Delirium and Other Neuropsychiatric Manifestations of COVID-19 Infection in People With Preexisting Psychiatric Disorders

A Systematic Review

Emma A. van Reekum; Tea Rosic; Anjali Sergeant; Nitika Sanger; Myanca Rodrigues; Reid Rebinsky; Balpreet Panesar; Eve Deck; Nayeon Kim; Julia Woo; Alessia D'Elia; Alannah Hillmer; Alexander Dufort; Stephanie Sanger; Lehana Thabane; Lawrence Mbuagbaw; Zainab Samaan

Disclosures

J Med Case Reports. 2021;15(586)

Abstract and Introduction

Abstract

Background: Psychiatric disorders increase risk of neuropsychiatric disease and poor outcomes, yet little is known about the neuropsychiatric manifestations of COVID-19 in the psychiatric population. The primary objective is to synthesize neuropsychiatric outcomes of COVID-19 in people with preexisting psychiatric disorders.

Methods: Data were collected during an ongoing review of the impact of pandemics on people with existing psychiatric disorders. All study designs and gray literature were included. Medline, PsychInfo, CINAHL, EMBASE, and MedRx were searched from inception to September 1 2020. Risk of bias was assessed using a published tool that can accommodate all study types. Two independent authors screened the studies and extracted data. Data were narratively synthesized, as there were insufficient data to meta-analyze. Evidence was appraised according to GRADE.

Results: Four case reports were included, comprising 13 participants from three countries. Many large-sample, relevant papers were omitted for not reporting psychiatric history, despite reporting other comorbidities. Included participants (n = 13) were hospitalized with COVID-19 and appeared to meet criteria for delirium. Myoclonus, rigidity, and alogia were also reported. The most commonly reported preexisting psychiatric diagnoses were mood disorders, schizophrenia, and alcohol use disorder.

Conclusions: People with preexisting psychiatric disorders may experience delirium, rigidity, myoclonus, and alogia during COVID-19 infection; although higher quality and longitudinal data are needed to better understand these phenomena. Relevant COVID-19 literature does not always report psychiatric history, despite heightened neuropsychiatric vulnerability within this population.

Trial Registration PROSPERO (CRD42020179611).

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Table 1. Summary of Study Findings
ID Country Sample size (n)	Case# Diagnosis Age Sex	Description of neuropsychiatric outcomes	Disposition	GRADE
Beach 2020 United States n = 4	(1) AUD—remitted, NCD 76 years Female	Admitted with aggression, paranoia, alogia, and abulia. On examination had myoclonus, increased tone, and palmomental reflex. She was febrile with elevated CRP and bibasilar opacity on CXR. She was COVID positive on PCR. Head CT was nil acute and MR, EEG, LP were not done. She was trialed on olanzapine and haloperidol for management with poor effect. Switched to chlorpromazine and clonidine patch	Palliative	Very low quality
	(2) AUD—remitted, NCD 70 years Male	Admitted with aggression, staring, alogia, and abulia. On examination had cogwheel rigidity and myoclonus. An EEG showed diffuse slowing and generalized discharges and head CT was nil acute. He was COVID positive on PCR. Lorazepam was trialed for query catatonia with poor effect. His aggression and delirium were managed with physical restraints and valproic acid	Improved
	(3) Schizophrenia 68 years Male	Admitted with a fall causing subdural hematoma (seen on head CT), UTI, AKI, and hypercalcemia. He was COVID positive on PCR. His longstanding clozapine and lithium were held, after which he developed agitation, alogia, abulia, and disorientation. He had mild tardive dyskinesia on examination. Delirium was managed with physical restraints and slow reintroduction of antipsychotics	Improved
	(4) MDD with psychosis, NCD 87 years Female	Admitted with agitation, disorientation, and slurred speech. On examination she had myoclonus. She was tachycardic and had elevated CRP and was COVID positive on PCR. Delirium was initially managed with physical restraints and haloperidol, and later with quetiapine	Deceased
Martinotti 2020 Italy n = 6	(5) MDD 61 years Male	Admitted with COVID pneumonia requiring NIMV. Hyperactive delirium managed with Abilify IM. Pre-dose-ICDSC score 6, post-dose score 2	NR	Very low quality
	(6) MDD with psychosis 60 years Male	Admitted with mild COVID pneumonia and fever. Developed hyperactive delirium, delusions of guilt, and suicidal ideation. Delirium managed with Abilify IM. Pre-dose ICDSC score 4, post-dose score 2	NR
	(7) BD 58 years Male	Admitted with COVID pneumonia requiring MV. Hyperactive delirium managed with Abilify IM. Pre-dose ICDSC score 5, post-dose 2	Recovered
	(8) MDD 64 years Male	Admitted with COVID pneumonia requiring NIMV. Hyperactive delirium managed with Abilify IM. Pre-dose ICDSC score 5, post-dose score 2	NR
	(9) BD 67 years Male	Admitted with COVID pneumonia requiring NIMV. Hyperactive delirium managed with Abilify IM. Pre-dose ICDSC score 5, post-dose score 2	NR
	(10) GAD 71 years Male	Admitted with COVID pneumonia requiring NIMV. Developed hyperactive delirium and persecutory delusions. Delirium managed with Abilify IM. Pre-dose ICDSC score 6, post-dose score 0	Recovered
Palomar-Ciria 2020 Spain n = 1	(11) Schizophrenia 65 years Male	Admitted with 20-day history of bizarre behavior and incoherent speech, as well as new aggression, insomnia, echolalia, and disorientation. Head MRI was performed because of abulia, showing findings of encephalopathy. He had COVID positive antibodies but a negative PCR. He was managed with melatonin, haloperidol, and amisulpride	Improved	Very low quality
Suwan-wongse 2020 United States n = 2	(12) BD 67 years Female.	Admitted with disorientation, incoherent speech, AKI, and lithium toxicity (2.3 mmol/L). She was febrile and had bilateral infiltrates on CXR. She was COVID positive on PCR. Her lithium toxicity was managed with fluid resuscitation	Deceased	Very low quality
Suwan-wongse 2020 United States n = 2	(13) ADHD, ASD, BD 18 years Male.	Admitted with altered consciousness, AKI, and lithium toxicity (2.6 mmol/L). He was febrile and tachycardic. His CXR was normal and he was COVID positive on PCR. He was managed conservatively with fluid resuscitation and cessation of lithium with plan to restart as an outpatient	Recovered	Very low quality

AKI Acute kidney injury, AUD alcohol use disorder, ADHD attention deficit hyperactive disorder, ASD autism spectrum disorder, BD bipolar disorder, CRP C-reactive protein, CXR chest X-ray, CT computed tomography, EEG electroencephalogram, GAD generalized anxiety disorder, ICDSC intensive care delirium screening checklist, IM intramuscular, LP lumbar puncture, MRI magnetic resonance imaging, MDD major depressive disorder, MV mechanical ventilation, NCD neurocognitive disorder, NIMV noninvasive mechanical ventilation, NR not reported, PCR polymerase chain reaction, UTI urinary tract infection

Table 3. Summary of neuropsychiatric manifestations of COVID-19
	Delirium	Agitation/aggression	Dysarthria	Abulia	Perceptual disturbance	Alogia	Myoclonus	Rigidity
Case 1	+	+	−	+	NR	+	+	+
Case 2	+	+	−	+	NR	+	+	+
Case 3	+	+	−	+	NR	+	−	−
Case 4	+	+	+	−	NR	−	+	−
Case 5	+	+	NR	NR	NR	NR	NR	NR
Case 6	+	+	NR	NR	+	NR	NR	NR
Case 7	+	+	NR	NR	NR	NR	NR	NR
Case 8	+	+	NR	NR	NR	NR	NR	NR
Case 9	+	+	NR	NR	NR	NR	NR	NR
Case 10	+	+	NR	NR	+	NR	NR	NR
Case 11	+	+	+	+	−	−	NR	NR
Case 12	+	NR	+	NR	NR	NR	NR	NR
Case 13	+	NR	−	NR	NR	NR	NR	NR
Tot	13	11	3	3	2	3	3	2