Immunocompromised populations and the risk of viral variants

What are viral variants and how do they emerge?

Viruses are constantly changing and evolving. These changes are called mutations and can sometimes lead to a new variant of a virus.1 All variants of a virus act differently – some have minimal impact on how a virus spreads or the severity of illness caused, and others are more concerning. Some variants might disappear quickly while others dominate and persist.1

When a virus – such as SARS-CoV-2 – is circulating widely in a population and successfully spreading infection between people, it is replicating more and the likelihood of new variants emerging increases.2 This poses a risk to strategies aimed at protecting individuals against infection and controlling the pandemic. Measures that reduce the spread of infection or ‘viral presence’ in the community, including vaccination, can slow the emergence of new, and potentially more dangerous, variants appearing.1

The World Health Organization, in collaboration with national authorities, expert networks and researchers, have been monitoring and assessing the emergence of SARS-CoV-2 variants around the world. The established global COVID-19 variants of concern, including B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta) and now B.1.1.529 (Omicron), all feature multiple mutations. These mutations have created variants that are associated with one or more of the following characteristics, which are considered to be of significance to global public health:

  • more likely to be transmitted
  • increased virulence causing more severe infection, or change in disease presentation
  • less susceptible to public health and social measures such as available diagnostics, vaccines or therapeutics.

Latest information on the tracking of SARS-CoV-2 variants, including SARS-CoV-2 variants of concern, can be found on the World Health Organization website.3

The immunocompromised and viral variants

Ensuring that as many people as possible are protected from a virus is key to preventing infection as well as the emergence of new variants. As more people in a community become protected, the circulation of a virus is expected to decrease, which leads to fewer mutations and variants.2

Recent studies have shown that people who are immunocompromised – meaning they have a weakened immune system and are less able to fight infection or disease – may inadvertently play a role in spurring the mutations of the virus that create new variants.4 This is because some immunocompromised individuals remain at risk of getting COVID-19 despite vaccination, and also experience more severe disease and remain contagious for longer if they become infected.5,6,7

Immunocompromised individuals represent approximately 2% of the overall population.8 Many of these people are unable to mount an adequate response to COVID-19 vaccination and remain at high-risk for the disease.5,7

Immunocompromised populations may include people:7,9

  • with blood cancers or other cancers receiving chemotherapy
  • on dialysis
  • taking medication following an organ transplant
  • taking immunosuppressive drugs for autoimmune conditions.

A trial from Israel showed that more than 40% of people hospitalised with breakthrough infections after vaccination were immunocompromised [retrospective, multicentre trial involving 152 patients].5 Immunocompromised patients often have more comorbidities and experience worse outcomes following hospitalisation for COVID-19 versus the general population.6 Additionally, immunocompromised patients are susceptible to being chronically infected and contagious for a much longer period.7

How does prolonged infection increase the risk of new SARS-CoV-2 variants emerging?

While the main cause of viral mutation is wide circulation in a population and successful transmission between people, evidence shows that prolonged or chronic infection with SARS-CoV-2 can also increase the possibility of highly mutated viral variants arising.2,4 This is because long-term infection in an individual gives the virus time to replicate and evolve in an unhindered way, and to develop mutations that can change the way that the virus infects cells or resists antibodies.10,11 Scientists report that SARS-CoV-2 variants with a high number of mutations can emerge during a single, persistent case of COVID-19.10,12

People who are immunocompromised have an increased risk of developing severe COVID-19 illness and experiencing prolonged infection and viral shedding.10 Some patients with severely weakened immune systems can take months to clear the COVID-19 virus.7 Evidence suggests that the evolution of the SARS-CoV-2 virus in people with prolonged illness, such as immunocompromised populations, may be another important factor in the emergence of new, more transmissible, or adaptive viral variants.4 This has implications for public health strategies aimed at tackling the global pandemic.

How can we better protect immunocompromised patients and reduce viral transmission?

Researchers are working to better understand immune responses following COVID-19 vaccination, as well as develop strategies to best treat immunocompromised people to clear their virus without the risk of treatment-resistant variants arising.

Stopping the spread of viruses and maximising protection against new variants remain key to tackling the global pandemic.2 Vaccination is the preferred option for providing individual immune protection, whilst also limiting broader disease transmission within a community.2 However, many immunocompromised individuals do not respond fully to vaccines and remain vulnerable, with the added threat of new variants of concern emerging.4,5,7 Additional options that could potentially offer longer-lasting protection may be helpful for those at high risk of chronic infection, and might assist in reducing viral transmission and controlling the ongoing global pandemic.


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1. Centers for Disease Control and Prevention. What You Need to Know About Variants. Available from: Last accessed: December 2021.

2. World Health Organization. The effect of virus variants on COVID-19 vaccines. Available at: Last accessed: December 2021.

3. World Health Organization. Tracking SARS-CoV-2 variants. Available at: Last accessed: December 2021.

4. Corey L, Beyrer C, Cohen M, et al. SARS-CoV-2 Variants in Patients with Immunosuppression. NEJM. 2021; 385:562-566.

5. Brosh-Nissimov T, Orenbuch-Harroch E, Chowers M, et al. BNT162b2 vaccine breakthrough: clinical characteristics of 152 fully vaccinated hospitalized COVID-19 patients in Israel. Clin Microbiol Infect. 2021;27:1652-1657.

6. Belsky J, Tullius B, Lamb M, et al. COVID-19 in immunocompromised patients: A systematic review of cancer, hematopoietic cell and solid organ transplant patients. J Infect. 2021; 82(3):329-338.

7. Abbasi J. Researchers Tie Severe Immunosuppression to Chronic COVID-19 and Virus Variants. JAMA. 2021; 325:2033-2035.

8. AstraZeneca Data on File 2021. REF-129335. 

9. Centers for Disease Control and Prevention. Altered Immunocompetence. General Best Practice Guideline for Immunization: Best Practices Guidance of the Advisory Committee on Immunization Practices. Available from: Last accessed: December 2021.

10. Weigang S, Fuchs J, Zimmer G, et al. Within-host evolution of SARS-CoV-2 in an immunosuppressed COVID-19 patient as a source of immune escape variants. Nat Commun. 2021; 12, 6405. 

11. Sutherland, S. COVID Variants May Arise in People with Compromised Immune Systems. Sci Amer. Available at: Last accessed: December 2021.

12. Kemp S, Collier D, Datir R, et al. SARS-CoV-2 evolution during treatment of chronic infection. Nature. 2021; 592: 277-282.

Veeva ID: Z4-40584
Date of preparation: December 2021