Real-time COVID-19 hospital admissions forecasting with leading indicators and ensemble methods in England

Hospitalisations from COVID-19 with Omicron sub-lineages have put a sustained pressure on the English healthcare system. Understanding the expected healthcare demand enables more effective and timely planning from public health. We collect syndromic surveillance sources, which include online search data, NHS 111 telephonic and online triages. Incorporating this data we explore generalised additive models, generalised linear mixed-models, penalised generalised linear models and model ensemble methods to forecast over a two-week forecast horizon at an NHS Trust level. Furthermore, we showcase how model combinations improve forecast scoring through a mean ensemble, weighted ensemble, and ensemble by regression. Validated over multiple Omicron waves, at different spatial scales, we show that leading indicators can improve performance of forecasting models, particularly at epidemic changepoints. Using a variety of scoring rules, we show that ensemble approaches outperformed all individual models, providing higher performance at a 21-day window than the corresponding individual models at 14-days. We introduce a modelling structure used by public health officials in England in 2022 to inform NHS healthcare strategy and policy decision making. This paper explores the significance of ensemble methods to improve forecasting performance and how novel syndromic surveillance can be practically applied in epidemic forecasting

SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract

The mode of acquisition and causes for the variable clinical spectrum of coronavirus disease 2019 (COVID-19) remain unknown. We utilized a reverse genetics system to generate a GFP reporter virus to explore severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis and a luciferase reporter virus to demonstrate sera collected from SARS and COVID-19 patients exhibited limited cross-CoV neutralization. High-sensitivity RNA in situ mapping revealed the highest angiotensin-converting enzyme 2 (ACE2) expres-sion in the nose with decreasing expression throughout the lower respiratory tract, paralleled by a striking gradient of SARS-CoV-2 infection in proximal (high) versus distal (low) pulmonary epithelial cultures. COVID-19 autopsied lung studies identified focal disease and, congruent with culture data, SARS-CoV-2-in-fected ciliated and type 2 pneumocyte cells in airway and alveolar regions, respectively. These findings high-light the nasal susceptibility to SARS-CoV-2 with likely subsequent aspiration-mediated virus seeding to the lung in SARS-CoV-2 pathogenesis. These reagents provide a foundation for investigations into virus-host in-teractions in protective immunity, host susceptibility, and virus pathogenesis

Forecasting influenza hospital admissions within English sub-regions using hierarchical generalised additive models.

BACKGROUND: Seasonal influenza places a substantial burden annually on healthcare services. Policies during the COVID-19 pandemic limited the transmission of seasonal influenza, making the timing and magnitude of a potential resurgence difficult to ascertain and its impact important to forecast. METHODS: We have developed a hierarchical generalised additive model (GAM) for the short-term forecasting of hospital admissions with a positive test for the influenza virus sub-regionally across England. The model incorporates a multi-level structure of spatio-temporal splines, weekly cycles in admissions, and spatial correlation. Using multiple performance metrics including interval score, coverage, bias, and median absolute error, the predictive performance is evaluated for the 2022-2023 seasonal wave. Performance is measured against autoregressive integrated moving average (ARIMA) and Prophet time series models. RESULTS: Across the epidemic phases the hierarchical GAM shows improved performance, at all geographic scales relative to the ARIMA and Prophet models. Temporally, the hierarchical GAM has overall an improved performance at 7 and 14 day time horizons. The performance of the GAM is most sensitive to the flexibility of the smoothing function that measures the national epidemic trend. CONCLUSIONS: This study introduces an approach to short-term forecasting of hospital admissions for the influenza virus using hierarchical, spatial, and temporal components. The methodology was designed for the real time forecasting of epidemics. This modelling framework was used across the 2022-2023 winter for healthcare operational planning by the UK Health Security Agency and the National Health Service in England

Forecasting influenza hospital admissions within English sub-regions using hierarchical generalised additive models

Abstract Background Seasonal influenza places a substantial burden annually on healthcare services. Policies during the COVID-19 pandemic limited the transmission of seasonal influenza, making the timing and magnitude of a potential resurgence difficult to ascertain and its impact important to forecast. Methods We have developed a hierarchical generalised additive model (GAM) for the short-term forecasting of hospital admissions with a positive test for the influenza virus sub-regionally across England. The model incorporates a multi-level structure of spatio-temporal splines, weekly cycles in admissions, and spatial correlation. Using multiple performance metrics including interval score, coverage, bias, and median absolute error, the predictive performance is evaluated for the 2022-2023 seasonal wave. Performance is measured against autoregressive integrated moving average (ARIMA) and Prophet time series models. Results Across the epidemic phases the hierarchical GAM shows improved performance, at all geographic scales relative to the ARIMA and Prophet models. Temporally, the hierarchical GAM has overall an improved performance at 7 and 14 day time horizons. The performance of the GAM is most sensitive to the flexibility of the smoothing function that measures the national epidemic trend. Conclusions This study introduces an approach to short-term forecasting of hospital admissions for the influenza virus using hierarchical, spatial, and temporal components. The methodology was designed for the real time forecasting of epidemics. This modelling framework was used across the 2022-2023 winter for healthcare operational planning by the UK Health Security Agency and the National Health Service in England