- Good afternoon, everyone. Welcome to another edition
of Medical Grand Rounds. And this one will have a COVID focus. I think I probably threatened
two or three months ago that we would stop doing
these or slow them down, but that clearly was not the right call. And there is a tremendous
amount of new information we'll be off for Grand Rounds
the next couple of weeks. And then we will return on January 6th with a talk by our UC presidential
chair, Dr. Camara Jones for Morehouse in a joint
medicine pediatrics Grand Rounds focused on health equity. And then on January 13th,
we'll do another COVID update. I'm assuming there will
be even newer information over the course of three or four weeks. And for that one we'll have Eric Topo will be the main speaker. Eric, as people know has been one of the foremost
commentators and analysts of what's going on in the
evidence-base with COVID. He is at the Scripps clinic and proudly he's another
former UCSF medicine resident who has made a splash. Today we will focus on the
rapidly evolving COVID landscape, particularly the fire hose of
new data related to Omicron. The ground rules were just
up there, just so you know, closed caption is
available, CME is available, stay on at the end if you want CME credit. And if you have questions,
please put them in the Q&A box. And Lakshmi Santos is monitoring that. And we'll try to get to as many as we can. The first 20 minutes we'll
hear from Carlos Del Rio, about what we have learned about Omicron in the last, I guess three
weeks, three or four weeks. And after Carlos' lecture, we'll have a panel discussion with Carlos, Rachel Byspritski and Paul
Sachs about what it all means and what we should all
be doing in response to this new and rapidly evolving threat. So quick introductions
of our three speakers, thank you all for joining us. Carlos Del Rio is distinguished
professor of medicine in the ID division at Emory and professor of global
health and epidemiology at the Rollins School of Public Health. He's also executive
associate Dean for Emory at Grady Hospital, PI and co-director of the Emory Center for Aids Research and among his many titles, he is president or president elect, you
taken over yet Carlos? You're on mute? - President elect. - President elect, okay of the Infectious Disease
Society of America, which is the major ID
society in the country. He's co-authored five
books, 30 book chapters, and over 500 scientific papers. And if I continue with his bio, he won't have time for his talk. So Carlos, we'll start with a brief talk and then we will have a panel that brings on Rachel Byspritski who is assistant professor of
medicine in our ID division at UCSF. Rachel was resident and
chief resident at Columbia. We were lucky enough to
recruit her as an ID fellow and she has joined our faculty. And since joining she's taken
on several leadership roles, including being medical director of our infectious disease clinic and our outpatient parenteral anti-microbial treatment program. So she serves as a key person
dealing with all of the issues of COVID that confront
a very busy ID clinic. So Rachel, thank you. And we also are really
honored to have Paul Sachs, Paul is clinical director of the division of infectious disease at Brigham Women's Hospital, where he's been on the faculty since '92, he was a resident at the Brigham, did his ID fellowship at MGH, and then returned to the Brigham to take on a variety of leadership roles, including running the aids
clinical trials unit there and associate program director of the Brigham MGH ID fellowship. And he's known far and
wide as a go-to clinician in the field of infectious disease. And I'm guessing he spends 99% of his time on COVID these days. So looking forward to the discussion, but let's hand it off to
Carlos to begin with an update on what we have learned about
Omicron in the last few weeks. - Thank you, Bob. And thanks for the invite. I hope people can see my slides. We're gonna be talking about Omicron and where we are with this new variant. So first of all, just remember
that the COVID pandemic is not over. We are in a fourth wave right now with about 82% of cases
current right now in Europe. Europe is really where the pandemic is very, very active right now. And this is when Omnicom surges, Omicron is a new SARS-CoV-2 variant that was first detected in
Botswana on November 11th, and then identified in South
Africa three days later, it was detected November 13th in Hong Kong in a travel returning from South Africa. The WHO labeled it a few
days later on November 26th, the variant of concern and
a total of 5,563 genomes from over 60 countries have
been uploaded thus far. South Africa was able to detect this because they have a very good network of genomic surveillance in place. And what they noticed very rapidly is they noticed this line in
blue, which is this huge spike when they were almost having no cases, you can see here, their
positivity being very, very low. They started to have this
rapid rise, this huge spike in cases that actually had an S gene or a spike gene target failure. And this is sort of a good
proxy for this variant and for this and they noticed
this very rapid increase. So test positivity rates
started to go very rapidly up in Gauteng province. And you can see here they were having very low
positivity rate in their testing. And all of a sudden they noticed this area with a greater 30% positivity rate. And again, you can see that their cases were really coming down almost everywhere, but they noticed this very slight increase the number of cases in Gauteng province. And this was related
initially to this outbreak among college students that
were among college students that went on a field trip. They were all on a bus
together, and many, many of them became infected and they
all had this mutation. As of December 15th, there has
been detected in 80 countries and it's spreading very rapidly
in many European countries, as I said, including
Denmark, Norway and the UK. And has been identified
so far in 36 US states. And you can see here how
this moved very rapidly around the world and how
this line show us the way this has disseminated across
countries to the point that today we have all
this countries impacted, and this are the number
of cases being reported with the UK now leading the
charge with over 10,000 cases, Norway with 6,000 behind. And you can see the other countries here and how the US already as number five. But you can see across Europe, when you look at the three
countries, Denmark, UK and France, there's very
rapid increase in cases in all of them, but yet not a huge spike in number of deaths, but
it's beginning to go up in some of them and something that we can talk about it later. And we can discuss during
doing our session later. In the US, California, you were the ones, San Francisco were the
ones to detect Omicron. But of course we all are against, or we should be against travel bans because they're really not in the space. And this cartoon shows very
clearly what travel bans are. We close the door to
Omicron, when in fact Omicron is already inside the house
and we don't didn't know it. So why is Omicron so concerning? Well, it has a lot of
mutations that do three things, they've been associated with
more efficient cell entry. They've been associated
with immune evasion and they've been associated
with immune infectivity. But again, we don't know how
this combination of mutation is gonna work together
and what's gonna happen when they all appear in one place. This is an unusually
high number of mutations, 45 to 52 amino acid changes,
deletions or insertions, 15 of them in the receptor binding domain. And as I said, they all been associated with different changes. But what really strikes you
is how this variant Omicron is so different from other variants. It doesn't seem to have evolved over time, but it seems to have evolved for one from one beta strain. And this is why some people
think that this evolved over time in one patient. And one of the theories
is that it's confirmed is this evolved by staying in a highly, somebody with advanced immune suppression like somebody with HIV that
is unable to clear the virus. And therefore the virus is able to mutate and to evolve over time. And again, this is a theory,
but it hasn't been confirmed, but this is a nice publication
showing this one individual, not this case, but another case. So is it more transmissible,
the answer is yes, likely two to three times
more transmissible than Delta, which is already highly transmissible. And again, I take it
to the positivity rate that we saw before. Well, this is what it
looks a few weeks later. I mean, you go one week later and you essentially have
a bunch of the province with having over 30% positivity rate. And you can see where we
were and where we are now. This is December 15th
where they are in cases. In the UK we're also seeing a rapid rise. You can see in green there, how Omicron is going up very rapidly. And the doubling time is about
two and a half to three days, which is just incredibly, incredibly fast for cases to go up. And that's why when somebody says, well, we have three cases today. Well think about 602, two and a half days, and it will keep on going exponentially. That's why you almost have
a straight line going up. A couple of outbreaks that are concerning. One is the so-called
Christmas party in Oslo, 111 persons attended a Christmas party at a restaurant in Oslo on November 26th, I guess, to celebrate
Christmas early over there, most were within 30 and 50 years old, all had been vaccinated,
none have been boosted. 80 people or 70% was
subsequently diagnosed with SARS-CoV-2. Mostly of the Omicron variant and more than 60 people
who visited the restaurant the same evening were
also confirmed infected. Everybody had to show a negative test one to three days before the party. And yet they were all,
there was infection there. And you can see the symptoms,
70% having cough, lethargy, headache, sore throat, but
nobody being hospitalized. The other outbreak, well infection, which is interesting is
this one in Hong Kong where two families were
quarantined across each other in the hallway. They were confined to their rooms. They were not in contact with each other, and yet they both tested positive and their genomes are very similar. And finally, there's data
from household transmissions suggesting that the household
setting Omicron is infecting, infectivity is roughly
two to three times higher than what it was in Delta. So does it cause more severe disease? And here we have no evidence yet that it causes more severe
disease, but I'll caution you that the samples are small
yet most patients are young. So we have to see. And the reality is a lot of
the cases are also in travelers and travelers by definition are healthy. This is the data from South Africa. You can see hospitalization. You can see cases, daily
cases in the orange line. You can see hospitalizations in blue, and again, hospitalizations
are starting to go up, but you can see ICU admissions and percent of hospitalized
for an event are not up and percent on the ICU are not up. So again, maybe some hospitalizations but when you talk to colleagues
in South Africa, they say, yeah, they get admitted
for two or three days. They get discharged. Many of them are because we pick them up because we're doing routine
testing and they were admitted for other reasons. In other words, they were
not admitted for COVID, but there were admitted and
then were found to have COVID on our initial testing. Can it evade the immune system? And here, the answer appears to be yes, and this is some data that I'll show you. If you look at neutralization. And so a lot of data here,
but shows multiple vaccines. The ChAdOx1 vaccine
which is the Astrazeneca, the BNT162b2 which is the Pfizer vaccine. And you can see here in all of them, if you look to the very
arrive right, the B.1.1.529 which is the Omicron strain, you can say neutralization
is almost gone to that strain in any of this vaccines for
any of this individuals, even in convalescent plasmas, there was some protection against
some of the other strains. There's no protection
here, but the good news. And I like the term is a
super immune individual. If you previously had infection
and then you get immunized, you receive a vaccination,
you get a very good response and you get good protection. The data with Pfizer, with three doses, again shows after two
doses, almost no protection against Omicron at 21 days
after the second dose. But one month after the third
dose you have here Omicron in pink, you have a very
significant protection, maybe not as good as it was
with the original strain, but comparable to what
it was against a beta and a little less that
it is against Delta. Summarizing the data, we all
heard about waning immunity to Delta after two doses at
five months have gone by, and you fully vaccinated with
Pfizer, about 60% protection. You get a booster shot, you can raise that to about 95% protection. Against Omicron, if you've
got two doses of Pfizer, you only have about 35% protection against infection, not
against severe disease. And if you boost yourself, you can get that to about 75% protection. So you do get an effect from the boosting. Similar data has now been
reported from the NIH with the Moderna vaccine,
seeing essentially no efficacy against infection two weeks
after the second dose. But two weeks after a boosting seeing a significant protection against, not as good as against a central strain. In real world data, because
that's all in the lab, in real world data in England, they're reporting that with Omicron, you essentially had no
protection against infection. But after boosting, you can
see two weeks after boosting a drop in the number of
infections with better protection. Past infection is not protective. You can see here in previous
waves in South Africa, how they saw in each one of those waves. If you are infected initially, you didn't really have
much risk of infection. In your second wave, after
infection in the first wave, third wave, same thing, but now you're having a
re-infection rate go up. And that re-infection
relative hazardous here, which is very similar to if you were not, hadn't been vaccinated. So this summarizes the
data if you're vaccinated with two doses, you get boosted, you get a very nice response. If you've been infected before, and you get one dose of vaccine, you get a very good response. So we need to get everybody who says, oh, I have natural immunity. I don't need to get protected to at least get one dose of
vaccine to get protected. And again, I like telling them that they will be super
immune if they do that. Monoclonal antibodies
don't look good at all. This is a lot of the
monoclonal antibodies. The one you need to know
of the ones available is sotrovimab and that
appears to have efficacy against the Omicron strain. All the others, well you're talking about
the really monoclonal mixture or the Regeneron, they
appeared to have no effect. I haven't found data with
the AZ and monoclonal, but that has been approved only
for pre-exposure prophylaxis at this point. So summary, decreased
neutralization from vaccines and prior infection expect the
vaccines to remain effective against severe illness and death and boosters restore
protection against infection, or the monoclonal is
pretty much no activity except for a sotrovimab
authorized monoclonals. And we don't have any data
from remdesivir, moinupiravir or PAXLOVID but they should be effective. A very large insurance
company in South Africa confirms this data. And one of the things
that I want to mention about their data is that hospitalizations appear to be going up in children. And that's something to be aware of that although these numbers are smaller. The data suggests that children
have about a 20% higher risk of hospitalization than
with previous variants. And I'm a little concerned about that. So a summary that was put
together by Eric Topo in Twitter, I think summarizes this, the cases doubling two or three days, three to four higher risk
of transmission than Delta in households. Immunity from vaccination
drops to 35% after two doses, but you can get a boost
that gets you up to 75%. We may see a lot more cases,
maybe less severe disease, but the numbers are still gonna be high and hospitals would likely be in trouble. There's immune escape and reinfection, prior infection doesn't protect you. So we need to get
vaccinated if we haven't, we need to get boosted
if we've been vaccinated. And I think really important, we need to get mentally
prepared to act more cautiously once Omicron proves to be,
if it is more infectious, immuno-based or both, I think we need to tell
people to follow the science because a lot more is gonna become clear. And CDC summarized it in
December MWR today with this data and saying, get boosted, increase
the detection, et cetera. Well, Omicron could lead
to a surge in the winter, what CDC says in Twitter,
Eric Topo corrected and said, Omicron will lead to
a surge in the winter. And I think we need to be ready for that. But I remind people that
forget about Omicron, Delta's our problem right now, we have over 55,000 people hospitalized and the numbers are going up. And yes, Bob told us
in Twitter this morning that he's really worried
about people saying, this is less severe and therefore don't need to be worried about it. And I showed you this data
looking at hospital admissions from COVID and compare the UK, which is having an increase in Omicron but their hospitalizations
are nowhere near ours. Look at the US where we
are on hospitalizations. This is our Delta wave. So super imposed on that Omicron and we may really be in big trouble and I will end by getting
you to read this article in the Atlantic Today, by Ed Young, who says, America can beat
Omicron one booster at a time. We weren't prepared for any of the surges, and we're not prepared now
for the Omicron arrival and Will Omicron overwhelm
the US health care system. And, he says, the question is mute because this system is
already overwhelmed. So I think the prognosis for
this winter is very concerning, and I'll be happy for
us to have a discussion about what do we think
and what should we do if there's anything we can do both locally as a health system and as a nation. And with that Bob I'll end
and let's have a discussion. - Carlos, thank you. That was masterful. That's a lot of information and a very beautifully presented. Let's go ahead and bring
on Rachel and Paul. There, there we are great. Let me start by just asking both of you to react to what you just heard. Obviously, I assume you know much of it, but hearing it in that
fire hose of information, as you think about your
practice and your patients, how has your thinking
about what Omicron means? How has it evolved in
the last week or two? Maybe we start with Rachel. - I think what is most striking for me is just the rapidity of spread in that very vertical epidemic curve. I think we were always concerned that something like this would happen, but this is beyond anything
that I would have thought in terms of the doubling time
of the number of infections and just how quickly things can change. So I think that's really
over the last few days as this information has
become more available and we've seen that the
case infection rates go up in Denmark and the UK and seeing what's
happening in South Africa, that's really what I take away. - Yeah. Paul how about you? - Yeah, it's been a really remarkable three to four week period. We have this excitement about nirmatrelvir which is the PAXLOVID generic name. We had the excitement
about the Astrazeneca pre-exposure prophylaxis, which would, people who are immunocompromised, some of them have been living in terror because they can't
respond to the vaccines. So we have that on one side. And then on the other
side, we have Omicron which really feels like
it's setting us back. I do think there is even among people who are generally pretty pessimistic, there is some thought that
this is kind of the pathway to end intimacy faster that with a highly transmissible virus and a fair amount of
immunity already in society, this is probably the way it's gonna go. And who knows, I've stopped
making predictions about this, except to say that I predict
we'll have a lot of Omicron in the United States very soon. - Yeah I get asked that all the time, are we moving from pandemic to epidemic? And that's a bit of
shorthand that I think the ID and public health world
is very familiar with and regular people are not. So what does that mean when you
say the pathway to intimacy, what does that mean in terms of real life in the way you're able to live your life? - Well, one of the really helpful things that one of my colleagues, Scott Dredon Peterson does each week is he summarizes the data for us in Boston and he shows the number of
people hospitalized with COVID and then he compares it to a
typical flu season at its peak. And we're way above that still. So since that's the case,
we can't possibly say we're at a comfortable endemic level yet, but we might be heading there. That's really, if you're
comparable to what you normally are in a winter respiratory virus season, then you're kind of heading
towards endemic levels. But we're way above that, our hospitals, like all around the country, I'm sure it's true in Atlanta
and San Francisco are jammed and jammed because there's
COVID plus everything else. - Yeah, we're not very jammed COVID wise at least in San Francisco yet. And we've done very well, but obviously that could
change very quickly looking at these data, Carlos? - Yeah I mean, we're not
jammed with COVID in Atlanta, but we're jammed because
of everything else. And I think one of the
questions that I would have for everybody is it's
time that we stop focusing on number of cases. Infections were useful at the beginning, but now we have infections in the setting of a significantly immunized population in the setting of a
significantly immune population because they've had infection in the past and do we need to focus the
metrics in something different hospitalizations,
mortality and other things rather than cases because
is cases a good enough proxy of what's happening? - Yeah, it's a point that's
being actively debated. Monica Gandhi and a
colleague had an editorial in New York Times this
week, arguing that point that it's time to focus more
on hospitalizations and cases. - Can I take that one? - Yeah go ahead Paul, give it a shot. - I mean, I am married to a pediatrician. The cases in her practice are as you know, most of them are mild, but
they're enormously disruptive and they cause all kinds of
problems with school, with work and some of the kids do get sick. So I think we're still, until we are a little bit further along, I'm still in the let's count the cases. Emergency room visits
for COVID related illness is a very good metric, we're way up than compared to where we were. - I agree, I think that's
a really good metric. It's a little bit like
what we do in influenza with ILI distance. Influenza, we look at influenza visits. - Yeah I guess I'm also a little bit, when I hear that argument, I'm still trying to decide whether I eat in an indoor restaurant and I kind of want to know
what is the probability that the waiter or the person
at the next table has COVID in part, because I just
still don't want to get it. Maybe that's old fashioned, but I'd still prefer not to get it. I don't understand long
COVID yet in Omicron, all that kind of stuff. So still in cases are useful until there's more of
a proven dissociation between cases and bad stuff. Maybe that'll happen with the Pfizer drug when that rolls out. Maybe it'll happen because
Omicron proves to be more mild, but I'm not quite there yet. Rachel, where are you on the cases versus
hospitalization metric? - I completely agree, I
think we're not there yet. We still don't even know how
hospitalizations will pan out with this, it's still very early. We know that hospitalizations
and deaths lag. And also I think the long
COVID point is well-taken, we don't know what the long-term effects of milder infection are gonna be. - Yeah. So when we think about less
severe, I noticed Carlos, you said that we don't
think it's more severe, but didn't put much of a nickel down on what seems to be the party line, which is it's significantly less severe. And you seem to feel like
there's so many confounders, it's too early to go to the bank on that. So explain that a little bit and I'd love to hear the
other reaction to that issue. - I want to see, first of all I think it
may be a little too early as you and I know it takes a
little bit to go from cases to hospitalizations and severe
illness, two to three weeks. So we should start knowing soon. But I also, the way it's happening when I talked to
colleagues in South Africa, the average age of the
population is young. And most of them have either been, for example, I spoke to our
friends Selma Bill Kareem, everybody in his unit is immunized. About 70% of people have been infected, but their average age is 35 years old. So it's very different population. It's like talking about a college. I want to see Omicron go
through a nursing home or go through a long-term care facility. And then we can talk about
whether it's more severe or not. And I'm worried that if
you've talked to people at CDC booster in our nursing
homes in our country is actually very low. And I want to see what happens, if we don't boost nursing homes quickly, we may see significant
outbreaks in our nursing homes and it may not be a mild disease. So I'm not ready to say this is more mild than the other ones. - Where do you stand on
that based on your take of the evidence and what
you've seen so far, Paul? - It's very hard to
disentangle prior immunity from these data. And if you look, people
who've been infected before and people who've been
vaccinated, that's prior immunity, they tend to get breakthrough
cases that are less severe, but the intrinsic variance of SARS-CoV-2 probably remains with this virus. So an un-immune person
encountering Omicron is probably just as likely to get sick as an un-immune person encountering the original Wuhan strain. So I'm not ready to buy
that it's less severe. I wish I've heard many people say, it's got so many mutations, it's got to do something
to its pathogenicity, but that's actually wishful thinking. It's not actually based in
any science that I know of. I hope it's true, I don't think it is. - Yeah, this is one where
your brain wants it to be true so much that it sets us up for a bias. And I think it's also,
if it's less severe, at least the hospitalization
data from South Africa said, maybe 30% lower hospitalization, but if it's twice or three
times as transmissible, the math works out badly there. I think Rachel, what's
your take on all this? - Yeah I think if we have
double the amount of cases, particularly in a short period of time, that 30% decrease in hospitalization will be overwhelmed by
the sheer number of cases. So we have to see. - Yeah. In terms of booster strategy, let me ask one more question, I haven't seen this piece of data around. It would be very useful. Paul just made the point
that he's most worried in addition to immunocompromised people, most worried about folks who
have neither been vaccinated nor infected, how many of those people do you think there are at this point? - When you do serial prevalence
studies around the country, I know that antibody is not
a perfect measure of this, but there's a substantial
fraction of the US population that has not been vaccinated
and has not caught COVID yet. That may not be true in all regions, obviously certain parts of the country. Like for example, here in Boston, there are certain very densely
populated neighborhoods that have very high seropositivity rates, but that's not the rule. And so it does concern me. So I can't give you a precise number, but our immunity wall is not
as high as Great Britain's. They like to show that off. - Well, you know South
Africa had from prior waves and their data from their blood banks, again, blood banks is not a perfect proxy, but 65, 70% of the population had evidence of prior immunity, whether
it's through vaccination or through natural infection. - Yeah and it still rolled
through there pretty badly. - What I worry in our country is we are about 60% vaccinated. And let's say the other 40%,
some of them have immunity from prior infection but if
immunity from prior infection doesn't protect you against Omicron, you got 40% of people in our country that are susceptible that even if you got
everybody else immunized, that is a lot of people
that have no immunity against this virus. - Right and then you take the people who got their two shots a year ago. And I guess they're
partly protected, I guess. Do you think, should
the CDC announce today that their definition of fully vaccinated is no longer two shots? Would you like that? Cause I see that in the
newspaper all the time, this percentage of the
population is fully vaccinated. - They think the J&J vaccine is still considered full vaccination. And almost every study shows
its effectiveness is lower. And even a recent study in
this flood of pre-prints that showed up about Omicron
showed that the antibody levels generated by boosting the J&J vaccine with one mRNA vaccine afterwards
were substantially lower than the third boosting
shot for the mRNA vaccine. So, it's looking like
if I had been a person who had the J&J vaccine originally, I would go for a third shot,
I would like to match up the number of shots with two
additional mRNA vaccines. - How long would you wait
after your first booster? - I don't think there's
any precise amount of time, and I wish there were data on
this, maybe Carlos or Rachel, you know it, but I would,
a few months later, go get your third shot. - Yeah, yeah. Rachel, as you were dealing with people in the clinic setting,
and I'm sure you get a ton of questions like this,
have you been successful in convincing people to get vaccinated? And if so, what's your strategy? And has it changed at
all in the last month? Is this sort of creating
a level of concern that's different than over the past year? - I think that, well, first of all, we haven't actually had a
lot of un-vaccinated patients practicing in San Francisco, at least with my primary care practice, which I recently left, but almost all my
patients were vaccinated. So that was great. I think in the ID clinic, we have more un-vaccinated patients, many are very difficult to convince, but I think with Delta that really changed a lot of people's minds. And I imagine with Omicron,
it will change more. And I think that just pointing out how many people have been vaccinated is reassuring to people, but there's some people who
are very difficult to convince. - Yeah. Paul or Carlos, have you
come up with any techniques or ways of framing the data
that seem to be working or are just frustrated. And at this point, if
you're not vaccinated, it seems like there's not much we can do? Carlos, what you think of it? - I mean, I think we still, it's almost like one person at a time and many of them, it's a personal issue. It's about, somebody I recently talked to into getting vaccines were two young men, two African-American men in their 30's. And it was basically their mom saying, if you want to come to Thanksgiving, you need to be vaccinated
otherwise you're not coming and they wanted to be with mom. That's why they got vaccinated. And the reason they hadn't been vaccinated is because they had heard this thing that it produces
infertility and sterility. So a lot of misinformation
is leading some people not to get vaccinated. Many young people also are saying, this is mild, why should I care about it? And you have to really tell them, well, you care when you
go home and see grandma and that's when you can be in trouble. So trying to find a
personal reason for somebody in a trusted messenger,
I think continues to be the way to get this across. - Yeah, Paul how about you? - Yeah I mean, again,
vaccine and vaccine hesitancy is such a part of my
dinner table discussion with my pediatrician wife. This existed before COVID
and it still exists. I totally agree that getting
misinformation is one reason that people don't get vaccinated. We did a clinical study
that paid a small amount for participation and some of our holdouts ended up just because they
wanted the a $100 stipend, got vaccinated. I don't know why that was
so beneficial to them. Not all of them needed the money, but it was just what it took. There are all kinds of reasons
why people make decisions. And I think we, it is
frustrating sometimes, so. - Yeah, sure is. Let me add a few practical questions. Paul already answered the J&J question, which comes up all the time. Rachel, what do you tell people
who've got a first Pfizer or their two shots with
Pfizer and are asking you about switching to
Moderna and vice-a-versa? - I think get whatever shot you can. At this point I think they're
probably pretty equivalent. And right now, one of the
things that we're coming across is that wait times to get
booster vaccines are long. Many of my patients are telling me they can't get an appointment until the second week of January. So I think whichever mRNA vaccine
you can get, get that one. - Yeah, I agree Rachel. But I think when you said
get whatever you can, get whatever mRNA vaccine.
- Yes, yes. - Are we, yeah Carlos,
are we done with J&J as a primary vaccine, should
we just get rid of it? - I'm done with J&J as a primary vaccine. I think the mRNA vaccines are
the things we need to be using I would not recommend
right now a J&J vaccine. I think a question we get a lot and there's not a lot of data. And I would love to hear,
a lot of people globally have been vaccinated with Astrazeneca based on the code blue study. I mean, what are you recommending
when somebody travels from Europe comes here from other country and says, I want to get
a booster, what do I do? - Yeah, what do you tell them? - Well, I mean, I tell them
to get an mRNA vaccine, but I tell you, if you go to your CVS and say, I'm here for
a booster for an mRNA and I got Astrazeneca, they tell you, oh, that's not in the
recommendation from CDC. And therefore we cannot
give you a booster. So you have to tell those
people, you need to lie. You need to go and say, you're
getting your vaccination for the first time. I mean, it's very unfortunate
that CDC has yet to come out with recommendations when we
live in a global community. - Yeah, yeah. Paul, any comments on that? - I agree, I mean, I've
recommended several people who've gotten the Astrazeneca
vaccine get mRNA vaccination, and they get signed up
for the two dose series because that's really what they're saying. Yeah I mean, I do feel
like the J&J vaccine was really of its time. We were looking for any glimpse that we could get out of this mess. And it was an alternative
vaccine strategy. It had some logistical advantages, but the data consistently
showed it was less effective. And we stuck with it for way too long. I think that that's unfortunate. And then this, I hear
the CDC is looking again at its thrombosis syndrome. - It's actually the ACFP
meeting was yesterday and today, they're having a vote on it today I think. - So is it possible they'll
withdraw the approval for it? - I don't think so. I mean, I really don't think so. But you know, it's not only
in the US I mean, globally. I was hearing in South Africa, they received a big
donation of J&J from the US and South Africa said, thank you very much send it somewhere else, we don't want it. - Interesting. Yeah I love that, Paul saying as well, it's so 2020 that vaccine, right. I've heard people say, I want
to not get my booster now. Cause I think I want to wait for the rejiggered
Omicron vaccine booster. What do you think about that strategy? Maybe Rachel, we'll start with you. - I think we know from the
data that we have available that the third, the booster
shot is actually quite effective at boosting immunity. Perhaps not as high as
for the prior variants, but still quite good. I don't even know that
they're gonna introduce variant specific boosters given depending on how the data plays out, but it's certainly not
gonna be for a long time. So I would certainly advise for people just to go ahead and get it now. - Okay, good I assume that's,
that's your, go ahead Paul. - One reason to advise that strategy is because the way that these surges come, they come in these periods
that last a couple of months, and that's probably how
long we'd have to wait before we have an
Omicron specific booster. And this may be a very
low disease activity. Remember last winter, which was dreadful, the activity started to wind
down by the end of January. And even though it was still winter, their case numbers dropped substantially before at the end of the winter. I hope that is what happens this time. Because even though it's a seasonal virus, it doesn't have to last the whole season. - Yeah, and is there evidence
emerging, maybe Carlos, is there evidence emerging that this thing is going to spike high and come down fast the way it did in India, actually
prior variants obviously, but just the nature of what
we've learned about Omicron, is that what we can expect
a couple of early bad months and then improvements? - Well, that's what I hear as you know CDC has sort of a think tank, a
center for pandemic preparedness that they're looking at
this and Mark Glitches is actually running that. And what Mark presented the other day was that this Omicron
is probably gonna peak in the second week of
January and then come down and by the end of February
will be gone from our country. So it looks like it's gonna peak quickly and come down quickly. We'll see what happens, but that's what at least
our predictions are modeling suggests based on the rapid increase in number of transmission in cases. - And when that happens, do we understand, is it just that so many
people have gotten infected that now the immunity
wall is higher than it was or is there some other a hand waving that we don't understand
about why these things come up and come down so fast? - I think there's human behavior, right? I mean, people start
not going to restaurants and not wearing masks and
being a little more careful. And I think it's just getting
more people get vaccinated. I mean, I can tell you right now, just the scare of Omicron has
increased the number of people ready to get vaccinated
and getting boosted, which I think is gonna change what the susceptible population is. So I think this is very dynamic. And when you talk to again, the other day I was talking to Chris Mary from Institute for Health
Metrics and Evaluation, and he was saying, in the older modeling, what they really have not
been able to model effectively is behavior. Because you can model the virus, you can model the transmission, but you can't model the behavior. - Yeah, yeah. So does that argue that even though every, many, many people and
politicians and health leaders are quote over it, the
next couple of months, people really should hunker down that we're in a period of high risk that's gonna last for a period of time and then probably go away. Paul is that how you're
thinking about this? - Infectious disease doctors
probably are not representative of the behavior that the entire
population is going to take. And I would certainly say that's true for the author of that
piece in the Atlantic that got so widely criticized by us, but I confess here in
Boston and I'm the son of a food journalist. I have not dined inside in a restaurant since the spring of
2020, I miss it greatly. And I'm gonna put that off until case numbers drop some more. I mean, unfortunately we had case numbers that were very low here in
the early part of summer, and then Delta kind of ruined that and it showed that you know what, we're still a very susceptible population. So you can get together with
your friends in small groups, but in crowded areas, that's
super spreader event in Norway, is like a perfect example of how you can disseminate
COVID very quickly, you put a bunch of people
together in a place that probably has poor ventilation
cause it's winter time. You have them talking loudly
at each other all night without a mask. I mean, they're basically
enjoying themselves. Of course, it's gonna
lead to lots of spread. To limit the size of the
gatherings makes a lot of sense when there's a lot of transmission. - And I think one thing that
is pretty clear now, Paul, it was clear with Delta, but
I think it's even more clear with Omicron is this is airborne. I mean, we made a lot of distinctions between respiratory
particles versus airborne is not really if or or,
it's a combination of both, but this clearly is airborne and can be transmitted airborne. I think there's some nice
data that I saw the other day saying that I didn't put
it in my presentation, but that it can remain in the
air for up to an hour or two after you leave the room. So, you could potentially,
again, in that restaurant, you could go there, you
can go to a room later and be infected. A question that is in the chat. And I think worth for us to ask is that you mentioned not eating outside. What are we gonna do for
Christmas and New Years and I'll be very curious to
hear what people are feeling cause of New Years. - Yeah so, I mean, so
Paul, you won't eat inside in a restaurant, will you eat outside? - Yeah, and airborne
viruses get distributed, diluted by ventilation
so efficiently outside. I've eaten outside in many restaurants, it's just very hard to do in
Boston in the winter time. - Yeah, still okay out here. Let's talk for a minute. I'm gonna get two holiday plans and those are the dominant
questions that are coming up. In terms of the oral antivirals. How excited are you about the Pfizer drug, maybe start with Rachel and how much of a game changer
do you think it will be? This is the PAXLOVID. - I think it's huge. I think that it would be a completely paradigm
shifting development. My concerns about it are
just the infrastructure and getting it to patients
in a soon enough timeframe. So I think that's gonna
be the major challenge of the coming months. - Mm hmm. And why is it a game changer and how do you expect to use it? So where does it fit in, in
a world with monoclonals? Are you using instead of, or with, or how are you thinking and
which patients would get it and not get it in the short
term, when, if it's available, it may have a limited
supply in the short term. - Yeah so I think it will be targeted to the high-risk patients. And I think, I'm not
sure which I would choose if I had access to both a
monoclonal antibody or PAXLOVID but the truth of the matter
is it's just much easier to get an oral medication and
to get it to somebody quickly. When we refer somebody
for a monoclonal antibody, it usually takes several days to set up. Many of my patients live far away. And so if we can get a good
distribution system going, then we'll be able to
get people treatments that prevent hospitalization,
prevent death in the outpatient setting
hopefully quickly. And that will hopefully make a huge step. - Yeah, Paul what are
your thoughts about it? - I mean, in addition to
agreeing with what Rachel said, remember this antiviral
lowers viral load tenfold. This might make people
less contagious quickly, and that's very exciting also. I think it's a terrific advance. I was all giddy about
it until Omicron hit. I mean, it was really
exciting to see the data because in the second press release, the full analysis of the high-risk study was just as robust as
in the first analysis that's contrasting with the moinupiravir. And then they also presented data on the standard risk patients. And that group also had a reduction in risk of hospitalization, which I thought was very notable. So I'm thrilled that we have an antiviral that has both clinical benefits as well as antiviral benefits. - Just to be clear,
you said you were giddy until Omicron hit the ground. When Omicron hit, it should
make you giddier right. because it actually will
be working against Omicron. - What I meant was actually they did do some in vitro analysis and they show that they should be
active against Omicron. What I meant is that Omicron put a damper in my otherwise cheerful mood. - Just took away your
giddiness in general, but anything the value of
this may actually go up in the Omicron world, right? - Absolutely. And not does the value of this go up, but I'm gonna actually bring up something very surprising, which is that remdesivir which has a very checkered
history on the inpatient side looks best when it's given to
outpatients early in disease. And in some ways with all of the concerns about immune escape for
monoclonal antibodies with Omicron that could be something that
would be very easy to do for some infusion company,
give three doses of remdesivir, you don't need any observation time. It goes in over 15 to 30 minutes, it prevented hospitalization, 90% reduction in hospitalization. So if we do have supply
issues with PAXLOVID, I would hope that we'd
be able to try to gear up to give remdesivir as outpatients. Nobody I know has been doing it, but unless some of you have, but I don't know of
anybody who has so far. - Yeah, yeah. Carlos, any comments about the new drug? - No, I think I'm very excited
about having oral agents. I mean, as Rachel said,
the issue with monoclonals or with remdesivir is the set up, the idea you have to do
this, you have to do that. And whether you like it or not, we're all struggling with
having enough nurses. And when we had the Delta surge. My CEO of the hospital said, look, I have nurses for
taking care of patients in the inpatient or doing the
infusion, we can't do both. We need to figure out a way to do this. So it's nice to have something oral. I think one issue that we
all need to think about, yes, I was talking to a colleague
from University of Miami and they were seeing a
surge of Omicron in Miami, but when people, but they have Delta and when people show up in the ER, you don't know what they have. And you give them monoclonal then. And if they have Omicron,
it's not gonna work. So at some point in time,
we have both epidemics happening at the same time
and know that some drugs are not gonna work versus others are. And I think we're having
both at the same time, I'd rather go with remdesivir
or I'd rather go PAXLOVID or something else rather than monoclonal that may not work in that
individual, if you give it. - And do you, and this
brings up the question, do you think that's what
we're destined to have for a while, the both
epidemics at the same time, or do you think Omicron just
rapidly becomes the virus that we're confronting? - You know, I don't know, because again, we're having a lot of Delta right now, so it's gonna take a while
for Omicron to take over. I think we may be having like a 50, 50 or something like that. And some places that have
little Delta right now may see a lot of Omicron but in Michigan or in
Minnesota and other places that have a lot of Delta right now, I think it's gonna take some
time for Omicron to take over. They may be having both at the same time. The issue with this drug
is we got to get testing, we got to get people diagnosed and we got to get them on
therapy within five days. This is no different than with the flu and with also time of year. You got to get people
on therapy very quickly. And again, our system is clunky. I mean, we have trouble
doing this kinds of things. I mean, this should be a no
brainer, get tested at home, get a sample, start here's your
prescription be done, right? - Yeah, yeah. No, it's non-trivial to figure out all the moving parts here. And particularly if there's
a shortage in the short term and everybody's gonna want it. And even people at lower
risk are gonna want it. And it's gonna be messy, Paul. - One thing is that I saw
someone was quoted saying, oh, the person's gonna need
to come in to see a doctor before he'd get their prescription. And that's definitely not the model. I mean, we've known for
influenza drugs for years that you can make a clinical
diagnosis of influenza. You don't necessarily
during the peak flu season need to bring someone in
to confirm the diagnosis and you could treat them with oseltamivir without them coming in at all. And I strongly suspect what
we'll be doing with this is people will be doing home tests. And if the home test is positive, they'll get their prescription
for antiviral treatment. And they'll never have to come into that and interface with the healthcare system. - Yeah. Actually the last thing you
want to do is bring them in, if you can possibly avoid it. Let's turn to a lot of questions about kind of practical issues and I'm sure the questions
you all are getting, holiday get togethers that
I had been planning on and looking forward to, and now Omicron. And should I cancel flying
to visit grandma in Florida? Should I cancel, I was
planning on going to Europe. Should I eat indoors,
all that kind of stuff. So Rachel, why don't you summarize what you're telling people or
maybe if you're comfortable summarizing what you are doing yourself and with family, telling family members. - Sure, so I can start with in general. So I think the travel and
the gathering decision kind of is an individualized decision based on your personal risk, the risk of the people around
you, your tolerance for risk. I think that certain things I probably wouldn't recommend doing, like going to Europe
right now, first of all, Omicron is surging there
and you need a negative test to get back into the United States. So I think there's a very practical issue, you may not be able to get,
come back until the quarantines. And then in terms of holiday plans, I think it depends on
the size of the holiday. It depends again on the risk
of the people around you. I probably wouldn't myself be too excited about flying to see my
97 year old grandmother. But for myself personally,
my family gathering is gonna be very small. Last year, we did it outside,
but there are only five of us. So we're gonna continue as usual, but we'll do rapid tests before which are very readily available. - And would you feel comfortable visiting 97 year old
grandma, God bless her and do a rapid test before
you came and saw her. Would that make you feel like this is a pretty safe thing to do? - That's a tough one and actually
one that I need to decide because I am seeing, I was supposed to see
my 97 year old grandma in a couple of weeks. I think in my situation I
would with a test before. I have a booster, she's
been fully vaccinated and I get to see her very rarely. So I would wear a mask,
she would wear a mask and that would be the
decision that I would make. - So even if she's fully
boosted, you're boosted, you do a rapid test in the
morning, you're negative. You would still not come
and sit down with her without both of you wearing masks? - She's not boosted. - She's not boosted, okay. - She was a late comer to
the COVID vaccines, which is. - Let's say she was. - Yeah let's say, personally,
I would still be nervous, but I think that's
probably overly cautious. - Yeah well, you're an ID
doc, that's who you are. Paul, take us through
the various scenarios and again, with your wife, a pediatrician, maybe layer in, you got young kids. - Yeah I've got young kids
interacting with my wife, but I don't have young
kids, I have adult kids and the adult kids are, we know adult kids are the highest risk for getting COVID. Adults, young adults,
teens, and young adults. They're the ones who
will socialize the most. And that's been the case from
the beginning of the pandemic. And one of the things about the vaccines that's been so liberating
is that we realized that we could see them relatively safely. And that's also been
one of the nice things about the home tests. Now, the home tests are not perfect. We have no illusions about them, but just to sort of take it
back to the elderly parent. I have two elderly
parents in New York City, and we've made the decision
that with a negative rapid test right before seeing them that
we're just gonna do that. And there was this actuarial cost of delaying too long that I worry about that we're just not gonna get
a chance to see them ever. And so for some time now
that's how we've been doing it. And in fact, we're
visiting them this weekend. - So the travel, you're driving or flying? - We're taking the train. - Train, okay. - And then the train,
they say their ventilation is very good and as good as the flights. Well, who knows. And then we're doing rapid tests right before we're seeing them. And it's important that people
who are using rapid tests, not do them that morning
or the day before, they should be done as
close to the actual visit as possible. And of course we wouldn't go at all if we had any respiratory symptoms. I mean, this is critical. People should not use the rapid tests when they have a
respiratory tract infection as a way of reassuring themselves, falsely that they may not have COVID. I've heard that mistake
made numerous times. - Really I guess I probably
have made that mistake. I wake up and if I have
a little scratchy throat, I'll test myself, I'm
negative, I feel pretty good, but that's-- - You should feel better, the likelihood that you don't
have COVID is decreased, but by no means does it rule COVID out. - Right, but doesn't it
come close to ruling out that I'm gonna infect grandma that day? - You know, I would not trust it. I would not go visit grandma with a respiratory tract infection in the COVID-19 era period. You know, in fact,
remember grandma previously was always vulnerable to
getting RSV and rhinovirus and metapneumovirus and those things. - Right, if you feel
crummy you have something and you're going to give it grandma. All right, you've gotten your test an hour before you saw grandma. You've all been boosted, you
wear a mask when you see here, do you hug her or not? No. So you're comfortable rapid test that day or right before the encounter. And everybody's boosted you act normally, no distancing, no nothing. Maybe you keep a window
open, but that's it. - Yep, that's okay. - Carlos, what do you think? - And that's what I do
with our friends too, when they come over for dinner. - Yeah, I agree, I agree with Paul. We're gonna get together with family. We have young adult kids and there'll be some
unvaccinated kids under five, two of them. And there's my mother
who's 90, 87 years old, she's vaccinated, but she's
only gonna get her booster this week so she's really
not gonna be boosted in time for Christmas. No symptoms. If you have any symptoms,
you don't come in. Everybody else is vaccinated. Most people are boosted, not everybody. And my contribution to the
dinner is having the rapid test. I bring the rapid test and
as people are walking in, they're getting the rapid test. This is part of the, oh
the procedure of coming in. I personally, I have been flying. I test myself a day before I fly, I fly. I can tell you, I've
been working with Delta throughout this process. And they really done an
incredible job of changing-- - That's the Delta airline,
not the Delta virus. - Not the Delta virus and changing filters and the ventilation. I've learned a lot
about plane ventilation. I think the plane is fine. The problem is, is when you
are boarding and deboarding, that's when you have a lot of crowding and a lot of things happen. And then quite frankly, what
you do when you get there. So, I test myself before
I fly, I fly and I test, I keep a mask on and I test
myself 48 hours after I fly. That's a way again to make
sure that I'm negative and I've done that pretty routinely. And so far have not gotten
infected during a trip. - And your family gathering,
masks or no masks? - Once everybody's test negative and everybody's vaccinated
and boosted, no masks. But again, the testing
is happening at entry. And if people want to test again, I remind people, for
example, the buy next now comes in package of two
is not to test two people. You can test yourself 24 hours
before and at the very moment because two tests increase
the positive predictive value. If you do two tests sequentially. - Well, it sounds pretty safe. So my son and daughter-in-law
live in Atlanta, they'll be over for dinner
in a couple of days. So thank you. Let's, we're coming to the end. Any, let's, I'll give you a chance
for any final comments and how you're processing all this and thinking about the next several months and what you want to
leave the audience with. Paul do you want to start? - Yeah I just want to mention something about the Astrazeneca
pre-exposure prophylaxis, because I was, as I mentioned before, I was so excited about
that for my patients who are immunocompromised
who have lived in terror of this virus for so long. And right now the data are
unclear whether Omicron will make the antibody
combination inactive. So stay tuned. I've seen confident reports that Omicron evades Astrazeneca's compound
and I've seen the opposite. And so we'll see, I mean,
I don't think we know yet. So.
- So when you talk to those patients, transplant patients on immunosuppressives, what do you tell them about
how to live their lives? - So some of them have
been totally housebound. And I say very important that
you be able to go outside, to feel safe going outside, unless you're having a
face-to-face conversation with someone at close quarters, outdoor activities are quite safe. So it's really tough to get them out of that hermit existence. And then the other thing is
to have people who visit them to do rapid testing before they come. - Yeah, thank you. Rachel, anything you
want to leave folks with? - I think just that we will
see how this will unfold. I think the next couple of
weeks will be very informative. - Yeah, Carlos. - Well, I think I tell people
a couple of things I say, while the current situation
continues to be serious, we're in a much better place
now than we were a year ago, I think that vaccines remain highly active and preventing severe disease,
hospitalization, and death. You need to get vaccinated if you haven't and you need to get boosted. I think masking indoors
continues to be important. And I tell people, especially
our colleagues in healthcare, we need a lot of resilience and I know we're running
very low in resilience, but at this time we need
to do whatever we can to cheer people and to help
people get through this process because people in healthcare
are, we're all very tired. People are exhausted. And I think we're still in
for some very tough weeks and months ahead. And we need to take care of each other. - Yeah definitely support
group for each other. - Yeah, well, thank you all three of you for a really informative discussion i a very rapidly evolving world. Up until really the last couple days, I've been telling people
for their holiday plans not to think that much about Omicron, that probably is wrong. I mean, it really, it
feels like it is here and it's an important player. So I know we're all tired of this, but it's important to still
be thoughtful and careful, and you've given people
some terrific advice. So thank you all have a
fantastic holiday to all of you and to all of our audience. And we'll see you back for
Grand Rounds in a few weeks, three weeks, January 6th. I thank you to our three speakers. Thank you to all of our folks
that put this on each week so flawlessly and be
well and happy holidays.
