Underlying illness risk factors for severe COVID-19 or death — Large UK cohort study

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Age, male sex, obesity, and underlying illness have emerged as risk factors for severe COVID-19 or death in the UK, according to the largest cohort study to date. The risk of death increases in the over 50s, as does being male, obese, or having underlying heart, lung, liver and kidney disease.

As the largest prospective observational study reported worldwide to date, it provides a comprehensive picture of the characteristics of patients hospitalised in the UK with COVID-19 and their outcomes. Because the study is ongoing, it has now recruited over 43,000 patients. The findings will help health professionals learn more about how the illness progresses and enable us to compare the UK with other countries, say the researchers.

Studies in China have reported risk factors associated with severe COVID-19, but studies describing the features and outcomes of patients with severe COVID-19 who have been admitted to hospital in Europe are lacking. To address this knowledge gap, a team of UK researchers analysed data from 20,133 patients with covid-19 admitted to 208 acute care hospitals in England, Wales, and Scotland between 6 February and 19 April 2020.

This represents around a third of all patients admitted to hospital with COVID-19 in the UK. The average age of patients in the study was 73 years, and more men (12,068; 60%) were admitted to hospital than women (8,065; 40%).

Besides increasing age, and underlying heart, lung, liver and kidney disease – factors already known to cause poor outcomes – the researchers found that obesity and gender were key factors associated with the need for higher levels of care and higher risk of death in hospital.

At the time of publication, just over a quarter (26%) of all COVID-19 patients in hospital had died, 54% were discharged alive, and a third (34%) remained in hospital. Outcomes were poorer for those requiring mechanical ventilation: 37% had died, 17% had been discharged alive, and 46% remained in hospital.

The pattern of disease we describe broadly reflects the pattern reported globally, say the researchers. However, obesity is a major additional risk factor that was not highlighted in data from China. They suspect that reduced lung function or inflammation associated with obesity may play a role.

This is an observational study, so can’t establish cause, and the researchers point to some limitations that may have affected their results. Nevertheless, they say this is the largest study of its kind outside of China and clearly shows that severe COVID-19 leads to a prolonged hospital stay and a high mortality rate.

“Our study identifies sectors of the population that are at greatest risk of a poor outcome, and shows the importance of forward planning and investment in preparedness studies,” they write.

These results have already been shared with the UK government and World Health Organisation, and are being compared with data from other countries around the world.

At the outset of the COVID-19 pandemic, it was natural to focus first on the people with severe disease who might need potentially scarce resources in hospital and intensive care, write US researchers in a linked editorial.

Cohort studies of such patients are important, they say, and this study is a testament to good planning and preparation before, and implementation of data collection during a pandemic.

But they add that if we are going to be managing COVID-19 for the next several years, “we need to understand and optimize care before, during, and beyond the hospital.”

Abstract
Objective: To characterise the clinical features of patients admitted to hospital with coronavirus disease 2019 (covid-19) in the United Kingdom during the growth phase of the first wave of this outbreak who were enrolled in the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) World Health Organisation (WHO) Clinical Characterisation Protocol UK (CCP-UK) study, and to explore risk factors associated with mortality in hospital.
Design: Prospective observational cohort study with rapid data gathering and near real time analysis.
Setting: 208 acute care hospitals in England, Wales, and Scotland between 6 February and 19 April 2020. A case report form developed by ISARIC and WHO was used to collect clinical data. A minimal follow-up time of two weeks (to 3 May 2020) allowed most patients to complete their hospital admission.
Participants: 20 133 hospital inpatients with covid-19.
Main outcome measures: Admission to critical care (high dependency unit or intensive care unit) and mortality in hospital.
Results: The median age of patients admitted to hospital with covid-19, or with a diagnosis of covid-19 made in hospital, was 73 years (interquartile range 58-82, range 0-104). More men were admitted than women (men 60%, n=12 068; women 40%, n=8065). The median duration of symptoms before admission was 4 days (interquartile range 1-8). The commonest comorbidities were chronic cardiac disease (31%, 5469/17 702), uncomplicated diabetes (21%, 3650/17 599), non-asthmatic chronic pulmonary disease (18%, 3128/17 634), and chronic kidney disease (16%, 2830/17 506); 23% (4161/18 525) had no reported major comorbidity. Overall, 41% (8199/20 133) of patients were discharged alive, 26% (5165/20 133) died, and 34% (6769/20 133) continued to receive care at the reporting date. 17% (3001/18 183) required admission to high dependency or intensive care units; of these, 28% (826/3001) were discharged alive, 32% (958/3001) died, and 41% (1217/3001) continued to receive care at the reporting date. Of those receiving mechanical ventilation, 17% (276/1658) were discharged alive, 37% (618/1658) died, and 46% (764/1658) remained in hospital. Increasing age, male sex, and comorbidities including chronic cardiac disease, non-asthmatic chronic pulmonary disease, chronic kidney disease, liver disease and obesity were associated with higher mortality in hospital.
Conclusions: ISARIC WHO CCP-UK is a large prospective cohort study of patients in hospital with covid-19. The study continues to enrol at the time of this report. In study participants, mortality was high, independent risk factors were increasing age, male sex, and chronic comorbidity, including obesity. This study has shown the importance of pandemic preparedness and the need to maintain readiness to launch research studies in response to outbreaks.

Authors
Annemarie B Docherty, Ewen M Harrison, Christopher A Green, Hayley E Hardwick, Riinu Pius, Lisa Norman, Karl A Holden, Jonathan M Read, Frank Dondelinger, Gail Carson, Laura Merson, James Lee, Daniel Plotkin, Louise Sigfrid, Sophie Halpin, Clare Jackson, Carrol Gamble, Peter W Horby, Jonathan S Nguyen-Van-Tam, Antonia Ho, Clark D Russell, Jake Dunning, Peter JM Openshaw, J Kenneth Baillie, Malcolm G Semple

 

BMJ material

 

BMJ abstract

 

BMJ linked editorial

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