COVID-19 vaccines in people with immunocompromise

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 ≥ 6 months with severe immunocompromise for optimal protection (in contrast to a 2-dose primary schedule for individuals with mild immunocompromise/immunocompetent individuals), with the third dose administered 2 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 are recommended to receive Spikevax (Moderna), Comirnaty (Pfizer) or Nuvaxovid (Novavax) brands for their 3-dose primary course.

(NB: Most studies involving a 3-dose primary course of COVID-19 vaccination for immunocompromised individuals involve mRNA vaccines meaning there is limited data available on the efficacy of Nuvaxovid in immunocompromised individuals)

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.

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.

Brand choice for individuals aged 6 months-< 5 years

Severely immunocompromised children aged 6 months-≤ 5 years can receive Spikevax (Moderna) (25µ dose) as their 3-dose primary course.

Severely immunocompromised children aged 6 months- ≤4 years can receive Comirnaty (Pfizer) (3µ dose) as a 3-dose primary course.

Following receipt of a 3-dose primary course of vaccination, severely immunocompromised individuals ≥ 5 years are recommended to receive additional booster doses to maintain an optimum level of protection. Where possible, bivalent mRNA COVID-19 vaccines are the preferred choice of vaccine for booster doses, however all currently available COVID-19 vaccines should provide some protection. The bivalent Comirnaty (Pfizer)  can be administered for those aged 12 and over and the bivalent Spikevax (Moderna) can be administered from 18 years. Those aged 5-11 years can receive an age-appropriate dose of original COVID-19 vaccine as a booster.

For more information refer to ATAGI 2023 booster advice.

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.

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.

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 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

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.

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.

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.

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

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:

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.

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.

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.

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.