Researchers are exploring COVID-19 vaccination in immunocompromised individuals
Researchers are exploring COVID-19 vaccination in immunocompromised individuals

Researchers are exploring COVID-19 vaccination in immunocompromised individuals

A review published in Journal of Allergy and Clinical Immunology discusses safety and efficiency of vaccination against coronavirus disease 2019 (COVID-19) and potential strategies to optimize protection in patients with impaired immunity.

Examination: SARS-CoV-2 vaccination in the immunocompromised host. Image credit: siam.pukkato / Shutterstock

Causes of a compromised immune system

Immunocompromised individuals have severely impaired immunity, which may be due to a congenital immunity defect (IEI); the effect of immunosuppressive drugs in an autoimmune disease, blood cancer, during an organ transplant; or poorly controlled human immunodeficiency virus (HIV). Due to weakened immunity, immunocompromised individuals are more prone to infections. However, the risk of preventable infections can be reduced by vaccination.

Safety of COVID-19 vaccines

Immunocompromised individuals have been excluded from COVID-19 vaccine trials. There are insufficient safety data on COVID-19 vaccinations in immunocompromised individuals. This has led to hesitation with vaccines. Several studies have shown that vaccination reactions in immunocompromised individuals are similar to those in the general population.

A study has shown that immunosuppressed patients with autoimmune diseases do not report any severe reaction or flare-up of underlying disease that would require hospitalization after vaccination. There are limited data on the safety of additional vaccine doses, but early reports are reassuring.

Immune response to vaccination

Antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) peak protein is a surrogate for immune protection due to COVID-19 vaccination or natural infection. COVID-19 vaccination induces robust antibody responses in immunocompetent individuals. However, levels of antibodies are lower in many immunocompromised individuals. Immune deficiency can dull the immune response to vaccination. An additional dose of vaccine is therefore recommended for immunocompromised individuals. Yet some immunocompromised individuals do not respond to multiple doses of vaccine.

What is immune protection in immunocompromised patients?

SARS-CoV-2 variants of concern (VOCs) contain mutations in the nail protein that allow the virus to escape the immune system. The Omicron variant requires higher levels of neutralizing antibodies for effective neutralization and prevention of infection. Immunocompromised individuals without neutralizing antibodies or a seronegative status have a high incidence of breakthrough infections. Seronegativity can be used to identify individuals at the highest risk of infection. Nevertheless, a definition of immune protection is required to calculate the risk and inform about additional protection strategies.

Potential strategies to increase the immune response

Booster doser

Additional vaccine doses may increase the decreasing vaccine immunity. Frequent vaccine doses are not a possible global option. Further studies are needed to determine the optimal time for re-dosing.

Choice of vaccine platform

Two-dose vaccination elicits a better response in immunocompromised individuals compared to a single dose of Ad.26.COV2.S.

The mRNA-1273 vaccination is associated with fewer breakthrough infections compared to the BNT162b2 vaccination. In addition, mixing the vaccines is associated with lower COVID-19 frequency compared to two doses of the same vaccine. However, we do not know if this also applies to immunocompromised individuals.

Pause immunosuppressive drugs

In immunocompromised individuals with autoimmune diseases, a temporary team of immunosuppressive drugs during the vaccination period elicits a better antibody response compared to the response while taking immunosuppressive drugs.

Therapeutic strategies

Prophylaxis with an anti-spike monoclonal antibody (mAb) combination of tixagevimab and cilgavimab (EVUsheld) may improve COVID-19 protection. EVUsheld is effective against the predominantly Omicron VOC.

It should be considered for all seronegative individuals. It should also be considered for post-exposure prophylaxis in individuals at high risk for severe COVID-19 outcomes.

In addition, there are new antiviral agents such as nirmatrelvir plus ritonavir and molnupiravir that can effectively prevent severe COVID-19 failure.

Nevertheless, these therapeutic measures should be added to other strategies for reducing public health risks, including masking, maintaining hand hygiene and social distance.


Immunosuppression suppresses COVID-19 vaccine response. Clinical correlates of immune protection and dynamics of vaccine response should be understood to inform the timing of additional vaccine doses to immunocompromised individuals. The role of cell-mediated immunity and its clinical relevance must also be evaluated.

Due to the rapid development of SARS-CoV-2, researchers should continue to dynamically expand their knowledge base. There is a need to develop new protection measures against COVID-19.

Immunocompromised individuals are a vulnerable population. Their protection requires a multifaceted strategy: optimization of vaccination plan and platform, modulation of immunosuppressive drugs during the vaccination period (whenever possible), use of immunoprophylaxis, early intervention with antiviral therapies and continued risk mitigation strategies. Immunocompromised individuals should be given priority for prophylaxis and prophylaxis.

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