ABSTRACT
Introduction: Chronic Kidney Disease (CKD) is a global burden on public health, both as a risk factor for mortality, and as the end syndrome of underlying diseases. CKD is a common comorbidity associated with increased risk of severe coronavirus infection and poor clinical outcomes. The pandemic has had both direct (through infection) and indirect impact. The direct impact on individuals with CKD and other underlying conditions is related to baseline risk, influenced by age, multimorbidity and other socio-demographic factors. However, previous studies of COVID-19 in CKD have been small scale (12-1099 cases), mostly focused on end-stage CKD, and ignored major comorbidities. Thus, using large-scale, population-based electronic health records, in people with incident CKD we aimed to (a) identify the most common comorbidities;(b) estimate 1-year (pre-pandemic) risk of mortality and (c) predict excess deaths related to COVID-19 over 1-year of pandemic based on pre-pandemic risk of mortality at different population infection rates and relative risks. Methods: We used linked primary and secondary care records (Clinical Practice Research Datalink GOLD data) from England;of 3,862,012 individuals aged ≥ 30 registered with a GP practice between 1997 and 2017. Incident CKD was identified based on diagnosis codes and eGFR levels;classified mutually exclusively into five CKD Stages. The underlying conditions were obtained using validated phenotyping algorithms in CALIBER and the most prevalent ones were identified. The 1-year mortality were estimated using Kaplan–Meier survival analysis;stratified by key demographic factors and number of comorbidities. Using these pre-pandemic risk estimates and our recently published Lancet model, we calculated excess COVID-19 related deaths at different population infection rates and relative risks. For validation, we identified the number of people who died with both CKD and positive COVID-19 test result during 1-year of pandemic using the contemporary NHSD TRE data of England (NHS Digital Trusted Research Environment, n=54 million). Results: We identified 294,381 individuals with incident CKD (mean age 72.5 years;female: 59%). Multimorbidity was common among CKD patients especially the presence of hypertension (61.4%) and CVD complications (35.6%) (Fig 1 ). The proportion of CKD patients having at least one underlying condition increases significantly either by age or CKD stage whilst age was the main confounder within each CKD stage. Age, Stage of CKD and underlying conditions combined to influence pre-pandemic risk (Fig 2 ). At an IR of 10%, we predicted 31003 and 46505 excess deaths at RR of 2 and 3 respectively (Table 1 ) which is close to actual observed mortality (47214) from the NHSD TREin England. [Formula presented] [Formula presented] [Formula presented] Conclusions: Individuals with CKD have high risk of pre-pandemic mortality particularly those with comorbidities. The data on multimorbidity, CKD stage and age together could help prioritise patients for vaccination, post-COVID policy, and designing stratified pathways for CKD patients. We illustrate that the direct burden of pandemic could be predicted using pre-pandemic large scale EHR data. Conflict of interest Potential conflict of interest: This study was funded by AstraZeneca and Health Data Research UK. AB has received research grants from AstraZeneca. JBM and TM are employed full-time by AstraZeneca UK Ltd, a biopharmaceutical company who develops, manufactures and markets medicines in the cardiovascular, renal and metabolic disease area.
ABSTRACT
OBJECTIVES: Obesity is a modifiable risk factor for coronavirus disease 2019 (COVID-19)-related mortality. We estimated excess mortality in obesity, both 'direct', through infection, and 'indirect', through changes in health care, and also due to potential increasing obesity during lockdown. STUDY DESIGN: The study design of this study is a retrospective cohort study and causal inference methods. METHODS: In population-based electronic health records for 1,958,638 individuals in England, we estimated 1-year mortality risk ('direct' and 'indirect' effects) for obese individuals, incorporating (i) pre-COVID-19 risk by age, sex and comorbidities, (ii) population infection rate and (iii) relative impact on mortality (relative risk [RR]: 1.2, 1.5, 2.0 and 3.0). Using causal inference models, we estimated impact of change in body mass index (BMI) and physical activity during 3-month lockdown on 1-year incidence for high-risk conditions (cardiovascular diseases, diabetes, chronic obstructive pulmonary disease and chronic kidney disease), accounting for confounders. RESULTS: For severely obese individuals (3.5% at baseline), at 10% population infection rate, we estimated direct impact of 240 and 479 excess deaths in England at RR 1.5 and 2.0, respectively, and indirect effect of 383-767 excess deaths, assuming 40% and 80% will be affected at RR = 1.2. Owing to BMI change during the lockdown, we estimated that 97,755 (5.4%: normal weight to overweight, 5.0%: overweight to obese and 1.3%: obese to severely obese) to 434,104 individuals (15%: normal weight to overweight, 15%: overweight to obese and 6%: obese to severely obese) would be at higher risk for COVID-19 over one year. CONCLUSIONS: Prevention of obesity and promotion of physical activity are at least as important as physical isolation of severely obese individuals during the pandemic.