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A major international study led by the Nuffield Department of Primary Care Health Sciences has developed a new, globally agreed approach to identifying and monitoring immunosuppressed adults at risk of severe COVID-19 illness.

The study, published in The Lancet eClinicalMedicine, aims to improve clinical care, disease surveillance, and resource allocation for the most vulnerable patient groups. 

The DESTINIES Study brought together 64 leading experts in immunology, virology and infectious disease from across 16 countries and four continents. Their goal: to resolve long-standing disagreements over which medical procedures and diagnoses would confer immunosuppression and which of these would carry the greatest risk of severe illness from COVID-19. 

The result is the DESTINIES Phenotype - a clinically grounded, COVID-specific classification system that groups individuals with immunosuppression into high, moderate or low risk bands based on their underlying diagnoses. Designed to work within electronic medical records, this new system categorises patients into ten risk categories and aims to improve disease surveillance and public health decision-making by giving a clearer picture of who is most at risk. 

The study reached several important conclusions: 

  • Patients with solid organ or bone marrow transplants, blood cancers and primary immunodeficiencies were consistently rated as high risk for severe COVID-19. 

  • Drug-managed HIV and cancer in remission were removed from immunosuppression classifications - a landmark change that recognises the effectiveness of modern treatments. However, experts noted exceptions, including cancers treated with bone marrow transplants and the long-lasting effects of certain therapies like rituximab, where immunosuppression may persist despite remission. 

  • The phenotype received overwhelming support from both the expert panel (94%) and a newly formed DESTINIES Patient Panel (89%). 

Meredith Leston, who led the study, explained: 

‘The DESTINIES study has far-reaching implications for public health. Without clearly identifying those at highest risk for COVID-19, it’s impossible to target life-saving resources such as vaccines, antiviral treatments, and protective measures effectively. Conversely, without identifying those least at risk, patients may face unnecessary restrictions and heightened fear during periods of COVID-19 transmission. Our newly developed system will provide the evidence base to support health care decisions that are more commensurate with patient risk. 

Managing the treatment of people with suppressed immune systems is complicated by a number of factors. They are often excluded from clinical trials, leaving significant blind spots in understanding treatment efficacy and safety. Disease surveillance systems also vary widely, with some grouping immunosuppressed patients into broad categories or focusing only on larger subgroups like cancer patients. These inconsistencies, compounded by international differences in defining immunosuppression, have undermined effective care.  

While not intended for direct clinical decision-making, the DESTINIES Phenotype is expected to strengthen COVID-19 disease surveillance in the first instance and enable more equitable distribution of vaccines, treatments and protective measures. 

Professor Richard Hobbs, Mercian Professor of Primary Care and a senior author of the study, concluded:  

‘We are confident that our new system will provide the detailed information needed to better protect this underserved group, including how infections may affect them and how well treatments could work. While it isn’t designed for direct clinical decisions, its ability to better highlight the more vulnerable of immunosuppressed patients is crucial step for improving health equity.’   

The research team is now working to validate the DESTINIES Phenotype in real-world data, with the aim of making it available for global use in future pandemic preparedness and infectious disease surveillance. 

 

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