Zika virus-induced TNF-α signaling dysregulates expression of neurologic genes associated with psychiatric disorders.

BACKGROUND: Zika virus (ZIKV) is an emerging flavivirus of global concern. ZIKV infection of the central nervous system has been linked to a variety of clinical syndromes, including microcephaly in fetuses and rare but serious neurologic disease in adults. However, the potential for ZIKV to influence brain physiology and host behavior following apparently mild or subclinical infection is less well understood. Furthermore, though deficits in cognitive function are well-documented after recovery from neuroinvasive viral infection, the potential impact of ZIKV on other host behavioral domains has not been thoroughly explored. METHODS: We used transcriptomic profiling, including unbiased gene ontology enrichment analysis, to assess the impact of ZIKV infection on gene expression in primary cortical neuron cultures. These studies were extended with molecular biological analysis of gene expression and inflammatory cytokine signaling. In vitro observations were further confirmed using established in vivo models of ZIKV infection in immunocompetent hosts. RESULTS: Transcriptomic profiling of primary neuron cultures following ZIKV infection revealed altered expression of key genes associated with major psychiatric disorders, such as bipolar disorder and schizophrenia. Gene ontology enrichment analysis also revealed significant changes in gene expression associated with fundamental neurobiological processes, including neuronal development, neurotransmission, and others. These alterations to neurologic gene expression were also observed in the brain in vivo using several immunocompetent mouse models of ZIKV infection. Mechanistic studies identified TNF-α signaling via TNFR1 as a major regulatory mechanism controlling ZIKV-induced changes to neurologic gene expression. CONCLUSIONS: Our studies reveal that cell-intrinsic innate immune responses to ZIKV infection profoundly shape neuronal transcriptional profiles, highlighting the need to further explore associations between ZIKV infection and disordered host behavioral states.

Risks of mental health outcomes in people with covid-19: cohort study.

OBJECTIVE: To estimate the risks of incident mental health disorders in survivors of the acute phase of covid-19. DESIGN: Cohort study. SETTING: US Department of Veterans Affairs. PARTICIPANTS: Cohort comprising 153 848 people who survived the first 30 days of SARS-CoV-2 infection, and two control groups: a contemporary group (n=5 637 840) with no evidence of SARS-CoV-2, and a historical control group (n=5 859 251) that predated the covid-19 pandemic. MAIN OUTCOMES MEASURES: Risks of prespecified incident mental health outcomes, calculated as hazard ratio and absolute risk difference per 1000 people at one year, with corresponding 95% confidence intervals. Predefined covariates and algorithmically selected high dimensional covariates were used to balance the covid-19 and control groups through inverse weighting. RESULTS: The covid-19 group showed an increased risk of incident anxiety disorders (hazard ratio 1.35 (95% confidence interval 1.30 to 1.39); risk difference 11.06 (95% confidence interval 9.64 to 12.53) per 1000 people at one year), depressive disorders (1.39 (1.34 to 1.43); 15.12 (13.38 to 16.91) per 1000 people at one year), stress and adjustment disorders (1.38 (1.34 to 1.43); 13.29 (11.71 to 14.92) per 1000 people at one year), and use of antidepressants (1.55 (1.50 to 1.60); 21.59 (19.63 to 23.60) per 1000 people at one year) and benzodiazepines (1.65 (1.58 to 1.72); 10.46 (9.37 to 11.61) per 1000 people at one year). The risk of incident opioid prescriptions also increased (1.76 (1.71 to 1.81); 35.90 (33.61 to 38.25) per 1000 people at one year), opioid use disorders (1.34 (1.21 to 1.48); 0.96 (0.59 to 1.37) per 1000 people at one year), and other (non-opioid) substance use disorders (1.20 (1.15 to 1.26); 4.34 (3.22 to 5.51) per 1000 people at one year). The covid-19 group also showed an increased risk of incident neurocognitive decline (1.80 (1.72 to 1.89); 10.75 (9.65 to 11.91) per 1000 people at one year) and sleep disorders (1.41 (1.38 to 1.45); 23.80 (21.65 to 26.00) per 1000 people at one year). The risk of any incident mental health diagnosis or prescription was increased (1.60 (1.55 to 1.66); 64.38 (58.90 to 70.01) per 1000 people at one year). The risks of examined outcomes were increased even among people who were not admitted to hospital and were highest among those who were admitted to hospital during the acute phase of covid-19. Results were consistent with those in the historical control group. The risk of incident mental health disorders was consistently higher in the covid-19 group in comparisons of people with covid-19 not admitted to hospital versus those not admitted to hospital for seasonal influenza, admitted to hospital with covid-19 versus admitted to hospital with seasonal influenza, and admitted to hospital with covid-19 versus admitted to hospital for any other cause. CONCLUSIONS: The findings suggest that people who survive the acute phase of covid-19 are at increased risk of an array of incident mental health disorders. Tackling mental health disorders among survivors of covid-19 should be a priority.

Loneliness among people with severe mental illness during the COVID-19 pandemic: Results from a linked UK population cohort study.

AIM/GOAL/PURPOSE: Population surveys underrepresent people with severe mental ill health. This paper aims to use multiple regression analyses to explore perceived social support, loneliness and factor associations from self-report survey data collected during the Covid-19 pandemic in a sample of individuals with severe mental ill health. DESIGN/METHODOLOGY/APPROACH: We sampled an already existing cohort of people with severe mental ill health. Researchers contacted participants by phone or by post to invite them to take part in a survey about how the pandemic restrictions had impacted health, Covid-19 experiences, perceived social support, employment and loneliness. Loneliness was measured by the three item UCLA loneliness scale. FINDINGS: In the pandemic sub-cohort, 367 adults with a severe mental ill health diagnosis completed a remote survey. 29-34% of participants reported being lonely. Loneliness was associated with being younger in age (adjusted OR = -.98, p = .02), living alone (adjusted OR = 2.04, p = .01), high levels of social and economic deprivation (adjusted OR = 2.49, p = .04), and lower perceived social support (B = -5.86, p < .001). Living alone was associated with lower perceived social support. Being lonely was associated with a self-reported deterioration in mental health during the pandemic (adjusted OR = 3.46, 95%CI 2.03-5.91). PRACTICAL IMPLICATIONS: Intervention strategies to tackle loneliness in the severe mental ill health population are needed. Further research is needed to follow-up the severe mental ill health population after pandemic restrictions are lifted to understand perceived social support and loneliness trends. ORIGINALITY: Loneliness was a substantial problem for the severe mental ill health population before the Covid-19 pandemic but there is limited evidence to understand perceived social support and loneliness trends during the pandemic.

Neuropsychiatric syndrome with myoclonus after SARS-CoV-2 infection in a paediatric patient.

We report the case of a 12-years-old patient who subacutely developed a positive and negative myoclonus of limbs and face, drowsiness and memory deficits after getting infected by SARS-CoV-2. On admission, nasopharyngeal swab for SARS-CoV-2, brain and spinal MRI with and without contrast, EEG, chest X-ray and abdominal ultrasound were negative. CSF physical-chemical examination, culture, PCR testing for SARS-CoV-2 and other pathogens, and oligoclonal IgG bands were negative as well. A full panel blood test, including clotting, autoimmunity and paraneoplastic blood studies, did not show any alteration. The neuropsychological examination showed an impairment in memory, visual-motor coordination, inductive reasoning skills, attention, and concentration. The patient was first treated with clonazepam and then with intravenous methylprednisolone for five days, with poor response. For this reason, he then received a cycle of IVIG, thus reaching a gradual and complete recovery. To date, this is the first case of a COVID-19 associated myoclonus affecting a paediatric patient.

Determinants of Hepatitis C Virus Prevalence in People With Serious Mental Illness: A Systematic Review and Meta-Analysis.

Objective: To perform a meta-analysis of hepatitis C virus (HCV) prevalence in people with serious mental illness (SMI) and to systematically review barriers to care with the contention that both individual complications and HCV community transmission can be reduced with enhanced health care strategies.Data Sources: PubMed, Scopus, Embase, CINAHL, and Web of Science were searched for articles published in English between April 21, 1989, and July 1, 2020. The terms Hepatitis C Virus, HCV, HCV seroprevalence, and HCV prevalence were cross-referenced with serious mental illness, severe mental illness, psychiatric illness, mental illness, and psychiatric patients.Study Selection: We identified 230 titles after removing duplicates. The final analysis included 36 publications drawn from prospective and large retrospective cohort studies that cross-sectionally screened for HCV in people with SMI ≥ 18 years of age.Data Extraction: Pooled HCV prevalence was analyzed, with random effects modeling due to significant attributable study heterogeneity. Demographic data and HCV risk factors were subanalyzed. Qualitative and semiqualitative data relating to control cohort prevalence and the HCV care cascade were also extracted.Results: The pooled HCV prevalence was 8.0% (95% CI, 6.0%-9.0%). Subanalysis of prospective studies (n = 9,015 individuals) demonstrated a similar prevalence, 8.0% (CI, 5.0%-11.0%), to retrospective studies (n = 289,247), 8.0% (CI, 6.0%-10.0%). HCV was 3.0- to 11.3-fold higher in people with SMI relative to controls. Semiqualitative analysis of seropositive cases showed that (1) 20.0%-58.1% did not have an identified HCV risk factor; (2) 12.5%-100% of cases were not previously known to have HCV; and (3) the majority, 57.0%-96.6%, of people with SMI were receptive to HCV screening.Conclusions: People with SMI have high HCV seroprevalence and should be recognized as a priority group for HCV screening and health care access.

Molecular mimicry of NMDA receptors may contribute to neuropsychiatric symptoms in severe COVID-19 cases.

Approximately 30% of individuals with severe SARS-CoV-2 infections also develop neurological and psychiatric complaints. In rare cases, the occurrence of autoimmune encephalitis has been reported after SARS-CoV-2 infection. In this systematic review, we have identified eight SARS-CoV-2-associated cases of anti-NMDA receptor encephalitis. All had cerebrospinal fluid antibodies against the NMDA receptor and a recent onset of working memory deficits, altered mental status, or psychiatric symptoms, such as confusion, agitation, auditory hallucination, catatonia and speech dysfunction. All patients received high-dose steroid and immunoglobulin therapeutics and conditions improved in each case. These findings suggest that clinical attention should be paid to warning signs of autoimmune encephalitis in severe COVID-19 cases. If characteristic features of autoimmune encephalitis are present, autoantibody diagnostics should be performed and confirmed cases should be treated with immunotherapy to minimize neurological impairments.

Dysregulated inflammation may predispose patients with serious mental illnesses to severe COVID­19 (Review).

Genetic and nongenetic factors associated with an increased inflammatory response may mediate a link between severe coronavirus disease 2019 (COVID­19) and serious mental illness (SMI). However, systematic assessment of inflammatory response­related factors associated with SMI that could influence COVID­19 outcomes is lacking. In the present review, dietary patterns, smoking and the use of psychotropic medications are discussed as potential extrinsic risk factors and angiotensin­converting enzyme (ACE) insertion/deletion (I/D) gene polymorphisms are considered as potential intrinsic risk factors. A genetics­based prediction model for SMI using ACE­I/D genotyping is also proposed for use in patients experiencing severe COVID­19. Furthermore, the literature suggests that ACE inhibitors may have protective effects against SMI or severe COVID­19, which is often linked to hypertension and other cardiovascular comorbidities. For this reason, we hypothesize that using these medications to treat patients with severe COVID­19 might yield improved outcomes, including in the context of SMI associated with COVID­19.

COVID-19 vaccine willingness amongst patients with mental illness compared with the general population.

Patients with mental illness are at an increased risk of COVID-19 infection, morbidity, and mortality, and prioritisation of this group for COVID-19 vaccination programmes has therefore been suggested. Vaccine uptake may, however, be compromised by vaccine hesitancy amongst patients with mental illness, posing a critical public health issue. We conducted two surveys to provide weighted estimates of vaccine willingness amongst patients with mental illness and the general population of Denmark. Vaccine willingness was high in both groups, but slightly lower amongst patients with mental illness (84.8%), compared with the general population (89.5%) (p < .001). Based on these findings, vaccine hesitancy does not appear to be a major barrier for vaccine uptake amongst patients with mental illness in Denmark, but may be so in other countries with lower general vaccine willingness. Replication of the present study in other countries is strongly warranted.

Efficacy of traditional herbal medicine for psychological sequelae in COVID-19 survivors: A protocol for systematic review and meta-analysis.

INTRODUCTION: This study is the protocol for a systematic review to evaluate the efficacy of herbal medicine on COVID-19 survivors with psychological sequelae. Currently, there are many COVID-19 survivors with psychological sequelae as COVID-19 has widely spread all over the world. However, there is no critically appraised evidence of the benefit of herbal medicine for COVID-19 survivors with psychological sequelae. MATERIALS AND METHODS: We will search 11 electronic databases from inception to December, 2022: 4 English databases, MEDLINE, PubMed, Excerpta Medica database (EMBASE), and the Cochrane Central Register of Controlled Trials (CENTRAL); 3 Chinese databases, the Chinese National Knowledge Infrastructure, the Chinese Scientific Journal database, and the Wan Fang database; and 4 Korean databases, the Oriental Medical Advanced Searching Integrated System, the Korean Studies Information Service System, the National Digital Science Links, and the Research Information Sharing Service. We will include randomized controlled trials (RCTs), non-RCTs, and quasi-RCTs for all formations of TRADITIONAL herbal medicine versus conventional drug, placebo, and no treatment for COVID-19 survivors. We will only include the COVID-19 survivors with psychiatric symptoms lasting at least 1 month, regardless of their race, sex, and age. DISCUSSION AND CONCLUSIONS: This systematic review will be published in a peer-reviewed journal. The findings will provide evidence and treatment directions for clinicians. This protocol does not need ethical approval because it will be based on published research. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42020210592.

Understanding the psychiatric symptoms of COVID-19: a meta-analysis of studies assessing psychiatric symptoms in Chinese patients with and survivors of COVID-19 and SARS by using the Symptom Checklist-90-Revised.

Understanding the psychiatric symptoms of COVID-19 could facilitate the clinical management of COVID-19 patients. However, the profile of psychiatric symptoms among COVID-19 patients has been understudied. We performed a meta-analysis of studies assessing psychiatric symptoms of COVID-19 and SARS patients and survivors by using the Symptom Checklist-90-Revised (SCL-90-R), an instrument covering a wide spectrum of psychiatric symptoms. Studies reporting SCL-90-R subscale scores among patients with and survivors of COVID-19 and SARS were retrieved from major English and Chinese literature databases. Patients' pooled SCL-90-R subscale scores were compared to the Chinese normative SCL-90-R data, and Cohen's d values were calculated to indicate the severity of psychiatric symptoms. The Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data was used to assess the quality of the included studies. The search yielded 25 Chinese studies with 1675 acute COVID-19 and 964 acute SARS patients, 30 COVID-19 and 552 SARS survivors during very early recovery (up to 1 month since discharge), 291 SARS survivors during early recovery (1-6 months after discharge), and 48 SARS survivors during late recovery (12 months after discharge). None of the included studies were rated as good quality. The ten SCL-90-R-defined psychiatric symptoms, which were of medium-to-severe severity (d = 0.68-3.01), were all exhibited in acute COVID-19 patients, and the severity of these symptoms decreased to mild-to-medium during very early recovery (d = 0.17-0.73). SARS patients presented eight psychiatric symptoms with mild-to-severe severity during the acute stage (d =0.43-1.88), and thereafter, the severity of symptoms decreased over the follow-up period. However, somatization (d = 0.30) and anxiety (d = 0.28) remained at mild levels during late recovery. A wide variety of severe psychiatric symptoms have been reported by acute COVID-19 patients, and these symptoms, despite decreasing in severity, persist in very early recovery. The changing trajectory observed with SARS suggests that psychiatric symptoms of COVID-19 may persist for a long time after discharge, and therefore, periodic monitoring of psychiatric symptoms, psychosocial support, and psychiatric treatment (when necessary) may be necessary for COVID-19 patients from the acute to convalescent stages.

Mental disorders, psychopharmacological treatments, and mortality in 2150 COVID-19 Spanish inpatients.

OBJECTIVE: To determine how mental disorders and psychopharmacological treatments before and during COVID-19 hospital admissions are related to mortality. METHODS: Subjects included in the study were all adult patients with a diagnosis of COVID-19, confirmed clinically and by PCR, who were admitted to a tertiary university hospital in Badalona (Spain) between March 1 and November 17, 2020. Data were extracted anonymously from computerized clinical records. RESULTS: 2,150 subjects were included, 57% males, mean age 61 years. History of mental disorders was registered in 957 (45%). Throughout admission, de novo diagnosis of mood or anxiety, stress, or adjustment disorder was made in 12% of patients without previous history. Delirium was diagnosed in 10% of cases. 1011 patients (47%) received a psychotropic prescription during admission (36% benzodiazepines, 22% antidepressants, and 21% antipsychotics). Mortality rate was 17%. Delirium during admission and history of mood disorder were independently associated with higher mortality risk (hazard ratios, 1.39 and 1.52 respectively), while previous year's treatments with anxiolytics/hypnotics and antidepressants were independently associated with lower mortality risk (hazard ratios, 0.47 and 0.43, respectively). CONCLUSION: Mental symptoms are very common in patients hospitalized for COVID-19 infection. Detecting, diagnosing, and treating them is key to determining the prognosis of the disease and functional recovery.

Evidence Synthesis of Digital Interventions to Mitigate the Negative Impact of the COVID-19 Pandemic on Public Mental Health: Rapid Meta-review.

BACKGROUND: Accumulating evidence suggests the COVID-19 pandemic has negative effects on public mental health. Digital interventions that have been developed and evaluated in recent years may be used to mitigate the negative consequences of the pandemic. However, evidence-based recommendations on the use of existing telemedicine and internet-based (eHealth) and app-based mobile health (mHealth) interventions are lacking. OBJECTIVE: The aim of this study was to investigate the theoretical and empirical base, user perspective, safety, effectiveness, and cost-effectiveness of digital interventions related to public mental health provision (ie, mental health promotion, prevention, and treatment of mental disorders) that may help to reduce the consequences of the COVID-19 pandemic. METHODS: A rapid meta-review was conducted. The MEDLINE, PsycINFO, and CENTRAL databases were searched on May 11, 2020. Study inclusion criteria were broad and considered systematic reviews and meta-analyses that investigated digital tools for health promotion, prevention, or treatment of mental health conditions and determinants likely affected by the COVID-19 pandemic. RESULTS: Overall, 815 peer-reviewed systematic reviews and meta-analyses were identified, of which 83 met the inclusion criteria. Our findings suggest that there is good evidence on the usability, safety, acceptance/satisfaction, and effectiveness of eHealth interventions. Evidence on mHealth apps is promising, especially if social components (eg, blended care) and strategies to promote adherence are incorporated. Although most digital interventions focus on the prevention or treatment of mental disorders, there is some evidence on mental health promotion. However, evidence on process quality, cost-effectiveness, and long-term effects is very limited. CONCLUSIONS: There is evidence that digital interventions are particularly suited to mitigating psychosocial consequences at the population level. In times of physical distancing, quarantine, and restrictions on social contacts, decision makers should develop digital strategies for continued mental health care and invest time and efforts in the development and implementation of mental health promotion and prevention programs.

Telepsychiatry and other cutting-edge technologies in COVID-19 pandemic: Bridging the distance in mental health assistance.

BACKGROUND: At the end of 2019, a novel coronavirus (COVID-19) was identified in China. The high potential of human-to-human transmission led to subsequent COVID-19 global pandemic. Public health strategies including reduced social contact and lockdown have been adopted in many countries. Nonetheless, social distancing and isolation could also represent risk factors for mental disorders, resulting in loneliness, reduced social support and under-detection of mental health needs. Along with this, social distancing determines a relevant obstacle for direct access to psychiatric care services. The pandemic generates the urgent need for integrating technology into innovative models of mental healthcare. AIMS: In this paper, we discuss the potential role of telepsychiatry (TP) and other cutting-edge technologies in the management of mental health assistance. We narratively review the literature to examine the advantages and risks related to the extensive application of these new therapeutic settings, along with the possible limitations and ethical concerns. RESULTS: Telemental health services may be particularly feasible and appropriate for the support of patients, family members and healthcare providers during this COVID-19 pandemic. The integration of TP with other technological innovations (eg, mobile apps, virtual reality, big data and artificial intelligence (AI)) opens up interesting future perspectives for the improvement of mental health assistance. CONCLUSION: Telepsychiatry is a promising and growing way to deliver mental health services but is still underused. The COVID-19 pandemic may serve as an opportunity to introduce and promote, among numerous mental health professionals, the knowledge of the possibilities offered by the digital era.

Prenatal exposure to viral infection and neuropsychiatric disorders in offspring: A review of the literature and recommendations for the COVID-19 pandemic.

The SARS-CoV-2 virus has emerged as a striking 21st century pandemic. Communities across the globe have experienced significant infection rates and widespread psychosocial stress and trauma, leading to calls for increased allocation of resources for mental health screening and treatment. In addition to the burden of psychosocial stress, there is increasing evidence of direct viral neuroinvasion of the central nervous system through physical contact with the nasal mucosa. In a parallel fashion, there is a significant body of ongoing research related to the risk of in utero viral transmission and the resulting neurodevelopmental impact in the fetus. Aberrant neurodevelopment secondary to viral transmission has previously been related to the later development of psychosis, schizophrenia, and schizophrenia spectrum disorders, generating the hypothesis that this population of individuals exposed to SARS-CoV-2 may see an increased incidence in future decades. We discuss the current understanding of the possible neurotropism and vertical transmission of SARS-CoV-2, and relate this to the history of viral pandemics to better understand the relationship of viral infection, aberrant immune response and neurodevelopment, and the risk for schizophrenia disorder.

Brain and COVID-19 Crosstalk: Pathophysiological and Psychological Manifestations.

The world is experiencing one of the major viral outbreaks of this millennium, caused by a plus sense single-stranded RNA virus belonging to the Coronaviridae family, COVID-19, declared as pandemic by WHO. The clinical manifestations vary from asymptomatic to mild symptoms like fever, dry cough, and diarrhea, with further increase in severity leading to the development of acute respiratory distress syndrome. Though primary manifestations are respiratory and cardiac, various studies have shown the neuroinvasive capability of this virus resulting in neurological complications, which sometimes can precede common typical symptoms like fever and cough. Common neurological symptoms are headache, dizziness, anosmia, dysgeusia, confusion, and muscle weakening, progressing toward severe complications like cerebrovascular disease, seizures, or paralysis. Older adults and critically ill people are in the high risk group and have shown severe neurological symptoms upon infection. COVID-19 also has a profound impact on the mental health of people across the world. In this review, we briefly discuss the neurological pathologies and psychological impact due to COVID-19, which has not only stressed the physical health of people but has also created social and economic problems resulting in mental health issues.

What could we learn from SARS when facing the mental health issues related to the COVID-19 outbreak? A nationwide cohort study in Taiwan.

There were several studies about the psychiatric and mental health issues related to the severe adult respiratory syndrome (SARS) outbreak in 2003, however, the association between SARS and the overall risk of psychiatric disorders and suicides has, as yet, to be studied in Taiwan. The aim of this study is to examine as to whether SARS is associated with the risk of psychiatric disorders and suicide. A total of 285 patients with SARS and 2850 controls without SARS (1:10) matched for sex, age, insurance premium, comorbidities, residential regions, level of medical care, and index date were selected between February 25 and June 15, 2003 from the Inpatient Database Taiwan's National Health Insurance Research Database. During the 12-year follow-up, in which 79 in the SARS cohort and 340 in the control group developed psychiatric disorders or suicide (4047.41 vs. 1535.32 per 100,000 person-years). Fine and Gray's survival analysis revealed that the SARS cohort was associated with an increased risk of psychiatric disorders and suicide, and the adjusted subdistribution HR (sHR) was 2.805 (95% CI: 2.182-3.605, p < 0.001) for psychiatric disorders and suicide. The SARS cohort was associated with anxiety, depression, sleep disorders, posttraumatic stress disorder/acute stress disorder (PTSD/ASD), and suicide. The sensitivity analysis revealed that the SARS group was associated with anxiety, depression, sleep disorders, PTSD/ASD, and suicide after the individuals with a diagnosis of psychiatric disorders and suicide were excluded within the first year, and with anxiety, depression, and sleep disorders, while those in the first five years were excluded. In conclusion, SARS was associated with the increased risk of psychiatric disorders and suicide.

Risk of Mortality in Elderly Coronavirus Disease 2019 Patients With Mental Health Disorders: A Nationwide Retrospective Study in South Korea.

OBJECTIVE: This study aimed to investigate the different clinical characteristics among elderly coronavirus disease 2019 (COVID-19) patients with and without mental disorders in South Korea and determine if these characteristics have an association with underlying mental disorders causing mortality. METHOD: A population-based comparative cohort study was conducted using the national claims database. Individuals aged ≥65 years with confirmed COVID-19 between January 1, 2020 and April 10, 2020 were assessed. The endpoints for evaluating mortality for all participants were death, 21 days after diagnosis, or April 10, 2020. The risk of mortality associated with mental disorders was estimated using Cox hazards regression. RESULTS: We identified 814 elderly COVID-19 patients (255 [31.3%] with mental disorder and 559 [68.7%] with nonmental disorder). Individuals with mental disorders were found more likely to be older, taking antithrombotic agents, and had diabetes, hypertension, chronic obstructive lung disease, and urinary tract infections than those without mental disorders. After propensity score stratification, our study included 781 patients in each group (236 [30.2%] with mental disorder and 545 [69.8%] with nonmental disorder). The mental disorder group showed higher mortality rates than the nonmental disorder group (12.7% [30/236] versus 6.8% [37/545]). However, compared to patients without mental disorders, the hazard ratio (HR) for mortality in elderly COVID-19 patients with mental disorders was not statistically significant (HR: 1.57, 95%CI: 0.95-2.56). CONCLUSION: Although the association between mental disorders in elderly individuals and mortality in COVID-19 is unclear, this study suggests that elderly patients with comorbid conditions and those taking psychiatric medications might be at a higher risk of COVID-19.