Outcomes and mortality of chronic haemodialysis patients in community-based dialysis centres in Singapore during the COVID-19 pandemic

INTRODUCTION The coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) arose in Wuhan, China, in December 2019[1] and spread rapidly worldwide. Singapore reported its first COVID-19 case on 23 January 2020 from an imported source, and local transmission in Singapore was reported on 4 Feb 2020. A surge in cases, the beginning of the first wave, began in early April 2020. Following on from the 2003 severe acute respiratory syndrome (SARS) outbreak, Singapore had a high level of overall pandemic preparedness and implemented wide-ranging public health measures as the number of COVID-19 cases increased.[2-4] Singapore was the first Asian country to approve the BioNTech/Pfizer COVID-19 vaccine (in December 2020)[5] and has a high vaccine uptake; as of 26 September 2022, the primary series of COVID-19 vaccination (with vaccines approved under the National Vaccination Programme only) was completed in 93% of the total population and 96% of the eligible population.[6] As of 20 September 2022, the number of confirmed COVID-19 cases recorded in Singapore was 1,876,584,[7] representing approximately 34% of the at-risk population (5,450,000).[8] Singapore has a low death rate of 0.1% for COVID-19-positive cases (1,608/1,876,584, as of 20 September 2022).[7] Chronic kidney disease (CKD) is a key risk factor for COVID-19 mortality,[9-11] and patients receiving maintenance haemodialysis (HD) are at increased risk for COVID-19 infection due to older age, comorbidities, immunocompromised status and frequent attendance at healthcare facilities.[12] This retrospective study reports the mortality rates and vaccination status from the National Kidney Foundation (NKF), Singapore, in patients with end-stage kidney disease (ESKD) receiving community-based HD treatment from the beginning of the pandemic to more than 2 years later. METHODS For this analysis, data were collected retrospectively from 1 February 2020 to 31 May 2022 from NKF Singapore for patients receiving community-based HD. As the analysis was a clinical audit of ongoing clinical services, it was exempt from institutional review board (IRB) approval. The NKF infection control team recorded its first COVID-19-positive case on 22 April 2020, and thereafter, each positive case and information on related hospitalisation and mortality were collected and reported by staff from each dialysis centre. There were 37 patients who contracted COVID-19 more than once; these patients were counted as single cases, and only their first positive infection episode was analysed. COVID-19 positivity was defined as any antigen rapid test-positive result, including patient-reported test results, or a polymerase chain reaction-positive test report received from any healthcare facility. Mortality due to COVID-19 was defined as death occurring during hospitalisation for patients admitted for COVID-19, patients who tested positive for COVID-19 during hospitalisation and patients who died at home or in other facilities (e.g. care home) due to COVID-19, in the opinion of a medical practitioner. There was no time frame defined for in-hospital mortality. RESULTS As of 31 May 2022, the total number of COVID-19-positive cases in HD patients (n = 5.504) was 1869 (33.5%). Patient demographics of COVID-19-positive cases (N = 1,869) are summarised in Table 1. Most patients were aged ≥61 years (66.5%), male (58.4%) and of Chinese ethnic origin (55.5%). Common comorbidities were hypertension (95.3%), diabetes mellitus (67.2%) and cardiovascular disease (52.3%). Diabetes mellitus was the most common cause of ESKD (58.2%).Table 1: Demographics of COVID-19-positive patients (N=1,869).Of all patients on HD, 4,651 (84.5%) received two vaccine doses, 75 (1.4%) were partially vaccinated (one dose), 3,511 (63.8%) received a booster dose and 838 (15.2%) were unvaccinated. mRNA vaccines were administered in all cases. Overall, 46.9% of patients with COVID-19 (n = 876) were hospitalised and there were 57 COVID-19-related deaths, representing 1.04% of the total cohort and 3.05% of COVID-19-positive patients. Of these, 45 deaths occurred before patients received their second dose of COVID-19 vaccination and 12 deaths occurred after patients received their second dose of vaccination. A further six patients died within 28 days of a COVID-19-positive result and, if included, would increase the total number of deaths to 63, or 1.1% of the total cohort and 3.4% of COVID-19-positive patients. Statistical analyses for COVID-19-related mortality rates by gender, ethnicity and age were conducted using the chi-square test. There was no statistically significant difference between males and females. Chinese, Malay, Indian and other races also did not show any differences [Table 2]. Patients aged >60 years had a higher mortality rate than those aged ≤60 years (odds ratio: 2.15, P = 0.022) [Table 2]. In addition to univariate analysis, a multivariate logistic regression model including demographics and other covariates, namely diabetes mellitus, hypertension and cardiovascular disease, revealed that age remained the only predominant predictor for mortality in our patient group after adjustment; the risk of death in patients aged >60 years was 2.14 times greater than in patients aged ≤60 years (odds ratio 2.14, 95% confidence interval [CI] 1.09–4.20, P = 0.026).Table 2: Mortality by gender, ethnicity and age.DISCUSSION Data in this study were collected retrospectively from patients receiving community-based dialysis treatment from the early stages of the COVID-19 outbreak in Singapore (February 2020) to May 2022. Approximately one-third of patients tested positive for COVID-19 over the study period, of whom 3.0% died. The overall mortality rate of the cohort was 1.0%. Deaths were considered as COVID-19-related by a positive test result on hospital admission or during hospitalisation, or death happening elsewhere considered by a medical practitioner to be due to COVID-19. As there was no time frame defined for in-hospital mortality, the mortality rate due to COVID-19 may be slightly overestimated. As COVID-19 vaccination in Singapore was initiated in December 2020, the study period spanned the pre- and post-vaccination periods. In keeping with the general Singaporean population, patients receiving HD have a high vaccine uptake, with 84.5% of patients receiving two vaccine doses. In HD patients, COVID-19 vaccination is effective in reducing infection, hospitalisation and death associated with COVID-19,[13,14] and these risks are reduced in home HD compared to outpatient HD.[15] Initial measures taken by NKF during the COVID-19 pandemic included a rapid transition to telemedicine service at NKF’s community-based dialysis centres,[16,17] amendments made to the Electronic Medical Record system and a universal shift for more frequent patient rounding by physicians. These measures avoided disruption to a patient’s dialysis treatment and ensured good medical outcomes for HD patients at NKF facilities during the pandemic. Other measures instituted were constant revision of triaging workflows for patients with confirmed or suspected COVID-19 and aligning staff shifts with their patients, empowering dialysis centre staff to make decisions and implement a rapid escalation process to the attending physician for urgent issues. The medical and nursing department underwent a systematic clinical governance exercise, where policy and procedures were reviewed, with adjustments made to cater to the unique issues being faced during the pandemic. An efficient communication mechanism was established between the heads of clinic teams at dialysis centres and those at either the hospital or national pandemic centres, to coordinate the movement and care of patients in a seamless manner. Sterilisation protocols for dialysis machines and at dialysis centres, and infection control testing for individual patients were escalated to more stringent standards. Personal protective equipment for clinical staff, support staff and patients was reviewed and escalated to meet the standards required to prevent COVID-19 spread at dialysis facilities. It is difficult to directly compare the low mortality rate observed in this study with the rates recorded from other countries or regions, due to differences in national policies, access to healthcare resources,[18] prevalence of COVID-19 in the general population, reporting criteria for COVID-19-related mortality and vaccine uptake rates. In addition, the timing of the period of study is highly variable: most published studies were in the pre-vaccination period (during 2020) when treatment of COVID-19 was evolving (dexamethasone, antivirals, neutralising monoclonal antibodies, etc.) and relatively few spanned both pre- and post-vaccination periods,[19-22] in common with the present study. These studies are reviewed briefly below. A retrospective cohort study in England analysed a national dataset of prevalent (n = 1,934,585) and incident (n = 144,969) CKD patients and reported respective SARS-CoV-2 infection rates of 6.7% and 7.8% in the first year of the pandemic. The 28-day COVID-19-related mortality rates were 1.8% and 1.7%, respectively.[19] A retrospective analysis of individual patient-level data in two Scottish cohorts included CKD (n = 14,054) and non-CKD (n = 72,910) patients who were tested for SARS-CoV-2 during a 13-month (1 February 2020 to 31 March 2021: Cohort 1) or an 11-month (28 February 2020 to 8 February 2021: Cohort 2) period. Although SARS-CoV-2-positive rates were comparable in CKD versus non-CKD patients in both Cohort 1 (12.5% vs. 9.7%) and Cohort 2 (10.5% vs. 8.8), the end-of-study COVID-19-related mortality rates were much higher in CKD compared to non-CKD patients in both Cohort 1 (36.8% vs. 13.6%) and Cohort 2 (36.8% vs. 11.6%).[20] A retrospective study in the Netherlands of patients hospitalised for COVID-19 (n = 4151) who were admitted from March 2020 to July 2021 included 389 patients with CKD (stages 2–5; treated with dialysis or kidney transplantation). Rates of 12-week mortality were significantly higher in patients with CKD stage 3a (46.7%), 3b (48.9%) and 4 (49.0%) compared to non-CKD patients (18.9%).[21] A retrospective analysis of all dialysis units in the West Bank of Palestine reported an incidence of COVID-19 among maintenance dialysis patients of 35.3% (548/1,554) during an 18-month period (5 March 2020 to 11 August 2021). Around half (50.2%) of the COVID-19-positive patients required hospitalisation, nearly a quarter (24.5%) were admitted to an intensive care unit, and the mortality rate (26.8%) was over 25-fold higher than that of the general population.[22] Although our analysis serves as an important record of COVID-19 and its effects on patients with ESKD in Singapore, it is limited by the fact that, due to logistical reasons, we were unable to break down and compare mortality rates by the time period (e.g. from 2020 to 2021 and from 2021 to 2022), or report mortality and infection rates before and after vaccines became widely available in Singapore. Moreover, our datasets were unable to capture mortality rates by severity (hospitalised vs. nonhospitalised). In conclusion, based on our analysis of COVID-19 cases and outcomes at NKF Singapore, our patients on HD had a relatively low mortality rate during the 28-month study period, which began at the start of the COVID-19 pandemic and continued for around 17 months after the COVID-19 vaccination programme was initiated. These findings may reflect Singapore’s overall pandemic preparedness and implementation of wide-ranging public health measures, including those initiated at HD centres. Nevertheless, despite the relatively low mortality rate, almost half of our patients on HD with COVID-19 were hospitalised during the pandemic. This observation highlights the greater burden of severe illness experienced by these immunocompromised patients and warrants further attention. Acknowledgement We thank Robert A Furlong (PhD) and David P Figgitt (PhD), ISMPP CMPP™, Content Ed Net, for providing medical writing support. We also thank the Infection Control Team, NKF Singapore, for providing COVID-19-related hospitalisation and mortality data. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.