Obesity and the increased risk for COVID-19: mechanisms and nutritional management

Abstract

The global COVID-19 (coronavirus disease 2019) pandemic has become a complex problem that overlaps with a growing public health problem, obesity. Obesity alters different components of the innate and adaptive immune responses, creating a chronic and low-grade state of inflammation. Nutritional status is closely related to a better or worse prognosis of viral infections. Excess weight has been recognised as a risk factor for COVID-19 complications. In addition to the direct risk, obesity triggers other diseases such as diabetes and hypertension, increasing the risk of severe COVID-19. The present review explains the diets that induce obesity and the importance of different foods in this process. We also review tissue disruption in obesity, leading to impaired immune responses and the possible mechanisms by which obesity and its co-morbidities increase COVID-19 morbidity and mortality. Nutritional strategies that support the immune system in patients with obesity and with COVID-19 are also discussed in light of the available data, considering the severity of the infection. The discussions held may contribute to combating this global emergency and planning specific public health policy.

Keywords: Coronavirus; Immunity; Nutritional status; Overweight; SARS-CoV-2; Viral infection.

Fig. 1.

Obesity and immune alterations in different tissues leading to impaired immune response and increased risk for the evolution of respiratory infectious to severe disease. Obesity determines the stress and disruption of many tissues’ integrity leading to inflammation. In the adipose tissue, the enlarging adipocytes present oxidative stress and increase the release of NEFA in the adipose tissue, activating classical macrophages (M1), which produce IL-1β, TNF-α and IL-6. An unfavourable hormone milieu also promotes inflammation: low adiponectin and high leptin productions are observed in obesity. In the lymphoid tissue, lipid accumulation occurs in the bone marrow, thymus and secondary lymphoid organs, altering the immune tissue architecture similarly to findings observed in ageing. In the gut, oxidative stress causes dysbiosis, increasing gut permeability and inducing endotoxaemia, characterised by an increase in gut-derived plasma lipopolysaccharide, which induces inflammation. In the lungs, experimental diet-induced obesity studies of influenza infections showed the reduced ability of dendritic cells (DC) to present antigens (Ag) to T cells, impairing monocyte and CD8⁺ T cell recruitment and reducing IL-2 and IL-12 production. Effector CD8⁺ T cells demonstrated a lower ability to kill influenza-infected cells, and the healing of pulmonary epithelial cells is compromised, resulting in microvascular permeability and protein leak. Overall, the inflammation induced by obesity causes altered activation of leucocyte subpopulations, impairing the immune response and increasing the risk of the evolution of respiratory infection to severe disease. ↑, Increase; ↓, decrease.

Fig. 2.

Obesity, co-morbidities and COVID-19 (coronavirus disease 2019): the triple burden. Obesity and its co-morbidities induce low-grade chronic inflammation and an increase in angiotensin-converting enzyme 2 (ACE2) receptors present in the lungs, intestine and kidneys. COVID-19, in turn, also induces inflammation and alterations overlapping those induced by obesity and its co-morbidities. These alterations occur as the disease severity increases and are in: glycaemia – increasing blood glucose; the renin–angiotensin system – causing higher pro-inflammatory responses; lung function – increasing vascular permeability and lung injury; the coagulation system – increasing prothrombotic effects; kidney function – inducing chronic kidney failure. Possible pathways to explain these worsened alterations in patients with obesity and with co-morbidities are: in the lungs – a higher ACE2 expression, unregulated lipogenesis and inflammation; in the coagulation system – a higher concentration of plasminogen activator inhibitor-1; and in the kidney – a higher expression of ACE2 and transmembrane protease serine (TMPRSS) genes. These overlapping alterations and inflammation associated with the cytokine storm induced by COVID-19 increase the risk of complications in patients with obesity, such as respiratory failure, septic shock, multiple organ failure, and, ultimately, increased mortality.