The magnitude and associated factors of anxiety and depression among non-communicable chronic disease patients during COVID-19 pandemic in a resource-limited setting

Objective To assess the magnitude and associated factors of depression and anxiety among chronic disease patients during the COVID-19 pandemic at the University of Gondar Comprehensive and Specialized Hospital, Northwest Ethiopia 2021. Methods A cross-sectional study was done from June 1 to August 30, 2021 among non-communicable chronic disease patients. A systematic random sampling technique was used to collect data from 400 patients. Data were entered into EPI Info and to SPSS version 23 for analysis. Descriptive data analysis was done and bivariable and multi-variable logistic regression was used to identify factors. Variables with a p-value of 0.05 were considered statically significant. Results The mean age of the respondents was 51.3 ± 0.8 years. The prevalence of anxiety and depression among non-communicable chronic disease patients was 17.9% (95%CI 14.2, 21.7) and 16.3% (95%CI 12.6, 20.1)) respectively. Being female (AOR = 2.56, 95% CI: 1.21, 5.41), divorced (AOR = 3.42, 95% CI: 1.02–11.50), and ever cigarette smoking (AOR = 5.00, 95% CI: 1.66–14.90) were significantly associated with depression. Whereas, ever cigarette smoking (AOR = 2.74, 95% CI: 1.04, 7.21), number of closed contacts (AOR = 1.16, 95% CI: 1.03, 1.31), and poor social support (AOR = 2.98, 95% CI: 1.16, 7.65) were significantly associated with the anxiety. Conclusion The magnitude of depression and anxiety was high. Thus, appropriate action should be taken to identify those patients and integration of psychiatric care into the usual care of non-communicable chronic disease patients is vital.


Introduction
A significant threat to both physical health and lives is posed by the COVID-19 virus's extreme contagiousness. It also contributed to psychological issues like panic disorder, anxiety, depression, and stress. 1 Self-quarantining, in addition to social and physical distancing, has been mandated in a number of nations. 2 These are practical steps to halt the transmission of the virus. 3 However, there have been numerous significant negative economic, social, and psychological impacts on people as well as a number of challenges and concerns, including psychological pressures. [4][5][6] Individual's mental health is a critical public health concern that is likely to be disrupted during pandemics, such as the COVID-19 pandemic. 6 During the recent COVID-19 pandemic, increased levels of stress, anger, anxiety, and depression have been reported among individuals in different parts of the world. 4,7 Individuals with non-communicable chronic illnesses (NCD) have the highest likelihood of being infected by the virus and have a higher risk of acquiring depression and anxiety than the general population. 8 Anxiety and depression have been reported to be caused by public emergencies including pandemics, affecting the mental health of people,. 9,10 The COVID-19 pandemic is thought to be responsible for a 25% rise in the prevalence of anxiety and depression globally, according to the WHO, who also voiced concern about the impact of COVID-19 on mental health and psycho-social consequences of an individual. 11 A rise in loneliness, anxiety, depression, insomnia, harmful alcohol and drug use, self-harm, or suicidal behavior may result from new policies like self-isolation and quarantine, which have an impact on people's daily lives, routines, and activities. 12 Compared to the time before the COVID-19 pandemic, there is strong proof that people's mental health declined during and after the pandemic. [13][14][15] Recent meta-analysis found that during the COVID-19 pandemic, depression, anxiety, and stress was all relatively common, occurring at 33.7%, 31.9%, and 29.6%, respectively. 16 According to a study conducted in China during the COVID-19 pandemic, 20.1% of the general population displayed depressive symptoms. 17 During the early stages of the COVID-19 pandemic, a different report from Spain found that 36% of research participants had moderate to severe psychological issues, of which 25% had mild to severe anxiety, 41% had depression, and 41% had stress-related symptoms. 18 In 2020, the pandemic caused a 27.6% rise in cases of major depressive disorders and a 25.6% increase in cases of anxiety disorders worldwide, according to the COVID-19 Mental Disorders Collaborators. The unprecedented stress brought on by the social seclusion brought on by the pandemic is one main factor contributing to the rise. 19 According to a recent study, those with the lowest incomes were significantly more likely than those with higher incomes to experience anxiety and depressive illnesses, demonstrating the causal link between poverty and mental health. 20 The COVID-19 pandemic has been shown to have a significant impact on the disease progression and survival of NCD patients. As a result, more concerns have been raised about the mental health state of NCD patients. Comorbid anxiety and depression impair patient medication compliance, reducing therapy safety and effectiveness and increasing disability and death. 21 However, comorbid mental disorders are often unrecognized and not always effectively treated. 21 Studies on the state of mental health in emerging nations like Ethiopia, however, are extremely scarce. Understanding and researching public psychological issues during this turbulent period is therefore practical. Therefore, the objective of this study was to assess the magnitude of anxiety, depression, and associated factors among NCD patients during the COVID-19 pandemic at the University of Gondar Comprehensive Specialized hospital. The information from this research may be used by policymakers, healthcare planners, medical professionals, and other interested parties to create a preventive strategy for COVID 19-induced depression and anxiety.

Study setting
The study was conducted at the University of Gondar Specialized Hospital, which is located in Gondar Town. It is about 725 km far from the capital city of Ethiopia, Addis Ababa and 180 km from the regional city Bahir Dar. This hospital is a teaching hospital serving more than 5 million people. The hospital provides outpatient, inpatient, major and minor surgery services, maternal and neonatal health services, burn treatment and care, physiotherapy services, etc.

Study design and study period
An institution-based cross-sectional study was employed on adult NCD patients. Data were collected from June 1 to August 30, 2021.

Source population and study population
All patients with NCD who visited the University of Gondar Comprehensive and Specialized Hospital were the source population, while all patients with NCD who visited the University of Gondar Comprehensive and Specialized Hospital during the data collection period were the study population.

Inclusion and exclusion criteria
All adult patients over the age of 18 and those with NCD were included in the study. On the other hand, critically ill patients who were unable to respond to the interview were excluded.

Sample size and sampling procedure
The sample size was determined by a single population proportion formula n = (Za /2)2 * P(1 − P)/d2 by considering the prevalence of depression among NCD during COVID-19 in Mettu Karl hospital 61.8% 11 with the assumption of a 95% confidence interval, a 5% margin of error and a 10% non-response rate.

=362.6ᵙ 363
After adding a non-response rate of 10%, the sample size was found to be 400.
A systematic random sampling technique was used to obtain the required 400 patients. Chronic patient's medical chart is ordered based on their time of arrival; this order of cards was used as a sampling frame. The sampling interval was calculated by dividing the expected number of patients visiting the follow-up clinic during the data collection period by the total sample size, and the first patient was selected by lottery method.

Data collection procedure
Data were collected using interviewer-administered adopted questionnaires from June 1 to August 30, 2021 by four trained psychiatrists by maintaining physical distance and by taking appropriate COVID-19 preventive methods. The questionnaire had five parts. The first section contained questions about the participant's sociodemographic characteristics, and the second part was about clinical and medical-related characteristics. The third section was about behavioral characteristics. The fourth part was about measuring social support and Oslo A 3-item social support scale was used to measure family/social support. 22 The tool consists of three items, each of which is scored on a likert scale. The raw scores were added together to create a sum index, which ranged from 3 to 14. "Poor social support" scored 3-8, "moderate social support" scored 9-11, and "strong social support" scored 12-14. 22 Depression and anxiety were measured by the Depression anxiety stress 21 scale (DASS 21). The DASS 21 consisted of 7 items divided into subscales, the depression scale assesses dysphoria, hopelessness, devaluation of life, self-depreciation and lack of interest/involvement and the anxiety scale assesses the subjective experience of anxiety. Participants with a score of 0-9 were considered not depressed, while those with a score of 10 were classified as depressed. A score of 0-7 indicated that the person was not anxious, while a score of 8 indicated that the person was anxious. 23 Those participants who were considered as depressed and anxious were linked to psychiatry clinic for further evaluation. The data collection tools were initially prepared in English, translated into Amharic (local language) by language expertise for data collection, and retranslated to English to check the consistency in the meaning of words.

Data quality and assurance
The training was delivered to data collectors on data handling and participant approach. The trained data collectors were supervised by two supervisors. A pre-test was conducted among 5% of patients at Felege Hiwot comprehensive and specialized hospital to assess the understandability and quality of data before starting the actual data collection. This questionarrie was used earlier and it has been established that it's appropriate, sensitive, reliable and valid. The questionnaire underwent preliminary testing, and the reliability of the translated tools was evaluated using the cronbach's alpha coefficients and it was found to be 0.99. . Daily close supervision was conducted during the time of data collection.

Data processing and analysis
The collected data were entered into EPI Info 7. After data entry, the data were analyzed by Statistical Package for Social Science (SPSS) version 23. Participants' sociodemographic characteristics were summarized by descriptive analysis (frequency. mean and standard deviation). The confidence interval was calculated and reported for the magnitude of depression and anxiety. Multicollinearity was tested and the result demonstrated the absence of multicollinearity. The data were also checked for outliers by box plot and no outshining outlier effect was observed.
The models' goodness of fit was also checked and the omnibus test result was significant with a p-value <0.05 and the Hosmer and Lemeshow test showed a good model fit with a p-value >0.05. Logistic regression was performed for each independent variable and a p-value <0.2 was included in the final model. Multivariable logistic regression was fitted to identify significant factors (P-value<0.05) associated with Depression and Anxiety.

Ethical consideration
Ethical clearance was secured from the University of Gondar College of medicine and health science, School of Pharmacy ethical review committee with approval number of SoP/272/2021. Necessary permission was gained from The university of Gondar comprehensive and specialized Hospital director. Data were recorded anonymously.
The purpose and importance of the study were explained to the participants. Data were collected after full informed written consent was obtained from the patients and confidentiality of the information was maintained by omitting their names and personal identification. Those subjects who refused to participate were respected.

Socio-demographic characteristics of the study participants
In this study a total of 400 respondents were approached, 380 with a response rate of 97.2% were involved in the study. Of those who were involved in the study, more than half of them were females 211 (55.5%) and the majority of them were urban dwellers (75%). The mean age of the respondents was 51.3 ± 0.8 years. In this study about 43.2% of the participants were unable to read and write. House wives accounted for (37.6%) of the participants and about 54.5% and 21.3% of respondents were married and widowed respectively (Table 1).

Clinical and behavioral related characteristics of study participants
Most of the study participants, 378 (99.5%) had comorbid disease. Moreover, about 313 (82.4%) of the participants had no family history of chronic medical illness. About 161 (39.2%) of them engaged in regular physical activity and the majority, 331 (80.5%), of them were prescribed 1-2 medication on a daily basis. Majority of the respondents (95%) did not take alcohol in the past 3 months and half of the participants 194(51.1%) reported that they had strong social support ( Table 2).

Factors associated with depression among non-communicable chronic disease patients
In the bivariate logistic regression analysis, it is illustrated that sex, number of medications, ever cigarette smoking, average monthly income and marital status were significantly associated with depression at a P-value < 0.2 level of significance. These variables were entered into multivariable logistic regression model. Consequently, the multivariable binary logistic regression analysis revealed that sex, divorced, and ever cigarette smoking were found to be significantly associated with depression.
The odds of having depression was about 3 times (AOR = 2.56, 95% CI: 1.21, 5.41) higher among female participants as compared to male counter parts.

Factors associated with anxiety among chronic medical patients at University of Gondar specialized & comprehensive hospital
After running the bivariate binary logistic regression ever cigarette smoking, number of close contact, number of medication, marital status and social support were associated with anxiety. The multivariable binary logistic regression analysis revealed that ever cigarette smoking, number of closed contacts and social support were found to be significantly associated with the anxiety level of the respondents. In this study, the history of cigarette smoking was found to affect the level of anxiety. The odds of having anxiety was about three times (AOR = 2.74, 95% CI: 1.04, 7.21) higher among ever smokers than non ever smokers.
Regard to number of close contacts with people, the odds of having anxiety was about one times (AOR = 1.16, 95% CI: 1.03, 1.31) higher for every one person increase in number of contacts. The level of social support was also significantly associated with the odds of having anxiety. It was found that the odds of having anxiety among those respondents who had poor social support was about three times (AOR = 2.98, 95% CI: 1.16, 7.65) higher than those respondents who had strong social support. Table 4 shows the bivariable and multivariable regression in detail.

Discussion
In this study, four key findings concerning the specified objectives were identified. First, the magnitude of depression and anxiety among NCD patients was determined using the DASS 21 measurement tool and it was found to be 16.3% (95 CI, (12.6, 20.1)) and 17.9% (95% CI 14.02, 21.7)) respectively. The second main finding is the identification of factors associated with depression and anxiety.
In the current study, 16.3% and 17.9% of the participants had depression and anxiety respectively. This finding is higher than the prevalence of depression (5.73%) and anxiety (32%) among patients living with a chronic medical condition in Ethiopia before the emergence of COVID-19. 24 On the other hand, this finding is lower than a study which was done at Mettu Karl Referral Hospital which was 55.7% and 61.8% respectively during COVID-19 pandemic. 8 This discrepancy might be explained by adherence to WHO guidelines in the initial phase of COVID-19 confinement correlated with both a worse current perceived anxiety and depression. 25 Moreover, The finding was low as compared to the findings of previously conducted studies during the COVID-19 pandemic in the United Kingdom (24.4%) 26 and Iran (31.4%). 27 This could be due to the availability of COVID-19 vaccine during the current study period which might ease the psychological burden and decrease the level of depression and anxiety. In addition, a difference in the study population, a sociocultural difference, and the measurement tool used to assess the outcome variables might be responsible for the discrepancy. The increased prevalence of depression anxiety might be due to As new measures imposed in many countries such as self-isolation and quarantine, which affects day-to-day activities, routines, and livelihoods of people, they may lead to an increase in loneliness, anxiety, depression, insomnia, harmful alcohol and drug use, and self-harm or suicidal behavior. 12 Spanish study discovered an increased suicide rate during the Spanish flu epidemic in 43 large cities, which was connected to the degree of social distancing, independent of the influenza fatality rate. 28 Being female increased the odds of depression compared to male counterparts. This discovery is consistent with research conducted in Ethiopia's Mettu Karl Referral Hospital during the COVID-19 pandemic, 8 as well as research conducted among general populations  in Gondar town. 29 Similar findings were reported in studies conducted in China 30 and the United States, 31 which revealed that women were more likely to experience depression during the COVID-19 pandemic. This could be attributable to genetic, hormonal, social, and psychological influences. 32 Furthermore, because males have androgen receptors, androgen has a protective impact, 33 and testosterone hormone does not cycle like estrogen in women, resulting in a lower risk of depression due to its protective function. Furthermore, testosterone is converted to estrogen in the male brain, which mediates protective effects via estrogen receptors. 34 Regarding cigarette smoking, smokers had higher odds of developing depression and anxiety than non-smokers.
An Ethiopian study 8 showed similar findings, which were also backed up by a study conducted in Australia. 35 This could be related to the effect of cigarette smoking on the lungs, which puts those persons at risk for respiratory issues. The development of COVID-19 in these smokers will result in a worsening of their lung disease and a worse prognosis. As a result, it will cause depression. Furthermore, smoking affects the amount of dopamine in the brain, which is responsible for pleasure.
On the other hand, being divorced was associated with higher odds of depression than single respondents. This finding is in agreement with a study that was carried out in Ethiopia. 8 Moreover, a study which was done in the USA also reported similar findings. 31 This might be due to a difference in stress coping mechanisms between being single and those who are divorced.
Having more close contact was associated with higher odds of anxiety than having no contact. This finding is concurrent with a study from Mexico. 36 This could be because of possible misinformation or information overload when there was a large number of close contacts. 36 Likewise, more close contact increases the likelihood of exposure to the deadly virus which in turn leads to anxiety. 29 Poor social support is an influencing factor for anxiety among chronic medical patients during the COVID-19 pandemic. This finding is consistent with the reports from World Health Organizationn 11 and China. 37 Social support is widely seen as having a beneficial effect on mental health. Positive social support has a significant role in improving quality of life by relieving stress. 38 Poor social support, on the other hand, leads to anxiety, depression, and social isolation, as social support is a key factor in reducing negative psychological reactions like hopelessness and depression, as well as reducing the harmful effects of negative life events on physical health and emotional well-being and acting as a stress buffer. 39,40

Limitation of the study
The limitation behind in this study is it lacks to show the temporal relationships between the exposure and outcome variables because of the cross-sectional nature of the data.

Conclusion
The magnitude of depression and anxiety in the current study was high. Being female, ever cigarette smoking and being divorced were significantly associated with depression. Moreover, ever cigarette smoking, number of closed contacts and social support were found to be significantly associated with the anxiety level of the respondent among chronic medical patients in Ethiopia during COVID. Furthermore, proper measures should be done to identify and diagnose individuals with depression and anxiety among chronic illness patients, as well as to treat them appropriately.

Recommendations
Chronic disease follow up units shall consider referring patients to psychiatric clinic for psychiatric evaluation. In addition, for early detection and treatment of depression and anxiety mass education about mental health and also prevention strategies such as mask utilization and vaccination shall be emphasized. Moreover, media should also be responsible when reporting facts about COVID -19 to avoid unnecessary fear and stress among the community.

Practical implications
Increasing access to psychiatric evaluation for Non-communicable chronic disease patients is the preliminary step toward improving the service for Management of NCD. Thus it is better to incorporate psychiatric care for Non-communicable chronic medical patients in order to identify depression and anxiety early.

Declarations
Ethics approval and consent to participate: The Ethical Review Committee of the University of Gondar's School of Pharmacy gave their approval. The study participants were informed about the study's purpose, and their consent to participate was acquired. Data was collected after written informed consent was obtained, and the information was kept confidential. All procedures were carried out in accordance with the applicable rules and regulations. While conducting this research, the Helsinki Declaration's standards were followed.
Consent for publication: The participants' permission to publish this work was obtained.
Availability of data and materials: On request, the corresponding author will provide the datasets used in and/or analyzed during the current work.
Competing interests: The authors declare that they have no any conflict of interest.
Funding: None. Authors' contributions: All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article and revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.