Catatonia Associated With Post-Acute COVID-19 in a Young Child

To date, there have been more than 800 million confirmed cases of severe acute respiratory  syndrome coronavirus 2 (SARS-CoV 2) infection globally, including  6.9 million deaths.¹ Numerous reports  have detailed neuropsychiatric  sequelae of COVID-19 infection,  including cognitive impairment, depression, and anxiety. There have  also been several reports describing  catatonia in the setting of COVID-19  infection. However, these reports have primarily been described in adults and  have been associated with the acute  phase of COVID-19 infection.² There  are limited but growing reports of  catatonia associated with acute  COVID-19 infection in pediatric  patients^3–5 and in the post-acute  phase of COVID-19 infection in  adults.^6–8 Varying definitions of “post-acute” or “post–COVID-19”  conditions led the World Health  Organization (WHO) to issue a clinical  case definition for a post–COVID-19  condition in children, which can be  summarized as symptoms causing  functional impairment that initially  occurred within 3 months of confirmed or probable SARS-CoV 2 infection and that have lasted at least  2 months.⁹ We present a case of  catatonia in a young pediatric patient  associated with the post-acute phase of SARS-CoV-2 infection.

Case Report

A 4-year-old girl with a history  of high-functioning autism spectrum  disorder (ASD) and no significant  medical history presented to her  primary care provider for cough with  confirmed SARS-CoV-2 infection. Two  weeks after diagnosis, she began a 10-  day course of amoxicillin-clavulanate  for lingering sinus symptoms, which  ultimately resolved. Four weeks after diagnosis, she appeared less interactive  and engaged in uncharacteristic  behaviors such as lying on the ground  and repeatedly covering her ears  and eyes. Over the next few weeks,  she exhibited a dramatic reduction  in meaningful speech, increased  repetitive purposeless movements  (jumping and rubbing limbs on  objects), increased repetitive speech,  grimacing, gait changes, ambitendency, and urinary incontinence. Three months after  initial diagnosis, she was admitted  to a tertiary care academic medical  center for further workup. Blood, urine, and cerebrospinal fluid (CSF)  studies—including autoimmune,  paraneoplastic, and infectious CSF  panels—were unremarkable except  for low ferritin (3.3 ng/mL). Antistreptolysin O titer was negative.  Magnetic resonance imaging of the  brain and spine was unremarkable.  Electroencephalogram showed slow and disorganized background but  was otherwise unremarkable. Rapid  whole-genome sequencing, including  mitochondrial DNA sequencing, was unremarkable. Given the negative  workup, she was discharged home.

At this point, catatonia was suspected, and empiric treatment  with oral lorazepam was started and  gradually increased to 0.7 mg 3  times daily. Seven days after beginning  lorazepam, she had her first formal  evaluation in the outpatient child and  adolescent psychiatry clinic. At this  visit, she displayed motor excitement;  constant stereotypies; frequent  mannerisms, grimacing, and impulsivity; and occasional mutism,  posturing, echolalia, verbigeration,  negativism, ambitendency, and  perseveration. She scored 21 on the  Bush-Francis Catatonia Rating Scale  (BFCRS).¹⁰ During this visit, her parents reported that since starting  lorazepam, she had become more  interactive, and her gait had become  more fluid. Contemporaneous  laboratory workup showed elevated  creatine phosphokinase (252 U/L).

Over the course of several months,  lorazepam was titrated to a maximum  of 8 mg daily in divided doses.  Treatment with lorazepam was  associated with further improvements  in meaningful speech and ambitendency, as well as resolution of  echolalia, mutism, verbigeration, and  perseveration. Unfortunately, relative  to baseline, symptoms of excitement,  posturing, stereotypies, mannerisms, and impulsivity persisted, albeit  improved from onset. At higher  lorazepam doses, she displayed  increased emotional lability and apparent fatigue; therefore, her dose  was gradually decreased. Her BFCRS  scores were serially monitored,  gradually decreasing from an initial  score of 21 to a score of 7 at 84 days  posttreatment initiation at a total  daily dose of 5.5 mg. Eventually,  lorazepam was tapered off at the  request of her parents, who opted to  pursue treatment with steroids. At  the time of the last contact in our  clinic and after initial steroid  treatment, she had not yet returned  to her baseline.

Discussion

To our knowledge, our patient is  the youngest to date to be diagnosed  with catatonia associated with SARS CoV-2 infection. Previous cases have  been documented in adolescents as  young as age 15 years. Our case is also  unique given the onset of catatonia  occurred 4 weeks after initial  laboratory diagnosis of SARS-CoV 2 infection and persisted for >3 months, which meets the WHO’s case definition for a post–COVID-19 condition in children  and adolescents.⁹

There have been multiple studies  describing the neuropsychiatric sequela  of COVID-19. Impaired concentration, memory loss, sleep difficulties, and increased risk for mood disorders,  anxiety disorders, and posttraumatic  stress disorder have been reported.^11,12  The incidence of catatonia associated  with SARS-CoV-2 infection remains  unclear. A study¹³ using the 2020 National Inpatient Sample  reported a discharge diagnosis of  COVID-19 infection co-occurred in  3.7% of hospitalizations for catatonia,  but the study also noted potential issues  with recognition of catatonia and  COVID-19 and likely errors in diagnostic  coding of catatonia. Cases of mild or  post-acute SARS-CoV-2 infection  associated with catatonia, such as our  case, may be underreported Given the suspected association  between catatonia and SARS-CoV-2,  several causal mechanisms have  been proposed. Ong et al¹⁴ recently  published a review of the proposed  mechanisms of neurological complications of post-acute COVID 19, which supports hypotheses  related to SARS-CoV 2 neuroinvasion, hypoxia, and  immune dysregulation. Spiegel et al⁷  previously reported a case of  catatonia associated with postacute  SARS-CoV-2 infection in a 59-year old patient with an initially severe  infection, in which they hypothesized  increased vulnerability to catatonia  may arise from reduced dopamine neurotransmission following the  entry of SARS-CoV-2 to the brain and  subsequent neuroinflammation.  Additional hypotheses for a causal  mechanism have been made, such as  molecular mimicry.¹⁵ γ-aminobutyric  acid (GABA)ergic intracortical  impairment has been observed in  patients with post-acute symptoms of  COVID-19.¹⁶ Interestingly, GABA-A  receptor levels have also been shown  to be downregulated in brains of  individuals with autism,¹⁷ which may  be related to the limited response to benzodiazepine treatment in our  patient. It is unclear whether the  mechanism by which SARS-CoV 2 infection precipitates catatonia might differ from the numerous other  medical conditions that have been  associated with catatonia in the  literature. It is also worth noting  that catatonia is relatively common in  patients with autism¹⁸; therefore,  an infection such as SARS-CoV-2 may  be regarded as an additional insult in  patients who are at a likely higher  vulnerability for catatonia.

It is also unclear whether the  patient’s partial response to benzodiazepine treatment is at all  related to SARS-CoV-2 infection  status, the timing of treatment for  catatonia after initial onset, or her  comorbidity of ASD. Partial response  to benzodiazepine treatment for  catatonia is well-documented. In a  prospective naturalistic cohort study  of 66 children and adolescents with  catatonia, benzodiazepines were  effective in 65% of cases when used,  with greater clinical response associated with less severe initial  symptoms of catatonia and with acute  onset (<10 days) of catatonia  symptoms.¹⁹ Numerous studies have  documented the association between  ASD and catatonia.²⁰ The delayed  diagnosis of catatonia by approximately 2 months after onset of  behavioral regression in the current  case is worth noting and underscores  frequent missed or misdiagnosis of  catatonia in both psychiatric and  general medical settings.^21–25 In a case  series²⁶ of 22 patients with ASD and  catatonia, most patients had partial or  no response to benzodiazepine  treatment and were ultimately treated  with electroconvulsive therapy (ECT).  ECT has been documented to  successfully treat catatonia associated  with COVID-19 in several adults^2,27 and  in an adolescent.⁵ ECT has been  shown to be effective for treating  catatonia in young children, although  this modality has not specifically been  studied in treatment of catatonia  associated with COVID-19. Given the  patient’s young age and her family’s preference, ECT was not pursued in  this case.

This case highlights the risk of  catatonia as an underlying etiology for  the clinical presentation of behavioral  regression during the post-acute  phase of SARS-CoV-2 infection in a  young child, especially when there  is a comorbid neurodevelopmental  disorder or ASD. Furthermore, as the  delay in treatment was approximately  2 months after initial onset of  behavioral regression, the adverse  effect of delayed treatment cannot  be ignored. It is recommended that  young patients presenting with  behavioral regression around the  time of SARS-CoV-2 infection be  monitored for catatonia and for  consideration of treatment with  benzodiazepines, with ongoing  monitoring for the need for further  interventions, such as ECT, as needed.

Article Information

Published Online: January 9, 2025. https://doi.org/10.4088/PCC.24cr03796
2025 Physicians Postgraduate Press, Inc.
Prim Care Companion CNS Disord 2025;27(1):24cr03796
Submitted: June 23, 2024; accepted September 12, 2024.
To Cite: Van Pay A, Mohiuddin S, Ghaziuddin N. Catatonia  associated with post-acute COVID-19 in a young child.  Prim Care Companion CNS Disord. 2025;27(1):24cr03796.
Author Affiliations: Department of Psychiatry, University  of Michigan, Ann Arbor, Michigan (Van Pay, Mohiuddin,  Ghaziuddin); Trinity Health IHA Medical Group, Ypsilanti,  Michigan (Van Pay).
Corresponding Author: Andrew Van Pay, MD, Trinity  Health IHA Medical Group, 5301 McAuley Dr, Ypsilanti,  MI 48197 ([email protected]).
Relevant Financial Relationships: None.
Funding/Support: None.
Patient Consent: Consent was received from the  patient’s guardian to publish the case report, and  information has been de-identified to protect anonymity.