A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster.

BACKGROUND: An ongoing outbreak of pneumonia associated with a novel coronavirus was reported in Wuhan city, Hubei province, China. Affected patients were geographically linked with a local wet market as a potential source. No data on person-to-person or nosocomial transmission have been published to date. METHODS: In this study, we report the epidemiological, clinical, laboratory, radiological, and microbiological findings of five patients in a family cluster who presented with unexplained pneumonia after returning to Shenzhen, Guangdong province, China, after a visit to Wuhan, and an additional family member who did not travel to Wuhan. Phylogenetic analysis of genetic sequences from these patients were done. FINDINGS: From Jan 10, 2020, we enrolled a family of six patients who travelled to Wuhan from Shenzhen between Dec 29, 2019 and Jan 4, 2020. Of six family members who travelled to Wuhan, five were identified as infected with the novel coronavirus. Additionally, one family member, who did not travel to Wuhan, became infected with the virus after several days of contact with four of the family members. None of the family members had contacts with Wuhan markets or animals, although two had visited a Wuhan hospital. Five family members (aged 36-66 years) presented with fever, upper or lower respiratory tract symptoms, or diarrhoea, or a combination of these 3-6 days after exposure. They presented to our hospital (The University of Hong Kong-Shenzhen Hospital, Shenzhen) 6-10 days after symptom onset. They and one asymptomatic child (aged 10 years) had radiological ground-glass lung opacities. Older patients (aged >60 years) had more systemic symptoms, extensive radiological ground-glass lung changes, lymphopenia, thrombocytopenia, and increased C-reactive protein and lactate dehydrogenase levels. The nasopharyngeal or throat swabs of these six patients were negative for known respiratory microbes by point-of-care multiplex RT-PCR, but five patients (four adults and the child) were RT-PCR positive for genes encoding the internal RNA-dependent RNA polymerase and surface Spike protein of this novel coronavirus, which were confirmed by Sanger sequencing. Phylogenetic analysis of these five patients' RT-PCR amplicons and two full genomes by next-generation sequencing showed that this is a novel coronavirus, which is closest to the bat severe acute respiatory syndrome (SARS)-related coronaviruses found in Chinese horseshoe bats. INTERPRETATION: Our findings are consistent with person-to-person transmission of this novel coronavirus in hospital and family settings, and the reports of infected travellers in other geographical regions. FUNDING: The Shaw Foundation Hong Kong, Michael Seak-Kan Tong, Respiratory Viral Research Foundation Limited, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund Limited, Marina Man-Wai Lee, the Hong Kong Hainan Commercial Association South China Microbiology Research Fund, Sanming Project of Medicine (Shenzhen), and High Level-Hospital Program (Guangdong Health Commission).

The Impact of Obstructive Sleep Apnea and Tobacco Smoking on Endothelial Function.

BACKGROUND: Endothelial dysfunction has been recognized to occur in the context of obstructive sleep apnea (OSA) or tobacco smoking. However, the deleterious effect on vascular function with concurrence of both conditions is largely unknown. OBJECTIVE: To investigate whether the concurrence of OSA and smoking poses an additive detriment to endothelial dysfunction. METHODS: Chinese men without a history of chronic medical illness were invited to complete a questionnaire including smoking pack-year exposure, polysomnography and peripheral arterial tonometry (PAT) for endothelial function. Serum 8-isoprostane, advanced oxidation protein products (AOPP) and monocyte chemo-attractant protein-1 (MCP-1) were measured. RESULTS: 114 men were successfully enrolled. PAT ratio, adjusted for age and body mass index, correlated inversely with overall severity of OSA: apnea-hypopnea index (AHI), r = -0.160 (p = 0.092); oxygen desaturation index, r = -0.214 (p = 0.024); duration of oxygen saturation <90%, r = -0.219 (p = 0.020); and minimum oxygen saturation, r = 0.250 (p = 0.008). The PAT ratio decreased with increasing pack-year group (p = 0.018). It was lower with concurrent smoking history and moderate-severe OSA (AHI ≥15/h) compared to having one or neither factor (p = 0.011). Serum levels of 8-isoprostane and AOPP were positively related to severity of OSA, while MCP-1 correlated with smoking quantity. Multiple linear regression analyses showed that severity of intermittent hypoxia, MCP-1 and pack-year exposure were independent predictors of PAT ratio. CONCLUSION: While OSA, in particular intermittent hypoxemia, and tobacco smoking were independent risk factors, the concurrence of moderate-severe OSA and smoking was associated with the most severe impairment in endothelial function.

Role of Metabolic Reprogramming in Pulmonary Innate Immunity and Its Impact on Lung Diseases.

Lung innate immunity is the first line of defence against inhaled allergens, pathogens and environmental pollutants. Cellular metabolism plays a key role in innate immunity. Catabolic pathways, including glycolysis and fatty acid oxidation (FAO), are interconnected with biosynthetic and redox pathways. Innate immune cell activation and differentiation trigger extensive metabolic changes that are required to support their function. Pro-inflammatory polarisation of macrophages and activation of dendritic cells, mast cells and neutrophils are associated with increased glycolysis and a shift towards the pentose phosphate pathway and fatty acid synthesis. These changes provide the macromolecules required for proliferation and inflammatory mediator production and reactive oxygen species for anti-microbial effects. Conversely, anti-inflammatory macrophages use primarily FAO and oxidative phosphorylation to ensure efficient energy production and redox balance required for prolonged survival. Deregulation of metabolic reprogramming in lung diseases, such as asthma and chronic obstructive pulmonary disease, may contribute to impaired innate immune cell function. Understanding how innate immune cell metabolism is altered in lung disease may lead to identification of new therapeutic targets. This is important as drugs targeting a number of metabolic pathways are already in clinical development for the treatment of other diseases such as cancer.

Imaging Profile of the COVID-19 Infection: Radiologic Findings and Literature Review.

PURPOSE: To present the findings of 21 coronavirus disease 2019 (COVID-19) cases from two Chinese centers with CT and chest radiographic findings, as well as follow-up imaging in five cases. MATERIALS AND METHODS: This was a retrospective study in Shenzhen and Hong Kong. Patients with COVID-19 infection were included. A systematic review of the published literature on radiologic features of COVID-19 infection was conducted. RESULTS: The predominant imaging pattern was of ground-glass opacification with occasional consolidation in the peripheries. Pleural effusions and lymphadenopathy were absent in all cases. Patients demonstrated evolution of the ground-glass opacities into consolidation and subsequent resolution of the airspace changes. Ground-glass and consolidative opacities visible on CT are sometimes undetectable on chest radiography, suggesting that CT is a more sensitive imaging modality for investigation. The systematic review identified four other studies confirming the findings of bilateral and peripheral ground glass with or without consolidation as the predominant finding at CT chest examinations. CONCLUSION: Pulmonary manifestation of COVID-19 infection is predominantly characterized by ground-glass opacification with occasional consolidation on CT. Radiographic findings in patients presenting in Shenzhen and Hong Kong are in keeping with four previous publications from other sites.© RSNA, 2020See editorial by Kay and Abbara in this issue.