key: cord-0954823-fx11s3rq
authors: Rivas‐Ramírez, Ángel Roberto; Tendilla‐Beltrán, Hiram; Gómez‐Mendoza, Laura Eréndira; Loaiza, Guillermo; Flores, Gonzalo
title: Patients with schizophrenia have decreased COVID‐19 prevalence among hospitalised patients with psychiatric and neurological diseases: A retrospective analysis in Mexican population
date: 2021-06-27
journal: Int J Clin Pract
DOI: 10.1111/ijcp.14528
sha: 68dfee6648d26899e998db2ad5bee9d8490c3f8c
doc_id: 954823
cord_uid: fx11s3rq

BACKGROUND: Increased coronavirus disease 2019 (COVID‐19) incidence and mortality in hospitalised patients with psychiatric and neurologic disorders have been reported. METHODS: The clinical records of 198 patients with psychiatric and neurological disorders hospitalised in the Dr Rafael Serrano Psychiatric Hospital in Puebla during the peak of the first wave of the COVID‐19 pandemic in Mexico were analysed for psychiatric or neurologic diagnosis, gender, age, medical diagnosis, and COVID‐19 prevalence. For patients with COVID‐19, the effects of gender, and medical diagnosis were explored. RESULTS: There was an increased COVID‐19 prevalence in the studied population (43.94%), compared with the national Mexican (~0.21% to 0.63%) and worldwide average in the general population (~0.13% to 4.28%). However, the mortality rate (5.75%) was lower than that reported in Mexico (11.28%‐13.55%), which was higher than the worldwide average (2.95%‐4.98%). We detected increased COVID‐19 prevalence in patients with comorbidities (odds ratios [OR] 0.4; 95% CI: 0.2‐1, P = .0447). Moreover, patients with schizophrenia spectrum disorders have a decreased predisposition to COVID‐19 (OR 0.4, 95% CI: 0.2‐0.8; P = .0250), as opposed to patients with intellectual disability that are predisposed to COVID‐19 (OR 2.2, 95% CI: 0.2‐0.8; P = .0434), in comparison with the rest of the hospital population. CONCLUSION: The prevalence of COVID‐19 in hospitalised patients with psychiatric disorders is increased compared with that of the general population; however, a lower mortality rate was detected. Also, an increased risk of COVID‐19 was detected in patients with comorbidities. Interestingly, the observed variation in COVID‐19 prevalence in patients with schizophrenia and intellectual disability was not associated with age or other specific medical diagnoses.

It is known that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of the coronavirus disease 2019 , has neurotropic properties. [1] [2] [3] Upper respiratory tract infections caused by SARS-CoV-2 may lead to brain infection via the olfactory bulb. 4, 5 Once in the brain, SARS-CoV-2 causes inflammation and disrupts the integrity of the brainblood barrier. 2,6-9

Moreover, several mental diseases have been associated with COVID-19, including anxiety, depression, and psychotic episodes, as well as cerebrovascular events. [10] [11] [12] [13] In a study of the New York City population, it was detected that 13.5% of COVID-19 patients have neurological symptoms. 14 Also, another study that analysed 236 379 patients with COVID-19 reported that around one-third of these patients developed psychiatric or neurological disorders. 15 In such a manner, COVID-19 is not only a risk factor for the development of mental disease but also psychiatric and neurological symptoms that are also part of the outcome of the disease.

Neurological disturbances caused by SARS-CoV-2 infection suggest that people diagnosed with mental diseases may be vulnerable to There is miscellaneous information about COVID-19 prevalence in psychiatric patients. It has been reported that people with a psychiatric diagnosis are susceptible to COVID-19 in the US 16 and UK populations. 17 Lee et al 18 did not find increased COVID-19 prevalence in psychiatric patients in the South Korean population, but these results have been questioned because of the variability of diagnostic criteria. 19 However, the impact of sociodemographic variables on COVID-19 prevalence cannot be neglected, since some reports indicate that COVID-19 prevalence and the outcome are affected by belonging to ethnic minorities and the lack of public health service access in both the general population 20 and people with mental diseases. 21 In this report, we analysed the prevalence of COVID-19 in hospitalised patients with psychiatric and neurological diseases grouped into schizophrenia spectrum disorders, intellectual disability, bipolar disorders, substance-related and addictive disorders, neurocognitive disorders, and neurological disorders, to detect if any specific diagnosis is associated with an increase in COVID-19 prevalence. 

After a clinical examination and direct or indirect questioning for COVID-19, polymerase chain reaction tests for SARS-CoV-2 were only performed in patients who had been in contact with a person who had tested positive for COVID -19, or which presented or referred COVID-19-related symptoms; this was applied for admitted and hospitalised patients. Not all the patients were tested for COVID-19. In such a manner, only patients who were tested for COVID-19 were selected for the prevalence study ( Figure 1 ). The baseline characteristics of What's known • Patients with psychiatric or neurological diseases seem to be vulnerable to coronavirus disease 2019 , evidenced by increased mortality.

• Increased risk for COVID-19, but a decreased risk of mortality due to severe acute respiratory syndrome coronavirus 2 infection was detected in hospitalized patients with psychiatric or neurological diseases, in comparison with the national and worldwide scenario. the selected patients for the prevalence study are shown in Table 2 .

Coronavirus disease 2019 was classified according to the symptoms as follows: asymptomatic (no symptoms), mild (fever, cephalea, cough, odynophagia, rhinorrhea, and asthenia), moderate (pneumonia), and severe groups (severe pneumonia and needing O 2 supplementation). 22 Patients who were suspected of, or confirmed with having COVID-19, were isolated in private rooms in the same hospital. Patients with moderate and severe COVID-19 were transferred to an intensive care unit in a special COVID-19 hospital in the city.

Continuous variables were expressed as mean and standard deviation (SD). Categorical variables were expressed as counts and percentages.

Fisher's exact test (two-sided) was used to compare gender, psychiatric diagnosis, and medical diagnosis between each diagnosis against the rest of the psychiatric population. Also, unadjusted odds ratios (OR) were calculated for gender, psychiatric diagnosis, and medical diagnosis as risk factors for COVID-19 prevalence in the patients with psychiatric or neurological disorders, as well as for gender and medical diagnosis in schizophrenia spectrum disorder and intellectual disability groups. The P-value for statistical significance was established at 0.05. Data analysis was carried out in GraphPad Prism 9.0.

The characteristics of the hospital population are shown in Table 1 . 

The baseline characteristics of the patients with positive COVID-19

test results are shown in Table 2 

Of the 87 patients with COVID-19, 32 were asymptomatic (36.78%), 42 developed mild symptoms (39.08%), 7 presented moderate clinical outcomes (18.39%), and 5 severe cases were detected (5.75%).

Most patients with schizophrenia spectrum disorders were asymptomatic (n = 9, 50.0%) in contrast with patients with mild symptoms 

Five deaths caused by COVID-19 were reported (6.9%), of which 2

were in patients diagnosed with schizophrenia spectrum disorders 

Among psychiatric diagnoses ( Although we did not have a non-psychiatric/neurologic group to compare our findings, and this represents a limitation of our work, in the next two sections, we contextualise our data with the COVID-19

statistics for the general Mexican and worldwide population from 29

June to 30 September 2020 (Table 3 ).

The percentage of positivity for COVID-19 among the psychiatric hospitalised tested population (64.44%) was higher than the general population Mexican positivity percentage during the studied period (45.61%-46.24%; for details, see Table 3 ). 23 Moreover, the COVID-19

prevalence in the studied psychiatric population (43.94%) was higher than the Mexican (~0.21%-0.63%) and worldwide (~0.13%-4.28%)

confirmed COVID-19 prevalence in the general population during the studied period. 23, 24 These results confirm the susceptibility of patients with psychiatric and neurological disorders to SARS-CoV-2 infection. Also, it has been reported that schizophrenia patients not only have an increased risk of SARS-CoV-2 infection 25 but also increased COVID-19-related mortality, [26] [27] [28] [29] which can be even three times higher than in control patients. 26 

Regarding the rate mortality of COVID-19 in this cohort of patients (5.75%), it is lower than that reported in the general Mexican population (13.55%-11.28%), 23 which is higher than the worldwide mortality (4.98%-2.95%) in the studied period (for details, see Table 3 ).

City and reported that the mortality rate is higher in people in active economically active sectors and of marginalised municipalities with a high population density. This reinforces the reports that sustain that socioeconomic conditions are a determining factor for mortality and the outcome of COVID-19 worldwide. 20 However, increased mortality in the hospitalised psychiatric population has been documented. 26, 27 Interestingly, in the cohort of patients studied in this research, only five deaths caused by COVID-19 were reported, representing 6.9% of the positive cases. This can be explained by the isolation protocols for suspicious and positive patients with COVID-19.

Another factor that may have contributed to the COVID-19 outcome reported here is that this psychiatric hospital, as well as other

Mexican mental health institutions, does not have to be converted into COVID units, as has been documented in other countries. 31, 32 Moreover, patients with schizophrenia disorders have an increased COVID-19-related death rate (11.10%) in comparison with patients with intellectual disability (3.57%). This can be explained by the proportion of people over 65 with COVID-19, which is higher in the schizophrenia disorder group (27.77%) than in the intellectual disability group (17.86) . This is congruent with the information about COVID-19 mortality, which is higher in patients age 65 years or older. 33-35

We found that the presence of comorbidities in patients with psychiatric or neurologic disorders favours SARS-CoV-2 infection. This is congruent with several reports that have associated comorbidities, including hypertension and diabetes, with an increased incidence and mortality in COVID-19. 36 Interestingly, neither hypertension nor diabetes seems to represent a risk factor for SARS-CoV-2 infection or the development of severe COVID-19 and did not affect the mortality rate in this cohort of patients. These results suggest that age may not be associated with moderate or severe COVID-19 symptoms in these patients, but study limitations cannot be neglected to influence these results (see Section 5).

Here, we analysed the association of psychiatric diagnosis with COVID-19 predisposition, finding that schizophrenia spectrum disorder patients have a decreased COVID-19 predisposition and intellectual disability patients have an increased COVID-19 predisposition compared with other psychiatric patients. Specifically, in schizophrenia, increased COVID-19 prevalence has been reported compared with that of patients without a psychiatric diagnosis. 26 However, in a couple of recent reports, the Crespo-Facorro group has detected decreased mortality in patients with schizophrenia treated with antipsychotics in the Spanish population, 37, 38 and our results support this finding. Among the diverse reasons that can explain the aforementioned findings, we hypothesise that the pharmacotherapy of schizophrenia may be related to this, 39 since antipsychotics (mainly second-generation or atypical ones) have anti-inflammatory, antioxidant, and neurotropic properties. 40 However, it is important to remember that antipsychotics can also prompt the development of metabolic-related diseases such as obesity and diabetes. 41 Thus, further studies must study the role of these drugs on the COVID-19

outcomes.

Although a low prevalence of patients with COVID-19 effects was detected (6.9%), it will be interesting to follow up with the patients who tested positive for the SARS-CoV-2 infection, since extensive evidence about its neurotropic properties and its neuroinflammatory effects have been documented. [1] [2] [3] [4] 6, 9 Also, neurological symptoms have been reported in patients with COVID-19. 11, 14, 42 Thus, it will be interesting to assess the long-term effects of COVID-19 in patients with mental diseases.

In addition to the previously mentioned lack of a non-psychiatric/ neurologic group for analysis, psychiatric and COVID-19 treatment information was not included Moreover, obesity has been associated with increased COVID-19 mortality, which has been confirmed in the Mexican population 36, 43, 44 ; in this cohort of patients, body mass index was not evaluated to explore the role of obesity in COVID-19

outcomes. Also, the study was not powered to detect statistical significance for all comparisons. Thus, the absence of significance should not necessarily imply non-association. Finally, the baseline male/female proportion was not equivalent; this could bias the presented data (unbeknown to us).

This study indicates that although the cohort of hospitalised psychiatric patients studied has an increased positivity ratio of COVID-19, mortality did not vary in comparison with that of the Mexican general population. Moreover, among the general psychiatric population, the presence of comorbidities increased the risk of SARS-CoV-2 infection. However, patients with schizophrenia spectrum disorder diagnosis are less susceptible to COVID-19. This is the opposite in patients with intellectual disabilities, who are susceptible to COVID-19. These data may contribute to the worldwide efforts for mental health care in the COVID-19 pandemic.

Hiram Tendilla-Beltrán acknowledges CONACYT for the PhD scholarship. Gonzalo Flores acknowledges "Sistema Nacional de 

The authors declared no conflict of interest. Guillermo Loaiza and Gonzalo Flores supervised the research. All authors had full access to the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

The data that support the findings of this study are available from the corresponding authors, upon reasonable request. 

SARS-COV-2 (COVID-19) has neurotropic and neuroinvasive properties

Microvascular Injury in the brains of patients with Covid-19

Effects of COVID-19 on the nervous system

Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19

Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia

Neuroinvasion of SARS-CoV-2 in human and mouse brain

SARS-CoV-2 infects brain astrocytes of COVID-19 patients and impairs neuronal viability

Neurochemical evidence of astrocytic and neuronal injury commonly found in COVID-19

ApoE-isoform-dependent SARS-CoV-2 neurotropism and cellular response

Covid-19 and promising solutions to combat symptoms of stress, anxiety and depression

Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study

Characteristics of ischaemic stroke associated with COVID-19

COVID-19 and cerebrovascular diseases: a comprehensive overview

A prospective study of neurologic disorders in hospitalized patients with COVID-19 in

6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records

Bidirectional associations between COVID-19 and psychiatric disorder: retrospective cohort studies of 62 354 COVID-19 cases in the USA

Pre-pandemic psychiatric disorders and risk of COVID-19: a UK Biobank cohort analysis

Association between mental illness and COVID-19 susceptibility and clinical outcomes in South Korea: a nationwide cohort study

Association between mental illness and COVID-19 in South Korea

Mental health and COVID-19: is the virus racist?

How mental health care should change as a consequence of the COVID-19 pandemic

World Health Organization. Clinical management of COVID-19: interim guidance

Secretaría de Salud Coronavirus -gob.mx

World Health Organization WHO Coronavirus (COVID-19) Dashboard

The COVID-19 global pandemic: implications for people with schizophrenia and related disorders

Increased in-hospital mortality from COVID-19 in patients with schizophrenia

Association of a prior psychiatric diagnosis with mortality among hospitalized patients with coronavirus disease 2019 (COVID-19) Infection

Association of psychiatric disorders with mortality among patients with COVID-19

COVID-19 Prevalence and mortality among schizophrenia patients: a large-scale retrospective cohort study

Comprehensive evaluation of the impact of sociodemographic inequalities on adverse outcomes and excess mortality during the COVID-19 pandemic in Mexico City

Mental health in the coronavirus disease 2019 emergency-the Italian response

Lessons learned from the coronavirus health crisis in Madrid, Spain: how COVID-19 has changed our lives in the last 2 weeks

COVID-19 mortality risk for older men and women

Age-specific mortality and immunity patterns of SARS-CoV-2

Infection fatality risk for SARS-CoV-2 in community dwelling population of Spain: nationwide seroepidemiological study

Predicting mortality due to SARS-CoV-2: a mechanistic score relating obesity and diabetes to COVID-19 outcomes in Mexico

Lower risk of SARS-CoV2 infection in individuals with severe mental disorders on antipsychotic treatment: a retrospective epidemiological study in a representative Spanish population

Aripiprazole as a candidate treatment of COVID-19 identified through genomic analysis

Due to their anti-inflammatory, antioxidant and neurotrophic properties, second-generation antipsychotics are suitable in patients with schizophrenia and COVID-19

The prefrontal cortex as a target for atypical antipsychotics in schizophrenia, lessons of neurodevelopmental animal models

Global incidence of neurological manifestations among patients hospitalized with COVID-19-a report for the GCS-NeuroCOVID consortium and the ENERGY consortium

Obesity is a strong risk factor for short-term mortality and adverse outcomes in Mexican patients with COVID-19: a national observational study

Health and institutional risk factors of COVID-19 mortality in Mexico, 2020