Immunocompromised require third COVID vaccine dose: ATAGI

Matt Woodley

8/10/2021 1:56:49 PM

The additional dose is considered part of the primary regimen and is intended to generate an immune response equivalent to the general population.

Cancer patient receiving COVID vaccine.
The recommended interval for the third dose for immunocompromised people is 2–6 months after their second dose.

Severely immunocompromised people should receive a third dose of a COVID-19 vaccine as part of their primary course, the Australian Technical Advisory Group on Immunisation (ATAGI) has confirmed.
The updated clinical guidance, initially flagged last month, is aimed at addressing the risk of a suboptimal or non-response to the standard two dose schedule in this cohort and maximise the level of immune response to ‘as close as possible to the general population’.
However, ATAGI still recommends that immunocompromised people continue risk mitigation strategies such as mask wearing and social distancing even after receiving their third dose.
Pfizer or Moderna mRNA vaccines are preferred to AstraZeneca for the third dose. The latter can be used for individuals who received it for their first two doses if there are no contraindications or precautions for use, or if a significant adverse reaction occurred after a previous mRNA vaccine dose, such as anaphylaxis or myocarditis.
The recommended interval for the third dose is 2–6 months after the second dose, but a minimum interval of four weeks may be considered in exceptional circumstances, ie anticipated intensification of immunosuppression or outbreaks. People who have had a second dose more than six months ago should receive a third dose whenever feasible.
The new guidance applies to all individuals aged 12 years or older with certain conditions or on therapies known to lead to severe immunocompromise.
Anyone with an unlisted condition should only be considered for a third dose where the treating physician has assessed the patient as having a similar level of severe immunocompromise to the listed conditions, and where the benefits of a third dose outweigh the risks.
Meanwhile, people who are not severely immunocompromised but later commence significant immunosuppressive therapy more than two weeks after their second dose will not require a third dose, ‘as it can be expected that an adequate response to two primary doses will be achieved’.
Likewise, at present ATAGI does not recommend subsequent doses beyond the third dose, as many patients who fail to respond to a third dose may not respond to further doses.
The vaccine advisory group has said it will continue to monitor the evidence around the duration of protection and advise on the need for subsequent (booster) doses in immunocompromised populations to address waning protection or the risk posed by variants of concern.
Further advice on booster doses, including for healthcare workers, older adults and the general population, is expected at a later date.
A third dose is recommended for people with the following immunocompromising conditions and therapies:

  • Active haematological malignancy
  • Non-haematological malignancy with current active treatment including chemotherapy, radiotherapy, and/or hormonal therapy, but excluding immunotherapy with immune checkpoint inhibitors
  • Solid organ transplant with immunosuppressive therapy
  • Haematopoietic stem cell transplant (HSCT) recipients or chimeric antigen receptor T-cell (CAR-T) therapy within two years of transplantation
    • These patients require revaccination with three additional doses of COVID-19 vaccine, irrespective of doses given prior to transplantation, commencing generally ≥3–6 months after their transplant after discussion with their treating specialist.
    • Those beyond two years from transplant should discuss with their treating specialist about the need for a third dose.
  • Immunosuppressive therapies, including:
    • high dose corticosteroid treatment equivalent to >20 mg/day of prednisone for ≥14 days in a month, or pulse corticosteroid therapy
    • multiple immunosuppressants where the cumulative effect is considered to be severely immunosuppressive
    • selected conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDS):
      • including mycophenolate, methotrexate (>0.4 mg/kg/week), leflunomide, azathioprine (>3 mg/kg/day), 6-mercaptopurine (>1.5 mg/kg/day), alkylating agents (eg cyclophosphamide, chlorambucil), and systemic calcineurin inhibitors (eg cyclosporin, tacrolimus)
      • excluding hydroxychloroquine or sulfasalazine when used as monotherapy
    • biologic and targeted therapies anticipated to reduce the immune response to COVID-19 vaccine:
      • including B cell depleting agents (eg anti-CD20 monoclonal antibodies, BTK inhibitors, fingolimod), anti-CD52 monoclonal antibodies (alemtuzumab), anti-complement antibodies (eg eculizumab), anti-thymocyte globulin (ATG) and abatacept
      • excluding agents with likely minimal effect on vaccine response such as immune checkpoint inhibitors, anti-integrins, anti-TNF-α, anti-IL1, anti-IL6, anti-IL17, anti-IL4 and anti-IL23 antibodies
  • Primary immunodeficiency, including combined immunodeficiency and syndromes, major antibody deficiency (eg, common variable immune deficiency [CVID] or agammaglobulinemia), defects of innate immunity (including phagocytic cells), defects of immune regulation, complement deficiencies and phenocopies of primary immunodeficiencies
  • Advanced or untreated HIV with CD4 counts <250/μL or those with a higher CD4 count unable to be established on effective antiretroviral therapy
    • a third primary dose is not required for people living with HIV, receiving ART with CD4 counts ≥250/μL
  • Long-term haemodialysis or peritoneal dialysis
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Dr Penelope Ann Martin   21/12/2021 2:07:04 PM

I have an immunosuppressed patient who has poorly controlled Crohn's Disease who has not been vaccinated at all.
Part of the reason is that her gastroenterologist says that she should not be vaccinated unless she comes of Imuran for 4 weeks prior to and 2 weeks post vaccination to improve the effectiveness of the vaccine. My patient will not take the chance of worsening already poorly controlled disease.
My understanding was that we vaccinated with a 3 dose course of covid vaccine to compensate for the effect of the immunosuppressant
medication on immune response.
I cannot find any ATAGI information which says that medications should be stopped. My colleagues say that they have heard specialists eg GEs rheumatologists tell patients to stop their immunosuppressants before vaccination.
What to do ?