Title: Tixagevimab–cilgavimab for preventing COVID-19 [ID6136]
Funder: Department of Health and Social Care

Abstract: COVID-19 is predominantly an acute respiratory illness caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease refers to any symptom resulting from the infection and these can vary widely in clinical severity. People who become critically ill may develop acute respiratory distress syndrome (ARDS), the leading cause of mortality among patients with COVID-19. _x000D_ _x000D_ The COVID-19 pandemic rapidly evolved globally, with countries facing different stages of the spread of disease. In England and Wales between 7 March 2020 and 1 July 2022, 180,642 deaths occurred involving COVID-19.[1] The gradual mutation of SARS-CoV-2 has led to increased cases of various variants of concern, each with different transmissibility, morbidity, and mortality effects. Data from the UK suggest that mortality due to COVID-19 is strongly associated with older age, male gender, deprivation and Black, Asian and minority ethnic family background.[2] Disabled people, people with a learning disability and people with pre-existing conditions, including people with dementia and Alzheimer’s disease, diabetes, heart disease or obesity, are more at risk from dying from COVID-19. [3],[4] People at increased risk from COVID-19 have been required to shield long-term during the COVID-19 pandemic, which may also impact their mental health.[5],[6] _x000D_ _x000D_ COVID-19 has a diverse range of clinical manifestations, ranging from mild infection to severe disease accompanied by high mortality.[7] It begins with infection, or the viral replication phase, with symptoms such as cough, fever and breathlessness. This disease stage is when viral shedding occurs and people are at the peak of infectiousness. Some people may also develop post-COVID syndrome, defined by the NICE’s rapid guideline on managing the long-term effects of COVID-19 as symptoms continuing for more than 12 weeks after the initial COVID-19 infection. _x000D_ _x000D_ Vaccination is the primary pharmaceutical intervention for preventing COVID-19. There are 3 vaccines authorised and currently available for use in the UK for preventing COVID-19 in adults. Adults in England are eligible for 2 initial doses of a COVID-19 vaccine followed by at least one booster dose.[8] Vaccination may be unsuitable for some people for example, if they have a history of severe allergic reactions or anaphylaxis to any of the ingredients in the vaccine. Some people also have an increased risk of inadequate response to COVID-19 vaccination. The OCTAVE trial showed 40% of people with specific immunocompromised or immunosuppressed conditions generate lower levels of SARS-CoV-2 antibody reactivity compared to healthy people after 2 COVID-19 vaccines. [9] The MELODY study aims to further improve the understanding of responses to COVID-19 vaccination in individuals who have had 3 doses of vaccine and have had a transplant or have disease treated with immunosuppressants. [10] In the PROVENT study, potential risk factors for poor vaccination response included being older than 60, obesity, being immunocompromised, having congestive heart failure, chronic obstructive pulmonary disease, chronic kidney disease or chronic liver disease.[11] An independent UK government advisory group has identified specific groups of people at highest risk of hospitalisation and death despite receiving COVID-19 vaccination. [12]_x000D_ _x000D_ References_x000D_ 1. Office for National Statistics (2022) Deaths registered weekly in England and Wales, provisional. Accessed July 2022._x000D_ 2. Government Actuary’s Department (2020) Mortality Insights from GAD - December 2020. Accessed July 2022._x000D_ 3. The King’s Fund (2021) Deaths from Covid-19 (coronavirus). Accessed July 2022._x000D_ 4. Public Health England (2020) Deaths of people identified as having learning disabilities with COVID-19 in England in the spring of 2020. Accessed July 2022._x000D_ 5. Department of Health and Social Care (2022) Guidance for people previously considered clinically extremely vulnerable from COVID-19. Accessed August 2022_x000D_ 6. Rettie, H and Daniels, J, (2022) The Mental Health Impact of the COVID-19 Pandemic Second Wave on Shielders and their Family Members. International Journal of Environmental Research and Publich Health._x000D_ 7. Cevik M, Kuppalli K, Kindrachuk J et al. (2020) Virology, transmission, and pathogenesis of SARS-CoV-2. The BMJ._x000D_ 8. NHS (2022) Coronavirus (COVID-19) vaccine. Accessed July 2022._x000D_ 9. National Institute for Health and Care Research (2021) OCTAVE trial: Initial data on vaccine responses in patients with impaired immune systems. Accessed August 2022_x000D_ 10.Imperial College London, Faculty of Medicine (2022) MELODY Study. Accessed August 2022_x000D_ 11.Levin M, Ustianowski A, De Wit S et al. (2022) Intramuscular AZD7442 (Tixagevimab-Cilgavimab) for Prevention of Covid-19. The New England Journal of Medicine._x000D_ 12.Department of Health and Social Care (2022) Defining the highest-risk clinical subgroups upon community infection with SARS-CoV2 when considering the use of neutralising monoclonal antibodies (nMABs) and antiviral drugs: independent advisory group report. Accessed August 2022

Lay abstract: To appraise the clinical and cost effectiveness of tixagevimab and cilgavimab within its marketing authorisation for the pre-exposure prophylaxis of COVID-19.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: INFECTION