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expert reaction to PHE report on excess weight and COVID-19

Public Health England (PHE) have released a report on the relationship between excess weight and COVID-19.

This Roundup accompanied an SMC Briefing

 

Dr David Nunan, Senior Researcher at the Centre for Evidence Based Medicine, University of Oxford, said:

“While some of the press release wording suggests the evidence is clear about a link between excess weight and COVID-19 severity, the report itself is more cautious. The report makes clear that the evidence looked at has limitations, that the conclusions made are tentative and more research is needed.”  

 

Dr Rebecca Dumbell, Lecturer in Pharmacology, Nottingham Trent University, said: 

“The report examines recent evidence for risk of contracting, and adverse outcomes from Covid-19 associated with BMI, finding that people with high BMI are more at risk, as is the case for many diseases. It is not yet clear what the mechanism may be for this increased risk in obese people. 

“The report touches on drivers of obesity in the general population, and we already know that some people may find it more difficult to maintain a lower BMI than others, based on physiological and genetic differences, busy lifestyles, the environment they live in, and the availability of healthier food options. Many of these issues are partly socio-economic. The report mentions that food purchasing activity has increased, however this may reflect that people have had less access to food and alcohol from pubs and restaurants during lockdown. Survey data suggest people have been doing more cooking from scratch and self reported healthy meals, but also snacking more on “unhealthy” options. However there is little data on how lockdown may have affected bodyweight or fitness levels, nor indeed dietary patterns. 

“The report suggests that more needs to be done to support people with a high BMI who wish to lose weight, highlighting that improved infrastructure to support more walking and cycling is a positive outcome from the lockdown, and there are opportunities to improve this further. The report also recommends improving access to weight management programmes to people who would benefit from weight loss.

“The report suggests that body weight may be one of the more modifiable risk factors for Covid19 (compared to unchangeable factors like age, and sex, or socio-ecomomicstatus, which is stated as being more complex to deal with). And it is welcome that the importance of obesity is being taken seriously, as it is recognised more and more widely as a disease in and of itself. For most overweight and obese people, weight loss will bring many different improved health benefits. However there is no “one-size fits all” approach to solving the obesity epidemic and this will require improved basic scientific understanding as well as making healthier options and lifestyles more accessible to the wider population. I welcome the report’s recommendation that “structural drivers of excess calorie intakes and low levels of physical activity will need to be tackled” to improve the situation at a population level.

“The press release uses the terms “excessively overweight” and “severely overweight” which are not terms defined in the report, and should be stated as “overweight” in the press release.

 

Prof Naveed Sattar, Professor of Metabolic Medicine, University of Glasgow, said:

“This is indeed a useful report, despite being written in a relatively short timescale.  Hopefully, it will provoke a much needed discussion around this sensitive but important topic which is perhaps even more important to the UK given its current poor international ranking on obesity rates. The evidence that excess weight causes worse COVID-19 outcomes is not definitive (all studies have varying limitations) BUT it is strongly suggestive as it is clear that higher BMI to COVID-19 associations have been seen across studies from many different countries, in different settings and with different study designs.  Also, as higher BMI is a cause of conditions that appear to be associated with more adverse outcomes (e.g. diabetes, heart disease, stroke, higher blood pressure, lung condition etc), it seems reasonable to speculate that by helping more people prevent weight gain, and others to lose some weight (even small amounts sustainably), we may be able to lessen their risks of more severe COVID-19 in the event of subsequent waves.  Formal trials would be useful to prove this, and whilst these may be difficult, they are not necessarily impossible. Even so, if this report helps bring obesity to the fore and leads to real systemic changes in the food and travel environments so more people can live healthier lives without much conscious effort, then so much the better, and many future generations will stand to benefit, a silver lining (perhaps) to this pandemic.  It should also help improve access to weight management options for people living with obesity.”  

 

Dr Simon Cork, Lecturer in Medical Education, King’s College London (KCL), said:

“This report provides further evidence that those people living with overweight or obesity have significantly worse outcomes when diagnosed with COVID-19 than those who are of healthy weight. The mounting evidence now states that those people who are overweight or obese are more likely to require hospitalisation and mechanical ventilation, are more likely to suffer from more severe disease and are more at risk of dying from COVID-19.

“The mechanisms which underlie this disparity are likely multifaceted and not yet fully understood. Obesity is associated with reduced lung capacity, and as such does not leave much redundancy in the face of a respiratory illness. Moreover, obesity is closely linked with type 2 diabetes, which can impact on a person’s ability to raise an immune response. Obesity is also associated with low level inflammation, which can exacerbate the inflammation associated with infection and also lead to higher circulating levels of clotting factors in the blood. One of the leading causes of death among those who suffer from COVID-19 are thrombotic events (e.g. heart attack, stroke of pulmonary embolism). Given that people with obesity are more at risk of thrombotic events anyway, this is further exacerbated by infection.

“The link to the BAME community is still less clear. Those who are of certain BAME backgrounds (e.g. south asian) suffer from metabolic complications (e.g. diabetes) at lower BMI than those of other races and this likely explains some of the increased impact that these communities have faced.” 

 

Prof. Sir Stephen O’Rahilly MD FRS FMedSci, Director, MRC Metabolic Diseases Unit, Institute of Metabolic Science, University of Cambridge, said:

“The topic is important and the report is timely.

“The report correctly points out that any data suggesting that people with obesity may have a higher rate of SARS-Cov2 infection has to be seen in the light of a high likelihood of selection bias. In essence the relevant data is not of high quality and we don’t know the answer to the question of whether obesity makes people more likely to acquire SARS-Cov2 viral infection or not.

“The report does, however, make it clear that once someone is infected with the SARS-Cov2 virus the chances of them being hospitalised, needing ventilation or dying is increased by obesity, with the size of the effect being related to the severity of the obesity. This seems to be supported by the data.

“Overall the part of the report that describes the epidemiology of the problem is written objectively and competently.

“The section on “Potential Plausible Mechanisms” is weaker. It simply lists a range of theories that have been published around possible explanations for the ways in which the obese state might exacerbate COVID19 pathology without any critical evaluation of how supported by evidence these theories are. The section should be grounded in an understanding of the peculiarities of the pathology of COVID19 that actually leads to fatality but there is no description of this.

“The description of mechanism unfortunately starts off with the notion that the “heavy chest” and “fatty deposits in the upper airways” found in obese patients are key factors in making COVID19 outcome worse. But COVID19 lung disease (which is what kills most of those who succumb) is specifically a pathology of the alveolar-capillary unit deep in the lung and is not predominantly an airways disease. Patients with COVID19 who are on ventilators are usually mechanically ventilated with ease (so the “heavy chest” is irrelevant). The key problem they face is that the alveolar capillary unit cannot transfer oxygen due to the specific pathology occurring there.  “Fat around the upper airway” is obviously irrelevant to an intubated ventilated patient, yet obese people who are ventilated still have worse outcomes.

“The report then moves on to another factor of dubious importance. i.e the so-called “high expression of ACE2 in adipose tissue”. This is a) a doubtful observation as its not replicated by several reports comparing relative expression of ACE2 in different tissues and b) likely to be of little relevance to disease as most high quality post mortem studies find evidence of abundant viral RNA in the lung but little evidence of it elsewhere. This makes sense, as it is the lung where the fatal pathology is largely occurring.

“The report actually misquotes the paper written by Sam Lockhart and myself by emphasising comments we made about cytokines and increased inflammation which we actually suggested were likely to be less significant than activation of the complement system, which is not mentioned at all in the report. Aberrant complement activation is likely to be at the heart of the pathology of COVID19 and obesity is associate with higher levels of key complement components. Experimental drugs inhibiting complement activation are available and are in clinical trials for COVID19. So this is not an arcane academic point. 

“A key point is that if obesity is exerting its bad effects through “mechanical/gravitational “ effects then a person has to get rid of a lot of fat before seeing any benefit. On the other hand if obesity is causing problems through its metabolic effects, many of the latter start to improve after only a few days of going into negative energy balance (eating less calories than one expends) and well before one sees an impact on weight or waist-band. It is daunting for markedly obese people to think they have to lose, say, 20kgs to protect themselves from COVID 19 and this may put them off even trying. But if we can inform people that even small amounts of weight loss may be beneficial. it could be quite motivating. A “Lose a pound, walk a mile” sort of message could be a useful public health one.

“The fact that the adverse effects of obesity on COVID outcome are seen at much lower levels of obesity in people of South Asian origin is further evidence supporting the “metabolic” vs “mechanical” theories, particularly as it is well established that people of South Asian origin are much more susceptible to metabolic derangement at lower levels of adiposity.

“The report also fails to mention that there are drugs available which can assist weight loss and improve the metabolic state of the obese and that are certainly worthy of consideration to combine with diet and exercise. For example, metformin which is generic, cheap and safe, resulted in a 6% additional weight loss , sustained over 10 years, in the Diabetes Prevention programme in the USA . Other, more powerful weight-loss drugs are licensed for use in certain circumstances in the UK (e.g. liragutide) and could be used in more severely affected and high risk patients.

“As so often happens, obesity is uniquely neglected when it comes to thinking about how behavioural efforts might be assisted pharmacologically to result in better health outcomes. Consider, for example, if high blood pressure had been found to be a major risk factor for COVID19 mortality and a PHE report focused entirely on dietary salt restriction and didn’t mention the additional appropriate use of anti-hypertensive drugs to help combat the problem. In the case of obesity, this multi-pronged approach is not even mentioned.

“On page 12 the report states “At the time of publication, treatment includes steroids and dexamethasone for severely ill people”. It is disconcerting that the authors of the report do not appear to know that dexamethasone is, in fact, a “steroid” (more precisely, a glucocorticoid). It would be surprising for this error to occur in a document contributed to by anyone with a current knowledge of clinical medicine and therapeutics. If expertise of that type was not sought this is concerning, as solving the problem of COVID19 and its disproportionate impact on the obese will require the mustering of a broad range of biomedical expertise.”

 

Prof Susan Jebb, Professor of Diet and Population Health, University of Oxford, said:

“This is a useful rapid review of the evidence as it stands relating to the relationship between excess weight and risks from covid-19. Evidence from diverse sources shows a clear and consistent trend of increasing risk of hospitalisation, admission to ICU and death as BMI increases. The association is almost linear – this means that even at a BMI of just 25 (classified as overweight) there is a modest increased risk which continues to rise as BMI increases.

“We already know that older people, men, those from South Asian and some other ethnic groups and people living in more deprived areas are at increased risk from covid-19. Even after adjusting for these factors, this review shows that excess weight  is another very important risk factor. 

“We don’t know for certain what the specific mechanism is to explain this association, but we know obesity leads to fat accumulation in vital organs like the heart and liver, and leads to insulin resistance and high blood pressure. Obesity puts extra pressure and metabolic strain on almost every organ system of the body, so it’s perhaps not surprising that it also exacerbates the risk of covid-19 complications.

“Although we cannot be certain that losing weight will reduce risk, we do know that weight loss is very effective at reducing the metabolic harm caused by too much fat in the body. We know from other diseases that if you are overweight, even small weight losses, which are achievable for most people, can have surprisingly big metabolic benefits.”

 

Dr Katarina Kos, Senior Lecturer and Honorary Consultant Physician in Diabetes and Endocrinology, University of Exeter Medical School, said:

“Obesity rates are disproportional high in the UK, with it being one of the worst affected countries in Europe. The PHE report pulls all current publications in view of obesity and COVID-19 together in context of statistics on deprivation and obesity across countries, regions and ethnicities.

“Current evidence has limitations which includes limited COVID-19 testing, BMI recording and inclusion of data from other than the UK, though 12 studies on UK populations were included representing very respectable patient numbers. Whilst data is mostly available on hospitalised patients, this is essentially most important, if we want to know how badly one becomes affected by COVID-19 with the implication of becoming infected in the first instance less crucial. Uniformly the findings show that the need of hospital stay and need of admission to ITU are higher with being overweight and obese. People in the higher obese category (BMI above 35kg/m2) are more than 4 times likely admitted to ITU. The mechanisms of why people with obesity are more prone to a severe outcome are mostly speculative. They range from an impaired immune response in a condition of high insulin levels and an elevated inflammatory cytokine response which is obesity, a higher risk of thrombosis, impaired lung function and lower body’s oxygen levels in obesity. Furthermore fat (adipose) tissue has high levels of angiotensin converting enzyme ACE2 expression, the enzyme used by the virus to enter cells) and may thus increase the chances of infection. Thus it is plausible that there are several reasons which in combination put these patients at increased risk of a poorer outcome.

“Health inequalities cannot be excluded to bias the finding of a worse COVID-19 outcome in obesity. BAME groups are not exempt from a high link with obesity and COVID severity. However, only black women have a higher rate of obesity than white women. In this population we needs to appreciate that the BMI thresholds are lower, e.g. as one defines the medical condition of obesity at a lower threshold as ill health of obesity occurs at lower BMI. BAME groups are prone to a less advantageous fat tissue distribution in and around inner organs which increases cardiometabolic risk and this has also been suggested as one possible mechanism to explain higher COVID-19 illness severity.

“Another interesting statistic is that more older people are affected by obesity with about 80% of men being overweight or obese in the 55 to 74 age group (whilst only 35% of men and women are obese in the age group below 25).

“In line with the speculation of mechanisms of a poor COVID-19 outcome in obesity, we know that these factors improve considerably with weight loss, albeit currently, time did not permit scientists to provide evidence from weight loss studies to provide ultimate evidence that their response to COVID-19,  should they become infected in future, becomes more favourable. Alongside the precautions we take to avoid a COVID-19 infection, it would be prudent not to limit the risk of a worse COVID-19 outcome and eventually death. Increased support and funding for obesity services should be made available this including psychosocial measures. Tackling health inequalities needs to remain a high priority.”

 

Professor Linda Bauld, Professor of Public Health, University of Edinburgh, said:

“This report that has almost certainly been released now to provide up to date evidence on the links between excess weight and Covid-19 in advance of next week’s anticipated announcement on obesity policies.  It includes a rapid review of the literature, meaning it is not systematic and doesn’t capture all the relevant studies. It is possible that some evidence has been missed including studies that may present conflicting findings.  Some of the included Covid-19 studies had not been peer reviewed, which means we can’t be absolutely confident about their findings. That said, the report does provide a useful overview.

“What is striking is that excess weight seems to affect many of the key indicators we use to assess outcomes from Covid-19. Overweight and obesity is associated with testing positive for Covid-19. More worryingly, it looks to be one predictor of who needs hospital care following a positive test, who is admitted to intensive care and also death with Covid-19.  A meta-analysis included in the review found that patients living with overweight and obesity were over three times more likely to die with Covid-19 than those of a healthy weight. This is consistent with the recent large UK study (20,133 patients) from the ISARIC consortium (cited in the report) that found a 33% increased risk of death among patients living with obesity who were hospitalised with Covid-19.

“The report highlights important research gaps. We still don’t fully understand the biological mechanisms between Covid-19 disease severity and excess weight. As the authors point out, routine data recording on weight or BMI is likely to be weak in some studies. These and other issues need further research before we can be confident. However, to have so many studies that point in the same direction is compelling and certainly suggests that now is an ideal time to combine Covid-19 responses with interventions to address overweight and obesity. This is particularly important because these interventions will contribute to preventing conditions that kill many more people than Covid-19 each year – including many cancers, diabetes and cardiovascular disease.

“It is worth remembering that the UK has the highest rates of overweight and obesity in Europe and some of the highest in the world. It is plausible that excess weight in our population has contributed to a greater number of excess deaths. If that is the case, even to a small extent, it’s a salutary lesson that action is urgently needed to support more of us to maintain a healthy weight.”

 

Prof Francesco Rubino, Chair of Metabolic and Bariatric Surgery, King’s College London, said:

“This is an excellent and comprehensive assessment of the current evidence linking obesity to higher risk of severe COVID-19. The report fairly highlights the limitations of current evidence, but the conclusions derived are plausible and meaningful in terms of informing clinical practice and policies.

“Limitations in available evidence are:

1. the relative paucity of high level scientific studies (i.e. less from data from studies with prospective analysis and with accurate/updated measures of weight as opposed to weight measures that are derived from historical records of patients months earlier)

2. Mechanisms to explain why obesity increases severity of Covid still unclear, but based on plausible hypothesis;

3. Difficult to rule out confounding from role of co-morbidities, socio-economic status and stigma.

4. The evidence that weight loss would reduce risk of covid-19 is also inevitably based on (very) plausible hypothesis but of course not yet on conclusive data.

“While it seems likely that many confounding may play a role in increasing risk of severe Covid-19, the evidence so far does seem solid enough to suggest that obesity can independently increase severity of COVID-19.

“We should be very concerned about the clash of two pandemics, Covid-19 and obesity. The pandemic really brings to the fore the need to tackle obesity more aggressively. At times when everybody understand the importance to fattening the curve of epidemics, we should also reckon that for the past 4 decades we have not been able to flatten the curve of the epidemic of obesity. This suggests we may need to  think differently about obesity, looking at what went wrong and learn some lessons. Until then – or as we do it – one lesson from the pandemic of Covid-19 is that not treating obesity is not an option.” 

 

 

https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/903546/PHE_Scientific_insight_Excess_weight_and_COVID-19.pdf

 

All our previous output on this subject can be seen at this weblink: www.sciencemediacentre.org/tag/covid-19

 

 

Declared interests

Dr Simon Cork: No conflicts of interest

Prof Susan Jebb: Peer-reviewed this report for PHE

Prof Linda Bauld: No conflicts of interest

Dr Katarina Kos: “I have no conflict of interest.”

None others received 

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