Prevalence and related risk factors of psychotic symptoms among inpatients infected with COVID-19 during the second wave pandemic

Background Possibility of psychotic symptoms and related risk factors among the normal person and infected patients during the outbreak of COVID-19 has been widely investigated in previous studies. With the arrival of the second wave of the epidemic in many countries around the word, the accordingly mental health outcomes were unclear yet, especially the mental health outcomes among infected patients. It aims to explore the prevalence of and related risk factors associated with psychotic symptoms in COVID-19 infected inpatients during the second wave. Method: A cross-sectional survey was conducted in ve isolated wards of a designated hospital in Beijing, China, from 1 July to 15 July, 2020. The Mini-International Neuropsychiatric Interview (M.I.N.I) was conducted to assess the psychiatric disorders, and a serious of scales was used to measure self-reported psychotic symptoms and psychosomatic factors. Multivariate regression analysis was used to analyze the risk factors associated with psychotic symptoms. Among 199 infected participants, the prevalence of generalized anxiety symptoms is 51.3%, of depressive symptoms 41.2%, of PTSD symptoms 33.6%. Loneliness, hope, coping strategies, history of mental disorders were shared risk or protective factors across several psychotic symptoms. Perceived impact by COVID-19 is the specic risk factor associated with state anxiety symptoms. The and high among infected inpatients during of in Beijing. Clinical doctors must during pandemic likely depressive anxiety disorders and PTSS/PTSD, as well some Specic mental health care is urgently needed help inpatients cope with the virus during the second wave of pandemic.


Introduction
The world is experiencing a pandemic, the new corona virus, which rst appeared in Wuhan City, Hubei Province, China in late 2019 [1]. Patients suffering from pain still suffered from major mental health issues in the reality of more and more infections and deaths. The emergency policies immediately implemented by China are early detection and isolation of suspected and con rmed cases, and the establishment of isolation units and hospitals, and others [2]. Currently, the COVID-19 pandemic was quickly under control. However, from June 10 to July 15, 2020, the second wave of COVID-19 outbreak in Beijing, China, with increased infected cases from 0 to 335.
The general medical complications that have attracted great attention due to the corona virus disease have rarely been studied on the possible direct impact of this pandemic on mental condition and neuronophagia [3]. It is necessary for infected patients to be treated in isolated hospitals under the treatment instructions in China. For these patients suffering from autism, anger, anxiety, depressive disorder, insomnia and PTSS/PTSD, the causes of these problems may come from social isolation, surrounding risks and uncertainties, pain suffering, drug reactions, worries of contagion to others, and negative information on social networks [4]. Lots of studies have showed mental health problems such as PTSS/PTSD, anxiety and depression among health care workers or general population during the rst wave of outbreak [5][6][7][8]. Few studies have investigated mental health problems among infected inpatients infected by COVID-19 during the second wave.
Our study aimed to explore the prevalence of psychotic symptoms and related risk factors among infected inpatients with COVID-19 infection during the second wave in Beijing, China.

Participants and Study design
This study was a cross-sectional design and was carried out during the second wave of COVID-19, from 1 July to 15 July, 2020. Infected inpatients were recruited by cluster sampling in Beijing Ditan Hospital, which was the designated isolation hospital for COVID-19 infections in Beijing, China. We invited 180 inpatients from ve isolated wards to participate our study, including the Mini-International Neuropsychiatric Interview and self-reported questionnaire. The Mini-International Neuropsychiatric Interview was conducted on the day before discharge from the hospital for each participant. Two experienced clinical psychiatrists conducted the systematic assessment of psychiatric symptoms by the Mini-International Neuropsychiatric Interview. 119 inpatients completed this study, with a response rate of 66.1%. Participants meeting the following criteria were included: (1) inpatients infected by the COVID-19; (2) Chinese citizens who understand Chinese; (3) be infected during the second wave of pandemic in Beijing.
All participants were informed of the purpose and procedures of the study before the survey began, and completing the survey implied online informed consent to participate the investigation. This survey was approved by the Beijing Ditan Hospital Ethics Committee.

Measures
Socio-demographic characteristics A variety of scales and demographic data were collected in the study, including sex, age, nationality, education, clinically diagnosed type of infection, community risk (announced by Beijing municipal government during the second wave), annual income and history of mental disorder (con rmed by psychiatrist).

COVID-19 related factors
Participants were surveyed for the frequency of exposure to information or news related to COVID-19 by two items (i.e. "How many times do you browse the related information on the pandemic per day in the past two weeks?" and "How many hours do you browse the pandemic-related information per day in the past two weeks?"). The scoring criteria for such items are respectively from "0 times" to "20 times" with a total score of 21 points and from "0 hours" to "8 hours" with a total score of 8 points. The responses formed the composite score of exposure to COVID-19 related information (α = .52), with higher mean scores indicating a higher exposure to COVID-19 related information or news.
Participants were surveyed the perceived impact by COVID-19 by 4 items, including the impact on economic income, daily life, work or study, and interpersonal relationship. According to the comprehensive score of perceived impact (a=.73) after different answers to these items from 1 (totally not) to 5 (to a large extent), with higher scores indicating a greater perceived impact on COVID-19 pandemic.

Psychological factors
Loneliness and hope were assessed as two psychological factors associated with psychotic symptoms. 6-Item short version of De Jong Gierveld Loneliness Scale was used to assess loneliness [9]. For each item, participants were asked to indicate the extent to which corresponding situations had happened on a 5point scale (1 = never; 5 = always), with Cronbach's α = 0.70 ~ 0.76. For example, "I experience a general sense of emptiness", "I miss having people around". In this study, we calculated a composite loneliness score α = .55, with higher scores indicating higher loneliness.
Hope was assessed by the Hope Scale, which includes 12 items concerning feeling of hope, with validated Cronbach's α = 0.74 ~ 0.84 [10]. The Hope Scale de ned hope as the process of thinking about one's goals, along with the motivation to move toward (agency subscale) and the ways to achieve (pathways scale) those goals. For example, "I energetically pursue my goals", "I can think of many ways to get out of a jam". Responses range on a 7-point scale, from 1 (de nitely false) to 7 (de nitely true). We calculated a composite hope score α = .91, with higher scores indicating higher hope.

Coping strategies
The 15-item COPE inventory was used to assess coping strategies participants used to manage their stress [11,12]. It is comprised of 4 subscales: active coping, avoidant coping, emotion-focused coping, and acceptance coping. Participants were asked to rate how frequency they used each coping strategy on a 7-point scale from 1 (never) to 7 (always). For instance, "I concentrate my efforts on doing something about it", "I pretend that it hasn't really happened", "I discuss my feelings with someone", "I learn to live with it". In this study, the composite cope subscale score α = 0.50 ~ 0.87, with higher scores indicating higher coping strategy in the corresponding subscale.

Social supports
Social supports were assessed by the Multidimensional Scale of Perceived Social Support (MSPSS) [13], consisting of 12 items. The MSPSS comprises three subscales, i.e., perceived support from family, from friends and from a signi cant other. Items includes "There is a special person who is around when I am in need", "I can talk about my problems with my friends", and so on. Each item was rated on a 7-piont Likert scale, ranging from 1 (very strongly disagree) to 7 (very strongly agree). The composite social support was calculated α = 0.95, with higher scores indicating higher perceived social supports.
Generalized anxiety was assessed by the Generalized Anxiety Disorder Scale (GAD-7), which is a self-reported screening scale consisting of 7 items on a 4point scale, from 1 (not at all) to 4 (nearly every day), with higher total score indicating severer anxiety symptoms [14]. The Chinese version of GAD-7 has been validated and demonstrated great reliability (α = 0.89) [15]. In our study, the cut-off score for anxiety symptoms was 12 [15], and internal consistency is excellent (α = 0.94).
Compared with the generalized anxiety, we also measure the state anxiety level of inpatients while hospitalized. The State-Trait Anxiety Inventory-State (SASI-S) was used to screen the situation-related anxiety, consisting of 20 items on a 4-point scale, from 1 (not at all) to 4 (very much), with higher summative score indicating higher levels of state anxiety, and had demonstrated good internal consistency (α = 0.94) [16]. In present study, the cut-off score for state anxiety symptom was 41 [17], and the Cronbach's α was 0.91. Similar to GAD-7, the self-screen 9-item Patient Health Questionnaire (PHQ-9) was used to assess the frequency of the occurrence of depressive symptoms over the past two weeks on a 4-point Likert scale, ranging from 1 (not at all) to 4 (nearly every day) [18]. It has been validated in China (Cronbach's α = 0.86) [19], and we produced a summative score with higher scores indicating severer depressive symptoms (α = 0.91). We use a cut-off score at 14 in this study [18].
The Impact of Events Scale-Revised (IES-R) was adapted to measure COVID-19 related PTSD [20]. It consists of 22 items on a 5-piont Likert-type scale (1 = not at all; 5= always) to produce a summative score with higher scores indicating higher level of events-related PTSD. Participants were asked to rate the frequency with which each symptom has occurred over the past week, and the event refers to COVID-19 event in present study. IES-R has been used in previous COVID-19 studies in China [21,22]. We calculated a COVID-19 related PTSD composite score (α = 0.97), and used a cut-off score of 46 [23].
The somatization subscale, interpersonal sensitivity subscale, hostility subscale, paranoid ideation subscale and psychoticism subscale of Brief Symptom Inventory (BSI) were used to assess the ve speci c psychotic symptoms [24]. Respondents rank each feeling item on a 5-point scale ranging from 1 (not at all) to 5 (extremely) during the past seven days, with higher scores indicating severer sub-dimensional symptoms. The present study demonstrated great internal consistency of the ve subscales (α = 0.83 ~ 0.87). There were few studies providing BSI-53 subscale cut-off scores to diagnose speci c psychiatric illness to our knowledge [25].

Data analysis
We used both the Mini-International Neuropsychiatric Interview diagnostic outcome and self-reported clinical symptoms outcome to calculated the prevalence of psychotic symptoms among participants. Descriptive statistics for socio-demographic variables and M.I.N.I outcomes were rst presented. Chi-square test was used to compare psychotic symptoms between males and females. Hierarchical linear regression models were used to explore the contribution of various factors to psychotic symptoms. Socio-demographic characteristics were rst entered to test their relationship with psychotic symptoms in step 1, followed by COVID-19 related factors in step 2, psychological factors in step 3, cope strategies in step 4 and social support in model 5. In addition, we used the biascorrected bootstrap method with 95% con dence intervals to test the regression models. All analyses were performed using SPSS version 23.0 and R version 4.0.2. Statistical signi cance level was set at 0.05 (two-sided).

Socio-demographic and clinical characteristics
The nal sample comprised 119 participants. As shown in Table 1, the average age of the participants were 40.25 (SD = 11.50) years old. The majority of the patients were male (62.2%), Han nationality (93.3%), with lower education level (68.9%) and annual income lower than 100,000 RMB (72.3%). Most patients were diagnosed as "Normal" infected (84%), and only 1.7% had history of mental disorders. According to M.I.N.I diagnosis by experienced clinical psychiatrists, 12.61% inpatients suffered from anxiety spectrum disorder, 5.9% suffered from depressive disorder, and 9.24% suffered from PTSS or PTSD. The diagnosis outcome of prevalence of psychotic symptoms by self-reported questionnaires was higher than by interview. That is, 51.3% inpatients suffered from generalized anxiety disorder, 41.2% suffered from depression, and 33.6% might suffered from PTSD.

Prevalence of psychotic symptoms
The prevalence of self-reported psychotic symptoms was high among inpatients. More than half suffered from whatever generalized anxiety (51.3%) or state anxiety (51.3%) symptoms. Nearly half of the patients suffered from depressive symptoms (41.2%). As shown in Figure 1, the inpatients with the normal infection type showed a relatively higher proportion of having psychotic symptoms, that is, 85.2% for generalized anxiety symptoms, 83.6% for state anxiety symptoms, 87.8% for depressive symptoms, and 92.5% for PTSD symptoms. Patients being 40 to 55 years old also accounts for a relatively higher proportion of psychotic symptoms. In addition, Chi-square test showed that there was no signi cant difference in the generalized anxiety, state anxiety or depressive symptoms between male and female (p > .05). However, female inpatients showed a signi cant higher proportion of PTSD symptoms (χ 2 (1) = 5.53, p < .05).

Discussion
The present study showed that at least one third of hospitalized patients exhibited symptoms of depression, anxiety, PTSD, somatization, interpersonal sensitivity, hostility, paranoid ideation or psychoticism symptoms, and the prevalence is much higher than that found in the general populations (about 20%) [26]. The reasons why the second outbreaks showed higher mental health risks are as follows: the rst reason may be that cytokines that directly or indirectly affect the brain are induced by COVID-19. For example, it has been reported that patients with severe infection in corona virus disease may cause delirium, together with various mental health problems and cerebropathy [27]. The other reason relates to the social distancing measures and quarantine policies [28]. It is necessary for infected patients to be temporarily arranged in isolated hospitals in China. Such infected patients will be more likely to suffer from autism, anger, anxiety, depressive disorder, insomnia, due to social isolation, uncertainties, drug reactions [29,30].
The prevalence of psychotic symptoms among inpatients during the second wave of pandemic in Beijing is lower than the rst wave in Wuhan, China. A preliminary survey at the end of January 2020 showed that more than half of the infected patients suffered from moderate to severe psychological health disorders [6]. There could be two reasons for this phenomenon. One reason may be timely mental health care was provided. In the second wave, health authority quickly dispatched psychiatrists, psychiatric nurses and clinical psychologists to support COVID-19 patients. Efforts should be made to help all patients with psychological health problems to receive professional psychotherapy and appropriate mental-health services. The other reason may be that patients have learnt more information about the COVID-19 disease from the rst wave and more clear about their physic health status. It may help patients address their sense of uncertainty and fear themselves. Besides, our study found that the prevalence of mental health symptoms might be higher by use of self-report questionnaires than of M.I.N.I diagnosis, which showed that most inpatients might have psychotic symptoms but have not meet the criteria for psychotic disorders yet.
Another prominent nding is that all psychotic symptoms were associated with loneliness, which may be due to quarantine and isolation policies and lack of social support. This is basically the same as previous studies [6,28]. Isolation can have negative effects on the mental health of children and adults [31,32]. People who receive isolation often dislike isolation, because it means that they are separated from their loved ones, lose freedom, are not sure about their illness at home, and feel bored. All these factors may increase their loneliness. O cials should specify that the time of individual isolation meets the requirements, provide clear reasons for isolation and information on relevant agreements, and ensure that adequate supplies would be provided to the isolated personnel. In addition, we found that avoidant coping strategy was risk factor whereas acceptance coping strategy was protective factor for some psychotic symptoms. It indicates that inpatients should be encouraged to accept the infected situations and not to get through it by avoiding it. Furthermore, we found that hope is a risk factor for some symptoms. One possible explanation is that individuals with more hope are hard to accept terrible situations and tend to avoid the reality [10]. Besides, the results showed that supports from signi cant others may increase inpatients' state anxiety and depression. It reminds us that too much unnecessary care, especially from people who are not family or friends but signi cant others (e.g., medical workers, colleagues, bosses) could make patients induce more anxious about their illness. Thus, "moderate" care is needed for infected patients.
Moreover, the sociodemographic information suggests that age and gender also in uence mental health among inpatients during the second wave of pandemic. Elderly and female inpatients, in particular, suffers greater psychological impact of the pandemic as well as higher levels of PTSS/PTSD, anxiety, depression and other psychotic symptoms. Consistent with prior studies, COVID-19 is known to exhibit a particularly severe course in the advanced age and individuals with accompanying chronic disease [31][32][33]. Therefore, elderly people exposed to COVID-19 may be more severely affected. In the second wave, most infected patients were 40 or above years old, who might be more susceptible to mental disorders. Females has been identi ed as the most potent predictor of PTSD symptoms after pandemic [34], and our results showed that PTSD and somatization symptoms were higher in female participants, which is consistent with previous studies. In addition, we found that COVID-19 related factors were not predominant factor associated with psychotic symptoms. For instance, exposure to COVID-19 related information or news shows no signi cant relation across all psychotic symptoms, indicating that psychotic symptoms relates to more stable variables, such as history of mental disorders.
This study has several limitations. First, the sample size was not large enough, due to limited positive cases (331 in total) during the second wave in Beijing.
Second, due to the lack of baseline psychiatric assessment, we cannot accurately estimate the incidence rate, and we rely on the point prevalence rate when conditions permit. Third, our study does not include objective biological indicators, such as peripheral blood heredity, in ammation, immune and metabolic function markers, cerebrospinal uid indicators, EEG or brain imaging.

Conclusions
In summary, this study investigated the prevalence of psychotic symptoms and related risk factors among hospitalized patients with COVID-19 infection during the second wave of pandemic outbreak. Clinicians must be aware that hospitalized patients may suffer higher depression, anxiety, post-traumatic stress disorder, and other neuropsychiatric syndrome. Therefore, we urgently need to provide infected patients with speci c mental health interventions and resources to help them cope with the virus and solve the corresponding mental health problems.

Declarations
Ethics approval and consent to participate All participants were informed of the purpose and procedure of the study prior to the survey. All participants completed the online informed consent before completing the survey. The Beijing Ditan Hospital Ethics Committee has approved this investigation (No: 2020-011-01).

Consent for publication
Not applicable. All participants participated in the survey anonymously.

Availability of data and materials
The datasets used during the current study are available from the corresponding author on reasonable request.

Competing interests
The authors declare that they have no competing interests. Note. The unit of annual income is RMB yuan. PTSD: posttraumatic stress disorder.