Understanding COVID-19 trajectories from a nationwide linked electronic health record cohort of 57 million people: phenotypes, severity, waves & vaccination

Abstract

Background: Updatable understanding of the onset and progression of individuals COVID-19 trajectories underpins pandemic mitigation efforts. In order to identify and characterise individual trajectories, we defined and validated ten COVID-19 phenotypes from linked electronic health records (EHR) on a nationwide scale using an extensible framework.

Methods: Cohort study of 57 million people in England alive on 23/01/2020, followed until 30/11/2021, using eight linked national datasets spanning COVID-19 testing, vaccination, primary & secondary care and death registrations data. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity using a combination of international clinical terminologies (e.g. SNOMED-CT, ICD-10) and bespoke data fields; positive test, primary care diagnosis, hospitalisation, ventilatory support (four phenotypes), and death (three phenotypes). Using these phenotypes, we constructed patient trajectories illustrating the transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status.

Findings: We identified 7,244,925 infected individuals (12.7%) with 13,990,423 recorded COVID-19 phenotypes. Of these, 460,737 (6.4%) were hospitalised and 158,020 (2.2%) died. Of those hospitalised, 48,847 (11%) were admitted to intensive care (ICU), 69,090 (15%) received non-invasive ventilation and 25,928 (5.6%) invasive ventilation. Amongst hospitalised patients, first wave mortality (30%) was higher than the second (23%) for those not receiving ventilatory support, but remained unchanged for ICU patients. The highest mortality was for patients receiving ventilatory support outside of ICU in wave 1 (51%). 15,486 (10%) COVID-19 related deaths occurred without diagnoses on the death certificate, but within 28 days of a first COVID-19 event while 10,884 (7% of deaths) were identified from mortality data alone with no prior phenotypes recorded. We observed longer patient trajectories in the second pandemic wave compared to the first.

Interpretation: Our analyses illustrate the wide spectrum of severity that COVID-19 displays and significant differences in incidence, survival and pathways across pandemic waves. We provide an adaptable framework to answer questions of clinical and policy relevance; new variant impact, booster dose efficacy and a way of maximising existing data to understand individuals progression through disease states.