Covid-19, not your normal flu: A case report on Covid-19 psychosis and mania in a Malaysian hospital

Abstract Evidence suggests that acute severe coronavirus disease 2019 (COVID-19) may be associated with neuropsychiatric symptoms. This is a case report of a patient who had recently been infected with COVID-19 and had no history of psychiatric disorders presenting a few days after inpatient discharge from COVID-19 treatment with acute onset of psychosis and manic symptoms. This case illustrates the psychiatric presentation, possible causes, and management of post-COVID-19 psychosis.


Introduction
Coronavirus disease 2019 (COVID-19) is an acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 1 It was the isolated cause of a pneumonia outbreak in Hubei Province, China, in December 2019 and spread globally. To date, COVID-19 is responsible for over 162 million confirmed cases and 3.3 million deaths worldwide. 2,3 SARS-CoV-2 is part of the orthocoronavirus subfamily and is the seventh coronavirus known to infect humans. 4 Multiple presentations of COVID-19 have been identified, from flu-like presentations to neurovascular symptoms and psychiatric manifestations. 5 We report on a case of post-COVID-19 psychosis and mania in a patient admitted to a local State Hospital in Malaysia.

Case Presentation
Mr. K, a 54-year-old married, employed man was admitted from January 6, 2021, to January 29, 2021, for COVID-19 infection presenting with intermittent dizziness, a 'floating feeling', dyspnoea, chest tightness, dry cough, anosmia, generalised headaches, and myalgia. He was confirmed positive for COVID-19 infection via reverse transcriptionpolymerase chain reaction (PCR) test and required assisted ventilation (nasal prongs, high-flow performance devices) and high-dose dexamethasone tablets.

Discussion
The 2019 novel coronavirus, once thought to be a 'normal flu', proved to be more, with evidence of neurological, cognitive, and psychological effects, even in patients who did not develop severe lung, heart, or circulatory problems. 6 Our patient was admitted for COVID-19 infection treatment and was well upon discharge but returned with acute onset of psychiatric symptoms, including mania, delusions, and hallucinations. All investigations suggested no medical cause, and delirium was excluded. He was started on antipsychotics at low doses and recovered rapidly.

Intensive care unit
COVID-19 Class 4B infection Given assisted ventilation for 2 days.

Discharged
Afebrile but started having disrupted sleep cycle and spoke of multiple ideas of businesses (flight of ideas).

First aggressive symptoms
Progressively becoming hot tempered.

A&E
First ever abnormal aggressive manic-like behaviour, disrupted sleep patterns and psychosis for 3 days. He was admitted.

Discharged
His aggressiveness was well controlled but manic-like behaviour still present T aripiprazole 10 mg ON T lorazepam 1 mg PRN

Discharged
Afebrile but started having disrupted sleep cycle and spoke of multiple ideas of businesses (flight of ideas).

First aggressive symptoms
Progressively becoming hot tempered.

A&E
First ever abnormal aggressive manic-like behaviour, disrupted sleep patterns and psychosis for 3 days. He was admitted.

Discharged
His aggressiveness was well controlled but manic-like behaviour still present T aripiprazole 10 mg ON T lorazepam 1 mg PRN In June 2020, Lancet Psychiatry released a study on neurological and psychiatric complications in 153 people who were hospitalised with COVID-19 in the U.K. It reported that 39 people had altered mental status, 10 of whom had new-onset psychosis. 7 Altered mental status is not uncommon in patients needing intensive care, but it predominates in the elderly, who often already have multiple medical comorbidities and polypharmacy. The authors observed a disproportionate number of neuropsychiatric signs in the young and cerebrovascular complications in the old. This might reflect the vulnerability of the central nervous system to COVID-19 infection or the increased accessibility of psychiatric aid to younger patients, whereas the elderly are often assumed to have delirium. 7 A publication in Neuroscience Letters that reviewed 42 cases of psychosis reported in COVID-19-infected patients suggested that patients could exhibit a range of neuropsychiatric symptoms. However, the underlying pathological mechanisms have not yet been fully established. 8 Much of the literature remains conceptual and conclusions are extrapolated from small studies conducted in the current pandemic and studies from previous epidemic viral infections. 7 More research is needed to identify which pathogenic biomechanisms are driving neuropsychiatric associations. For now, this association is thought to be due to: 1) direct neuronal viral infection; 2) post-infectious neuronal autoimmunity; 3) vasculopathies, including those resulting from impaired coagulation; and 4) systemic (e.g., inflammatory) effects of a pervasive, severe pathogen and/or critical illness. 7,9 Since 2010, research has focussed on the influence of inflammation and immunity in the onset of schizophrenia; therefore, a renewing interest in the idea that viruses can cause 'insanity' or, more specifically, psychoses, is not unusual. 10 Meanwhile, a study on newonset psychosis in people with COVID-19 in Spain reported that the time needed for an episode to develop, the length of the episode, and rapid recovery on low-dose antipsychotics helped to distinguish primary psychotic cases from secondary psychosis. 11 Although steroids have been reported to trigger psychoses, the pathophysiology remains unclear. It is hypothesised that the synthetic steroids disrupt the cortisol pathway of the hypothalamic-pituitary-adrenal axis, resulting in mood disorders. Therefore, they create an imbalance between glucocorticoid and mineralocorticoid receptor stimulation, leading to cognitive impairment and emotional disturbances. 12 A hypothesised pathophysiology of COVID-19 precipitating a manic episode is the hyperinflammatory cascade activating the kynurenine pathway and neurotropism, which causes a range of psychiatric presentations, including psychosis, bipolar disorder, depression, and suicide. 13,14 A recent study discovered that inflammatory changes coincide with acute episodes of mania in patients with bipolar disorder. 15 A lacunar infarct occurs due to an occlusion of a single penetrating artery and is responsible for one-quarter of cerebral infarctions. Interestingly, silent lacunar infarcts are more common because of their small size; they are often asymptomatic and only discovered on imaging as incidental findings. Depending on the area of brain involvement and the number of lacunar infarctions, they can lead to significant disabilities. However, cortical findings, such as behavioural changes, are absent as the infarction occurs only in subcortical areas of the brain. 16,17 Therefore, in our patient's case, his lacunar infarct may not have significantly contributed to his abnormal behaviour as this type of infarct is not associated with psychotic and manic-like symptoms. Moreover, his condition settled more rapidly than post-stroke psychosis, which would likely have had a longer duration of manifestation.

Conclusion
COVID-19 has a significant impact on patients who are infected, even after physical recovery. As evidenced in other viral infections, COVID-19 can trigger psychiatric conditions, including psychoses and mania. Follow-up of patients in recovery after COVID-19 infection should include screening for psychiatric sequelae and appropriate investigations to rule out other causes, such as delirium. Early identification and treatment of this condition are likely to produce more favourable outcomes.

Conflicts of interest
The authors report no conflicts of interest.

Patients' consent for the use of images and content for publication
Informed consent obtained and given via verbal means from patient for this case report.

What is new in this case report compared to the previous literature?
• It reports mania-like symptoms present in post-COVID-19 psychosis.
• It highlights that this condition is something to be aware of, especially in the immediate recovery phase. • It highlights COVID-19 pathophysiology in mania and psychosis.
• The patient had no prior mental disorder or evidence of delirium.
• Is there a certain undiscovered viral strain or a predisposition for COVID-19 psychosis?
What is the implication to patients?
• Increasing awareness among medical staff that post-COVID-19 psychosis can present with mania. • Raising awareness that serious post-COVID-19 psychiatric morbidity can occur in previously mentally healthy individuals. • It describes how to manage post-COVID-19 psychosis with mania in a case that responded well to antipsychotics. • It warrants further studies on the long-term psychiatric effects of COVID-19 infection.