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Background: Coronavirus (COVID-19) has emerged as a human catastrophe worldwide and it has impacted human life more detrimentally than the combined effect of World war I and II. Various research studies reported that the disease is not confined to the respiratory system but also leads to neurological and neuropsychiatric disorders suggesting that the virus is potent to affect the Central Nervous System (CNS). Moreover, the damage to CNS may continue to rise even after the COVID-19 infection subsides which may further induce a long-term impact on the brain, resulting in cognitive impairment. Proposed Hypothesis: Neuroimaging techniques provide the ability to detect and quantify pathological manifestations in the brain of COVID-19 survivors. In this context, a scheme based on structural, spectroscopic, and behavioral studies could be executed to monitor the gradual changes in the brain non-invasively due to COVID-19 which may further help in quantifying the impact of COVID-19 on the mental health of the survivors. Discussion: Extensive research is required in this direction for identifying the mechanism and implications of COVID-19 in the brain. Additionally, longitudinal follow-up studies are also needed to perform for monitoring the effects of this pandemic on individuals over a prolonged period.
Journal of Alzheimer’s Disease 83 (2021) 523–530
DOI 10.3233/JAD-210287
IOS Press
Brain Stress Mapping in COVID-19
Survivors Using MR Spectroscopy:
New Avenue of Mental Health Status
Avantika Samkariaa, Khushboo Punjabia, Shallu Sharmaa, Shallu Joona, Kanika Sandala,
Tirthankar Dasguptab, Pooja Sharmacand Pravat K. Mandala,d,
aNeuroimaging and Neurospectroscopy (NINS) Laboratory, National Brain Research Centre, Gurgaon, India
bMoner Alo, Psychiatric Clinic, Kolkata, West Bengal, India
cMedanta Institute of Education and Research, Medicity, Gurgaon, India
dFlorey Institute of Neuroscience and Mental Health, Melbourne School of Medicine Campus,
Melbourne, Australia
Accepted 29 June 2021
Pre-press 9 July 2021
Abstract. Coronavirus (COVID-19) has emerged as a human catastrophe worldwide, and it has impacted human life more
detrimentally than the combined effect of World Wars I and II. Various research studies reported that the disease is not
confined to the respiratory system but also leads to neurological and neuropsychiatric disorders suggesting that the virus
is potent to affect the central nervous system (CNS). Moreover, the damage to CNS may continue to rise even after the
COVID-19 infection subsides which may further induce a long-term impact on the brain, resulting in cognitive impairment.
Neuroimaging techniques is the ideal platform to detect and quantify pathological manifestations in the brain of COVID-19
survivors. In this context, a scheme based on structural, spectroscopic, and behavioral studies could be executed to monitor the
gradual changes in the brain non-invasively due to COVID-19 which may further help in quantifying the impact of COVID-
19 on the mental health of the survivors. Extensive research is required in this direction for identifying the mechanism and
implications of COVID-19 in the brain. Cohort studies are urgently required for monitoring the effects of this pandemic on
individuals of various subtypes longitudinally.
Keywords: Brain, cognition, COVID-19, gamma-aminobutyric acid, glutathione, magnetic resonance spectroscopy, mental
health, psychiatry
$Prof. Pravat Mandal dedicates this article to the fond memory
of Prof. Partha Raghunathan, a brilliant mind, who left us due to
Correspondence to: Pravat Kumar Mandal, Professor and Sci-
entist VII, Neuroimaging and Neurospectroscopy Laboratory,
National Brain Research Centre, India. E-mails: pravat.mandal@,; Honorary Professor, Florey Inst-
itute of Neuroscience and Mental Health, Melbourne School of
Medicine Campus, Melbourne, Australia. E-mail: pravat.mandal
Coronavirus (COVID-19) is an infectious disease
caused by severe acute respiratory syndrome corona
virus-2 (SARS-CoV-2). COVID-19 came into exis-
tence from Wuhan City, China in December
2019 [1]. The World Health Organization (WHO)
declared COVID-19 a pandemic on 11 March
2020 due to the continual dissemination of this
disease throughout the world [2]. According to
ISSN 1387-2877/$35.00 © 2021 – IOS Press. All rights reserved.
524 A. Samkaria et al. / Monitoring COVID-19 Induced Mental Health Using MRS
the WHO, as of 29 June 2021, a total of
181,176,715 cases including 3,930,496 deaths have
been confirmed globally due to COVID-19, where
30,316,897 cases with 397,637 fatalities are reported
solely from India [3]. A variety of precautionary
measures have been outlined by the WHO to pro-
tect humans from this infectious disease such as
social distancing, wearing a mask, avoiding crowds,
and regular cleaning of hands, etc. [4]. Despite con-
sidering these protective measures, the virus is still
continuously spreading worldwide and the number
of individuals affecting by COVID-19 is increasing
day by day. The mortality rate is too high in elderly
patients with low immunity due to nutritional defi-
ciencies [5]. In view of this, the identification of
effective drugs is vital for eradicating viral load from
the body of the individuals affected with COVID-
19 [6]. According to the WHO, a total of fifteen
vaccines have been developed up to now and some
of them are approved to use on an emergency basis
from the United States of America, Germany, United
Kingdom, Russia, China and India.
The main characteristic of this disease is pneumo-
nia [7]; however, cough, fever, dyspnea, anosmia,
myalgia, sore throat, gastrointestinal penetrations,
and rhinorrhea are the clinical manifestations that
are possessed by an individual infected by COVID-
19 [2, 8–10]. The infection is not limited to the
respiratory system but also adversely affects other
vital organs such as the heart, liver, and kidney as
well as brain [10–12]. Increased loneliness, isola-
tion, distress, anxiety, and depression can trigger the
onset of psychological illness in people [9, 13]. As
a matter of this fact, post-traumatic stress disorder,
depression, obsessive-compulsive disorder, and anx-
iety have been found as the most prevalent disorders
in the patients recovered from COVID-19 [14–16].
Human ability to perceive, manage, update, and
act on information in accordance with past experi-
ences contribute to cognitive function which largely
depends on the structural and functional integrity of
the prefrontal cortex [17]. Exposure to stress can
disrupt prefrontal cortex (PFC) function, causing
cognitive impairments [18, 19]. Numerous mental
illnesses—including obsessive-compulsive disorder,
depression, and anxiety disorders, etc., are character-
ized by PFC dysfunction [20]. Two recent studies,
one from the ward of a general hospital and the other
from a temporary quarantine facility, have shown
that as high as 9.4%, 15.1%, 24.5%, and 96.2% of
the COVID-19 patients had severe depressive, anx-
iety, and post-traumatic stress disorder symptoms.
COVID-19 itself can put a lot of stress on the brain
due to lockdown and complete isolation [21–23].
Many researchers and scientists have determined the
presence of the SARS-CoV-2 virus in a variety of
brain tissues such as cerebrospinal fluid (CSF), glial,
and neuronal cells via genomic sequencing which is
indicative of serious damage to the CNS [24]. The
presence of SARS-CoV-2 RNA in CSF suggests a
possible association of SARS-CoV-2 infection with
neurological symptoms in COVID-19 patients [10,
The FLAIR and diffusion weighted images have
also reported non confluent multifocal white mat-
ter hyper-intensities in the affected individuals along
with other imaging alterations [8, 28–30]. More-
over, the damage to CNS may continue to rise even
after the pulmonary infection subsides. COVID-19
infection in the brain can be associated with ext-
reme physical and psychological stress which stim-
ulates the hypothalamic-pituitary-adrenal axis and
aggravates neuroinflammation [31]. It is important
to note from a previous study that cognitive dis-
orders and neuroinflammation are correlated with
each other [9, 32]. A significant decline in cog-
nitive functioning has also been identified through
low scores of neuropsychological tests (continuous
performance test), greater reaction time, a deficit
in attention and executive functioning of COVID-
19 recovered patients [21, 22, 33–36]. Structural
changes have also been determined in the brain of
COVID-19 patients as compared to the non-infected
ones from a variety of studies where the researchers
claimed enlarged volumes of several brain regions
like the hippocampus, Heschl’s gyrus, olfactory cor-
tices, cingulate gyrus, and Rolandic operculum [23,
37]. Anatomically distinct regions of the nasophar-
ynx and brain show the presence of SARS-CoV-2
RNA and protein. This has been confirmed by the
autopsy studies of the patients [37]. Furthermore, a
description of morphological changes related to the
infection such as thromboembolic ischemic infarc-
tion of the CNS has been given. This suggests the
evidence of SARS-CoV-2 neurotropism. A meta-
analysis study indicates that no virus is present in
the CSF of patients and there is no direct neuroinva-
sion [38]. However, other groups of researchers have
suggested that SARS-CoV-2 seems to follow neu-
roanatomical structures which further penetrates into
defined neuroanatomical areas such as the primary
respiratory and cardiovascular control center in the
medulla oblongata [37, 39]. Therefore, it is impor-
tant to implement long-term studies for determining
A. Samkaria et al. / Monitoring COVID-19 Induced Mental Health Using MRS 525
the correlations among the clinical profile, laboratory
investigations, and radiological observations besides
neuropathological studies for an in-depth understand-
ing of the neurological manifestations in the patients
recovered from COVID-19. In this context, a scheme
for examining the glutathione (GSH), glutamatergic,
and GABAergic systems in hippocampal and dorso-
lateral prefrontal cortex (DLPFC) area of the brain
has been proposed. Additionally, the implications of
neuropsychological evaluation in diagnosing early
mental health problems in COVID-19 survivors has
also been outlined. The major rationale behind the
proposed scheme is the increased level of oxidative
stress in COVID-19 survivors which further con-
tributes to the pathogenesis of several neurological
diseases due to depletion of antioxidants.
Recent research findings suggest that coronavirus
may enter the CNS via two pathways: direct [40] and
indirect [41]. In the direct pathway, the virus may
enter via the blood-brain barrier, blood-CSF barrier,
and retrograde axonal transport to reach the neuronal
cell bodies in the CNS (see Fig. 1). The olfactory,
respiratory, and enteric nervous system networks are
the three possible pathways through which retro-
grade axonal transport can occur [12–15]. Ongoing
research suggests that SARS-CoV-2 is likely to enter
the nervous system by crossing the neural–mucosal
interface in olfactory mucosa, which subsequently
deteriorates the close domain of olfactory endothelial,
mucosal, and nervous tissue, involving the delicate
sensory and olfactory nerve endings [37]. Other
researchers have also reported that from the olfac-
tory bulb, the virus may tend to target deeper parts of
the brain such as the brainstem and thalamus by trans-
synaptic transfer which has also been described for
several distinct viral diseases. They suggest that the
infection of the respiratory center of the brain might
take place which explains the respiratory breakdown
in patients [42].
In respect to the indirect mechanisms, researchers
proposed that respiratory failure-induced hypoxia
and immune system malfunction may lead to neu-
ronal damage [4, 43]. The pro-inflammatory cytok-
ines (IL-6 and TNF-) are released in abundance in
response to a viral infection which causes excessive
Fig. 1. A schematic representation of COVID-19 virus routes to the respiratory system and the brain. A) COVID-19 infection routes for brain
and lung damage, B) invasion of the SARS-CoV-2 into the nervous system through the blood-brain barrier, and C) intrusion of SARS-CoV-2
into lungs by fusing with an angiotensin-converting enzyme (ACE2). Reproduced with permission from the publisher [40]. Ab, antibody;
ACE2, angiotensin-converting enzyme 2; CSF, cerebrospinal fluid; ER, endoplasmic reticulum; TNF, tumor necrosis factor.
526 A. Samkaria et al. / Monitoring COVID-19 Induced Mental Health Using MRS
inflammation of the blood-brain barrier [10, 41]. Con-
sequently, the permeability of the blood-brain barrier
is increased which further provides a pathway for
the virus to enter the brain indirectly. Infection of
the peripheral myeloid cells is another possibility
through which the virus may give rise to the psy-
chiatric symptoms indirectly by causing neuroinflam-
mation and virus-induced neuropathology [44].
Oxidative stress can be described as the increased
production of reactive oxygen species and deple-
tion of antioxidants which further contributes to the
pathogenesis of several neurological diseases [5].
In patients infected with COVID-19, a high neu-
trophil to lymphocyte ratio has been observed which
is strongly associated with an excessive level of reac-
tive oxygen species. Consequently, the increasing
load of viral infection causes a decrease in antioxi-
dant defense. GSH deficiency appears to be a primary
factor in enhancing SARS-CoV-2-induced oxidative
damage which further gives rise to many clinical
expressions such as multiorgan failure, acute respi-
ratory distress syndrome, and even death in patients
with COVID-19 infection [40]. GSH is the most
important antioxidant in the human brain which
plays a vital role in antioxidant defense. A variety
of studies related to postmortem and neurologi-
cal disorders have observed a significant depletion
in GSH through magnetic resonance spectroscopy
(MRS) [45]. Detection of extended and closed con-
formers of GSH has also been performed using the
MEGA-PRESS sequence [46]. Alterations of GSH
conformers is also detected [47]. Thus, measuring
GSH for comparison between patient and control
groups can be performed. Recently, it has also been
found that GSH and its precursor’s supplements aid in
recovery from respiratory distress in patients infected
with COVID-19 [48, 49]. GSH has been identified as
a source that can inhibit the main protease (Mpro) of
COVID-19 [50]. In this context, the use of GSH as
a supportive strategy for the treatment of COVID-19
infection can be recommended after a successful trial.
Primary excitatory and inhibitory neurotransmit-
ters, i.e., GABA and glutamate also play a key
role in modulating activity in the brain circuitry
[51, 52]. Prolonged stress can cause loss of pre-
frontal glutamate transmission that may alter the
hippocampal memory formation leading to dysfunc-
tion in cognitive function [53]. Dysfunction of the
glutamatergic system can give rise to defects in
neurotransmission, and cell viability which is fur-
ther implicated in various psychiatric disorders [54].
Stress-induced alterations in the functionality of
GABAergic inhibitory neurotransmission and synap-
Fig. 2. Detection of GSH, GABA+, and Glx metabolite from the DLPFC of a healthy young volunteer using 3T (Philips, Innova) scanner
at NBRC. A) T2w image with a voxel placed in DLPFC region in the brain for acquiring GSH and GABA. B) Closed and extended GSH
conformers at 2.95 and 2.80 ppm [46] with aspartate moiety signals from N-Acetyl-Aspartate at 2.67 ppm (NAA). C) MRS signal representing
the peaks of GABA and glutamine/glutamate (Glx) where the baseline spectra and fitted spectra are shown in blue and red, respectively.
A. Samkaria et al. / Monitoring COVID-19 Induced Mental Health Using MRS 527
tic integrity in the PFC may lead to dysfunction of
PFC microcircuitry. This may further trigger cogni-
tive impairments due to disruption in the execution
of behavioral responses [55]. Therefore, the level
of glutamate and GABA can serve as a promising
parameter to monitor mental health and psychi-
atric disease-associated conditions. SARS-CoV-2 has
neurotrophic properties which cause various CNS
manifestations including psychiatric diseases [56].
There has been growing evidence of patients suffering
from psychiatric diseases possibly due to COVID-19
[57]. In view of this, the involvement of GABAgeric
neuronal dysfunction in psychiatric disorders and
associated mechanism has become an active area of
research. Many studies have shown heterogeneous
results while measuring the GABA level in patients
with psychiatric disorders [58]. The level of GABA
for some patients has increased while the GABA level
remained unaltered for other patients. Hence, a lon-
gitudinal follow-up study can also be performed to
correlate the GABA level with psychiatric problems.
All the above-discussed antioxidants and neu-
rotransmitters have potential implications for psy-
chiatric disorders in COVID-19 affected patients.
Implementation and validation of imaging and spec-
troscopy technologies (MRI and MRS) can help in
finding out structural as well as metabolic changes
in the brain [59]. Literature describing the neuro-
logic symptoms of COVID-19 infection is increasing
rapidly. Despite this, there are only a few pub-
lished sources that demonstrate the findings based
on neuroimaging techniques to monitor neurological
infection in COVID-19 patients [29]. Researchers are
analyzing the hyperintensities from FLAIR images
and metabolites information from single-voxel MRS
which indicates the changes in structure and the level
of metabolites in the brain, respectively [60, 61].
Based on the prior knowledge, we are proposing a
scheme for examining the GSH, glutamatergic sys-
tems in the hippocampal and dorsolateral prefrontal
cortex area of the brain. Additionally, a neuropsycho-
logical evaluation is also likely to help in diagnosing
the mental health problems in COVID-19 survivors
In this COVID-19 pandemic situation, worldwide
intense efforts have helped to detect the pathology
of the SARS-CoV-2 virus in humans and determined
the post-recovery effects of the virus on their men-
tal health. A variety of case studies and reports have
suggested a probable relationship between the viral
infection due to SARS-CoV-2, oxidative stress, and
neurological symptoms. The possibility of gradual
damage to the brain and indistinct neurologic clinical
manifestation requires further investigation to deter-
mine its long-term neurologic consequences. The
non-invasive imagining-based strategy supported by
psychiatric and neuropsychological evaluation could
be a combined initiative in the direction of finding a
correlation between the alteration in antioxidant’s and
neurotransmitters’ concentration besides the struc-
tural changes in the brain to quantify the neurological
impact caused by the virus on the mental health of
COVID-19 survivors. This manuscript is a sincere
attempt to highlight the impact of the SARS-CoV-2
for neurological and neuropsychiatric manifestation
to make a top research priority. We have initiated
cohort study specifically focused on mental health
monitoring using brain structural and neurochemi-
cal data by MRI/MRS and behavioral data analysis
Dr. Pravat Mandal (Principal Investigator) thanks
for partial financial support from various agencies
(Tata Innovation grant, and Indo Australian strategic
funding to PKM). Thanks to the computing support
of NBRC for basic infrastructure support.
Authors’ disclosures available online (https://
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... Psychological factors may represent one of the important mechanisms responsible for the exacerbation and/or maintenance of a various neurological COVID-19-related symptoms in acute and post-acute period of COVID-19. In acute COVID-19, depression, fears and social isolation can worsen clinical condition and lead or contribute to exacerbation of a various neurologic and psychiatric conditions, such as anxiety and post-traumatic stress disorder (PTSD) (Fu et al., 2021;Samkaria et al., 2021) and fatigue (Morgul et al., 2021). Psychological stress related to acute COVID-19 is likely to be caused by the fear of death, fear of infecting family and other people and by social isolation due to quarantine. ...
Full-text available
Theoretical considerations related to neurological post-COVID complications have become a serious issue in the COVID pandemic. We propose 3 theoretical hypotheses related to neurological post-COVID complications. First, pathophysiological processes responsible for long-term neurological complications caused by COVID-19 might have 2 phases: (1) Phase of acute Sars-CoV-2 infection linked with the pathogenesis responsible for the onset of COVID-19-related neurological complications and (2) the phase of post-acute Sars-CoV-2 infection linked with the pathogenesis responsible for long-lasting persistence of post-COVID neurological problems and/or exacerbation of another neurological pathologies. Second, post-COVID symptoms can be described and investigated from the perspective of dynamical system theory exploiting its fundamental concepts such as system parameters, attractors and criticality. Thirdly, neurofeedback may represent a promising therapy for neurological post-COVID complications. Based on the current knowledge related to neurofeedback and what is already known about neurological complications linked to acute COVID-19 and post-acute COVID-19 conditions, we propose that neurofeedback modalities, such as functional magnetic resonance-based neurofeedback, quantitative EEG-based neurofeedback, Othmer’s method of rewarding individual optimal EEG frequency and heart rate variability-based biofeedback, represent a potential therapy for improvement of post-COVID symptoms.
Full-text available
Post-COVID-19 complications involve a variety of long-lasting health complications emerging in various body systems. Since the prevalence of post-COVID-19 complications ranges from 8–47% in COVID-19 survivors, it represents a formidable challenge to COVID-19 survivors and the health care system. Post-COVID-19 complications have already been studied in the connection to risk factors linked to their higher probability of occurrence and higher severity, potential mechanisms underlying the pathogenesis of post-COVID-19 complications, and their functional and structural correlates. Vaccination status has been recently revealed to represent efficient prevention from long-term and severe post-COVID-19 complications. However, the exact mechanisms responsible for vaccine-induced protection against severe and long-lasting post-COVID-19 complications remain elusive. Also, to the best of our knowledge, the effects of new SARS-CoV-2 variants and SARS-CoV-2 reinfections on post-COVID-19 complications and their underlying pathogenesis remain to be investigated. This hypothesis article will be dedicated to the potential effects of vaccination status, SARS-CoV-2 reinfections, and new SARS-CoV-2 variants on post-COVID-19 complications and their underlying mechanisms Also, potential prevention strategies against post-COVID complications will be discussed.
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The ongoing Coronavirus Disease 2019 (COVID-19) pandemic has affected more than 100 million people and clinics are being established for diagnosing and treating lingering symptoms, so called long-COVID. A key concern are neurological and long-term cognitive complications. At the same time, the prevalence and nature of the cognitive sequalae of COVID-19 are unclear. The present study aimed to investigate the frequency, pattern and severity of cognitive impairments 3-4 months after COVID-19 hospital discharge, their relation to subjective cognitive complaints, quality of life and illness variables. We recruited patients at their follow-up visit at the respiratory outpatient clinic, Copenhagen University Hospital, Bispebjerg, approximately four months after hospitalisation with COVID-19. Patients underwent pulmonary, functional and cognitive assessments. Twenty-nine patients were included. The percentage of patients with clinically significant cognitive impairment ranged from 59-65% depending on the applied cut-off for clinical relevance of cognitive impairment, with verbal learning and executive functions being most affected. Objective cognitive impairment scaled with subjective cognitive complaints, lower work function and poorer quality of life. Cognitive impairments were associated with d-dimer levels during acute illness and residual pulmonary dysfunction. In conclusion, these findings provide new evidence for frequent cognitive sequelae of COVID-19 and indicate an association with the severity of the lung affection and potentially restricted cerebral oxygen delivery. Further, the associations with quality of life and functioning call for systematic cognitive screening of patients after recovery from severe COVID-19 illness and implementation of targeted treatments for patients with persistent cognitive impairments.
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Abstract Background A large-scale global outbreak of coronavirus disease-19 (COVID-19) out of Wuhan, from China, occurred in January 2020. To examine the clinical characteristics of COVID-19 in infected patients out of Wuhan, from China. Methods Thirteen patients were confirmed to be infected with novel coronavirus-2019 (2019-nCoV) between January 27 and February 8, 2020, in Baoji city, Shannxi, northwestern China. Epidemiological and clinical information, and computed to morphology imaging data from all COVID-19 patients were collected; cases were divided into two groups according to the severity of infection (mild or severe). Results Nine (9/13) COVID-19 patients exhibited mild disease severity, and defined as second-generation human-to-human transmission cases. Most patients (11/13) had a history of travel to or from Wuhan. There were no differences in sex and age between the mild and severe cases (all P > 0.05). A moderate degree of fever (11/13), cough (13/13), and fatigue (8/13) were common symptoms; however, there was no statistical difference between mild and severe cases in this regard (all P > 0.05). Oxyhemoglobin saturation and oxygenation index decreased, and C-reactive protein (CRP) and serum amyloid A (SAA) levels were elevated in all patients with COVID-19 infection, with statistically significant differences between those with severe disease and mild infection (all P
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Objective: The "Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)" disease caused a challenging and threating pandemic (COVID-19) worldwide with a great loss to life and the global economy. SARS-CoV-2 mainly involves the respiratory system, however, with Magnetic Resonance Imaging (MRI), neurological and special senses clinical manifestations have been reported rarely. The present study aims to investigate the MRI findings, clinical manifestations of neurological and special senses involvement in SARS-CoV-2 patients. Materials and methods: In this study, 284 articles from the databases "Pub-Med, Web of Science-Clarivate Analytics, Embase and Google Scholar" were identified. The keywords, coronavirus, SARS-CoV-2, COVID-19 pandemic, MRI, brain, special senses, neurological involvement were entered into the search engines and the concerned documents were selected and reviewed. The descriptive information was recorded from the particular studies; finally, we included 48 publications. Results: The common neurological manifestations in SARS-CoV-2 patients were headache, impaired consciousness, acute cerebrovascular disease, ataxia, tremors, meningitis, encephalitis, cerebral bleeding, subarachnoid hemorrhage, frontal lobe, temporal lobe and intracerebral hematoma, hemiparesis and seizures. However, common special senses manifestations in SARS-CoV-2 patients were olfactory, auditory and gustatory disorders including red eyes, painless monocular visual disturbance, anosmia, ageusia, dysgeusia, dysosmia and hypoacusis. Moreover, the MRI findings identified in SARS-CoV-2 patients were isolated oval-shaped lesion in the corpus callosum, bilateral basal ganglia hemorrhage, ischemic lesions involving the corpus callosum, basal ganglia, cerebellum and vasogenic edema extending to the cerebral peduncles, pons and ventricles. Conclusions: The neurologic manifestations of SARS-CoV-2 patients are highly variable. The SARS-COV-2 exerts its damaging effects on the nervous system and special senses by developing determinant numerous neurological and special senses' clinical manifestations. Physicians with the help of MRI must rule out the neurological and special senses manifestations among SARS-CoV-2 patients.
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Neuropsychiatric complications associated with coronavirus disease 2019 caused by the Coronavirus SARS-CoV-2 (COVID-19) are increasingly appreciated. While most studies have focused on severely affected individuals during acute infection it remains unclear whether mild COVID-19 results in neurocognitive deficits in young patients. Here, we established a screening approach to detect cognitive deficiencies in post-COVID-19 patients. In this cross-sectional study, we recruited 18 mostly young patients 20 to 105 days (median 85 days) after recovery from mild to moderate disease who visited our outpatient clinic for post-COVID-19 care. Notably, 14 (78%) patients reported sustained mild cognitive deficits and performed worse in the Modified Telephone Interview for Cognitive Status (TICS-M) screening test for mild cognitive impairment compared to 10 age-matched healthy controls. While short-term memory, attention and concentration were particularly affected by COVID-19, screening results did not correlate with hospitalisation, treatment, viremia or acute inflammation. Additionally, TICS-M scores did not correlate with depressed mood or fatigue. In two severely affected patients we excluded structural or other inflammatory causes by magnetic resonance imaging, serum and cerebrospinal fluid analyses. Together, our results demonstrate that sustained subclinical cognitive impairments might be a common complication after recovery from COVID-19 in young adults, regardless of clinical course that were unmasked by our diagnostic approach.
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Objective: This mini review aims to provide insight into the neurological imaging in patients with coronavirus disease 2019 (COVID-19). Methods: PubMed, Embase, and Web of Science were searched through July 21, 2020, for relevant studies reporting the neuroimaging findings in COVID-19 patients with neurological manifestations. Proportion estimates with a 95% confidence interval (CI) were pooled after the Freeman–Tukey transformation. The heterogeneity across the included studies was also assessed. Results: Overall, 11 studies with a total of 659 patients were included. The pooled proportion estimate of abnormal neuroimaging finding in patients who exhibited neurological manifestation and underwent brain CT or MRI was 59% (95% CI, 39–77%). The proportions of acute/subacute ischemic infarction, intracranial hemorrhage, and subcortical or deep white matter abnormalities were 22% (95% CI, 17–28%), 24% (95% CI, 17–30%), and 27% (95% CI, 12–45%), respectively. Conclusion: This mini review comprehensively detailed neuroimaging findings of patients with COVID-19 and neurological manifestations. Clinicians should be familiar with the neuroimaging patterns to catch the sight of brain abnormalities caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel human coronavirus that has sparked a global pandemic of the coronavirus disease of 2019 (COVID-19). The virus invades human cells through the angiotensin-converting enzyme 2 (ACE2) receptor-driven pathway, primarily targeting the human respiratory tract. However, emerging reports of neurological manifestations demonstrate the neuroinvasive potential of SARS-CoV-2. This review highlights the possible routes by which SARS-CoV-2 may invade the central nervous system (CNS) and provides insight into recent case reports of COVID-19-associated neurological disorders, namely ischaemic stroke, encephalitis, encephalopathy, epilepsy, neurodegenerative diseases, and inflammatory-mediated neurological disorders. We hypothesize that SARS-CoV-2 neuroinvasion, neuroinflammation, and blood-brain barrier (BBB) dysfunction may be implicated in the development of the observed disorders; however, further research is critical to understand the detailed mechanisms and pathway of infectivity behind CNS pathogenesis.
Objective We sought to review the literature on cerebrospinal fluid (CSF) testing in patients with COVID-19 for evidence of viral neuroinvasion by SARS-CoV-2. Methods We performed a systematic review of Medline and Embase between December 1, 2019 and November 18, 2020 to identify case reports or series of patients who had COVID-19 diagnosed based on positive SARS-CoV-2 polymerase chain reaction (PCR) or serologic testing and had CSF testing due to a neurologic symptom. Results We identified 242 relevant documents which included 430 patients with COVID-19 who had acute neurological symptoms prompting CSF testing. Of those, 321 (75%) patients had symptoms that localized to the central nervous system (CNS). Of 303 patients whose CSF was tested for SARS-CoV-2 PCR, there were 16 (5%) whose test was positive, all of whom had symptoms that localized to the central nervous system (CNS). The majority (12/16, 75%) of these patients were admitted to the hospital because of neurological symptoms. Of 58 patients whose CSF was tested for SARS-CoV-2 antibody, 7 (12%) had positive antibodies with evidence of intrathecal synthesis, all of whom had symptoms that localized to the CNS. Of 132 patients who had oligoclonal bands evaluated, 3 (2%) had evidence of intrathecal antibody synthesis. Of 72 patients tested for autoimmune antibodies in the CSF, 4 (6%) had positive findings. Conclusion Detection of SARS-CoV-2 in CSF via PCR or evaluation for intrathecal antibody synthesis appears to be rare. Most neurological complications associated with SARS- CoV-2 are unlikely to be related to direct viral neuroinvasion.
In this mini-review, we aim to summarize some of the most common neuroimaging findings seen in patients with COVID-19.
PurposeCOVID-19, a disease that can be transmitted from person to person and with serious health problems, can be associated with mental health disorders. In this study, we evaluated the prevalence and severity of depression, anxiety, stress, and stress perception among a group of patients with COVID-19 who were hospitalized.Methods In this cross-sectional study, 106 inpatients with COVID-19 who had stable clinical conditions were evaluated psychologically by two questionnaires: Depression, Anxiety and Stress Scales-21 (DASS-21) and Perceived Stress Scale (PSS-4).ResultsMore than one third of patients had underlying disease. Overall, 97.2% of patients with COVID-19 had some degree of depression. Severity of depression, according to the DASS questionnaire, was 85.8%. All patients (100%) had severe (0.9%) and very severe (99.1%) anxiety. Regarding to stress levels, 97.1% of patients had some degree of stress. In the severity of stress category, 84.9% of patients had severe and very severe stress. In terms of perceived stress, 73.6% of patients had high levels and 22.6% had moderate levels. A positive strong correlation was found between depression and perceived stress (Coefficient: 0.33, P-value: 0.001). Correlation between anxiety and perceived stress was statistically significant (Coefficient: 0.2, P-value: 0.04).Conclusions The existence of such a high prevalence and severity of psychiatric disorders among hospitalized patients with COVID-19 underscores the need for serious attention to the mental health status of these patients. It seems that health policymakers need to have coherent plans for screening cases and managing related situations.
Apart from respiratory symptoms, encephalopathy and a range of central nervous system complications have been described in COVID-19 (Coronavirus Disease 2019). However, there is a lack of published literature on the rehabilitative course and functional outcomes of severe COVID-19 with encephalopathy. Additionally, the presence of subclinical neurocognitive sequelae during post-acute rehabilitation has not been described and may be under-recognized by rehabilitation providers. We report the rehabilitative course of a middle-aged male patient with severe COVID-19 who required intensive care and mechanical ventilation. During post-acute inpatient rehabilitation for severe ICU-related weakness, an abnormal cognitive screen prompted brain MRI imaging which revealed destructive leukoencephalopathy. Subsequently, detailed psychometric evaluation revealed significant impairments in the domains of processing speed and executive function. After 40 days of intensive inpatient rehabilitation, he was discharged home with independent function. This report highlights the need for an increased awareness of covert subclinical neurocognitive sequalae, the role of comprehensive rehabilitation and value of routine cognitive screening therein; and describes the neurocognitive features in severe COVID-19.