Risk of death in England following a positive SARS-CoV-2 test: A retrospective national cohort study (March 2020 to September 2022)

Background We aimed to estimate the relative risk of mortality following a first positive SARS-CoV-2 test during the first, second, and third waves of the COVID-19pandemic in England by age, sex, and vaccination status, taking into account pre-existing health conditions and lifestyle factors. Methods We conducted a retrospective cohort study of all individuals registered with the National Health Service (NHS) in England from 1 March 2020 to September 2022. Data for all individuals were obtained and linked including primary care records, hospital admission episodes, SARS-CoV-2 test results, vaccinations, and death registrations. We fitted Cox Proportional Hazards models with time dependent covariates for confirmed SARS-CoV-2 infection to model the risk of subsequent mortality. Results The hazard ratio for death after testing positive for subsequent, compared with those not testing positive, amongst unvaccinated individuals, ranged from 11 to 89 by age and sex, in the first four weeks following a positive test in wave one and reduced to 14 to 50 in wave three. This hazard was further reduced amongst those who had three vaccines to between 1.4 and 7 in wave three. Conclusions This study provides robust estimates of increased mortality risk among those who tested positive over the first three waves of the COVID-19 pandemic in England. The estimates show the impact of various factors affecting the risk of mortality from COVID-19. The results provide the first step towards estimating the magnitude and pattern of mortality displacement due to COVID-19, which is essential to understanding subsequent mortality rates in England.