- Good afternoon. Welcome to UCSF Medical Grand Rounds. I'm Bob Wachter, chair of the department of medicine. We normally take July and
August off for grand rounds. And when we decided to do that in June, it didn't seem crazy. As far as COVID stood on June 1st, San Francisco was running
about 10 cases a day. Today that number is 250. At UCSF we had one COVID
patient in the hospital, never quite hit zero, but got down to one. Today that number is 41. And on June 1st, the Delta Variant made up 3% of the cases in the United States and
now it's more than 90%. So as they say back by popular demand, unfortunately we felt a need
to build in the special session to talk about where we are in the pandemic and talk about the current
surge, the Delta variant. Vaccines boosters and more we didn't think we could
fit it into 60 minutes so we will go 75 minutes
and really pleased to have two of our favorite speakers. Both who've been with us in the past and have two really important lenses on some of the key issues in the pandemic. They are Shane Crotty who's professor at the Center for Infectious
Diseases and Vaccine Research at the La Jolla Institute for immunology. Shane's lab studies new
vaccine ideas and strategies that are applicable to many diseases based on the fundamental understanding of the immune response. Shane received his PhD in
molecular biology and virology from UCSF so he's a proud
product of our system. Welcome back. Our other guest is Carlos Del Rio. Carlos is executive
associate Dean for Emory at the Grady Health System
and professor of medicine in the division of
infectious diseases at Emory. He's also professor of global health in the department of Global Health and professor of epidemiology at the Rollins School of Public Health. Carlos you must have a
humongous business card. He serves as the
co-director for the Emory, The Center for Aids Research
and Co-PI of the Emory CDC, HIV clinical trials unit. And he's really emerged as one
of the nation's go to experts on the pandemic public health aspects, epidemiology clinical care,
and is really very wise about, about all matters COVID. So I thought that the
combo of Shane and Carlos would really be perfect as we explore the various parts of the pandemic that we are grappling with. Our format will be that both Shane and Carlos will each just speak for about 15 minutes and we'll go quickly through a whole lot of new data which is emerging even as we speak. And then at the end of that, we'll have our Q&A
discussion with me and the and both of them that
we'll go for probably a half hour or so. We will take your questions. My colleague Queenie Chang
will be monitoring the Q&A box. So if you have them, please type them into the Q&A box. Other ground rules are up here, Zoom window and full screen mode. I'll get to as many questions as I can. The session is being recorded
and will be posted on YouTube tonight at about 7:00 PM. And prior episodes in our series have received over 2 million views. Just in terms of advanced planning I think this will be the
last session this month, although we'll see how things go. We'll start back up with our
regular grand rounds series on the first Thursday after Labor day, I think that's September 9th and it will also be a COVID update. This one with era UCSF,
threesome of Monica Gandhi, Peter Chin-Hong and George Rutherford. We'll then toggle into
our regular grand rounds, which will be a mixture of non COVID and COVID topics right now. COVID topics being planned for the first Thursday of every month for the foreseeable future. Hopefully not forever. So with that, let me turn
things over to Shane, to talk a little bit about
the biology and immunology and the variants. Shane welcome. - Thanks Bob. Yeah, so there's been, there's been a tsunami
of information on Delta and all kinds of different
aspects of Delta. It used to seem like
it was monthly changes than weekly changes, then daily changes. And then now there's been changes even between this morning and now. So what I'm gonna do is start with where I think we're on pretty firm ground. Things I think we understand pretty well and then work towards more
into the areas of uncertainty, even though those areas of uncertainty are some of the areas where we have the biggest questions okay. And starting from things that have certainly
changed during the summer that are relevant. So our understanding of the
durability of vaccine immunity and immune memory. What do we know about that? Well, your vaccine efficacy comes from right components of your immune system and so we can measure those individually. And so those were really
coming in four categories certainly the antibodies are important, but also these other components,
let's see the pointer. And so we know, data a good
six months or seven months, seven months from the first
immunization since the second immunization for Moderna. And in fact, there's new data on this and science magazine
that came out an hour ago, but here's the data it's basically
the same from last month. Where there clearly is durability
of antibody responses out at seven months at the same
time, they have declined. The decline is pretty
similar across age groups but it is measurable
and I think data today are maybe a five fold decline from peak. So what about T-cell responses. We've actually got the most
public data on this topic T-cell memory out at six
months after vaccination. This is in a pre-print
and isolate specifically, we were looking at the
low dose Moderna vaccine, but same general topic. And at six months after
the second immunization 97% of people still had a CD4 T cell memory. And notably it was, it was
pretty stable not much of a decline in that six month period, which is pretty impressive. So it seems like the Moderna
vaccines are doing a good job with generating T-cell memory. There's been a little more confusion about CD8 T cell memory, but at this point we know
that both the Moderna and the Pfizer vaccines
generate CDA T cells and actually the majority
of people ended up making a CDA T-cell response as well as a CD4, fewer people are positive at six months. And I think that's basically because there's actually just not a
very big CD8 T cell response so it's closer to limited protection. It doesn't actually change that much between one and six months. So we've got some, so from memory B cells and we don't have data out at six months, we have six month data for
antibodies C4 and CDH now at least for Moderna vaccines. For memory B cells we don't, but multiple groups have
reported memory B cells at two months or so after immunization and those responses look quite good. And so my prediction from
those would actually be that the memory B cells
and to the RNA vaccine will be quite robust and long lasting there's no guarantee there,
but that's my, that's my bet. I don't think that's a creative one to do just simplify this word. So that's what we know
about the immune responses, the immune rate to the
vaccines pretty good stability, I would say over six months. So, what do we know about efficacy? So here I'm gonna refer to
really the clinical trial data that's what's on this slide, right. The phase three clinical trial
data for Pfizer and Moderna. We've gotten more
information from both of them in the past weeks and certainly
in the past couple months for their six months
efficacy trial results, Pfizer reported 91%, Moderna recorded 93. And notably, Pfizer's reporting a 95%
early and out of the six month and 84% to give an overall efficacy of 91. Moderna reported 93% overall and that's where there
are question marks here I haven't seen a pre-print yet. Presumably that means that early efficacy of something like 95 and
then a six months of 90. And these are the phase
three clinical trial results those would be against D614G and Alpha and just for reference, right. These are the data sets
that are being submitted to the FDA for vaccine approval. And they're really important
reference points because these are the actual placebo control
clinical trials, controlling for lots of confounders I think. So with those data in mind, what are we looking at
going forward in terms of how long the vaccine
might last both in terms of having immune memory
lasting and vaccine protection. Well in an imaginary world
without Delta, right? And that's an easy one
to think about first and because you can directly extrapolate and it really does depend on
your definition of protection. And then it's gonna
depend on the durability of these antibodies and that's
because it really comes down to between six and 12 months
or six months, 12 months and two years do the antibodies stabilize, or do they keep declining
at the same rate? Because the data that I just
showed you in on the T-cells is that the T-cells are
actually relatively stable. So whatever they're doing now, it looks like they're still gonna be doing you know, six months from now. And the memory B cells there's no data, but my inference based on the other data is that be quite stable as well. And in the context of COVID infections let's say natural immunity,
antibody titers declined to around the six month time point and then they really
stabilized pretty well. Not completely, but maybe
have a two fold decline you know, between six months and 12 months not a big decline. And that's because it's
at this time window that really have a long
lasting response is occurring and we just don't have that
data yet for the RNA vaccine. So, you know the optimistic
look would be that it would stabilize a lot
like natural immunity and in a pessimistic view would be that it would decline at the
same rates it is already, in which case it really
wouldn't be much antibody around at 12 months. Given the overall quality
of the rest of the immunity, the rest of the memory I should say, my prediction would be
that it would stabilize a substantial amount between
six months and 12 months. And then the second point was to get at well you know, again in a
magical world imaginary Delta, would there still be protection,
at a 12 months now that we have data at six months. And really that depends a lot on your definition of protection. Are we are you talking about protection from infection, asymptomatic
only, PCR positive or you know, Pauci-asymptomatic
really cold-like, flu-like, hospitalized,
ICU or fatal, right? Each of those resulting
in different definitions of predictions about protection and this is definitely
relevant for Delta as well, which is why I'm introducing it. And to me, a lot of this does come down to the anatomy of this viral infection in the anatomy of a immunity to S. And I generally talk about
this as a viral infection in two phases, the upper
respiratory tract infection phase and the lung infection phase,
or the nasal infection phase and the oral cavity phase,
and then the lung phase and that's because obviously not only are
they different locations, but this is a virus that
replicates very fast and these are fragile new
spaces and in the oral cavity. So it's a very it's a hard, it's a relatively hard virus
to stop in those spaces because it replicates
fast and transmits fast. Whereas the lung infection
is actually relatively slow in contrast to say for flu,
whereas if it gets too long, it's a very fast infection for SARS-CoV-2, it's relatively slow, which is why we generally talk about
hospitalizations at 14 to 21 days and measuring mortality at 28 days, as opposed to these upper
respiratory tract infections in looking at sort of the six
day time window, all right. And so because of that if
we're talking about protection from infection or protection
from asymptomatic infections. Really, if you're looking out at 12 months it is probably gonna depend
a lot on the antibody titers, because the T-cell responses will take several days to kick
in and they're less likely to be major players in
preventing the asymptomatic. But preventing you know,
Pauci-asymptomatic or cold-like if it's six days to time of symptom onset, that's a decent amount
of time for the T-cells and memory B-cells to
kick in and contribute even if the antibody
titers are relatively low, you can have reasonable
protection against those. But most importantly,
like if we're talking out at the hospitalization,
ICU, fatal cases again. There's a lot more time
to protect against those every 24 hours matters a lot for speed of the immune response, because your T-cells can expand 10 times every single day essentially,
so 72 hours you have easily 1,000-fold more T-cells available. So a seven day window
right before you actually have significant problems in
the lung is plenty of time, it looks like the T-cells and
other components to respond and prevent these more severe outcome. Which still probably have antibody as a correlate of protection. So with those things in mind, you know what are the mechanisms
of protective immunity, really the simplest option
for any vaccine development it's high level long long-lasting
neutralizing antibodies and that's still true for COVID-19. And correlative immunity,
correlative protection keep pointing to antibodies
as a key correlate. And there's a new Moderna
study out yesterday, day before yesterday, reinforcing that with some
really nice calculations. But those are really talking about cases, like prevention of
cases, PCR positive cases or symptomatic cases. And we're talking about
the more severe outcomes the hospitalization level disease. There variety of lines
is evidence to point to contributions to
T-cells against COVID-19 and particularly at that level of disease. And I think it's still
quite reasonable to consider the hospitalization-
level disease is prevented by any decent combination
of antibodies, CD4 and CDB. So with that in mind, what about Delta? Right, because that's definitely
the world that we live in. This is what I said a month ago, which is not unlike what
a lot of people said at this point you're either vaccinated or you're going to catch Delta. And that's basically because
it's so incredibly infectious or transmissible, depending
on your preferred word. And, that simply based on what we've known about SARS-CoV-2 all along, it does have a relatively high level of
hospitalization compared to other competent infectious diseases. So let's start with the good
news about immunity to variants and Delta and then go
onto the not so good news. Really the good news
about immunity to variants is that the vaccines are doing quite well at generating immune
responses that are good at targeting variant
and I love this summary in Scientific American which
really kind of points out your immune system has really
evolved to deal with variants. And Delta has a modest to moderate degree of antibody escape, no
obvious escape from T-cells and in memory B cells
have been shown to have an excellent repertoire
against this virus. And one of the clearest examples of that has come from people who
had natural immunity, where they had COVID-19 cases, and then got one dose of RNA vaccines which I called hybrid immunity. And those people made huge
antibody responses but notably, they made very broad antibody
responses, antibodies that could even neutralize
original SARS-COV 1. And so that's a very good sign for being able to recognize
both Delta and other variants. And specifically about Delta it does fit into antibody
recognition of variants. Here's my favorite summary of
those from moderna actually, so here's the initial neutralization and here's Delta over here. So it's a two fold decline, whereas for Beta there's
an eight fold decline. So that's good news number one
that's specific about Delta as opposed to general about variants. And I'd say good news number two is really the Public health England paper
in the New England journal with Pfizer vaccine showing
88% efficacy symptomatic and vaccine prevention of hospitalizations and this other pre-print by
them was it equal to Alpha really in the 95% range, okay. And that, Carlos will
talk about this some more, but that's consistent with
a lot of the experience in the US of really looking like a pandemic of the vaccine. Like most deaths in cases
are predominantly occurring in counties and regions
with low vaccination rates. And that's true as well
for San Diego where I live, where that's been largely the experience. So the bad news about Delta, really the big challenge
with Delta is that it's so much more transmissible
than the original strain. It's incredibly hard to stop and really this is possibly an
unprecedented change in terms of the amount of the R knot shift. So that's the first thing it being so much more
transmissible is a big challenge. Second, is that definitely not all of the vaccine efficacy
studies agree like at all and we can come back to that later. And then third is really, you know a bit of bad news is
that why is Delta so dominant that we don't know, it really
wasn't anticipated based on the viral sequence
that Delta would become such a big deal and so I'm right near the end of it here,
summarizing the virology. How is Delta different virus? What do we know? I think there's still
a lot of possibilities there's still a lot of uncertainty here. The real world experience
is a human experiment so to speak of so many
people being infected is way out ahead of the
virology at this point. The simplest scenario that could explain why Delta is so different is really just three spite mutations that the Delta NTD is seen in
all the variants of concern and mostly in lives. The 452 mutation is an L to R. This is certainly a key mutation in Delta and it was actually originally seen in the California variant
of the California variants. Certainly important, some for escape but probably also for transmissibility. And really Raul Andino UCSF,
who was actually my PhD mentor. I think his neutralization
of plaque assays data on this virus on this mutation
still are some of the key data there that it looks like
it makes bigger plaques and it's a more vigorous virus. And then the 681 mutation. So this is also seen in Alpha and so this mutation is
important for processing of the spike into some units but also that really
sets the spring loading so essentially how easy or hard is it to, to pop that spike open and
drive the fusogenic event. And alpha has mutation at
exactly the same location, not the exact same mutation. And so it's possible that, that these are just really
key sites for the virus and Delta hit upon the perfect combination of those four for
gaining transmissibility. The more complex scenario would be to say, yes, those are important. But there are also other spike mutations in a whole series of non spiked mutations that really might be driving
fitness of this virus. And really one of the challenges
we trying to parse this is that we don't know for sure which ways this virus is
better viral loads faster almost certainly still
uncertain but symptoms faster, transmission faster, more
infectious, more viral particles, more virulent all of those question marks. There's actually still a
significant uncertainty about the partial antibody evasion is confident. And then all of those could play into this over here as well. And then these other factors
that could be driven by non spike mutations, such as
faster replication machinery, or innate immune evasion. So there's uncertainty and
really the speed of the virus affects how good the immunity is and which parts of the
immunity are important. And so our uncertainties
on the virology side still do drive some
uncertainties about immunity since it's a race. And is it a race here, here, here, and is the race the same or different, and how does it tie into disease severity? So I will stop there, hopefully
setting the table for, for Carlos, thanks Bob. - Thank you, Shane. That was terrific. A huge amount of data and I appreciate the certainty and the uncertainty, this is a rapidly evolving story. And, you know, you were one
of the handful of experts in the universe and the
fact that you were confused, maybe reassuring, maybe
not, but you know, so much. - I like to give talks when I have a, when I have a clear message, you know, and all my data in place. You prefer that I give talks when there's a lot of uncertainty. - Well, that's a natal week. We could have waited a year or two, but that probably would
not have been acceptable on other levels. All right, let me bring on Carlos. And as I said, we'll bring
Shane back after Carlos is done. If you don't have a lot of questions that you want Shane to answer,
then you weren't listening. And Carlos's talk will
bring up even more questions I'm sure. So Carlos, it's all yours. - Thank you, Bob. And thanks again for the invitation to be in your Department of
Medicine Grand Rounds. This is just a terrific event and I like watching them all the time. And I really appreciate what you've done for educating everybody about COVID. And in particular, you know, not only your grand rounds
that you post on YouTube, but also your Twitter feeds
and all the different things that are just being incredibly
helpful for all of us throughout the pandemic. So where are we in the global pandemic? Well, as you can see here we are entering what globally is called the third wave because we went down up again and down and up again right now. And we have passed a critical number of 200 million infections globally and over 4 million deaths. And I try to remind people
that this pandemic is not over. It's accelerating. You can see here that we
passed 200 million cases on August 6. You can see we passed 4 million
deaths in July the eighth and you can see in this
table how those cases went. And, you know, in the last 53 days, we accumulated another 25 million cases. And in fact, we have had
now in 2021 more deaths and we're not done with this year that we had in the entire year of 2020. So when people say, well, I'm glad the pandemic is almost
over, this was before Delta I remind them of globally it's not. Now even globally the
pandemic is very different. I'm putting two countries here. You see India one side
and Brazil on the other and you can see India
had this massive spike in March, April, you know,
April, may and then came down. And that spike was primarily due to Delta. You can see that 94% of
the cases then in India, were Delta and Delta
created this massive spike similar to what we're seeing. Brazil hasn't seen that. Brazil really has not had multiple waves. It's sort of like a mountain that keeps on getting
higher and never comes down. And you can see that their
epidemic is primarily a gamma epidemic. And you can see how nicely the sort of, they had a little Delta and then again, is being taken over by gamma again. So every country is a little different in that transmission dynamics. A lot of it are going to depend on what the prevalent
variant is in that side. Now, many people are
saying, well, you know, India came down so rapidly. The UK is coming down so rapidly. Maybe same thing is
gonna happen in the U.S. We're gonna reach a
peak is gonna come down. But I remind you that the
U.K did not come down. There was an inflection
point after a rapid descent from the Delta surge in the UK. And a lot of people are asking why. And I think a big part of it could be the fact that if you
remember the U.K had this day of independence in which they say, we lift all restrictions
we're done with this. And maybe that's caused that
they didn't continue going down as opposed to India and
other places where it did. So I caution you that what we are not in a rapid accelerated growth
right now in the U.S. we cannot say, well, you
know, once we reach a peak, it's gonna come down very
rapidly and going back to where we were before. So this is where we are now. And you can see, this is what we're concerned about is this big surge we're
seeing in our country. And it's primarily, we are
driving the pandemic globally. If you normalize cases
per million population, it is the U.S. that is
driving the global pandemic. This is where the epidemic
is accelerating the fastest. And this is why many of us
are very, very concerned And while it's growing While you can see the
states that it's growing, you know, Louisiana, Florida, Arkansas, you know, it's growing
throughout the country, but some states are really
driving the pandemic. And in fact of the entire United States, Florida has one out of
every five new diagnosis and the rate in Florida. If Florida was a country at a rate of 127 per 100,000 population, it would have the highest rate of any
country in the world. And in fact, if Florida was a country, the United States would
have issued travel warnings and travel restrictions that will not allow people from Florida to travel into this country. This is what community
transmission looks like. And currently about 70%
of counties in the U.S. are in what we call the
high transmission area. And 18% are in substantial transmission. In high transmission, being in red, substantial transmission being in orange and where you wanna be
as in yellow and blue. And you can see that not
much of the countries in yellow and blue, but this
has changed very dramatically. If I showed you the exact
same figure from a month ago, you would see a very different picture. And again, it just shows you how rapidly Delta has spread throughout our country. Now it is spreading
faster in places where hot where low vaccination rates. And you can see here the spike in cases, again, that rapid increase in cases that you're seeing in Louisiana. You can see the changes
in the, in the R knot, but more importantly what you see here is a percent unvaccinated, or if the percent vaccinated in this case, and you can see that only
37.2% of the population of Louisiana is fully vaccinated, which is exactly what is driving
the pandemic in that state and in many parts, the United States. So talking about vaccines,
let's talk about vaccines, about variants, about mandates. So this is a national
picture on vaccination and dark blue is where you wanna be. You wanna be a state that has high percentage of the
population of vaccinated like Vermont, Massachusetts, Maine, Connecticut, Rhode Island, you go down. And where you don't wanna be as in the sort of light blue area of the country. And that's, you know, Tennessee, you're truly here in Georgia, Louisiana, Arkansas, Mississippi, Alabama. And in fact, you know, the good news is 70% of adults in the U.S. have had only one have
had at least one dose. That was a goal remember for
the Biden administration. The bad news is one dose
doesn't do much against Delta. And we'll see that later. So you really need to have people who have received at least two
doses and be two weeks out. So even we are very proud in our country that people over 65, you
know, fully vaccinated. We say, well, 78% of people
over 65 are fully vaccinated. Well, in fact, the U.S. have
vaccinated fewer people over 65 than in England. So again, when we talk about
duke having done a good job, we've done a good job, not as good a job as we could have done. And I think this is a
good example of that. England has done a much better job vaccinating the older individuals than what we have in our country. This is the graph that CDC put out last a couple of weeks ago. And again, scared all of us. And it scared all of us
because it showed the how the Delta variant R knot had changed. And as Shane said, we've never seen a virus do this, right? And it went from an R
knot the ancestral strain, somewhere around two
and a half to an R knot somewhere between five and eight. And this is where, you know, CDC said, well, Delta is as
transmissible as chicken pox. I would say, I don't agree
necessarily with that statement, but that has been made as
a very important statement, but not only is maybe it's as
transmissible as chickenpox, but you can see that the
fatality for chickenpox is very low and the
fatality for this infection is much higher and that is a problem. Because when you tell people
this is like chicken pox, they say, well, you know, in
my house, when we were young, before we have vaccines, my
mom, my grandma would have chicken box parties. We all got vaccinated, we all
got infected and that was it. Well, that's not the case with COVID and using the example of
chicken pox is not helping. So why does the change of the R knot of that variant could means? Well, what it means is that if you go 10 cycles of transmission of a virus in a fully nine population, you will go, if an R knot was 2.5, you will have about
9,536 persons infected. If your R knot goes to six,
now you have, after 10 cycles, 60 million point four, point five, 60.5 million people infected. That is the difference. This is significantly important. And people don't realize what the impact of that change in R knot does. The other thing that it
does, it also changes your heart immunity dramatically when the R knot what's 2.5, we said, well, 60% between infected and vaccinated, it gets us to herd immunity. When you got to an R knot of six, your herd immunity threshold
is somewhere around 84, 85%. In other words, a place
you're unlikely gonna get just by asking people to be vaccinated. Now, this is the case it's in the U.S. at that as percent of the
population vaccinated. And you can see a very nice relationship between those states with
low vaccination rates percent of the population vaccinated here and those, the hike accounts, the seven-day case gone
per 100,000 population. And this shows you very nicely
that that correlation exists, but even in states with
very high vaccination rate, and remember I said, an R
knot needs to be somewhere in the order of 80% or so you're not going to get there yet, even in states that were
doing very, very well. So mandates are appearing and
many healthcare institutions are issuing mandates. I only put this there because
there's a pretty good website run out of Brown in which
they are trying to track healthcare institutions
that are issuing mandates. And I would encourage
if your institution is to use the form available
there and complete it. But more importantly, companies
are requiring mandates. And you can see here,
this is from August 7th. There's a list of companies
that at that point in time had issued mandates. There's even more companies right now. But I think the going
phrase that we're hearing over and over is no jab, no job. And I think mandates are
gonna make a big difference and it's gonna be corporate America that is gonna do that. Unfortunately or unfortunately, there are many people in
America that are employed outside of corporate America. Corporate America employees are about 145 million individuals. So we're gonna get
mandates from other places that are outside corporate
America, such you know, educational institutions. And we're seeing that from
colleges, universities, and other places, but we may see them go down to
high schools or junior high, or even elementary schools. So will vaccines work
against the variants? The short answer is yes. Here's this graph recently put
out by a colleague of mine, BK Tijani, and again, you can look at it. What she's trying to
show you is the different you know, variants of wild
type alpha, beta, gamma, Delta, and the efficacy of different vaccines and whether you get one shot
or two shot, and what happens. And you can see that some
of the problems is we have a lot of data missing, and
we have a lot of variability. So Eric Topol put recently this out, and I think couple of things here is that you first see this all over the place, you know, public health, England, the article that was mentioned previously Pfizer, 88% effectiveness
against a Delta variant Astrazeneca 60%. I think what some of us
are getting concerned about is the data coming out
below that from Israel, from the REACT study, from the Mayo clinic
recently as a pre-print, from Qatar showing much,
much lower vaccine efficacy. So I'm gonna focus on the Israel study with 39% vaccine efficacy. And I wanna reassure you that the decline on vaccine protection
against Delta infection reported in that study did not impact hospitalizations and deaths. And you can see here while
you had symptomatic COVID with the vaccine efficacy of 40%, the vaccine efficacy against
hospitalization was 88%. And the vaccine efficacy
against severe COVID was 91%. So emphasize this
because people say, well, it doesn't work. Well, it still works against some of the most important
outcomes that we have, which is hospitalizations and deaths. So how about breakthroughs? Or, you know, big sort of a
turning point in breakthrough as Paul Sachs call it
sort of the case study is the Provincetown outbreak that occurred during the 4th of July. A weekend, in which what we've heard is several things is that many of the cases were fully vaccinated. Those fully vaccinated cuts
cycle thresholds very similar that those spaces who are not vaccinated cycled thresholds about
22 and people, you know, said this is very concerning. And in fact, this is what led CDC to change their masking recommendations. But a couple of things
that haven't been said, people interpreted this
outbreak by saying, vaccines don't work. This was a stress test for vaccines. And to me what this shows
exactly the opposite, the vaccines worked. Because they work because
out of those thousand people or more that have now been
traced back to this outbreak, five had been hospitalized
and non has died. So the vaccines were highly effective in protecting against
hospitalization and death. This is summary again from Eric Topol, who does this great
tables of the different Delta breakthrough studies. I'm not gonna go through them, but suffice to say that
outbreaks that breakthroughs aren't gonna happen, and we
need to get used to them. And that, you know, the risk is calculated
that your risk of getting COVID disease if you're fully vaccinated it's eight times lower than if your not. Your risk of getting
hospitalized is 25 per lower. And your risk of dying is 25 per lower. So we're trying to educate
people in our state, the department of health here in Georgia recently did this graph, which I don't totally like because the 24 should have been a little dot down here, but they try to say
that a 4 million people fully vaccinated, a lot of, little bit under 5,000
have tested positive, 118 are hospitalized
and only 24 have died. So your chance of dying
if your fully vaccinated are somewhere in the 0.00058%. Again, emphasizing that
the vaccines are working because when you hear about breakthroughs and you hear about low effectiveness, people are saying, well,
why should I get vaccinated if it doesn't work anyway? We need to say they do work. The other positive study
that is still in pre print has not been formally published is this coming out of
Singapore showing that yes, while people have
similar cycles thresholds between vaccinated and unvaccinated, what you see in the vaccinated
is a much rapid clearance of the virus. So the immune system is doing something in rapidly clearing the virus much rapidly than in those that aren't vaccinated. So we really don't know, yes, you have similar cycle
thresholds, but for how long? what are the kinetics? And what's that gonna determine? So I have to end by
quoting my good friend, George Rutherford, which says, you know, "If you're vaccinated, this is nothing. If you're not vaccinated your hosed." And I couldn't agree with him more. How about our children? Well, you know, the single
most important thing parents can do is to get vaccinated and to vaccinate all their
kids who are 12 and older. And masks are the second most
important thing we can do. Universal masking of
children over the age of two indoors, including in schools
adds an additional protection. And to me has been very distressing how much politicized we have made the mask to the point that in many states, you know, local state boards
have been prohibited by to, to have mask mandates. And I think that's a travesty
that simply just, we, you know, I don't know
why is it happening? I cannot even believe it. So will we need booster shots. And my answer is no, not at
this point and not everybody. And I just point to there an
editorial I recently wrote in the New York times about this. There are gonna be needs for
boosters for some people, but you don't need to go out there and run and get a booster. As I remind people, I'm
62, I'm fully vaccinated. I got vaccinated in
December, early January. I'm not out there running,
looking for a vaccine because the people I'm
seeing in the hospital are unvaccinated individuals. So in summary, I think vaccinated persons are much safer than unvaccinated persons, but
they're not completely safe. Breakthrough infectious
occur often enough with Delta that you will see them. And the frequency with which
a vaccinated person transmits it's not clear. So we're hearing well, vaccinated persons can get
infected and can transmit true, but we don't know how much they transmit. And I think that's an important component. I think masking indoors is important. It needs to continue to be important. And I remind my friends
that most of us ID docs never stopped wearing mask indoors after the third surge even after CDC said, oh, you no longer need to mask. And this is indeed a
pandemic of the unvaccinated. And it's really time to
have vaccine mandates because by asking people
to get vaccinated, we are not gonna get to a
level of vaccination we need to really get to herd immunity. In fact, I don't think
we're ever gonna get to herd immunity against this pandemic. And with that Bob I'll just
acknowledge some people that have provided slides and information, and thank you for your listening and happy to answer any questions and have the discussion we talked about. - Thank you so much, Carlos. That was terrific. An enormous amount of information
in a short period of time and lots of fodder for discussion. So let let's start. Oh, even where to start. This issue of can a breakthrough infection of a vaccinated person transmit? You have these sort of
competing pieces of data. One that the viral load
seem to be similar, or the other that maybe you're you clear the virus more quickly. Is it fair to say that
we're fairly confident that, that a vaccinated person
who gets an infection can transmit maybe at
a slightly lower level than an unvaccinated person? Is that how you interpret that? = The way I would interpret it Bob is I will say a vaccinated
person can transmit yes, but as for a shorter period of time. So there are time. The number of days that are infectious are significantly lower. And therefore, if that, you know, especially that information
from Singapore is repeated and I've heard from a couple of people that are doing similar studies
are getting similar results. So I would say, yes, you can transmit, but you transmit for a
shorter period of time. And therefore your
contribution to transmission is much lower if you're
vaccinating that if you're not. - Okay, Shane, I don't know if you're on, I don't see you on my screen. So in terms of, there we go, in terms of how a vaccinated
person should feel, there's just seems like a
lot of ambiguity in the data about how likely it is that
you will get an infection. And Carlos, you made the point that, that even if you get an
infection, very likely to be mild, not to lead to a hospitalization
and not to lead to death. But I guess there are two things that have always weighed on
me as a vaccinated person. One is, can I transmit it to others, the second is, can I get a mild case that might lead to lung COVID? And you know, I'm gonna
approach this differently if I know I'm gonna have a mild, like, like a cold for three days, then if I might still have brain
fog more than I usually do, I'm sure half the department
is saying to themselves, you know, six weeks out or
I'm gonna have headaches, or I'm not gonna be able to
smell or taste two months out. So we already talked
about transmissibility. It sounds like, yes, you probably can maybe for a shorter period of time. How about lung COVID, do we
know anything about that? And maybe both of you
might wanna weigh in. Shane you wanna start? - Carlos, you wanna go first? - Well, I would just say I
was gonna pass it over to you because I think my feeling,
my gut feeling is that you're less likely to get lung COVID once you've been immunized,
if you get reinfected, because what the data that
is beginning to emerge is that a strong immune response is actually sort of
protected for lung COVID. So having some degree of immune, I look at re-infection with COVID,
especially mild cases as infection limiting to the nose and the upper respiratory system and not going systemically,
not going to the lungs. So my gut feeling is you're less likely to get lung COVID. - Less, less, but not
you're impervious to it. - Yes, again, because
you're not impervious because some people who get reinfected develop severe disease. - Yeah. - But if you have a mild
case, I don't think, I don't think if you got a
URI kind of nasal congestion with reinfection, you're
gonna get lung COVID, but maybe Shane you think differently. - Go ahead Shane. - Oh, I mean its, I think
it's a really hard question. And one that, again, there
isn't much solid data on. I fully agree with
Carlos's intuition that, that in general, a truly mild, not simply mild being
defined as, you know, it didn't have to go to
the hospital, but you know, really post symptomatic,
little cold like symptoms. And for a short period of
time is unlikely to result in longer term sequela and than other infections
of a similar magnitude. I think the big unknowns are, is the, what basically what is
resulting in lung COVID right? Is it essentially a
really extensive infection for a long while that caused
damage in various places, that's still been difficult to define and then thus is a result of magnitude and duration of viral load or a certain types of
immune responses to that, which for example, would be autoimmune, which has largely been seen
in people with severe disease. So again, less likely substantially, less likely in virus that. I mean, I think people have
highlighted that there, there is the healthcare
workers study that said that some people would
break into infection, still had some symptoms six weeks later. And my understanding was that
a big caveat of that is that there's not a control group there. So it's sort of, you're always gonna see people reporting symptoms to a survey so that that's certainly not my wheelhouse for how to control for
that kind of variable. - Right, I mean, that
was a study out of Israel from two weeks ago that a
roughly small number of people had breakthrough infections. 19% still had symptoms, six
weeks out, no control group. So hard to know if you've
just asked random people, do you have headaches or have brain fog? Some would probably say yes. So it is tricky to adjust for that. - I'll be most interested in
seeing the Inazuma numbers for breakthrough infections. I think that's gonna be one
that's pretty quantifiable. And the duration of that, you know, it could be that that's
a pretty clear-cut one. So far the ones that I've
heard have been transient. - Yeah, got it. Carlos, you said herd immunity when you do the fancy math,
you say, we might need 80% of a population vaccinated, and then you said we'll never get there. And is that because the vaccine
efficacy to get to that 80% has to be 100% efficacious or the vaccines are not 100% efficacious
then more has to be higher? I was struck by that in San Francisco 'cause we're the most vaccinated
major city in the country. We're 70% of all people, including kids are fully vaccinated. And we're seeing a
pretty decent size spike despite you know, numbers that are not that far off from 80%. - You know, I think it's because the, I think it's because of efficacy. And I think you have a combination of, I think you know, the
numbers of herd immunity are predicated on the
basis of full protection. You know, they come from
measles and other diseases where the vaccines are highly
protective against infection. I think when you start
seeing the drop in efficacy, David Paltel had a paper
this morning actually, or yesterday in the mid
pre-print that I didn't mention, but I'll mention now. And he did some modeling and said, you know, talking about
college campuses and opening and talking about the fact
that if you had a vaccine with, you know, you had 90%
coverage with a vaccine about 50% efficacy, which pretty
much where we could be, you will still have enough cases in campus that you can open and
you will be, you know, you can open safely, but it's gonna be an ongoing transmission happening. You mean you're not gonna
have, you know, outbreaks, but you're gonna have ongoing cases. And I think that's what that may be. I think we need to start
shifting our thinking from eradication and disease
elimination in COVID anytime soon to more disease management,
the way we think about flu. - So let's talk about
boosters for a second. If you have somebody both said that, that the good news about the vaccines is they still prevent you from
getting very sick and dying. The bad news is some combination of maybe waning immunity over time. Although it's Shane said
not a ton, but a little plus Delta being a nasty ear bug is leading to efficacy numbers
that are very different than the ones we thought
we were dealing with. You know, nobody's talking about
95% total efficacy anymore. We're debating whether
it's 50 or 70 or 80. If that number could be
boosted back up to 80 or 90% efficacious with a booster. And I don't know whether it can, but what's the argument against boosters. Is it just limited resource? We wanna concentrate on
vaccinating, unvaccinated people, limited resource we wanna send
vaccines to other countries that have no one vaccinated, or is it just on an individual basis would you say there isn't
a strong enough case for me who got my Pfizer vaccine
seven or eight months ago if I could walk down
to the Walgreens today and get an extra shot that I
should, or shouldn't do that? Shane why don't you start with that and then we'll turn to Carlos. I know it's a lot. (laughs)
- Yeah, okay. So where I normally start is top-line the boosters are gonna
work first of all right. So, so there's clear immunogenicity, clinical trial data from
both Moderna four months ago and more recently from Pfizer that certainly the RNA
vaccine boosts will work. And also RNA vaccine boosts
on top of an Astrazeneca are boosting really well. And that those boosts take people up to the same antibody titers
to the head before, or maybe twice as high, but also better breadth against variants. And so there are, there are
positives about that and, you know, your immune system, your immune system is always dealing with immune memory duration
of protection, right? It is a cost benefit analysis, right? Is it really worth
making that much antibody for several years? And so every time you get
reinfected or re-exposed by a booster, your immune
system is reevaluated, right? So if something shows
up three times, right, I.E the third booster immunization, your immune system is likely
to make a more durable response to that because the information is right, the initial responses weren't enough. And given the quality of the immune memory I think those things will happen. So I think first of all, in the short term booster immunization certainly
make better immune responses and take them up to higher
levels than they were. And they probably also will drive better longterm immune responses. Then you get into, do you
need them, then it becomes, yeah, what's your individual goal and what's the public health goal. - From where you said the little doubt that they would
work to make you more immune, is there any doubt that they would work to decrease your risk of transmitting? - No, I think they would. I mean, to me, even for Delta the data, even for example, out
of some of the studies that Carlos highlighted, right, that were showing less efficacy, the efficacy at early time points, even against just having a positive case when it was still pretty,
was still pretty high. So I think if you got the boost and the efficacy would be
back in the 90% plus range and it probably would stay
higher for longer, and yes, would reduce transmission. - So it sounds like
the, you know, the real, the only the, maybe the argument against really is this public
health trade-off argument, not so much at an individual level, Carlos, but what do you think? I'm kind of grappling with
this 'cause, you know, we hear about there is
enough vaccine around obviously theoretically send
it all to India today but - You know, I think we
have plenty of vaccine in our country. And I think there is there's problems in getting vaccines globally. Sending vaccine is not
going to be sufficient. I think in a letter that many
of us wrote to administration, what we need is, is to really ramp up production
in other places globally 'cause just sending vaccine
it's a little bit like, you know, trying to, you know, take care of the damage in the Titanic, by having a bucket and
getting water off the ship is just not gonna do it right. So you need to really ramp
up and you need to therefore release some of the
patents and restrictions and allow those vaccines
to be produced globally at multiple facilities. But that's another story. I mean, I think the approach
to the global vaccine shortage is it's an issue of equity, but it's also an issue of logistics, distribution, manufacturing, many other things that
go beyond, you know, I don't wanna fall into this
thing that many of us have, you know, when our parents
were little, somebody will say, you know, you got to
finish your food because kids in India are not eating. Well, you know, that's not gonna make the difference to the kid in India not eating the fact that I finished my food or not. So I think we need to
also realize that that, that solution I'm saying, well, we should wait and not do that. However, I do think there is a, an important where the WHO
director is asking for it by saying, let's put a pause on boosters as he's trying to put attention globally. And from the companies and trying to get at least 10% of the population
globally vaccinated. I get very concerned that
colleagues overseas for physicians or healthcare providers
are still not vaccinated. People over 60 are not vaccinated in many countries, they're dying. We need to get those high risk individuals vaccinated in those countries
before we start doing, you know, giving them boosters to 16 year olds in this country, right? Now, do we need to give additional doses to people in this country that are severely municipally,
compromised, older individuals? I think so. And if we haven't the
vaccines we ought to do it because that's the right thing to do. But I just don't want, you
know, to have a 30 year old, you know, relative of mine saying, oh, you know, I need to get a booster because this is what
everybody else is going to do. And I think that's, what's gonna happen. I also will say that I think Bob, and this is something that
I've been thinking lately, that quite frankly, one of the reasons the FDA may be delaying the approval of the
vaccines is in fact that, because as you know, once the FDA gets full approval of the vaccines, they can advertise the
vaccines in television, but they can also make
them available for sale. And that at that point you will, you know, right now you've got a booster you're essentially violating the EUA. The EUA has not written to give boosters. And that's what the FDA wants
to do to change the EUA. But once they get full approval, anybody can walk and get an
additional dose of vaccines. For that matter of me, I,
as a physician can say, well, my ten-year-old, or I
couldn't give them vaccine, I'll do it outside the
range that it's allowed. So you will start seeing
things done with the vaccines once they're approved that
you're not seeing right now. And I'm thinking that that may
be part of the FDA thinking of why wait on the approval. - But just in terms of the,
you know, you're my age. I assume you got vaccinated with an mRNA. - At the same time. - More than seven or eight months ago. Let's put the global
thing aside for a second. I understand we shouldn't exactly, but it's in some ways
a different question. If you got the call from
CVS today that we got extra Pfizer and Modernas,
you can get a third shot, would you take it? - I'm not ready to take a third shot. I don't think I need it. I think of how it was, you
know, not 62 but 72 or 82 I may, it may be a different situation. Or if I was receiving a biological, if I was a transplant patient, it may be a different situation, but given the fact that I'm
otherwise a healthy adult and I'm 62, I'm not running out there to get a shot right now. - Okay, great. Let's talk for a second
about what you both do. We've got a few questions about that. So how, as Delta's become a thing over the last couple of months, has your behavior changed in
terms of restaurants travel, going to a sports stadium or going to some other
place with a big crowd? Do you wear a different mask than you did if you do wear masks going indoors? Shane, do you wanna start out? How has your behavior change
in the last couple of months? - Sure. I definitely went to not wearing a mask, like essentially the,
between time, so to speak. - The magical month that
was kind of okay, right? - In most situations, unless I was indoors in
a place where I thought there were lots of unvaccinated people, but now certainly at work
as of several weeks ago, we started having, I loved
having our in person lab meetings and I'd say two weeks ago, we went back to having masks
at in person lab meetings. And around then I went back to yeah, N95 indoor spaces the K95, the easy ones and starting next week,
we're going back to remote lab meeting, Zoom
lab meetings for awhile for a couple reasons related to that in terms of personal well, I was, I was doing a, my daughter's about to go to college. So we did a little holiday
past couple of days. And so we went, we ate
at restaurants outdoors, and we were mostly
stayed in outdoor spaces. We had to take a ferry. And on that, I sat indoors with N95 on. I haven't gone to any large
events and don't plan on it. I guess I've had older relatives who were gonna go to an
indoor wedding, you know, decent size in the coming weeks. And I said, you know, if it's
important to you go, but, but otherwise that's, that's not a good, that's not a great spot to, yeah. I think given some of the
uncertainties still around and in terms of boosters, I'm not, to answer the booster question, which I think ties into the same thing. If I was offered one today,
no I wouldn't take it. But for relatives of mine who
were over the age of 65, yeah. I'm keeping, so keeping an eye on it. I definitely think it's appropriate for, for certain at-risk groups
to be offered at this point, I think for sure. And then how big that group should be, I think is the question. - Okay, Carlos, what, how's
your behavior different? - Well, I will start by saying that there's a couple of
questions in the chat around if, asking me, well, would
you do the same thing if we had J&J, had received J&J? And since you and San Francisco
have already gone into giving boosters to people with J&J I would say, yeah, I'm a
little more anxious about J&J. And if I had just been received J&J I would be looking for another
vaccination on top of that. Having said that - Just to make clear would
be, it would be an mRNA. It would not be another J&J right? - Yeah, it would be an mRNA vaccine. Having said that, when I look at the, and I think we're gonna
learn a lot from this mix and match studies, and having said that it's not
like the hospitals are full of people that got J&J. When we look at the people admitted, it's equal, it's really no different than what actually the distribution of vaccinated people in the country is. So again, we're not seeing
more failures with J&J more clinical failures with J&J. But there is clearly a lower, you know, so the dropout higher drop in neutralizing antibodies
that you see in J&J at least documented by some people so then conflicted information, The, personally, so I
started going to restaurants and then the, during that magical time, I went to a couple of restaurants and then I stopped going
to restaurants again, I'm going, I will go to restaurants. I went to one last Friday. It was indoors than outdoors. But I went in at 5:30 in the
afternoon and my wife said, why are we going so early? And I said, because there
will be nobody there. And indeed we were the, we
were the only people there and it was totally safe, right? - It's 'cause you're in
Georgia, not Florida. In Florida 5:30 is late for dinner. - Right, right, in Georgia
was, you know, I knew, I knew there would be
nobody at the restaurant. So it was fine. But if I had gone there at
eight or nine o'clock at night, I would have not gone indoors. I would have felt totally uncomfortable. You know, my work, we were, you know, we're all in wearing masks all the time and my research team
and that hasn't changed, but I do, I would have liked to have more in-person meetings with
my administrative staff and my office staff. And we're back to doing virtuals. I'm still traveling. I've done a lot of, you know, traveling even throughout the pandemic, not a lot, but some traveling,
even throughout the pandemic. You know, I did a podcast
for Shea last week about what do I do when I travel? And again, I think we haven't talked about the value of testing, but
I think mass, you know, eye protection and testing go a long way in protecting you when you're traveling. And again, the problem with traveling is not getting on the plane, it's what'd you do after
you're traveled, right? Because when you get somewhere, you go to restaurants and
you're gonna do things that are putting you at higher risk. - So how does that test that? It sounds right, but trying
to integrate that into a plan, I get asked all the time. I'm gonna go, I need to
visit my elderly parents. I'm gonna fly, I'm gonna wear an N95 and be super careful in the airport. I'm gonna get there, should I be tested? Yes, no, when? Given those dynamics it's tricky. - So what I do is a 72 hours
before I got on the plane PCR test, if I can, and then I take one of those rapid tests and I take them with me. And when I arrive to my destination, I do a rapid test. And then I repeat a rapid
test five days later. - Okay. - And now the Rapid tests
are readily available. I think it's a good
approach to try to detect if you know, if whatever
reason you got infected. And I was doing that a lot more, even when I was traveling
and there were no vaccines, I wasn't vaccinated. I would tell you that
was a big drop for me with the first trip after I was vaccinated as the first time that I got
on a plane without an N95. - Got it. All right we talked a tiny
bit about the kids in schools. The questions comes up all the time. So one question from
one of our viewers was, I think Shane said, and we've
heard this more and more. You're either going to
get immune from a vaccine or from COVID. Is that true for kids and
the kids who are under 12, who can't be vaccinated now, at least for the next several months? - Yeah, I mean it's just,
it's so transmissible it's I mean, certainly if they
mask everywhere, stay at home. - But if a 12, if a 10
year old is going to school and wearing a mask carefully and the school is being
careful, let's say every, all the teachers and staff are vaccinated what would you say to the parent today that your kid is still
fairly likely to get COVID or maybe with those steps, you can forestall this for several months until the vaccine comes. - That's a good question. I don't know. - That's probably the right answer, right? Carlos, what would you say? - You know, I think we should
try to do as much as we can to protect our kids. I'm worried that a lot of
kids are gonna get infected. I also worry, I'm already
seeing it among our employees and people are, I don't know
what you guys are doing. I'll be very curious and knowing Bob, but young faculty have
kids going to school. Kid is now having the sniffles. And does that mean that
everybody has to stay home until they get tested and what's gonna do to absenteeism. And, you know, I need somebody who needs to work in the wards and do we need to
substitute for that person until that person comes? So those are all new things that we're trying to look at what to do and come up with ideas to
make testing readily available for that kid and make
things easy for that parent. Otherwise, if you go by standard
public health practices, you would put everybody in
quarantine until you had the test and people knew, and the
absenteeism is gonna go crazy. So I do think that part of the protection is having testing
available at home, right? And being able to do that testing. So, again, that parent with
a kid with the sniffles can know my kid has COVID has to stay home and we got to put them
on isolation at home. Or my kid is fine can go back to school. Because we have, you know,
we talk a lot about this, this cultural present ism
we've had in our society that we go to work sick, but we also have this culture
of sending kids to school when they're sick. I mean, all of us, I'm sure at some point in time in our lives, we gave a kid a couple of
Tylenols and said, you're fine. You're gonna go to school. And we need to make it easy
for people who have kids who's potentially sick, not
sending that kid to school so we can prevent
transmission in the schools. 'Cause I think when you look at there's a lot of the data coming out, a lot of the transmission having said that is not happening in the schools, it's happening in the house. The biggest risk a kid has is the parents are not vaccinated. - And the tests are reliable now, reliable enough that you use
them as a kind of dichotomous. If you're negative, you're good to go. If it's positive, it's real. - Well, I think, you
know, again, that depends, the tests are pretty
good if your symptomatic are not as good of your asymptomatic. And some of the concerns that people have are not the false negatives,
but the false positives, if you test positive in a rapid test, you should go ahead and get a PCR to be absolutely sure that
it's true, a true positive, but I think they're good enough. And, you know, (indistinct) Dave Paltel wrote a paper in JAMA open network, couple, you know, last year, sometime talking about, again, returning
to colleges and saying, if you had a less test
with low sensitivity, but you do it frequently enough, you will be able to detect individuals. You can use them for surveillance, and they may not be great for diagnosis, but they're really good for surveillance. And they're really good
for sort of a, you know, screening of individuals. - Okay, Shane, you talked about the, what we know about immunity and whether it wanes after vaccines, have we learned anything recently about what happens to immunity over time for after natural infection? 'Cause obviously a few
people are gonna get immune one way or the other, a lot of people are gonna get immune through natural infection and the end game here depends
on how long that lasts. - Yeah, there are aspects of it certainly to me the numbers that I
see that seem reasonable, were probably 20% of the U.S. as has been previously infected. So, you know, in theory, you can, you can add that number
on top of the vaccination, number four for assessing herd immunity. And so how long does that last, if we lived in a magical
world without Delta, it still looks to me
like that immunity lasts against the alpha and other
things for quite a while. There hasn't been any
big, big shift in that, but for Delta there's very
little information at the moment. And so I very much agree
with the recommendations by, I think by most of the
scientists and doctors who have studied natural immunity that the recommendation is
go get a dose of RNA vaccine and again, then you'll have
really fantastic and broad antibodies better than a regular
vaccinated person, right? Against variants and that also
deals with, I think the major uncertainties about natural immunity, where certainly plenty of
the people that talk to me about them having natural immunity I'm like, okay, so did you
have a PCR positive test? And they're like, well,
no, but I, you know, but I got sick and I'm
pretty sure it's, COVID. I'm like, that does not count
there's way too much of that. And so people behaving as
if they're naturally immune, when in fact they caught something else, it's definitely a big problem. So if you really did
have a PCR positive test and were antibody
positive, that's one thing, but a lot of those aren't. And so I still think a blanket policy of people getting a vaccine post-infection makes sense all round. - And are you, the FDA has not said you can get away with a single shot they're still saying even
after a documented infection, what you need to do is your sense that you really only need one and that would be the right call? - Yeah, that is my sense. My understanding is that there are complex reasons the, the FDA or the CDC wouldn't change a requirement like that, including what I just referred to is how do you define somebody
with a previous infection? And even if you were PCR positive, we did the test and where, where you see a positive
well by what test? I mean, it gets complicated. And so that's, their
reasons not to get two doses would be just sort of the added complexity right of going back twice and
concerns about reactogenicity and really the reactogenicity data in the actual clinical
trials and the Pfizer and the Moderna clinical trials, but particularly on the Pfizer. Essentially, there was more reactogenicity after the first dose, but
less after the second dose. So that overall people who had evidence of previously been infected essentially had the same reactogenicity as people who didn't but it just, it was much more tilted to the first dose and the second dose. And so places that are requiring
or recommending two doses, it's still okay because it's really not, if you're not adding risk. I think though (indistinct)
with the boosters too, right? 'Cause they're like, well, you know, you're certainly gonna have
reactogenicity to the booster. How much is that? Those studies have been
pretty small, right? They're just immunogenicity
trials of like 50 people. So going back to your question
of why not do it, right? It's like, well, that's
still fairly limited, right? Reactogenicity data. And I was trying to answer
the question you asked, right? As I fully agree with Carlos's stand which is more the flip side
of do you need it, right? There's sort of the, will it
help versus do you need it? And those are different I'll stop. - Thanks, Carlos. - I think one thing that this issue of, vaccination after you
had PCR proven COVID, it's interesting, right? Because the Europeans are
accepting COVID plus one dose as being fully vaccinated. And in fact I was called
by somebody I know from Spain saying, look, I have COVID I got one
dose I'm fully vaccinated. I would like to get a second dose, but the span, in Europe,
they won't give it to me because they are considering
me fully vaccinated. And that's gonna create
some interesting challenges. Because for example, we hear that administration
is soon gonna require that international travelers be vaccinated well for the Europeans, that
person is fully vaccinated, for the Americans that person is not. And so even deciding who's
fully vaccinated is different. And I think that's gonna create some interesting policy challenges. - I can - Definitely practically speaking those people are certainly immune. - Absolutely. - And they're probably
about the best immune people you could possibly have
standing next to you, you know? - Right, and people have asked me this, it doesn't matter which
direction this happened. So if you got vaccinated, then you had a breakthrough infection, is that as good as if you had an infection and then you get vaccinated? - There's no data to my knowledge. So it's definitely quite
impressive if you've, if you've had an infection
and then you get vaccinated, certainly at least with the
RNA vaccine, single dose, those are phenomenal responses,
high quality, high quantity, probably very durable. The reverse would happen with
a breakthrough infection. The speculation actually
from my side would be, it wouldn't be the same magnitude jump, but the speculation would be that the downside of the vaccine is that they're creating
circulating immunity, not local immunity, right? And the deal with natural infection is, well, your body knows this
is where you were infected and so it keeps some memory there. And that probably helps explain why is it that people
with natural immunity actually don't get very many infections, even though their antibody titers are substantially less, right? It's good and that's
probably this local immunity plus the T-cells. Also now if you get a
breakthrough infection, maybe it does actually pull
that fit those vaccine T-cells and every piece that was
in antibiotics to be like, oh, this is where the
immunity is more valuable. And then to leave that. So not necessarily a bigger magnitude, but a location, location,
location solution of that second exposure. - So we only have a few minutes left. I wanna have you both end with what you, there's a wonderful
article that Ed Young wrote in the Atlantic today about
sort of the end game here and how that's going to look and feel. What is your sense of life
six to 12 months from now and how likely it is that
we're gonna be talking about a different variant that's
even worse and nastier than what we're currently dealing with? Shane, do you wanna start with that, then we'll finish the Carlos? - I'll stick with the variant part of it. So there's several aspects. So one is, is there a
variant that's gonna escape vaccine immunity? 'Cause I get that question all the time. And my answer is no, which
I think Carlos gave as well. And my answer for that is
that all the mutations, it keeps being the same
mutations that show up in terms of antibody escape, and we and others haven't
really seen any signatures of T-cell escape. And so far it really doesn't look like this virus has many ways
of evading immunity, adaptive immunity. And again, the vaccine listed immunity sort of keeps getting broader and broader with each exposure. So those things look good. But also in the Delta
showed that this virus can really get a lot more transmissible. And again, those questions that I listed as of the uncertainties about
why is this virus right, spreading so much better? Those are still big unanswered questions for looking at how worrisome
will variants be in the future. So basically if the more,
the higher, the viral loads, certainly the harder it is for your immune system to control it, the more infectious the virus is, the more, the harder it is for
immune system to control it. So it's not that the virus is specifically escaping some
specific thing, right? It's just overall a tougher virus. So I do think we have to
get some of those answers on Delta before anybody
who says, well, you know, alpha happened and then
Delta, why not something more problematic six months from now? At the moment I can't
are you against that? But like I said, in the
slides, if the simple answer, if the simple scenario is really that it's the 452 and the 681, which are actually
mutations that we saw before and just that combination, then than maybe the virus doesn't
have too many tricks left, but it's hard to bet
against that at this point. - Right, right, right, right. And that's been a good
point for 18 months. Been hard to bet against the
virus being pretty smart. Carlos I'll give you the last word. What do you think the
end game looks like here? - Well, you know, I would start by saying
that pandemics end. You know, we've had, the history of humanity has
had pandemics multiple times and whether you read about the 1918 flu or you read about the plague or whatever, they may last X number of
years, per pandemics scan. And so I think that at the
end, when the pandemics end it's not up to us politicians, you don't decide the virus
or the pathogen decides and the immune system and that complex those pathogen interactions. So the one thing is, is not to, it's not gonna end the day we want. And I can think about, I was talking to somebody this morning. It reminds me about George
W. Bush standing in front in an Earth Craft carrier saying, you know, mission accomplished. You can't do that. And I think Biden made the
mistake of coming out in July 1st and July 4th and saying, oh, this is day of
independence from the virus. Well, you know, that's not his call. And I think that was a mistake. I think that controlling this pandemic is gonna be very challenging, especially with a virus
with such a high R knot. And I think it's gonna
require lots of vaccination, mandates, lots of ongoing vaccination. It's not just a one way vaccination, there's new generations happening. I think about, you know, how many years we continue
vaccinating against polio and measles, despite the fact that we don't have the disease. So we need to remember that, that this may become part of
our routine immunization scheme going forward for many years,
until we finally control this. I think we're gonna see eventually levels of population immunity that are gonna turn this
virus from a pandemic to an endemic disease very much like what happened to the 1918 H1N1 flu that eventually stayed
there in the population for long periods of time. And I think that a lot is going to depend on really how our society behaves 'cause at the end of the day, behavior is really important and human behavior is very important. And you're gonna see societies where the virus is well controlled. You know, where, you know,
in the Orient in Japan, where all the kids are coming
to school wearing masks, and they're not gonna have outbreaks. And then you're gonna have
outbreaks in states like mine or Tennessee, where you
have this school districts where kids are not using
mask and everything is crazy and there's no mandates and
all sorts of things happen. So I think a lot of it is gonna depend on local factors and behavior that have little to do with
the virus and the host, but it has to do with
how transmission happened because of behavior. And I think the last thing
that worries me the most Bob is for, of us working in HIV, we saw HIV start as an
epidemic in our country, primarily impacting, you know, you know, well to do middle class gay men. And then the pandemic in our country has become a pandemic primarily
of the poor communities and the underrepresented communities. And I worry that this pandemic is going to do something similar, right? It's gonna become an
issue of San Francisco and other cities and high, you know, high-income individuals, high vaccination, we're gonna be doing fine. And you're going to see, you
know, minority communities, underserved communities that are gonna be in the front lines,
having a lot of disease, a lot of transmission and
low vaccination rates. And I think again, health inequities are gonna be a major factor in determining
how we end this pandemic and what we do. So by saying that is, we need to really focus on health equity, not only globally, but locally. And if we don't do that, I think the pandemic is gonna hang around for a lot longer than we actually want. - Yeah, well, thank you both, you know, the breadth of the conversation, everything from virology and
immunology to health equity, to behavior, to politics, it's part of, what's been so fascinating and challenging about this. There's no one discipline
that you need to work. You need all of them to work together. And it's endlessly
interesting and complicated and troubling. And the good news is it
will end at some point as Carlos said, but
when and where and how, probably more on the viruses
terms than ours to decide. So thank you both for taking
the time to talk to us today. Thank you all for joining in. We won't have another one, unless something very different happens. And then we'll have
another COVID Grand Rounds on the 9th of September
with George Weatherford, Monica Gandhi, and Peter Chin-Hong and then we'll go on from there. I thank you to my correct production team. You see them, their names there and stay safe and talk to you soon.
