New-Onset Psychosis Secondary to COVID-19 Infection

Virus-borne infections play a significant role in neuropsychiatric manifestations, with delirium being a systemic infection’s most common secondary complication.¹ HIV, herpes simplex virus, varicella-zoster virus, influenza A and other influenza viruses, and hepatitis C virus are viruses that result in infections associated with depression and anxiety. HIV infection may also result in psychosis and mania.² Respiratory viruses have been associated with psychosis since the 1918 influenza (Spanish flu) pandemic.³ In 1919, Menninger published a case series of 100 patients with neuropsychiatric sequelae associated with influenza infection, including 23 patients with “other psychosis.”^3,4

About one-third of the patients with SARS-CoV-2 develop neuropsychiatric symptoms, such as anxiety, depression, psychosis, brain fog, and suicidal behavior.⁵ Recently, several cases have reported new-onset psychotic symptoms in individuals following an infection with SARS-CoV-2.^5,6 The possible etiologic factors are viral exposure, treatment modality (possibly steroids), and psychosocial stress.^7,8 From studying recently published case reports,^9–11 the psychotic symptoms develop approximately 2 weeks after the remission of fever and flu-like and upper respiratory symptoms. However, these symptoms can develop within the week of the onset of upper respiratory symptoms.⁴

Besides the respiratory system, SARS-CoV-2 targets the central nervous system (CNS), which can lead to cerebrovascular diseases, encephalopathy, and encephalitis.¹² Acute psychosis is a rare CNS condition possibly triggered by the inflammatory response to a SARS-CoV-2 infection.^7,9 Direct viral infiltration in the CNS triggers the neuroinflammatory reaction, and the microglial-induced demyelinating process causes encephalopathy. Peripheral hypercytokinemia triggers a noninflammatory response, disrupting the blood-brain barrier. The transmigration of the peripheral immune cell into the CNS causes an imbalance in neurotransmitters, which may be responsible for neuropsychiatric manifestations.¹³ Although it is commonly thought that psychosis related to COVID-19 is due to inflammation, sometimes the inflammatory markers are normal.¹⁴

To better understand the neuropsychiatric symptoms and their management following a COVID-19 infection, we reviewed some case reports in the pediatric and adult population. One report¹⁵ was of a 15-year-old girl with no known psychiatric history who presented with visual and tactile hallucinations, delusions, and paranoia 2.5 weeks after being infected with COVID-19. She was treated with dexamethasone 4 mg for 5 days for COVID-19, with all her laboratory results being within normal limits except for a positive SARS-CoV-2 serology. Her psychosis was treated with olanzapine 5 mg, which was increased to 7.5 mg, to which she responded. Her symptoms improved, and she was discharged within 5 days.¹⁵ In March 2021, a 69-year-old woman presented with symptoms of catatonia, bizarre behavior, visual hallucinations, and paranoid delusions following a resolved COVID-19 infection.¹⁶ Her catatonia responded to a trial of therapeutic lorazepam. Other case reports^4,9–11 reveal persecutory delusions, auditory and visual hallucinations, disorganized behavior, and agitation as some of the most commonly presenting symptoms. COVID-19–related psychosis tends to respond well to antipsychotics, mood stabilizers, and benzodiazepines. The widely used antipsychotics are haloperidol, risperidone, aripiprazole, and olanzapine.^4,9–11

A study from China¹⁷ demonstrated the relationship between psychosis-like experiences (PLEs) and COVID-19–related psychological symptoms, including depression, anxiety, neurasthenia, fear, obsession-compulsion, and hypochondriasis. The study¹⁷ suggested the predictive value of PLEs for measuring the psychological impact of a public health emergency. The PLEs are associated with many psychosocial factors, such as ethnic minority, urbanization, perceived stress, and childhood trauma.¹⁷ In addition, there is evidence of coronavirus-associated psychosis through neuroinflammation, with linked factors including stress, isolation, and uncertainty, further showing how pandemics can increase the risk of psychosis.¹⁸

As neuropsychiatric complications can develop within weeks of a COVID-19 infection, health care providers should consider COVID-19 a causative agent of sudden and new-onset psychotic disorders. We propose well-designed and large-scale research studies to explore the pathophysiology behind SARS-CoV-2 and other coronaviruses altering neuronal activity and neurotransmission.

Article Information

Published Online: July 13, 2023. https://doi.org/10.4088/PCC.22br03436
© 2023 Physicians Postgraduate Press, Inc.
Prim Care Companion CNS Disord. 2023;25(4):22br03436
Submitted: October 22, 2022; accepted January 13, 2023.
To Cite: Sultana T, Kamil SH, Billoo F, et al. New-onset psychosis secondary to COVID-19 infection. Prim Care Companion CNS Disord. 2023;25(4):22br03436.
Author Affiliations: Department of Psychopharmacology Research, Manhattan Psychiatric Center, New York, New York (Sultana); Department of Psychiatry, Austin Family Psychiatry, Austin, Texas (Kamil); Department of Family Medicine, Family Medicine Associates, Northridge, California (Billoo); Department of Radiology, Mayo Clinic, Rochester, Minnesota (Lahori); Department of Psychiatry, Griffin Memorial Hospital, Norman, Oklahoma (Shah); Department of Psychiatry, The University of Texas Rio Grande Valley, Harlingen (Vadukapuram); Department of Psychiatry, Boston Children’s Hospital/Harvard Medical School, Boston, Massachusetts (Mansuri); Department of Psychiatry, Texas Tech University Health Sciences Center at Permian Basin, Midland (Jain).
Corresponding Author: Saher Hoda Kamil, MBBS, Department of Psychiatry, Austin Family Psychiatry, 4407 Bee Cave Road, Austin, TX 78746 (saherumair@gmail.com).
Author Contributions: Drs Sultana and Kimil share equal credits for first authorship. Drs Jain and Mansuri share equal credits for senior authorship.
Relevant Financial Relationships: None.
Funding/Support: None.