Vaccine Confident mark
An initiative to help pharmacists strengthen vaccine confidence in their patients and communities
How to talk to people about COVID-19 vaccines Addressing concerns that the COVID-19 vaccines were “rushed” Addressing concerns about COVID-19 vaccine side effects Addressing concerns related to pregnancy, breastfeeding, and fertility Addressing the belief that COVID-19 vaccination is “not needed” Addressing concerns about COVID-19 breakthrough infections Addressing concerns related to religious beliefs Understanding the “COVID skeptics” Addressing concerns about staying up to date with COVID-19 vaccines How to restart the vaccine conversation Understanding the “system distrusters” Addressing concerns about SARS-CoV-2 variants Identifying credible information about COVID-19 Vaccines Addressing COVID-19 vaccine myths Understanding the “cost anxious” Addressing concerns about vaccinating children and teens Addressing COVID-19 vaccine misinformation and disinformation Addressing COVID-19 vaccine misunderstandings Addressing concerns about administering COVID-19 vaccines with other vaccines Addressing concerns of people who are immunocompromised Effectiveness of COVID-19 vaccines during pregnancy and after delivery Using numbers to communicate COVID-19 risk to patients Managing pandemic-related exhaustion

Addressing Concerns of People Who Are Immunocompromised

Note: While this section was written with COVID-19 vaccines in mind, many of the general principles apply to other vaccines as well. Individual vaccines may vary in their antigenic components or dosage forms, but the principles of human behavior and good communication skills transcend most differences between vaccines.

The Issue

People with compromised immune systems have been disproportionately affected by the COVID-19 pandemic: they are both more susceptible to SARS-CoV-2 infection and more vulnerable to severe COVID-19 illness and death. Unfortunately, messaging that COVID-19 vaccination is ineffective for immunocompromised persons or works less well in that population may have caused some people to question the value of COVID-19 vaccines. Confusing and changing guidance and terminology left many patients and pharmacists unsure about recommendations for COVID-19 vaccination in immunocompromised persons.

Sound Bites

  • People who are moderately or severely immunocompromised (have a weakened immune system) have an increased risk of severe COVID-19 illness (e.g., hospitalization, admission to the intensive care unit, intubation or mechanical ventilation) and death.
  • The immune response to COVID-19 vaccination in people who are immunocompromised may not be as strong as in people who are not immunocompromised. However, the vaccines still provide important protection against severe COVID-19 illness and death.
  • Immunocompromised persons are protected best from severe COVID-19 illness and death when they stay up to date with their COVID-19 vaccines.
  • People are allowed to self-attest to their moderately or severely immunocompromised status. This means they do not need any documentation of their status to receive COVID-19 vaccine doses for which they are eligible, wherever they are offered.

Questions for Exploring Patient Concerns

  • What do you know about the effectiveness of COVID-19 vaccines in people with weakened immune systems?
  • What concerns you most about getting a COVID-19 vaccine?
  • What would have to be true for you to think it was important to get a COVID-19 vaccine?
  • What if I told you…? (Provide information relevant to the patient’s concerns.)

What We Know

The first COVID-19 vaccines were authorized in December 2020, less than 1 year after the genetic blueprint of the novel coronavirus SARS-CoV-2 was identified. This unprecedented timeline was achieved in part because phase 3 trials were conducted during a time of very high community transmission, making it possible for researchers to tell within months whether a vaccine was effective in protecting the vaccinated groups (compared with the placebo groups).

Because those phase 3 trials had to be completed as quickly as feasible and were focused on determining vaccine efficacy and safety in the general adult population, they excluded nearly all people with compromised immune systems (e.g., patients with cancer, patients with rheumatological disorders, organ transplant recipients). And because vaccines work by harnessing the capability of a fully competent immune system, there was concern about the immune response to COVID-19 vaccines in immunocompromised persons and the level of protection vaccination would offer.

Early data were not promising. An analysis of a convenience sample of 436 solid organ transplant recipients who received a first dose of an mRNA vaccine between December 16, 2020, and February 5, 2021, found that less than 20% mounted appreciable antispike antibody responses.1 A follow-up study showed some improvement in antispike antibody responses after a second vaccine dose compared with dose 1, but the gains were relatively modest. Of the 658 transplant recipients included in that analysis (396 of whom were part of the first study), 98 (15%) had measurable antibody response after dose 1 and dose 2; 301 (46%) had no antibody response after dose 1 or dose 2; and 259 (39%) had no antibody response after dose 1 but subsequent antibody response after dose 2.2 A meta-analysis confirmed lower seroconversion rates and antibody concentrations after COVID-19 vaccination in immunocompromised patients than immunocompetent individuals.3 Organ transplant recipients showed the lowest rates of seroconversion; patients with solid tumors showed the highest.

These data were concerning because people who are moderately or severely immunocompromised are at higher risk for severe illness from COVID-19. People are considered to be moderately or severely immunocompromised due to conditions and treatments that include4:

  • Active treatment for solid tumor and hematologic malignancies.
  • Receipt of solid-organ transplant and taking immunosuppressive therapy.
  • Receipt of chimeric antigen receptor T-cell (CAR-T) therapy or hematopoietic cell transplant (within 2 years of transplantation or taking immunosuppressive therapy).
  • Moderate or severe primary immunodeficiency (e.g., DiGeorge syndrome, Wiskott-Aldrich syndrome).
  • Advanced or untreated HIV infection (people with HIV and CD4 cell counts less than 200 cells/mm3, history of an AIDS-defining illness without immune reconstitution, or clinical manifestations of symptomatic HIV).
  • Active treatment with high-dose corticosteroids (i.e., 20 mg or more of prednisone or equivalent per day when administered for 2 or more weeks), alkylating agents, antimetabolites, transplant-related immunosuppressive drugs, cancer chemotherapeutic agents classified as severely immunosuppressive, tumor necrosis factor blockers, and other biologic agents that are immunosuppressive or immunomodulatory.

To help explain the scientific basis for its recommendations, the CDC maintains a dedicated web page with specific COVID-19 vaccine guidance for moderately or severely immunocompromised people. The CDC emphasizes that immunocompromised people are best protected against serious COVID-19 illness, hospitalization, and death when they stay up to date with COVID-19 vaccines. Current recommendations are summarized in the CDC COVID-19 Vaccination Schedule for People Who Are Moderately or Severely Immunocompromised.

The CDC allows people to self-attest to their moderately or severely immunocompromised status. This means they do not need any documentation of their status to receive COVID-19 vaccine doses for which they are eligible, wherever those doses are offered.5

Immunocompromised persons should be reassured that COVID-19 vaccines do indeed work by providing robust protection against severe illness. In a case-control analysis using data from 21 hospitals across the United States (the co-called IVY Network), vaccine effectiveness for three original mRNA vaccine doses to prevent hospital admission was high for both immunocompetent persons (97%; 95% CI 95%–98%) and immunocompromised persons (87%; CI 78%–92%) when the Delta variant was dominant (July 4 to December 25, 2021).6 Another case-control analysis using IVY Network data evaluated vaccine effectiveness against the most severe outcomes of COVID-19 hospitalizations: invasive mechanical ventilation and in-hospital death.7 Across the surveillance period (March 2021 to January 2022), vaccine effectiveness was 92% (CI 91%–94%) among immunocompetent persons and 74% (CI 64%–81%) among adults with immunocompromising conditions. However, of the 123 vaccinated COVID-19 case patients with immunocompromising conditions, only 17 (14%) had received three vaccine doses and were considered fully vaccinated.

References

  1. Boyarsky BJ, Werbel WA, Avery RK, et al. Immunogenicity of a single dose of SARS-CoV-2 messenger RNA vaccine in solid organ transplant recipients. JAMA. 2021;325(17):1784–1786. doi: 10.1001/jama.2021.4385
  2. Boyarsky BJ, Werbel WA, Avery RK, et al. Antibody response to 2-dose SARS-CoV-2 mRNA vaccine series in solid organ transplant recipients. JAMA. 2021;325(21):2204–2206. doi: 10.1001/jama.2021.7489
  3. Lee ARYB, Wong SY, Chai LYA, et al. Efficacy of COVID-19 vaccines in immunocompromised patients: systematic review and meta-analysis. BMJ. 2022;376:e068632. doi: 10.1136/bmj-2021-068632
  4. Centers for Disease Control and Prevention. People with certain medical conditions. Updated April 15, 2024. Accessed April 15, 2024. https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html
  5. Centers for Disease Control and Prevention. COVID-19 vaccines for people who are moderately or severely immunocompromised. Updated March 8, 2024. Accessed April 12, 2024. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/immuno.html
  6. Lauring AS, Tenforde MW, Chappell JD, et al.; Influenza and Other Viruses in the Acutely Ill (IVY) Network. Clinical severity of, and effectiveness of mRNA vaccines against, COVID-19 from omicron, delta, and alpha SARS-CoV-2 variants in the United States: prospective observational study. BMJ. 2022;376:e069761. doi: 10.1136/bmj-2021-069761
  7. Tenforde MW, Self WH, Gaglani M, et al.; IVY Network. Effectiveness of mRNA vaccination in preventing COVID-19–associated invasive mechanical ventilation and death—United States, March 2021–January 2022. MMWR Morb Mortal Wkly Rep. 2022;71(12):459–465. doi: 10.15585/mmwr.mm7112e1

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