The Covid-19 pandemic has introduced an array of organspecific and systemic phenotypessome previously observed in viral infections, including severe acute respiratory syndrome (SARS) and others that appear to be unique to SARScoronavirus (CoV)-2. Rapidly emerging information from clinical observations, autopsy-based findings, extrapolations from in vitro and ex vivo studies and dynamic modeling are informing management guidelines; however, many questions remain unanswered and clinical trials that are required to provide evidence have not been completed in most areas. Among the many questions that require careful thought, reflection and investigation are the mechanism(s) underlying the development of a systemic coagulopathy and acquired thrombophilia characterized in a majority of cases by a proclivity for venous, arterial and microvascular thrombosis. The following review summarizes emerging insights into the pathobiology, mechanism(s), diagnosis, management, foundations for research and either planned or ongoing clinical trials for Covid-19-associated coagulopathy.

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COVID-19 update: Covid-19-associated coagulopathy.

Despite the ongoing spread of MERS, there is limited knowledge of the factors affecting its severity and outcomes. We analyzed clinical data and specimens from fourteen MERS patients treated in a hospital who collectively represent a wide spectrum of disease severity, ranging from mild febrile illness to fatal pneumonia, and classified the patients into four groups based on severity and mortality. Comparative and kinetic analyses revealed that high viral loads, weak antibody responses, and lymphopenia accompanying thrombocytopenia were associated with disease mortality, whereas persistent and gradual increases in lymphocyte responses might be required for effective immunity against MERS-CoV infection. Leukocytosis, primarily due to increased neutrophils and monocytes, was generally observed in more severe and fatal cases. The blood levels of cytokines such as IL-10, IL-15, TGF-β, and EGF were either positively or negatively correlated with disease mortality. Robust induction of various chemokines with differential kinetics was more prominent in patients that recovered from pneumonia than in patients with mild febrile illness or deceased patients. The correlation of the virological and immunological responses with disease severity and mortality, as well as their responses to current antiviral therapy, may have prognostic significance during the early phase of MERS.

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Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity

Background 
In order to review the epidemiologic evidence concerning previous lung diseases as risk factors for lung cancer, a meta-analysis and systematic review was conducted.


Methods 
Relevant studies were identified through MEDLINE searches. Using random effects models, summary effects of specific previous conditions were evaluated separately and combined. Stratified analyses were conducted based on smoking status, gender, control sources and continent.


Results 
A previous history of COPD, chronic bronchitis or emphysema conferred relative risks (RR) of 2.22 (95% confidence interval (CI): 1.66, 2.97) (from 16 studies), 1.52 (95% CI: 1.25, 1.84) (from 23 studies) and 2.04 (95% CI: 1.72, 2.41) (from 20 studies), respectively, and for all these diseases combined 1.80 (95% CI: 1.60, 2.11) (from 39 studies). The RR of lung cancer for subjects with a previous history of pneumonia was 1.43 (95% CI: 1.22–1.68) (from 22 studies) and for subjects with a previous history of tuberculosis was 1.76 (95% CI = 1.49, 2.08), (from 30 studies). Effects were attenuated when restricting analysis to never smokers only for COPD/emphysema/chronic bronchitis (RR = 1.22, 0.97–1.53), however remained significant for pneumonia 1.36 (95% CI: 1.10, 1.69) (from 8 studies) and tuberculosis 1.90 (95% CI: 1.45, 2.50) (from 11 studies).


Conclusions 
Previous lung diseases are associated with an increased risk of lung cancer with the evidence among never smokers supporting a direct relationship between previous lung diseases and lung cancer.

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Previous Lung Diseases and Lung Cancer Risk: A Systematic Review and Meta-Analysis

Early detection of COVID-19 based on chest CT enables timely treatment of patients and helps control the spread of the disease. We proposed an artificial intelligence (AI) system for rapid COVID-19 detection and performed extensive statistical analysis of CTs of COVID-19 based on the AI system. We developed and evaluated our system on a large dataset with more than 10 thousand CT volumes from COVID-19, influenza-A/B, non-viral community acquired pneumonia (CAP) and non-pneumonia subjects. In such a difficult multi-class diagnosis task, our deep convolutional neural network-based system is able to achieve an area under the receiver operating characteristic curve (AUC) of 97.81% for multi-way classification on test cohort of 3,199 scans, AUC of 92.99% and 93.25% on two publicly available datasets, CC-CCII and MosMedData respectively. In a reader study involving five radiologists, the AI system outperforms all of radiologists in more challenging tasks at a speed of two orders of magnitude above them. Diagnosis performance of chest x-ray (CXR) is compared to that of CT. Detailed interpretation of deep network is also performed to relate system outputs with CT presentations. The code is available at https://github.com/ChenWWWeixiang/diagnosis_covid19 .

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Development and evaluation of an artificial intelligence system for COVID-19 diagnosis

Persistent inflammation within the respiratory tract underlies the pathogenesis of numerous chronic pulmonary diseases including chronic obstructive pulmonary disease, asthma and pulmonary fibrosis. Chronic inflammation in the lung may arise from a combination of genetic susceptibility and environmental influences, including exposure to microbes, particles from the atmosphere, irritants, pollutants, allergens, and toxic molecules. To this end, an immediate, strong, and highly regulated inflammatory defense mechanism is needed for the successful maintenance of homeostasis within the respiratory system. Macroautophagy/autophagy plays an essential role in the inflammatory response of the lung to infection and stress. At baseline, autophagy may be critical for inhibiting spontaneous pulmonary inflammation and fundamental for the response of pulmonary leukocytes to infection; however, when not regulated, persistent or inefficient autophagy may be detrimental to lung epithelial cells, promoting lung injury. This perspective will discuss the role of autophagy in driving and regulating inflammatory responses of the lung in chronic lung diseases with a focus on potential avenues for therapeutic targeting. Abbreviations AR allergic rhinitis AM alveolar macrophage ATG autophagy-related CF cystic fibrosis CFTR cystic fibrosis transmembrane conductance regulator COPD chronic obstructive pulmonary disease CS cigarette smoke CSE cigarette smoke extract DC dendritic cell IH intermittent hypoxia IPF idiopathic pulmonary fibrosis ILD interstitial lung disease MAP1LC3B microtubule associated protein 1 light chain 3 beta MTB Mycobacterium tuberculosis MTOR mechanistic target of rapamycin kinase NET neutrophil extracellular traps OSA obstructive sleep apnea PAH pulmonary arterial hypertension PH pulmonary hypertension ROS reactive oxygen species TGFB1 transforming growth factor beta 1 TNF tumor necrosis factor.

https://www.tandfonline.com/doi/pdf/10.1080/15548627.2017.1389823

Autophagy and inflammation in chronic respiratory disease.

Inflammation is the body's response to insults, which include infection, trauma, and hypersensitivity. The inflammatory response is complex and involves a variety of mechanisms to defend against pathogens and repair tissue. In the lung, inflammation is usually caused by pathogens or by exposure to toxins, pollutants, irritants, and allergens. During inflammation, numerous types of inflammatory cells are activated. Each releases cytokines and mediators to modify activities of other inflammatory cells. Orchestration of these cells and molecules leads to progression of inflammation. Clinically, acute inflammation is seen in pneumonia and acute respiratory distress syndrome (ARDS), whereas chronic inflammation is represented by asthma and chronic obstructive pulmonary disease (COPD). Because the lung is a vital organ for gas exchange, excessive inflammation can be life threatening. Because the lung is constantly exposed to harmful pathogens, an immediate and intense defense action (mainly inflammation) is required to eliminate the invaders as early as possible. A delicate balance between inflammation and anti-inflammation is essential for lung homeostasis. A full understanding of the underlying mechanisms is vital in the treatment of patients with lung inflammation. This review focuses on cellular and molecular aspects of lung inflammation during acute and chronic inflammatory states.

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X Sarmiento

Papers

Inflammatory mechanisms in the lung