Welcome to another MedCram COVID-19 update. We're going to talk about variants that have been
discovered here in the United States. We're going to talk about the variant that has been discovered
in New York, but first we'll talk about the variant that's been discovered here in California,
and it's got two names. One of them is B.1.427 and the other is B.1.429.
And this variant has three mutations in the spike protein, and again the spike protein
is that protein on the surface of the SARS-CoV-2 that interacts with the ACE2 receptor on human
cells. The most important of those mutations is something known as the L452R mutation, and it's
this mutation that has raised concern from some researchers, based on data that has not yet been
published or peer reviewed. There's actually been a couple of teams that have looked at this at UC-
San Francisco, and according to their work, which has not yet been peer reviewed or published,
they found a couple of things that are interesting. Number one: they found that the virus seems to bind
to the receptor more efficiently and that, as a result, causes the virus to infect tissue
about 40 percent more. They also found that because of this, it is about 19
to 24 percent more transmissible, and as a result of this in patients who were infected with this
variant of SARS-CoV-2 that there was two times the amount of virus in the nasopharynx.
Now in some of this research that came out of UC- San Francisco, they looked at 324 patients who were
hospitalized, and 69 of them had this particular variant where 255 did not, and out of those 69
that did have the variant, seven patients died. And out of the 255 that did not, five died. And
you can see here that there's a higher mortality rate, but again the numbers may not tell the whole
story there, because they don't know whether or not the variant was associated with a surge in cases,
which could have increased the mortality rate, and so there's still work that needs to be done
in terms of determining whether or not this was truly due to the type of virus or variant.
The other thing that they did was they did experiments to try to determine the amount
of neutralizing antibodies that were required, and so basically for this, they took an individual who
had been vaccinated and they drew blood from this individual to check their antibodies. And what they
wanted to do was see how much of the antibody was required to neutralize the regular virus.
And what I mean by "regular virus" is the original SARS-CoV-2 virus that was discovered in Wuhan
at the start of this pandemic. This is also referred to as the "wild type virus."
Now, the amount of antibodies that are produced in someone who's vaccinated
is several times the amount of antibodies that are necessary to neutralize the regular virus,
so they diluted down the amount of antibodies until it neutralized, just neutralizing the
virus so it would not be able to infect cells. And what they did was they went ahead and designed a
California variant and did the same experiment until they found that the virus was not able
to infect any of these cells. So the question was, how much were they able to dilute it before it
wasn't able to neutralize the virus's ability to infect cells? Before we get to that though, I just
wanted to give you, as a reference, that they've done the same experiment with the South African
variant. As a reference, we know how much we can dilute the antibody from a vaccinated person
before we stop infection from the South African variant, and as it turns out, you need six times
the antibodies that you would need here in the original virus to be able to neutralize the South
African variant from infecting cells. What we mean to say there is that the antibodies produced by
a vaccination is only one-sixth as powerful at neutralizing the South African variant, and yet
we still see pretty good efficacy of the vaccine against patients with the South African variant
and its ability to prevent infections in those populations. And I'm referring, specifically, to the
Pfizer-BioNTech vaccine, the Moderna vaccine, and the Johnson & Johnson vaccine that was just recently
given emergency-use authorization. And when they did this with the California variant of SARS-
CoV-2, it was only two times, which means that in terms of the vaccine's ability to neutralize the
California variant, it seems like it's somewhere in between the regular wild type SARS-CoV-2 virus
and the South African variant. Now, remember at one point during the winter epidemic here in
California, 50 percent of the COVID cases were deemed to be this California variant. And as we've
showed you before, look what's happened to the daily new cases in California. They've come down.
Daily new deaths in California are also coming down. And remember, even the Johnson & Johnson vaccine,
which had a 66 percent efficacy overall, in the South African variant where 15 percent of the study in
the Johnson & Johnson phase 3 trials were done in South Africa, and 95 percent of those cases
were of the South African variant. There were no deaths or even hospitalizations 49 days out after
the vaccination. So it seems as though if we're losing efficacy in the antibodies, it's allowing
more milder cases, and we're still not seeing, at least in the Johnson & Johnson vaccine, an escape
causing severe disease. The other thing that's interesting to note as well is realize that we're
only looking at antibody response, which is just one tool in the toolshed of the immune system. The
immune system also has memory T cells, cytotoxic T cells, the innate immune system, and several other
aspects of its immune system and defense system to mitigate against the SARS-CoV-2 infection.
And here's the article in the San Francisco Chronicle titled "California coronavirus
variant is resistant to antibodies but vaccines should still work." And this article
quotes Dr. Jay Levy, an infectious disease expert at UCSF, who basically found that the results released
this week were reassuring. He said the vaccines will work unless it mutates to become worse.
You're still neutralizing the virus and as the article states, there are several caveats
to these early results. The most important of which is that these are laboratory experiments
that analyze interactions between the virus and the antibodies in a highly controlled setting. In
real life, the body mounts, as we mentioned, a complex immune response to the virus.
So while some headlines state that new research is showing that the California coronavirus variant is
more transmissible, it seems as though when you dig down deeper, you'll find that that
increased transmissibility can be mitigated with measures that are already in place,
and that the vaccine rollout, both with the Pfizer and Moderna, soon to be joined with
the Johnson & Johnson, will mitigate further transmission and reduce hospitalizations and death.
And along those lines, Moderna is already saying that it's ready to test its new version of the
COVID-19 vaccine in humans. This new version is specifically designed to combat head-on the South
African strain, and according to this article, it's not just Moderna, but other companies including
Pfizer and Johnson & Johnson have said that they are tweaking their vaccines or working on boosters
that better match the variants. And of course, one of the issues with the Pfizer vaccine has been
the requirement for the ultra freezers that are required to store the Pfizer vaccine. What we're
seeing here is a proposed US EUA or emergency use authorization label that would update and
enable the vaccine to be stored at just negative 25 degrees celsius to negative 15 degrees celsius
for a total of two weeks. And if that gets approved based on this press release from
Pfizer, that would greatly simplify the ability for the Pfizer vaccine to be distributed
at those more reasonable temperatures. There is currently one other variant that
is quickly being discovered, and it's based on two papers that have not been peer reviewed
or published, but are available on Medical Archive, and that is the New York variant.
So the New York variant is otherwise known as B.1.526, and the mutation that keeps coming
up independently across the globe is also found in this variant, and that's the E484K
mutation in the spike protein. In this case there's also another mutation called the S477
mutation. As it turns out this E484K mutation has been shown in some papers recently to indicate
resistance to some of the monoclonal antibodies that have been used, for instance by Eli Lilly,
as you can see in this paper, which we will give a link to in the description below.
It actually goes through and looks at a number of the different variants, specifically the B.1.1.7
and also the B.1.351, both the UK and South African variants, respectively.
And as you can see, it is probably largely due to the E48 mutation
that there was some challenges there in terms of monoclonal antibody therapy.
And again that's exactly the mutation that we're seeing here in the New York variant as well.
Now, there are actually two teams that looked at this. One team was from Cal Tech and the other
one was from Columbia, and we'll give links to the papers that are available to both of
those. The CalTech group basically was scanning the databases looking at different mutations,
and they noticed these mutations, specifically the E484K and the S477N, and they noticed that
at least in New York that by mid-February that about 27 of the isolates in New York
were containing these mutations, and there's a nice article in the New York Times that summarizes a
lot of what we're talking about here titled "A New Coronavirus Variant Is Spreading in New York,
Researchers Report." And here you can see the paper that was put on BioArchive.org.
This is from Cal Tech in Pasadena, California, and they mentioned here the B.1.526 variant.
They mention here in the abstract that it accounts for about 25 of coronavirus genome
sequenced and deposited from New York during February of 2021. They also have renderings of
the three-dimensional structure of the spike protein at the end of the article as well.
Now, the other group at Columbia looked at about 1,142 patients from their medical center and found
that about 12 percent of them had this mutation the E484K mutation, and in looking through that article, they
noticed that the patients were about six years older. They noticed that there was an increased
risk of hospitalization with this New York variant, and as you can see in their abstract, they conclude
that the phylogenetic analysis of sequences in the database further revealed that the
B.1.526 variant is scattered throughout the northeast of the United States, and its unique
set of spike mutations may also pose an antigenic challenge for current interventions and that would
include vaccines. They also have some very useful graphs here at the end of the article, which show
the prevalence of the wild type SARS-CoV-2 infection here over time and how there has been
an increase in the E484K mutation as we've talked about. You can also see the phylogenetic tree,
and you can see how these different variants have come about. So in terms of the experts, there is
a little bit of a mixed opinion as to what the consequences of all this means. In the New York
Times article, Dr. Nuzenwig, who is an immunologist at Rockefeller University states that people who
have recovered from the coronavirus or who have been vaccinated are very likely to be
able to fight this variant off. There's no doubt about that, but they may get a little bit sick
from it, whereas Dr. Reed, who is a microbiologist from Penn State says "These things are a little
bit less well controlled by vaccine, but it's not orders of magnitude down, which would terrify me."
The article goes on to say, "as the virus continues to evolve, the vaccines will need to be tweaked" in
the words of Dr. Reed, "but in the scheme of things, those aren't huge worries compared to not having
a vaccine. I'd say the glass is three-quarters full compared to where we were last year."
And if we look at the daily new cases in New York, we can see that they have been on the way down,
but they seem to be at least leveling off here in the last week or so, and the amount of daily
deaths also seems to be on the downward trend in the state of New York. And as we've said before,
really what happens with these variants is a mix of how well can our immune system -- either from
natural immunity or from the vaccine -- neutralize these variants? Ultimately, time will tell. So while
the virus is fine-tuning its approach and mutating to improve its transmissibility, we on this side
of the conflict are also making adjustments and changes to help meet those challenges.
And from a global standpoint, looking at new cases on a daily basis around the world, that couldn't
come at a better time for more information. Please visit us at MedCram.com. Thanks for joining us.