This
case
report
highlights
the
prolonged
SARS-CoV-2
reverse
transcriptase
polymerase
chain
reaction
positivity
in
a
32-year-old
immunocompromised
male
with
history
of
kidney
transplants
and
chronic
disease.
The
whole
genome
sequencing
nasopharyngeal
samples
for
collected
12
days
apart
showed
presence
BA.1.1
Omicron
variant.
It
revealed
evidence
intra-host
viral
evolution,
showing
development
loss
specific
mutations
over
time.
emphasizes
need
continuous
monitoring
strategies
patients,
as
they
may
serve
reservoirs
evolution
potentially
give
rise
to
immune
escape
variants.
Science Translational Medicine,
Год журнала:
2024,
Номер
16(731)
Опубликована: Янв. 24, 2024
Despite
vaccination
and
antiviral
therapies,
immunocompromised
individuals
are
at
risk
for
prolonged
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)
infection,
but
the
immune
defects
that
predispose
an
individual
to
persistent
disease
2019
(COVID-19)
remain
incompletely
understood.
In
this
study,
we
performed
detailed
viro-immunologic
analyses
of
a
prospective
cohort
participants
with
COVID-19.
The
median
times
nasal
viral
RNA
culture
clearance
in
immunosuppression
due
hematologic
malignancy
or
transplant
(S-HT)
were
72
40
days,
respectively,
both
which
significantly
longer
than
rates
autoimmunity
B
cell
deficiency
(S-A),
nonsevere
immunodeficiency,
nonimmunocompromised
groups
(
P
<
0.01).
Participants
who
severely
had
greater
SARS-CoV-2
evolution
higher
developing
resistance
against
therapeutic
monoclonal
antibodies.
Both
S-HT
S-A
diminished
SARS-CoV-2–specific
humoral
responses,
whereas
only
group
reduced
T
cell–mediated
responses.
This
highlights
varied
COVID-19
across
distinct
immunosuppressive
conditions
suggests
suppression
responses
results
highest
contributing
infection.
Viruses,
Год журнала:
2024,
Номер
16(2), С. 217 - 217
Опубликована: Янв. 31, 2024
Among
the
anti-Spike
monoclonal
antibodies
(mAbs),
S-309
derivative
sotrovimab
was
most
successful
in
having
longest
temporal
window
of
clinical
use,
showing
a
high
degree
resiliency
to
SARS-CoV-2
evolution
interrupted
only
by
appearance
BA.2.86*
variant
interest
(VOI).
This
success
undoubtedly
reflects
rational
selection
target
highly
conserved
epitope
coronavirus
Spike
proteins.
We
review
here
efficacy
against
different
variants
outpatients
and
inpatients,
discussing
both
randomized
controlled
trials
real-world
evidence.
Although
it
could
not
be
anticipated
at
time
its
development
introduction,
sotrovimab's
use
immunocompromised
individuals
who
harbor
large
populations
viruses
created
conditions
for
eventual
demise,
as
antibody
viral
led
withdrawal
due
inefficacy
later
lineages.
Despite
this,
based
on
observational
data,
some
authorities
have
continued
promote
sotrovimab,
but
lack
binding
newer
strongly
argues
futility
use.
The
story
highlights
power
modern
biomedical
science
generate
novel
therapeutics
while
also
providing
cautionary
tale
need
devise
strategies
minimize
emergence
resistance
antibody-based
therapeutics.
Journal of Clinical Investigation,
Год журнала:
2023,
Номер
133(6)
Опубликована: Март 14, 2023
COVID-19
in
immunocompromised
hosts
has
emerged
as
a
difficult
therapeutic
management
problem.
Immunocompromised
mount
weak
responses
to
SARS-CoV-2
and
manifest
infection
outcomes
ranging
from
severe
disease
persistent
infection.
Weakened
immune
systems
mean
greater
viral
loads
increased
opportunities
for
evolution.
Gupta,
Konnova,
et
al.
report
the
emergence
of
resistant
variants
patients
after
monoclonal
antibody
(mAb)
therapy.
mAbs
target
only
single
determinant
Spike
protein,
which
is
weakness
such
therapy
when
treating
mutagenic
variable
virus.
Hence,
mAb
resistance
could
have
been
anticipated,
but
its
documentation
important
because
it
major
public
health
implications,
since
potential
spread
escape
vaccine
immunity.
For
patients,
these
findings
suggest
need
combination
with
antiviral
drugs
use
polyclonal
preparations
convalescent
plasma.
The Lancet Microbe,
Год журнала:
2024,
Номер
5(5), С. e452 - e458
Опубликована: Март 22, 2024
IntroductionContinued
SARS-CoV-2
infection
among
immunocompromised
individuals
is
likely
to
play
a
role
in
generating
genomic
diversity
and
the
emergence
of
novel
variants.
Antiviral
treatments
such
as
molnupiravir
are
used
mitigate
severe
COVID-19
outcomes,
but
extended
effects
these
drugs
on
viral
evolution
patients
with
chronic
infections
remain
uncertain.
This
study
investigates
how
affects
prolonged
infections.MethodsThe
included
five
treated
four
not
(two
two
non-immunocompromised).
We
selected
who
had
been
infected
by
similar
variants
high-quality
genomes
across
timepoints
allow
comparison
between
groups.
Throat
nasopharyngeal
samples
were
collected
up
44
days
post
treatment
sequenced
using
tiled
amplicon
sequencing
followed
variant
calling.
The
UShER
pipeline
University
California
Santa
Cruz
genome
viewer
provided
insights
into
global
context
Treated
untreated
compared,
mutation
profiles
visualised
understand
impact
evolution.FindingsPatients
showed
large
increase
low-to-mid-frequency
little
10
after
treatment,
whereas
no
change
was
observed
patients.
Some
became
fixed
population,
including
non-synonymous
mutations
spike
protein.
distributed
unique
commonly
found
omicron
genomes.
Notably,
G-to-A
C-to-T
dominated
mutational
profile
patients,
persisting
treatment.InterpretationMolnupiravir
led
accumulation
distinctive
pattern
beyond
recommended
5
treatment.
maintained
persistent
PCR
positivity
for
duration
monitoring,
indicating
clear
potential
transmission
subsequent
variants.FundingAustralian
Research
Council.
Cell chemical biology,
Год журнала:
2024,
Номер
31(4), С. 632 - 657
Опубликована: Апрель 1, 2024
Over
four
years
have
passed
since
the
beginning
of
COVID-19
pandemic.
The
scientific
response
has
been
rapid
and
effective,
with
many
therapeutic
monoclonal
antibodies
small
molecules
developed
for
clinical
use.
However,
given
ability
viruses
to
become
resistant
antivirals,
it
is
perhaps
no
surprise
that
field
identified
resistance
nearly
all
these
compounds.
Here,
we
provide
a
comprehensive
review
profile
each
therapeutics.
We
hope
this
resource
provides
an
atlas
mutations
be
aware
agent,
particularly
as
springboard
considerations
next
generation
antivirals.
Finally,
discuss
outlook
thoughts
moving
forward
in
how
continue
manage
this,
next,
Vaccines,
Год журнала:
2024,
Номер
12(2), С. 129 - 129
Опубликована: Янв. 26, 2024
The
emergence
of
SARS-CoV-2
mutant
variants
has
posed
a
significant
challenge
to
both
the
prevention
and
treatment
COVID-19
with
anti-coronaviral
neutralizing
antibodies.
latest
viral
demonstrate
pronounced
resistance
vast
majority
human
monoclonal
antibodies
raised
against
ancestral
Wuhan
variant.
Less
is
known
about
susceptibility
evolved
virus
camelid
nanobodies
developed
at
start
pandemic.
In
this
study,
we
compared
nanobody
repertoires
in
same
llama
after
immunization
Wuhan’s
RBD
variant
subsequent
serial
variety
variants,
including
that
SARS-CoV-1.
We
show
initial
induced
highly
potent
nanobodies,
which
efficiently
protected
Syrian
hamsters
from
infection
virus.
These
however,
mostly
lacked
activity
omicron-pseudotyped
viruses.
contrast,
different
resulted
generation
demonstrating
higher
degree
somatic
mutagenesis
broad
range
neutralization.
Four
recognizing
distinct
epitopes
were
shown
potently
neutralize
spectrum
omicron
those
XBB
sublineage.
Our
data
broadly
may
be
readily
by
immunization.
eNeuro,
Год журнала:
2025,
Номер
12(1), С. ENEURO.0219 - 24.2024
Опубликована: Янв. 1, 2025
Brain-derived
neurotrophic
factor
(BDNF)
and
tropomyosin
receptor
kinase
B
(TrkB)
are
known
to
contribute
both
protective
pronociceptive
processes.
However,
their
contribution
neuropathic
pain
after
spinal
cord
injury
(SCI)
needs
further
investigation.
In
a
recent
study
utilizing
TrkB
