Acute SARS-CoV-2–induced Psychosis in an Adolescent

A 16-year-old male, unvaccinated for SARS-CoV-2, was admitted to the hospital with breathlessness and chest pain. He tested positive for SARS-CoV-2 on a lateral flow test at home a day before admission. On examination, he was propped up in bed, breathing heavily, and had difficulty completing full sentences. His vital signs were: blood pressure, 135 over 90; heart rate, 120 to 130 beats per minute; respiratory rate, 25 to 30 per minute; temperature 38.4°C; oxygen saturations between 95% and 100% on air; and Glasgow coma score of 15 of 15. Electrocardiogram revealed sinus tachycardia and chest x-ray findings were nonspecific. He had a low level of lymphocytes and slightly raised C-reactive protein of 39 µg/mL. Computed tomography with pulmonary angiogram on admission showed lung consolidation within the posterior segment of the left lower lobe, with the remainder of the lung clear and no pulmonary embolism visible. The initial impression was SARS-CoV-2 pneumonitis. He was treated with oral amoxicillin for 7 days and discharged 5 days postadmission. He did not require supplemental oxygen therapy.

He was readmitted 3 days later because of a sudden change in behavior. Family members reported that he was more anxious, had started to not make sense verbally, swore at parents (which was unusual for him), disrobed to his underwear, and used unusual gestures. He was oriented to time, place, and person, and there were no neurologic abnormalities other than his mentation. He would stare at the ceiling saying he could see messages and that he had special powers and exhibited increasing signs of paranoia and agitation. He expressed that the information system in his brain had been deleted and the government was “coming for him.” He experienced auditory hallucinations; “everyone around the world is saying not to let the doctors do the test” and believed the tests would kill him. However, he maintained reasonable eye contact and engagement throughout the review. He was bizarre and delusional, with fast tangential speech, and demonstrated hallucinations with some catatonic features. He reported feeling strong as a result of “putting blocks of combinations until maximum security was reached” and that the data in his brain could not be decoded again. He described characters from a computer game (Aida, from Fortnite) and jail break with “a constant flow of data” and needing to “overcome negative things.” He felt he needed to stabilize data. He typed in the air and mouthed inaudible words. He stated he could see 8 to 12 people in the room, and he believed he could read their minds. He expressed suicidal ideation.

The family reported that the child’s mother had a normal pregnancy and natural birth with no complications. There were no concerns regarding his developmental milestones or other notable issues during childhood. He had been functioning at an age-appropriate level and was thriving academically and socially with no history of physical illness. He had not been prescribed any regular medications except for the short course of antibiotics during his SARS-CoV-2 illness. There was no history of alcohol or illicit substance use, and there was no record of personal or family history of psychiatric illnesses within his immediate family.

Our clinical diagnosis was new onset florid psychosis and we investigated possible organic causes. Blood tests for liver, renal and thyroid functions, and inflammatory markers were all normal. Computed tomography and MRI of the brain were normal (Fig 1). Lumbar puncture revealed normal pressure, clear appearance of cerebrospinal fluid, protein 0.22mg/mL, and no cells. Culture of the cerebrospinal fluid was negative after 48 hours. The patient declined an EEG. We made a diagnosis of acute psychosis secondary to SARS-CoV-2 infection.

We recommended initial therapy with a low-dose antipsychotic, haloperidol, but the patient declined because he stated that “the ward staffs were poisoning” him. He had no insight into his illness and was deemed to lack capacity regarding his care and treatment. He was often agitated and unsettled and broke a glass in the ward door in an attempt to leave. He was administered antipsychotic and anxiolytic medication (haloperidol and lorazepam) under best interests with parental assent with some improvement in his presentation. He underwent an assessment under the Mental Health Act and was detained under Section 2 of the United Kingdom Mental Health Act (an involuntary detention for assessment and treatment of suspected mental illness for up to 28 days). During the course of his admission, he became calmer, although his psychotic features persisted. He was mostly mute and had few verbal interactions. He walked aimlessly around his room, smiling incongruously, and invaded the personal space of others. We transferred him to an acute general adolescent psychiatric unit for further management.

At the time of admission to the general adolescent psychiatric unit, he was placed on 1:1 observation. He was started on olanzapine 5 mg at night and, within a week, gradual improvement in his hallucinatory and paranoid experiences was noticed; that is, he was observed to be responding less to perceptual abnormalities and was more trusting of staff. Over the period of his stay, he continued to show gradual improvement with an increase in his olanzapine to 15 mg at night. He remained in the hospital voluntarily after expiration of his Section 2. By the time of his discharge, he was not experiencing any psychotic symptoms and he was able to understand that he had developed psychotic illness after SARS-CoV-2 infection. He was advised to continue the medication for at least 6 months before considering any changes. At his most recent psychiatric nurse review, it was learned that the patient continued his antipsychotic therapy for 4 months, at which time his parents made the decision to discontinue because of a side effect of significant weight gain. He continues to exhibit no psychiatric signs or symptoms and is reported to have returned to his premorbid state.

Neuropsychiatric manifestations of coronavirus disease 2019 have now become well-known sequelae of this virus in adults. Mao et al described neurologic manifestations in 36.4% of 214 hospitalized patients, including headache, nausea, confusion, ataxia, acute cerebrovascular disease, and seizures.²  Psychosis in adults has been reported multiple times as a complication of both SARS-CoV-1 and -2 infections.⁴  Parra et al described 9 adults who had presented with psychotic symptoms, who, similarly to our patient, presented with delusions, orientation/attention disturbances, and auditory and visual hallucinations thought to be because of SARS-CoV-2 infection.³  Furthermore, to date, 3 individual cases of SARS-CoV-2–related psychosis have been reported in young adults between 16 and 17 years of age.^5,6 

The most striking feature of this case was the absence of recognized prodromal features. This young person had been functioning at his usual level, thriving academically, with no premorbid concerns about his physical or mental health before contracting SARS-CoV-2. Psychosis after taking corticosteroids is a well-documented occurrence, typically starting within 1 to 2 weeks of starting treatment.⁷  Unlike many patients with acute SARS-CoV-2 illness, he was neither previously prescribed nor started on corticosteroids on this admission, which excluded this as a possible etiology. The only medication the patient received before this illness was a short course of amoxicillin, a widely used antibiotic that was unlikely to explain the later onset of his symptoms.⁸  The patient did not have a history of alcohol or illicit substance use. We considered delirium initially as a possible cause of his presentation and included in a differential diagnosis. However, we eliminated this diagnostic possibility because of the lack of fluctuation or impairment in his level of consciousness or disruption in his sleep–wake cycle. We also noted that delirium was less likely to occur in his age group, but more strikingly, his psychotic symptoms emerged after resolution of his infectious illness, which renders delirium to be less credible as a cause of his presentation.

We excluded a large number of organic causes before making a diagnosis of acute and transient polymorphic psychotic disorder/post–SARS-CoV-2 psychosis. His diagnosis of psychosis was on the basis of acute presentation with variable psychotic features of delusions (grandiose, paranoid, and persecutory types), hallucinations (visual and auditory)/perceptual disturbances, thought interference, and severe disruption in his usual behaviors, consistent with International Classification of Diseases, 10^th Revision, classification of mental disorders.⁹ 

The pathophysiology of neuropsychiatric complications after SARS-CoV-2 infection is unknown. One possibility is that psychosis follows an exaggerated inflammatory response that releases abundant proinflammatory cytokines into the circulation. This “storm of cytokines” can trigger a hypercoagulable state and consequent ischemic events in the central nervous system may play a role in neuropsychiatric symptoms.¹⁰  However, our patient was not hypoxic and did not demonstrate elevated inflammatory markers. Neuropsychiatric symptoms have been described in patients who had contracted similar human coronaviruses: SARS and Middle Eastern respiratory syndrome.¹¹  Both viruses have been shown to have neuroinvasive and neurotropic ability, causing central and peripheral nervous system disease.¹²  Therefore, it is possible that SARS-CoV-2 may lead to direct neuronal injury.

In summary, psychotic symptoms with visual and auditory hallucinations may develop as later sequelae of SARS-CoV-2 infection and should be recognized and acted on promptly.

We thank the patient and his parents for giving us permission to publish his data.

SARS-CoV-2

severe acute respiratory syndrome coronavirus 2