8  Metabolic disorder and inflammation in COVID-19
Metabolic disarray and inflammation are important factors in the pathogenesis of acute diseases. COVID-19, severe respiratory disease, is an adverse clinical outcome of the ongoing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic (Docea et al., 2020; Goumenou et al., 2020; Shi et al., 2020), and has recently been correlated to obesity-dependent inflammation (Petrakis et al., 2020). Indeed, in its most severe form, it entails a bilateral interstitial pneumonia requiring intensive care unit (ICU) ventilation support and has concomitant high mortality rate due to and multi-organ failure. Clinical reports have demonstrated that the most common comorbidities are CVD, hypertension and T2DM, age also being an important risk factor (Grasselli et al., 2020; Zhou et al., 2020). Lifestyle-associated factors, such as smoking, have also been associated with rapid disease progression (Farsalinos et al., 2020; Mesnage et al., 2020; Tsatsakis et al., 2020). A recent US study indicates that obesity is an underappreciated risk factor for COVID-19 (Kass et al., 2020). The authors found, in a cohort of 265 hospitalized patients, that age and the body-mass index (BMI) were inversely correlated with risk, hence indicating that younger obese patients were more likely to be admitted to hospital. Kass et al. concluded that a higher prevalence of obesity in each population will result in a higher COVID-19 incidence in younger individuals than previously reported. In addition to a mechanical impediment of ventilation, obesity was correlated with lower immune response to viral infection (Honce and Schultz-Cherry, 2019). Moreover, besides obesity, metabolic disarray and inflammation were suggested to contribute to COVID-19 pathogenesis (Petrakis et al., 2020). Indeed, specific fat-resident regulatory T cells (Treg) and enhancement of TH17 (T-cell sub-lineage)-biased immunity (Poutahidis et al., 2013; Winer et al., 2009) could be positively correlated to COVID-19 prevalence and increased mortality risk in obese individuals (Petrakis et al., 2020; Skalny et al., 2020). The “obese” pattern of immune cells subtypes was correlated to increased secretion of pro-inflammatory mediators including IL-6, IL-23/IL-17, TNF-α and macrophage inflammatory protein-1α (Sumarac-Dumanovic et al., 2009). Importantly, these inflammatory mediators were proved to disrupted tight junctions of the respiratory epithelium, which facilitates pathogen entry (Wittekindt, 2017).
COVID-19 is impacting to a greater extent the patients having underlying metabolic impairments (diabetes mellitus and/or obesity), as WHO is pointing out. On the other hand, increased levels of inflammatory markers cytokines with pro-inflammatory outcomes constitute predictors of adverse outcome in COVID-19 patients (Skalny et al., 2020).
Thus, reducing the inflammatory pathways, through the long-term employment of lifestyle changes (dietary measures, smoking cessation, moderate but constant physical activity, etc) could contribute to a better reaction of the immune system when affected by aggressive pathogens, such as SarsCov2. Improving diet (such as adding polyphenols, PUFAs, fibres, etc) can contribute to a reduction of inflammation, thus increasing the chances for a better response of patients affected by the virus (Butler and Barrientos, 2020; Rajkumar, 2020; WHO, 2020).