Greasing the inflammatory pathogenesis of viral pneumonias in diabetes.

Type 2 diabetes (T2D) and obesity are independent risk factors for increased morbidity and mortality associated with influenza and SARS-CoV-2 infection. Skewed cellular metabolism shapes immune cell inflammatory responsiveness and function in obesity, T2D, and infection. However, altered immune cell responsiveness and levels of systemic proinflammatory mediators, partly independent of peripheral immune cell contribution, are linked with SARS-CoV-2-associated disease severity. Despite such knowledge, the role of tissue parenchymal cell-driven inflammatory responses, and specifically those dominantly modified in obesity (e.g., adipocytes), in influenza and SARS-CoV-2 infection pathogenesis remain poorly defined. Whether obesity-dependent skewing of adipocyte cellular metabolism uncovers inflammatory clades and promotes the existence of a 'pathogenic-inflammatory' adipocyte phenotype that amplifies SARS-CoV-2 infection diseases severity in individuals with obesity and individuals with obesity and T2D has not been examined. Here, using the knowledge gained from studies of immune cell responses in obesity, T2D, and infection, we highlight the key knowledge gaps underlying adipocyte cellular functions that may sculpt and grease pathogenic processes associated with influenza and SARS-CoV-2 disease severity in diabetes.

Adipocyte inflammation and pathogenesis of viral pneumonias: an overlooked contribution.

Epidemiological evidence establishes obesity as an independent risk factor for increased susceptibility and severity to viral respiratory pneumonias associated with H1N1 influenza and SARS-CoV-2 pandemics. Given the global obesity prevalence, a better understanding of the mechanisms behind obese susceptibility to infection is imperative. Altered immune cell metabolism and function are often perceived as a key causative factor of dysregulated inflammation. However, the contribution of adipocytes, the dominantly altered cell type in obesity with broad inflammatory properties, to infectious disease pathogenesis remains largely ignored. Thus, skewing of adipocyte-intrinsic cellular metabolism may lead to the development of pathogenic inflammatory adipocytes, which shape the overall immune responses by contributing to either premature immunosenescence, delayed hyperinflammation, or cytokine storm in infections. In this review, we discuss the underappreciated contribution of adipocyte cellular metabolism and adipocyte-produced mediators on immune system modulation and how such interplay may modify disease susceptibility and pathogenesis of influenza and SARS-CoV-2 infections in obese individuals.

[Consensus of the Genetics Branch of the Chilean Society of Pediatrics on the prioritization of people with Down syndrome and rare diseases for vaccination against SARS-CoV-2]. / Consenso de la Rama de Genética de la Sociedad Chilena de Pediatría sobre priorización de personas con Síndrome de Down y otras condiciones poco frecuentes en la Campaña de Vacunación COVID-19.

In the framework of the vaccination campaign against the SARS-CoV-2 virus, the Chilean Ministry of Health requested advice from the Genetics Branch of the Chilean Society of Pediatrics, to define the level of prioritization for people with Down Syndrome . A panel of geneticists worked on the development of this consensus, in which not only patients with Down syndrome were included, but the search was extended to patients with other types of disabilities, in both pediatric and adult ages in or der to contribute to the development of public health measures against the COVID-19 pandemic. The consensus concludes that, given the prevalence of comorbidities associated with Down syndrome, the higher incidence of cases with severe COVID-19 in this population group and a higher mortality, individuals with trisomy 21 should be considered as a high-risk population, and therefore, vaccina tion against SARS-CoV-2 should have a high priority for all people with Down syndrome regardless of their age (except for the age limit established by the clinical trials of each vaccine), and should be preceded only by the groups of health personnel and adults aged > 60-65 years. Likewise, this group of experts urges health authorities to include people with intellectual disabilities and related conditions as a priority population (other chromosomal abnormalities other than Down syndrome, intellectual disability, congenital anomalies and conditions that cause disability with microcephaly), as well as the caregivers of people with this type of conditions. Vaccination in children with this type of disorders should be considered as part of the first priority group, once safe vaccines against SARS-CoV-2 are available for use in children and adolescents.