Skip to main content
NCBI home page
PLOS One logoLink to PLOS One
. 2020 Oct 23;15(10):e0241263. doi: 10.1371/journal.pone.0241263

Sociodemographic features and mortality of individuals on haemodialysis treatment who test positive for SARS-CoV-2: A UK Renal Registry data analysis

Manuela Savino 1,*, Anna Casula 1, Shalini Santhakumaran 1, David Pitcher 1, Esther Wong 1, Winnie Magadi 1, Katharine M Evans 1, Fran Benoy-Deeney 1, James Griffin 1, Lucy Plumb 1,2, Retha Steenkamp 1,#, Dorothea Nitsch 1,3,4,#, James Medcalf 1,5,6,#
Editor: Muhammad Adrish7
PMCID: PMC7584244  PMID: 33095841

Abstract

Kidney disease is a recognised risk factor for poor COVID-19 outcomes. Up to 30 June 2020, the UK Renal Registry (UKRR) collected data for 2,385 in-centre haemodialysis (ICHD) patients with COVID-19 in England and Wales. Overall unadjusted survival at 1 week after date of positive COVID-19 test was 87.5% (95% CI 86.1–88.8%); mortality increased with age, treatment vintage and there was borderline evidence of Asian ethnicity (HR 1.16, 95% CI 0.94–1.44) being associated with higher mortality. Compared to the general population, the relative risk of mortality for ICHD patients with COVID-19 was 45.4 and highest in younger adults. This retrospective cohort study based on UKRR data supports efforts to protect this vulnerable patient group.

Introduction

Coronaviruses (CoVs) are important pathogens in both humans and other vertebrate animals. In their reservoirs, CoV infections mainly affect respiratory, gastrointestinal, liver and central nervous systems [1]. At the end of 2019, a novel coronavirus called Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) started spreading across the world, causing a substantive number of cases. The new infectious disease was named COVID-19.

Current evidence shows that comorbidities, such as diabetes, hypertension and chronic kidney disease, and advanced age, are risk factors associated with worse outcomes from COVID-19 [2–4]. Children appear to be less affected than adults [5, 6], although coexisting kidney disease is reported among cases of children requiring intensive care support [7].

A recent meta-analysis reported that patients with COVID-19 developing acute kidney injury had significant 4-fold increased risk of death than patients without acute kidney injury [8].

In-centre haemodialysis (ICHD) patients regularly visit hospital for their treatment and are at especially high risk, not just because of older age, kidney failure and higher frequency of comorbidities [9], but also because COVID-19 is more likely to spread among hospitalised patients [10]. Moreover, patients with end-stage kidney disease have impairment in both innate and adaptive immunity in uremic state with decreased endocytosis, impaired maturation of monocytes and dendritic cells and malfunction of toll-like receptors [11].

The aim of this retrospective cohort study was to describe the features and mortality of patients on ICHD in England and Wales who had laboratory-confirmed COVID-19.

Methods

On behalf of the Renal Association, the UK Renal Registry (UKRR) collects patient data without consent under section 251 from the Health Research Authority’s Confidentiality Advisory Group. The data were pseudonymised prior to being analysed. This study was approved by the North East Newcastle & North Tyneside 1 Research Ethics Committee (16/NE/0042).

Data on ICHD patients with a positive laboratory test for SARS-CoV-2 were collected by the UK Renal Registry (UKRR) between 26 March and 30 June 2020 using weekly returns from renal centres in England and Wales about each patient (NHS number, date of birth and date of positive test). This collection included all paediatric cases and covered the 18-week period from 3 March to 30 June.

Data were checked and NHS numbers validated, with queries returned to the submitting centre. Using NHS number and date of birth, the Demographics Batch Service was used to retrieve sex, postcode and date of death, if applicable, for every patient in England and Wales. Postcode was used to determine the lower super output area and the associated Index of Multiple Deprivation (IMD) [12].

The Demographics Batch Service is only available in the UK for England and Wales–it was therefore not possible to include in this analysis data from Northern Ireland and Scotland. In addition, Scotland only reports aggregated COVID-19 data to the UK Renal Registry (UKRR).

For survival analysis, patients with a test date after 23 June 2020 were excluded to allow for at least 7 days of follow-up time. Survival time was calculated from the date of positive test to either the date of death or the end of follow-up (30 June). Kaplan Meier unadjusted survival and Cox proportional-hazards models were used to describe survival and hazard ratios. The assumption of proportional hazards was tested and met for the Cox model. To investigate if vintage (time on renal replacement treatment) was associated with an increased risk of mortality, vintage was divided into 3 categories: pre-2016, 2016–2018 and 2019 onwards.

Relative risk of death for English ICHD patients by age and English NHS region were calculated using the England ICHD population (end of 2018, the most recent data available), England mid-year 2018 general population (based on the 2011 census), England ICHD COVID-19 deaths (3 March to 30 June) and England general population COVID-19 deaths (3 March to 30 June).

Analyses were performed using SAS version 9.4. Alpha level of 0.05 and two-sided tests were used throughout.

Results

At the end of 2018, there were 21,509 adult ICHD patients alive in England and Wales. Between 3 March and 30 June 2020, 50 of 51 renal centres in England and 5 of 5 in Wales reported 2,385 adult ICHD patients with COVID-19 to the UKRR. London had the highest percentage of ICHD patients with COVID-19 (18.7%), with a range of 10.4–24.0% among its 7 renal centres. The remaining regions ranged from 3.5%–12.2% of ICHD patients with COVID-19. Three COVID-19 cases in ICHD patients aged <18 years were reported from a prevalent paediatric ICHD cohort of 116 (2.6%).

Among adults, most patients with COVID-19 were aged 60–79 years (50.8%) and 18.5% were aged ≥80 years. 62.6% were male, which was just above the proportion of ICHD male patients in the UK (61.8%). A similar proportion of patients that tested positive for SARS-CoV-2 were from ethnic minorities (15.2% were Asian and 11.6% were Black), compared to the overall ICHD population in England and Wales (14.7% Asian and 11.9% Black, respectively) (Table 1).

Table 1. Demographic comparison between adult patients on ICHD in England and Wales at the end of 2018 and adult patients on ICHD in England and Wales with COVID-19 from 3 March to 23 June 2020.

Variable ICHD adults end 2018 (n = 21,509)a ICHD adults with COVID-19b (n = 2,385)c
Age, y
    Median (IQR) 67 (55–77) 68 (55–77)
    18–39 (%) 7 5
    40–59 (%) 27 26
    60–79 (%) 48 51
    ≥80 (%) 18 18
Male (%) 62 63
Ethnicity (%)
    White 69 70
    Asian 15 15
    Black 12 12
    Other 4 3
Most deprived quintile (%) 30 31
Open in a new tab

ICHD, in-centre haemodialysis

aPercentages exclude missing data: there were 3% of patients with missing ethnicity and <1% with missing deprivation.

bFor UK renal centres that submitted patients with COVID-19 to the UKRR.

cPercentages exclude missing data: there were 3% with missing ethnicity and 1% with missing deprivation.

dExcluded 3 patients aged <18 and 9 patients without at least 1 week follow-up.

Survival (unadjusted) at 1 week from the date of a positive SARS-CoV-2 test was 87.5% (95% CI 86.1–88.8%) and 80.0% at 2 weeks (95% CI 78.3–81.5%) (Fig 1).

Fig 1. Kaplan Meier unadjusted survival for Sars-CoV-2 positive patients—2-week survival.

Fig 1

Open in a new tab

There were no deaths in children. Patients on ICHD with COVID-19 aged ≥80 years had a mortality risk of about 4.2 times that of those aged 18–59 years (Table 2). There was weak evidence of males with COVID-19 on ICHD doing worse than females (HR 1.19, 95% CI 1.01–1.40). Asian patients on ICHD with COVID-19 had a borderline 16% higher mortality risk than White patients, with no difference seen between Black and White patients. Deprivation was not associated with mortality on ICHD and no interactions were observed. Patients on renal replacement treatment for more than 5 years had a 42% higher mortality risk compared to patients who started dialysis during the last year.

Table 2. Multivariable analysis of time to death amongst ICHD adult patients in England and Wales with COVID-19 positive test results, 3 March to 30 June 2020.

Variable No. of patients No. of deaths Hazard ratio 95% CI
Age, y
    18–59 718 86 1.00
    60–79 1,190 340 2.57 2.03–3.26
    ≥80 428 187 4.24 3.28–5.49
Sex
    Male 1,461 398 1.19 1.01–1.40
    Female 875 215 1.00
Ethnicity
    White 1,638 424 1.00
    Asian 353 107 1.16 0.94–1.44
    Black 277 60 0.86 0.65–1.14
    Other 68 22 1.36 0.89–2.10
Vintage
    <2016 887 276 1.42 1.15–1.75
    2016–18 788 196 1.12 0.90–1.39
    ≥2019 661 141 1.00
Open in a new tab

aAll variables in the table were mutually adjusted for each other.

bPatients with missing ethnicity data were excluded n = 49.

Compared to the general population in England with COVID-19, the relative risk of death in English ICHD patients with COVID-19 was 45.4 (95% CI 41.9–49.1), and decreased with age from a peak in the 20–39 years age group to 9.8 times the risk of death in the general population at ≥80 years (Table 3), with a high interregional variability.

Table 3. Relative risk of death for ICHD patients with COVID-19 by age group and NHS region in England.

Variable England COVID-19 death rate per 10,000a ICHD COVID-19 death rate per 10,000b Relative risk
ICHD/England COVID-19 death rates 95% CI
Age, y
    20–39 0.1 60.5 432 213.4–873
    40–59 1.5 143.4 94.1 75.1–118
    60–79 10.5 346.9 33.1 29.7–36.9
    ≥80 55.7 548.5 9.8 8.5–11.3
Region
    East of England 5.4 253.2 46.7 33.5–65.2
    London 6.9 433.3 63.2 55.8–71.7
    Midlands 5.4 293.7 54.6 45.7–65.2
    North East & Yorkshire 5.2 267.7 51.5 40.9–65
    North West 6.5 223.7 34.5 26.1–45.8
    South East 3.7 276.5 73.9 57.3–95.2
    South West 2.3 130.6 57.7 36.8–90.5
Open in a new tab

ICHD, in-centre haemodialysis

aNumber of deaths recorded 3 March to 30 June 2020 in England divided by the England mid-2018 population estimate.

bNumber of deaths recorded 3 March to 30 June 2020 in the English ICHD population divided by the end-2018 prevalent English ICHD population.

Discussion

The relative risk of death associated with COVID-19 among ICHD patients was much higher than that of the general population in England, especially among those of younger age. So far, and in contrast to the adult population, no deaths have been reported in paediatric patients aged <18 years. There was borderline evidence both for males with COVID-19 on ICHD doing worse than females and Asian patients having a 16% higher mortality than White patients.

As observed in other countries, to now, most deaths in the UK have been in people aged ≥50 years, with 55% of these males [13]. Data from the UK Intensive Care National Audit and Research Centre, indicate that among patients with COVID-19 admitted to intensive care, 1.7% had a history of kidney replacement therapy, 70.3% were male and there was an over-representation of those of Asian and Black ethnicities [14], similar to what we report for the ICHD population.

ICHD increases the risk of transmission of infection among patients and the high relative risk of death among younger individuals with COVID-19 on ICHD highlights their extreme vulnerability.

Despite level of deprivation correlating to the percentage of ICHD patients with COVID-19, deprivation was not a major predictor of mortality from COVID-19 on ICHD.

Previous studies have demonstrated the effects of length of time spent on dialysis treatment (vintage) on mortality, concluding that prolonged dialysis increases the mortality risk of patients receiving haemodialysis [15, 16]. A few studies have also shown the specific association between length of time on dialysis and higher risk for infection-related mortality [17, 18].

Moreover, a recent retrospective cohort study in a single centre in Spain analysed the clinical course and outcomes of 36 maintenance haemodialysis patients hospitalised with COVID-19 during the period March to April 2020. The authors concluded that none of the classical cardiovascular risk factors in the general population were associated with higher mortality, and that compared to survivors, non-survivors had significantly longer dialysis vintages [19]. In line with these results, in our study we found a positive association between treatment vintage and survival of ICHD patients with COVID-19.

To better understand the potentially higher mortality from COVID-19 seen for the Asian group, but not in the Black group, other factors such as comorbidities and their effect on survival of COVID-19 patients should be investigated. People of Asian origin are the UK’s largest ethnic minority in several cities [20] and type 2 diabetes is up to 6 times more common in Asian than White people [20, 21], which translates to a higher prevalence of diabetes as a cause of requiring ICHD [22].

Although the multivariable analysis was controlled for important factors related to the outcomes, the possibility of residual confounding from unmeasured variables cannot be excluded. We were unable to adjust for comorbidities and/or biochemical data for which both factors detailed comparison data for the general population were not available at the time of our analysis.

Moreover, we could not compare to other treatment modalities, such as peritoneal dialysis or transplantation, because reporting of COVID-19 in these populations is currently unreliable but may be better investigated in future thanks to development of further linkage of UKRR dataset to the national test result data. Data on mortality in ICHD patients as a result of causes not directly related to COVID-19 were not available, but in the future will explain the real burden of mortality associated with COVID-19 among ICHD patients in the UK.

Conclusions

Despite some limitations, results of this study show the extremely high relative mortality of COVID-19 patients on ICHD and are important to support collective efforts to minimise risk of transmission in this very vulnerable patient group.

Acknowledgments

We thank staff at all adult and paediatric renal centres in the UK who submit data to the UKRR and who care for kidney patients affected by COVID-19. We are also grateful to the Renal Association COVID-19 National Renal Data Coordinating Group for their guidance on this analysis: Paul Cockwell, Ron Cullen, Rachel Gair, Daniel Gale, Matt Graham-Brown, Thomas Hiemstra, Toby Humphrey, Carol Inward, Rachel Johnson, Graham Lipkin, Fiona Loud, Stephen Marks, Lisa Mumford, Matthew Robb, Adnan Sharif, Neil Sheerin, Laurie Tomlinson and Charlie Tomson.

Data Availability

The data underlying the results are available from the UK RENAL registry (contact ukrr-research@renalregistry.nhs.uk) for researchers who meet the criteria for access to confidential data.

Funding Statement

The author(s) received no specific funding for this work.

References

  • 1.Xu J, Zhao S, Teng T, Abdalla AE, Zhu W, Xie L, et al. Systematic comparison of two animal to human transmitted human coronaviruses: SARS-CoV-2 and SARS-CoV. Viruses. 2020; 12(2): 244. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Wu Z, McGoogan J. Characteristics of and Important Lessons from the Coronavirus Disease 2019 (COVID 2019) Outbreak in China: Summary of a Report of 72,314 Cases from the Chinese Centre for Disease Control and Prevention. JAMA. 2020; 323(13): 1239–1242. 10.1001/jama.2020.2648 [DOI] [PubMed] [Google Scholar]
  • 3.Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020; 395(10229): 1054 10.1016/S0140-6736(20)30566-3 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Li LQ, Huang T, Wang YQ, Wang ZP, Liang Y, Huang TB, et al. COVID-19 patients' clinical characteristics, discharge rate, and fatality rate of meta-analysis. J. Med. Virol. March 2020. 10.1002/jmv.25757 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Ludvigsson JF. Systematic review of COVID‐19 in children shows milder cases and a better prognosis than adults. Acta Paediatr. Mar 2020. 10.1111/apa.15270 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Lee PI, Hu YL, Chen PY, Huang YC, Hsueh PR. Are children less susceptible to COVID-19? J. Microbiol. Immunol. February 2020. 10.1016/j.jmii.2020.02.011 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Lu X, Zhang L, Du H, Zhang J, Li YY, Qu J, et al. SARS-CoV-2 infection in children. N. Engl. J. Med. April 2020. 10.1056/NEJMc2005073 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Ali H, Daoud A, Mohamed MM, Salim SA, Lenar Yessayan L, Baharani J, et al. Survival rate in acute kidney injury superimposed COVID-19 patients: a systematic review and meta-analysis. Ren. Fail. 2020; 42(1): 393–7. 10.1080/0886022X.2020.1756323 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk factors associated with Acute Respiratory Distress Syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Inter. Med. May 2020. 10.1016/j.kint.2020.0994 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Naicker S, Yang CW, Hwang SJ, Liu BC, Chen JH, Jha V. The novel coronavirus 2019 epidemic and kidneys. Kidney Int. May 2020. 10.1016/j.kint.2020.03.001 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Salim AS, Akula YV, Noszály NB, Afshan S, Agarwal M, Fülöp T. Potential role of plasmapheresis in severe cytomegalovirus infection with ongoing immunomediated hemolysis and low complement level. J Renal Inj Prev. 2017; 7(3): 206–10. [Google Scholar]
  • 12.Noble M, Wright G, Smith G, Dibben C. Measuring multiple deprivation at the small-area level. Environ Plann A. 2006; 38: 169–85. [Google Scholar]
  • 13.Office for National Statistics. Weekly provisional figures on deaths registered in the UK. 2020. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/datasets/weeklyprovisionalfiguresondeathsregisteredinenglandandwales [Accessed 16 July 2020].
  • 14.Intensive Care National Audit and Research Centre. ICNARC Case Mix Programme Database 2020. Available from: https://www.icnarc.org/Our-Audit/Latest-News/2020/04/10/Report-On-3883-Patients-Critically-Ill-With-Covid-19 [Accessed 16 July 2020]. [DOI] [PMC free article] [PubMed]
  • 15.Chertow GM, Johansen KL, Lew N, Lazarus M, Lawrie EG. Vintage, nutritional status, and survival in hemodialysis patients. Kidney Int. 2000; 57: 1176–1181. 10.1046/j.1523-1755.2000.00945.x [DOI] [PubMed] [Google Scholar]
  • 16.Iseki K, Tozawa M, Takishita S. Effect of the duration of dialysis on survival in a cohort of chronic haemodialysis patients. Nephrol Dial Transplant. 2003; 18: 782–787. 10.1093/ndt/gfg145 [DOI] [PubMed] [Google Scholar]
  • 17.Sumida K, Yamagata K, Iseki K, Tsubakihara Y. Different impact of hemodialysis vintage on cause-specific mortality in long-term hemodialysis patients, Nephrol Dial Transplant. 2016; 31(2): 298–305. 10.1093/ndt/gfv402 [DOI] [PubMed] [Google Scholar]
  • 18.Allon M, Depner TA, Radeva M, Bailey J, Beddhu S, Butterly D, et al. Impact of dialysis dose and membrane on infection-related hospitalization and death: Results of the HEMO Study. J Am Soc Nephrol. 2003; 14: 1863–1870. 10.1097/01.asn.0000074237.78764.d1 [DOI] [PubMed] [Google Scholar]
  • 19.Goicoechea M, Sánchez Cámara LA, Nicolás Macías N, Munoz de Morales A, Gonzalez Rojas A, Bascunana A, et al. COVID-19: clinical course and outcomes of 36 hemodialysis patients in Spain. Kidney Int. 2020; 98(1): 27–34. 10.1016/j.kint.2020.04.031 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Dixon AN, Raymond NT, Mughal S., Rahim A, O’ Hare JP, Kumar S, et al. Prevalence of microalbuminuria and hypertension in South Asians and white Europeans with type 2 diabetes: a report from the United Kingdom Asian Diabetes Study (UKADS). Diabetes Vasc. Dis. Res. 2006; 3(1): 22–25. [DOI] [PubMed] [Google Scholar]
  • 21.Mather HM, Chaturvedi N, Kehely AM. Comparison of prevalence and risk factors for microalbuminuria in South Asians and Europeans with Type 2 diabetes mellitus. Diabet. Med. 2018; 15(8): 672–677. [DOI] [PubMed] [Google Scholar]
  • 22.Udayaraj U, Pruthi R, Casula A, Roderick P. UK Renal Registry 16th Annual Report: Chapter 6 Demographics and outcomes of patients from different ethnic groups on renal replacement therapy in the UK. Nephron Clin Pract. 2013; 125: 111–125. 10.1159/000360025 [DOI] [PubMed] [Google Scholar]

Decision Letter 0

Muhammad Adrish

Transfer Alert

This paper was transferred from another journal. As a result, its full editorial history (including decision letters, peer reviews and author responses) may not be present.

4 Aug 2020

PONE-D-20-21371

Sociodemographic features and mortality of individuals on haemodialysis treatment who test positive for SARS-CoV-2: a UK Renal Registry data analysis

PLOS ONE

Dear Dr. Savino,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

==============================

ACADEMIC EDITOR: I have received the comments of the reviewers on your manuscript. The specific comments of the reviewers are included below. Please provide point by point response in your revised manuscript.

==============================

Please submit your revised manuscript by due date. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Muhammad Adrish

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. We suggest you thoroughly copyedit your manuscript for language usage, spelling, and grammar. If you do not know anyone who can help you do this, you may wish to consider employing a professional scientific editing service.  

Whilst you may use any professional scientific editing service of your choice, PLOS has partnered with both American Journal Experts (AJE) and Editage to provide discounted services to PLOS authors. Both organizations have experience helping authors meet PLOS guidelines and can provide language editing, translation, manuscript formatting, and figure formatting to ensure your manuscript meets our submission guidelines. To take advantage of our partnership with AJE, visit the AJE website (http://learn.aje.com/plos/) for a 15% discount off AJE services. To take advantage of our partnership with Editage, visit the Editage website (www.editage.com) and enter referral code PLOSEDIT for a 15% discount off Editage services.  If the PLOS editorial team finds any language issues in text that either AJE or Editage has edited, the service provider will re-edit the text for free.

Upon resubmission, please provide the following:

  • The name of the colleague or the details of the professional service that edited your manuscript

  • A copy of your manuscript showing your changes by either highlighting them or using track changes (uploaded as a *supporting information* file)

  • A clean copy of the edited manuscript (uploaded as the new *manuscript* file)

3. In the ethics statement in the manuscript and in the online submission form, please provide additional information about the patient records used in your retrospective study, including: a) whether all data were fully anonymized before you accessed them; and b) the source of the medical records analyzed in this work (e.g. hospital, institution or registry name).

4. To comply with PLOS ONE submission guidelines, in your Methods section, please provide additional information regarding your statistical analyses. For more information on PLOS ONE's expectations for statistical reporting, please see https://journals.plos.org/plosone/s/submission-guidelines.#loc-statistical-reporting.

5. PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. Please see the following video for instructions on linking an ORCID iD to your Editorial Manager account: https://www.youtube.com/watch?v=_xcclfuvtxQ

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

Reviewer #3: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: Yes

Reviewer #3: I Don't Know

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This analysis tries to identify factors associated with mortality in a group of 1173 HD patients infected with COVID.

The objective of this study is to evaluate the survival of HD patients after 1 week and 2 weeks of positive diagnosis of SARS-COV-2.

Unadjusted survival at 1 week was 89%. (mortality was 11%)

Unadjusted survival at 2 weeks was 81% (mortality was 19%)

.

The main conclusion is that the relative risk of death associated with COVID -19 in HD patients was much higher that of the general population in England.

What were the factors associated with COVID infection?

The authors analyzed only age, gender and ethnicity.

For a global analysis of mortality, in a multivariable analysis, other factors that are classically associated with higher risk of death in dialysis patients, should also have been included: time on dialysis, diabetes, albumin, CRP, phosphate levels, etc.

In my opinion, though interesting, this analysis is merely descriptive.

I had not access to the Kaplan Meyer curve.

Reviewer #2: Technically sound well written with appropriate statistical analysis. It would have been interesting to know the association of diabetes as it effected various socio-demographic groups and whether is was the main a factor for high mortality in Asian population.

Reviewer #3: Author has made an reasonable attempt to publish mortality of COVID-19 in Incentre hemodialysis patients using UKRR which has not been published before. Overall the paper reads well but I would recommend a few suggestions as below.

1. Page 3 under Introduction, 2nd paragraph please add "A recent meta-analysis reported that patients with COVID-19 developing acute kidney injury had significant 4-fold increased risk of death than patients without acute kidney injury".

Please cite paper: Survival rate in acute kidney injury superimposed COVID-19 patients: a systematic review and meta-analysis. Renal Failure. 2020 Jan 1;42(1):393-7.

2. It would be good to add in the introduction that patients with ESRD have relative immunodeficiency. I would recommend adding the following sentence to Page 3 under introduction, Paragraph 3. "ESRD patients have impairment in both innate and adaptive immunity in uremic state with decreased endocytosis, impaired maturation of monocytes and dendritic cells and malfunction of toll-like receptors contributing to relative immunodeficiency"

Please cite paper: Potential role of plasmapheresis in severe cytomegalovirus infection with ongoing immunemediated hemolysis and low complement level. Journal of Renal Injury Prevention. 2017 Sep 8;7(3):206-10.

3. Why do we think asian patients have higher mortality. I see that you have explained in the paper to a certain extent. But curious to know what age group would asians mostly fit into? Was obesity a known factor in these patients? I see that asians mostly had diabetes which by itself is a higher comorbid condition. I hope we are not biased by the fact that there is missing data on ethnicity of 22% of patients and overestimating the effect or the fact that we were unable to adjust for comorbidities?

4. Completely agree that higher age >80 mortality is very high and is a good point highlighted in the paper.

5. Would recommend adding a few lines of Conclusion after discussion part highlighting points.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Teresa Adragão

Reviewer #2: Yes: Aasim Ahmad

Reviewer #3: Yes: Sohail Abdul Salim

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2020 Oct 23;15(10):e0241263. doi: 10.1371/journal.pone.0241263.r002

Author response to Decision Letter 0

21 Sep 2020

Comments Reviewer 1:

1) This analysis tries to identify factors associated with mortality in a group of 1173 HD patients infected with COVID.

The objective of this study is to evaluate the survival of HD patients after 1 week and 2 weeks of positive diagnosis of SARS-COV-2.

Unadjusted survival at 1 week was 89%. (mortality was 11%)

Unadjusted survival at 2 weeks was 81% (mortality was 19%)

The main conclusion is that the relative risk of death associated with COVID -19 in HD patients was much higher that of the general population in England.

What were the factors associated with COVID infection?

The authors analyzed only age, gender and ethnicity.

Author's response:

We thank the reviewer for the thorough review of our paper and believe her input has been important in making our paper more balanced.

The reviewer’s comment raises the important point related to factors associated with Covid-19 infection. While we agree that other risk factors are important, we do not have comparative data for the general population, because these were not reported to Public Health England at the time of our analysis. Therefore, even if we had had data on other factors to include, such as comorbidities, we could not have used them for a comparison with the general population. Additionally, our data on comorbidities for the ICHD population are currently incomplete and need linkage to hospital records to augment them.

We have highlighted this issue in the discussion.

2) For a global analysis of mortality, in a multivariable analysis, other factors that are classically associated with higher risk of death in dialysis patients, should also have been included: time on dialysis, diabetes, albumin, CRP, phosphate levels, etc.

In my opinion, though interesting, this analysis is merely descriptive.

Author's response: We agree that our analysis is descriptive, but nevertheless it was instrumental in prompting the UK government to change policy on shielding of dialysis patients, because of the stark difference in mortality between the ICHD and general populations.

This revised version of our paper now also includes a much larger cohort of 2,385 ICHD patients up to 30 June 2020 and our findings confirm a striking higher relative risk of mortality (45.4 times higher) of dialysis patients compared to the general population (this change is tracked in both the methods and Table 3 in results). We therefore think that our analysis has an important contribution to the epidemiological question regarding whether dialysis patients are different in risk of mortality compared to the general population.

Among the additional factors listed associated with higher risk of death in dialysis patients, we could only adjust our analysis for dialysis vintage and found a positive association. This is now highlighted in the methods sessions and in the results session (Table 2). The importance of these findings has been highlighted in the discussion too. We have highlighted in the discussion possible limitations related to remaining unmeasured confounders.

3) I had not access to the Kaplan Meyer curve.

Author's response: Thank you for the important point raised about the Kaplan-Meier curve which is now available as Figure 1 in the results.

Comments Reviewer 2:

1) Technically sound well written with appropriate statistical analysis.

Author' s response: We thank the reviewer for the thoughtful review of our work and kind words.

2) It would have been interesting to know the association of diabetes as it effected various socio-demographic groups and whether is was the main a factor for high mortality in Asian population.

Author's response: Unfortunately, we did not have a break down for diabetes status and ethnicity for the general population as at the time of our analysis these data were not available from Public Health England. Moreover, our data on dialysis patients' diabetes status are currently incomplete and require linkage with hospital records, which is being addressed but beyond the scope of this paper. We have highlighted this issue in our discussion.

Comments Reviewer 3:

1) Author has made a reasonable attempt to publish mortality of COVID-19 in Incentre hemodialysis patients using UKRR which has not been published before. Overall, the paper reads well but I would recommend a few suggestions as below.

1. Page 3 under Introduction, 2nd paragraph please add "A recent meta-analysis reported that patients with COVID-19 developing acute kidney injury had significant 4-fold increased risk of death than patients without acute kidney injury".

Please cite paper: Survival rate in acute kidney injury superimposed COVID-19 patients: a systematic review and meta-analysis. Renal Failure. 2020 Jan 1;42(1):393-7.

2. It would be good to add in the introduction that patients with ESRD have relative immunodeficiency. I would recommend adding the following sentence to Page 3 under introduction, Paragraph 3. "ESRD patients have impairment in both innate and adaptive immunity in uremic state with decreased endocytosis, impaired maturation of monocytes and dendritic cells and malfunction of toll-like receptors contributing to relative immunodeficiency"

Please cite paper: Potential role of plasmapheresis in severe cytomegalovirus infection with ongoing immunemediated hemolysis and low complement level. Journal of Renal Injury Prevention. 2017 Sep 8;7(3):206-10.

Author's response: We thank the reviewer for his thoughtful and thorough review. We have thoroughly re-reviewed the manuscript and accepted his suggestions. Both citations were added to the introduction.

2) Why do we think Asian patients have higher mortality? I see that you have explained in the paper to a certain extent. But curious to know what age group would Asians mostly fit into?

Author's response: We thank the reviewer for the points and observations raised. The variables included in the multivariable model are adjusted for each other. Additionally, to respond to the point raised, while we know that the total Asian prevalent ICHD population is younger compared to the White population, we found that in the COVID-19 positive cohort the median age of the Asian group is the same as that of the White group. We attach to this response letter supplementary tables related to these analyses.

3) Was obesity a known factor in these patients?

Author's response: A primary aim was to compare the risk between dialysis patients and the general population and general population data we had access to did not report ethnicity or BMI. Moreover, BMI data at dialysis start are incomplete. BMI is known to not show the usual associations with death on dialysis [1] so we believe that it is unlikely to explain associations seen.

1. Kalantar-Zadeh K, Rhee CM, Chou J, et al. The Obesity Paradox in Kidney Disease: How to Reconcile it with Obesity Management. Kidney Int Rep. 2017;2(2):271-281. doi:10.1016/j.ekir.2017.01.009

4) I see that Asians mostly had diabetes which by itself is a higher comorbid condition. I hope we are not biased by the fact that there is missing data on ethnicity of 22% of patients and overestimating the effect or the fact that we were unable to adjust for comorbidities?

Author's response: For comparisons of those on ICHD with and without Covid-19 these more detailed analyses are beyond the scope of this paper as we require linkage to hospital records to address missing comorbidity data.

This analysis is descriptive, and we did not explore comorbidities in detail. In this revised version of our paper we have also updated the cohort to the 30th of June including 2,385 ICHD patients and reduced missing ethnicity data in the previous cohort (from 22% to 3%). Findings from the updated version confirm a striking higher relative risk of mortality of dialysis patients compared to the general population of 45.4 and still confirm a borderline association between the Asian group and risk of mortality which is 16% higher than the risk of the White group.

5) Completely agree that higher age >80 mortality is very high and is a good point highlighted in the paper.

Author's response: We thank the reviewer for his support.

6) Would recommend adding a few lines of Conclusion after discussion part highlighting points.

Author's response: We thank the reviewer for this suggestion and added a Conclusion section to highlight the key points of our manuscript.

Attachment

Submitted filename: Response_letter_14092020.docx

Click here for additional data file. (54.6KB, docx)

Decision Letter 1

Muhammad Adrish

13 Oct 2020

Sociodemographic features and mortality of individuals on haemodialysis treatment who test positive for SARS-CoV-2: a UK Renal Registry data analysis

PONE-D-20-21371R1

Dear Dr. Savino,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Muhammad Adrish

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

You have satisfactorily answered all the queries that have been raised by the reviewers.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: Thank you for addressing our comments and suggestions and explaining the reasons for those that could not be addressed

Reviewer #3: Thank you for addressing the concerns and incorporating my suggestions into the paper. Paper reads well at this time.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: Yes: Professor Aasim Ahmad

Reviewer #3: No

Acceptance letter

Muhammad Adrish

16 Oct 2020

PONE-D-20-21371R1

Sociodemographic features and mortality of individuals on haemodialysis treatment who test positive for SARS-CoV-2: a UK Renal Registry data analysis

Dear Dr. Savino:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Muhammad Adrish

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    Attachment

    Submitted filename: Response_letter_14092020.docx

    Click here for additional data file. (54.6KB, docx)

    Data Availability Statement

    The data underlying the results are available from the UK RENAL registry (contact ukrr-research@renalregistry.nhs.uk) for researchers who meet the criteria for access to confidential data.

    Articles from PLoS ONE are provided here courtesy of PLOS

    RESOURCES