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Prognostic models to predict the risk of clinical deterioration in acute COVID-19 are required to inform clinical management decisions. Among 75,016 consecutive adults across England, Scotland and Wales prospectively recruited to the ISARIC Coronavirus Clinical Characterisation Consortium (ISARIC4C) study, we developed and validated a multivariable logistic regression model for in-hospital clinical deterioration (defined as any requirement of ventilatory support or critical care, or death) using 11 routinely measured variables. We used internal-external cross-validation to show consistent measures of discrimination, calibration and clinical utility across eight geographical regions. We further validated the final model in held-out data from 8,252 individuals in London, with similarly consistent performance (C-statistic 0.77 (95% CI 0.75 to 0.78); calibration-in-the-large 0.01 (−0.04 to 0.06); calibration slope 0.96 (0.90 to 1.02)). Importantly, this model demonstrated higher net benefit than using other candidate scores to inform decision-making. Our 4C Deterioration model thus demonstrates unprecedented clinical utility and generalisability to predict clinical deterioration among adults hospitalised with COVID-19.

BackgroundThe Coronavirus disease 2019 (covid-19) pandemic has spread rapidly across the globe. Accurate clinical characterisation studies conducted early in the pandemic are essential to informing research, diagnosis and clinical management efforts. In this scoping review we identify the clinical characteristics of patients admitted to hospital in the early months of the pandemic, focusing on symptoms, laboratory and imaging findings, and clinical outcomes.MethodsA scoping review. MEDLINE, EMBASE and Global Health databases were searched for studies published from January 1st2020 to April 28th2020. Studies which reported on at least 100 hospitalised patients with covid-19 of any age were included.ResultsOf 1,249 studies identified through the search 78 studies were eligible for inclusion; one randomized control trial and 77 observational studies presenting data on 77,443 patients admitted with covid-19. Most studies were conducted in China (82%), 9% in the US and 10% in Europe and two studies were set in more than one country. No studies included patients from low and middle income countries. Coagulopathy was underrecognised as a complication in the early months of the pandemic. Use of corticosteroids varied widely, and the use of anticoagulants was reported in only one study. Fever, cough and dyspnoea are less common in older adults; gastrointestinal symptoms, as the only presenting feature was underrecognised. The most common laboratory finding was lymphocytopenia. Inflammatory biomarkers were commonly elevated, including C-reactive protein and interleukin-6. Typical computed tomography findings include bilateral infiltrates however imaging may be normal in early disease. Data on clinical characteristics in children and vulnerable populations were limited.ConclusionsClinical characterisation studies from early in the pandemic indicated that covid-19 is a multisystem disease, with biomarkers indicating inflammation and coagulopathy. However, early data collection on symptoms and clinical outcomes did not consistently reflect this wide spectrum. Corticosteroid use varied widely, and anticoagulants were rarely used. Clinicians should remain vigilant to the possibility of covid-19 in patients presenting without fever, cough and dyspnoea, particularly in older adults. Further characterisation studies in different at-risk populations is needed.Review registrationAvailable athttps://osf.io/r2ch9