COVID-19-associated brief psychotic disorder.

A 36-year-old previously healthy woman with no personal or family history of mental illness presented with new-onset psychosis after a diagnosis of symptomatic COVID-19. Her psychotic symptoms initially improved with antipsychotics and benzodiazepines and further improved with resolution of COVID-19 symptoms. This is the first case of COVID-19-associated psychosis in a patient with no personal or family history of a severe mood or psychotic disorder presenting with symptomatic COVID-19, highlighting the need for vigilant monitoring of neuropsychiatric symptoms in these individuals. © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Background

The novel coronavirus (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2), the causative agent of the COVID-19, is rapidly emerging. From 29 December 2019, when the first cases of COVID-19 were documented in Wuhan, China, COVID-19 has resulted in more than 3.9 million infections in the USA, representing nearly 30% of cases worldwide.1 2

Typical symptoms of COVID-19 are dyspnoea, cough, fever, myalgia and sore throat, though nervous system involvement, resulting in cerebrovascular diseases, encephalopathy, encephalitis and new-onset anosmia and dysgeusia, has been documented.3–5

Recent cases of reactive psychosis in the context of the COVID-19 pandemic have emerged in the literature, but less attention has been given to incident psychosis affecting patients with COVID-19.6 Although a recent report documented cases of COVID-19-related psychosis in Madrid, this did not include a clinical description of affected patients.7 Ferrando et al8 described three cases of new-onset psychosis in patients with asymptomatic COVID-19, though two of these patients had a pre-existing psychiatric illness, and there were concerns for concurrent delirium.

Here, we report a case of symptomatic COVID-19-related psychosis in a patient with no personal or family history of mental illness and briefly discuss the relevant literature on coronavirus-associated psychosis.

Case presentation

A 36-year-old African–American woman employed at a skilled nursing facility with a remote history of erythema multiforme, and no psychiatric history, was diagnosed with COVID-19 by nasopharyngeal swab after a known exposure at work. Symptoms at the time of diagnosis with COVID-19 were notable for rhinorrhoea and nasal congestion without any concomitant dyspnoea or documentation of anosmia or dysgeusia. Approximately 4 days following onset of upper respiratory symptoms, she was noted to have an acute, rapidly progressive change in her behaviour characterised by prominent persecutory delusions and decreased sleep. Her delusions were primarily directed at her partner and focused on the safety of her children and personal finances. She believed her partner was attempting to kidnap her children and steal her COVID-19 stimulus money. Collateral information from the patient’s family revealed that she had been engaging in ruminative, persecutory thought patterns centring around being ‘tracked by cell phones’ in the days preceding hospitalisation. This began after a domestic dispute with her partner. Her symptoms culminated in the patient attempting to pass her children through a local fast-food restaurant drive-through in an effort to prevent their kidnapping, at which time first responders were notified and she was transported to the hospital.

Due to the acute onset of psychosis of unclear aetiology and her positive COVID-19 status, the patient was initially admitted to the general medicine service, whereupon psychiatry was consulted for further evaluation and management. At the time of her initial psychiatric interview, she was avoiding eye contact, but had no psychomotor agitation or retardation. She did not appear to be responding to internal stimuli. Her speech was noted to be increased in rate, though interruptible with repeated prompts. She described her mood as ‘worried’, and her affect was congruent to mood. She exhibited a tangential thought process with content notable for persecutory delusions. At the time of initial assessment she denied any suicidality or homicidality. Attention, concentration and orientation were intact on bedside testing.

Investigations

Vital signs on admission were: temperature 36.8°C, heart rate 79 beats per minute, respiratory rate 19 breaths per minute and blood pressure 114/85 mm Hg. Laboratory testing revealed positive SARS-CoV-2 nasopharyngeal swab, mild leucocytosis (white cell count 11.5×109/L, 86.4% neutrophils), elevated C-reactive protein (2.37 mg/dL), elevated D-dimer (2274 ng/mL fibrinogen equivalent units), but otherwise normal electrolytes, ferritin, renal function, urine analysis and toxicology. Interleukin levels were not measured as it was not part of the standard of care at our institution. CT scan and MRI of the head were normal. A lumbar puncture revealed: cerebrospinal fluid colour was colourless, hazy, red cell count 187×1012/L, and nucleated cell count 1/μL in tube 1, glucose 69 mg/dL and protein 20 mg/dL. Extended meningitis PCR panel was negative.

Differential diagnosis

Given the paucity of alternative aetiologies for her development of acute psychosis, it was felt that the patient’s symptoms were either representative of a first-episode psychosis, triggered by psychosocial stressors secondary to her recent COVID-19 diagnosis, a brief psychotic disorder in the setting of an obvious stressor, or a direct sequela of COVID-19 infection and representative of a brief psychotic disorder. Delirium was also considered, but she lacked alterations in attention or awareness on bedside evaluation and did not screen positive using our institution’s nursing delirium observation scale.

Treatment

Due to the severity of the patient’s psychiatric symptoms, inability to engage in reality testing and perceived elevated risk of both harm to self and others (as her acute illness limited her ability to engage in and appreciate the need for social isolation as an active carrier of COVID-19), the patient was initially involuntarily committed, and pharmacotherapy was initiated. She was initially treated with two daily doses of olanzapine 2.5 and 5 mg in an effort to target both her underlying psychotic symptoms and aid in sedation to promote restoration of the patient’s sleep-wake cycle. Despite initiation of olanzapine, the patient remained paranoid with prominent delusional thinking and minimal insight, leading to an episode of acute agitation. Given the severity of her ongoing symptoms, clonazepam 0.5 mg twice daily was added for acute anxiolysis and reduced to once daily. Considering the possibility that she would need to be on antipsychotics at discharge, and that olanzapine is not recommended as first-line therapy in psychosis (due to metabolic side effects) she was transitioned to risperidone. With titration to 3 mg of risperidone daily, the patient had significant improvement in her persecutory delusions and subsequently exhibited improvement in her insight and judgement. Clonazepam was discontinued and she was discharged on hospital day 7 on risperidone 3 mg nightly with a plan for close outpatient follow-up with psychiatry. Of note, she did not require any therapy for her COVID-19 infection as she remained on room air after hospitalisation with resolution of her respiratory symptoms.

Outcome and follow-up

Follow-up documentation from her outpatient provider 1 week after discharge noted that she had not attended her psychiatry intake appointment, though she had noted near resolution of her psychiatric symptoms and had self-discontinued the risperidone without return of her persecutory delusions.

Discussion

To our knowledge, this case represents the first description of symptomatic COVID-19-associated brief psychotic disorder in an individual with no personal or family history of primary psychiatric illness. A case series in Madrid noted an unspecified number of potential cases of COVID-19-related psychosis in their hospital, but did not detail the clinical course of affected patients.7 A recent case series in New York described three cases of new-onset psychosis in patients with COVID-19.8 However, all patients were incidentally found to have positive SARS-CoV-2 test and did not present with other symptoms to suggest infection, calling into question whether the diagnosis of COVID-19 was related to the psychosis. Further, one patient had a comorbid panic disorder, which may lead to heightened vulnerability to psychotic illness, and another was experiencing homelessness and was on 120 mg of methadone for opioid use disorder, again confounding the diagnosis of COVID-19 psychosis.9

In the case presented herein, there was no history of prodromal symptoms, no personal or family history of mental illness and a relatively rapid resolution of psychosis. Further, she did not have a history of substance use or propsychotic medication (such as steroids) use, and the onset of psychosis coincided with upper respiratory symptoms. Given the temporality between infection and psychiatric symptoms, along with the resolution of symptoms with improvement of COVID-19-related symptoms, a working diagnosis of brief psychotic disorder associated with COVID-19 was given.10 The mechanism by which COVID-19 may have precipitated psychosis in this patient is not entirely clear, but could be related to the diagnosis of COVID-19, increased stress in the setting of ongoing infection or a viral mediated psychosis.

Indeed, respiratory viruses have been associated with psychosis since the 1918 influenza pandemic when Menninger published a report of 100 patients with neuropsychiatric sequelae associated with influenza infection, including 25 with ‘dementia praecox’ and 23 with ‘other psychoses’.11 12 Coronaviruses, too, have been linked to psychosis. A recent rapid review of epidemic and pandemic literature identified five papers (four observational studies and one case series) reporting incident psychosis in SARS and one paper reporting psychosis in Middle East respiratory syndrome.13–19 The incident rate of psychotic symptoms across observational studies was between 0.9% and 11.8%.14–16 19 SARS-related psychotic symptoms were associated with higher doses of corticosteroids, severity of SARS symptoms and family history of psychiatric illness and psychosocial stressors.14 15 The single case series of three patients with SARS-related psychosis suggested that SARS severity, steroid treatment and social isolation were contributing factors.18

Severance et al17 reported an association between coronaviruses and psychotic symptoms by measuring immunoglobulin G (IgG) response against four human coronavirus strains in patients with recent onset of psychotic illness compared with healthy controls. The authors found that patient IgG levels for two strains of coronavirus (HKU1 and NL63) were significantly higher in patients with psychotic symptoms when compared with controls, suggesting these two coronaviruses may be risk factors for neuropsychiatric illness.

Although heightened stress of a COVID-19 diagnosis or medications (such as corticosteroids) may unmask an underlying primary psychotic disorder in a vulnerable individual, the idea that SARS-CoV-2 may itself trigger psychosis through direct neurotoxicity or a heightened immune response is not unreasonable.13 Coronaviruses are neurotropic, for example, and SARS-CoV-2 RNA has recently been isolated from the central nervous system of a patient.4 20 Moreover, the antipsychotics haloperidol and chlorpromazine have displayed antiviral activity against SARS-CoV-2 in vitro and in a mice model, respectively.21 22 In a review of the literature, Troyer et al23 offer direct infection, blood circulation, neuronal involvement, hypoxic injury, immune injury and ACE2 binding as possible culprits of coronavirus nervous system damage.

With these data in mind, we contend that a relevant neuropsychiatric review of systems and full exam should be completed in patients presenting with suspected or confirmed COVID-19. New-onset psychosis in a patient with suspected or confirmed COVID-19, without personal or family history of mental illness and no other clear precipitant, should prompt further medical workup (eg, head imaging and lumbar puncture). This is consistent with the the American Psychiatric Association’s draft 2019 guidelines for schizophrenia treatment, which state that clinicians should be alert to features that suggest a need for additional physical or laboratory evaluation in first-episode psychosis.24

Although studies investigating the treatment of COVID-19 psychosis have not been undertaken, treatment of secondary psychosis should be geared towards treating the underlying illness while managing psychotic symptoms with antipsychotics and benzodiazepines at the lowest possible dose.25 Given concerns for dysrhythmias in patients with pre-existing cardiac injury and COVID-19, intravenous haloperidol should be avoided in this population, where possible.26

Individuals with COVID-19 may be at risk of developing neuropsychiatric symptoms, including psychosis.

COVID-19 diagnosis could predispose vulnerable patients to psychosis and clinicians should be aware of this.

A diagnosis of COVID-19 should prompt a neuropsychiatric review of systems and psychiatric exam.

In individuals presenting with new-onset psychosis in areas endemic to COVID-19, consideration should be made for testing in the absence of respiratory symptoms.