Altered sphingolipid pathway in SARS-CoV-2 infected human lung tissue.

Introduction: The SARS-CoV-2 mediated COVID-19 pandemic has impacted millions worldwide. Hyper-inflammatory processes, including cytokine storm, contribute to long-standing tissue injury and damage in COVID-19. The metabolism of sphingolipids as regulators of cell survival, differentiation, and proliferation has been implicated in inflammatory signaling and cytokine responses. Sphingosine-kinase-1 (SK1) and ceramide-synthase-2 (CERS2) generate metabolites that regulate the anti- and pro-apoptotic processes, respectively. Alterations in SK1 and CERS2 expression may contribute to the inflammation and tissue damage during COVID-19. The central objective of this study is to evaluate structural changes in the lung post-SARS-CoV-2 infection and to investigate whether the sphingolipid rheostat is altered in response to SARS-CoV-2 infection. Methods: Central and peripheral lung tissues from COVID-19+ or control autopsies and resected lung tissue from COVID-19 convalescents were subjected to histologic evaluation of airspace and collagen deposisiton, and immunohistochemical evaluation of SK1 and CERS2. Results: Here, we report significant reduction in air space and increase in collagen deposition in lung autopsy tissues from patients who died from COVID-19 (COVID-19+) and COVID-19 convalescent individuals. SK1 expression increased in the lungs of COVID-19+ autopsies and COVID-19 convalescent lung tissue compared to controls and was mostly associated with Type II pneumocytes and alveolar macrophages. No significant difference in CERS2 expression was noted. SARS-CoV-2 infection upregulates SK1 and increases the ratio of SK1 to CERS2 expression in lung tissues of COVID-19 autopsies and COVID-19 convalescents. Discussion: These data suggest an alteration in the sphingolipid rheostat in lung tissue during COVID-19, suggesting a potential contribution to the inflammation and tissue damage associated with viral infection.

Overproduction of TNF-α and lung structural remodelling due to chronic exposure to volcanogenic air pollution.

Volcanogenic air pollution studies and their effects on the respiratory system are still outnumbered by studies regarding the effects of anthropogenic air pollution, representing an unknown risk to human population inhabiting volcanic areas worldwide (either eruptive or non-eruptive areas). This study was carried in the archipelago of the Azores- Portugal, in two areas with active volcanism (Village of Furnas and Village of Ribeira Quente) and a reference site (Rabo de Peixe). The hydrothermal volcanism of Furnas volcanic complex is responsible for the release of 1000 t d-1 of CO2, H2S, the radioactive gas - radon, among others. Besides the gaseous emissions, particulate matter and metals (Hg, Cd, Zn, Al, Ni, etc.) are also released into the environment. We tested a hypothesis whether chronic exposure to volcanogenic air pollution causes lung structural remodelling, in the house mouse, Mus musculus, as a bioindicator species. Histopathological evaluations were performed to assess the amount of macrophages, mononuclear leukocyte infiltrate, pulmonary emphysema, and the production of pro-inflammatory cytokine TNF-α. Also, the percentage of collagen and elastin fibers was calculated. Mice chronically exposed to volcanogenic air pollution presented an increased score in the histopathological evaluations for the amount of macrophages, mononuclear leukocyte infiltrate, pulmonary emphysema and production of TNF-α; and also increased percentages of collagen and elastin. For the first time, we demonstrate that non-eruptive active volcanism has a high potential to cause lung structural remodelling. This study also highlights the Mus musculus as a useful bioindicator for future biomonitoring programs in these type of volcanic environments.