Background

COVID-19 vaccination is strongly recommended for all age-eligible people. Vaccination is particularly important for those who are immunocompromised due to the increased risk of developing severe disease (hospitalisation/intensive care admission, death) if exposed to SARS-CoV-2. All COVID-19 vaccines in Australia are inactivated (non-live) vaccines and are safe to be administered to immunocompromised individuals.

The following guidance details the vaccination recommendations for individuals with immunocompromise and provides specific considerations for a broad group of immunocompromising conditions and therapies, as well as providing specific recommendations and/or links where available.

Vaccination for immunocompromised individuals

  • Primary schedule

    Real-world evidence has demonstrated no safety concerns relating to the administration of COVID-19 vaccines in immunocompromised individuals however, the level of protection may be suboptimal. It is for this reason that a 3-dose primary course of COVID-19 vaccination is recommended for all individuals aged ≥ 5 years for optimal protection (in contrast to a 2-dose primary schedule for immunocompetent individuals), with the third dose administered 2-6 months following the second dose (this interval can be shortened to 4 weeks in exceptional circumstances eg. impending transplant).

    Brand choice for individuals ≥ 18 years

    The preferred vaccine brands for individuals aged ≥ 18 years are Spikevax (Moderna) or Comirnaty (Pfizer). Nuvaxovid (Novavax) can also be administered, however there is minimal efficacy data available on it’s use in this patient group. Those aged ≥ 18 years who received Vaxzevria (AstraZeneca) without any serious adverse event for their first two doses may choose to receive Vaxzevria (AstraZeneca) as their third dose however alternate brands are recommended.

    Brand choice for individuals 12-17 years

    Immunocompromised adolescents aged 12-17 years can receive Spikevax (Moderna) or Comirnaty (Pfizer) brands only for their 3-dose primary course.

    Brand choice for individuals 5-11 years

    Immunocompromised children aged 5-11 years can receive Paediatric Comirnaty (Pfizer) (10µ) as their 3-dose primary course, or alternatively Spikevax (Moderna) (50µ dose) for those aged 6-11 years.

    NB: Individuals ≥ 12 years receiving Spikevax (Moderna) as their third primary dose should receive a full dose (100µg). This differs from the recommended Spikevax (Moderna) booster dose where only a half dose (50µg) is indicated.

  • Booster doses

    Following a 3-dose primary course of vaccination, severely immunocompromised individuals ≥ 12 years should receive an initial booster dose (4th dose) ≥ 3 months from completion of the primary course. An additional “winter booster” dose (5th dose) is recommended for those ≥ 16 years, ≥ 4 months after receiving a first booster.

    mRNA COVID-19 vaccines (Comirnaty (Pfizer) and Spikevax (Moderna) for those ≥ 18 years, and Comirnaty (Pfizer) only for those < 18 years), are the preferred brands for booster doses

    Booster doses are not currently recommended for individuals < 12 years.

  • Timing of vaccination

    Vaccination to protect against COVID-19 in immunosuppressed patients should follow the general principles of vaccination and immunosuppression. Vaccine administration should be planned with the treating specialist. In some instances, the timing of immune suppressive therapies may be altered to increase the response to vaccination. In other circumstances, the intervals between vaccine doses may be altered to accommodate treatment regimes.

    There is no direct evidence for the temporary cessation of immunosuppressive therapy before or after COVID-19 vaccination. There are some specific immunosuppressive therapies (eg. B-cell depleting therapies eg. rituximab or ocrelizumab; or medications that block T-cell dependent B-cell dependent memory cells eg. abatacept) that are highly likely to reduce COVID-19 vaccine response, based on evidence extrapolated from responses to other inactivated vaccines such as influenza.

    Current evidence demonstrates that a 2-week period is needed to generate an adequate immune response to the COVID-19 vaccine. Therefore, in general 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 doses of COVID-19 vaccine doses can be reduced depending on the individual circumstances and the type of vaccine being used. If it is not feasible to complete all doses prior to immunosuppression, then the subsequent doses should still be given as per the recommended schedule, with some protection thought to be better than none.

  • Other measures

    Following vaccination immunocompromised individuals are encouraged to continue the use of other preventative measures such as social distancing, mask wearing and hand hygiene. Vaccination of eligible household contacts is strongly recommended to reduce the potential for transmission.

Considerations for individuals with immunocompromising conditions taking immunomodulatory or immunosuppressive therapies

  • Patients undergoing cancer treatment

    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.

  • Solid organ transplant recipients who are on immune suppressive therapy

    Solid organ transplant recipients show reduced COVID-19 vaccine response with reduced rates of seroconversion (15 to 66% following mRNA vaccines).

    Timing of vaccination should be discussed with the treating specialist and the level of immunosuppressive therapy should be considered (ie. considering delaying vaccination for up to 3 months if T cell or B cell depleting therapy is being used in induction).

    For more information refer to ISHLT: COVID-19: Information for Transplant Professionals

  • Haematopoietic Stem Cell Transplant (HSCT) recipients

    Individuals who received vaccination prior to allogenic or autologous HSCT or CAR-T cell therapy require re-vaccination with 3 additional doses of COVID-19 vaccine (ie. new primary course). This is due to the risk of partial or complete loss of protective immunity following HSCT or CAR-T cell therapy. Vaccination or re-vaccination (where applicable) is advised to commence 3-6 months after transplantation due to the risk of reduced vaccine response in the initial 3-6 months. The optimal time to commence vaccination should be guided by the treating specialist. The dosing interval should follow the recommend dosing intervals.

  • Graft-versus-Host Disease (GvHD)

    COVID-19 vaccination is recommended in individuals with stable GvHD on therapy. Immunisation with inactivated vaccines has not been associated with flares of GvHD.

    For more information refer to Clinicians guide to COVID-19 vaccination for patients with cancer.

  • Haematological malignancy

    Patients with haematological cancers (Including leukaemia, lymphoma or myeloma resulting in immunocompromise) have lower vaccine responses after mRNA vaccines (seroconversion rates 39%-85%).

    The impaired vaccine response is likely multifactorial and related to the treatments for these malignancies (anti-B cell therapies, cytotoxic chemotherapy) but is also due to the underlying disease.

  • Non-haematological malignancy

    Patients with solid cancer have been shown to have lower vaccine responses (seroconversion 81-98%). Factors associated with poorer vaccine response included radiotherapy, chemotherapy and hormonal therapy. In general, patients should be vaccinated at the earliest opportunity and upon consultation with their treating specialist.

    For more information refer to MOGA: COVID-19 vaccination in patients with solid tumours

  • Medication specific recommendations

    Medications used in the treatment of cancers Recommendation
    Cyclophosphamide Do not delay/modify medication or adjust vaccine administration timing. Prescribers should anticipate when the peak of neutropaenia will occur and avoid vaccinating at this point.
    Rituximab Do not delay oncology related rituximab treatment. Immunisation whilst on rituximab treatment may vaccine effectiveness.
    Checkpoint inhibitor (eg. anti-PD-L1, PD-1 or CTLA-4) The use of immune checkpoint inhibitors (ICI) is not expected to cause significant immunosuppression and a 3rd primary dose is not currently recommended for patients treated only with ICIs.
    Medication containing polyethylene glycol (PEG) or polysorbate PEG or polysorbate is a known component of COVID-19 vaccine and also some conventional chemotherapeutic drugs. In the event of a previous serious/severe immediate allergic reaction (anaphylaxis), referral for specialist review via the VicSIS is recommended.

Considerations for COVID-19 vaccination in individuals with rheumatological and other disorders taking immunomodulatory or immunosuppressive therapies

  • Chronic inflammatory conditions treated with disease modifying anti-rheumatic drugs (DMARDs) or immune-suppressive or immunomodulatory therapies

    People with chronic inflammatory conditions treated with disease modifying anti-rheumatic drugs (DMARDs) or other immunosuppressive or immunomodulatory therapies may have reduced immune response to COVID-19 vaccines. Specific guidance surrounding the COVID-19 vaccines and commonly used therapies are adapted from Australian clinician guide for the use of immunomodulatory drugs in autoimmune rheumatic diseases at the time of COVID-19 vaccination and summarised in the following table:

    Medications used in the treatment of autoimmune inflammatory rheumatic diseases Recommendation
    Methotrexate (when used as a DMARD) Consider stopping methotrexate for 1 to 2 weeks on an individual basis balancing benefits and risks. eg. delay methotrexate for 1 week after each vaccine dose for those with well-controlled disease.
    Hydroxychloroquine, Sulfasalazine, Leflunomide Do not delay/modify medication or adjust vaccine administration timing. The prolonged elimination half-lives of leflunomide and hydroxychloroquine would make dose interruption for vaccine impractical.
    Cytokine inhibitors (TNF, IL-1, IL-6, IL-12/23, IL-17) Do not delay/modify medication or adjust vaccine administration timing.
    JAK inhibitors Do not delay/modify medication or adjust vaccine administration timing. The interruption of therapy may increase the risk of disease flare without any clear evidence of improvement in vaccine efficacy.
    Abatacept SC: Withhold subcutaneous abatacept from one week before to one week after the first COVID-19 vaccine dose only. No interruption is required before or after the second vaccine dose.

    IV: Schedule vaccination so that the first vaccine dose is initiated approximately 4 weeks after the abatacept infusion (ie. the entire dosing interval), and postpone the subsequent abatacept infusion by one week (eg. a 5week gap in total). No interruption is required before or after the second vaccine dose.

    Rituximab Where possible, aim to administer COVID-19 vaccines towards the end of a rituximab dosing cycle or before initiation of rituximab therapy. eg. schedule vaccination so that the first vaccine dose is administered approximately 4 weeks prior to the next scheduled rituximab cycle. Delay rituximab 2-4 weeks after the second vaccine dose, if disease activity allows.

    NB: Immunisation whilst on rituximab treatment may limit the protective effect of the vaccine.

    Glucocorticoids  

    *High dose is equivalent >20mg/day of prednisolone for ≥ 14days in a month or treatment with pulse corticosteroid therapy

    Vaccine immunogenicity is influenced by dose, duration of therapy and use in combination with other DMARDs. In cases where reducing the dose is impractical, COVID-19 vaccination should not be delayed. However, in cases where steroid tapering is planned and the risk of COVID-19 can be suitably mitigated (ie. low community transmission), some may elect to defer COVID-19 vaccination until the steroid taper is complete or a stable low dose of glucocorticoids is achieved.
    Mycophenolate Do not delay/modify medication or adjust vaccine administration timing. Most people with AIRD using mycophenolate are at risk of adverse consequences if there were loss of disease control.
    Cyclophosphamide IV: Perform vaccination as close as possible to the end of the cyclophosphamide dosing schedule ie. suggest waiting 3-4 weeks after the most recent IV dose and allowing about 1 week before the following dose.

    PO: Do not delay/modify medication or adjust vaccine administration timing. Most people with AIRD using cyclophosphamide are at risk of adverse consequences if there were loss of disease control, interruption of cyclophosphamide therapy is not recommended.

    Apremilast Do not delay/modify medication or adjust vaccine administration timing.
    Belimumab Do not delay/modify medication or adjust vaccine administration timing.
  • Chronic neurological conditions

    There is a paucity of data on the efficacy of COVID-19 vaccines in patients with neurological conditions receiving immunomodulatory or immunosuppressive therapies. Many current recommendations for these patients are extrapolated from studies of immunological response to other vaccines or specific to the therapy being used.

    Further information from the Australian and New Zealand Association of Neurologists (ANZAN) in collaboration with MS Research Australia, regarding COVID-19 vaccination and safety can be found here.

Other conditions and therapies

  • Human Immunodeficiency Virus (HIV)

    People living with well controlled HIV, on anti-retroviral therapy with CD4 counts ≥ 250/µL and low or undetectable viral load, do not require a 3-dose primary course. Studies have shown a similar immune response following COVID-19 vaccination when compared to healthy controls.

    ATAGI currently recommends a 3-dose primary course, followed by a booster dose, for individuals with advanced or untreated HIV with CD4 counts <250/µL or those unable to be established on effective anti-retroviral therapy.

    Foe more information refer to ASCIA: Immunodeficiency, Autoimmunity and COVID-19 Vaccination.

  • Long term haemodialysis or peritoneal dialysis

    Individuals receiving dialysis generally have reduced vaccine responses. Due to concerns regarding poor COVID-19 vaccine response and breakthrough COVID-19 infections in fully vaccinated patients receiving dialysis, a 3-dose primary schedule, followed by a booster dose, is recommended.

    More information can be found at Renal Society of Australasia- COVID-19 updates.

  • Intravenous immunoglobulin (IVIg)

    Where possible, it is recommended to schedule COVID-19 vaccination on a different day from regular infusion treatments. Patients on monthly IVIg may be advised by their specialist to be vaccinated 2 weeks after an IVIg infusion. This avoids confusion about the cause of side effects or allergic reactions if they occur in response to the COVID-19 vaccine or the infusion treatment.

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 (MVEC Medical Lead), Francesca Machingaifa (MVEC Education Nurse Coordinator) and Rachael McGuire (MVEC Education Nurse Coordinator)

Reviewed by: Francesca Machingaifa (MVEC Education Nurse Coordinator) and Rachael McGuire (MVEC Education Nurse Coordinator)

Date: June 9, 2022

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.