Clinical Infectious Diseases,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 17, 2024
Abstract
Background
PAXLOVID
consists
of
nirmatrelvir,
an
inhibitor
SARS-CoV-2
main
protease
(Mpro),
copackaged
with
ritonavir,
a
pharmacokinetic
enhancer.
Nirmatrelvir/ritonavir
received
emergency
use
authorization
in
the
United
States
2021
and
was
approved
2023.
However,
there
is
limited
published
information
on
clinical
resistance
to
nirmatrelvir/ritonavir.
Methods
To
investigate
development
nirmatrelvir/ritonavir
treated
patients,
we
analyzed
baseline
matching
post-baseline
next-generation
sequencing
data
from
1,862
participants
(912
nirmatrelvir/ritonavir,
950
placebo)
EPIC-HR
EPIC-SR,
which
were
Phase
2/3,
randomized,
double-blind,
placebo-controlled
trials
mild-to-moderate
COVID-19.
Potential
resistance-associated
substitutions
(RAS)
defined
as
those
that
enriched
nirmatrelvir/ritonavir-treated
or
occurred
at
Mpro
positions
interest,
using
nonclinical
data.
sequence
databases
characterize
temporal
frequencies
RAS
circulating
viruses.
Results
In
EPIC-HR,
included
T21I
(n=1),
E166V
(n=3),
A173T
T304I
being
clearest
observed.
no
detected.
not
associated
hospitalization
death.
Analyses
did
reveal
concerning
increases
over
time.
Conclusions
trials,
emergence
infrequent
(<0.3%-1.1%).
Surveillance
currently
indicate
low
frequency
variants
RAS.
Collectively,
these
results
provide
most
comprehensive
analysis
setting
date.
Viral
sequences
should
continue
be
closely
monitored
identify
potential
nirmatrelvir/ritonavir-resistant
variants.
The Journal of Infectious Diseases,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Aug. 1, 2024
The
global
research
community
attacked
the
COVID-19
pandemic
and
its
causative
agent,
SARS-CoV-2,
with
intense
ferocity.Over
past
four
years,
one
could
argue
that
SARS-CoV-2
was
most
intensely
studied
virus
on
planet
dwarfing
publication
outputs
of
important
pathogens
such
as
HIV
influenza
virus*.In
addition,
prior
to
pandemic,
coronaviruses
(CoV)
had
been
researched
for
decades
since
their
discovery
in
1960s
(1)
experienced
experimental
renaissances
emergence
SARS-CoV
2002
(2)
MERS-CoV
2012
(3)
(Fig.
1).Yet
despite
volumes
research,
questions
about
CoV
biology
from
relatively
simple
complex,
remain
unclear.For
example,
what
is
clinical
course
infection?While
answering
this
early
may
have
garnered
a
straightforward
answer,
astronomical
case
numbers,
enterprising
scientists
time
collectively
worked
together
provide
insights
into
disease
gone
unnoticed
otherwise,
benefit
studying
rapid
explosive
infectious
disease.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 16, 2024
In
late
2019,
SARS-CoV-2
spilled-over
from
an
animal
host
into
humans,
where
it
efficiently
spread,
resulting
in
the
COVID-19
pandemic.
Through
both
natural
and
experimental
infections,
we
learned
that
many
species
are
susceptible
to
SARS-CoV-2.
Importantly,
animals
close
proximity
including
companion,
farmed,
those
at
zoos
aquariums,
became
infected,
studies
demonstrated
transmission
to/from
humans
these
settings.
this
study,
first
review
literature
of
infections
tigers
lions,
compare
species,
sex,
age,
virus
antibody
detection
assay,
types,
frequency
length
clinical
signs,
demonstrating
broad
heterogeneity
amongst
infections.
We
then
describe
a
outbreak
hyenas
Denver
Zoo
2021.
Animals
were
tested
for
viral
RNA
(vRNA)
four
months.
Lions
had
significantly
more
nasal
swabs
than
hyenas,
individual
lions
experienced
recrudescence
after
weeks
undetectable
vRNA.
Infectious
was
correlated
with
high
levels
vRNA
likely
be
detected
earlier
during
infection.
Four
months
post-infection,
all
generated
robust
neutralizing
titers.
infected
Delta
lineage
AY.20
identical
variant
circulating
less
1%
Colorado
time,
suggesting
single
spillover
event
human
spread
within
between
housed
zoo.
Better
understanding
epidemiology
susceptibility
is
critical
limit
current
future
protect
health.
Clinical Infectious Diseases,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 17, 2024
Abstract
Background
PAXLOVID
consists
of
nirmatrelvir,
an
inhibitor
SARS-CoV-2
main
protease
(Mpro),
copackaged
with
ritonavir,
a
pharmacokinetic
enhancer.
Nirmatrelvir/ritonavir
received
emergency
use
authorization
in
the
United
States
2021
and
was
approved
2023.
However,
there
is
limited
published
information
on
clinical
resistance
to
nirmatrelvir/ritonavir.
Methods
To
investigate
development
nirmatrelvir/ritonavir
treated
patients,
we
analyzed
baseline
matching
post-baseline
next-generation
sequencing
data
from
1,862
participants
(912
nirmatrelvir/ritonavir,
950
placebo)
EPIC-HR
EPIC-SR,
which
were
Phase
2/3,
randomized,
double-blind,
placebo-controlled
trials
mild-to-moderate
COVID-19.
Potential
resistance-associated
substitutions
(RAS)
defined
as
those
that
enriched
nirmatrelvir/ritonavir-treated
or
occurred
at
Mpro
positions
interest,
using
nonclinical
data.
sequence
databases
characterize
temporal
frequencies
RAS
circulating
viruses.
Results
In
EPIC-HR,
included
T21I
(n=1),
E166V
(n=3),
A173T
T304I
being
clearest
observed.
no
detected.
not
associated
hospitalization
death.
Analyses
did
reveal
concerning
increases
over
time.
Conclusions
trials,
emergence
infrequent
(<0.3%-1.1%).
Surveillance
currently
indicate
low
frequency
variants
RAS.
Collectively,
these
results
provide
most
comprehensive
analysis
setting
date.
Viral
sequences
should
continue
be
closely
monitored
identify
potential
nirmatrelvir/ritonavir-resistant
variants.
