Asian Journal of Psychiatry 63 (2021) 102761

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Asian Journal of Psychiatry

journal homepage: www.elsevier.com/locate/ajp

Association between COVID-19 and catatonia manifestation in two

adolescents in Central Asia: Incidental findings or cause for alarm?
Svetlana Kopishinskaia a, b, Paul Cumming a, c, d, Svetlana Karpukhina e, Ivan Velichko f,
Galiya Raskulova g, Nazerke Zheksembaeva h, Dina Tlemisova h, Petr Morozov a, i,
Konstantinos N. Fountoulakis a, j, 1, Daria Smirnova a, e, *, 1
a
International Centre for Education and Research in Neuropsychiatry, Samara State Medical University, Samara, Russia
b
Department of Neurology, Neurosurgery and Neurorehabilitation, Kirov State Medical University, Kirov, Russia
c
Department of Nuclear Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
d
School of Psychology and Counselling, Queensland University of Technology, Brisbane, Australia
e
Department of Psychiatry, Narcology, Psychotherapy and Clinical Psychology, Samara State Medical University, Samara, Russia
f
Kuban State Medical University, Krasnodar, Russia
g
Nuclear Medicine Department, University Medical Center, Nur-Sultan, Kazakhstan
h
Regional Children’s Clinical Hospital, Karaganda, Kazakhstan
i
Department of Psychiatry, Faculty of Advanced Medical Studies, Russian National Medical Research University n.a. Pirogov, Moscow, Russia
j
3rd Department of Psychiatry, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece

A R T I C L E I N F O A B S T R A C T

Keywords: Catatonia is a rare neuropsychiatric syndrome that can accompany various medical conditions, including
Catatonia schizophrenia, autoimmune encephalitis, and infectious diseases. We present two cases of catatonia in males
COVID-19 aged 12 and 17 years from Central Asia who tested positive for SARS-Cov-2 antibodies. Detailed medical as­
FDG-PET
sessments declined other potential precipitating factors, including schizophrenia or anti-NMDA receptor auto­
Frontotemporal cortex
Neuropsychiatric complications
immune encephalitis. FDG-PET in the younger patient demonstrated focal hypometabolism in left frontotemporal
Psychomotor symptoms and right associative visual cortex, matching patterns previously seen in adults with catatonia. These isolated
findings raise concerns about a possible causal relationship between COVID-19 infection and risk of catatonia
manifestation in adolescents.

1. Introduction hyperthermia, rhabdomyolysis) (Cooper and Ross, 2020). Focusing on

Catatonia is a psychomotor syndrome associated with various mental
disorders and somatic conditions, which is often misdiagnosed by non-
psychiatrists as a manifestation of schizophrenia (Smith et al., 2012).
Post-encephalitic stupor and parkinsonism resembling catatonia was
registered after the Spanish influenza epidemic (Cheyette and Cum­
mings, 1995). Catatonia manifests in three clinical symptom clusters,
namely (i) excited catatonia (e.g., automatic obedience, echolalia, motor
repetition), (ii) the stuporous cluster (e.g., mutism, negativism,
posturing), and (iii) the malignant cluster (e.g., confusion,
dopaminergic mechanisms underlying catatonia, Buchsbaum et al.
(2007) demonstrated that younger adolescents were more vulnerable to
develop dopamine-mediated neuropsychiatric conditions.
Clinical reports of neuropsychiatric complications of COVID-19 point
to extensive immune response, vascular disturbances, hypoxic brain
damage, and neurotropic effects of the virus, which together might in­
crease the risk of developing catatonia (Banerjee and Viswanath, 2020;
Conde et al., 2020; Troyer et al., 2020). There is case report of catatonia
in association with peaking proinflammatory factors in an elderly
COVID-19 patient with preexisting schizophrenia (Gouse et al., 2020),

* Corresponding author at: International Centre for Education and Research in Neuropsychiatry, Samara State Medical University, 89 Chapayevskaya Str., Samara,
443099, Samara, Russia.
E-mail addresses: kopishinskaya@gmail.com (S. Kopishinskaia), paul.cumming@insel.ch (P. Cumming), karpukhinasb@bk.ru (S. Karpukhina), md.velichko@
mail.ru (I. Velichko), radiolog1710@mail.ru (G. Raskulova), Nazzon09@mail.ru (N. Zheksembaeva), Tlemisova5272@mail.ru (D. Tlemisova), profmorozov@
gmail.com (P. Morozov), kostasfountoulakis@gmail.com (K.N. Fountoulakis), daria.smirnova.md.phd@gmail.com (D. Smirnova).
1
Senior authors.

https://doi.org/10.1016/j.ajp.2021.102761
Received 23 May 2021; Received in revised form 29 June 2021; Accepted 7 July 2021
Available online 10 July 2021
1876-2018/© 2021 Elsevier B.V. All rights reserved.
S. Kopishinskaia et al.
and of catatonia as part of an acute psychotic exacerbation in a
middle-aged schizophrenic patient with COVID-19-related hypona­
tremia (Zandifar and Badrfam, 2021). A middle-aged male without
psychiatric history presented with catatonia during hospitalization for
COVID-19 (Caan et al., 2020).
Positron emission tomography (PET) with [18F]fluorodeoxyglucose
(FDG) revealed predominately left-sided hypometabolism in the frontal,
frontotemporal cortex regions in patients with catatonia after aseptic
encephalitis (Iseki et al., 2009), speech-sluggish catatonia (Lauer et al.,
2001), catatonia caused by paraneoplastic encephalitis (Kaestner et al.,
2008), and in catatonia of anti-NMDA receptor encephalitis (Endres
et al., 2019). There are several reports of hypometabolism in
orbito-frontal cortex of patients with post− COVID-19 anosmia (see
Afshar-Oromieh et al., 2021). Here we present two cases of clinically
diagnosed catatonia in adolescents from the same area of Central Asia,
with no history of psychiatric disorders or vaccination against
COVID-19, but with motor symptoms arising in asymptomatic
COVID-19 marked by SARS-Cov-2 antibodies. We also report FDG-PET
findings of cerebral metabolism in one of the adolescents.
2. Case report 1
Patient D., a 12-year-old male with history of perinatal encepha­
lopathy, was admitted to the inpatient pediatric department with the
referral diagnosis: “G 09 (ICD-10) Sequalae of inflammatory diseases of
central nervous system. Secondary parkinsonism after contracting
COVID-19. Akinetic-rigid syndrome, bradykinesia type” on 10/12/
2020. He tested positive for COVID-19 IgG but had neither pulmonary
symptoms, nor anosmia before onset of psychomotor disturbances.
D. was born from a first pregnancy complicated with toxicosis, but
with delivery on time and normal birth weight. With diagnosis of peri­
natal encephalopathy at birth and brief febrile seizures at six months and
(following sunstroke) at eight years, D. had developed physically ac­
cording to age norms, but with first use of language at four years. D. had
difficulties in coping with the standard school program, and had few
friends due to his reticence in communication with classmates.
Within onset in summer of 2020, D. demonstrated slowness in
movement and weight loss due to reduced appetite and spontaneous
fluid intake. D. was unable to begin school that September, but remained
in bed for extended periods in a fixed embryonic position. During hos­
pitalization across most of December, he demonstrated the pillow sign
within catatonic rigidity (Fig. 1), posturing, slow gait with festination,
sometimes walking by the wall, and trampling, but responding appro­
priately to simple commands of medical staff.
A child and adolescent psychiatrist, adult psychiatrist, and neurol­
ogist assessed D’s mental status via online videoconference on 18/01/
Fig. 1. Catatonic symptom “pillow sign” in 12-year-old adolescent after con­
tracting COVID-19.
2
Asian Journal of Psychiatry 63 (2021) 102761
2021. D. was dressed neatly, but sitting in a hunched position with hands
adducted to the body, and showing little movement. D. recognized his
mother and medical staff; he smiled at the consultants via videocall, but
responded to questions with quiet voice and low modulated prosody
after a long pause, with simple words or short monosyllabic answers. He
ignored several repeated questions, but responded correctly to simple
instructions such as “stand up” and “go”, whereupon he took a few short
steps at slow tempo. When requested by medical staff to drink, D. raised
the bottle to his mouth very slowly with a tensed hand in intermittent
movements, nearly spilling on himself. During muscle tonus examina­
tion, D. assumed a frozen position with raised hands, remaining in this
posture for minutes despite requests to put his hands down. Mimic re­
actions were monotonous. Intelligence level was evaluated as below the
age norm.
Extensive medical examination demonstrated the following signs: (i)
bilaterally enhanced reflexes via neurological examination, (ii) moder­
ate EEG disorganization with decreased bioelectric activity and singular
sharp beta-waves in frontal electrodes, (iii) increased level of cerulo­
plasmin (78 mg/dL; normal 30–35), (iv) positive infectious serologies
for cytomegalovirus IgG, and (v) thyroid hypoplasia alongside normal
T3/T4 levels. Anti-NMDA receptor encephalitis test was negative.
PET was undertaken with FDG (5.5 mCi) with a single frame
recording at 40 min after injection using an Ingenuity TF PET/CT, with
image normalization using the NeuroQ statistical package (Philips,
Netherlands). Investigation on 05/02/2021 demonstrated globally
normal metabolism, but with focal regions of relative hypometabolism
in inferior frontal (z = -3.17), inferior lateral posterior temporal cortex
(z = -2.22) and right associative visual cortex (z = -2.67) (Fig. 2).
3. Case report 2
Patient A., 17-year-old male, had been developing according to age
norms. He entered college after completing his ninth grade with satis­
factory school performance. With onset in May 2020, A. experienced
sleep disturbances, nocturnal waking, sitting up in bed, and telling his
mother about nightmares. His gait began to show hesitancy and
freezing, and his speech became mumbling. While visiting the toilet at
night, he would remain in the corridor treading in one place, and
Fig. 2. FDG-PET findings on hypometabolism in 12-year-old patient with
catatonia after contracting COVID-19. *.
* Hypometabolism in rAVC (right Associative Visual Cortex), lGFi (left inferior
Frontal Cortex), lLPT (left inferior lateral posterior Temporal Cortex).
S. Kopishinskaia et al.
repetitively vocalizing “now, now” to his mother. He reported that
something “terrible” was in the corridor, and became afraid of being
alone at home. A. might stay at a public transport stop for two hours
without being able to board a bus. In August 2020, he stopped going out
at all, remained in bed, and produced inarticulate vocalizations. There
was left side ptosis of the lower lip. In January 2021 he was admitted to a
psychiatric hospital where he was treated with risperidone. No psychi­
atric diagnosis was conveyed to his mother, but he tested positive for
IgM antibodies to SARS-Cov-2.
Mental status was assessed by the same group of specialists via
videoconference consultation on 26/01/2021. A. was then neatly
dressed, sitting in a hunched posture beside his mother. He was per­
forming tongue movements and still showed lower lip drop on the left
side. A. apparently understood the conversation and replied appropri­
ately to questions, but answered rapidly and abruptly in telegraphic
speech. He terminated words, with a swallowing of some phonemes. A.
did not perceive himself to be ill, and could not identify the reason for
his hospitalization, nor could he account for his slow walking, frozen
postures, and fearfulness. Nonetheless, there were no overtly psychotic
symptoms of thought or perception disturbances. Emotional reactions
were subdued and mimic was flat. General intelligence was slightly
below the age norm. A detailed clinical, laboratory, and instrumental
investigation revealed no significant medical conditions. Anti-NMDA
receptor encephalitis test was negative. FDG-PET was not available for
A. Due to the limited availability of FDG-PET in the region, the second
adolescent did not undergo this important investigation (Supplementary
material).
4. Discussion
There are a few reports of catatonia as a rare neuropsychiatric
complication among adults and elderly COVID-19 patients, occasionally
in those with history of schizophrenia (Caan et al., 2020; Gouse et al.,
2020; Zandifar and Badrfam, 2021). We now present psychopathologi­
cal descriptions of mental status of two adolescents with catatonia, both
from the same region of Central Asia and testing positive for SARS-Cov-2
antibodies. Neither patient had been vaccinated, so their positive anti­
body tests most likely indicate an immune response to the virus. Previ­
ous literature reports that acute and severe COVID-19 infection in adults
can increase the risk of developing catatonia (Conde et al., 2020; Troyer
et al., 2020). Despite these two adolescents having neither pulmonary
symptoms, nor the almost “pathognomonic” neurological sign of
anosmia, they developed distinct catatonia symptoms, including (i)
stuporous cluster symptoms – catatonic rigidity with cogwheel sign and
pillow sign, food refusal, mutism, posturing, postural instability, waxy
flexibility, and (ii) excited cluster symptoms – automatic obedience,
echolalia, motor repetition.
After consider both cases in detail, we speculated about a possible
causal relationship between their catatonia and SARS-Cov-2 infection.
According to anamnesis and clinical evaluation, neither patient had any
personal or family history of schizophrenia, nor indeed any prior psy­
chotic symptoms preceding their catatonia. Predisposing factors (such as
perinatal encephalopathy, brief infantile seizures) and comorbid con­
ditions (thyroid hypoplasia along with normal hormonal levels) are
unlikely to have caused the prolonged state of catatonia in case 1.
However, we speculate that this medical history might have increased
the adolescent’s vulnerability to develop neuropsychiatric complica­
tions in response to a neurotropic SARS-Cov-2 infection.
The examining psychiatrists did not find evidence supporting
schizophrenia diagnosis according to ICD-10 criteria. These include at
least one very clear symptom from a–d (thought echo, delusions of
control, hallucinatory voices, persistent delusions of other kinds) or two
very clear symptoms from e–i (persistent hallucinations in any modality,
breaks or interpolations in the train of thought, catatonic behavior,
negative symptoms such marked apathy, paucity of speech, and blunting
or incongruity of emotional response, a significant and consistent
3
Asian Journal of Psychiatry 63 (2021) 102761
change in overall quality of personal behavior) (WHO, 2004). While
showing distinct catatonic behavior, both patients remained emotion­
ally reactive, smiling in response to interlocutors and following con­
versation, albeit impeded by motor retardation. Moreover, the second
patient demonstrated a neurological symptom, namely a left-sided low
lip ptosis, pointing to a potential organic origin. However, we should
consider that the patient D. (case 1) might have had onset of psychotic
symptoms preceding or in conjunction to viral infection, a possibility
that cannot be resolved at present. Notably, laboratory investigations of
both cases were negative for anti-NMDA receptor autoimmune en­
cephalitis, a frequent cause of organic catatonia. Detailed medical
evaluation shed no light on other potential organic etiologies of cata­
tonia, including persistent somatic disorders. Moreover, the elevated
ceruloplasmin in the younger case may be a marker of a previously
active viral infection (Andreou et al., 2020). That same child showed
relative hypometabolism in the left frontotemporal area, which seems
consistent with earlier FDG-PET findings in catatonia associated with
exogenous/organic (e.g., infectious, autoimmune) origins, as distinct
from endogenous/schizophrenia conditions (Lauer et al., 2001; Kaestner
et al., 2008; Iseki et al., 2009). He also showed focal hypometabolism in
right associative visual cortex, perhaps consistent with visuospatial
processing impairments reported in some patients with mild COVID-19
(de Paula et al., 2021). Neither patient experienced anosmia, which is
associated with orbitofrontal hypometabolism in adult COVID-19 pa­
tients (for review, Afshar-Oromieh et al., 2021). We propose prospec­
tively studying frontotemporal cortex function in relation to catatonic
symptoms occurring in COVID-19 patients. We note that patient D.
responded to appropriate treatment with benzodiazepines, while patient
A. had inappropriate initial treatment with antipsychotic medication
(risperidone), which can worsen infection-related organic neuropsy­
chiatric disorders such as catatonia (Caan et al., 2020; Buchsbaum et al.,
2007; Zandifar and Badrfam, 2021). Differences in the two investigation
protocols represent a key limitation of this study. The professional
community should be alert to the possible significance of psychomotor
symptoms spontaneously appearing in adolescents during the present
COVID-19 pandemic, especially in those with the predisposing soma­
tic/neurological conditions.
Authors’ contributions
SKo, NZ, DT diagnosed the patients, in conjunction with remote
consultations for evaluation of mental status by DS, SKa, SKo, NZ, DT,
along with discussions with PM, KF and PC. SKo, GR and PC evaluated
FDG-PET results, SKo, IV, PC and DS reviewed the literature, PC and DS
interpreted results; DS wrote the first draft of the manuscript, which was
revised by PC, PM, KF and SKo and by all other coauthors.
Financial disclosure
None.
Declaration of Competing Interest
None to declare.
Acknowledgements
We express our gratitude to our patients and their families for their
agreement and participation in the cases investigation which has been
managed by the team of experts from International Centre for Education
and Research in Neuropsychiatry, Samara State Medical University.
Appendix A. Supplementary data
Supplementary material related to this article can be found, in the
online version, at doi:https://doi.org/10.1016/j.ajp.2021.102761.
S. Kopishinskaia et al. Asian Journal of Psychiatry 63 (2021) 102761

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