Background

COVID-19 is an acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).1 The virus was identified as the cause of an outbreak of pneumonia in Hubei Province, China, in December 2019 and has spread globally, so far responsible for over 2 million cases and 150 000 deaths worldwide.2 SARS-CoV-2 is the seventh coronavirus known to infect humans and is a member of the orthocoronavirus subfamily.3 It appears to be principally transmitted via respiratory droplets and contact with surfaces conveying the pathogen.3 Entry into the host cells is reportedly via the ACE-2 receptor.4 The most common initial symptoms of COVID-19 are fever, dry cough, fatigue and myalgia.5 The primary complication is acute lung injury resulting in type 1 respiratory failure, with a significant proportion requiring intensive care unit admission.6 7 However, in addition to these respiratory features, the disease affects multiple organs including the cardiovascular system and gastrointestinal system.4 6 8 There have been few case reports of primarily neurological presentations of the disease.9–12

This article outlines a case of COVID-19 presenting with an acute manic episode necessitating emergency intubation and discusses potential mechanisms for the development of neuropsychiatric disease.

Case presentation

A 41-year-old man with no significant medical history other than congenital nystagmus presented to the emergency department in the early hours of the morning. He had woken at night restless, agitated and reported feeling like his ‘brain was racing’. He told his wife that he felt like he was ‘going to die’. He also confessed to numerous hitherto undisclosed homosexual encounters and other sexual behaviours described as uncharacteristic by his wife. This acute presentation was preceded by a 1-day history of severe occipito-parietal headache, described as the ‘worst headache ever’, and a 10-day history of a dry cough and fever. His wife also reported similar but milder symptoms. He did not report anosmia. He had no significant smoking or alcohol history and denied any illicit drug use. He did however report a severe transient mood reaction with some possible paranoid features to cannabis in 2004 with no further use since then. His sister had a previous episode of postpartum psychosis and was subsequently diagnosed with bipolar disorder.

Physical examination revealed fine bibasal inspiratory crepitations and a nystagmus in all directions. Neurological examination was otherwise normal. His mental state examination however was abnormal. He was loud and highly aroused with sexual disinhibition and overfamiliar behaviour, inappropriately questioning and touching members of staff. His speech was pressured, and his mood subjectively and objectively elevated. His thoughts were grandiose with persecutory elements, and he had persistent strong religious ideas, manifestations of which included attempts to anoint fellow patients with water. He also obsessively wrote down every personal interaction and bodily sensation. He said he found this experience ‘liberating’. He did not report visual or auditory hallucinations. This abnormal behaviour worsened while in the emergency department to the point where it was deemed necessary for him to be transferred to intensive care for sedation and mechanical ventilation despite no respiratory indication.

Investigations

A nose and throat swab taken on admission subsequently tested positive for the presence of SARS-CoV-2 viral RNA and chest X-ray showed features consistent with a COVID-19 pneumonitis. Bloods results during admission are shown in table 1. His CRP and neutrophils were raised initially but settled shortly after admission, as did his mild lymphopaenia. Liver function tests were initially normal, but he developed a mild transaminitis soon after admission. Thyroid stimulating hormone, B12 and folate were normal. Serological screening was negative for HIV antigen and antibody, hepatitis B surface and core antigen, hepatitis C IgG antibodies and Treponema pallidum antibodies. No common autoantibodies were found in the serum, apart from mildly raised Hep2 antinuclear antibodies of uncertain significance. A coeliac screen was also negative, as were N-methyl-D-aspartate receptor (NMDA) and voltage-gated K+ channel autoantibodies.

CT and MRI brain showed no acute intracranial pathology or evidence of encephalitis. A lumbar puncture with normal opening pressure demonstrated gin-clear cerebrospinal fluid (CSF) and no erythrocytes, leucocytes or other organisms. Glucose level in the CSF has 4.8 mmol/L (plasma glucose 8.4 mmol/L) and protein level 0.19 g/L. The sample was also was negative for herpes simplex virus DNA, varicella zoster virus DNA, enteroviorus RNA and parechovirus RNA not detected. Initial screening for SARS-CoV-2 in the CSF were also negative, although a validated assay was not yet available making interpretation difficult.

Treatment

Empirical antimicrobial and antiviral treatment to cover for bacterial meningitis, community-acquired pneumonia and viral encephalitis were commenced but ceased after 48 hours in the absence of any evidence of ongoing infection on clinical and biochemical investigation. The patient was extubated after less than 24 hours of mechanical ventilation and moved to a level one ward environment. The patient’s respiratory symptoms settled within 2 days of step down, but his mental state remained abnormal. An Addenbrokes Cognitive Examination scored 90/100 with 18/18 in attention tasks and 25/26 in memory tasks while a frontal assessment battery scored 14/18 losing points for inhibitory control and lexical fluency and motor assessment. By day 8, his behaviour had escalated further culminating in a security call and emergency sedation for the safety of himself, the ward staff and other patients. He was subsequently detained under Section 2 of the Mental Health Act 1983, transferred to an acute inpatient psychiatric hospital and commenced on regular olanzapine.

Outcome and follow-up

During this admission, he continued on regular antipsychotics and benzodiazepines for sedation. He required transfer to the emergency department while still an inpatient where he was investigated for severe left-sided chest pain. A CT pulmonary angiogram confirmed ongoing inflammatory changes consistent with COVID-19 pneumonitis but no other pathology.

His mania improved on return to the psychiatric unit, and he was discharged 12 days after instigation of the Section 2 order. His medications on discharge included olanzapine 10 mg daily with a plan to reduce this to 7.5 mg within the next week and 1 mg twice daily of clonazepam also to be weaned in the community. At follow-up 23 days from the original presentation, he was well at home, and he and his wife reported that he was now at his baseline level of function.