ADDITIONAL CONTENT
An author video to accompany this article is available at: https://academic.oup.com/ndt/pages/author_videos.
A timely analysis and call to action by the Council of the ERA-EDTA and the European
Renal Association COVID-19 Database (ERACODA) Working Group has recently highlighted
the extremely high burden of coronavirus disease 2019 (COVID-19) infection in chronic
kidney disease (CKD) patients, who, compared with patients suffering from other major
disorders, are at the highest risk to develop severe COVID-19 and to die from it [1].
The authors call for greater recognition of this risk and for inclusion of patients
with CKD in clinical trials. Here, the European Dialysis (EUDIAL) Working Group issues
a strong call for priority access to severe acute respiratory syndrome coronavirus
2 (SARS-CoV-2) vaccines for the most vulnerable group of patients with kidney disease:
those receiving in-centre haemodialysis (ICHD) (Figure 1).
FIGURE 1
Call of the EUDIAL Working Group to prioritize COVID-19 vaccination in patients receiving
ICHD.
Living well with haemodialysis (HD) generally requires three sessions per week. For
those receiving ICHD, this translates into at least 156 dialysis sessions per year,
each one an unavoidable occasion with risk of exposure to COVID-19. ICHD carries the
risk of contact with potentially infected health professionals, other high-risk patients
or risks inherent to commuting. Recognition of the high risk of virus spread among
patients on ICHD has driven reorganization of dialysis care delivery. Physical interventions
(social distancing, barriers, personal protection) and strict infection control (triage,
isolation) have been implemented to ensure the safety of patients and staff [2]. Recommendations
to transition patients from in-centre to home dialysis to reduce their risk during
the pandemic have not been clinically feasible for most patients receiving ICHD. ICHD
in patients infected with SARS-CoV-2 is complicated by requirements for strict infection
control, patient isolation and dedicated staff, which puts dialysis centres under
additional strain. Patients who test positive for SARS-CoV-2 but are not sick enough
for hospital admission are managed in outpatient units to avoid overwhelming inpatient
dialysis services. On arrival to the dialysis unit, patients with known COVID-19 are
dialysed in an isolation room or on ‘COVID-19’ shifts, with dedicated staff equipped
with adequate personal protective equipment. These patients require careful observation
and monitoring, and a proportion requires subsequent admission [3].
Vulnerability in uraemic patients is a combination of intrinsic frailty, increased
risk of infection (vascular access, exposure to infected individuals) and a high burden
of comorbidities [1]. Although patients on dialysis have a similar overall high risk
of death from COVID-19 to patients with kidney transplants [4], patients on HD and
on the waiting list have a 2-fold higher risk of infection because of risk inherent
to the HD process [5]. Age per se is a less significant risk factor among those on
dialysis compared with the general population [1]. Younger adults, children on ICHD
and their carers face high risks of exposure to infection but are unable to shield
themselves at home, and children are unable to return to school. All patients receiving
ICHD are therefore highly vulnerable [1].
In patients on HD, abnormalities in the immune response are characterized by abnormal
activation and reduced function of the innate and adaptive immune systems, associated
with a reduction in dendritic cells, skewed Th1/Th2 T-cell ratios, less T-cell activation
and an increase in senescent, hyporeactive T cells [6]. These factors may contribute
to relative hyporesponsiveness to vaccines in some patients. Concerns regarding potential
vaccine hyporesponsiveness should not prevent patients on dialysis from receiving
vaccinations, however. Indeed, multiple vaccines (influenza, pneumococci, hepatitis
B, zoster, human papillomavirus, etc.) are standard of care in patients on HD [7].
The majority of patients do respond effectively: hepatitis B has been virtually eradicated
in many countries through vaccination and hygiene practices. During the 2009 influenza
A virus (H1N1) pandemic, vaccination was strongly recommended by the World Health
Organization and led to seroconversion in 57–64.2% of patients on HD [8]. Vaccine
dose was an independent factor predicting responsiveness in HD subjects [9]. Booster
doses may therefore be required. These observations emphasize the urgent need to include
patients receiving dialysis in vaccine trials. Importantly, patients on ICHD appear
to seroconvert at a similar rate to the general population after SARS-CoV-2 infection,
suggesting the likelihood of response to a vaccine [10]. In regions where the SARS-CoV-2
prevalence in the general population is high, high rates of asymptomatic seroconversion
in patients were also observed [11]. Surveillance post-vaccination is advisable to
identify vaccine non-responders among patients receiving ICHD, although a level of
‘herd immunity’ achieved through vaccination of patients and staff in dialysis units
should confer some protection. Units will also need to plan for patients (or staff)
who decline vaccination. It is important that such individuals should not be stigmatized.
Strict adherence to physical protective measures remains necessary.
Current global recommendations suggest prioritization of healthcare workers at high
risk, along with older adults [12]. Given the extreme vulnerability of patients receiving
ICHD, there should be little doubt that dialysis staff meet the criteria for prioritization.
Where the highly vulnerable patients receiving ICHD will fall along the prioritization
spectrum is not yet clear.
From an ethical perspective, given that the vaccine supplies will be limited at least
during the initial phases of vaccine roll-out, stewardship and accountability are
required. Ethical principles underlying allocation decisions include (i) balancing
benefit versus harm, (ii) prioritization of vulnerable populations, (iii) promotion
of justice—meeting the needs of populations with disproportionate burdens, avoiding
exacerbation of health inequities, fair vaccine distribution and (iv) transparent
communication and accountability by decision-makers [12, 13]. Two major questions
arise: (i) is the vaccine safe for patients on ICHD and (ii) should patients on ICHD
be prioritized over other groups for vaccination?
The first question highlights a major inequity pervasive in most vaccine trials, where
vulnerable patients are often excluded. Based on the experience with other vaccines,
there are no reasons to expect higher risks of complications in patients receiving
dialysis. Concerns regarding potential harm from induction of alloimmunity through
vaccination in patients with or awaiting transplantation have not been confirmed.
If the benefit versus risk ratio of the vaccine is considered to be favourable for
other vulnerable patients, this should apply similarly to patients on ICHD [12–14].
Transparency is crucial. Patients must be fully informed about the limits of current
safety data, as well as the reasons why vaccination is being strongly encouraged.
As more vaccine candidates become approved, ongoing surveillance of efficacy and consequences
in patients on dialysis may permit favouring one type of vaccine over another over
time.
The second question about prioritization of patients on ICHD for vaccination over
other patient groups is more complex. Dialysis and transplantation are the leading
global risk factors for death from COVID-19. When matched for age and sex, however,
patients with kidney transplants have an almost 30% higher risk of death compared
with those on dialysis [4]. Patients receiving ICHD are, however, highly vulnerable
because in comparison with patients with transplants or with other chronic diseases,
they are not able to shield optimally. If initial dose availability is limited, the
elevated risk of both infection and death in patients receiving ICHD would justify
their initial prioritization, followed as closely as possible by patients living with
transplants and advanced CKD. Patients receiving dialysis at home, whether peritoneal
dialysis or HD, have similar intrinsic risk, and are only less vulnerable than patients
on ICHD because they do not travel frequently for care. These patients should therefore
also be prioritized as soon as supplies permit. Furthermore, given their multiple
comorbidities and high frailty scores, patients receiving dialysis may not be considered
for limited intensive care beds if triage protocols are implemented [15]. Thus, in
accepting potentially limiting access to treatment for severe COVID-19 in patients
receiving dialysis, it can be argued that society ‘owes’ optimal preventive measures
to this population. Such prioritization based on reciprocity would apply to all high-risk
patient groups that may be ineligible for intensive care. Justice demands that their
disadvantage should not be exacerbated through delay in vaccination.
In terms of justice, as soon as a country decides to allocate vaccines for patients
on ICHD, vaccine distribution must be equitable, between units and between patients
within units. There should be no favouring of access based on unacceptable criteria
such as private versus public dialysis units or patient age. The dose, efficacy and
long-term safety of COVID-19 vaccines in children are not known, and vaccine trials
have only just extended to the paediatric population. Whether vaccines should be withheld
in children receiving ICHD based on the lack of data, or whether they should be prioritized
for vaccination, must be discussed. Strong consideration must be given to vaccination
of parents of children receiving ICHD.
In conclusion, it is clear that patients receiving ICHD are highly vulnerable to infection,
severe disease and death from COVID-19, and are likely to respond to vaccination.
They represent a vulnerable population that is additionally disadvantaged due to lack
of inclusion in clinical trials, and potential ineligibility for intensive care should
they become severely ill. There remain many ‘known unknowns’ in the safety, efficacy
and duration of antibody response to the SARS-CoV-2 vaccines in patients with kidney
failure. Clinical trials to monitor the antibody response to vaccination and safety
in these patients are imperative to promote transparent evidence-based decision-making.
Clinically and ethically, the grounds to support vaccination are strong. We therefore
strongly call for the inclusion of patients on ICHD, and subsequently all patients
with transplants and those receiving home dialysis, in priority risk groups for early
vaccination against SARS-CoV-2.
ACKNOWLEDGEMENTS
Sandip Mitra, Adrian Covic, Dimitrios Kirmizis and Vassilios Liakopoulos are Board
Members of the EUDIAL Working Group.
FUNDING
No funding was received for the drafting of this article.
CONFLICT OF INTEREST STATEMENT
The authors have no conflicts of interest related to this manuscript.
DATA AVAILABILITY STATEMENT
This publication includes no original data except those extracted from the cited publications.