Psychiatric and neuropsychiatric syndromes in presentations of... · Varatharaj et al, JAMA Psychiatry 2020 Affective disorder: 4. GBS: a cautionary tale ‘GBS incidence fell between

Psychiatric and

neuropsychiatric syndromes in

coronavirus infectionsDr Jonathan Rogers MRCP MRCPsych

Wellcome Trust Clinical Training Fellow, UCL Division of Psychiatry

Specialty Registrar in GA/OA Psychiatry, SLAM

Outline

Coronaviruses

Reason for concern

Systematic search

Acute presentations

Post-illness presentations

Implications

Further reading

Coronaviruses

Coronaviruses

Common forms (HCoV-229E, -OC43, -NL63, -HKU1)

SARS (SARS-CoV, 2002)

MERS (MERS-CoV, 2012)

COVID-19 (SARS-CoV-2, 2019)

Lu R, Zhao X, Li J, et al. Lancet 2020; 395: 565–74.

Desforges M, Le Coupanec A, Dubeau P, et al. Viruses 2019; 12.

Coronaviruses and psychiatry

2 case control studies

Antibodies against common coronavirus subtypes

Okusaga et al.: mood disorder vs healthy controls

OR 2.7 (1.9-3.9) for HCoV-NL63 infection

Severance et al.: psychotic disorders vs healthy controls

OR 1.3 (1.0-1.7) for HCoV-HKU1 infection

OR 2.4 (1.3-4.7) for HCoV-NL63

Okusaga O, Yolken RH, Langenberg P, et al. Association of seropositivity for influenza and coronaviruses with history of mood disorders and suicide attempts. J Affect Disord 2011; 130: 220–5.

Severance EG, Dickerson FB, Viscidi RP, et al. Coronavirus Immunoreactivity in Individuals With a Recent Onset of Psychotic Symptoms. Schizophr Bull 2011; 37: 101–7.

Reason for concern

Encephalitis lethargica?

Psychological impact

Severe illness

Mass anxiety

Isolation

Difficulties communicating with staff

Employment & financial difficulties

Iatrogenic impact

Intubation

Sedation (different agents)

Corticosteroids

Does SARS-CoV-2 affect the CNS?

Retrospective review notes of 214 consecutive hospitalised patients in Wuhan

36.4% ‘had neurologic manifestations’

Dizziness 16.8%

Headache 13.1%

Impaired consciousness 7.5%

Altered smell 5.1%

Associations with neuro Sx: older, more comorbidity, fewer typical COVID symptoms

Does SARS-CoV-2 affect the CNS?

‘Although there are

reports of neurological

complications in

patients with COVID-19,

it is unclear if SARS-

CoV-2 is neurotropic in

humans.’

Enters cells via ACE2 receptor

Neurons

Microglia

Astrocytes

Oligodendrocytes

Plausible routes of entry:

Transsynaptic transfer

Entry via olfactory nerve

Infection of vascular endothelium

White cell migration across BBB Zubair et al, JAMA Neurology 2020

Systematic search

Search strategy

MEDLINE, Embase, PsycINFO, CINAHL

Pre-print databases (medRxiv, bioRxiv, PsyArXiv)

Suspected or confirmed coronavirus infection + (neuro)psychiatric

complications

Cut-off: April 10, 2020

Results

Acute impact

SARS/MERS: qualitative data

Loneliness, boredom and frustration

Concern about infecting family members

Gratitude for the support they received

Almutairi AF, Adlan AA, Balkhy HH, Abbas OA, Clark AM. J Infect Public Health 2018; 11: 187–91.

Koller DF, Nicholas DB, Goldie RS, Gearing R, Selkirk EK. Qual Health Res 2006; 16: 47–60.

Maunder R, Hunter J, Vincent L, et al. CMAJ 2003; 168: 1245–51.

Mok E, Chung BP, Chung JW, Wong TK. Int J Nurs Pract 2005; 11: 150–60.

Tiwari A, Chan S, Wong A, et al. Severe acute respiratory syndrome (SARS) in Hong Kong: patients’

experiences. Nurs Outlook 2003; 51: 212–9.

SARS/MERS: systematic assessment of

symptoms

Studies (n) Cases (n) Sample (n)

Prevalence

(%)

Insomnia 2 54 129 41.9%

Anxiety 2 46 129 35.7%

Depressed mood 2 42 129 32.6%

Pressured speech 1 21 102 20.6%

Euphoria 1 8 102 7.8%

Aggression 1 2 27 7.4%

Irritability 1 5 102 4.9%

Auditory hallucinations 2 6 129 4.7%

Persecutory ideas 1 4 102 3.9%

Visual hallucinations 1 2 102 2.0%

Suicidality 1 2 102 2.0%


Prevalence

(%)

Impaired

concentration/attention 1 39 102 38.2%

Impaired memory 2 44 129 34.1%

Confusion 2 36 129 27.9%

Emotional lability 1 30 102 29.4%

Altered consciousness 1 17 82 20.7%

From Rogers J* & Chesney E*, Oliver D, Pollak T, McGuire P, Fusar-Poli P, Zandi M, Lewis G, David AS, 2020,

Lancet Psychiatry. *Joint 1st authors

Kim H-C, Yoo S-Y, Lee B-H, Lee SH, Shin H-S. Psychiatry Investig 2018; 15: 355–60.

Sheng B, Cheng SKW, Lau KK, Li HL, Chan ELY. Eur Psychiatry 2005; 20: 236–42.

DELIRIUM

SARS/MERS: systematic assessment of

symptoms

SARS/MERS: psychiatric diagnoses

Depression (2 cases)

Anxiety disorder (2)

Acute stress reaction (2)

Psychotic depression (1)

Deterioration of dementia (1)

Psychotic disorders (16)

CHENG SKW, WONG CW, TSANG J, WONG KC. Psychol Med 2004; 34: 1187–95.

Kim H-C, Yoo S-Y, Lee B-H, Lee SH, Shin H-S. Psychiatry Investig 2018; 15: 355–60.

Lee DTS, Wing YK, Leung HCM, et al. Clin Infect Dis 2004; 39: 1247–9.

SARS: acute psychosis

15 cases of psychosis (0.9% of cases of SARS). Compared to 30 age- &

sex-matched SARS patients. 13/15 diagnosed by psychiatrist with

steroid-induced mania/psychosis.

Risk factors for psychosis: family psychiatric history (5/15 vs 0/30),

higher cumulative corticosteroid dose

Some evidence that steroids associated with poorer outcomes in

COVID-19, but RECOVERY trial is using dexamethasone

Lee DTS, Wing YK, Leung HCM, et al. Factors Associated with Psychosis among Patients with Severe

Acute Respiratory Syndrome: A Case-Control Study. Clin Infect Dis 2004; 39: 1247–9.

https://www.recoverytrial.net/

https://www.recoverytrial.net/

Delirium in COVID-19?

2 studies have systematically assessed neuropsychiatric Sx

1. 58 ITU patients in France after extubation.

Agitation: 40/58

Confusion: 26/40

At discharge, 5/45 had a dysexecutive syndrome (inattention, disorientation etc)

2. 82 patients who subsequently died in Wuhan

17/82 had ‘altered consciousness’

4 other studies reported confusion (not systematically): 2.0 – 22.2%

Helms J, Kremer S, Merdji H, et al. N Engl J Med 2020; : NEJMc2008597.

Zhang B, Zhou X, Qiu Y, et al. medRxiv 2020; : 2020.02.26.20028191.

Huang Y, Yang R, Xu Y, Gong P. medRxiv 2020; : 2020.02.27.20029009.

Chen N, Zhou M, Dong X, et al. Lancet (London, England) 2020; 395: 507–13.

Qi D, Yan X, Tang X, et al. medRxiv 2020; : 2020.03.01.20029397.

Leung KS-S, Ng TT-L, Wu AK-L, et al. medRxiv 2020; : 2020.03.30.20045740.

Delirium in COVID-19?

UK data from International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC):

20,133 hospitalised patients

Used routine health records

Docherty et al, BMJ 2020

Delirium as a presenting feature of

COVID-19?

59 elderly patients in a

dementia residential home

with confirmed COVID-19

‘Delirium-onset COVID-19’

(DOC) in 21/57 (36.8%)

Mixture of

hypoactive/hyperactive

DOC associated with higher

mortality (OR 17.0, 2.8-

102.7)

CoroNerve initial findings

Limitation: substantial reporting

bias

153 cases

Median age: 71 (IQR 58-79)

Stroke: 77 (62%)

Mostly ischaemic

Altered mental status: 39 (31%)

Encephalopathy: 9

Encephalitis: 7

Psychiatric diagnoses: 23

Psychosis: 10

Neurocognitive (dementia-like)

syndrome: 6

Affective disorder: 4Varatharaj et al, JAMA Psychiatry 2020

GBS: a cautionary tale

‘GBS incidence fell between March

and May 2020 compared to the

same months of 2016-2019.’

No correlation with COVID-19 &

GBS incidence

No difference in clinical

presentations

Key points

Stress of having a severe infection

Delirium is very common and may be a presenting

feature in the elderly

Specific neuropsychiatric syndromes are probably

rare

Post-illness impactAll SARS and MERS data

Symptoms

Signs and Symptoms Post-illness (n)


Prevalence

(%)

Insomnia 4 34 280 12.1%

Anxiety 2 21 171 12.3%

Impaired concentration/attention 2 34 171 19.9%

Impaired memory 3 44 233 18.9%

Depressed mood 5 35 332 10.5%

Confusion 1 1 621 0.16%

Emotional lability 1 24 102 23.5%

Pressured speech 1 12 102 11.8%

Euphoria 1 11 102 10.8%

Aggression 1 1 102 1.0%

Irritability 3 28 218 12.8%

Auditory hallucinations 1 1 102 1.0%

Persecutory ideas 1 2 102 2.0%

Fatigue 4 61 316 19.3%

Frequent recall of traumatic memories 1 55 181 30.4%

Sleep disorder 1 14 14 100%

Psychotic symptoms (unspecified) 1 4 90 4.4%

Self-harm 1 1 102 1.0%

Anxiety disorders

From Rogers J* & Chesney E*, Oliver D, Pollak T, McGuire P, Fusar-Poli P, Zandi M, Lewis G, David

AS, Lancet Psychiatry 2020. *Joint 1st authors

Depression



Post-traumatic stress disorder



Hospital Anxiety and Depression Scale

(HADS)

3 papers, n = 364

Anxiety subscale: mean 6.5 (95% CI: 3.9 to 9.1, clinical

cutoff = 8)

Depression subscale: mean 6.2 (95% CI: 3.7 to 8.6, clinical

cutoff = 8)

Quality of life

Short Form (36) Health Survey (SF-36)

Range 0 to 100

Compared to general population

3 relevant domains: social functioning, role limitation due to

emotional problems, mental health

SF-36: social functioning

A



SF-36: role limitation due to emotional

problemsB



SF-36: mental health

C



Employment

76.9% (95% CI: 68.1% to 84.6%) had returned to work at

mean follow-up time of 35.3 months.

Implications

Limitations

Lack of control groups

Lack of data of premorbid mental health

Reporting bias

Lack of data on those who aren’t hospitalised / diagnosed

Comparability

Mortality of those infected varies substantially

ICU admission among hospitalised patients more similar:

SARS: 12.8% (k = 5, n=37, 95% CI 6.9% to 22.5%)

MERS: 59.8% (k = 2, n=102, 95% CI 38.9% to 77.6%)

COVID-19: 18.3% (k = 4, n=93, 95% CI 13.3% to 24.6%)

Delirium implications

Difficulties with diagnosis

Prolonged hospital stay

Protracted recovery

Implications for mental capacity and ceilings of care

Follow-up implications

BTS guidelines

recommend asking about

psychosocial status at

follow-up

Assessing cognition

Depression

Anxiety

PTSD

Chronic fatigue

?Cognitive problems

Further information

Video abstract: https://youtu.be/E4Dw__V2SaU

https://youtu.be/E4Dw__V2SaU

SUMMARY

Delirium is common in patients hospitalised for COVID-19

Depression, anxiety and PTSD are likely to be significant in the follow-up

period

Specific neuropsychiatric syndromes are probably rare

Most patients will not have a mental illness after COVID-19

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Psychiatric and neuropsychiatric syndromes in presentations of... · Varatharaj et al, JAMA Psychiatry 2020 Affective disorder: 4. GBS: a cautionary tale ‘GBS incidence fell between

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