Corona virus disease 2019 has emerged as the most critical global crisis of the 21st century. COVID-19 cases have exceeded 4.3 million as of May 15,2020. 1 A number of studies indicate increase in symptoms of anxiety, depression, and other psychopathologies among the participants during the COVID-19 pandemic. [2] [3] [4] [5] [6] [7] In a previous study, we screened 13,332 individuals worldwide for general psychological disturbance, depression, and post-traumatic stress disorder (PTSD). Findings demonstrated increased odds for these conditions in individuals with pre-existing psychiatric conditions. Patients with previous history of psychiatric illness who reported worsening of their condition in response to the COVID-19 pandemic were identified as having higher risk for general psychological disturbance, contraction of the virus and relapse in condition. 8 Worsening of psychiatric conditions is also associated with a higher risk of suicidal ideation, as demonstrated in the results of our study. 9, 10 Psychiatric conditions constitute a significant burden on health-care systems. Previous findings have associated these conditions with increased rates of mortality, disability and reduced overall economic output. 4, [11] [12] [13] Recently, the COVID-19 pandemic has given rise to even greater mental healthcare challenges for an already struggling system. Recent reports have called attention to the need for better mental health management of health-care workers, psychiatric patients, and general population. [3] [4] [5] [6] There has been an increase in utilization of mental health and suicide prevention helplines 14 and new methods of psychological/psychiatric care delivery through telemedicine are being increasingly adopted. 15 It is paramount for the optimization of mental health care delivery during these challenging times that the most vulnerable populations are identified and protected.
To address this, we performed a sub-analysis of data from participants with preexisting psychiatric conditions from our global study on the mental health impact of COVID-19. Each patient report of worsening of psychiatric conditions was then crossanalyzed with participants' demographics, opinions/outlooks, personality traits, current household conditions, previous history, and other factors associated with COVID-19
to identify risk and resilience factors for worsening psychiatric condition. The results were then verified in an independent clinical cohort of psychiatric patients that consulted a psychiatry practice in Houston, TX, USA during the COVID-19 pandemic.
The study comprised two independent evaluations; 1. A cross-sectional electronic survey-based assessment of individuals above the age of 18 years willing to participate in the study, 2. Evaluation of anonymized clinical records of psychiatric patients above the age of 18 years.
The anonymous online survey was conducted among participants from diverse demographic groups to examine the status of their pre-existing psychiatric conditions that were verified via standardized self-report scales for general psychological disturbance, risk for PTSD, symptoms of depression, and suicidal ideation. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted May 30, 2020. . https://doi.org/10.1101/2020.05.28.20116178 doi: medRxiv preprint traits (level of optimism, level of extroversion), previous history of psychiatric disease and/or trauma, previous exposure to human crisis, and level of satisfaction with actions of the state and employer during the current crisis. All questionnaires were rated on binary (yes/no) responses or Likert-type scales.
The other sections contained general health assessment based on WHO Self-Reporting Questionnaire-20 (SRQ), Impact of Event Scale (IES), and Beck's Depression Inventory II (BDI). [16] [17] [18] These scales were chosen based on their usage and efficacy in previously employed works studying the psychological impact of human crises such as the SARS epidemic. [19] [20] [21] [22] [23] [24] [25] [26] [27] IES wording was purposefully adjusted to assess the impact of an ongoing event rather than a past event.
Using a non-randomized referral sampling (snowball sampling) method, participants were contacted by a team of 70 members (study authors and volunteers that have An overall total of 13,332 responses were collected. Surveys were excluded if they were completed by participants who were younger than 18 (n=34), were missing responses for all dependent variables (n=112), had been submitted previously (n=325), were missing geographic location (n=20), or were from WHO AFRO region (n=24). When the responses were missing for individual items, the missing data were considered null and excluded from the analysis for that particular variable. In this follow-up study, however, only responses from participants who reported suffering from a previous psychiatric condition (n=2,734) were considered valid.
The clinical data was extracted and analyzed for all the adult patients who consulted for online follow-up clinical evaluations at a Psychiatric care facility (Texas Behavioral Health) based in Houston, TX, USA during March 29-April 14, 2020. The inclusion . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted May 30, 2020. . https://doi.org/10.1101/2020.05.28.20116178 doi: medRxiv preprint criteria were previous diagnosis of major depressive disorder or anxiety disorders (generalized anxiety disorder and PTSD). Patients with diagnoses other than these and those under the age of 18 were excluded. Only the data from patients consenting to use of their records for this research were included in the study.
Clinical data for each patient was examined by clinic assistants blinded to the study design. The following information was extracted; age, gender, home-isolation status during COVID-19, social support during COVID-19, past exposure to trauma or a human crisis situation, and clinical diagnosis. Worsening of psychiatric conditions was assessed based on clinician report of new symptoms, need to increase or adjust the medication, and referral for a new therapy.
Data from 318 patients was considered valid for analysis. When the responses were missing for individual items, the missing data were considered null and excluded from the analysis for that particular variable.
Informed consent was obtained from each survey and clinical participant to allow anonymous recording, analysis, and publication of their answers. The data was collected in a completely anonymous fashion without recording any personal identifiers and the confidentiality of the participants was maintained throughout all phases of the study. The study procedures were reviewed and approved by University is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint this version posted May 30, 2020. . https://doi.org/10.1101/2020.05.28.20116178 doi: medRxiv preprint included gender, residential status, education level, employment status, being a medical professional, working remotely from home, satisfaction with employer, satisfaction with the state (government), home-isolation status, interaction with family and friends, social media usage, ability to share concerns with a mental health professional, ability to share concerns with family and friends, prior exposure to a human crisis situation, previous exposure to trauma, level of extroversion, prediction about COVID-19 resolution and one's self-determined role in the pandemic. For the clinical study, the categorical predictors included age, gender, home isolation status, and social support during home isolation.
Multiple logistic regression models were built to generate odds ratios (ORs) for worsening of psychiatric conditions both in the survey and the clinical cohorts. All statistical analyses were performed by the analysis team comprising MP, SG, PR, and AJ in consultation with ZB. There was a disproportion in valid responses, with higher numbers from those participants who were female (79.44%), residing in urban areas (84.6%), with advanced educational qualification, i.e., bachelor's degree or higher (71.5%), . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint this version posted May 30, 2020. . https://doi.org/10.1101/2020.05.28.20116178 doi: medRxiv preprint working/studying remotely from home (65%), and currently under home-isolation with a partner/family (82.77%). Also notable were responses expressing some level of satisfaction with COVID-19-related employer (52.67%) and state response (64.26%) and spending less than 15 minutes on daily physical exercise (52.99%). A majority of participants also reported increased social media usage (65.42%), less-than-usual or minimal interaction with family and friends (64.88%), and feeling some level of control in protecting themselves and others during the COVID-19 pandemic (94.36%).
Participants' report of worsening of psychiatric conditions was verified by comparing the SRQ, IES, and BDI scores between patients reporting worsening of psychiatric conditioning versus those reporting no change. All scores were significantly (p<0.05) higher in patients reporting worsening of psychiatric conditions. Distribution of patients reporting no change in their condition in comparison to worsening along the SRQ, IES, and BDI scaled further confirmed this pattern (Main Item 2).
Unadjusted Chi-square analysis of association between different patient factors and their report of psychiatric condition worsening revealed significantly higher reports of worsening in women, patients with advanced education, patients who reported being home isolated, and those with previous trauma exposure. Moreover, patients reporting dissatisfaction with the response of their government and employer during COVID-19 were more likely to report worsening of psychiatric condition. Finally, patients who identified themselves as a pessimist, felt lack of control during the current situation and had negative prediction about COVID-19 resolution were more likely to report worsening of their psychiatric condition.
On the contrary, patients that were able to interact and share concerns with their family and friends or with a health professional like usual during COVID-19 were less like to report worsening of their pre-existing psychiatric conditions. The details of the unadjusted categorical analysis are present in Main Item 3.
Adjusted analysis was then performed for patients' report of psychiatric condition worsening via logistic regression to adjust for confounding associations. Report of feeling . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 
This study highlights a significant impact of the COVID-19 pandemic on psychiatric patients worldwide. At least 50% of the psychiatric patients evaluated in this study from 8 of the 12 featured countries reported worsening of psychiatric conditions. Notably, the selfreported worsening of psychiatric conditions was cross-validated with patients' scores on validated scales assessing general psychological disturbance, risk for PTSD, and . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint this version posted May 30, 2020. . https://doi.org/10.1101/2020.05.28.20116178 doi: medRxiv preprint depression. Severity of psychopathology assessed through these scales confirmed the patients' report of psychiatric condition worsening. Finally, clinician-reports from an independent cohort of psychiatric patients in the US confirmed that more than half of the patients reported new symptoms and required treatment adjustments during the COVID-19 pandemic.
In addition to ascertaining if there has been a general worsening of psychiatric conditions during COVID-19, a major aim of this study was to identify risk factors for such worsening. Identifying factors that are associated with worsening of psychiatric conditions has important implications for psychiatric prognostics and therapeutics. In our previous study, patients with prior psychiatric disease reported increased suicidal ideation. 10 Understanding factors associated with psychiatric disease during a pandemic can help . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint this version posted May 30, 2020. . https://doi.org/10.1101/2020.05.28.20116178 doi: medRxiv preprint the patients, their family, and care-givers to screen and identify those at an increased risk of mental health crises situations such as suicide attempts. Factors identified in this study including gender-based factors and prior exposure to trauma warrant further investigation to ensure that health systems can provide for the needs of a vulnerable population.
Previous research has highlighted increased gender-based disparity and violence associated with humanitarian crises. 32 During the Ebola outbreak of 2014-16, women were increasingly at risk of abuse, violence and a lack of access to protective instructions. 29 Moreover, existing gender norms and inequality can exacerbate the effects of economic insecurity, social-isolation, disaster-related unrest, reduced health service accessibility, inability to escape abusive partners, and violence against healthcare workers for women. Measures such as social-isolation have increased women's exposure to domestic violence: early reports from a police station in China's Hubei Province recorded thrice the amount of domestic violence reports during the COVID-19 quarantine period of February 2020. 29 Since women also have an increased risk of psychiatric disease such as depression and anxiety compared to men, the genderbased disparity and violence associated with the pandemic intersects with pre-existing conditions and puts women more at risk. Hence, governments and public health experts should recognize the needs of women and women with psychiatric diseases to counter the vulnerability and risk they face.
There are several strengths of our global and immediate approach to the examination of the vulnerable population of psychiatric patients during COVID-19. First, the sample size is large: participants from 12 countries responded to reliable measures to predict and analyze their mental well-being. Second, to avoid a weak external validity, the study was administered in 11 different languages, ensuring generalizability across countries and cultures. Participants from the 12 countries represented a diverse perspective according to the economic structure and government support provided by their respective countries. For instance, countries like Canada, France, Germany, Italy, Spain, Switzerland, and USA are classified as high-income economies according to the World Bank Atlas, whereas, Bosnia and Herzegovina, Iran, Pakistan, and Turkey are considered middle or lower-income countries. 33 Third, as one of the earliest examinations of the mental health impact of COVID-19, our study carries the unique strength of immediate data collection during the peak of the COVID-19 pandemic in . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint this version posted May 30, 2020. This study also has potential limitations that warrant consideration for the interpretation of results. First, the sampling method is non-randomized for the survey cohort. While a non-randomized approach has potential disadvantages, we hope that the results of this study can nonetheless serve as a resource and catalyst for further investigation. For a similar global or continent-wide study, entities such as the World Health Organization (WHO) and the EU (European Union) could develop and administer a similar study with a wider reach. Second, the data were exclusively collected online for the survey -this may have excluded those less well-versed in webusage such as underdeveloped, rural or disadvantaged populations. Nevertheless, to counter existing language-barriers that may be furthered by computer illiteracy, we translated the survey in native and official languages for each of the featured countries.
Lastly, a longitudinal assessment of the evolution of psychological symptoms in response to the COVID-19 pandemic is imperative and indeed, an on-going investigation by our group of researchers.
In conclusion, this effort highlights a significant impact of the COVID-19 pandemic on the mental health of psychiatric patients and elucidates prominent associations with their demographics, house-hold conditions, personality traits, and attitude towards COVID-19. These results could serve to inform mental health professionals and policymakers across the globe, aiding in dynamic optimization of mental health services during and following the COVID-19 pandemic, and reducing its long-term morbidity and mortality.
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The copyright holder for this preprint this version posted May 30, 2020. . https://doi.org/10.1101/2020.05.28.20116178 doi: medRxiv preprint Main Item 1. Geodemographic representation of the survey participants with pre-existing psychiatric condition that reported worsening of their condition. The map shows the percentage of worsening pre-existing psychiatric conditions separately for each of the featured countries, and for each of WHO regions.
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The copyright holder for this preprint this version posted May 30, 2020. Less than usual (n = 832) 21% 79%
Like usual (n = 1589) 51% 49%
No (n = 1977) 38% 62%
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The copyright holder for this preprint this version posted May 30, 2020. 
It will resolve after many months or years (n = 1037)
It will resolve in the summer but not within a month (n = 1457)
It will resolve within a month . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted May 30, 2020. . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
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