RESUMEN
The novel coronavirus SARS-CoV-2 was identified as the causative agent of the ongoing pandemic COVID 19. COVID-19-associated deaths are mainly attributed to severe pneumonia and respiratory failure. Recent work demonstrated that SARS-CoV-2 binds to angiotensin converting enzyme 2 (ACE2) in the lung. To better understand ACE2 abundance and expression patterns in the lung we interrogated our in-house single-cell RNA-sequencing dataset containing 70,085 EPCAM+ lung epithelial cells from paired normal and lung adenocarcinoma tissues. Transcriptomic analysis revealed a diverse repertoire of airway lineages that included alveolar type I and II, bronchioalveolar, club/secretory, quiescent and proliferating basal, ciliated and malignant cells as well as rare populations such as ionocytes. While the fraction of lung epithelial cells expressing ACE2 was low (1.7% overall), alveolar type II (AT2, 2.2% ACE2+) cells exhibited highest levels of ACE2 expression among all cell subsets. Further analysis of the AT2 compartment (n = 27,235 cells) revealed a number of genes co-expressed with ACE2 that are important for lung pathobiology including those associated with chronic obstructive pulmonary disease (COPD; HHIP), pneumonia and infection (FGG and C4BPA) as well as malarial/bacterial (CD36) and viral (DMBT1) scavenging which, for the most part, were increased in smoker versus light or non-smoker cells. Notably, DMBT1 was highly expressed in AT2 cells relative to other lung epithelial subsets and its expression positively correlated with ACE2. We describe a population of ACE2-positive AT2 cells that co-express pathogen (including viral) receptors (e.g. DMBT1) with crucial roles in host defense thus comprising plausible phenotypic targets for treatment of COVID-19.
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<p><b>BACKGROUND</b>The extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae has increasingly become a major contributor to nosocomial infections and can exhibit multiple antibiotic resistance. Previous studies have focused on the resistance genes in ESBL-producing strains, and the resistance-associated genetic environment of non-ESBL-producing strains has been ignored until now. Here, we investigated the occurrence and characteristics of non-ESBL-producing K. pneumoniae, which potentially carries unexpressed resistance genes.</p><p><b>METHODS</b>K. pneumoniae strains were collected from five medical institutions in China from February 2010 to August 2013. The VITEK-2 ESBL detection system was used as a primary screen to identify the ESBL-producing phenotype, and the three primary types of ESBL-associated genes (CTX, SHV, and TEM) were detected by polymerase chain reaction (PCR) to confirm the strains presenting with a non-ESBL-producing phenotype. mRNA expression in the non-ESBL-producing strains was further screened by reverse-transcription PCR (RT-PCR) to validate their transcriptional efficiency.</p><p><b>RESULTS</b>Out of 224 clinically isolated antibiotic-sensitive K. pneumoniae strains with a non-ESBL-producing phenotype, 5 (2.2%) were identified to carry inactivated ESBL blaSHV genes with intact upstream promoter regions and resistance gene sequences. Interestingly, three of the five antibiotic-sensitive K. pneumoniae strains containing ESBL blaSHV genes still exhibited mRNA transcription of blaSHV, while the other two exhibited no mRNA transcription.</p><p><b>CONCLUSION</b>These findings suggest that inactivated ESBL genes exist in non-ESBL-producing antibiotic-sensitive K. pneumoniae strains, which have the potential to transform the strain into an ESBL phenotype if an inappropriate application or overdose of antibiotics is implemented during clinical management.</p>
Asunto(s)
Humanos , Antibacterianos , Farmacología , China , Farmacorresistencia Bacteriana Múltiple , Genética , Klebsiella pneumoniae , Genética , Pruebas de Sensibilidad Microbiana , beta-Lactamasas , GenéticaRESUMEN
Previous studies have shown that cost of illness (COI) measures are lower than the conceptually correct willingness-to-pay (WTP) measure of the economic benefits of disease prevention. We compare COI with stated preference estimates of WTP associated with shigellosis in a rural area of China. COI data were collected through face-to-face interviews at 7 and 14 days after culture-confirmed diagnosis. WTP to avoid an episode similar to the one the respondent just experienced was elicited using a sliding-scale payment card. In contrast to previous studies' findings, average COI estimates (2002 PPP adjusted US dollars 28.2) approximate an upper bound estimate of WTP, rather than a lower bound. One explanation for the similarity between COI and WTP is that preventive expenditures and disutility due to pain and suffering are low for shigellosis. WTP to avoid additional cases in children aged 0-5 years is higher than in adults. Also, average COI (2002 PPP adjusted US dollars 28.4) for children is similar to a lower bound estimate of WTP (2002 PPP adjusted US dollars 16.4) and lies within the WTP range. Because the monetary loss associated with another episode in children is small, caregivers' higher WTP may be attributable to the disutility of illness due to the children's pain and suffering. These findings suggest that for some diseases, COI may approximate more comprehensive measures of economic benefits.