Scientific Reports,
Год журнала:
2024,
Номер
14(1)
Опубликована: Фев. 9, 2024
Abstract
This
study
aimed
to
explore
the
effectiveness
and
safety
of
azvudine,
nirmatrelvir/ritonavir,
molnupiravir
in
adult
patients
with
mild-to-moderate
COVID-19.
retrospective
cohort
included
COVID-19
(asymptomatic,
mild,
common
types)
at
First
Hospital
Changsha
(Hunan
Province,
China)
between
March
November
2022.
Eligible
were
classified
into
or
groups
according
antiviral
agents
they
received.
The
outcomes
times
nucleic
acid
negative
conversion
(NANC).
157
treated
azvudine
(n
=
66),
nirmatrelvir/ritonavir
25).
There
no
statistically
significant
differences
time
from
diagnosis
NANC
among
molnupiravir,
[median,
9
(95%
CI
9–11)
vs.
11
10–12)
8–12)
days,
P
0.15],
administration
8–10)
10
9.48–11)
8.708
7.51–11)
0.50],
hospital
stay
11–13)
13
12–14)
12
10–14)
0.14],
even
after
adjustment
for
sex,
age,
type,
comorbidities,
Ct
level,
treatment,
number
symptoms.
cumulative
rates
15.2%/12.3%/16.0%
day
5
(
0.858),
34.8%/21.5%/32.0%
7
0.226),
66.7%/52.3%/60.0%
days
0.246),
86.4%/86.2%/80.0%
14
0.721).
No
serious
adverse
events
reported.
Azvudine
may
be
comparable
regarding
NANC,
stay,
AEs.
Nature Microbiology,
Год журнала:
2023,
Номер
8(5), С. 771 - 786
Опубликована: Май 4, 2023
Vaccines
and
monoclonal
antibody
treatments
to
prevent
severe
coronavirus
disease
2019
(COVID-19)
illness
were
available
within
a
year
of
the
pandemic
being
declared
but
there
remained
an
urgent
need
for
therapeutics
treat
patients
who
not
vaccinated,
immunocompromised
or
whose
vaccine
immunity
had
waned.
Initial
results
investigational
therapies
mixed.
AT-527,
repurposed
nucleoside
inhibitor
hepatitis
C
virus,
enabled
viral
load
reduction
in
hospitalized
cohort
did
reduce
outpatients.
The
molnupiravir
prevented
death
failed
hospitalization.
Nirmatrelvir,
main
protease
(Mpro),
co-dosed
with
pharmacokinetic
booster
ritonavir,
reduced
hospitalization
death.
Nirmatrelvir–ritonavir
received
Emergency
Use
Authorization
United
States
at
end
2021.
Immunomodulatory
drugs
such
as
baricitinib,
tocilizumab
corticosteroid,
which
target
host-driven
COVID-19
symptoms,
are
also
use.
We
highlight
development
challenges
that
remain
anticoronavirals.
Therapeutics
their
during
reviewed,
including
future
prospects
Annals of Internal Medicine,
Год журнала:
2023,
Номер
176(3), С. 348 - 354
Опубликована: Фев. 20, 2023
Although
symptom
and
viral
rebound
have
been
reported
after
nirmatrelvir-ritonavir
treatment,
the
trajectories
of
symptoms
load
during
natural
course
COVID-19
not
well
described.To
characterize
in
untreated
outpatients
with
mild
to
moderate
COVID-19.Retrospective
analysis
participants
a
randomized,
placebo-controlled
trial.
(ClinicalTrials.gov:
NCT04518410).Multicenter
trial.563
receiving
placebo
ACTIV-2/A5401
(Adaptive
Platform
Treatment
Trial
for
Outpatients
With
COVID-19)
platform
trial.Participants
recorded
severity
13
daily
between
days
0
28.
Nasal
swabs
were
collected
SARS-CoV-2
RNA
testing
on
14,
21,
Symptom
was
defined
as
4-point
increase
total
score
improvement
any
time
study
entry.
Viral
an
at
least
0.5
log10
copies/mL
from
immediately
preceding
point
3.0
or
higher.
High-level
5.0
higher.Symptom
identified
26%
median
11
initial
onset.
detected
31%
high-level
13%
participants.
Most
events
transient,
because
89%
95%
occurred
only
single
before
improving.
The
combination
observed
3%
participants.A
largely
unvaccinated
population
infected
pre-Omicron
variants
evaluated.Symptom
relapse
absence
antiviral
treatment
is
common,
but
rare.National
Institute
Allergy
Infectious
Diseases.
Annals of Internal Medicine,
Год журнала:
2023,
Номер
176(12), С. 1577 - 1585
Опубликована: Ноя. 13, 2023
Background:
Data
are
conflicting
regarding
an
association
between
treatment
of
acute
COVID-19
with
nirmatrelvir−ritonavir
(N-R)
and
virologic
rebound
(VR).
Objective:
To
compare
the
frequency
VR
in
patients
without
N-R
for
COVID-19.
Design:
Observational
cohort
study.
Setting:
Multicenter
health
care
system
Boston,
Massachusetts.
Participants:
Ambulatory
adults
use
N-R.
Intervention:
Receipt
5
days
versus
no
therapy.
Measurements:
The
primary
outcome
was
VR,
defined
as
either
a
positive
SARS-CoV-2
viral
culture
result
after
prior
negative
or
2
consecutive
loads
above
4.0
log10
copies/mL
that
were
also
at
least
1.0
higher
than
load
below
copies/mL.
Results:
Compared
untreated
persons
(n
=
55),
those
taking
72)
older,
received
more
vaccinations,
commonly
had
immunosuppression.
Fifteen
participants
(20.8%)
1
(1.8%)
who
(absolute
difference,
19.0
percentage
points
[95%
CI,
9.0
to
29.0
points];
P
0.001).
All
result.
In
multivariable
models,
only
associated
(adjusted
odds
ratio,
10.02
[CI,
1.13
88.74];
0.038).
Virologic
common
among
started
therapy
within
symptom
onset
(26.3%)
(0%)
(P
0.030).
Among
receiving
N-R,
prolonged
shedding
replication-competent
virus
compared
did
not
have
(median,
14
vs.
3
days).
Eight
16
(50%
25%
75%])
reported
rebound;
completely
asymptomatic.
No
post-VR
resistance
mutations
detected.
Limitations:
study
design
differences
treated
groups;
used
surrogate
marker
risk
ongoing
transmission.
Conclusion:
occurred
approximately
people
often
rebound,
virus.
Primary
Funding
Source:
National
Institutes
Health.
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.
