As many people begin the countdown to their summer holidays, the COVID-19 lockdown is now an afterthought. However, a subset of the population are still trapped inside, remaining as at-risk as they were when COVID first arrived in the UK over two years ago. The recent MHRA approval of a pre-COVID exposure biological drug may now provide these individuals with a way out...

Individuals with a compromised immune system, whether because of an immunodeficiency or immunosuppressive treatment, remain among those most susceptible to SARS-CoV-2. For them, the lockdown restrictions of March 2020 never ended. According to Governmental guidance, immunocompromised individuals are still encouraged to wear face masks when meeting others from outside of their household and are urged to stay away from highly populated places. They are not to go near anyone who is showing signs of illness and are warned to stay away from anyone who has not been vaccinated.¹

The UK has now fully removed its requirements for masks and mandatory self-isolation, instead pushing ahead with its 'living safely with COVID' strategy.² This leaves the UK's ~500,000 immunocompromised individuals trapped in their homes, limiting their social contact based on vaccination and health status, in fear that they have been forgotten. The recent retraction of free lateral flow tests for the public also leaves their family and friends out-of-pocket should they want to ensure they are free from the disease prior to visiting.

Not only are this group of individuals at the highest risk of severe or fatal disease, but they are also less likely to mount a sufficient immune response to COVID-19 vaccination.^3,4 To mitigate this risk, the World Health Organisation (WHO) recommended those who are moderately or severely immunocompromised should receive an additional vaccine dose.⁵ In the UK, this jumps to four doses for eligible patients.¹ Yet the extent to which these patients will benefit from additional doses of vaccine remains uncertain.

A recent study by Imperial College London found that 19% of 239 kidney transplant recipients who received four vaccine doses had not shown any immune response.⁶ The UK strategy for COVID-19 management focuses heavily on vaccines and has left those for whom vaccines don't work with few viable options for living with COVID.

There has also been some pushback from individuals over what constitutes 'moderately or severely immunocompromised'.¹ Millions of people live with chronic illness or disability, and while these may not fall under the umbrella of immunocompromised, they are living with an increased susceptibility to the disease and this may not be reflected properly in their treatment options.

However, the COVID-19 pandemic has shown us just how quickly science can work; alongside the development of multiple vaccines, there are now three anti-viral treatments available in the UK: Paxlovid (nirmatrelvir and ritonavir), Veklury (remdesivir) and Lagevrio (molnupiravir). These increase the arsenal of weapons against COVID-19. However, all are only licensed to individuals who have already contracted SARS-CoV-2; something which the immunocompromised population are desperately trying to avoid.

More recently, several biologics have also been approved. These include Ronapreve (casirivimab and imdevimab), Xevudy (sotrovimab) and most recently Evusheld (tixagevimab and cilgavimab). Ronapreve was the first monoclonal antibody treatment for SARS-CoV-2 to gain MHRA approval, with Xevudy and Evusheld following.^7-9 These biologics consist of monoclonal antibodies that target the spike protein on the outside of SARS-CoV-2 particles, where they neutralise the virus and prevent it from entering human cells and replicating.

While the mechanism of action for Ronapreve, Xevudy and Evusheld is comparable, each is licensed for use in differing situations:

• Xevudy is for the treatment of symptomatic at-risk individuals with acute COVID-19 infection¹⁰
• Ronapreve can be given both prior to infection (prophylaxis) or for treating an infection¹¹
• Evusheld is indicated for pre-exposure prophylaxis only¹²

The recent approval of Evusheld solely as a pre-exposure prophylaxis could be huge for individuals living with immunosuppression. Evusheld has been approved specifically for use in individuals that are unlikely to mount a sufficient response to vaccination, or for whom vaccination is not recommended. This could allow individuals with immunosuppression the freedom they have been waiting for, where ongoing treatments with Evusheld would let them live a life outside of their own home. Following the recent approval by the MHRA,⁹ it is now in the hands of the UK Government and NHS to decide to what extent this will be rolled out, how much they will buy and who will be eligible for treatment.

For immunosuppressed individuals in the UK, it will be a nervous wait while the government decides their fate.

References

1. UK Health Security Agency and Department of Health and Social Care. COVID-19: guidance for people whose immune system means they are at higher risk. May 2022. Available at: https://www.gov.uk/government/publications/covid-19-guidance-for-people-whose-immune-system-means-they-are-at-higher-risk (accessed May 2022).
2. UK Health Security Agency. Living safely with respiratory infections, including COVID-19. April 2022. Available at: https://www.gov.uk/guidance/living-safely-with-respiratory-infections-including-covid-19 (accessed May 2022).
3. Lee ARYB, et al. BMJ 2022;376:e068632.
4. Thomson T, et al. medRxiv 2022;doi: 10.1101/2022.04.29.22274396.
5. United Nations News. WHO advisory group recommends extra COVID-19 vaccine dose for immunocompromised. October 2021. Available at: https://news.un.org/en/story/2021/10/1102732 (accessed May 2022).
6. Parker EPK, et al. Lancet 2022;10:E326-E328.
7. Medicines and Healthcare products Regulatory Agency (MHRA). First monoclonal antibody treatment for COVID-19 approved for use in the UK. August 2021. Available at: https://www.gov.uk/government/news/first-monoclonal-antibody-treatment-for-covid-19-approved-for-use-in-the-uk (accessed May 2022).
8. Medicines and Healthcare products Regulatory Agency (MHRA). MHRA approves Xevudy (sotrovimab), a COVID-19 treatment found to cut hospitalisation and death by 79%. December 2021. Available at: https://www.gov.uk/government/news/mhra-approves-xevudy-sotrovimab-a-covid-19-treatment-found-to-cut-hospitalisation-and-death-by-79 (accessed May 2022).
9. Medicines and Healthcare products Regulatory Agency (MHRA). Evusheld approved to prevent COVID-19 in people whose immune response is poor. March 2022. Available at: https://www.gov.uk/government/news/evusheld-approved-to-prevent-covid-19-in-people-whose-immune-response-is-poor (accessed May 2022).
10. Ronapreve (casirivimab and imdevimab). Summary of Product Characteristics.
11. Xevudy (sotrovimab). Summary of Product Characteristics.
12. Evusheld (tixagevimab and cilgavimab). Summary of Product Characteristics.