Clinical Guidance on COVID- 19 Vaccines for People with Kidney Disease

(Dialysis, Non-Dialysis with Advanced Disease, Glomerulonephritis)

This guidance is intended for nephrologists and other health-care providers. It is based on known evidence as of
September 20, 2021.

Background and Context

This guidance is based on a review of three of the vaccines approved by Health Canada for the prevention of COVID-19
disease caused by the SARS-CoV-2 virus: Pfizer-BioNTech (BNT162b2)1, Moderna (mRNA-1273)2, and
AstraZeneca/COVISHIELD (ChADOx1-S)3 which is a replication-defective adenoviral vector vaccine.

Currently, anyone aged 12+ (born in 2009 and later) in British Columbia is eligible for COVID-19 immunization. Both of
the mRNA vaccines, Pfizer-BioNTech and Moderna, are authorized for youth aged 12-17. Studies of the COVID-19
vaccines in younger children are ongoing.

As per the National Advisory Committee on Immunization (NACI)4, the two mRNA vaccines authorized in Canada (Pfizer-
BioNTech and Moderna) can be interchanged for the second dose to complete the series, if the vaccine received for the
first dose is not available or is unknown. No data currently exist on the interchangeability of the COVID-19 mRNA
vaccines. However, there is no reason to believe that mRNA vaccine series completion with a different authorized mRNA
vaccine product will result in any additional safety issues of deficiency in protection.

Third doses:

To date, people who are moderately to severely immunocompromised have been observed to have generally lower
antibody responses and lower vaccine effectiveness from COVID-19 vaccines compared to the general population. NACI
has reviewed this evidence and recent studies that demonstrate that some people who are immunocompromised
develop an improved antibody response after a third dose of vaccine.5

As such, as of September 15, 2021, people who are severely immunocompromised in B.C. are eligible to receive a third
dose of an mRNA COVID-19 vaccine. People who are moderately immunocompromised will be eligible for a third dose of
an mRNA COVID-19 vaccine in the weeks following.
COVID-19 Vaccines for People with Kidney Disease
Updated: September 20, 2021

A minimum interval of 28 days between dose 2 and dose 3 is recommended for those eligible for a third dose. As per the
BC Immunization Manual, Moderna COVID-19 vaccine is preferred for the third dose. However if Moderna is unavailable
(or if the individual prefers), the Pfizer-BioNtech COVID-19 vaccine may be provided.6

Specifics on current eligibility for a third dose may be reviewed here: www2.gov.bc.ca/gov/content/covid-
19/vaccine/register#immunocompromised

Other vaccines:

The AstraZeneca/COVISHIELD COVID-19 vaccine program has been stopped in B.C. for first doses, due to rare (1:50,000)
but serious Vaccine-Induced Thrombotic Thrombocytopenia (VITT) blood clotting events and the large supply of other
vaccines without this safety concern. The risk of VITT is six times lower for the second dose (1:600,000). People who
received the AstraZeneca/COVISHIELD vaccine for their first dose have the option of receiving AstraZeneca/COVISHIELD
or an mRNA vaccine for their second dose. Receiving a mixed vaccine series (AstraZeneca/COVISHIELD for first dose and
an mRNA vaccine for the second dose) is permitted based on small studies that suggest that this is likely safe and likely
as effective and may be even more effective, but not enough is known to make firm conclusions and data collection is
ongoing. There may also be heightened side effects experienced with a mixed vaccine series. The BCCDC has prepared
two information sheets to help navigate that choice:

For health care professionals: www.bccdc.ca/resource-

gallery/Documents/Guidelines%20and%20Forms/Guidelines%20and%20Manuals/Immunization/Vaccine%20Inf
o/COVID-19-vaccine-second-dose-considerations-HCP-QandA.pdf

For patients: www.bccdc.ca/Health-Info-Site/Documents/COVID-19_vaccine/AstraZeneca_2ndDose.pdf

Another viral vector vaccine, Janssen/Johnson & Johnson (Ad26.COV2.S),7 has been approved by Health Canada but will
not be part of BC’s COVID-19 immunization program at this time. As well, another emerging vaccine candidate
developed by Novavax may also be approved by Health Canada in the coming months. This vaccine works differently
than the approved vaccines in Canada. This guidance will be updated as more information becomes available.

The risk of mortality from COVID-19 disease appears to be higher in patients with kidney disease. In a UK National Health
Service study using a living risk predictor algorithm (QCOVID) for the risk of hospital admission and mortality due to
COVID-19, chronic kidney disease (CKD) patients stage 5 (with or without dialysis or transplant) were found to be at
increased risk of complications.8 Other risk factors included patients on oral steroids or immunosuppressive agents. The
majority of these patients had multi-morbidities (including diabetes, heart disease, lung diseases) and many were over
the age of 70.

Compounding these risk factors is the need for hemodialysis patients to travel to and receive dialysis care three times
per week at hospital or community-based dialysis units where social distancing is more difficult and multiple exchanges
with care teams and other patients occur.

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Is COVID-19 immunization recommended for people with kidney disease?

COVID-19 vaccines are not contraindicated and should be encouraged for people with kidney disease, including those
who have had a COVID-19 infection.

This recommendation is based on the following review:

 The National Advisory Committee on Immunization recommends that immunosuppressed individuals may be
offered the vaccine if the benefits of vaccine outweigh the potential risks.4
 Patients with kidney disease have an increased risk of hospitalization and death related to COVID-19 infection.8
 The Canadian Society of Nephrology supports the use of COVID-19 immunization in this population and has
advocated to all provinces and the federal government for the urgent prioritization of dialysis patients for COVID-19
vaccinations.10
 Aside from a very rare risk of an allergic reaction (only a handful of people to date), there is no concern that the
vaccine will cause kidney patients harm. There is only uncertainty regarding its effectiveness for those who are
immunosuppressed.

While data specific to the safety and efficacy of COVID-19 vaccines in people with kidney disease is currently limited, the
authors of this guidance agree that the benefits of COVID-19 immunization with these vaccines outweigh any theoretical
risks of immunization.

Is the COVID-19 vaccine efficacious and safe for people with kidney disease?

Patients with kidney disease (including on dialysis, with a kidney transplant or on immunosuppressive agents) were
generally excluded from COVID-19 vaccine trials. As per NACI, safety data in immunocompromised individuals, including
those receiving immunosuppressive therapy, were available from observational studies in people who were taking
immunosuppressive therapies.4 The frequency and severity of adverse events following vaccination with an mRNA
COVID-19 vaccine were comparable to that of non-immunocompromised individuals in these studies and what was
reported in clinical trials. Safety data in these populations following vaccination with a viral vector vaccine is not
available.

It is unknown if the currently available COVID-19 vaccines are efficacious in people with kidney disease as in those
without kidney disease or who are not treated with immunosuppressive agents. As with most vaccines, there is a
potential for blunted diminished immune response in individuals who are immunocompromised due to their disease or
treatment. Informed consent should include discussion about the possibility that individuals who are
immunosuppressed may have a diminished immune response to any of the authorized COVID-19 vaccines.

There are currently no data on the actual efficacy or effectiveness of a third dose with any of the COVID-19 vaccines in
immunocompromised individuals. Small studies on third doses of the mRNA COVID-19 vaccines have shown that

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immunogenicity (immunity measured in the blood) may increase with a third dose. The safety of a third dose is
unknown at this time, but in these small studies reactions were found to be similar to that of prior doses. The impact of
additional doses on the worsening of underlying disease or on rare adverse events, including the risk of myocarditis
and/or pericarditis, is unknown at this time.5

There are currently no known factors that would predispose individuals with chronic kidney disease to different or more
frequent adverse events associated with the vaccines when compared to the general population.

Are there any specific contraindications or exceptions for kidney patients?

Individuals should not receive the vaccines if they have a history of severe allergic reaction to a previous dose of the
respective vaccine or any component of the vaccines.7 For a list of components in the vaccine and packaging consult the
respective COVID-19 vaccine product monographs found at:

 Pfizer BioNTech: https://covid-vaccine.canada.ca/info/pdf/pfizer-biontech-covid-19-vaccine-pm1-en.pdf

 Moderna: https://covid-vaccine.canada.ca/info/pdf/covid-19-vaccine-moderna-pm-en.pdf
 AstraZeneca: https://covid-vaccine.canada.ca/info/pdf/astrazeneca-covid-19-vaccine-pm-en.pdf and
COVISHIELD: https://covid-vaccine.canada.ca/info/pdf/covishield-pm-en.pdf

People with a history of anaphylaxis without known or obvious cause, and those with suspected hypersensitivity or non-
anaphylactic allergy to COVID-19 vaccine components, are advised to consult with an allergist prior to immunization.
Health-care providers with patients with a history of severe allergic reactions should refer to the product monographs to
review the full ingredient list.1,2, 3, 4 Potential allergens that are known to cause type 1 hypersensitivities in the mRNA
vaccines include polyethylene glycol (PEG), and Polysorbate 80 in the replication-defective adenovirus vaccines.

Health Canada continues to monitor any adverse events following immunization through their post-authorization
surveillance process.

There are no specific contraindications or exceptions for those with kidney disease. Health-care providers of those who
have had a kidney transplant should refer to the clinical guidance on COVID-19 vaccines for people who have received an
organ transplant.

Are there specific recommendations or considerations for safe and/or most effective
administration?
Patients on kidney transplant waiting list
For those on the kidney transplant waiting list, there are some considerations related to immunization timing. It is
recommended that immunization proceed as quickly as possible, given that the response to the vaccine is likely
diminished in the immediate post-transplant period. Thus, completing immunization prior to transplant will be
important for those high on the waiting list or those highly sensitized patients.

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Patients on immunosuppressive therapy

People who take immunosuppressant/immunomodulating therapy were excluded in COVID-19 vaccine trials. Therefore,
it is unknown if the COVID-19 vaccines are as efficacious in those who take immunosuppressants compared to those
who are not considered immunosuppressed.

Kidney patients who take immunosuppressants (with or without transplants) should be informed there are not yet
studies that examine the direct benefit and safety of COVID-19 immunization in this population, and that these
recommendations/clinical guidance are based on extrapolation of data from other viral infections, immunology of
immunizations and from expert opinion.

The benefits of immunization are considered to outweigh the potential risks. Immunization is recommended in this
group, preferably once ‘induction’ therapy has been completed.

People who may have severe systemic disease (lupus, vasculitis, etc.) who need to receive immunosuppressive therapy
(Rituximab, Prednisone 20 mg/day or greater, Cyclophosphamide, Plasma Exchange) should complete that course of
treatment before receiving the vaccine and should not delay treatment of their life threatening condition in order to be
immunized. See special considerations for Rituximab and Prednisone below.

In general, it is preferred that patients complete immunization before starting high-dose immunosuppressive therapy, if
possible, based on the timing of the treatments and the availability of vaccines at the time. This should ideally be at least
14 days after the second dose of any of the vaccines. *Life-saving or prolonging therapy should not be delayed solely
for the purposes of completing immunization.

Any other timing would require case-by-case assessment based on:

a. Risk of morbidity related to COVID-19 infection (including local prevalence of the pandemic, comorbidities that
confer higher risk categories in general population, etc.).
b. Suboptimal immunity protection due to insufficient time between immunization and immunosuppressive
therapy.

Special considerations for Hepatitis B vaccination and IGRA testing in the context of COVID-19 vaccination for
hemodialysis patients

The following considerations and recommendations for HD care should be taken into account as hemodialysis patients
begin receiving vaccination against COVID-19:

 COVID-19 vaccines can be given concomitantly with, or any time before or after any other indicated vaccine. This
is a change from the previous recommendation for a 14-day interval before or after receipt of a COVID-19
vaccine. The original advice against co-administration was based on a cautionary approach, as specific studies of
co-administration with other vaccines have not been performed. However, substantial data have now been
collected regarding the safety of COVID-19 vaccines currently authorized by Health Canada. Extensive
experience with non-COVID-19 vaccines has demonstrated that immunogenicity and adverse event profiles are
generally similar when vaccines are administered simultaneously as when they are administered alone. The
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basis for this change in recommendation is referenced to general administrative guidance for vaccines and
guidance from the US Advisory Committee on Immunization Practice (ACIP).

 For new hemodialysis patients requiring TB screening:

o Blood samples may be sent for IGRA testing if the patient has not had a COVID-19 vaccine dose in the
last 28 days.
o IGRA testing should be deferred until 28 days after the most recent COVID-19 vaccine dose.

Special considerations for immunotherapy: Rituximab and Prednisone

Patients receiving these agents may have a blunted immune response to vaccines in general that can extend to up to six
months following treatment completion.

 For patients on rituximab, COVID-19 immunization should ideally be timed four to five months after their last
infusion and 2 to 4 weeks prior to their next infusion, when possible, in order to optimize vaccine response.
However, in patients that require immediate infusion or who are unable to optimize timing of infusion product
and vaccine, treatment is paramount. Patients should be counselled to get the vaccine as soon as it is available
to them, but to not delay rituximab treatment for the sake of a vaccine appointment.
 For patients on prednisone 20mg/day or higher (or equivalents), consider waiting until the prednisone dose is
tapered to below 20mg/day to receive both vaccine doses, but only if the time needed to taper the prednisone
dose below 20mg/day is short.

References

1. Pfizer. Pfizer-BioNTech COVID-19 vaccine product monograph. Kirkland, Quebec. 9 December 2020.
2. Moderna. Moderna COVID-19 vaccine product monograph. Cambridge, MA, USA. 23 December 2020.
3. AstraZeneca COVID-19 vaccine product monograph. https://covid-vaccine.canada.ca/info/pdf/astrazeneca-
covid-19-vaccine-pm-en.pdf Accessed: March 7, 2021.
4. National Advisory Committee on Immunization. Recommendations on the use of COVID-19 vaccine(s). 7 April
2021. Available at: https://www.canada.ca/en/public-health/services/immunization/national-advisory-
committee-on-immunization-naci/recommendations-use-covid-19-vaccines.html.
5. National Advisory Committee on Immunization (NACI) rapid response: Additional dose of COVID-19 vaccine in
immunocompromised individuals following 1- or 2- dose primary series. Sept 10 2021.
https://www.canada.ca/en/public-health/services/immunization/national-advisory-committee-on-
immunization-naci/statement-september-10-2021-additional-dose-covid-19-vaccine-immunocompromised-
following-1-2-dose-series.html. Accessed on: Sept. 10 2021
6. BC Immunization Manual Update – Administrative Circular. September 14 2021. http://www.bccdc.ca/resource-
gallery/Documents/Guidelines%20and%20Forms/Guidelines%20and%20Manuals/Epid/CD%20Manual/Admin%
20Circulars/2021/AC_2021-35_Chapter_2_Immunization_Sep_14%20_2021.pdf. Accessed September 15, 2021.
7. Janssen COVID-19 vaccine product monograph. https://covid-vaccine.canada.ca/info/pdf/janssen-covid-19-
vaccine-pm-en.pdf, Accessed: March 7, 2021.

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8. BMJ 2020; 371:m3731. Living risk prediction algorithm (QCOVID) for risk of hospital admission and mortality
from coronavirus 19 in adults: national derivation and validation cohort study.
https://www.bmj.com/content/371/bmj.m3731.
9. Canadian Society of Nephrology. Advocacy for prioritization of dialysis patients for COVID-19 vaccination.
https://www.csnscn.ca/cms/media/2021/02/Urgent-Prioritization-of-Dialysis-Patients-for-COVID-19-
Vaccinations.pdf

Authors

Dr. Adeera Levin, MD FRCPC FCAHS CM, Executive Director BC Renal, Head Division of Nephrology University of British
Columbia

Gloria Freeborn, Director of Strategic Initiatives, Education and Development, BC Renal

Reviewers

Dr. Michael Copland, Medical Director, Kidney Services Vancouver Coastal Health/Providence Health Care, Senior
Medical Lead, BC Renal

Dr. John Antonsen, Medical Director, Kidney Services Island Health, Senior Medical Lead, BC Renal

Dr. Janis Dionne, Medical Director, Pediatric Kidney Services, British Columbia Children’s Hospital