Symposium 5.2 – COVID-19 in haemodialysis patients

Symposium Summary

Written by Jasna Trbojevic-Stankovic
All the speakers reviewed and approved the contents

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Prevention strategies for minimizing SARS-CoV-2 infection in dialysis facilities

Mario Cozzolino, Italy

The coronavirus disease 19 (COVID-19) initially emerged in China on December 8, 2019, and has since rapidly spread across the globe putting an enormous strain on healthcare systems worldwide. The disease is caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and in the majority of cases remains asymptomatic or only mildly symptomatic. Nevertheless, around 10% of the affected individuals develop severe respiratory symptoms requiring intensive care. According to the latest data the mortality rate among hospitalized patients is around 12%.

Impaired kidney function has emerged as an important factor for adverse outcomes in COVID-19 patients, along with older age, hypertension, type-2 diabetes, cardiovascular disease, and dementia. Patients on in-centre haemodialysis (HD) are particularly vulnerable since they must come together thrice weekly for the treatments and because they are at higher risk of complication and death due to older age and multiple comorbidities. For this reason, guidance has been provided by the proper authorities on how to best protect this population. All guidance emphasizes the importance of hand and respiratory hygiene, coughing etiquette, use of personal protective equipment (PPE), suggest active screening for the most common symptoms – fever, new cough, or dyspnoea; and establishing a triage protocol before patients arrive at the dialysis facility. Nevertheless, discrepancies exist concerning the suggested management of symptomatic or infected HD patients. While the majority of guidelines agree that multiple confirmed or suspected cases should be cohorted and cared for by designated staff, some also advise hospitalization and admission to an airborne infection isolation room, others recommend admission to infectious disease ward, and some suggest that positive but clinically stable HD patients can resume dialysis in designated outpatient units or dialysis shift, an isolation room, or merely a separate room with the door closed. It is generally agreed that being on chronic dialysis per se should not limit critically ill patients’ access to intensive care, but directives in favour of or against intubation could be proposed on a case-by-case basis to frail and elderly patients or their relatives.

Figure 1. General prophylactic measures and pathways for high-risk patients 

The spread of the COVID-19 pandemic has highlighted the importance of limiting social activities to hinder the risk of exposure to the virus. This has emphasized considering home-based renal replacement therapies as possible advantageous alternatives to the in-centre HD. Besides peritoneal dialysis, home HD is also a reasonable choice due to the advantage of the isolation of patients but requires systemic measures to implement the program.

Infection control in dialysis units

Patricia De Sequera, Spain

Spain was one of the most affected European countries in the current COVID-19 pandemic, and Madrid was the national epicentre. The epidemic evolved through four waves, with the first one exhibiting the highest peak, facing the city with one of the most draconian lockdowns in Europe and a collapse of the city’s public hospital system. This situation has also affected the highly vulnerable group of haemodialyzed patients, among whom in the University Hospital Infanta Leonor, 13% were immigrants or refugees and 17% were older than 80 years putting them at especially high risk of a more severe form of the disease.

A steep and sudden rise in the number of infected HD patients in the first wave of the pandemic in Madrid elicited a prompt response. Dialysis units were reorganized to assure a safe distance between the patients in the waiting areas and create designated posts for seropositive patients. Within days a protocol of action has been presented to the staff and everyone underwent training for placement and removal of PPE. An information sheet containing facts on COVID-19, preventive measures, and instructions on what to do in case of suspected infection were delivered to all dialysis patients. An active triage, which included temperature check and screening for respiratory symptoms, myalgia, and diarrhoea, was set up at the entrances to the dialysis units. Patients were advised to use masks at all times and change them frequently. Public transport and collective ambulances were identified as potential high-risk sites for disease spreading and patients were advised to use individual means of transport. All HD patients and their companions were issued documents for circulation to allow them to reach dialysis units during lockdowns. Snacks during dialysis were withdrawn eventually. Infected patients were dialyzed by designated staff members who did not attend to non-COVID patients. Treatment protocols ensued for infected patients who did not require hospitalization.

In the first wave of COVID-19, a high percentage of asymptomatic HD patients was identified by active screening, thus underlining the importance of the proactive approach in this particular population. Also important is the fact that 20% of the dialysis staff had required sick leave in this period in relation to COVID-19, and as many as 40% had positive antibodies against SARS-CoV-2. The lack of appropriate PPE was the single factor significantly associated with COVID-19 infection among Spanish nephrologists, coinciding with the fact that the majority of these professionals got infected in the first pandemic wave, more specifically in the first month.

Figure 2. Risk factors for COVID-19 infection among nephrologists in Spain

The development of vaccines brought up other questions. Initial reports communicated that the decline of anti-SARS-CoV-2 antibodies appeared to be more rapid in HD patients, especially the asymptomatic ones, compared to the general population. More recent studies, however, conclude that HD patients mount durable immune responses six months post SARS-CoV-2 infection, with fewer than 3% of patients showing no evidence of humoral or cellular immunity. Thanks to the initiative undertaken by the Spanish Society of Nephrology HD patients in Spain were placed high on the priority list for vaccination and the complete Spanish HD population has been successfully vaccinated. The currently ongoing follow-up shall provide insight into the level of protection from the infection and serious forms of the disease this vaccination has provided.

Outcomes in dialysis patients infected with SARS-CoV-2

Marian Goicoechea, Spain

Initial reports on the epidemiology of COVID-19 identified older age, male sex, obesity, hypertension, diabetes, cardiovascular disease, and chronic lung disease as major mortality risk factors. More recently, however, it became clear that a graded association exists between the level of kidney dysfunction and the risk of COVID-19 mortality. Studies have even demonstrated that severe forms of CKD were associated with a higher risk of COVID-19 mortality than other known high-risk groups.

Spain was among the most affected countries by the COVID-19 pandemic in Europe with 3,636,000 cases and nearly 80,000 deaths confirmed by May 2021. As of May 2020, a Spanish COVID-19 registry started collecting data on end-stage renal disease (ESRD) patients who contracted COVID and within a year gathered data on 5,155 cases. The population registered was old (mean age 65 years), with a notable male preponderance. Mostly affected were haemodialyzed patients, followed by the transplanted ones. The mortality rate ranged from as low as 3% for the non-hospitalized patients, to as high as 63% for patients who required intensive care. Haemodialyzed patients exhibited a higher overall mortality rate than the transplanted ones. Older age was remarkably associated with mortality in hospitalized patients, especially in the transplanted group, but no clear correlation was found between mortality and patients’ sex. Clinical features at admission associated with the 30-day-in-hospital mortality adjusted by age and dialysis vintage were dyspnoea, pneumonia, and need for mechanical ventilation. The main laboratory parameters associated with mortality in hospitalized HD patients were low lymphocyte count and high LDH, and total bilirubin and CRP levels at day 7 after clinical onset.

It is encouraging that the mortality rate among HD patients decreased by half in the second and third waves of the pandemic. Also, the ratio of hospitalized to non-hospitalized patients declined over time, thus suggesting a reduction in the burden to healthcare resources. These results corresponded well with the data collected in the ERACODA registry, the database that has been established by the ERA-EDTA to collect individual-level data of patients that receive kidney replacement therapy and have COVID-19.

Figure 3. Predictors of mortality in COVID-19 patients on maintenance haemodialysis

The approach to treatment has also changed over time, as certain therapeutics gained or lost popularity in particular waves of the pandemic. Hydroxychloroquine, for example, was commonly applied in the first wave, but never in the later waves. On the other hand, corticosteroids use shows a steady increase over time. Unfortunately, none of the treatments used so far has shown superior results in reducing mortality. Even the administration of convalescent plasma has not significantly contributed to outcome improvement. Only the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization.

The monoclonal antibodies – bamlanivimab, etesevimab, casirivimab, and imdevimab, which have been recently authorized for COVID treatment in the United States of America, decrease viral load when administered early in the course of the disease and favourably impact clinical outcomes in patients with mild to moderate disease presentation. Still, their effect in patients with chronic kidney disease is yet to be investigated.

Further reading

Kliger AS, Cozzolino M, Jha V, Harbert G, Ikizler TA. Managing the COVID-19 pandemic: international comparisons in dialysis patients. Kidney Int. 2020;98(1):12-16. doi: 10.1016/j.kint.2020.04.007.

Priori A, Baisi A, Banderali G, et al. The Many Faces of Covid-19 at a Glance: A University Hospital Multidisciplinary Account From Milan, Italy. Front Public Health. 2021;8:575029. doi: 10.3389/fpubh.2020.575029.

Cozzolino M; ERA-EDTA Council. ERA-EDTA sharing Milan experience on coronavirus management in dialysis centres. Clin Kidney J. 2020;13(3):473-474. doi: 10.1093/ckj/sfaa050.

Cozzolino M, Conte F, Zappulo F, Ciceri P, Galassi A, Capelli I, Magnoni G, La Manna G. COVID-19 pandemic era: is it time to promote home dialysis and peritoneal dialysis? Clin Kidney J. 2021;14(Suppl 1):i6-i13. doi: 10.1093/ckj/sfab023.
Galassi A, Magagnoli L, Cozzolino M; COVID-19 Renal Working Group at ASST Santi Paolo & Carlo in Milan. COVID-19 in a dialysis center in Milan from March to June 2020: understanding how to respond to the second wave of the pandemic. J Nephrol. 2021;34(1):11-14. doi: 10.1007/s40620-020-00933-8.

Albalate M, Arribas P, Torres E; Grupo enfermería HUIL. High prevalence of asymptomatic COVID-19 in haemodialysis: learning day by day in the first month of the COVID-19 pandemic. Nefrologia (Engl Ed). 2020;40(3):279-286. English, Spanish. doi: 10.1016/j.nefro.2020.04.005.

Quiroga B, Sánchez-Álvarez E, Ortiz A; Spanish Society of Nephrology. Suboptimal personal protective equipment and SARS-CoV-2 infection in Nephrologists: a Spanish national survey. Clin Kidney J. 2021;14(4):1216-1221. doi: 10.1093/ckj/sfab009.

Clarke CL, Prendecki M, Dhutia A, et al. Longevity of SARS-CoV-2 immune responses in hemodialysis patients and protection against reinfection. Kidney Int. 2021;99(6):1470-1477. doi: 10.1016/j.kint.2021.03.009.

Gansevoort RT, Hilbrands LB. CKD is a key risk factor for COVID-19 mortality. Nat Rev Nephrol. 2020;16(12):705-706. doi: 10.1038/s41581-020-00349-4.

Flythe JE, Assimon MM, Tugman MJ; STOP-COVID Investigators. Characteristics and outcomes of individuals with pre-existing kidney disease and COVID-19 admitted to intensive care units in the United States. Am J Kidney Dis. 2021;77(2):190-203.e1. doi: 10.1053/j.ajkd.2020.09.003.

Berenguer J, Borobia AM, Ryan P; COVID-19@Spain and COVID@HULP Study Groups. Development and validation of a prediction model for 30-day mortality in hospitalised patients with COVID-19: the COVID-19 SEIMC score. Thorax. 2021:thoraxjnl-2020-216001. doi: 10.1136/thoraxjnl-2020-216001
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Goicoechea M, Sánchez Cámara LA, Macías N, et al. COVID-19: clinical course and outcomes of 36 hemodialysis patients in Spain. Kidney Int. 202098(1):27-34. doi: 10.1016/j.kint.2020.04.031.

WHO Solidarity Trial Consortium. Repurposed Antiviral Drugs for Covid-19 – Interim WHO Solidarity Trial Results. N Engl J Med. 2021;384(6):497-511. doi: 10.1056/NEJMoa2023184.

Simonovich VA, Burgos Pratx LD, Scibona P; PlasmAr Study Group. A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia. N Engl J Med. 2021;384(7):619-629. doi: 10.1056/NEJMoa2031304.

RECOVERY Collaborative Group, Horby P, Lim WS, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021;384(8):693-704. doi: 10.1056/NEJMoa2021436