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Severe mental illness and risks from COVID-19

August 5, 2020

Sarah Barber, Lara Reed, Nandana Syam, Nicholas Jones 

On behalf of the Oxford COVID-19 Evidence Service Team
Centre for Evidence-Based Medicine, Nuffield Department of Primary Care Health Sciences
University of Oxford

Correspondence to sarah.barber12@nhs.net

VERDICT

  • People with severe mental illness (SMI) are a vulnerable population. In the context of COVID-19, there is reason to suspect they may be at increased risk of contracting SARS-CoV-2 and have worse outcomes following infection, however we found no existing data that quantified these risks.
  • Public health measures associated with COVID-19, including quarantine of suspected cases and lockdowns may negatively affect the mental health status of people with SMI, through change of environment, disruption of services, increased stress and isolation.
  • Existing research points to greater psychological distress during the pandemic for people with SMI, rather than demonstrating this distress is due to the pandemic.

BACKGROUND
The term severe mental illness is often used to describe schizophrenia and bipolar disorder, but it can be more broadly applied to any mental illness that causes severe functional impairment (1). People living with SMI may be at increased risk of contracting SARS-CoV-2: As a result of the severity and chronic nature of their illness, and the associated social disadvantage, many people with SMI live in residential, congregate settings such as psychiatry inpatient units, supported housing, hostels, homeless shelters and prisons. Such environments are at increased risk of outbreaks of infectious diseases, including COVID-19, due to shared spaces and, in some cases, over-crowding (2–7). In addition, behavioural factors relating to cognitive impairment and poor risk awareness may prevent some people with SMI from following infection control measures, further increasing their risk of infection with SARS-CoV-2 (3–5,8–12). Indeed, outbreaks of COVID-19 on psychiatric wards have been reported in various countries. For example, Xiang and colleagues describe an outbreak in a hospital in Wuhan, China, where 50 inpatients and 30 health professionals tested positive in February 2020 (5). Kim and Su describe an outbreak on a Korean psychiatric ward, in which 102 of 103  inpatients tested positive for COVID-19 (13). In the USA, NBC News reported that by 17th April 2020, 63 state-run psychiatry hospitals in the USA had outbreaks of COVID-19, with reported cases at state mental health facilities roughly double the total in the federal prison system (14).

People living with SMI may also be at risk of worse outcomes from COVID-19 than the general population. A range of clinical syndromes are associated with COVID-19, from asymptomatic or mild disease to severe infection with complications such as acute respiratory distress syndrome, with high associated mortality (15). Risk factors for severe infection are highly prevalent in the SMI population. For example, increased rates of obesity, cardiovascular disease and chronic obstructive pulmonary disease are found in people with SMI (16). In part, this may reflect lifestyle factors, including smoking and physical inactivity, but also is a consequence of psychiatric medication side-effects. In particular, atypical antipsychotics are associated with a metabolic syndrome encompassing weight gain, hyperlipidemia and impaired glucose control (17). These factors have been associated with severe infection with SARS-CoV-2 (16). There are additional concerns relating to clozapine, the gold-standard antipsychotic for treatment-resistant schizophrenia (18). Clozapine is associated with haematological side effects including neutropenia and rarely life-threatening agranulocytosis (19), resulting in cessation of clozapine treatment if white cell counts are less than < 3.0 x 109/L (21). Prior to COVID-19, clozapine treatment has been associated with a higher rate of hospital admissions due pneumonia (although the mechanism is debated) (20). However, there is concern that interruption of clozapine treatment, in the case of low white cell count during SARS-CoV-2 infection, may in fact pose a greater challenge to safely managing a COVID-19 infected patient, due to risk of relapse of their psychotic disorder (22). Theoretical concerns have also been raised about benzodiazepines, which are associated with depression of respiratory function, and COVID-19 infection outcomes (3). Finally, access to healthcare may affect outcomes following infection with SARS-CoV-2 in people with SMI. It has previously been shown that people with SMI experience reduced access to healthcare, for example through delayed presentation, misattribution of symptoms and stigmatising attitudes of health professionals (16).

Infection with SARS-CoV-2 and the wider effect of the pandemic may negatively affect the mental health status of people living with SMI. Where people with SMI are infected with SARS-CoV-2, isolation policies may negatively affect their mental health status, especially where there is cognitive impairment and poor understanding of risk. More broadly, the pandemic has created a climate of heightened stress and anxiety, social isolation and disruption of psychiatry services (2,3,11,23–25). There have been reports of disrupted medication supply chains (5,9,25), suspension of community services on which many people with SMI rely (26,27), switching to remote consultation methods (which may not be as effective) (2,3), barriers to admission to inpatient units (28,29) and reduced access to electro-convulsive therapy, considered by some to be a life-saving treatment option for SMI (30). Any of these factors could lead to deterioration in the mental state of a person with SMI.

This rapid review seeks to answer the following questions in relation to SMI and COVID-19:

  • Are people with SMI at increased risk of contracting the SARS-CoV-2 virus?
  • Are people with SMI at increased risk of severe COVID-19 infection and associated complications?
  • What is the effect of COVID-19 on the mental health status of people with SMI?

CURRENT EVIDENCE

Search strategy
We searched 5 databases (PubMed, LitCOVID, medRxiv, Google scholar & Google, PsychINFO) with search terms relating to COVID-19 and SMI. The initial search on 6th May 2020 yielded a total of 670 results, from which 43 titles were selected for full-text review. The search was repeated on 4th June 2020, yielding a further 1057 results, of which 36 titles were selected for full-text review (after duplications were removed, n=2). Full text screening was completed by three authors (LR, NS, SB). A total of 4 studies are included in the review.

Overview of included studies
An overview of included studies is provided in the Characteristics of Included Studies Table (Table 1). The studies include one case-control (31), two cross-sectional analytic studies (32,33) and one retrospective review of routinely collected clinical notes (34). The studies were conducted in three countries: China, Italy and Denmark (all high-income or upper-middle income settings). One study recruited people with SMI who had suspected COVID-19 and controls without COVID-19 from inpatient psychiatric units (31), two studies recruited people with SMI living in the community and excluded those with confirmed or suspected COVID-19 (32,33) and one did not clearly state the setting or infection status of participants (34). Two studies excluded participants with chronic medical illness (32,33). The sample sizes ranged from 51 to 918. Across all studies with comparator groups, the method of recruitment is poorly described, for example both Liu et al and Hao et al refer to convenience methods with no further information (31,33), whereas Iasevoli et al describe only random selection from the phone book (32). Generally, where a comparator group was relevant, the group was well matched. However, there were differences in economic status (32) and education status (33) in some studies. Outcomes of interest were largely psychiatric in nature, including measures of stress, anxiety, depression, sleep quality and symptoms of psychosis. Two studies used clinician-rated (31,32) scales and one used self-rated scales (33). Only one study reported psychiatric medication use (31).

Table 1: Characteristics of Included Studies

 

Author Period of data collection Design Setting Sample size COVID-19 status Population of interest, n (% female if known, mean age if known) Comparator population, n (% female if known, mean age if known) Comparator group matching Outcome measures
Liu et al (31) 30th January – 21st February 2020 Case-

control

 Inpatient, Hubei province, China 51 Suspected COVID-19 infection1 People with schizophrenia with suspected COVID-19, n = 21 (57% female, mean age 43) People with schizophrenia without suspected COVID-19, n = 30 (50% female, mean age 45) ·         No difference in age, sex, co-morbidities or schizophrenia symptom severity between groups (PANSS score, t = 1.17, p = 0.248) ·         Psychiatric medications

·         PANSS

·         PSS

·         HAMD

·         HAMA

·         PSQI
Iasevoli et al (32) 13th April – 17th April 2020 Cross-sectional, analytic Community, Naples, Italy 461 No suspected COVID-19 infection People with schizophrenia, bipolar disorder or recurrent major depression living who had been stable at last clinical evaluation in January-February 2020, aged 18-70, n = 205 Care givers (first-degree relatives who spend the majority of the day with the patient), n = 51

Controls = 205

 

 

 ·         No difference in age, gender or educational achievement between groups

·         Patient group had lower economic status (χ = 49.92, p < 0.002) and higher rates of co-morbid medical diseases (χ = 11.87, p = 0.001)  than controls

 ·         PSS

·         GAD-7

·         PHQ-9

·         SPEQ (paranoia and grandiosity subscale)
Hao et al (33) 19th February – 22nd February 2020 Cross-sectional, analytic Community, Chongqing, China 185 No suspected COVID-19 infection People with depressive or anxiety disorders living in the community, aged > 18, n = 76, (67% female, mean age 33) Controls, n = 109 (62% female, mean age 33) ·         Excluded people with suspected COVID-19

·         No difference in age or gender between groups

·         Higher percentage of controls had undergraduate degree

 ·         Physical symptoms

·         IES-R

·         DASS-21

·         ISI

·         Other psychiatric symptoms
Rohde et al (34) 1st February – 23rd March 2020 Service evaluation Not stated, Central Denmark Region, Denmark 918 Unknown COVID-19 status People with mental illness receiving treatment from secondary care psychiatric services in either inpatient or outpatient setting, aged > 18, n = 918 (67% female, mean age 38) – – ·         Pandemic-related psychiatric symptoms

DASS-21, Depression, Anxiety and Stress Scale; GAD-7, Generalised Anxiety Disorder Scale 7; HAMA, Hamilton Anxiety Rating Scale; HAMD, Hamilton Depression Rating Scale; IES-R, Impact of Event Scale-Revised; ISI, Insomnia Severity Index; PANSS, Positive and Negative Syndrome Scale; PHQ-9, Patient Health Questionnaire 9; PSQI, Pittsburgh Sleep Quality Index; PSS, Perceived Stress Scale; SPEC, Specific Psychotic Experience Questionnaire

  1. Defined as respiratory symptoms and/or abnormal chest CT findings

Quality assessment
Quality assessment of the included studies was informed by the MMAT tool (35). All included studies were quantitative, non-randomised studies. All studies included participants with mental illness under the care of secondary care services, and it was therefore assumed that the nature of the illness was severe. Some studies excluded participants with co-morbid physical health problems but this was poorly defined (32,33). Two studies were cross-sectional, analytic studies, one of which was at high risk of non-response bias (33), whilst the other did not report response rate (32). In three studies, measurements of psychological symptoms relied on clinician or patient-rated scales (31–33), with limited discussion of validity and reliability in the population and context. There was no reporting of incomplete data or drop-outs. Overall, the case-control and cross-sectional studies did not account for confounding variables in their design and analysis, in particular the baseline severity of the psychiatric illness and associated psychological symptomatology, limiting conclusions around association of symptoms with the COVID-19 pandemic. Overall, the quality of the small number of included studies is low, with high risk of bias within studies.

Results

  • Are people with SMI at increased risk of contracting the SARS-CoV-2 virus?

Although there are case reports of outbreaks of COVID-19 in psychiatric institutions, we found no direct evidence as to the risk of COVID-19 among people with SMI compared to the general population. However, this does not rule out an association, as more data becomes available during and after the pandemic.

  • Are people with SMI at increased risk of severe COVID-19 infection and associated complications? 

Again, we did not find any study comparing disease severity or clinical outcomes among people with SMI compared to the general population.

  • What is the effect of COVID-19 on the mental health status of people with SMI?

All four of the included studies addressed the question of whether COVID-19 impacted upon the mental health status of people with SMI.

Liu et al compared people with schizophrenia in an inpatient setting with and without suspected COVID-19 infection (31). It should be noted that only 1/21 had a positive PCR-test for COVID-19 and only 11/21 are described as meeting the clinical criteria for a confirmed case, therefore it is the suspicion of COVID-19 that defines the group rather than confirmed infection. Patients in the suspected COVID-19 group had higher mean Perceived Stress Score (PSS) (26.5 vs 11.6, t = 9.907, p < 0.001), Hamilton Anxiety Rating Scale score (HAMA) (13.9 vs 2.2, t = -5.099, p < 0.001), Hamilton Depression Rating Scale score (HAMD) (14.1 vs 0.4, t = -6.318, p < 0.001) and Pittsburgh Sleep Quality Index score (PSQI) (8.0 vs 4.7, t = -2.835, p = 0.005), indicating higher levels of stress, anxiety, depression and difficulty sleeping. There was no significant difference in antidepressant (4.5% vs 0%, p = 0.412) or mood stabiliser (33.3% vs 16.7%, t = 1.907, p = 0.167) use between groups. However, 57.1% in the suspected COVID-19 group were prescribed benzodiazepines, compared to 16.7% in the comparison group (t = 9.107, p = 0.003). For almost 30% of patients in the suspected COVID-19 group, benzodiazepine use increased after detection of CT chest abnormalities, consistent with their higher stress and anxiety scores. In this study, there is a risk of selection bias, as cases and controls are selected from different hospitals which may have a different case mix. In addition, there is no evidence of blinding, resulting in high risk of observer bias in the clinician-rated scales.

Iasevoli et al compared people with schizophrenia, bipolar disorder or major depression to non-psychiatric controls (32). The patient group had higher mean PSS scores (16.3 vs 14.1, t = 2.64, p = 0.009), Generalised Anxiety Disorder (GAD-7) scores (6.9 vs 5.5, t = 2.6, p = 0.01), Patient Health Questionnaire (PHQ-9) scores (9.3 vs 6.2, t = 5.9, p < 0.0001) and higher Specific Psychotic Experience Questionnaire (SPEQ) paranoia subscale scores (10.7 vs 3.8, t = 5.47, p < 0.0001), indicating higher stress, anxiety, depression and paranoia in the SMI group compared to controls. There was no difference in SPEC grandiosity subscale score. In addition, patients had higher odds of suffering severe psychopathology compared to controls. The odds ratio for high perceived stress (PSS score > 26) was 4.23, with a 95% confidence interval from 1.8 to 9.7. Similarly, the odds ratio of moderate-to-severe anxiety (GAD score > 7) was 2.14 (95% CI 1.2-3.6) and severe depression was 2.5 (95% CI 1.5-4.2). After adjustment, the authors report that concomitant medical diseases showed an independent effect on PSS, GAD-7 and PHQ-9 score. However, the exclusion of participants with severe chronic medical disorders limits the conclusions that can be drawn from this association.

Hao et al compared 76 patients with major depression or anxiety disorders and 109 controls. The structured questionnaire was sent via SMS in February 2020, when strict lock down measures were in place in Chongqing (33). There was a higher mean Impact of Event Scale (IES-R) score in the patient group compared to controls (17.7 vs 11.3, p < 0.001) and significantly more patients scored 24 or above, indicative of possible Post-Traumatic Stress Syndrome (PTSD) (31.6% vs 13.8%, p = 0.003). In addition, the mean DASS-21 anxiety, depression and stress score was higher in patients compared to controls: 6.6 vs 1.5, (p < 0.001) 8.3 vs 2.2 (p < 0.001) and 8.0 vs 2.7 (p < 0.001) respectively. Similarly, mean insomnia severity index scale scores were significantly higher in the patient group (10.1 vs 4.63, p < 0.001). There were higher rates of moderate-to-severe symptoms in patients compared to controls for anxiety (23.6% vs 2.7%), depression (22.4% vs 0.9%), stress (17% vs 0.9%) and insomnia (27.6% vs 0.9%). The authors enquired about other psychiatric symptoms and report higher anger and impulsivity (p < -0.001) and suicidal ideation (p = 0.003) in the psychiatric patient group, but no difference in rates of paranoid ideas, auditory hallucinations, alcohol use or intention to harm others. The authors also report self-reported symptoms of COVID-19 in the past 14 days and found a higher percentage of patients reported symptoms (30.3%) compared to controls (5.5%), which they report as significant with (p < 0.0001). In addition, a higher percentage of patients self-report poor or worse physical health status compared to controls (9.2% vs 2.8%,) (p < 0.001). However, the exclusion of participants with suspected COVID-19 symptoms and chronic medical conditions makes this difficult to meaningfully interpret. In addition, the evidence for validation of the IES-R scale in this population is weak and risk of non-response bias is high: the response rates was 11% for patients and 84% for controls.

Rohde et al used routinely collected clinical data to assess the impact of COVID-19 on patients across five psychiatric hospitals providing inpatient and outpatient treatment in Denmark (34). The authors conducted an electronic search for COVID-19 related terms in clinical notes dated between 1st February to 2nd March 2020. 11,072 clinical notes were manually screened by two authors who sought to identify pathological reactions to the pandemic, for example descriptions of worsening of otherwise stable psychopathology. We are led to believe these symptoms are new or represent a deterioration in mental state, rather than simply being a shift of focus in an illness that is unchanged in nature or degree.

The authors identified 1357 notes from 918 patients (6% of the total) which described pandemic-related psychiatric symptoms. Of the 918 patients, 21% had schizophrenia, 17% anxiety disorder (generalised, OCD and PTSD), 14% major depression, 13% reactive and adjustment disorder, 7% bipolar disorder and the remainder various diagnoses including eating disorders and autism spectrum disorders. The authors report that in the 1357 clinical notes, the most common pandemic-related psychopathology identified was anxiety (n = 539), followed by non-specific stress (n = 174), depression (n = 146), delusions (n = 149), suicidality (n = 102) and obsessive-compulsive symptoms (n = 85). Less commonly reported symptoms included mania, hallucinations, and substance misuse. The authors plotted the cumulative incidence of clinical notes describing pandemic-related psychopathology, which mirrored the growth in numbers of confirmed cases of COVID-19 in Denmark. The strength of this approach is the large sample size and demonstration of temporality. However, the results are limited to a tally of the different categories of psychopathology (for example, suicidality, with no data regarding suicide attempts or completed suicide) and the association between symptoms and the COVID-19 pandemic, whilst approached systematically, remains subjective.

The results of the included studies can be summarised in three main points: 1) suspicion of COVID-19 and subsequent transfer to an isolation ward is a potential stressor for patients with schizophrenia, and has been shown to be associated with differences in benzodiazepine use between patient groups (31), 2) people with severe mental illness in the community, who did not have COVID-19, tended to have higher levels of psychological distress (non-specific stress, anxiety, depression and sleep disturbance) compared to controls, as measured by clinician and self-rated scales (32,33) and 3) there is data suggestive of a range of COVID-19 related psychopathology in routinely collected clinical notes in one setting (34). However, there are limitations to what can be concluded from these studies. Most importantly, the higher levels of psychological distress and symptom burden amongst people living with SMI in the community compared to controls cannot be causally associated with the COVID-19 pandemic, as the measures used are non-specific and there is an absence of baseline (or pre-COVID-19) data to demonstrate temporality.

EMERGING EVIDENCE IN COVID-19
Moore and colleagues have published a protocol for a study aiming to assess the mental health impact of COVID-19 on people with SMI who are receiving outpatient care in the USA (36). People with a diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder or major depressive disorder with psychotic symptoms who have preiously participated in observational studies will be recruited. Data will be collected at two time points via phone interview between April and August 2020. Unlike previously mentioned studies, certain measures can be compared to a pre-COVID baseline where data is available from the parent study. These measures include items about engagement in daily activities, social interactions, mood, symptoms, and other behavioural indicators of health. In addition, scales relating to depression, anxiety, stress, loneliness, support, and coping will be administered. Results will be published in a peer-reviewed journal.

The Coronavirus Outbreak Psychological Experiences (COPE) study is also underway. As outlined on the Kings College London website, people aged above 16 who live in the UK are invited to take part in an online survey, with the aim to investigate the effect of public health measures in response to the COVID-19 pandemic on people with and without lived experience of mental health problems, as well as carers of people with mental health difficulties.

CONCLUSIONS
Of the four studies included in this review, one considered the impact of suspected infection with SARS-CoV-2, and three the wider impact of the COVID-19 pandemic on people with SMI. There are no available data to assess whether people with SMI are at higher risk of contracting SARS-CoV-2, and following this, at higher risk of severe infection and complications, than other groups.

We found some evidence that COVID-19 has negatively impacted upon the mental status of people with pre-existing SMI. For people living with SMI in the community, it appears that the burden of psychological symptoms, including stress, anxiety, depression, and insomnia may have been greater than for the general population during the pandemic. These data come from Italy and China. Review of routinely collected clinical notes in Denmark has revealed pandemic-related psychopathology in people with pre-existing mental health problems ranging from non-specific stress, to delusions, obsessive-compulsive symptoms, and suicidality. A single study of psychiatry inpatients also reported that suspected COVID-19 infection and transfer to an isolation unit was associated with higher psychological distress and benzodiazepine use in the short term for people with schizophrenia.

These observational studies fall short of attributing causality for the psychological symptoms directly to the pandemic and lockdown measures nor do they inform on the long-term impact on people with SMI. Further research into the effect of COVID-19 on the mental health status of people with SMI is urgently needed across all income settings. The ongoing study by Moore and colleagues (36) is anticipated to overcome some of the limitations of the studies included in this review. It is vital that the impact of COVID-19 on people with SMI, a vulnerable population, is better understood. 

End.

Disclaimer:  the article has not been peer-reviewed; it should not replace individual clinical judgement and the sources cited should be checked. The views expressed in this commentary represent the views of the authors and not necessarily those of the host institution, the NHS, the NIHR, or the Department of Health and Social Care. The views are not a substitute for professional medical advice.

AUTHORS

  • Sarah Barber is an FY3 Doctor currently working in Rehabilitation Psychiatry
  • Lara Reed is a fourth-year medical student at Oxford University
  • Nandana Syam is a fourth-year medical student at Oxford University
  • Nicholas Jones is a GP and Wellcome Trust Doctoral Research Fellow based at the University of Oxford, Nuffield Department of Primary Care Health Sciences

SEARCH TERMS

Search terms Original Update Database
((((((“Depressive Disorder, Major”[Mesh]) OR “Bipolar and Related Disorders”[Mesh]) OR “Schizophrenia Spectrum and Other Psychotic Disorders”[Mesh]) OR (serious mental* OR seriously mental* OR severe mental* OR severly mental OR serious psych* OR seriously psych* OR severe psych* OR severely psych*)) OR ((schizophren*[Title/Abstract] OR psychosis[Title/Abstract] OR psychotic[Title/Abstract] OR paranoid disorder*[Title/Abstract] OR major depress*[Title/Abstract] OR bipolar depress*[Title/Abstract] OR bipolar disorder*[Title/Abstract]))) OR (psychiatric disorder*[Title] OR mental disorder*[Title] OR mental illness[Title] OR mentally ill*[Title])) AND ((coronavirus*[Title] OR coronovirus*[Title] OR coronoravirus*[Title] OR coronaravirus*[Title] OR corono-virus*[Title] OR corona-virus*[Title] OR “Coronavirus”[Mesh] OR “Coronavirus Infections”[Mesh] OR “Wuhan coronavirus” [Supplementary Concept] OR “Severe Acute Respiratory Syndrome Coronavirus 2″[Supplementary Concept] OR COVID-19[All Fields] OR CORVID-19[All Fields] OR “2019nCoV”[All Fields] OR “2019-nCoV”[All Fields] OR WN-CoV[All Fields] OR nCoV[All Fields] OR “SARS-CoV-2”[All Fields] OR HCoV-19[All Fields] OR “novel coronavirus”[All Fields])) Filters: from 2019 – 2020 214 534 PubMed
“major depress*” OR psychosis OR psychotic OR schizophrenia OR bipolar OR “severe mental*” OR “severely mental*” OR “serious mental*” OR “seriously mental*” OR “severe psychiatr*” OR “serious psychiatr*” 218 523 LitCOVID
abstract or title “”major depress*” OR psychosis OR psychotic OR schizophrenia OR bipolar” (match any words) and full text or abstract or title “coronavirus OR covid-19” (match whole any) 26 no new studies medRxiv
“psychiatric” (match any words) and abstract or title “coronavirus OR covid-19” 53 no new studies medRxiv
“mental” (match any words) and abstract or title “coronavirus OR covid-19” 159 no new studies medRxiv
(coronavirus OR covid-19) AND (“major depression” OR “major depressive” OR schizophrenia OR psychosis OR psychotic OR bipolar) Google Scholar & Google
(coronavirus OR covid-19) AND (“severe mental” OR “serious mental” OR “severely mentally” OR “seriously mentally” OR “severe psychiatric” OR “serious psychiatric”) Google Scholar & Google

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