AbstractObjectivesTo derive and validate risk prediction algorithms (QCOVID4) to estimate the risk of covid-19 related death and hospital admission in people with a positive SARS-CoV-2 test result during the period when the omicron variant of the virus was predominant in England, and to evaluate performance compared with a high risk cohort from NHS Digital.DesignCohort study.SettingQResearch database linked to English national data on covid-19 vaccinations, SARS-CoV-2 test results, hospital admissions, and cancer and mortality data, 11 December 2021 to 31 March 2022, with follow-up to 30 June 2022.Participants1.3 million adults in the derivation cohort and 0.15 million adults in the validation cohort, aged 18-100 years, with a positive test result for SARS-CoV-2 infection.Main outcome measuresPrimary outcome was covid-19 related death and secondary outcome was hospital admission for covid-19. Risk equations with predictor variables were derived from models fitted in the derivation cohort. Performance was evaluated in a separate validation cohort.ResultsOf 1 297 922 people with a positive test result for SARS-CoV-2 infection in the derivation cohort, 18 756 (1.5%) had a covid-19 related hospital admission and 3878 (0.3%) had a covid-19 related death during follow-up. The final QCOVID4 models included age, deprivation score and a range of health and sociodemographic factors, number of covid-19 vaccinations, and previous SARS-CoV-2 infection. The risk of death related to covid-19 was lower among those who had received a covid-19 vaccine, with evidence of a dose-response relation (42% risk reduction associated with one vaccine dose and 92% reduction with four or more doses in men). Previous SARS-CoV-2 infection was associated with a reduction in the risk of covid-19 related death (49% reduction in men). The QCOVID4 algorithm for covid-19 explained 76.0% (95% confidence interval 73.9% to 78.2%) of the variation in time to covid-19 related death in men with a D statistic of 3.65 (3.43 to 3.86) and Harrell’s C statistic of 0.970 (0.962 to 0.979). Results were similar for women. QCOVID4 was well calibrated. QCOVID4 was substantially more efficient than the NHS Digital algorithm for correctly identifying patients at high risk of covid-19 related death. Of the 461 covid-19 related deaths in the validation cohort, 333 (72.2%) were in the QCOVID4 high risk group and 95 (20.6%) in the NHS Digital high risk group.ConclusionThe QCOVID4 risk algorithm, modelled from data during the period when the omicron variant of the SARS-CoV-2 virus was predominant in England, now includes vaccination dose and previous SARS-CoV-2 infection, and predicted covid-19 related death among people with a positive test result. QCOVID4 more accurately identified individuals at the highest levels of absolute risk for targeted interventions than the approach adopted by NHS Digital. QCOVID4 performed well and could be used for targeting treatments for covid-19 disease.