: This paper examines the potential link between COVID-19 and the presence of comorbidities and assesses the role of inflammation in this correlation. In COVID-19 patients, the most frequently associated diseases share a pathogenic inflammatory basis and apparently act as a risk factor in the onset of a more severe form of the disease, particularly in adulthood. However, in children, the understanding of the underlying pathogenic mechanisms is often complicated by the milder symptoms presented. A series of theories have therefore been put forward with a view of providing a better understanding of the role played by inflammation in this dramatic setting. All evidence available to date on this topic is discussed in this review.