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Male or overweight associated with more serious COVID-19 hospital admissions

UK research has found that being male or having obesity reduces chance of survival from COVID-19. The findings come from a study of almost 17,000 patients with COVID-19, in which researchers from three UK universities aim to answer important questions about the course of and risk factors for the disease, The researchers have found that after adjusting for other medical problems such as lung, heart and kidney disease that are already known to cause poor outcomes, being male or having obesity (with a BMI>30) is a significant factor associated with death in UK hospitals, a feature not seen in China, where it is thought that fewer people have obesity.

"This study is quite amazing in that it was launched with such speed and collected so much data. It highlights several crucial questions which researchers, healthcare professionals, the public and patients need answers to,” said Professor Peter Openshaw from the National Heart & Lung Institute at Imperial. “Our research provides an exceptional picture of the illness and risk factors and will underpin a huge range of research."

According to the Department of Health and Social Care, COVID-19 can be more severe in older people and people with chronic heart, lung, and kidney disease, a weakened immune system, diabetes, and some cancers. However, less is known about how the virus exploits age, sex and other underlying health conditions.

In an effort to better understand who is most severely affected by the virus, what happens to them in hospital and why some people have better outcomes than others, ISARIC4C, a consortium of researchers from Imperial College London, the University of Liverpool and the University of Edinburgh, analysed data obtained from 16,749 COVID-19 patients in the UK.

Although the reasons for why obese people are suffering such severe COVID-19 and dying more than other groups are not clear, the researchers believe it could be because they have reduced lung function and possibly more inflammation in adipose tissue, the fatty tissue under the skin and around internal organs. According to the researchers, this might contribute to an enhanced 'cytokine storm' – a potentially life-threatening overreaction of the body's immune reaction which causes harm.

The study is being led by Professor Kenneth Baillie at Edinburgh University, Professor Calum Semple at Liverpool University and Professor Openshaw at Imperial. The analysis that found the relationship between sex, obesity and poor outcome was done by Dr Annemarie Docherty and Professor Ewen Harrison at Edinburgh University.

"One in three people admitted to hospital with of COVID-19 in the UK have contributed to this vital research. The contribution of UK patients in such tragic circumstances been critical to improving the global understanding of this terrible disease,” added Professor Semple, from the University of Liverpool. “We must do everything humanly possible to understand this disease, so that we are better prepared for the next wave of this pandemic."

The analysis is based on information obtained by more than 2,500 research nurses and medical students from 166 UK hospitals. It is the largest study of its kind outside of China, where this coronavirus first emerged. The results of the study have already been shared with UK Government and the World Health Organization and are being compared with data from other countries around the world.

"Hard data cannot convey the human story of individuals and their loved ones who have suffered, changed or sadly passed due to COVID-19,” said Dr Docherty from the University of Edinburgh, said. “Yet with every contribution to this important study, patients and their carers, with the assistance of dedicated researchers, have struck a blow in the fight to curb this pandemic."

In a separate summary of preliminary data about obesity and severity of COVID-19, published in Nature Reviews Endocrinology ‘Comment’, authors from the German Center for Diabetes Research (DZD), the Boston Children's Hospital and the Harvard TH Chan School of Public Health call for more research about the relationships of obesity, disproportionate fat distribution and impaired metabolic health with the severity of COVID-19.

The authors raise the point that most of the studies that have reported comorbidities in patients with COVID-19 did not provide data on body weight and height, which are used to estimate adipose tissue mass, by calculating the BMI. In their Comment they also briefly summarise novel research findings, deriving in part from articles which have not yet undergone peer-review, indicating that overweight and, particularly, obesity may associate with a substantial risk of a severe course of COVID-19. Importantly, these studies suggest that this risk is independent of cardiometabolic diseases and other comorbidities (Figure 1).

Figure 1: Obesity-related comorbidities and mechanisms of a severe course of COVID-19
Figure 1: Obesity-related comorbidities and mechanisms of a severe course of COVID-19

The authors then discuss possible mechanisms explaining this relationship. Among them respiratory dysfunction in obesity may result in hypoventilation-associated pneumonia and hypoxia-induced cardiac stress. Furthermore, they highlight that not only the calculation of the BMI, but also the measurement of the waist circumference and of glucose and insulin levels, which can be used to determine the presence of prediabetes and insulin resistance, may be important, as these parameters are independent determinants of cardiometabolic diseases, pneumonia and mortality.

They conclude that “while it is widely recognised that the presence of comorbidities such as hypertension, diabetes mellitus and CVD is associated with a more severe course of COVID-19, obesity has hardly been investigated so far. Obesity is a main risk factor for these comorbidities and more generally for impaired metabolic health (such as dyslipidaemia and insulin resistance) and is also linked to an increased risk of pneumonia. Measurement of anthropometric characteristics and metabolic parameters is crucial to better estimate the risk of complications in patients with COVID-19.”

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