This systematic review of the available evidence highlights the relationship between obesity and the COVID–19 pandemic. Several clinical characterization studies, case series and case reports have shown that obesity is an independent significant predictor of worse outcomes and increased complications from COVID–19 infections. This includes more severe disease, higher rates of hospital admission, intensive care management, and mortality, as compared to lean subjects (summarized in Table 2). Other risk factors include male gender, age, and co-morbidities like hypertension and diabetes.
Our review also suggests that obesity is a significant public health problem that predates the COVID–19 pandemic and will expectedly worsen due to psychological factors, behavioral changes and implemented health policies. The role of obesity in COVID–19 can be contextualized in the wider framework of infectious diseases and needs further attention.
Obesity in pandemics
To date, there is limited evidence elucidating the pathophysiological mechanisms linking obesity and severe COVID–19 disease. SARS-CoV–2 has been shown to gain access to the host via angiotensin-converting enzyme 2 (ACE–2) receptors which are upregulated in adipocyte and adipocyte-like cells such as pulmonary lipofibroblasts. This makes obese and diabetic individuals particularly vulnerable to severe lung infection and may explain the development of associated pulmonary fibrosis (34). Moreover, low-grade systemic inflammation and end-organ damage seen in obese individuals are associated with the development of insulin resistance, type 2 diabetes, hypertension, atherosclerosis, dyslipidemia and asthma—well-known co-morbidities that negatively affect the outcomes of patients with COVID–19(14). Difficult airway management and prone positioning (critical in the treatment of ARDS) which are routinely encountered with elevated BMI, further exacerbate the problem(35, 36).
Additionally, extrapolations can also be made from studies in subjects from past pandemics, given that SARS-CoV–2 has 85% and 50% sequence similarity to known coronaviruses SARS-CoV–1 and MERS-CoV, respectively (37). Increased adiposity has been implicated in higher rates of complications in other pandemics—MERS-CoV, SARS-CoV–1 and H1N1 influenza, including development of acute respiratory distress syndrome (ARDS), acute lung injury (ALI), hospitalization and mortality(38).
During the H1N1 swine flu of 2009, obesity was postulated to be an independent risk factor for increased morbidity and mortality in viral illnesses. In a study that spanned from April to August 2009 in California, Louie et al. found that over half of 534 adult hospitalized patients with H1N1 were obese, with a BMI >30. Of the 92 cases who died, 61% were obese(5). Fezeu et al. revealed that severely obese H1N1 patients (BMI>40) were twice as likely to be admitted to the intensive care unit, with a higher mortality rate than those with a lower BMI(6).
The outbreaks of MERS and SARS in the early 2000s further established obesity as being positively associated with mortality, along with male gender, older age, hypertension, diabetes, COPD, and chronic heart diseases (9, 39, 40). The clinical features of both of these coronaviruses SARS-CoV–1 and MERS-CoV are similar, and can range from asymptomatic or mild disease, to ARDS and multi-organ failure. However, 75% of MERS cases are associated with underlying comorbidities, with a mortality rate of MERS is 60% in this subgroup, while only 10–30% of SARS patients have underlying health conditions with a mortality rate of 46% within this subgroup(41)
Obese individuals may be more infectious
Several human and animal studies have demonstrated a positive correlation between infectivity and increased weight. Maier et al. demonstrated that symptomatic obese individuals shed influenza A particles up to 104% longer than their lean counterparts(42). Similarly, in a study of 178 young adults, Yan et al. concluded that the concentration of viral RNA found in aerosols from collected breath correlated positively with BMI(43). The obesity microenvironment may also be conducive to the development of more virulent viral strains. For example, obese mice models infected with influenza were observed to have a decreased type I interferon response, and had increased viral replication as compared to non-obese mice(44). There is a paucity of evidence on the infectivity of obese individuals in the COVID–19 pandemic, but extrapolations can be made from investigations on other viruses. While the pathophysiology of SARS-CoV2 infection has not been completely elucidated, it has been proposed that the virus gains entry into cells through ACE2-dependent mechanisms, much like SARS-CoV and human respiratory coronavirus NL63(45). It is spread by human-to-human transmission via droplets, aerosolized particles, and direct contact(46). Infection has been estimated to have an incubation time varying from 2 to 14 days, with a mean of 6.4 days)(46, 47). Taking into considering prolonged viral shedding and increased viral load in expired air in obese persons, longer quarantine periods should be considered in individuals with increased adiposity as compared to their lean counterparts(48).
Viral infections may induce obesity
The association between obesity and viral infection is not unidirectional. Certain infections by pathogens like adenovirus 36 (Ad36) have been demonstrated to induce obesity. In a systematic review published in 2020, Kim et al. conclude that Ad36 infection increases adipogenesis (through hypertrophy and hyperplasia) in animals and is associated with human obesity. Moreover, Ad36 infection was shown to induce acute and chronic inflammation leading to angiogenesis in fatty tissues(49). Another systematic review by Xu et al. concludes that Helicobacter pylori infection may be a risk factor for the development of obesity(50). However, a causal relationship cannot be established due to the nature of the study design of the included studies.
Indirect impact of COVID19 on the obese population and obesity services
We have recognized that obesity is a risk factor for poor outcomes in COVID–19 infection(28, 51). However, it is inevitable that the pandemic will only exacerbate the existing levels of obesity for several reasons. Firstly, the lifestyle of the average individual during a state of social isolation and global unrest will drastically change. Specifically, in the early phases of the pandemic and during lockdown measures, there will likely be a tendency towards an unhealthy diet coupled with a sedentary lifestyle (52). Over a longer time, this may lead to considerable weight gain for most people. Secondly, the reallocation of hospital resources from elective surgeries to managing COVID–19 patients has led to the nationwide pause of most bariatric surgery as well as most other multidisciplinary services that comprise of the tier 3 weight management programs (31). This is not only to free up inpatient capacity and redirect healthcare workers towards managing COVID–19 patients, but also to avoid intraoperative risks of viral contagion among patients and staff(29). Hence, there is a pre-existing level of obesity that we have not managed yet. In combination, we predict a rise in obesity and its complications in the post-COVID era (53).
Globally, the majority of governments have instituted a “lockdown” approach in an effort to limit the transmission of COVID–19 cases. While this has been proven to be effective as containment measures, there are multiple negative effects of this approach. From an obesity perspective, it is highly likely that the cessation of active lifestyles will lead to an increase in weight gain amongst a significant proportion of the population(33). This can be attributed to a reduction in physical exercise as well as poorer dietary lifestyle. In the early phases of the outbreak, panic-buying and stockpiling depleted most stores of perishable healthy food items, including meat, fruits and vegetables(54). These reactions had severe repercussions on both food access and utilization(55). Consequently, most people had to rely on unhealthy food items as sustenance. Previously, Scully et al had shown that both lockdown and confinement would also lead to erratic dietary patterns and frequent snacking, both of which are associated with higher caloric intake and increased risk of obesity(56). Furthermore, studies from China showed a negative impact on psychological health, which has previously been linked to unhealthy dietary patterns and poor quality of the diet (30, 57, 58). Hence, the current lockdown is likely to increase the prevalence of obesity, and we should actively seek measures to overcome them.
The COVID–19 crisis has led to the cessation of most elective surgical procedures globally at different times. In the UK, NHS England has asked for elective procedures to be halted for three months starting from April 15, 2020 (59, 60). Accordingly, early guidelines from the International Federation for the Surgery of Obesity and metabolic disorders (IFSO) recommended postponing any bariatric procedure(31). But, delaying bariatric surgery extends the progression of metabolic complications of obesity, including type 2 diabetes, obesity hypoventilation syndrome, obesity-associated heart failure and cancers(61–66). This directly increases the disease burden amongst patients. For example, previous modelling work and the multi-cantered Swedish Obesity Study have consistently showed longstanding disease as a strong predictor of disease remission(67–69). The impact of cancelling elective bariatric surgery will be expensive. Previous economic analyses have shown that diseases that can be corrected with surgery is more cost-effective than medical management. For example, the management of type 2 diabetes with several medications is far more costly than bariatric surgery. Hence, delaying surgery for these patients will make it less cost-saving over time.
There are several solutions for the afore-mentioned issues. Firstly, there should be a coordinated effort from governments and food and beverage industry to ensure an adequate supply chain to prevent food insecurity. There needs to be increased public awareness about the “lockdown lifestyle” can make them obese and provide strategies to avoid it. Already, WHO has provided a list of exercises that can be performed at home to stay physically active(70). Secondly, in the context of a long backlog of operations and patients with higher likelihood of complications, it is possible that there will be a shortage of staff and hospital beds to accommodate this surge. Traditionally, patients have been listed for surgery on a first-come-first-serve basis, prioritized on clinical need. Now, we must generate guidelines for prioritizing patients based on disease severity, taking into account any co-existing microvascular and macrovascular complications of obesity (indicators of organ dysfunction)(71). For example, the Diabetes Surgery Summit (DSS) recommends that patients using insulin and patients with disease duration longer than 5 years be prioritized(32). In the meanwhile, patients should be optimized for surgery and ensure that their weight and metabolism is controlled through lifestyle and pharmacological measures. Surgery should be expedited for patients not responding to such conservative measures. Obesity management / bariatric surgical teams must be advocates for their patients during these difficult times, otherwise there is a significant risk of the patients’ needs being ignored due to continued public perception, that obesity is still a choice and not a disease(72). Through these measures, we may be able to mitigate the afterburn of COVID–19 on the bariatric population.