AI transcript
Hi everyone, welcome to the A6NZ podcast, I’m Sonal.
We’ve been covering the novel coronavirus and COVID-19 disease on our other show, 16
Minutes, which you can find in a separate feed if you haven’t subscribed already, but
given that the topic of health system preparedness is top of mind right now and that the latest
CDC briefing touched on issues with test kits, the patient perspective of how the U.S. health
care system works, with clinicians calling the health department and so on, we’re running
last week’s episode of 16 Minutes in this feed because in it we covered how these tests
work, how the U.S. health care system works today when it comes to epidemics and preparedness
and where we might go in the future.
As a reminder, you can visit cdc.gov and who.int for more information, but as of now, the World
Health Organization reported on February 25th that for the first time since the onset of
symptoms of the first identified case of COVID-19, there have been more new cases reported from
countries outside of China than from China, and the CDC reported on February 26th that
there’s news about community spread, which means that cases of COVID-19 are appearing
without a known source of exposure.
And those communities currently include Hong Kong, Italy, Iran, Singapore, South Korea,
Taiwan, and Thailand.
So that’s the latest updates, now onto last week’s episode.
Hi everyone, welcome to the 23rd episode of 16 Minutes, our show where we cover the headlines
and what’s in the news, what’s happening, and tease apart what’s hype, what’s real
from our vantage point in tech.
I’m Sonal.
Today we’re doing another update on the topic of coronavirus.
We did a deeper dive in episode 21, which you can find in this feed or on our website
at a6nz.com/16minutes.
Much of that background is still relevant today, but in this episode we’re going to
cover two segments.
First, we’ll do a high-level overview of some of the practical implications for the U.S.
healthcare system with a6nz.bio general partner Julie Yu, and then the second segment is a
quick situation update from our previous episode with Judy Svitskaya.
As a reminder, all the sources and reports cited in this episode will be included in
the show notes, and we are not covering the clinical infectious disease specifics as we
will bring on our other experts for that in an upcoming episode.
So that’s a context.
Now before we chat, let me quickly share the latest updates, which are that the day after
we dropped our last episode, the World Health Organization declared on January 30th that
the coronavirus outbreak is a, quote, “public health emergency of international concern.”
And then the day after that, the Health and Human Services Secretary of the United States
declared a public health emergency to aid the nation’s healthcare community in responding
to the novel coronavirus, which, by the way, was officially named last week.
It is now known as COVID-19.
And to be clear, that’s the name of the disease, not the virus, which, as mentioned in our
last episode, was known as 2019 NCOV, but is now known as SARS-CoV-2.
And then also, as of last week, a lot happened in a week, the CMS, the U.S. Centers for
Medicare and Medicaid Services, developed a new billing code for providers and laboratories
to test patients for this virus that causes COVID-19.
And we’ll share details about how that test works in the second half of this episode, as
well as the latest global numbers.
But first, now let’s cover the U.S. care delivery aspects.
According to the CDC, as of February 17th, there are a total of 467 persons under investigation
for this in the United States, identified across 42 states, with 15 confirmed positive
for it and 60 pending.
So Julie, practically speaking, what’s actually happening here in our health care system as
it works today?
What happens when someone walks into a hospital?
So it depends a lot on where you’re walking into.
Most of the time, because our health care system is characterized by such access constraints,
you may see a lot of these patients actually showing up in the emergency room.
What happens is that they will check in with a registrar, essentially, and be asked, “What
is your reason for being here?”
Typically, they’ll also be collecting your insurance information.
You will do a physical visual assessment.
They might ask some very generic questions.
One of the training motions that’s happening in hospitals is that people are trying to
train those frontline staff to ask questions like, “Have you traveled to China in the last
two weeks?”
Et cetera.
And so you have to deploy field resource to make sure that even those frontline questions
are being asked.
Right.
I get it.
Sort of the difference between a generalist triage model and a more specialist triage
model.
Exactly.
Because that’s the biggest blind spot right now.
One of the big risks of this particular virus is that the pre-syntomatic period while you
are still contagious is fairly lengthy.
And so that’s one of the big sort of gaps right now is, you know, how do we just identify
those people?
So after they go through the ER and then what happens?
So assuming that people are being appropriately assessed and there is a determination that
there’s a potential risk that you are a coronavirus patient, you administer the test, again, assuming
that the test kits are in supply and based on those results.
If the patient is quarantined and assuming, again, that they are in an acute care facility
that has infrastructure to actually perform an appropriate quarantine, typically those
quarantine rooms are what are called negative pressure rooms, which basically means the
air in that room is sort of minimal seepage externally.
You’re essentially isolating the potential germs and contagion.
But again, that sort of begs again the point of, “Are you showing up at an ED of a facility
that actually has all this infrastructure?”
Many of these patients might just be walking into an urgent care clinic or a primary care
clinic.
And so oftentimes it might be the case that the patient could get sent home or referred
into one of these facilities with further delay, further exposure points, et cetera.
So basically there’s a potential for a lot of chaos on the front lines because we don’t
clearly understand where the risk points are.
And we’re sort of waiting for the patients to essentially show up versus being able to
be proactive.
Right.
And how about on the treatment side?
So there currently is no treatment for this.
My partner Jorge and I, and Jorge being an expert in genomics, oftentimes talk about the
areas of medicine and healthcare where clearly there’s an application for technology that
makes complete sense, but oftentimes it’s the business model component of it that holds
things back.
What do you guys mean by that?
So we have the capabilities to rapidly sequence bugs and other viral forms.
And there’s in theory a capability that says if you are able to quickly identify and rapidly
identify in the field, what type of bug you’re dealing with, that you could also synthesize
a vaccine on demand based on the fact that we can increasingly print genomic tools and
genomic content.
That’s technically possible right now?
The technology exists.
It’s not yet been deployed into practice.
There’s still a great degree of validation and testing.
Obviously we have a very rigorous system through which these types of technology are brought
to market with regards to clinical trials and regulation and whatnot.
The other piece is historically vaccines and other types of treatments like this have not
been a lucrative area for businesses to go into for a number of reasons.
And that’s another area that’s TBD is can you actually find the reimbursement path for
getting these products to market?
Okay.
So where we are right now, it seems like the focus is on what I’m calling the 3Gs, gowns,
goggles, and gloves.
I’m also very interested at a broader level because the World Health Organization did their
first annual report on global preparedness for health emergencies.
They basically wrote in their report, just came out last year, and they have targets
to September 2020 for progress towards that, that countries, donors, and multilateral institutions
must be prepared for the worst, quote, “A rapidly spreading pandemic due to a lethal
respiratory pathogen, whether naturally emergent or accidentally or deliberately released,
poses additional preparedness requirements, and that we must ensure adequate investment
in developing innovative vaccines and therapeutics as you talked about, surge manufacturing capacity,
appropriate non-pharmaceutical interventions, et cetera, et cetera.”
I guess I have two questions for you here.
One, where are we as a country from a systemic point on that readiness?
And then two, what does it say about where we should be?
So this to me is one of the biggest cases to be made for this concept of the unbundling
of the hospital.
When you look back at the history of how the facility side of healthcare has evolved, hospitals
were something that were born in the last century or so on the premise that if you were
to centralize the scarce resources, the doctors, the clinicians in a central location that
you could get efficiencies.
And by the way, also have the infrastructure, like the op-ex and cap-ex required to do big
labs and centralize the facilities and high-end procedures.
Right.
Exactly.
Not just the people.
Exactly.
And so the unfortunate consequence of that is that, yes, you can have these now very
high-end facilities that perform very advanced procedures, but where, again, we are forcing
the patients to travel outside of their homes, but also get exposed to others who have other
illnesses.
In fact, hospital-acquired infections are one of the major contributors to comorbidities
for patients who come to these acute care facilities.
We are in the middle of flu season, remember?
Yes.
So you’re already having rooms full of patients who suspect that they have some kind of illness.
That’s kind of like an iconic motion within our healthcare system is that we force patients
to come to these central monolithic facilities to get any kind of care versus going to them,
making it convenient to them.
And actually, it’s interesting that when you look back in the early 1900s, nearly half
of healthcare was actually delivered in the home.
Less than 1% of healthcare is now delivered in the home, even for the most senior and
frail patients in America.
Right.
And it’s also an access issue, because it means that people who can’t afford or live
in big hubs where you can afford these types of high, varying quality.
What that’s predicated on, though, it requires productization of the types of technologies
that you see in these hospital settings in such a way that can be decentralized.
A great basic but kind of elegant example of this is you see companies, one in particular
comes to mind that is doing a connected thermometer.
It’s marketed towards parents as something that they can use for their kids.
And when you look at the back end of their business, it’s basically a data company that
is acting as a sentinel to collect information about temperatures in communities and essentially
predict when there will be a flu outbreak or a cold outbreak, et cetera.
And they actually notify not only the end users, but they have connectivity into schools,
churches, other institutions.
And you can imagine that a system like that at scale for various types of diseases could
actually enable this sort of truly decentralized model.
But the only way that this can happen is if you have interoperable data systems that can
not only collect data from the clinical setting and make it readily available on an ad hoc
basis and across facilities across the country, but also take into account non-traditional
data sources like these smart devices that are connected in the communities to augment
your visibility across patient populations.
Okay.
So that’s sort of the unbundling of the hospital.
In that context, it all comes together like connects the dots.
This is how interoperability and data liquidity and data from unconventional sources and all
this stuff comes together.
That’s on the future of where we could go and what the ideal state could be.
What are some of the things that can happen now inside the hospital?
There’s, I would say, the human elements, the operational elements, and then the technology
elements.
So on the human side, this is what these organizations are sort of designed to do is deploy large
swaths of human labor in such a way that can sort of react to healthcare needs.
Operationally speaking, we mentioned earlier the logistics of how a patient flows through
the hospital.
You need to anticipate all the potential entry points that patients are coming in.
The hospital these days are health systems, really, and they need to have connectivity
into their primary care clinics, their urgent care clinics, et cetera, to really understand
systematically what’s going on across the network.
And now the tech part.
That’s what I’m most interested in given your vantage point.
Yeah.
Here’s what I’m going to say.
One nice thing about EHRs now, they are literally the primary tool that frontline clinicians
are using.
You’ve seen this now, hospitals literally interjecting very basic questions into the medical record
to prompt them to ask the things that could qualify whether or not a patient might potentially
be at risk for coronavirus.
So that’s where the fact that we now have this broad infrastructure layer laid down can
actually provide tremendous value in that you can make one change that does get propagated
to all of the endpoints in the care delivery system.
So doing things at scale through technology, basically.
So bottom line for me, Julie, how should we think about this in terms of the tech and
the delivery side and preparedness for the epidemic at that level?
I think this is shedding light on the fact that we as a healthcare system have many nodes
of potential failure when it comes to widespread epidemics and pandemics, but the direction
and everything that we’ve talked about around the notion of decentralization, of unbundling
of hospital, of using technology and distributed data streams to be able to be more responsive
and nimble is coming to light.
And so we will take learnings from this and apply it towards what the future of healthcare
needs to look like.
Thank you for joining this segment.
All right.
Thank you so much.
Now let me introduce Judy Savitskaya on the A6NZ Bio team.
Welcome, Judy.
Thanks, Donald.
Okay.
So let me just give a quick update on the stats of the disease.
This is Situation Report Number 25 from the World Health Organization.
We just came out February 14th.
Here’s the high-level summary of the numbers.
So globally, there are now 49,053 laboratory-confirmed cases.
In China, there are 48,548 laboratory-confirmed ones.
And then outside of China, there are 505 across 24 countries with two deaths outside of China.
The other thing, though, is there was a huge spike in the numbers.
And that was because they will include the number of clinically diagnosed cases into
the number of confirmed cases so that patients could receive timely treatment.
And previously, patients could only be diagnosed by test kits.
What does this mean scientifically?
Yeah.
So these cases have in the past been basically labeled as coronavirus cases, whether they
have the right nucleic acid sequence that belongs to that virus.
What they’re saying now is that they’re also going to count anybody who is symptomatic
in all the same ways that the virus has been presenting itself in other patients and has
the CT scan evidence.
So the former FDA commissioner, Scott Gottlieb, noted that this is happening because it’s
in the absence of a PCR test, which we briefly talked about last time.
There’s an open question about why these are not yet available at scale.
But can you give us a little bit more detail about what is the PCR test scientifically?
Yeah.
So PCR test stands for polymerase chain reaction, basically with amplifying a piece of DNA or
RNA nucleic acid by copying it over and over and over again.
What you’re doing in this test is basically you’re taking a sample from the patient.
There’s some nucleic acids in there.
The sequence is very long, but you take a small sequence of DNA, RNA, whatever you’re
trying to amplify.
This is an RNA virus.
So you’re trying to bind it with a sequence that you know belongs to that virus.
You attach it, it’s about 20 bases in length.
You use the polymerase chain reaction to extend out that 20 base primer to cover the entire
sequence or whatever like piece of the sequence that you’re trying to amplify.
And then you get many, many copies this way.
What does that give you having the many, many copies?
Surveillance or absence, right?
So, and amounts, it’s called real time PCR.
I actually don’t love the name.
I think QPCR is a better name for this quantitative PCR because it’s telling you how many pieces
of essentially like what is the viral load in the bloodstream or the load of whatever
pathogen you’re looking for.
So Keith Robison, who’s currently principal scientist at Ginkgo wrote about, you know,
how some of these tests work.
And he basically agrees with you that it should be called QPCR because as you note, what you’re
basically describing as it’s quantitative.
Yeah.
And real time doesn’t really mean much.
But there’s another critical reason why people don’t like RT-PCR is because there’s a completely
different concept that is called reverse transcriptase PCR.
That’s why it’s kind of hard to talk about this with this virus because it’s an RNA virus.
Right.
In fact, he also talks about the fact that PCR works with DNA.
But yet you’re telling me coronavirus is RNA, so can you help explain that distinction?
Absolutely.
So in this reaction, what you’re doing is using a polymerase that is used to binding either
DNA or RNA and then extending it.
So in the case of the RNA viruses, you need the reverse transcriptase.
So this is a weirdo polymerase that binds RNA templates and then extends and produces
DNA.
And the reason that you want DNA is that it’s really stable.
We have a ton of ways to measure it.
RNA is a little bit more fickle.
So if you can turn this RNA signature, this RNA message into a DNA output that actually
substantially simplifies downstream processing.
So this reverse transcriptase piece is what is doing the RNA to DNA translation.
Okay.
So we’ve talked about what’s going on in the test.
Let’s quickly talk about some of the differences from what we last talked about.
We talked about R0 last time, which is really practically how many people, a newly infected
person is likely to pass a virus on to and you explained what variables go into it.
What is your take on where we are with the R0?
Yeah.
We just talked about the spike, the definition of what this disease is.
Is it the viral load or is it like these symptoms?
That’s changing as well.
So I still think it’s too early to calculate an R0.
There’s still a ton of cases out there that are not showing symptoms, so we can’t really
calculate the number of people who have gotten infected.
I think we have technically approached the point where it is a pandemic, although the
definition for pandemic is quite loose.
The World Health Organization defines it as a worldwide spread of a new disease.
The Centers for Disease Control and Prevention, the CDC and the U.S. have a bit looser of
a definition describing as a disease that spreads across regions.
And quote from the CDC website is the fact that this virus has caused illness, including
illness resulting in death and sustained person-to-person spread in China is concerning.
These factors meet two of the criteria of a pandemic.
And by the way, people want to read an excellent piece.
Helen Branswell, and I mentioned her in our last episode, has a great piece in stat news
with the headline quote, “Undershining Pandemics, What They Mean, Don’t Mean, and What Comes
Next with the Coronavirus.”
From your take, why is it so freaking confusing?
The term pandemic is not particularly useful in this case because it only tells you about
the geographical spread.
It’s not actually telling you about the danger of the disease.
Like flu is a global pandemic annually, but the term doesn’t necessarily mean, you know,
very fatal or spreads very fast.
It just means it’s been into more than two geographies outside of its original origin.
So if a flu is a pandemic, that’s also endemic in that it is in our population and circulates.
Can you actually explain endemic?
Because my understanding of the word comes from like understanding evolution and Darwin
and knowing about endemic species and the Galapagos.
Yeah.
What does that mean?
So endemic is a more useful term than pandemic.
It’s something that is going to live in a latent way in the population or in the environment.
We should see a returning flu as the quintessential example of this.
It’s still an open question as to whether this coronavirus is going to become endemic.
Okay.
So that’s the difference between pandemics, endemic, and add one more name to the list,
which is misinfodemic.
I’ve read a lot of people describing this potentially as an infodemic because of the
spread of some fantastic rapid science, which you talked about last time, but there’s also
a spread of misinformation as well.
And so the two of these things are going hand in hand.
There’s a group that has already published an epidemiological model of what they expect
the spread to be.
Again, if any of the data that’s going into there is either intentionally falsified or
it is just too early.
Incomplete.
We don’t have good enough data.
Or like the measurements have changed, right?
So in the middle of last week, the way that Chinese hospitals were measuring cases changed.
So that’s going to mess up the data pretty substantially.
So I think that these models are going to suffer if garbage in, garbage out.
If this infodemic issue continues.
Okay.
So beyond the numbers and the definition, let’s quickly talk about some of the weightings.
According to the World Health Organization, some of the data from China last before this
big spike suggested that 82% of confirmed cases have only mild infection.
About 15% are severe enough to require hospital care and about 3% need intensive care.
And then preliminary data suggested that roughly 2% of the people who tested positive for the
virus have died.
And that’s important because last time we reported the CFR, the case fatality rates,
which for SARS was at 10%.
And for MERS, it was actually 37% in Saudi Arabia, but 34% outside of that region.
So last time you talked about the paradox between deadliness and the R0.
What’s your updates, if any, on that?
So the reason for that is that you can’t really have a high fatality rate and a fast
spreading virus.
Basically, dead people can’t spread the disease and people who are, you know, confined to
their beds also can’t spread the disease as fast.
But there’s another variable, which is incubation time.
So this is the length of time that it takes for the infection to demonstrate some symptoms.
And there’s a different period of time that’s called the latent period, which is the time
between getting infected and becoming infectious.
So these are two different variables.
And these interplay in a really interesting way.
If the latent time is really short, so you are infectious almost as soon as you’ve been
infected, but the incubation time is long, you have no idea that you’re infected.
You have no symptoms.
You feel completely normal, but it turns out that you’re actually spreading the virus.
So in that case, this sort of paradox between the case fatality and the spread rate is going
to break because you can start spreading without actually having symptoms.
It’s also probably too early to tell what the exact incubation period is going to be.
Most estimates I’ve seen have topped out at about 14 days, but that’s still pretty long.
So it’s something to definitely take into consideration.
Okay.
So bottom line it for me, where are we now in the situation update from the news and
your perspective?
So the bottom line is it’s still too early to put hard numbers on any of these facts.
It’s important to keep track of where the cases are coming up, where they’re being reported,
and don’t jump to any conclusions about case fatality rates, about R knots, because it’s
just too early.
Other than that, the same precautions apply.
Thank you for joining the segment.
We’ve been covering the novel coronavirus and COVID-19 disease on our other show, 16
Minutes, which you can find in a separate feed if you haven’t subscribed already, but
given that the topic of health system preparedness is top of mind right now and that the latest
CDC briefing touched on issues with test kits, the patient perspective of how the U.S. health
care system works, with clinicians calling the health department and so on, we’re running
last week’s episode of 16 Minutes in this feed because in it we covered how these tests
work, how the U.S. health care system works today when it comes to epidemics and preparedness
and where we might go in the future.
As a reminder, you can visit cdc.gov and who.int for more information, but as of now, the World
Health Organization reported on February 25th that for the first time since the onset of
symptoms of the first identified case of COVID-19, there have been more new cases reported from
countries outside of China than from China, and the CDC reported on February 26th that
there’s news about community spread, which means that cases of COVID-19 are appearing
without a known source of exposure.
And those communities currently include Hong Kong, Italy, Iran, Singapore, South Korea,
Taiwan, and Thailand.
So that’s the latest updates, now onto last week’s episode.
Hi everyone, welcome to the 23rd episode of 16 Minutes, our show where we cover the headlines
and what’s in the news, what’s happening, and tease apart what’s hype, what’s real
from our vantage point in tech.
I’m Sonal.
Today we’re doing another update on the topic of coronavirus.
We did a deeper dive in episode 21, which you can find in this feed or on our website
at a6nz.com/16minutes.
Much of that background is still relevant today, but in this episode we’re going to
cover two segments.
First, we’ll do a high-level overview of some of the practical implications for the U.S.
healthcare system with a6nz.bio general partner Julie Yu, and then the second segment is a
quick situation update from our previous episode with Judy Svitskaya.
As a reminder, all the sources and reports cited in this episode will be included in
the show notes, and we are not covering the clinical infectious disease specifics as we
will bring on our other experts for that in an upcoming episode.
So that’s a context.
Now before we chat, let me quickly share the latest updates, which are that the day after
we dropped our last episode, the World Health Organization declared on January 30th that
the coronavirus outbreak is a, quote, “public health emergency of international concern.”
And then the day after that, the Health and Human Services Secretary of the United States
declared a public health emergency to aid the nation’s healthcare community in responding
to the novel coronavirus, which, by the way, was officially named last week.
It is now known as COVID-19.
And to be clear, that’s the name of the disease, not the virus, which, as mentioned in our
last episode, was known as 2019 NCOV, but is now known as SARS-CoV-2.
And then also, as of last week, a lot happened in a week, the CMS, the U.S. Centers for
Medicare and Medicaid Services, developed a new billing code for providers and laboratories
to test patients for this virus that causes COVID-19.
And we’ll share details about how that test works in the second half of this episode, as
well as the latest global numbers.
But first, now let’s cover the U.S. care delivery aspects.
According to the CDC, as of February 17th, there are a total of 467 persons under investigation
for this in the United States, identified across 42 states, with 15 confirmed positive
for it and 60 pending.
So Julie, practically speaking, what’s actually happening here in our health care system as
it works today?
What happens when someone walks into a hospital?
So it depends a lot on where you’re walking into.
Most of the time, because our health care system is characterized by such access constraints,
you may see a lot of these patients actually showing up in the emergency room.
What happens is that they will check in with a registrar, essentially, and be asked, “What
is your reason for being here?”
Typically, they’ll also be collecting your insurance information.
You will do a physical visual assessment.
They might ask some very generic questions.
One of the training motions that’s happening in hospitals is that people are trying to
train those frontline staff to ask questions like, “Have you traveled to China in the last
two weeks?”
Et cetera.
And so you have to deploy field resource to make sure that even those frontline questions
are being asked.
Right.
I get it.
Sort of the difference between a generalist triage model and a more specialist triage
model.
Exactly.
Because that’s the biggest blind spot right now.
One of the big risks of this particular virus is that the pre-syntomatic period while you
are still contagious is fairly lengthy.
And so that’s one of the big sort of gaps right now is, you know, how do we just identify
those people?
So after they go through the ER and then what happens?
So assuming that people are being appropriately assessed and there is a determination that
there’s a potential risk that you are a coronavirus patient, you administer the test, again, assuming
that the test kits are in supply and based on those results.
If the patient is quarantined and assuming, again, that they are in an acute care facility
that has infrastructure to actually perform an appropriate quarantine, typically those
quarantine rooms are what are called negative pressure rooms, which basically means the
air in that room is sort of minimal seepage externally.
You’re essentially isolating the potential germs and contagion.
But again, that sort of begs again the point of, “Are you showing up at an ED of a facility
that actually has all this infrastructure?”
Many of these patients might just be walking into an urgent care clinic or a primary care
clinic.
And so oftentimes it might be the case that the patient could get sent home or referred
into one of these facilities with further delay, further exposure points, et cetera.
So basically there’s a potential for a lot of chaos on the front lines because we don’t
clearly understand where the risk points are.
And we’re sort of waiting for the patients to essentially show up versus being able to
be proactive.
Right.
And how about on the treatment side?
So there currently is no treatment for this.
My partner Jorge and I, and Jorge being an expert in genomics, oftentimes talk about the
areas of medicine and healthcare where clearly there’s an application for technology that
makes complete sense, but oftentimes it’s the business model component of it that holds
things back.
What do you guys mean by that?
So we have the capabilities to rapidly sequence bugs and other viral forms.
And there’s in theory a capability that says if you are able to quickly identify and rapidly
identify in the field, what type of bug you’re dealing with, that you could also synthesize
a vaccine on demand based on the fact that we can increasingly print genomic tools and
genomic content.
That’s technically possible right now?
The technology exists.
It’s not yet been deployed into practice.
There’s still a great degree of validation and testing.
Obviously we have a very rigorous system through which these types of technology are brought
to market with regards to clinical trials and regulation and whatnot.
The other piece is historically vaccines and other types of treatments like this have not
been a lucrative area for businesses to go into for a number of reasons.
And that’s another area that’s TBD is can you actually find the reimbursement path for
getting these products to market?
Okay.
So where we are right now, it seems like the focus is on what I’m calling the 3Gs, gowns,
goggles, and gloves.
I’m also very interested at a broader level because the World Health Organization did their
first annual report on global preparedness for health emergencies.
They basically wrote in their report, just came out last year, and they have targets
to September 2020 for progress towards that, that countries, donors, and multilateral institutions
must be prepared for the worst, quote, “A rapidly spreading pandemic due to a lethal
respiratory pathogen, whether naturally emergent or accidentally or deliberately released,
poses additional preparedness requirements, and that we must ensure adequate investment
in developing innovative vaccines and therapeutics as you talked about, surge manufacturing capacity,
appropriate non-pharmaceutical interventions, et cetera, et cetera.”
I guess I have two questions for you here.
One, where are we as a country from a systemic point on that readiness?
And then two, what does it say about where we should be?
So this to me is one of the biggest cases to be made for this concept of the unbundling
of the hospital.
When you look back at the history of how the facility side of healthcare has evolved, hospitals
were something that were born in the last century or so on the premise that if you were
to centralize the scarce resources, the doctors, the clinicians in a central location that
you could get efficiencies.
And by the way, also have the infrastructure, like the op-ex and cap-ex required to do big
labs and centralize the facilities and high-end procedures.
Right.
Exactly.
Not just the people.
Exactly.
And so the unfortunate consequence of that is that, yes, you can have these now very
high-end facilities that perform very advanced procedures, but where, again, we are forcing
the patients to travel outside of their homes, but also get exposed to others who have other
illnesses.
In fact, hospital-acquired infections are one of the major contributors to comorbidities
for patients who come to these acute care facilities.
We are in the middle of flu season, remember?
Yes.
So you’re already having rooms full of patients who suspect that they have some kind of illness.
That’s kind of like an iconic motion within our healthcare system is that we force patients
to come to these central monolithic facilities to get any kind of care versus going to them,
making it convenient to them.
And actually, it’s interesting that when you look back in the early 1900s, nearly half
of healthcare was actually delivered in the home.
Less than 1% of healthcare is now delivered in the home, even for the most senior and
frail patients in America.
Right.
And it’s also an access issue, because it means that people who can’t afford or live
in big hubs where you can afford these types of high, varying quality.
What that’s predicated on, though, it requires productization of the types of technologies
that you see in these hospital settings in such a way that can be decentralized.
A great basic but kind of elegant example of this is you see companies, one in particular
comes to mind that is doing a connected thermometer.
It’s marketed towards parents as something that they can use for their kids.
And when you look at the back end of their business, it’s basically a data company that
is acting as a sentinel to collect information about temperatures in communities and essentially
predict when there will be a flu outbreak or a cold outbreak, et cetera.
And they actually notify not only the end users, but they have connectivity into schools,
churches, other institutions.
And you can imagine that a system like that at scale for various types of diseases could
actually enable this sort of truly decentralized model.
But the only way that this can happen is if you have interoperable data systems that can
not only collect data from the clinical setting and make it readily available on an ad hoc
basis and across facilities across the country, but also take into account non-traditional
data sources like these smart devices that are connected in the communities to augment
your visibility across patient populations.
Okay.
So that’s sort of the unbundling of the hospital.
In that context, it all comes together like connects the dots.
This is how interoperability and data liquidity and data from unconventional sources and all
this stuff comes together.
That’s on the future of where we could go and what the ideal state could be.
What are some of the things that can happen now inside the hospital?
There’s, I would say, the human elements, the operational elements, and then the technology
elements.
So on the human side, this is what these organizations are sort of designed to do is deploy large
swaths of human labor in such a way that can sort of react to healthcare needs.
Operationally speaking, we mentioned earlier the logistics of how a patient flows through
the hospital.
You need to anticipate all the potential entry points that patients are coming in.
The hospital these days are health systems, really, and they need to have connectivity
into their primary care clinics, their urgent care clinics, et cetera, to really understand
systematically what’s going on across the network.
And now the tech part.
That’s what I’m most interested in given your vantage point.
Yeah.
Here’s what I’m going to say.
One nice thing about EHRs now, they are literally the primary tool that frontline clinicians
are using.
You’ve seen this now, hospitals literally interjecting very basic questions into the medical record
to prompt them to ask the things that could qualify whether or not a patient might potentially
be at risk for coronavirus.
So that’s where the fact that we now have this broad infrastructure layer laid down can
actually provide tremendous value in that you can make one change that does get propagated
to all of the endpoints in the care delivery system.
So doing things at scale through technology, basically.
So bottom line for me, Julie, how should we think about this in terms of the tech and
the delivery side and preparedness for the epidemic at that level?
I think this is shedding light on the fact that we as a healthcare system have many nodes
of potential failure when it comes to widespread epidemics and pandemics, but the direction
and everything that we’ve talked about around the notion of decentralization, of unbundling
of hospital, of using technology and distributed data streams to be able to be more responsive
and nimble is coming to light.
And so we will take learnings from this and apply it towards what the future of healthcare
needs to look like.
Thank you for joining this segment.
All right.
Thank you so much.
Now let me introduce Judy Savitskaya on the A6NZ Bio team.
Welcome, Judy.
Thanks, Donald.
Okay.
So let me just give a quick update on the stats of the disease.
This is Situation Report Number 25 from the World Health Organization.
We just came out February 14th.
Here’s the high-level summary of the numbers.
So globally, there are now 49,053 laboratory-confirmed cases.
In China, there are 48,548 laboratory-confirmed ones.
And then outside of China, there are 505 across 24 countries with two deaths outside of China.
The other thing, though, is there was a huge spike in the numbers.
And that was because they will include the number of clinically diagnosed cases into
the number of confirmed cases so that patients could receive timely treatment.
And previously, patients could only be diagnosed by test kits.
What does this mean scientifically?
Yeah.
So these cases have in the past been basically labeled as coronavirus cases, whether they
have the right nucleic acid sequence that belongs to that virus.
What they’re saying now is that they’re also going to count anybody who is symptomatic
in all the same ways that the virus has been presenting itself in other patients and has
the CT scan evidence.
So the former FDA commissioner, Scott Gottlieb, noted that this is happening because it’s
in the absence of a PCR test, which we briefly talked about last time.
There’s an open question about why these are not yet available at scale.
But can you give us a little bit more detail about what is the PCR test scientifically?
Yeah.
So PCR test stands for polymerase chain reaction, basically with amplifying a piece of DNA or
RNA nucleic acid by copying it over and over and over again.
What you’re doing in this test is basically you’re taking a sample from the patient.
There’s some nucleic acids in there.
The sequence is very long, but you take a small sequence of DNA, RNA, whatever you’re
trying to amplify.
This is an RNA virus.
So you’re trying to bind it with a sequence that you know belongs to that virus.
You attach it, it’s about 20 bases in length.
You use the polymerase chain reaction to extend out that 20 base primer to cover the entire
sequence or whatever like piece of the sequence that you’re trying to amplify.
And then you get many, many copies this way.
What does that give you having the many, many copies?
Surveillance or absence, right?
So, and amounts, it’s called real time PCR.
I actually don’t love the name.
I think QPCR is a better name for this quantitative PCR because it’s telling you how many pieces
of essentially like what is the viral load in the bloodstream or the load of whatever
pathogen you’re looking for.
So Keith Robison, who’s currently principal scientist at Ginkgo wrote about, you know,
how some of these tests work.
And he basically agrees with you that it should be called QPCR because as you note, what you’re
basically describing as it’s quantitative.
Yeah.
And real time doesn’t really mean much.
But there’s another critical reason why people don’t like RT-PCR is because there’s a completely
different concept that is called reverse transcriptase PCR.
That’s why it’s kind of hard to talk about this with this virus because it’s an RNA virus.
Right.
In fact, he also talks about the fact that PCR works with DNA.
But yet you’re telling me coronavirus is RNA, so can you help explain that distinction?
Absolutely.
So in this reaction, what you’re doing is using a polymerase that is used to binding either
DNA or RNA and then extending it.
So in the case of the RNA viruses, you need the reverse transcriptase.
So this is a weirdo polymerase that binds RNA templates and then extends and produces
DNA.
And the reason that you want DNA is that it’s really stable.
We have a ton of ways to measure it.
RNA is a little bit more fickle.
So if you can turn this RNA signature, this RNA message into a DNA output that actually
substantially simplifies downstream processing.
So this reverse transcriptase piece is what is doing the RNA to DNA translation.
Okay.
So we’ve talked about what’s going on in the test.
Let’s quickly talk about some of the differences from what we last talked about.
We talked about R0 last time, which is really practically how many people, a newly infected
person is likely to pass a virus on to and you explained what variables go into it.
What is your take on where we are with the R0?
Yeah.
We just talked about the spike, the definition of what this disease is.
Is it the viral load or is it like these symptoms?
That’s changing as well.
So I still think it’s too early to calculate an R0.
There’s still a ton of cases out there that are not showing symptoms, so we can’t really
calculate the number of people who have gotten infected.
I think we have technically approached the point where it is a pandemic, although the
definition for pandemic is quite loose.
The World Health Organization defines it as a worldwide spread of a new disease.
The Centers for Disease Control and Prevention, the CDC and the U.S. have a bit looser of
a definition describing as a disease that spreads across regions.
And quote from the CDC website is the fact that this virus has caused illness, including
illness resulting in death and sustained person-to-person spread in China is concerning.
These factors meet two of the criteria of a pandemic.
And by the way, people want to read an excellent piece.
Helen Branswell, and I mentioned her in our last episode, has a great piece in stat news
with the headline quote, “Undershining Pandemics, What They Mean, Don’t Mean, and What Comes
Next with the Coronavirus.”
From your take, why is it so freaking confusing?
The term pandemic is not particularly useful in this case because it only tells you about
the geographical spread.
It’s not actually telling you about the danger of the disease.
Like flu is a global pandemic annually, but the term doesn’t necessarily mean, you know,
very fatal or spreads very fast.
It just means it’s been into more than two geographies outside of its original origin.
So if a flu is a pandemic, that’s also endemic in that it is in our population and circulates.
Can you actually explain endemic?
Because my understanding of the word comes from like understanding evolution and Darwin
and knowing about endemic species and the Galapagos.
Yeah.
What does that mean?
So endemic is a more useful term than pandemic.
It’s something that is going to live in a latent way in the population or in the environment.
We should see a returning flu as the quintessential example of this.
It’s still an open question as to whether this coronavirus is going to become endemic.
Okay.
So that’s the difference between pandemics, endemic, and add one more name to the list,
which is misinfodemic.
I’ve read a lot of people describing this potentially as an infodemic because of the
spread of some fantastic rapid science, which you talked about last time, but there’s also
a spread of misinformation as well.
And so the two of these things are going hand in hand.
There’s a group that has already published an epidemiological model of what they expect
the spread to be.
Again, if any of the data that’s going into there is either intentionally falsified or
it is just too early.
Incomplete.
We don’t have good enough data.
Or like the measurements have changed, right?
So in the middle of last week, the way that Chinese hospitals were measuring cases changed.
So that’s going to mess up the data pretty substantially.
So I think that these models are going to suffer if garbage in, garbage out.
If this infodemic issue continues.
Okay.
So beyond the numbers and the definition, let’s quickly talk about some of the weightings.
According to the World Health Organization, some of the data from China last before this
big spike suggested that 82% of confirmed cases have only mild infection.
About 15% are severe enough to require hospital care and about 3% need intensive care.
And then preliminary data suggested that roughly 2% of the people who tested positive for the
virus have died.
And that’s important because last time we reported the CFR, the case fatality rates,
which for SARS was at 10%.
And for MERS, it was actually 37% in Saudi Arabia, but 34% outside of that region.
So last time you talked about the paradox between deadliness and the R0.
What’s your updates, if any, on that?
So the reason for that is that you can’t really have a high fatality rate and a fast
spreading virus.
Basically, dead people can’t spread the disease and people who are, you know, confined to
their beds also can’t spread the disease as fast.
But there’s another variable, which is incubation time.
So this is the length of time that it takes for the infection to demonstrate some symptoms.
And there’s a different period of time that’s called the latent period, which is the time
between getting infected and becoming infectious.
So these are two different variables.
And these interplay in a really interesting way.
If the latent time is really short, so you are infectious almost as soon as you’ve been
infected, but the incubation time is long, you have no idea that you’re infected.
You have no symptoms.
You feel completely normal, but it turns out that you’re actually spreading the virus.
So in that case, this sort of paradox between the case fatality and the spread rate is going
to break because you can start spreading without actually having symptoms.
It’s also probably too early to tell what the exact incubation period is going to be.
Most estimates I’ve seen have topped out at about 14 days, but that’s still pretty long.
So it’s something to definitely take into consideration.
Okay.
So bottom line it for me, where are we now in the situation update from the news and
your perspective?
So the bottom line is it’s still too early to put hard numbers on any of these facts.
It’s important to keep track of where the cases are coming up, where they’re being reported,
and don’t jump to any conclusions about case fatality rates, about R knots, because it’s
just too early.
Other than that, the same precautions apply.
Thank you for joining the segment.
This episode covers the following — since our previous deep-dive on the novel coronavirus outbreak — including:
- practical implications for the U.S. healthcare system given how it works today, and where we might go in the future — with a16z general partner Julie Yoo, given our vantage point in tech; and
- how the rt-PCR test works — with a16z bio partner Judy Savitskaya;
…in conversation with Sonal Chokshi.
Sources for updates at top:
- CDC’s latest briefing February 26, 2020, transcript
- WHO situation report #27 February 25, 2020 [we covered #6 and #25 on previous episodes]
Sources for last week’s episode:
- latest numbers: cases in the U.S. (CDC, as of February 17, 2020); global cases (WHO situation report #25, February 14, 2020); spike in diagnosing cases as reported in China (SCMP, Scott Gottlieb)
- situation & policy statements/reports: CDC summary (as of February 14, 2020); “Annual report on global preparedness for health emergencies”, WHO (Global Preparedness Monitoring Board, 2019)
- on definitions (of pandemics, endemics), other terms, and various naming conventions: “Understanding pandemics: What they mean, what they don’t mean, and what comes next with the coronavirus”, Helen Branswell, StatNews (February 12, 2020); on disease occurrence and levels (CDC); “misinfodemic“; best practices on naming new human infectious diseases (WHO); qPCR (Keith Robison)
image: CDC test kit for COVID-19/ Wikimedia Commons
