Psychological distress and associated factors among kidney transplant recipients and living kidney donors during COVID-19

The Coronavirus disease (COVID-19) outbreak has resulted in significant public health burdens globally; over 150 million confirmed cases and two million deaths have been reported from 223 countries, areas or territories as of 27 February 2021 [1]. Many countries have responded to the outbreak by adopting multi-faceted interventions including lockdowns, travel restrictions, social distancing, and protective measures (e.g., wearing masks) [2]. However, the disruptions in economic development, personal routines, and social interactions may have posed heavy psychological distress worldwide. Systematic reviews and meta-analyses of up to 68 studies from 19 countries found that around 30% of the general population and 55% of high-risk patients (e.g., cancer, type 2 diabetes, COVID-19) had symptoms of anxiety or depression during COVID-19 [3, 4]. By evaluating psychological distress and its associated factors, urgent interventions to mitigate its impact can be initiated during future pandemics.

Female gender, younger adults, lower socioeconomic status, longer media exposure, and individuals having pre-existing physical conditions have been identified by previous studies of the general population as risk factors for increased psychological distress [4]. Patients with chronic kidney disease (CKD), especially those who are on chronic immunosuppression following kidney transplant surgeries, are at particularly high risk of COVID-19 infection and mortality [5‐7]. To the best of our knowledge, the prevalence of psychological distress and associated factors during the COVID-19 pandemic have not been explored among kidney transplant recipients and living kidney donors. This knowledge would be especially informative as a recent study showed that stress-related disorders increase the risk of CKD progression and acute kidney injury by 23% [8].

Therefore, we aimed to evaluate the prevalence of, and factors associated with psychological distress during the COVID-19 pandemic among kidney transplant recipients and living kidney donors and compare the differences between the two groups. We hypothesize that the prevalence of psychological distress during the COVID-19 pandemic is significantly higher among kidney transplant recipients compared to donors; and younger age and lack of knowledge regarding COVID-19 will be associated with higher odds of psychological distress.

Among 1132 (862 recipients and 270 donors) individuals that were asked to participate in the current study, 497 participants (325 recipients and 172 donors) completed the survey. The overall response rate was 43.9% (95% confidence interval: 41.3–46.8%), and it was higher among donors (63.7% [57.8–69.2%]) compared to recipients (37.7% [34.5–41.0%]; P < 0.001). The characteristics of recipients and donors are shown in Table 1 and Additional file 2. Among all participants, 69.4% (n = 345) were aged 50 years and above, and 65.4% (n = 325) were men. In addition, 78.5% (n = 390) were Chinese, 13.3% (n = 66) were Malays and 4.43% (n = 22) were Indians. A similar proportion of respondents (78.6%) were living in government housing as per national census. Among kidney recipients, 13 recipients (4%) had their kidney transplant surgeries less than one year ago, 72 had transplant surgeries between 1- < 5 years ago, and the remaining recipients (n = 240; 73.8%) had their transplant surgeries for 5 years and longer. The prevalence of psychological distress was 14.3% (11.5–17.6%) in the overall study population, and it was 12.8% (9.79–16.6%) in recipients and 13.4 (9.08–19.6%) in donors with no statistically significant difference (P = 0.67). The prevalence of its component (depression, anxiety, and stress) was also similar between recipients and donors (all Ps > 0.05). Similarly, the overall and subscale mean DASS-21 score was comparable between recipients and donors (all Ps > 0.05).

The prevalence of psychological distress stratified by participants’ characteristics is shown in Table 2. The prevalence of psychological distress was higher among younger adults (21–49 vs. ≥50 years old), Chinese (versus Malays), unmarried individuals, non-Singapore citizens and those of worse health status or had worries about their physical and mental health or had received insufficient information about COVID-19 situation in Singapore (Table 2).

Factors associated with psychological distress from univariable and multivariable linear regression models are presented in Additional file 3 and Table 3. In the final model (Model 4), younger age versus older age (21–49 vs. ≥50 years; β-coefficient: 1.30 [95% confidence interval: 0.27 to 2.33]), unmarried versus married status (1.09 [0.04 to 2.14]), non-Singapore citizen versus Singapore citizen (5.02 [2.58 to 7.46]), worse self-perceived health (2.14 [0.94 to 3.34]), more frequent doctor consultations (0.98 [0.04 to 1.92]), presence of general or respiratory symptoms (1.23 [0.10 to 2.36]), worrying about physical health of household members (0.84 [0.27 to 1.41]), worrying about mental health (1.56 [0.72 to 2.41]) and feeling lonely or isolated during COVID-19 (2.28 [1.36 to 3.20]) were associated with higher psychological distress. Malays (versus Chinese: − 2.03 [− 3.39 to − 0.68]), taking precautionary measures (hand sanitization: − 0.84 [− 1.48 to − 0.20]), and receiving enough information about COVID-19 (− 1.97 [− 3.41 to − 0.53]) were associated with lower psychological distress (Table 3). No interaction has been observed between factors of psychological distress with patient type (kidney recipients versus donors).

To test the robustness of our results, in the sensitivity analysis, we used five age groups instead of the binary age variable. Similar to the current results, younger versus older age (21–39 vs. 50–59 years; 2.44 [0.75 to 4.13]; 21–39 vs. 60–69 years; 2.25 [0.54 to 3.96]) was associated with higher psychological distress.

In the current study in Singapore, we found that at least one in ten kidney transplant recipients and donors suffered from psychological distress during the COVID-19 pandemic. In the overall population, younger age (21–49 vs. ≥50 years), unmarried status, non-Singapore citizenship, worse health conditions, and worrying about physical and mental health were associated with higher psychological distress. Malays (versus Chinese), taking precautionary measures (hand sanitization), and receiving enough information about COVID-19 were associated with lower psychological distress. The relationship of the determinants with psychological distress did not vary between the recipients and donors. Interventions such as targeted-health education including encouragement towards physical exercise, more frequent telehealth consults and rapid access to mental health care or supportive online groups for younger adults, unmarried individuals, non-Singapore citizens, and those with worse health conditions could potentially reduce the risk of psychological distress in these vulnerable groups [16‐19].

The prevalence of psychological distress among kidney donors who were largely healthy (13.4 [9.08–19.6%]), was much lower compared to the 30% among a predominantly general population reported from 68 studies in 19 countries during the COVID-19 pandemic [3, 4]. The lower prevalence of psychological distress in Singapore compared to the rest of the world was also observed in a prior study conducted among healthcare workers (7% [95% confidence interval: 5–9%] versus 26% [18–34%]) [3, 13]. Of note, Singapore also had one of the lowest number of COVID-19 cases (10,473 per million population as of 14 February 2021) and mortality (5 deaths per million population) [1] globally, which was likely due to efficient national responses and high-quality medical care. Specifically, since the start of the outbreak, the Singapore government had proactively established official COVID-19 resources and subscription services, as well as frequent briefings and press conferences by the Prime Minister and other officials, to keep the public informed of the latest COVID-19 situation in Singapore [20]. In addition, protective measures such as wearing masks and social distancing were mandated by the law and strictly enforced in Singapore since April 2020 [21], while free masks and sanitizers were distributed across the country. Furthermore, easy access to free COVID-19 testing, robust contact-tracing, and sufficient medical care capacities were instrumental in arresting the spread of COVID-19 and related mortality; various resources and schemes were also promptly established to target financial disruptions, and 24-h National Care hotlines and other online platforms were provided to alleviate the worries of the public [22‐25]. In the current study, more than 90% of both recipients and donors showed confidence in the government and healthcare system of Singapore to control the spread of COVID-19, which suggests that the existing comprehensive interventions may have contributed to the low prevalence of psychological distress.

It is also interesting to observe a low prevalence of psychological distress among high-risk kidney transplant recipients in the current study (12.8% [9.79–16.6%]), which was substantially lower compared to the 55% among other high-risk patients (e.g. cancer, type 2 diabetes, COVID-19) [3], and the 39% (clinical anxiety or depression symptoms) among patients with end-stage kidney disease on hemodialysis [26]. In addition to the effective national responses, the low psychological distress among recipients could also be attributed to the high-quality medical care and intensive follow-ups by the SGH transplant program [27]. Since the COVID-19 outbreak, the SGH transplant program has adopted a multi-pronged approach to alleviate the impact of the pandemic including rapid transition to video and tele-consults to minimize potential patient exposure to COVID-19, ensuring safe paths for patients who needed to come to hospital, ensuring a stable supply chain of immunosuppression, and sustaining patient and staff education programs via video conferencing [27]. Specifically, two COVID-19 webinars (on May 9th, 2020 and May 30th, 2020) were held to improve COVID-19 knowledge of recipients, in addition to the official social media platform for the kidney recipients which provided a portal for dissemination of electronic education material and peer-support [28, 29]. As a result of the intensive education, recipients had higher COVID-19 knowledge compared to donors and were more likely to adopt precautionary measures (e.g., hand sanitization), and report that they have received enough COVID-19 information from healthcare providers (79.3% versus 36.2%). Adopting precautionary measures and receiving enough information about COVID-19 were both independently associated with lower psychological distress in the current study, suggesting that the intensive intervention and health education at SGH could have contributed to the substantially lower prevalence of psychological distress among the high-risk kidney transplant recipients in the current study. Nevertheless, we noted that only 36.2% of the donor population thought that they have received enough information from healthcare providers. Programs in Singapore and elsewhere should proactively engage their kidney donors for health education especially during public health crisis.

In addition, the higher psychological distress during COVID-19 among non-Singapore citizens versus Singapore citizens could be partly attributed to outbreaks of COVID-19 occurring in dormitories of migrant workers in Singapore [30, 31]; the potentially higher expenses of medical care for non-Singapore citizens might have also contributed to the higher psychological distress. Thus, proactive health education, access to mental health counselling services, high quality affordable medical care and avenues to alleviate the economic impact of the pandemic must include this vulnerable population to reduce health inequities locally and globally [32‐34]. It is also important to underscore that Malay ethnicity was independently associated with lower psychological distress compared to Chinese ethnicity. This was consistent with findings during non-COVID periods in Singapore [35], and might be explained by differences in religious beliefs, strengths of family ties and social networks between the Malay and Chinese communities. Our results were in contrast to studies in Canada, United Kingdom and United States where ethnic minorities had worse mental health [36, 37], and further studies are warranted to understand the unique protective factors of the Malay community in Singapore. Although the prevalence of psychological distress was relatively low among kidney recipients and donors, targeting younger adults, unmarried individuals, non-Singapore citizens, and those with worse health conditions could further improve psychological distress in high-risk kidney transplant recipients and kidney donors.

It is noteworthy that the current study was conducted before the availability of COVID-19 vaccines. As of 10 December 2021, 96% of the Singapore’s eligible population (aged 12 years or older) has been fully vaccinated against COVID-19 [38]. Since the vaccines have significant potential to reduce COVID-19-associated morbidity and mortality among recipients and donors [39, 40] and to improve the mental health distress [41, 42], the high vaccination rate in Singapore and subsequent boosters, as indicated, may have the potential to reduce the psychological distress among recipients and donors as observed in the current study. Further studies are warranted to validate our findings.

To the best of our knowledge, this is the first study assessing psychological distress and associated factors among kidney transplant recipients and donors. We approached all kidney recipients and donors in our registry for study enrollment, and our results could be generalized to countries with similarly low COVID-19 transmission rates. In addition, we used a validated instrument (DASS-21) in assessing psychological distress, thus ensuring the validity of our study outcomes.

However, our study had several limitations. First, potential selection bias may exist as we recruited patients from a single medical center. However, our center is the largest kidney transplant program in Singapore and provides medical care to majority of kidney transplant recipients in Singapore. Second, we observed a low response rate for the current study (43.9% [41.3–46.8%]), which may be due to the lack of face-to-face communication. However, 40% response rate is not unusual for remotely administered anonymous surveys [43, 44]. Moreover, we accounted for a response rate of 40% in calculating the sample size, thus ensuring sufficient sample size and statistical power for the current analysis. Since all surveys were anonymous in the current study, we were not able to compare the characteristics between those we responded to our survey compared to those who did not. Third, the number of patients with psychological distress was relatively small; therefore, the power to demonstrate associations in multivariable adjusted analyses may be limited. Fourth, the present study did not have information on the graft function or immunosuppressive regimens, which may also impact the anxiety levels of transplant patients [45]. Fifth, the current study was a cross-sectional survey, and we could not adjust for baseline prevalence of psychological distress and mental health diagnoses; thus, the observed associations in the current study should be considered correlative not causative. Sixth, our results may not be generalizable to low-income settings where kidney recipients and donors may not receive sufficient medical care or countries with high COVID-19 transmission rates. In addition, some of the variables (e.g., having worries about physical or mental health, and feeling lonely and isolated) may not be entirely independent from symptoms of psychological distress; due to time constraints of the pandemic, we did not develop a pilot survey to standardize or validate all the questions in our study unlike the DASS-21 instrument and hence the results of those questions will require validation in other study populations. However, the primary outcome was based on the DASS-21 scale, which is validated for psychological distress and has been used previously in studies in Singapore [13].

In conclusion, we observed that at least one in ten kidney transplant recipients and donors suffered from psychological distress during COVID-19 pandemic. Younger age, unmarried status, non-Singapore residence, worse health conditions, and worrying about physical and mental health were associated with higher psychological distress. Malays (versus Chinese), taking precautionary measures (hand sanitization), and receiving enough information about COVID-19 were associated with lower psychological distress. Focused health education targeting younger adults, unmarried individuals, non-Singapore citizens, and those with worse health conditions could potentially prevent psychological distress in high-risk kidney transplant recipients and the donor population.