Background

COVID-19 vaccination is recommended for all people who are immunocompromised due to the increased risk of developing severe disease if exposed to SARS-CoV-2All COVID-19 vaccines in Australia are inactivated (non-live) vaccinesThe following guidance encompasses a broad group of conditions and therapies, as well as providing specific recommendations and/or links where available. People who are immunocompromised include those who are immunocompromised due to pre-existing illness (eg. cancer, immune deficiencies) as well as those who are taking immunomodulatory or immunosuppressive therapies. 

Due to the restricted eligibility criteria in early vaccine clinical trials, there is currently minimal data on the safety and efficacy of COVID-19 vaccination in this group. In principle, there are no theoretical safety risks and no vaccine safety signals have been identified for people with immunocompromise to date. Information on safetyefficacy and specific timing of immunosuppression and vaccination is expected in the coming months. People with immunocompromise receiving COVID-19 vaccination should be counselled about the possibility of reduced efficacy and the need to continue other preventative measures such as social distancingmask wearing and hand hygiene. Household contacts should be encouraged to receive the COVID-19 vaccine when it is offered because vaccination has also been shown to reduce transmission. 

ATAGI has provided both a COVID-19 vaccination decision guide for people with immunocompromise and a provider guide to COVID-19 vaccination of people with immunocompromise. 

Is there a specific vaccine preference for people who are immunocompromised?

Both Comirnaty™ and COVID-19 AstraZeneca can be used in people with immunocompromise in accordance with the ATAGI recommendations based on age. 

Some immunocompromising conditions such as cancer carry an increased risk of clotting and may result in deep vein thrombosis (DVT) and pulmonary embolism (PE). Having a past history of these conditions has not been linked to the development of thrombosis with thrombocytopenia syndrome (TTS) following administration of COVID-19 AstraZeneca vaccine. Currently ATAGI recommends that people aged < 50 years, as well as those of any age with a past history of only idiopathic splanchnic vein thrombosis, antiphospholipid syndrome with thrombosis, cerebral venous sinus thrombosis (CVST) or heparin-induced thrombocytopenia (HIT) should preferentially receive an alternate COVID-19 vaccine (eg. Comirnaty™).

Are there any safety concerns with the use of COVID-19 vaccines in people who are immunocompromised?

Much like other non-live vaccines, there are no specific safety concerns regarding the administration of COVID-19 vaccines in patients who are immunocompromised. Similarly, there have been no safety signals indicating disease flares in people with inflammatory/autoimmune conditions observed in the global rollout of COVID-19 vaccines thus far.  

To avoid confusion between side effects of vaccination and certain immunomodulatory therapies, where possible treating clinicians should consider administering vaccination on a different day from treatment/therapy. The Australasian Society of Clinical Immunology and Allergy (ASCIA) has provided guidance about COVID-19 vaccination and the timing of immunomodulatory therapies. Specifically, the Australian and New Zealand Association of Neurologists (ANZAN) in collaboration with MS Research Australia, have recommended that people with multiple sclerosis be vaccinated against COVID-19 and provided general advice about immunosuppressive and immunomodulatory therapy, as well as vaccine safety. 

People on immune checkpoint inhibitors (ICI) are recommended to be vaccinated against COVID-19. A small study of 134 patients on ICI showed no difference in short-term safety or undesired/harmful effects (reactogenicity) compared with the control group. However, people on dual ICI therapy should discuss optimal timing of vaccination with their treating clinician prior to vaccination.  

What is the efficacy of COVID-19 vaccines in people who are immunocompromised? 

People who are immunocompromised may have a reduced response to vaccination. Similar to other inactivated vaccines, some immunocompromising conditions and immunosuppressive medications are also expected to reduce the immune response to COVID-19 vaccines. Currently, there is no established immune correlate of protection against COVID-19 to provide guidance about either the requirement for booster doses or reducing the need for other preventative measures. 

There are currently limited peer-reviewed studies in people who have received COVID-19 vaccines and who are on concurrent immunosuppressive treatment for rheumatological and musculoskeletal conditionsinflammatory bowel disease or following a solid-organ transplant 

Are there recommendations for the timing of immunosuppressive medications and the administration of COVID-19 vaccines in people who are taking immunomodulatory or immunosuppressive therapies? 

There is no information specific to COVID-19 vaccination to support recommendations about modifying immunosuppressive medication timing or doses to increase vaccine efficacy. Vaccination to protect against COVID-19 should therefore follow the general principles of vaccination and immunosuppressionAdministration of COVID-19 vaccine should be planned with the treating specialist and in some instances, the timing of immune suppressive therapies may be altered to increase the response to vaccination.  

Delaying initiation or interrupting cancer therapy to potentially improve the response to vaccination is not recommended. When considering vaccination during cancer treatment, it is preferable to defer vaccination if severe neutropenia is present (< 0.5 x 109/L) and where possible, to time vaccination between treatment cycles.  

Two doses of COVID-19 vaccination should preferably be completed at least two weeks prior to the commencement of immunosuppressive therapy, transplant or planned splenectomy. For people who are about to start immunosuppressive therapy or are between courses of treatment, the interval between COVID-19 vaccine doses can be reduced from 21 days to 19 days for Comirnaty  and from 12 weeks to 28 days for COVID-19 AstraZeneca. If it is not feasible to complete the 2nd dose prior to immunosuppression, then the 2nd dose should still be given as per the recommended schedule.    

There is no direct evidence for the temporary cessation of immunosuppressive therapy before or after COVID-19 vaccination. For the inactivated influenza vaccination in patients with rheumatoid arthritis, temporary methotrexate discontinuation improves the antibody response to influenza vaccines but it is not known whether this improves clinical protection. People with rheumatological and inflammatory conditions with low disease activity or people nearing planned completion of immunosuppressive therapy should discuss the timing of their vaccination with their treating clinician. Persons who have received a solid organ or stem cell transplant should discuss the timing of their COVID-19 vaccination with their treating clinician. Further information for people with autoinflammatory and rheumatological diseases on immunomodulatory therapies can be found on the Australian Rheumatology Association FAQ and evidence review on COVID-19 vaccination or guidance from ASCIAGESA and MS Australia. 

There are some specific therapies that are highly likely to reduce vaccine responses based on what is known about their responses to other inactivated vaccines. People who take B cell depleting therapies (eg. rituximab or ocrelizumab) or medications that block T-cell dependent B memory cells (eg. abatacept) should discuss timing of their vaccines with their treating clinicians. We recommended that patients on rituximab be vaccinated against COVID-19. For patients on 6 monthly rituximab, where possible should receive the first dose of their COVID-19 schedule 4 weeks prior to the next scheduled infusion and delay the next infusion by 2-4 weeks after the 2nd vaccine dose (noting the different interval requirements for each COVID-19 vaccine brand). This may not always be possible due to activity of the underlying condition and should be decided on a case-by-case basis. Whilst COVID-19 incidence remains low in Australia, it may be reasonable to defer vaccination for patients who are scheduled to cease B-cell depleting therapy and vaccinate once there is immune reconstitution. 

Should people who are immunosuppressed have a booster dose or have SARS-CoV-2 antibodies measured after vaccination?  

Antibody testing or additional booster doses are not recommended at this time as there is no established immune correlate of protection against COVID-19 disease.

Resources

Authors: Jeremy Carr (Paediatric Infectious Diseases Consultant, Monash Health), Shidan Tosif (Paediatrician, Royal Children’s Hospital), Andres Noe (DPhil candidate, The Jenner Institute), Nigel Crawford (SAEFVIC Director, Murdoch Children’s Research Institute), Daryl Cheng (Medical Lead, MVEC), Francesca Machingaifa (Education Nurse Coordinator, MVEC) and Rachael McGuire (Education Nurse Coordinator, MVEC)

Reviewed by: Rachael McGuire (MVEC Education Nurse Coordinator)

Date: June 2021

Materials in this section are updated as new information and vaccines become available. The Melbourne Vaccine Education Centre (MVEC) staff regularly reviews materials for accuracy.

You should not consider the information in this site to be specific, professional medical advice for your personal health or for your family’s personal health. For medical concerns, including decisions about vaccinations, medications and other treatments, you should always consult a healthcare professional.