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\begin{document}

\title{Managing a Patient with Bipolar Disorder Associated with COVID-19: A
Case Report}



\author[1]{Mohamad  Khatib}%
\author[1]{Omer  Mahgoub}%
\author[1]{Marwa  Elzain}%
\author[1]{Amna  Ahmed}%
\author[1]{Ahmed soliman Mohamed}%
\author[1]{Abdulqadir Nashwan}%
\affil[1]{Hamad Medical Corporation}%


\vspace{-1em}



  
  \date{May 26, 2024}


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\begin{abstract}
This case highlights an atypical presentation of a patient with no
history of mental illness who has been diagnosed with a bipolar disorder
associated with severe COVID-19 symptoms. Neuroimaging was only positive
for subtle white matter changes; he was treated with antipsychotics and
mood-stabilizing agents until he reached partial remission.%
\end{abstract}%



\sloppy


Mohamad Y. Khatib\textsuperscript{1}, Omer B.
Mahgoub\textsuperscript{2}, Marwa E. Elzain\textsuperscript{2}, Amna A.
Ahmed\textsuperscript{1}, Ahmed S. Mohamed\textsuperscript{1},
Abdulqadir J. Nashwan\textsuperscript{1,2}

\begin{enumerate}
\tightlist
\item
  Critical Care Medicine Department, Hazm Mebaireek General Hospital
  (HMGH), Hamad Medical Corporation (HMC), Doha, Qatar.
\item
  Mental Health Services (MHS), Hamad Medical Corporation (HMC), Doha,
  Qatar.
\item
  University of Calgary in Qatar, Doha, Qatar
\end{enumerate}

Corresponding author: Abdulqadir J. Nashwan anashwan@hamad.qa

Tel: (+974) 40240487

Mob: (+974) 66473549

P.O.Box 3050 Doha, Qatar

www.hamad.qa

\textbf{Abstract}

This case highlights an atypical presentation of a patient with unknown
history of mental disease who has been diagnosed with a bipolar disorder
associated with severe COVID-19 symptoms. Neuroimaging was only positive
for subtle white matter changes; he was treated with antipsychotics and
mood-stabilizing agents until he reached partial remission.

Keywords: SARS-CoV-2, COVID-19, Bipolar, Mental Health

\textbf{Key Clinical Message:}

The authors urge clinicians to consider the impact of the COVID-19
pandemic on patients with mental illness and the urgent need for
vigilant monitoring of presenting signs and symptoms.

\textbf{Background:}

The novel coronavirus disease 2019 (COVID-19) is caused by the severe
respiratory syndrome coronavirus 2 (SARS-COV-2) and according to the
World Health Organization (WHO) declared the COVID-19 outbreak a
pandemic on 11\textsuperscript{th} of March 2020, which require national
and global measurement to control this pandemic and strong public health
response. (1) The presentation of COVID-19 in most of the cases was in
the form of cough, fever, sore throat, dyspnea and myalgia. In addition,
the nervous system involvement, can be presented in the form of
cerebrovascular disease, new-onset anosmia, encephalitis and dysgeusia.
(2, 3) It has emerged in the COVID-19 literature many cases of reactive
psychosis, however, less attention has been given to incident psychosis
in patients with COVID-19. (4) Here we reported a case of new-onset
psychosis in a patient with no previous background of mental illness
following a severe course of SARS-COV-2 infection.

\textbf{CASE PRESENTATION}

A 52-year-old man with a background of longstanding well-controlled
epilepsy. He was not known to have a previous history of any mental
illness. He tested positive for the novel SARS-COV-2 virus on a
nasopharyngeal and throat swab after community exposure to a confirmed
case. He was asymptomatic at the time of testing positive but was
admitted to a governmental quarantine facility as per the country's
guidelines (Table 1). Eight days following his initial presentation, he
was transferred from the quarantine facility to a designated COVID-19
hospital after developing fever, cough and shortness of breath. Clinical
imaging confirmed the diagnosis of severe covid-19 pneumonia; he was
commenced on antibiotics (Oral azithromycin and intravenous cefuroxime),
hydroxychloroquine, dexamethasone and oxygen therapy. Hemoglobin A1c was
found to be high and he was diagnosed with diabetes mellitus and started
on insulin. One week following hospitalization, he was noted to be
confused and complained of severe headache and abdominal pain. He was
transferred to the intensive care unit to be investigated and managed
for an impression of an acute confusional state. The initial workup
revealed hyponatremia for which he was started on hypertonic saline.
Computed tomography of the brain did not show any abnormalities.

During his stay in the intensive care unit, he was assessed by the
consultation-liaison psychiatry team. The team's assessment was
consistent with an acute confusional state based on disorientation to
time, impaired concentration and memory, visual and auditory
hallucinations (seeing and hearing Jesus), persecutory beliefs against
hospital staff, labile mood, and delinquent behavior requiring sedation
with oral quetiapine and injectable haloperidol.

The patient responded well to treatment, he was transferred to a medical
ward after spending four days in the intensive care unit and was
discharged home two days later. Upon discharge, he was fully oriented,
and his mental state examination did not show any abnormalities. He was
discharged from the hospital on oral hypoglycemic agents, antiepileptic
medications, and quetiapine 50 mg twice daily. His repeated
Nasopharyngeal and throat swab was still Positive for SARS-COV2 but was
declared to be non-infectious based on an RdRp-gene ct value of 32.3.

Two days after his discharge from the hospital, he presented to the
emergency department following an episode of physical aggression in a
hotel where he was residing, during the assessment, he justified his
behavior by dereliction from the hotel staff. He was threatening to be
physically aggressive if his demands were not immediately met. He was
noted with a grandiose attitude and claimed to be a Master of Yoga. He
demanded to be released from the hospital citing that he does not
believe that he has any mental illness based on his medical, educational
background. His family members and friends have reported that he was
calling and messaging them repeatedly throughout the day.

His mental state examination was remarkable for psychomotor agitation,
overfamiliar attitude, pressured speech, ``very happy'' mood, an
expansive effect, persecutory and grandiose delusions and poor insight.
Attention and orientation were found to be intact.

Physical and neurological examinations didn't reveal any abnormalities.

His medical history is significant of epilepsy since childhood, he was
well maintained on medications (levetiracetam 1000 mg and sodium
valproate 1500 mg), his last seizure was 20 years prior to presentation.
He was newly diagnosed with diabetes mellitus and was on two oral
hypoglycemic agents. He denied any background of mental illness in
himself or his family.

He had maintained a job as a financial consultant for the past 10 years.
He is married for 25 years with 3 children. He was living alone, and his
family resided in his home country. He is a non-smoker and had no
history of alcohol or illicit substance use.

\textbf{INVESTIGATIONS}

MRI of the brain showed subtle white matter changes which were ruled to
be of no clinical correlation.

\textbf{DIFFERENTIAL DIAGNOSIS}

Bipolar affective disorder, manic episode with psychotic features.

Acute confusional state.

Mood disorder secondary to a general medical condition.

\textbf{TREATMENT}

He was started on risperidone at 1 mg once daily as an antipsychotic and
mood-stabilizing agent under the impression of a manic episode and a
decision was made to admit him to an inpatient psychiatry ward for
further management.

Risperidone was gradually increased up to a dose of 2 mg twice daily but
was later reduced to 2 mg daily due to the emergence of bilateral hand
tremors.

Clonazepam 1 mg at bedtime was added for a few days during his
hospitalization as he was noted to have disturbed sleep.

His antiepileptic and oral hypoglycemic medications were resumed.

\textbf{OUTCOME AND FOLLOW-UP}

He showed gradual improvement in his manic and psychotic symptoms over
the course of his hospitalization and he has discharged home after 3
weeks on Risperidone 2 mg once daily. He was contacted via phone 2 weeks
following discharge and he reported maintained improvement other than
difficulties with the initiation of sleep for which his dose of
Risperidone was increased to 3 mg once daily.

\textbf{Discussion}

In this case, we present a middle-aged patient with no previous mental
illness background who presented with full-blown manic symptoms
following a severe course of SARS-COV2 infection. There were few other
reported cases of first onset manic-like symptoms in patients following
a severe SARS-COV2 infection. (5, 6) These cases discussed the
possibility of the neuroinvasive properties of the virus being directly
related to the emergence of symptoms given previous reports of CNS
infections associated with the novel virus. (7) However, they have
highlighted the limitations of the lack of CSF-PCR assays for validation
of this hypothesis. Given the patient's age, lack of past personal or
family psychiatric history and the prodrome of an acute confusional
state preceding the onset of manic symptoms, a neuroinvasive etiology is
possible. However, the possibility of a primary mood disorder cannot be
dismissed without a longer period of follow-up.

COVID-19's clinical manifestations range from no symptoms to a more
severe form of the disease resulting in multiorgan failure and sepsis
requiring ICU care and mechanical ventilation. (8) Nalleballe et al.
reported neuropsychiatric manifestations in 22.5\% of more than 40,000
patients who had COVID-19; including Mood disorders, anxiety, stroke,
seizures, and encephalopathy. The prevalence of mood disorders was
estimated to be 3.8\% in the study sample. (9)

The novel SARS-COV2 virus neurotropic properties were discussed in the
literature. Several mechanisms were proposed to explain the
neuropsychiatric manifestation of COVID-19 including direct cytokine
network dysregulation, Central nervous system (CNS) infiltration,
peripheral immune cell transmigration, and post-infectious autoimmunity.
(10)

The possibility of a primary bipolar affective disorder cannot be ruled
out in our patient. He initially experienced an acute confusional state
during the acute phase of COVID-19 infection as evident by
disorientation and visual hallucinations which subsided before his
discharge from the COVID-19 facility. He later presented with classical
features of mania after he was declared to have recovered from COVID-19
and was in clear sensorium at that time. The patient's medical history
of epilepsy can be considered another risk factor for developing a mood
disorder. Reports from the united states revealed that around 12\% of
individuals with epilepsy screened positive for symptoms of bipolar
disorder in comparison to 1 to 2\% lifetime incidence in the general
population. (11)

\textbf{Conclusion}

A 52-year-old man with no history of mental disorder and multiple
medical comorbidities presented following exposure to a COVID-19
patient; his test result was shown to be positive and soon started to
develop symptoms of fever, cough and shortness of breath. His course of
an illness complicated further after he developed headache and confusion
after he was transferred to the intensive care unit; his mental state
was shown to be abnormally ranging from cognitive deficit initially to
grandiosity, lack of sleep, talkativeness and persecutory beliefs with
an intact cognitive function, later he was admitted to a psychiatric
facility under the impression of a manic episode, His laboratory results
were evident for increased inflammatory markers praising severe
infection, neuroimaging was only positive for subtle white matter
changes, he was treated with antipsychotics and mood-stabilizing agent
until reached partial remission.

\textbf{Abbreviations}

COVID-19: Coronavirus disease

MRI: Magnetic Resonance Imaging

PCR: Polymerase chain reaction

\textbf{Declarations}

\textbf{Ethics approval and consent to participate}

The article describes a case report. Therefore, no additional permission
from our Ethics Committee was required.

\textbf{Consent for publication}

The consent for publication was obtained.

\textbf{Availability of data and material}

All data generated or analyzed during this study are included in this
published article.

\textbf{Competing interests}

The authors declare that they have no competing interests.

\textbf{Funding}

This study was not funded.

\textbf{Authors' contributions}

MYK, OBM, MEE, AAA, ASM, AJN: Data Collection, Literature Search,
Manuscript Preparation

All authors read and approved the final manuscript

\textbf{Acknowledgments}

Open Access funding provided by the Qatar National Library.

\textbf{Reference}

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global respiratory perspective on the COVID-19 pandemic: commentary and
action proposals. Eur Respiratory Soc; 2020.

2. Guan W-j, Ni Z-y, Hu Y, Liang W-h, Ou C-q, He J-x, et al. Clinical
characteristics of coronavirus disease 2019 in China. New England
journal of medicine. 2020;382(18):1708-20.

3. Mao L, Jin H, Wang M, Hu Y, Chen S, He Q. Neurologic manifestations
of hospitalized patients with coronavirus disease 2019 in Wuhan, China.
JAMA Neurol. 2020 Apr. 2020.

4. Vald\selectlanguage{ngerman}és-Florido MJ, López-Díaz Á, Palermo-Zeballos FJ, Martínez-Molina
I, Martín-Gil VE, Crespo-Facorro B, et al. Reactive psychoses in the
context of the COVID-19 pandemic: clinical perspectives from a case
series. Revista de psiquiatria y salud mental. 2020.

5. Lu S, Wei N, Jiang J, Wu L, Sheng J, Zhou J, et al. First report of
manic-like symptoms in a COVID-19 patient with no previous history of a
psychiatric disorder. Journal of Affective Disorders. 2020;277:337-40.

6. Mawhinney JA, Wilcock C, Haboubi H, Roshanzamir S. Neurotropism of
SARS-CoV-2: COVID-19 presenting with an acute manic episode. BMJ Case
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7. Moriguchi T, Harii N, Goto J, Harada D, Sugawara H, Takamino J, et
al. A first case of meningitis/encephalitis associated with
SARS-Coronavirus-2. International Journal of Infectious Diseases. 2020.

8. Cascella M, Rajnik M, Cuomo A, Dulebohn SC, Di Napoli R. Features,
evaluation and treatment coronavirus (COVID-19). Statpearls
{[}internet{]}: StatPearls Publishing; 2020.

9. Nalleballe K, Onteddu SR, Sharma R, Dandu V, Brown A, Jasti M, et al.
Spectrum of neuropsychiatric manifestations in COVID-19. Brain,
behavior, and immunity. 2020;88:71-4.

10. Diaz AD, Baweja R. The role of neurotropism in psychiatric patients
with COVID-19. European Archives of Psychiatry and Clinical
Neuroscience. 2020:1-2.

11. Mula M, Schmitz B, Jauch R, Cavanna A, Cantello R, Monaco F, et al.
On the prevalence of bipolar disorder in epilepsy. Epilepsy \& Behavior.
2008;13(4):658-61.

Table 1. laboratory investigations

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