Investigating the Neuroimmune, Cerebrovascular, and Cognitive Disturbances Associated with SARS‑CoV‑2 Infection: A Systematic Review of Post‑Acute Outcomes
Research Square (Research Square),
Год журнала:
2025,
Номер
unknown
Опубликована: Март 11, 2025
Abstract
Background
SARS-CoV-2,
initially
identified
as
a
respiratory
pathogen,
has
emerged
significant
driver
of
neurological
morbidity
in
the
post-acute
phase
infection.
A
substantial
body
evidence
now
underscores
persistent
neuroimmune
dysregulation,
cerebrovascular
injury,
and
cognitive
impairment
critical
contributors
to
long-term
disability
among
COVID-19
survivors.
However,
mechanistic
interplay
between
these
processes
their
clinical
implications
remains
incompletely
characterized.
Objectives
This
systematic
review
synthesizes
global
(1)
elucidate
pathophysiological
mechanisms
underlying
sequelae
COVID-19,
(2)
evaluate
prevalence
spectrum
neuroimmune,
cerebrovascular,
disturbances,
(3)
propose
actionable
strategies
for
management
future
research.
Methods
comprehensive
search
PubMed,
EMBASE,
Cochrane
Library
was
conducted
studies
published
January
1,
2020,
31,
2025.
Included
reported
on
neuroinflammatory
biomarkers,
events,
or
dysfunction
assessed
≥
4
weeks
after
acute
SARS-CoV-2
Two
independent
reviewers
screened
records,
extracted
data,
appraised
study
quality
using
PRISMA
2020
guidelines.
narrative
synthesis
performed,
supported
by
tabulated
summaries
descriptive
visualizations
key
findings.
Results
From
2,178
15
(n
=
73,435
participants)
met
inclusion
criteria.
Three
interrelated
pathological
domains
were
identified:
Neuroimmune
Dysregulation:
Persistent
elevation
pro-inflammatory
cytokines
(e.g.,
IL-6,
TNF-α),
microglial
activation,
neuronal
autoantibodies
42%
patients,
implicating
chronic
neuroinflammation.
Cerebrovascular
Complications:
3.7-fold
increased
stroke
risk
microvascular
injury
(22%
prevalence)
linked
SARS-CoV-2-induced
endothelial
dysfunction,
blood-brain
barrier
disruption,
thromboinflammatory
pathways.
Cognitive
Dysfunction:
Deficits
memory,
executive
function,
processing
speed
(58%
correlated
with
neuroimaging
grey
matter
atrophy
functional
connectivity
loss.
Conclusions
Post-acute
manifests
triad
vascular,
pathologies,
driven
synergistic
such
inflammation.
Early
detection
via
multimodal
screening
neuroimaging,
cytokine
profiling)
multidisciplinary
care
models
are
essential
mitigate
disability.
Future
research
must
prioritize
standardized
diagnostic
criteria,
elucidating
viral
neurotropism,
trials
evaluating
therapies
targeting
stabilization
immunomodulation.
Addressing
priorities
will
inform
evidence-based
interventions
improve
outcomes
growing
population
survivors
grappling
sequelae.
Язык: Английский
Investigating the Neuroimmune, Cerebrovascular, and Cognitive Disturbances Associated with SARS‑CoV‑2 Infection: A Systematic Review of Post‑Acute Outcomes
Research Square (Research Square),
Год журнала:
2025,
Номер
unknown
Опубликована: Март 21, 2025
Abstract
Background
SARS-CoV-2,
initially
identified
as
a
respiratory
pathogen,
has
emerged
significant
driver
of
neurological
morbidity
in
the
post-acute
phase
infection.
A
substantial
body
evidence
underscores
persistent
neuroimmune
dysregulation,
cerebrovascular
injury,
and
cognitive
impairment
critical
contributors
to
long-term
disability
among
COVID-19
survivors.
However,
mechanistic
interplay
between
these
processes
their
clinical
implications
remains
incompletely
characterized.
Objectives
This
systematic
review
meta-analysis
aim
(1)
elucidate
pathophysiological
mechanisms
underlying
outcomes
COVID-19,
(2)
evaluate
prevalence
spectrum
neuroimmune,
cerebrovascular,
disturbances
using
both
qualitative
quantitative
data,
(3)
propose
strategies
for
early
detection
management
based
on
rigorous,
evidence-based
findings.
Methods
comprehensive
search
PubMed,
EMBASE,
Cochrane
Library
was
conducted
studies
published
January
1,
2020,
31,
2025.
Included
reported
neuroinflammatory
biomarkers,
events,
or
dysfunction
assessed
≥
4
weeks
after
acute
SARS-CoV-2
Two
independent
reviewers
screened
records,
extracted
appraised
study
quality
PRISMA
2020
guidelines.
narrative
synthesis
supplemented
by
key
outcomes,
with
pooled
effect
estimates
calculated
random-effects
models
address
heterogeneity.
Results
From
2,178
10
(n
≈
77,300)
met
inclusion
criteria.
Three
interrelated
pathological
domains
were
identified:
Neuroimmune
Dysregulation:
Persistent
cytokine
elevations
(e.g.,
IL-6,
TNF-α),
microglial
activation,
neuronal
autoantibodies
(detected
~
18%
patients)
indicate
state
chronic
neuroinflammation.
Cerebrovascular
Complications:
3.7-fold
increased
risk
stroke,
along
blood–brain
barrier
(BBB)
disruption
microvascular
role
endothelial
thromboinflammatory
pathways.
Cognitive
Dysfunction:
Deficits
memory,
executive
function,
processing
speed,
up
58%
patients,
correlated
neuroimaging
findings
grey
matter
atrophy
altered
functional
connectivity.
The
yielded
standardized
mean
difference
IL-6
elevation
0.78
(95%
CI:
0.55–1.01;
p
<
0.001)
odds
ratio
stroke
3.7
2.1–6.4;
0.001).
Moderate-to-high
heterogeneity
(I²
50%
70%)
addressed
sensitivity
analyses,
which
confirmed
robustness
associations.
Conclusions
Post-acute
manifests
triad
vascular,
disturbances,
supported
analyses.
Early
identification
through
multimodal
screening
including
advanced
neuroimaging,
inflammatory
biomarker
profiling,
validated
assessments
are
essential.
Targeted
therapeutic
focusing
stabilization
immunomodulation
may
prove
pivotal
mitigating
disability.
Future
research
should
prioritize
outcome
measures
further
refine
interventional
approaches
inform
policy.
Язык: Английский
AI-based decoding of long covid cognitive impairments in mice using automated behavioral system and comparative transcriptomic analysis
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Май 15, 2025
Long
COVID
(LC)
following
SARS-CoV-2
infection
affects
millions
of
individuals
world-wide
and
manifests
with
a
variety
symptoms
including
cognitive
dysfunction
also
known
as
"brain
fog".
This
is
characterized
by
difficulties
in
executive
functions,
planning,
decision-making,
working
memory,
impairments
complex
attention,
loss
ability
to
learn
new
skills
perform
sophisticated
brain
tasks.
No
effective
treatment
options
currently
exist
for
LC-related
dysfunction.
Here,
we
use
the
IntelliCage,
which
an
automated
tracking
system
mice,
measuring
each
mouse
within
group
tasks
that
mimic
human
behaviors,
such
flexibility,
memory.
Artificial
intelligence
machine
learning
analyses
data
classified
LC
mice
into
distinct
behavioral
categories
from
non-infected
control
permitting
precise
identification
quantification
controlled,
replicable
manner.
Importantly,
find
brains
exhibit
transcriptomic
alterations
similar
those
observed
humans
suffering
impairments,
altered
expression
genes
involved
learning,
synaptic
neurotransmitters
Together,
our
findings
establish
validated
murine
model
unbiased
approach
study
first
time,
providing
valuable
tool
screening
potential
treatments
therapeutic
interventions.
Язык: Английский
Impacts of systemic milieu on cerebrovascular and brain aging: insights from heterochronic parabiosis, blood exchange, and plasma transfer experiments
GeroScience,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 23, 2025
Abstract
Aging
is
a
complex
biological
process
that
detrimentally
affects
the
brain
and
cerebrovascular
system,
contributing
to
pathogenesis
of
age-related
diseases
like
vascular
cognitive
impairment
dementia
(VCID)
Alzheimer’s
disease
(AD).
While
cell-autonomous
mechanisms
occur
within
cells,
independent
external
signals
from
neighboring
cells
or
systemic
factors,
account
for
some
aspects
aging,
they
cannot
explain
entire
aging
process.
Non-autonomous,
paracrine
endocrine,
pathways
also
play
crucial
role
in
orchestrating
aging.
The
milieu
modulates
through
pro-geronic
anti-geronic
circulating
factors
mediate
decline
confer
rejuvenative
effects.
This
review
explores
impact
on
with
particular
focus
findings
heterochronic
parabiosis,
blood
exchange,
plasma
transfer
experiments.
We
discuss
how
these
influence
fundamental
cellular
molecular
processes
endothelial
function,
neurovascular
coupling
mechanisms,
blood–brain
barrier
integrity,
neuroinflammation,
capillary
density,
amyloid
pathologies,
significant
consequences
function.
Additionally,
we
address
translational
potential
challenges
modifying
promote
health
prevent
impairment.
Язык: Английский
The Molecular Mechanisms of Cognitive Dysfunction in Long COVID: A Narrative Review
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(11), С. 5102 - 5102
Опубликована: Май 26, 2025
Cognitive
dysfunction
represents
one
of
the
most
persistent
and
disabling
features
Long
COVID,
yet
its
molecular
underpinnings
remain
incompletely
understood.
This
narrative
review
synthesizes
current
evidence
on
pathophysiological
mechanisms
linking
SARS-CoV-2
infection
to
long-term
neurocognitive
sequelae.
Key
processes
include
neuroinflammation,
blood–brain
barrier
(BBB)
disruption,
endothelial
dysfunction,
immune
dysregulation,
neuroendocrine
imbalance.
Microglial
activation
cytokine
release
(e.g.,
IL-6,
TNF-α)
promote
synaptic
neuronal
injury,
while
inflammasomes
such
as
NLRP3
amplifies
CNS
inflammation.
Vascular
abnormalities,
including
microthrombosis
BBB
leakage,
facilitate
infiltration
peripheral
cells
neurotoxic
mediators.
Hypothalamic–pituitary–adrenal
axis
reduced
vagal
tone
further
exacerbate
systemic
inflammation
autonomic
Biomarkers
GFAP,
NFL,
S100B
have
been
associated
with
both
neuroinflammation
cognitive
symptoms.
Notably,
transcriptomic
signatures
in
COVID
overlap
those
observed
Alzheimer’s
disease,
highlighting
shared
pathways
involving
tau
oxidative
stress,
glial
reactivity.
Understanding
these
is
critical
for
identifying
at-risk
individuals
developing
targeted
therapeutic
strategies.
underscores
need
longitudinal
research
integrative
biomarker
analysis
elucidate
trajectory
impairment
COVID.
Язык: Английский