Will the COVID-19 vaccines be safe for immunocompromised patients?

I’ve gotten this question from a few people, and I initially put out a detailed post explaining what the current guidances are from ACIP, IDSA, and the Immune Deficiency foundation but I decided that regardless of how many disclaimers I put, it was too close to medical advice and it was probably too technical for most people wondering about it to benefit from it.

In general, when an individual has altered immunocompetence (which is to say, their immune system cannot effectively respond to antigens either because of HIV infection, genetic causes, certain drugs, surgical removal of the spleen, etc.) there are some important differences in how they need to be vaccinated. Principally, the big concern is live attenuated vaccines. Live attenuated vaccines contain a real, replicating pathogen that has been adapted to grow poorly in humans. Examples include MMR, and the BCG vaccine for tuberculosis (not routinely given in the US). In an immunologically competent person, these are no problem. But because people with altered immunocompetence can have trouble clearing pathogens, in some cases live attenuated vaccines can be dangerous and reproduce the disease they are intended to prevent. For some of these individuals live bacterial vaccines may be okay but live viral ones may not or vice versa. This depends on the specific immunological problems, and you should speak to the specialists managing your care regarding which vaccines you should and should not receive.

In some cases, live vaccines may be safe in the setting of a specific condition in which they ordinarily would not be. For example patients who have severe combined immunodeficiency can receive a hematopoietic stem cell transplant to replace their immune system, and when their cell counts are sufficiently high, may be able to receive certain live attenuated vaccines e.g. MMR.

In addition, some vaccines can become more important with certain immunodeficiencies. For example, in individuals who have asplenia (absence of a spleen, either functionally or due to surgical removal), vaccines for meningococcal, pneumococcal, and Hib disease are ESPECIALLY important because their ability to defend against these pathogens is dramatically reduced from the absence of a spleen.

For nonviable vaccines, these are no more risky in those with altered immunocompetence than those without. However, individuals with altered immunocompetence are less likely to generate protective responses against from these vaccines (though this depends on the specific immunological issues at play). Some argue that in individuals in which there is essentially no possibility of a productive response e.g. severe combined immunodeficiency, nonviable vaccines are not useful and should not be given. Both the Advisory Committee on Immunization Practices and Infectious Disease Society of America do feel that these patients should receive nonviable vaccines.

Unfortunately, in general, there are limited data on which to base these recommendations. The specialists managing your (a patient who has altered immunocompetence) care are the best resource you have regarding the safety of any given vaccine for you.

Key Resources for Patients with Altered Immunocompetence

1. The care team managing your immunodeficiency.

2. Immune Deficiency Foundation, and especially their handbook.

3. Advisory Committee on Immunization Practice Guidelines

4. Infectious Disease Society of America Guidelines for Vaccination of the Immunocompromised Host 2013

These are somewhat US-centric so be sure to explore what local resources are available to you.

COVID-19 Vaccines

The COVID-19 vaccines farthest advanced in the clinical trials process are mRNA vaccines, which are inviable- though they encode a fragment of a viral protein, they do not encode a functional virus. As a result, they likely can generally be given safely to patients with altered immunocompetence (but their efficacy is entirely unknown in this patient cohort). Replication-deficient adenovirus vectors are also considered inviable, and thus should be generally safe to give to patients with altered immunocompetence (ChAdOx vaccine from Oxford and Astra-Zeneca). This of course presupposes regulatory approval of these vaccine candidates, which is not yet guaranteed.

Patients are, however, unique and not every disease or treatment has the same presentation so be sure to consult your treating physician before making changes to any aspect of your lifestyle, including vaccination.

References (these are copied from the more detailed post on altered immunocompetence that I took down)

1. Ajitkumar A, Yarrarapu SNS, Ramphul K. 2020. Chediak Higashi Syndrome. In: StatPearls. Treasure Island (FL): StatPearls Publishing.

2. Almarza Novoa E, Kasbekar S, Thrasher AJ, Kohn DB, Sevilla J, Nguyen T, Schwartz JD, Bueren JA. 2018. Leukocyte adhesion deficiency-I: A comprehensive review of all published cases. J Allergy Clin Immunol Pract. 6(4):1418-1420.e10.

3. Altered Immunocompetence. 2020 Nov 18. Cdc.gov. https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/immunocompetence.html.

4. Bousfiha A, Jeddane L, Picard C, Ailal F, Bobby Gaspar H, Al-Herz W, Chatila T, Crow YJ, Cunningham-Rundles C, Etzioni A, et al. 2018. The 2017 IUIS phenotypic classification for primary immunodeficiencies. J Clin Immunol. 38(1):129–143.

5. Kathleen E. Sullivan ERS. 2020. Stiehm’s Immune Deficiencies. London, England: Elsevier.

6. Medical Advisory Committee of the Immune Deficiency Foundation, Shearer WT, Fleisher TA, Buckley RH, Ballas Z, Ballow M, Blaese RM, Bonilla FA, Conley ME, Cunningham-Rundles C, et al. 2014. Recommendations for live viral and bacterial vaccines in immunodeficient patients and their close contacts. J Allergy Clin Immunol. 133(4):961–966.

7. Panday A, Sahoo MK, Osorio D, Batra S. 2015. NADPH oxidases: an overview from structure to innate immunity-associated pathologies. Cell Mol Immunol. 12(1):5–23.

8. Skokowa J, Dale DC, Touw IP, Zeidler C, Welte K. 2017. Severe congenital neutropenias. Nat Rev Dis Primers. 3:17032.

9. Sobh A, Bonilla FA. 2016. Vaccination in primary immunodeficiency disorders. J Allergy Clin Immunol Pract. 4(6):1066–1075.

10. Sullivan KE. 2019. Neutropenia as a sign of immunodeficiency. J Allergy Clin Immunol. 143(1):96–100.

11. Wen L, Atkinson JP, Giclas PC. 2004. Clinical and laboratory evaluation of complement deficiency. J Allergy Clin Immunol. 113(4):585–93; quiz 594.

12. Yu H-H, Yang Y-H, Chiang B-L. 2020. Chronic granulomatous disease: A comprehensive review. Clin Rev Allergy Immunol. doi:10.1007/s12016-020-08800-x. http://dx.doi.org/10.1007/s12016-020-08800-x.