08They tested negative for all the
23:10viruses on our panel and see if we
23:12can find people who who looks like
23:14their body was fighting a viral
23:15infection and maybe they have a
23:17viral infection that we don't know
23:19of so we can find out what other
23:21viruses are causing disease in
23:22our patient population that were
23:24not catching with our panel.
23:26And so Amelia just took one week
23:28of January 2017 and screens 250.
23:31One negative samples with our biomarker
23:34that we talked about here CL.
23:3610 and she had 60 of them that were
23:39had high levels of the biomarker
23:42at that time.
23:44We were not doing testing for
23:46the seasonal coronaviruses or
23:47parrot influenza virus.
23:494 so she did that testing an interesting Lee.
23:53Half of these patients had
23:55seasonal coronaviruses and
23:56that actually tipped our hat.
23:58Let us know that seasonal Corona
23:59viruses are circulating in our patient
24:01population and actually Marie Landry
24:03has now added that to the clinical panel.
24:05So now that is those four
24:06viruses are on our panel,
24:08but this also as a proof of concept
24:10that our strategy works of picking up
24:12viral infections that we're not testing for.
24:15Um, Interestingly,
24:15we also have half the samples
24:17where we didn't.
24:18We still don't know exact
24:19well for some of them we do,
24:21but many of them we don't know what what
24:24infectious agents are in the sample,
24:26and we're working that up and
24:27finding some interesting things,
24:28and we hope this will be a good strategy.
24:31Going forward to get an even more
24:33comprehensive view of the viruses
24:35that are circulating so we can be
24:37prepared for ones that we aren't
24:39necessarily testing for right now.
24:41So, just to summarize, um,
24:43uh,
24:44we're interested in studying the host
24:46response to fight coronavirus today.
24:48I talked about diagnostic applications
24:51were also really interested in getting
24:54insights into early stage pathogenesis.
24:56And how this differs among people
24:58who have different outcomes.
25:00Uhm,
25:00I talked about a host response based
25:03screening test that we've been working on,
25:06which allowed us to identify for
25:08undiagnosed cases from early March
25:10and we're looking at other utilities
25:13to sort of fill in the gaps in
25:16some of our testing strategies,
25:17and hopefully I'll be able to
25:20update you in a future talk on our
25:23undiagnosed viruses project as well.
25:26I saw with that before,
25:28I conclude I'd like to thank all the many,
25:31many people in this Yale environment
25:33have contributed to projects
25:35on COVID-19. Definitely could
25:36have been done in a silo.
25:39It was very great to have lots
25:42of collaborators an it still is.
25:44I want to acknowledge my my lab
25:46members including ready tomorrow.
25:48I mentioned who spearheaded the project.
25:50I talked about as well as Marie
25:52Landry on the clinical virology lab,
25:55especially Marino in and Robin Garner,
25:57who really helped us alot.
25:59Dezhen Zou, who's been helping
26:01with our bioinformatics,
26:02I didn't really talk about that today,
26:05but he's been a great help the whole group,
26:08all lab and Nate grew bath for their
26:11constant participation and help
26:13with the molecular Epidemiology.
26:14As well as lab working group depicted here
26:17from March 2nd which includes Albert Konate,
26:20grew Bhasa Domer Akiko Isaki Marie Landreau.
26:23That's me actually.
26:24And this was back when there's only
26:2745,000 global cases on March 2nd.
26:30Uh, so with that?
26:31Uhm, I think I made up some time.
26:33Uh, in in speaking a little quickly,
26:35but hopefully you're able to follow.
26:36And if there's any questions I
26:38would be happy to answer them now.
26:41Thank you
26:41Ellen. Thank you and congratulations to
26:43you and your entire research group on that
26:46impressive body of work in a relatively
26:48short time to address the pandemic.
26:50and I know we're just about
26:52the top of the hour or so,
26:54and if folks can submit questions,
26:56but let me just offer up a couple.
26:59One is specifically.
27:00I mean, I think the work you're doing
27:02on sort of the biomarkers is really
27:04interesting in terms of testing strategy,
27:07and you mentioned that you're
27:08anticipating one of my questions,
27:10which was, how does it change
27:12over the course of the illness?
27:14But I'm curious,
27:15do we have a sense of biomarkers that
27:17might predict the severity of illness
27:19that is almost to predict who's
27:21more likely to need more intensive
27:23care at the time of diagnosis?
27:26Yeah, that that's very interesting people.
27:28There's been a some work already published
27:31about blood like cytokines in the blood
27:33that could be indicated indicative
27:35of that we're looking even earlier.
27:37I mean it at the at the early stage
27:40of infection, the nasopharynx.
27:42And that's one reason why we're
27:44really interested in this potential
27:46difference between adults and kids.
27:48Because, you know,
27:49kids are seem relatively protected from
27:51pulmonary disease compared to adults,
27:53older adults.
27:54So that's one reason why we
27:56struck up this collaboration with
27:58Pediatrics to try to understand.
28:00Is there some difference in the robustness
28:02of that initial response that could you
28:04know that could possibly explain this?
28:06There's many explanations,
28:07but that's one,
28:08so that's that's the kind of thing
28:10we're going to we're looking into,
28:12but I don't have the answer yet.
28:15This is it's very rare to give a talk on a
28:18project that started like two months ago,
28:21but so that's why there's a more
28:23questions than answers at this point,
28:25but we hope to find that out.
28:27We're looking at the whole.
28:29The entire pattern of gene expression.
28:31Um and not just this one biomarker to try
28:33to get it that in some specific groups
28:36of patients with different outcomes.
28:39So you know just to follow up on that.
28:42So do we think that, uh, I mean,
28:44likely the airway response.
28:45It is before the subsequent
28:47sort of larger immune response.
28:48The airway response is likely
28:50very different across ages.
28:51And you think that could be one
28:53of the major explanations why age
28:55is such a strong predictor for
28:57outcome in this illness. Possibly
28:59possibly, I'd like to have the
29:01data to answer you definitively,
29:03so hopefully will have
29:04that soon. Yeah, well,
29:06it sounds like more to follow.
29:08Well, channel and for two really superb
29:10talks and the work that they do.
29:13Thank you all for joining us today.
29:15I know a lot of folks also watch
29:18online as we as the labs reopened but.
29:21Enjoy the rest of your day and
29:22thank you all for your work.
29:24Thank you very much.