COVID-19 and people with obesity; what does the evidence say?

The COVID-19 pandemic has led to worldwide research efforts to identify risk factors for morbidity and mortality in order to identify high-risk populations and assist in the development of effective preventive strategies.

Initial data indicated that elderly people were particularly vulnerable, in addition to people with diabetes, or cardiovascular, respiratory or renal disease. And there is now a growing body of evidence that has identified obesity to be a risk factor for more severe COVID-19 illness and death.

Early research on the Chinese COVID-19 experience found patients with obesity had a 33.3% probability of more severe COVID-19 infection.

The OpenSAFELY cohort study in the UK actively sought to identify factors associated with COVID-19-related hospital death by reviewing the linked electronic health records of more than 17 million adult National Health Service (NHS) patients. Most comorbidities were associated with increased risk, including obesity. For individuals already living with overweight or obesity, as their body mass index (BMI) increased, so did their risk of dying from COVID-19.

To date, the virologic and physiological mechanisms between severe obesity and COVID-19 infection severity are poorly understood. I would venture a hypothesis that more severe COVID-19 in patients with obesity may be the consequence of underlying low-grade chronic inflammation, and suppression of innate and adaptive immune responses, as described in earlier research.

It is well documented in the literature that adipose tissue in obesity is ‘pro-inflammatory,’ with increased expression of cytokines, particularly adipokines. Obesity is already recognised as an independent and causal risk factor for the development of immune-mediated disease such as psoriasis and many others.

I would also suggest that people with obesity have a higher risk factor of acquiring COVID-19 due to an impaired host response, given obesity is already known to impair adaptive immune responses to influenza virus. A similarly impaired adaptive immune response is conceivable with COVID-19.

Research has found the 2009 H1N1 swine flu could induce ‘distinct alterations in the lung metabolome, perhaps contributing to aberrant pH1N1 immune responses’ in mice with obesity.

By analogy to other respiratory infections, obesity may also play an important role in COVID-19 transmission. For example, in the case of influenza A, obesity increases the duration of virus shedding, as symptomatic patients with obesity shed the virus 42% longer than adults who do not have obesity. This suggests potential for great viral exposure, especially if several family members are above a healthy weight. It also appears that severe obesity can be an aggravating risk factor for death from COVID-19 infection.

One explanation of the above findings is that COVID-19 has high affinity for human angiotensin converting enzyme 2 (ACE-2), which has been shown to be the putative receptor for the entry of COVID-19 into host cells.

Individuals with obesity have more adipose tissue and therefore an increased number of ACE-2-expressing cells, and consequently, a larger amount of ACE-2. Furthermore, some people with obesity may be taking angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) for the treatment of concurrent hypertension, which will increase expression of ACE-2. All of these factors increase the susceptibility of people with obesity to viral host cell entry and propagation.

What do we know from overseas experience?

In a French study, the risk for invasive mechanical ventilation in patients with COVID-19 infection admitted to the intensive treatment unit was more than seven-fold higher for those with BMI >35 compared with BMI <25 kg/m2.

This study found that BMI seemed to be associated with ventilator treatment, independently of age, diabetes or hypertension. More broadly, mechanical dysfunction due to severe obesity may increase the severity of lower respiratory tract infection and contribute to secondary infection.

Research from a large New York hospital system shows the presence of obesity increases the risk of severe illness approximately three-fold with a consequent longer hospital stay. Having obesity and being aged older than 60 is a newly identified epidemiologic risk factor which may contribute to increased morbidity rates.

The retrospective analysis study examined BMI stratified by age in COVID-19-positive symptomatic patients who presented to a large academic hospital system in New York City. The BMI range of individuals in this study appears representative of the US, where 37% of the patients have a BMI ≥30, and is similar to Australia where one-third of the Australian adult population has obesity, according to the Australian Bureau of Statistics.

What does this mean for healthcare professionals?

In short, people with obesity:

• have a higher risk of acquiring COVID-19 due to an impaired host response
• may exhibit greater viral shedding if they acquire COVID-19, which suggests potential for great viral exposure, especially if several family members have overweight or obesity
• who are younger than 60 and have acquired COVID-19 are at increased risk of requiring hospital admission
• who acquire COVID-19 have worse health outcomes, ie increased morbidity (requiring assisted ventilation etc) and increased mortality.

In addition, people with the highest BMI are more often seen in critical cases and non-survivors.

As a result, I would recommend extra attention paid and precautions taken for people living with obesity during this pandemic.

This includes using appropriate CDC codes to identify people with obesity, especially those with severe obesity. This should assist all practice staff in identifying at-risk patients, so appropriate preventive strategies can be implemented.

We must also share this information with the community, particularly those at risk, in a sympathetic and non-alarming fashion.

What we don’t want is at-risk people being too scared to seek the medical help and support they need and deserve.

The RACGP is a member of the National COVID-19 Clinical Evidence Taskforce, which is regularly preparing and updating guidelines for clinical practice.

The current guidance advises that people with pre-existing conditions and older people are at higher risk of COVID-19. The taskforce will be updating its advice about people with obesity in the near future.