iScience,
Год журнала:
2023,
Номер
26(10), С. 107779 - 107779
Опубликована: Авг. 30, 2023
Emergence
of
new
SARS-CoV-2
VOCs
jeopardize
global
vaccine
and
herd
immunity
safeguards.
interactions
with
host
microbiota
might
affect
clinical
course
outcome.
This
longitudinal
investigation
involving
Pre-VOC
(Delta
&
Omicron)
holo-transcriptome
based
nasopharyngeal
microbiome
at
taxonomic
levels
followed
by
metabolic
pathway
analysis
integrative
host-microbiome
interaction.
showed
enrichment
Clinical Infectious Diseases,
Год журнала:
2022,
Номер
76(8), С. 1403 - 1411
Опубликована: Дек. 7, 2022
This
phase
2b
part
of
a
randomized
2/3
study
assessed
the
efficacy
and
safety
ensitrelvir
for
mild-to-moderate
coronavirus
disease
2019
(COVID-19)
during
Omicron
epidemic.Patients
were
(1:1:1)
to
orally
receive
fumaric
acid
125
mg
(375
on
day
1)
or
250
(750
placebo
once
daily
5
days.
The
co-primary
endpoints
change
from
baseline
in
severe
acute
respiratory
syndrome
2
(SARS-CoV-2)
titer
4
time-weighted
average
up
120
hours
total
score
predefined
12
COVID-19
symptoms.
Safety
was
through
adverse
events.A
341
patients
(ensitrelvir
125-mg
group:
114;
250-mg
116;
111;
male:
53.5-64.9%;
mean
age:
35.3-37.3
years)
included
analyses.
SARS-CoV-2
significantly
greater
with
both
doses
than
(differences
placebo:
-0.41
log10
50%
tissue-culture
infectious
dose/mL;
P
<
.0001
both).
symptoms
did
not
show
significant
difference
between
groups
group.
versus
several
subtotal
scores,
including
Most
events
mild
severity.Ensitrelvir
treatment
demonstrated
favorable
antiviral
potential
clinical
benefit
an
acceptable
profile.Japan
Registry
Clinical
Trials:
jRCT2031210350
(https://jrct.niph.go.jp/en-latest-detail/jRCT2031210350).
Nature Communications,
Год журнала:
2022,
Номер
13(1)
Опубликована: Авг. 24, 2022
Omicron
SARS-CoV-2
is
rapidly
spreading
worldwide.
To
delineate
the
impact
of
emerging
mutations
on
spike's
properties,
we
performed
systematic
structural
analyses
apo
spike
and
its
complexes
with
human
ACE2
or
S309
neutralizing
antibody
(NAb)
by
cryo-EM.
The
preferentially
adopts
one-RBD-up
conformation
both
before
after
binding,
which
in
sharp
contrast
to
orchestrated
conformational
changes
create
more
up-RBDs
upon
binding
as
observed
prototype
other
four
variants
concern
(VOCs).
Furthermore,
found
that
S371L,
S373P
S375F
substitutions
enhance
stability
prevent
exposing
triggered
binding.
increased
restricts
accessibility
S304
NAb,
targets
a
cryptic
epitope
closed
conformation,
thus
facilitating
immune
evasion
Omicron.
These
results
expand
our
understanding
receptor
mechanism.
Abstract
New
genetic
variants
of
severe
acute
respiratory
syndrome
coronavirus
2
(SARS‐CoV‐2)
constantly
emerge
through
unmitigated
spread
the
virus
in
ongoing
Coronavirus
disease
2019
pandemic.
Omicron
(B.1.1.529),
latest
variant
concern
(VOC),
has
so
far
shown
exceptional
and
infectivity
established
itself
as
dominant
recent
months.
The
SARS‐CoV‐2
spike
glycoprotein
is
a
key
component
for
recognition
binding
to
host
cell
angiotensin‐converting
enzyme
receptors.
harbors
cluster
substitutions/deletions/insertions,
more
than
30
mutations
are
located
spike.
Some
noticeable
mutations,
including
K417N,
T478K,
N501Y,
P681H,
shared
with
previous
VOCs
Alpha,
Beta,
Gamma,
or
Delta
have
been
proven
be
associated
higher
transmissibility,
viral
infectivity,
immune
evasion
potential.
Studies
revealed
that
partially
resistant
neutralizing
activity
therapeutic
antibodies
convalescent
sera,
which
poses
significant
challenges
clinical
effectiveness
current
vaccines
antibodies.
We
provide
comprehensive
analysis
summary
epidemiology
escape
mechanisms
variant.
also
suggest
some
strategies
against
This
review,
therefore,
aims
information
further
research
efforts
prevent
contain
impact
new
during
Abstract
Background
Limited
data
are
available
on
the
effectiveness
of
inactivated
and
Ad5-nCoV
COVID-19
vaccines
in
real-world
use—especially
against
Omicron
variants
SARS-CoV-2
infection-naïve
population.
Methods
A
matched
case-control
study
was
conducted
among
people
aged
≥
3
years
between
2
December
2021
13
May
2022.
Cases
were
SARS-CoV-2-infected
individuals,
individuals
with
severe/critical
COVID-19,
or
COVID-19-related
deaths.
Controls
selected
from
consecutively
test-negative
at
same
time
as
cases
diagnosed
exact-matched
year-of-age,
gender,
birthplace,
illness
onset
date,
residential
district
ratios
1:1
infected
4:1
death.
Additionally,
two
subsets
constructed
to
analyze
separate
vaccine
(VE)
(subset
1)
Ad5-vectored
2)
each
three
outcomes.
Results
Our
included
612,597
documented
infections,
which
1485
progressed
severe
critical
568
died.
Administering
provided
limited
protection
infection
across
all
age
groups
(overall
VE:
16.0%,
95%
CI:
15.1–17.0%)
but
high
(88.6%,
85.8–90.8%)
death
(91.6%,
86.8–94.6%).
In
subset
1,
showed
16.3%
(15.4–17.2%)
effective
infection,
88.6%
(85.8–90.9%)
COVIID-19,
91.7%
(86.9–94.7%)
Booster
vaccination
enhanced
(92.7%,
90.1–94.6%)
(95.9%,
91.4–98.1%).
Inactivated
VE
began
wane
12
weeks
after
last
dose,
doses
sustained
levels
(>
80%)
death,
while
13.2%
(10.9–15.5%)
77.9%
(15.6–94.2%)
COVIID-19.
Conclusions
found
durable
two-
three-dose
Omicron-associated
groups,
lower
reinforces
importance
full-series
timely
booster
dose
administration
for
eligible
individuals.
The
Omicron
BA.1
variant
of
SARS-CoV-2
escapes
convalescent
sera
and
monoclonal
antibodies
that
are
effective
against
earlier
strains
the
virus.
This
immune
evasion
is
largely
a
consequence
mutations
in
receptor
binding
domain
(RBD),
major
antigenic
target
SARS-CoV-2.
Previous
studies
have
identified
several
key
RBD
leading
to
escape
from
most
antibodies.
However,
little
known
about
how
these
interact
with
each
other
RBD.
Here,
we
systematically
map
interactions
by
measuring
affinity
all
possible
combinations
15
(2
=32,768
genotypes)
4
(LY-CoV016,
LY-CoV555,
REGN10987,
S309)
distinct
epitopes.
We
find
can
lose
diverse
acquiring
few
large-effect
reduce
others
through
small-effect
mutations.
our
results
also
reveal
alternative
pathways
antibody
does
not
include
every
mutation.
Moreover,
epistatic
shown
constrain
decline
S309
but
only
modestly
shape
landscapes
Together
previous
work
on
ACE2
landscape,
suggest
mediated
groups
mutations,
whose
deleterious
effects
compensated
another
group
(most
notably
Q498R
N501Y).
Medicine,
Год журнала:
2023,
Номер
102(8), С. e33024 - e33024
Опубликована: Фев. 22, 2023
Limited
treatment
options
exist
for
patients
with
mild-to-moderate
coronavirus
disease
2019
(COVID-19),
irrespective
of
vaccination
history
or
risk
status.
Ensitrelvir
is
a
novel
oral
severe
acute
respiratory
syndrome
2
(SARS-CoV-2)
3C-like
(3CL)
protease
inhibitor.
While
phase
studies
ensitrelvir
have
demonstrated
promising
results
in
treating
COVID-19,
evaluation
its
clinical
efficacy
due
to
shifting
status
and
emergence
the
Omicron
variant
represents
significant
challenges.
Here,
we
describe
protocol
3
study
designed
evaluate
safety
regardless
history.This
multicenter,
randomized,
double-blind,
placebo-controlled,
study.
Patients
COVID-19
within
120
hours
from
onset
will
be
randomized
1:1:1
ratio
into
arms-ensitrelvir
125
mg
(375
loading
dose
on
Day
1),
250
(750
placebo.
The
interventions
administered
orally,
once-daily,
5
days.
primary
endpoint
time
resolution
symptoms
(stuffy
runny
nose,
sore
throat,
cough,
feeling
hot
feverish,
low
energy
tiredness),
key
secondary
endpoints
include
change
baseline
4
amount
SARS-CoV-2
viral
ribonucleic
acid
(RNA)
first
negative
titer.
population
<72
randomization
and,
subsequently,
entire
patient
(<120
hours)
group.
Closed
testing
procedure
used
both
populations.
All
assessments
adverse
events
(AE)
reported.In
post
hoc
analysis
2b
study,
compared
placebo,
reduced
COVID-19.
Through
this
intend
validate
establish
Pathophysiology,
Год журнала:
2023,
Номер
30(2), С. 155 - 173
Опубликована: Апрель 22, 2023
In
recent
years,
the
elderly
has
become
a
rapidly
growing
proportion
of
world's
population
as
life
expectancy
is
extending.
Immunosenescence
and
inflammaging
contribute
to
increased
risk
chronic
non-communicable
acute
infectious
diseases.
Frailty
highly
prevalent
in
associated
with
an
impaired
immune
response,
higher
propensity
infection,
lower
response
vaccines.
Additionally,
presence
uncontrolled
comorbid
diseases
also
contributes
sarcopenia
frailty.
Vaccine-preventable
that
threaten
include
influenza,
pneumococcal
herpes
zoster,
COVID-19,
which
significant
disability-adjusted
years
lost.
Previous
studies
had
shown
conventional
vaccines
only
yielded
suboptimal
protection
wanes
shorter
time.
This
article
reviews
published
papers
on
several
vaccination
strategies
were
developed
for
solve
these
problems:
more
immunogenic
vaccine
formulations
using
larger
doses
antigen,
stronger
adjuvants,
recombinant
subunit
or
protein
conjugated
vaccines,
newly
mRNA
giving
booster
shots,
exploring
alternative
routes
administration.
Included
are
publications
senolytic
medications
under
investigation
boost
system
elderly.
With
all
those
regard,
currently
recommended
presented.
Mathematics,
Год журнала:
2023,
Номер
11(2), С. 369 - 369
Опубликована: Янв. 10, 2023
The
aim
of
this
paper
is
to
investigate
the
qualitative
behavior
COVID-19
pandemic
under
an
initial
vaccination
program.
We
constructed
a
mathematical
model
based
on
nonlinear
system
delayed
differential
equations.
time
delay
represents
that
vaccine
takes
provide
immune
protection
against
SARS-CoV-2.
impact
transmission
rates,
vaccination,
and
dynamics
system.
was
developed
for
beginning
implementation
programs
control
pandemic.
perform
stability
analysis
at
equilibrium
points
show,
using
methods
systems,
undergoes
Hopf
bifurcation.
theoretical
results
reveal
some
conditions
related
values
parameters
basic
reproduction
number,
approaches
disease-free
point,
but
if
number
larger
than
one,
endemic
SARS-CoV-2
cannot
be
eradicated.
Numerical
examples
corroborate
methodology.
Finally,
conclusions
discussions
about
are
presented.
Heliyon,
Год журнала:
2024,
Номер
10(9), С. e30208 - e30208
Опубликована: Апрель 25, 2024
The
rapid
emergence
of
multiple
strains
Severe
Acute
Respiratory
Syndrome
Coronavirus-2
(SARS-CoV-2)
has
sparked
profound
concerns
regarding
the
ongoing
evolution
virus
and
its
potential
impact
on
global
health.
Classified
by
World
Health
Organization
(WHO)
as
variants
concern
(VOC),
these
exhibit
heightened
transmissibility
pathogenicity,
posing
significant
challenges
to
existing
vaccine
strategies.
Despite
widespread
vaccination
efforts,
continual
SARS-CoV-2
presents
a
formidable
obstacle
achieving
herd
immunity.
Of
particular
is
coronavirus
spike
(S)
protein,
pivotal
viral
surface
protein
crucial
for
host
cell
entry
infectivity.
Mutations
within
S
have
been
shown
enhance
confer
resistance
antibody-mediated
neutralization,
undermining
efficacy
traditional
platforms.
Moreover,
undergoes
molecular
under
selective
immune
pressure,
leading
diverse
with
distinct
mutation
profiles.
This
review
underscores
urgent
need
vigilance
adaptation
in
development
efforts
combat
evolving
landscape
mutations
ensure
long-term
effectiveness
immunization
campaigns.
Vaccines,
Год журнала:
2023,
Номер
11(3), С. 545 - 545
Опубликована: Фев. 24, 2023
Over
the
years,
several
distinct
pathogenic
coronaviruses
have
emerged,
including
pandemic
SARS-CoV-2,
which
is
difficult
to
curtail
despite
availability
of
licensed
vaccines.
The
difficulty
in
managing
SARS-CoV-2
linked
changes
variants’
proteins,
especially
spike
protein
(SP)
used
for
viral
entry.
These
mutations,
SP,
enable
virus
evade
immune
responses
induced
by
natural
infection
or
vaccination.
However,
some
parts
SP
S1
subunit
and
S2
are
considered
conserved
among
coronaviruses.
In
this
review,
we
will
discuss
epitopes
proteins
that
been
demonstrated
various
studies
be
may
immunogenic
development
a
vaccine.
Considering
higher
conservancy
S2,
further
likely
challenges
could
limit
from
inducing
robust
promising
approaches
increase
its
immunogenicity.