Title: Rapid Outcomes of COVid therapeutics in Eave II (ROCOVE)
Funder: Chief Scientist Office, Scotland

Abstract: Following recent clinical trials, new medications have been approved to treat people with COVID-19. _x000D_ _x000D_ These include a type of medication called ‘monoclonal antibodies’. Antibodies are proteins made by the body which recognise an infection. Monoclonal antibodies stick to specific parts of bacteria or viruses. This can stop viruses from entering cells or tag them for destruction by immune cells._x000D_ Monoclonal antibody treatments for COVID-19 are made in a lab and work in the same way as the immune system. They stick to the SARS-CoV-2 virus, which causes COVID-19._x000D_ _x000D_ The monoclonal antibody treatments currently available in the UK are in limited supply. They are designed for people who have tested positive for SARS-CoV-2 and are:_x000D_ • Known to be at high risk of being very unwell with COVID-19_x000D_ • Showing symptoms after five days, but no signs of recovery._x000D_ _x000D_ Find out more about who is eligible for treatment [NHS Inform]: https://www.nhsinform.scot/illnesses-and-conditions/infections-and-poisoning/coronavirus-covid-19/coronavirus-covid-19-treatments_x000D_ _x000D_ It is important to monitor the use of these new treatments in national populations. Using large groups of people can help us look for patterns that might not be obvious in smaller clinical trials._x000D_ _x000D_ What are we planning to do?_x000D_ _x000D_ We want to understand who is most likely to benefit from monoclonal antibody and other treatments, and how many people might be suitable for it._x000D_ _x000D_ To answer questions about the new treatments that are available, we will look at:_x000D_ • Uptake: how many people have been given the new treatments. We will look at this in terms of their age, sex, location, ethnicity and COVID-19 risk;_x000D_ • Safety: if the people who had the treatments experienced any side effects. Where possible we will also look at how the treatments interact with other medications people are taking;_x000D_ • Effectiveness: how well the treatments work. We will look at the different COVID 19 virus types and how well the medications work when we combine them with other treatments. _x000D_ _x000D_ We will also look at factors shared by people who remain unwell after receiving their treatment. We think that age, medical history and existing prescriptions may be important._x000D_ _x000D_ This research is needed because of the emergence of new viral variants like Omicron. Evidence suggests that this variant spreads more easily. It may also cause vaccines to be less effective than for existing variants like Delta._x000D_ _x000D_ What data will we use? _x000D_ _x000D_ To carry out this study, we will look at all adults in Scotland who:_x000D_ • Are registered with a GP_x000D_ • Tested positive for SARS-CoV-2 after 1 December 2021._x000D_ _x000D_ To answer the research questions listed above, we will look at:_x000D_ • GP, hospital and death records_x000D_ • Community- and hospital-based prescriptions, including monoclonal antibody treatments_x000D_ • Data on viral testing and variants_x000D_ • COVID-19 vaccination records_x000D_ • Data on existing infections and immunity to COVID-19 (based on blood tests)_x000D_ _x000D_ This research is part of the EAVE II project. The data used in this project are held securely by Public Health Scotland. Our research team cannot see, or identify, who each individual is. _x000D_ _x000D_ Find out more about EAVE II: https://www.ed.ac.uk/usher/eave-ii/about-eave-ii_x000D_ _x000D_ How will we produce the results?_x000D_ _x000D_ We will follow patients from the day the treatment started until any stop or change in treatment, or the end of the study period. This includes ‘cocktails’ of more than one treatment._x000D_ _x000D_ To study the treatments’ effectiveness, we will look at the impact on:_x000D_ • The amount of time between a person starting treatment and dying or being admitted to hospital or intensive care, within 28 days of a positive test for COVID-19;_x000D_ • The length of time people spend in hospital or intensive care with COVID-19._x000D_ _x000D_ Important factors like a person’s age, sex, location, health history and vaccination status will be taken into account. _x000D_ _x000D_ Some of our analysis needs a ‘control group’ to compare to treated patients. To do this we will include people who were eligible for the treatment but did not receive it._x000D_ _x000D_ How will this research benefit the public?_x000D_ _x000D_ This research will benefit the public by giving evidence on how different groups of people respond to treatments. This will help to ensure that the treatments recommended to patients are safest and most effective for them._x000D_ _x000D_ The EAVE II Public Advisory Group, who work alongside the researchers, have contributed to the analysis design, and plans for sharing our results. This group includes people who are eligible for monoclonal antibody treatment._x000D_ _x000D_ As a direct result of Public Advisory Group involvement, we have made changes to the study design. This includes:_x000D_ • describing safety and effectiveness in terms of interactions with existing medication that people take;_x000D_ • including the symptom of breathlessness, which was a key measure of recovery for potential patients;_x000D_ • analysing the time between diagnosis and receiving treatment._x000D_ _x000D_ Acknowledgments_x000D_ _x000D_ This work is being funded by the National Institute for Health Research (NIHR)._x000D_ Thank you to Lynn Laidlaw and Kamil Sterniczuk from the Public Advisory Group for reviewing this summary.

Lay abstract: This study is investigating the uptake, safety, and effectiveness of mAb therapy for COVID-19. In January 2022, the UK is experiencing a new wave of COVID-19 infections with the Omicron variant, at the same time as high circulating levels of Delta. There is evidence that the Omicron variant is more transmissible and concerns that existing interventions (e.g., COVID-19 Vaccines) may be less effective and some monoclonal antibodies (mAbs) may become ineffective due to mutations. Novel mAbs are limited resources and need to be targeted to those at highest risk of poor COVID-19 outcomes who are most likely to benefit. Interim guidance has been produced for use of novel mAbs and there is an urgent need to determine those likely to be eligible for these treatments to inform planning/ordering. It is also necessary to determine uptake to ensure they are being used in line with guidance. Rapid real-world evidence is also needed of the likely effectiveness of treatments alone and in combination to identify those patients who remain at risk despite treatments. This research will address a number of key questions, using existing research-ready datasets. We will use a data platform containing pseudonymised, linked data from vaccination records, virological testing and sequencing, clinical, and mortality records with coverage for the whole Scottish population. All data and analyses will be hosted within Public Health Scotland (PHS) and in due course in the Scottish national Trusted Research Environment.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: INFECTION