Risk factors for clinical progression in patients with COVID-19: a retrospective study of electronic health record data in the United Kingdom
Authors: Fletcher Robert A , Matcham Thomas , Tibúrcio Marta , Anisimovich Arseni , Jovanović Stojan , Albergante Luca , Lipunova Nadezda , Hancock Anne , Mackillop Lucy , Tarassenko Lionel , McCarthy Alex , Vizcaychipi Marcela P , Khan Rabia Tahir 
Published: May 2020

Background: The novel coronavirus disease 2019 (COVID-19) outbreak presents a significant threat to global health. A better understanding of patient clinical profiles is essential to drive efficient and timely health service strategies. In this study, we aimed to identify risk factors for a higher susceptibility to symptomatic presentation with COVID-19 and a transition to severe disease.

Methods: We analysed data on 2756 patients admitted to Chelsea & Westminster Hospital NHS Foundation Trust between 1st January and 23rd April 2020. We compared differences in characteristics between patients designated positive for COVID-19 and patients designated negative on hospitalisation and derived a multivariable logistic regression model to identify risk factors for predicting risk of symptomatic COVID-19. For patients with COVID-19, we used univariable and multivariable logistic regression to identify risk factors associated with progression to severe disease defined by: 1) admission to the hospital AICU, 2) the need for mechanical ventilation, 3) in-hospital mortality, and 4) at least one measurement of elevated D-dimer (equal or superior to 1,000 ug/L) indicative of increased risk of venous thromboembolism.

Results: The patient population consisted of 1148 COVID-19 positive and 1608 COVID-19 negative patients. Age, sex, self-reported ethnicity, C-reactive protein, white blood cell count, respiratory rate, body temperature, and systolic blood pressure formed the most parsimonious model for predicting risk of symptomatic COVID-19 at hospital admission. Among 1148 patients with COVID-19, 116 (10.1%) were admitted to the AICU, 71 (6.2%) required mechanical ventilation, 368 (32.1%) had at least one record of D-dimer levels ≥1,000 μg/L, and 118 patients died. In the multivariable logistic regression, age (OR = 0.953 per 1 year, 95% CI: 0.937-0.968) C-reactive protein (OR = 1.004 per 1 mg/L, 95% CI: 1.002-1.007), and white blood cell counts (OR = 1.059 per 109/L, 95% CI: 1.010-1.111) were found to be associated with admission to the AICU. Age (OR = 0.973 per 1 year, 95% CI: 0.955-0.990), C-reactive protein (OR = 1.003 per 1 mg/L, 95% CI: 1.000-1.006) and sodium (OR = 0.915 per 1 mmol/L, 0.868-0.962) were associated with mechanical ventilation. Age (OR = 1.023 per 1 year, 95% CI: 1.004-1.043), CRP (OR = 1.004 per 1 mg/L, 95% CI: 1.002-1.006), and body temperature (OR = 0.723 per 1oC, 95% CI: 0.541-0.958) were associated with elevated D-dimer. For mortality, we observed associations with age (OR = 1.060 per 1 year, 95% CI: 1.040-1.082), female sex (OR = 0.442, 95% CI: 0.442, 95% CI: 0.245-0.777), Asian ethnic background (OR = 2.237 vs White ethnic background, 95% CI: 1.111-4.510), C-reactive protein (OR = 1.004 per 1 mg/L, 95% CI: 1.001-1.006), sodium (OR = 1.038 per 1 mmol/L, 95% CI: 1.001-1.006), and respiratory rate (OR = 1.054 per 1 breath/min, 95% CI: 1.024-1.087).

Conclusion: Our analysis suggests there are several demographic, clinical and laboratory findings associated with a symptomatic presentation of COVID-19. Moreover, significant associations between patient deterioration were found with age, sex and specific blood markers, chiefly C-reactive protein, and could help early identification of patients at risk of poorer prognosis. Further work is required to clarify the extent to which our observations are relevant beyond current settings.