A unifying model to explain frequent SARS-CoV-2 rebound after nirmatrelvir treatment and limited prophylactic efficacy
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Июнь 28, 2024
Abstract
In
a
pivotal
trial
(EPIC-HR),
5-day
course
of
oral
ritonavir-boosted
nirmatrelvir,
given
early
during
symptomatic
SARS-CoV-2
infection
(within
three
days
symptoms
onset),
decreased
hospitalization
and
death
by
89.1%
nasal
viral
load
0.87
log
relative
to
placebo
in
high-risk
individuals.
Yet,
nirmatrelvir/ritonavir
failed
as
post-exposure
prophylaxis
trial,
frequent
rebound
has
been
observed
subsequent
cohorts.
We
develop
mathematical
model
capturing
viral-immune
dynamics
nirmatrelvir
pharmacokinetics
that
recapitulates
loads
from
this
another
clinical
(PLATCOV).
Our
results
suggest
nirmatrelvir’s
vivo
potency
is
significantly
lower
than
vitro
assays
predict.
According
our
model,
maximally
potent
agent
would
reduce
the
approximately
3.5
logs
at
5
days.
The
identifies
earlier
initiation
shorter
treatment
duration
are
key
predictors
post-treatment
rebound.
Extension
10
for
Omicron
variant
vaccinated
individuals,
rather
increasing
dose
or
dosing
frequency,
predicted
incidence
significantly.
Язык: Английский
Modeling suggests SARS-CoV-2 rebound after nirmatrelvir-ritonavir treatment is driven by target cell preservation coupled with incomplete viral clearance
Journal of Virology,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 4, 2025
ABSTRACT
In
a
subset
of
SARS-CoV-2-infected
individuals
treated
with
the
antiviral
nirmatrelvir-ritonavir,
virus
rebounds
following
treatment.
The
mechanisms
driving
this
rebound
are
not
well
understood.
We
used
mathematical
model
to
describe
longitudinal
viral
load
dynamics
51
20
whom
rebounded.
Target
cell
preservation,
either
by
robust
innate
immune
response
or
initiation
N-R
near
time
symptom
onset,
coupled
incomplete
clearance,
appears
be
main
factor
leading
rebound.
Moreover,
occurrence
is
likely
influenced
treatment
relative
progression
infection,
earlier
treatments
higher
chance
A
comparison
an
untreated
cohort
suggests
that
early
nirmatrelvir-ritonavir
may
associated
delay
in
onset
adaptive
response.
Nevertheless,
our
demonstrates
extending
course
10-day
regimen
greatly
diminish
people
mild-to-moderate
COVID-19
and
who
at
high
risk
severe
disease.
Altogether,
results
suggest
some
individuals,
standard
5-day
starting
around
completely
eliminate
virus.
Thus,
after
ends,
can
if
effective
has
fully
developed.
These
findings
on
role
target
preservation
clearance
also
offer
possible
explanation
for
other
SARS-CoV-2.
IMPORTANCE
Nirmatrelvir-ritonavir
initial
reduction
followed
once
stopped.
show
timing
influence
stops
growth
preserves
cells
but
lead
full
adequately
developed,
remaining
Our
provide
insights
into
help
develop
better
strategies
minimize
possibility.
Язык: Английский
Management of SARS-CoV-2 Infection-Clinical Practice Guidelines of the Polish Association of Epidemiologists and Infectiologists, for 2025
Journal of Clinical Medicine,
Год журнала:
2025,
Номер
14(7), С. 2305 - 2305
Опубликована: Март 27, 2025
The
first
Polish
recommendations
for
the
management
of
COVID-19
were
published
by
Society
Epidemiologists
and
Infectiologists
(PTEiLChZ)
on
31
March
2020,
last
three
years
ago.
emergence
new
SARS-CoV-2
variants,
a
different
course
disease,
as
well
knowledge
about
therapies
vaccines,
requires
updating
diagnostic,
therapeutic,
prophylactic
guidelines.
Despite
reduction
in
threat
associated
with
COVID-19,
there
is
risk
another
epidemic
caused
coronaviruses,
which
was
an
additional
reason
developing
version
In
preparing
these
recommendations,
Delphi
method
used,
reaching
consensus
after
survey
cycles.
Compared
to
2022
version,
names
individual
stages
disease
have
been
changed,
adapting
them
realities
clinical
practice,
attention
paid
differences
observed
immunosuppressed
patients
children.
Some
previously
recommended
drugs
discontinued,
including
monoclonal
antibodies.
addition,
general
principles
vaccination
presented,
issues
related
post-COVID
syndrome.
Язык: Английский
Modeling suggests SARS-CoV-2 rebound after nirmatrelvir-ritonavir treatment is driven by target cell preservation coupled with incomplete viral clearance
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 16, 2024
Abstract
In
a
subset
of
SARS-CoV-2
infected
individuals
treated
with
the
oral
antiviral
nirmatrelvir-ritonavir,
virus
rebounds
following
treatment.
The
mechanisms
driving
this
rebound
are
not
well
understood.
We
used
mathematical
model
to
describe
longitudinal
viral
load
dynamics
51
20
whom
rebounded.
Target
cell
preservation,
either
by
robust
innate
immune
response
or
initiation
nirmatrelvir-ritonavir
near
time
symptom
onset,
coupled
incomplete
clearance,
appear
be
main
factors
leading
rebound.
Moreover,
occurrence
is
likely
influenced
treatment
relative
progression
infection,
earlier
treatments
higher
chance
Finally,
our
demonstrates
that
extending
course
treatment,
in
particular
10-day
regimen,
may
greatly
diminish
risk
for
people
mild-to-moderate
COVID-19
and
who
at
high
severe
disease.
Altogether,
results
suggest
some
individuals,
standard
5-day
starting
around
onset
completely
eliminate
virus.
Thus,
after
ends,
can
if
an
effective
adaptive
has
fully
developed.
These
findings
on
role
target
preservation
clearance
also
offer
possible
explanation
other
SARS-CoV-2.
Importance
Nirmatrelvir-ritonavir
initial
reduction
followed
once
stopped.
show
timing
influence
stops
growth
preserves
cells
but
lead
full
adequately
developed,
remaining
Our
provide
insights
into
help
develop
better
strategies
minimize
possibility.
Язык: Английский
Coronavirus Disease 2019 Rebound in Nirmatrelvir Plus Ritonavir Treatment and Control Groups: A Prospective Cohort Study
Research Square (Research Square),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 6, 2024
Abstract
Observation
of
COVID-19
rebound
after
Nirmatrelvir
Plus
Ritonavir
(NPR)
has
driven
important
questions
surrounding
one
the
only
direct
acting
antiviral
treatments
for
COVID-19.
This
prospective
cohort
study
to
investigate
incidence
enrolled
917
positive
outpatients
via
a
digital
proctored
test-to-treat
solution.
Among
669
included
in
evaluation
493
intended
take
NPR
and
176
did
not.
Participants
were
provided
frequent
tests
symptom
surveys
15
days.
Time
initial
viral
or
clearance
was
not
different
between
groups.
Overall,
15-day
three-fold
higher
group
(15.2%
vs
5.4%,
p
<0.001)
double
(16.4%
8.4%,
<0.01).
those
experiencing
resolution,
resolution
notably
(43.8%
17.5%).
demonstrates
that
while
occurs
both
treated
untreated
outpatients,
is
group.
Язык: Английский
Meeting Report of the 37th International Conference on Antiviral Research in Gold Coast, Australia, May 20–24, 2024, organized by the International Society for Antiviral Research
Antiviral Research,
Год журнала:
2024,
Номер
232, С. 106037 - 106037
Опубликована: Ноя. 13, 2024
Язык: Английский
A theory for viral rebound after antiviral treatment: A study case for SARS-CoV-2
Mathematical Biosciences,
Год журнала:
2024,
Номер
unknown, С. 109339 - 109339
Опубликована: Ноя. 1, 2024
Язык: Английский
Molnupiravir clinical trial simulation suggests that polymerase chain reaction underestimates antiviral potency against SARS-CoV-2
medRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 22, 2024
Molnupiravir
is
an
antiviral
medicine
that
induces
lethal
copying
errors
during
SARS-CoV-2
RNA
replication.
reduced
hospitalization
in
one
pivotal
trial
by
50%
and
had
variable
effects
on
reducing
viral
levels
three
separate
trials.
We
used
mathematical
models
to
simulate
these
trials
closely
recapitulated
their
virologic
outcomes.
Model
simulations
suggest
lower
potency
against
pre-omicron
variants
than
omicron.
estimate
vitro
assays
underestimate
vivo
7-8
fold
omicron
variants.
Our
model
suggests
because
polymerase
chain
reaction
detects
molnupiravir
mutated
variants,
the
true
reduction
non-mutated
underestimated
∼0.5
log
10
two
conducted
while
dominated.
Viral
area
under
curve
estimates
differ
significantly
between
RNA.
results
reinforce
past
work
suggesting
are
unreliable
for
estimating
drug
endpoints
respiratory
virus
clinical
should
be
catered
mechanism
of
action.
Язык: Английский