ARTICLE | doi:10.20944/preprints202108.0440.v1
Online: 23 August 2021 (13:23:05 CEST)
Although, severe acute respiratory syndrome coronavirus – 2 (SARS-CoV 2) represents one of the biggest challenges in the world today, the exact immunopathogenic mechanism that leads to severe or critical Coronavirus Disease 2019 (COVID-19) has remained incompletely understood. Several studies have indicated that high systemic plasma levels of inflammatory cytokines result in the so-called “cytokine storm”, with subsequent development of microthrombosis, disseminated intravascular coagulation, and multiorgan-failure. Therefore, we reasoned that elevated inflammatory cytokine might act as prognostic factors. Here, we analyzed 245 serum samples of patients with COVID-19, collected at hospital admission. We assessed the levels of heat shock protein 27 (HSP27), soluble suppressor of tumorigenicity- 2 (sST2), caspase cleaved cytokeratin 18 (cCK18), 20S proteasome, and tumor necrosis factor receptor 1 (TNFR-1) and explored their associations with overall-, 30-, 60-, 90-day- and in-hospital mortality. Moreover, we investigated their association with the risk of ventilation. We demonstrated that increased serum sST2 was uni- and multivariably associated with all endpoints. However, we also identified 20S proteasome as independent prognostic factor for in-hospital mortality. Furthermore, elevated HSP27, sST2, and 20S proteasome levels at hospital admission were univariably associated with higher risk of invasive ventilation. These findings could help to identify high-risk patients early in the course of COVID-19.
ARTICLE | doi:10.20944/preprints202112.0033.v1
Subject: Life Sciences, Cell & Developmental Biology Keywords: IPF; alveolar epithelial cells; intermediate epithelial cells; transitional states, lysotracker; flow cytometry; lung transcriptomic profile, CK5; NGFR; CD24
Online: 2 December 2021 (11:38:12 CET)
Idiopathic lung fibrosis (IPF) is a progressive and fatal degenerative lung disease of unknown etiology. Although in its final stages it implicates in a reactive manner all lung cell types, the initial damage involves the alveolar epithelial compartment, in particular the alveolar epithelial type 2 cells (AEC2s). AEC2s serve dual progenitor and surfactant secreting functions, both of which are deeply impacted in IPF. Thus, we hypothesize that the size of the surfactant processing compartment, as measured by Lysotracker incorporation, allows the identification of different epithelial states in the IPF lung. Flow cytometry analysis of epithelial Lysotracker incorporation delineates two populations (Lysohigh and Lysolow) of AEC2s which behave in a compensatory manner during bleomycin injury and in the donor/IPF lung. Employing flow cytometry and transcriptomic analysis of cells isolated from donor and IPF lungs, we demonstrate that the Lysohigh population expresses all classical AEC2 markers and is drastically diminished in IPF. The Lysolow population, which is increased in proportion in IPF, co-expresses AEC2s and basal cell markers resembling the phenotype of the previously identified intermediate AEC2 population in the IPF lung. In that regard, we provide an in-depth flow-cytometry characterization of Lysotracker uptake, HTII-280, proSP-C, mature SP-B, NGFR, KRT5 and CD24 expression in human lung epithelial cells. Combining functional analysis with extra- and intra- cellular marker expression and transcriptomic analysis, we advance the current understanding of epithelial cell behavior and fate in lung fibrosis.