No abstract

The SARS-CoV-2 is responsible for the pandemic COVID-19 in infected individuals, who can either exhibit mild symptoms or progress towards a life-threatening acute respiratory distress syndrome (ARDS). It is known that exacerbated inflammation and dysregulated immune responses involving T and myeloid cells occur in COVID-19 patients with severe clinical progression. However, the differential contribution of specific subsets of dendritic cells and monocytes to ARDS is still poorly understood. In addition, the role of CD8 + T cells present in the lung of COVID-19 patients and relevant for viral control has not been characterized. With the aim to improve the knowledge in this area, we developed a cross-sectional study, in which we have studied the frequencies and activation profiles of dendritic cells and monocytes present in the blood of COVID-19 patients with different clinical severity in comparison with healthy control individuals. Furthermore, these subpopulations and their association with antiviral effector CD8 + T cell subsets were also characterized in lung infiltrates from critical COVID-19 patients.Collectively, our results suggest that inflammatory transitional and non-classical monocytes preferentially migrate from blood to lungs in patients with severe COVID-19. CD1c + conventional dendritic cells also followed this pattern, whereas CD141 + conventional and CD123 hi plasmacytoid dendritic cells were depleted from blood but were absent in the lungs. Thus, this study increases the knowledge on the pathogenesis of COVID-19 disease and could be useful for the design of therapeutic strategies to fight SARS-CoV-2 infection.

Animal models are useful to understand the myriad physiological effects of hypoxia. Such models attempt to recapitulate the hypoxemia of human disease in various ways. In this mini-review, we consider the various animal models which have been deployed to understand the effects of chronic hypoxia on pulmonary and systemic blood pressure, glucose and lipid metabolism, atherosclerosis, and stroke. Chronic sustained hypoxia (CSH)—a model of chronic lung or heart diseases in which hypoxemia may be longstanding and persistent, or of high altitude, in which effective atmospheric oxygen concentration is low—reliably induces pulmonary hypertension in rodents, and appears to have protective effects on glucose metabolism. Chronic intermittent hypoxia (CIH) has long been used as a model of obstructive sleep apnea (OSA), in which recurrent airway occlusion results in intermittent reductions in oxyhemoglobin saturations throughout the night. CIH was first shown to increase systemic blood pressure, but has also been associated with other maladaptive physiological changes, including glucose dysregulation, atherosclerosis, progression of nonalcoholic fatty liver disease, and endothelial dysfunction. However, models of CIH have generally been implemented so as to mimic severe human OSA, with comparatively less focus on milder hypoxic regimens. Here we discuss CSH and CIH conceptually, the effects of these stimuli, and limitations of the available data.