Abstract

Key words : Anxiety, COVID-19, Depression, Kidney transplantation

Introduction

On March 11, 2020, the World Health Organization declared the pandemic status of a new type of coronavirus (severe acute respiratory syndrome coronavirus 2) infection (COVID-19). The outbreak emerged from Wuhan city in China.¹ Many countries and governments have taken unprecedented measures to control the spread of the infection, including those as drastic as nationwide lockdowns or states of emergency.

Despite its central geographical position and status as a travel hub, Turkey managed to delay the penetration of the infection through its borders, at least partially due to timely infection control measures. However, the first confirmed case by polymerase chain reaction was identified on March 10, 2020. Since then, a plethora of regulations from the government has come into effect.

On March 16, 2020, primary schools, middle schools, high schools, and universities began to close. On the same day, all public gathering places, such as cafes, gyms, internet cafes, and movie theaters, were closed. Moreover, individuals over 65 years of age (later regulated as those over 60 years of age), pregnant, disabled, and with chronic disease were ordered to be on administrative leave. On March 21, 2020, the Ministry of Interior announced a total curfew for those who over 60 years of age and with chronic illnesses. On the same day, restaurants, dining places, and patisseries were closed and only home delivery or take away was allowed. On April 3, 2020, a 15-day entry ban to the 30 provinces with metropolitan status was announced. The curfew was further extended to people younger than 20 years. On April 10, 2020, a total lockdown during weekends was performed in the 30 provinces with metropolitan status. Still, as of April 24, 2020, Turkey was heavily
hit by COVID-19, with a total of 104 212 confirmed cases.

In addition to nationwide measures, other measures, mainly guided by the National Scientific Committee and executed by the Ministry of Health, were carried out in the health system to stand up against the effects of the pandemic. On March 20, 2020, the Ministry of Health issued an order to declare all hospitals with at least 2 specialists in infectious disease, pulmonology, internal medicine, and clinical microbiology, including private and foundation hospitals, as “coronavirus pandemic hospitals.” The number of outpatient clinics was greatly reduced to prioritize the care of COVID-19 patients. Many inpatient clinics were transformed for the care of COVID-19 patients, and elective surgical operations were postponed as far as possible. All of these unprecedented measures have deeply affected social lives and the health care system.²

Kidney transplantation is the best form of renal replacement therapy because it leads to better quality of life and survival compared with other renal replacement therapies.³ Still, kidney transplant recipients have an increased risk for infectious diseases, mainly due to the immunosuppressive drugs that they should use.⁴ However, it is not clear whether their susceptibility to infectious diseases makes them more vulnerable to psychological stress during social isolation and lockdowns that take place during infectious epidemics.

In this study, we aimed to investigate the impact of pandemic control measures on the mood profiles of kidney transplant recipients.

Materials and Methods

Study design
We performed a cross-sectional study and collected data on demographics, mood status, anxiety, and depression status using an electronic survey. We also used medical records to collect clinical and biochemical data of eligible patients.

The study was conducted between March 29 and April 19, 2020, in a tertiary medical care university hospital. As of March 22, 2020, our hospital was declared as a pandemic hospital, where patients with COVID-19 could receive medical care. The study was approved by the local medical ethics committee (approval no. 83045809-604).

Participants
Only adults (>18 years of age) were eligible to participate in the study. The first group of participants consisted of kidney transplant recipients who were under regular follow-up in our renal transplant unit. The second group consisted of individuals without self-reported chronic kidney disease. We used a snowball sampling strategy to recruit participants to the control group. Most participants in the control group consisted of the academic staff of a nonmedical university, which was also located in the same city.

Survey and data collection
We used an electronic survey created by the SurveyMonkey© platform. We evaluated psycho­logical status using 2 metrics: the Profile of Mood States (POMS) and the Hospital Anxiety and Depression Scale (HADS).^5,6 The survey consisted of 3 sections. In the first section, demographic, clinical, and social data were collected. In the second section, an electronic version of the POMS questionnaire was provided. Finally, in the last section, the HADS questionnaire was provided. Kidney transplant recipients in the patient group were asked to fill in their names and surnames, whereas individuals in the control group were left to their own choices for filling out this information.

Participants were first informed about the survey with phone calls or WhatsApp messages, followed by the forwarding of a Web link to the survey individually via the WhatsApp application. The survey could be completed using smartphones or computers. The same administrative staff member was assigned to help participants to fill the survey via phone calls in case they declared that they did not have access to the survey or the ability to complete it.

Clinical data of kidney transplant recipients were collected from patient files and from the electronic database of the hospital. Because different curfew measures were carried out for individuals who were younger than 20 years and those who were 60 years or older, we analyzed the results of only those between 20 and 59 years of age.

Profile of Mood States
The POMS is a self-assessment questionnaire that is used to measure transient distinct mood states rapidly and reliably.⁵ It is designed to evaluate an individual’s current mood status and mood changes.⁵ The POMS questionnaire assesses 6 mood subscales: tension-anxiety, depression-dejection, anger-hostility, vigor-activity, fatigue-inertia, and confusion-bewilderment.⁵ The total mood disturbance score is computed by adding the 5 negative subscales scores and subtracting the vigor score. The total and average scores for each subscale and total form are reported; higher scores for the total mood disturbance score indicate a greater degree of mood disturbance.⁵ Selvi and colleagues⁵ previously translated and validated the 65-item POMS into Turkish. We used the Turkish version of POMS in our study.

Hospital Anxiety Depression Scale
The HADS was originally developed by Zigmond and Snaith and is commonly used to assess anxiety and depression of patients.⁶ The term “hospital” in its title suggests that it is used for hospitalized patients only, but many studies have confirmed that it can also be used in community settings and primary care medical practices.⁷ The scale consists of 14 items that make it easy to administer, assessing both anxiety and depression, which commonly coexist.⁸

Aydemir and colleagues translated and validated the 14-item HADS into Turkish.⁹ We used the Turkish version of HADS in our study. The HADS scores can be interpreted using cut-off values. For the Turkish version, a cut-off value of 10 for the HADS-anxiety score and a cut-off value of 7 for the HADS-depression score were proposed to classify scores as “abnormal”.9

Statistical analyses
Descriptive statistics were expressed as mean and SD, median, minimum, and maximum for continuous data and as count and proportion for categorical data. After exclusion based on age, we matched the kidney transplant and control groups according to age and sex using propensity scoring. Categorical data were analyzed with chi-square or Fisher exact tests. The distribution normality of the continuous variables was calculated with the Shapiro-Wilk test. We compared the 2 groups with t tests for normally distributed variables and with Mann-Whitney U tests for nonnormally distributed variables. Pearson or Spearman correlation analysis was used to find the relationship between continuous variables, depending on the distribution. The association between POMS and HADS scores and independent factors was examined with univariate analysis, with stepwise regression then used for multivariate analysis.

Statistical analyses were performed using IBM SPSS version 24 for Windows software and were reported with 95% confidence intervals (95% CI). Values of P < .05 were considered significant.

Results

Participants and demographic, clinical, and sociocultural data
Our study included 584 individuals who assessed the questionnaire, with at least 1 of the questionnaires (POMS or HADS) completely filled by 451 individuals. After age-based exclusion and propensity score matching were completed, 308 participants (154 kidney transplant recipients, 154 control participants) were eligible for analysis (Figure 1). The demographic, clinical, and sociocultural data of the kidney transplant and control groups are shown in Table 1. There was no statistically significant difference with regard to age, sex, marital status, and having children between the 2 groups. Both groups were generally middle-aged and were mostly composed of men. Most kidney transplants (78.6%) were performed using grafts from living donors, and the mean posttransplant period was 107.5 ± 73.50 months. Most transplant recipients had good renal function, and their mean creatinine level was 1.56 ± 1.03 mg/dL (median of 1.27 mg/dL). In the control group, 17.5% of the participants reported having a chronic disease. The list of self-reported diseases is shown in Table 2.

Regarding sociocultural status, kidney transplant recipients were usually married and had children. More than half had graduated from high school or university. In general, they lived in a family of fewer than 4 people and an old member of the family did not live with them. Nearly all of them took the outbreak seriously and were following the stay-home orders (Table 1).

Profile of Mood States and Hospital Anxiety Depression Scale results
Subscale and total POMS scores are shown in Table 3. Except for vigor, every subscale score, as well as the total score, was significantly lower in the kidney transplant group compared with the control group. There is a well-known difference between males and females with regard to posttraumatic mood changes.¹⁰ Therefore, we subgrouped the study participants according to sex and compared men and women separately (Table 4 and Table 5). Again, in the male/female subgroups, total POMS score and most subscale scores were significantly lower in the kidney transplant group versus the control group. There was no statistically significant difference between kidney transplant recipients and control participants with regard to vigor subscale score in both sex subgroups and with regard to tension subscale score in women.

The HADS scores for both groups according to anxiety and depression scores are shown in Table 6. Both the HADS-anxiety and HADS-depression scores were significantly lower in kidney transplant recipients compared with the control group. The stratification of the study groups according to sex is also shown in Table 6. In male kidney transplant patients, both the HADS-anxiety and the HADS-depression scores were significantly lower compared with the control group. In contrast, although female kidney transplant recipients had a trend toward higher HADS scores for both anxiety and depression, there were no significant differences with regard to both HADS-anxiety and HADS-depression scores between groups (Table 6).

The percentage of patients classified as abnormal according to the HADS score for each study group is shown in Figure 2. Frequencies of abnormal HADS-anxiety and HADS-depression scores were signi­ficantly different between groups, with anxiety (P = .009) and depression (P = .029) scores lower in the kidney transplant group compared with the control group.

Determinants of Profile of Mood States and Hospital Anxiety Depression Scale results
To reveal the factors associated with POMS, HADS-anxiety, and HADS-depression scores, we performed a univariate analysis using all study parameters listed in Table 1, including the study group. We used parameters that were significantly associated with POMS and both HADS scores (Table 7) to construct multivariate models. Kidney transplantation was an independent predictor of better POMS, HADS-anxiety, and HADS-depression scores (Table 8).

Discussion

According to our findings, kidney transplant recipients seemed to be more resilient to the effects of social distancing and lockdown compared with a nontransplant control group. To the best of our knowledge, this is the first study to examine the effects of social isolation and lockdown in kidney transplant recipients during the COVID-19 pandemic.

Social isolation and quarantine practices due to pandemics cause anxiety because these can be unfamiliar and unpleasant experiences that involve separation from friends and family, as well as a departure from usual, everyday routines. Isolation is known to cause psychological problems. In addition, during pandemics, other mechanisms might also impact mood status, such as information pollution and lack of medical supplies, including masks and hand sanitizers. According to a recent study, overall society anxiety elevated as prices of medical supplies and the exploitation of some consumers increased.¹¹

We suggest that the relatively better mood profile scores of kidney transplant recipients might at least partially be explained by 3 concepts: experience, knowledge, and traumatic growth. First, because of immunosuppression, kidney transplant recipients are acquainted with the risk of infection, especially at the early period of renal transplant. They are instructed to wear a mask in crowded places and on public transportation. They know that they should try to stay away from people who show signs of infections. They are informed about the importance of self-care, such as frequent hand washing and regular tooth brushing. Therefore, at least partially, they are used to practicing personal infection control measures.

Second, during the pretransplant period, kidney transplant candidates frequently visit the hospital and interact with transplant doctors, nurses, coordinators, and fellow patients. Moreover, informed consent regarding their procedure is given. They become familiar with medical concepts and complications related to transplant procedures, including infectious diseases and viral infections. They even know some “exotic” virus names, such as BK virus or cytomegalovirus. Therefore, “the fear of the unknown” might be less than for the healthy population.

Finally, social distancing and lockdown might be an unpleasant experience for most people. However, kidney transplant patients have an additionally greater disturbing personal experience during their life, which is the failure of their kidneys and dialysis treatment. Having endured such a hard period may cause “traumatic growth” and be a factor for the psychiatric resilience of these patients. Posttraumatic growth may give kidney transplant patients the opportunity to be more flexible in adapting to new stressful situations, thus leading to better mood and coping scores.¹²

The following variables were also independently associated with mood scores, at least in 2 of the 3 multivariate models. The perception of appropriate medical support was an independent determinant for POMS and HADS-depression scores. The perception of no medical support was associated with higher/worse mood scores. Interventions using telemedicine methods may help to improve this perception.¹³ Finally, male sex was associated with lower/better POMS, HADS-anxiety, and HADS-depression scores. The psychological vulnerability of females was previously described in several studies and in different contexts, and it seems that the psychological dynamics of quarantining a city were especially detrimental in women.^10,14,15 Therefore, a setting with social isolation and lockdowns prioritizing women for psychological support might be advised.

An important potential confounder might be the high prevalence of male patients among our kidney transplant population. First, we want to point out that this finding is likely not related to selection bias; similar to other countries, in Turkey, there is a well-documented male/female discrepancy in living kidney donations. Women are more likely to become a donor and less likely to become a recipient than men.^16,17 According to the latest Turkish renal registry report, nearly 64% of kidney transplant recipients were male patients.¹⁷ Therefore, the disbalance in males versus females is characteristic of kidney transplants performed from living donors, such as for our cohort. Second, we repeated our analysis after male versus female stratification, and the statistically significant trend toward better mood profile scores in kidney transplant patients persisted in POMS subscales, total POMS, and HADS-anxiety scores. Finally, according to multivariate analysis, kidney transplant was an independent predictor of better total POMS and both HADS scores.

Limitations of our study should be kept in mind when interpreting our findings; some limitations, such as “information bias” and lack of longitudinal data are inherent to cross-sectional questionnaire study design. It should be noted that the effects of social isolation might be correlated with its duration. Therefore, despite the relatively short duration (3 weeks) of data collection, our study groups may not be homogenous regarding this effect size. Finally, sociocultural status may have also affected individuals’ responses, and the generalizability of our results to other populations in different countries might be limited in this regard.

Conclusions

We found that kidney transplant recipients were at least as resilient as nontransplant individuals to the physiological effects of social deprivation. This is encouraging for advising strict compliance with social distancing to control the risk of contagion in this infection-prone population.

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