Chest‐Laminated and Sweat‐Permeable E‐Skin for Speech and Motion Artifact‐Insensitive Cough Detection

Assessment of the cough severity is essential when dealing with respiratory diseases such as chronic obstructive pulmonary disease and COVID‐19. Although a few wearable devices have been reported for cough detection, they mostly rely on microphones, accelerometers, or throat‐fixed flexible sensors, which suffer from key issues including privacy disclosure and speech/motion artifacts. This study presents a chest‐laminated electronic skin (e‐skin) for reliable cough detection. Mixed dumbbell‐like networks and through‐holes are engineered on hard‐to‐stretch composite films for high stretching force sensitivity and sweat permeation, respectively. The e‐skin can effectively reduce speech‐signal and motion artifacts owing to firm adhesion and conformal contact with the chest even on sweaty skin. Experimental results show that the specificity for cough identification is as high as 99.75% through machine learning of automated acoustic analysis, even in the presence of hard‐to‐distinguish daily activities such as throat clearing. The developed chest‐laminated e‐skin is a simple, comfortable, yet reliable method to detect cough for the primary diagnosis of respiratory diseases by extracting subtle acoustic information from cough. [ FROM AUTHOR]

Effects of traditional Chinese medicine on treatment outcomes of severe COVID-19 patients: A single-centre study. (preprint)

No specific effective therapeutic drugs have been identified for COVID-19. Critically ill COVID-19 36 patients in the ICU experience high mortality. This project aims to study the effects of traditional 37 Chinese medicine (TCM) treatment on deadly outcomes caused by COVID-19. A total of 123 critically 38 ill COVID-19 patients who received close monitoring at the ICU of Vulcan Hill Hospital between 39 ICU patients received supportive management. Eighty-one patients were given additional TCM 41 treatment. Clinical characteristics during the treatment period (up to 39 days) and the clinical outcome 42 of each patient were closely monitored and analysed. We observed that patients treated with TCM had 43 lower mortality than the non-TCM treatment group (16 of 81 vs. 31 of 42; 0.3 person/month vs. 2.9 44 person/month). In the adjusted Cox proportional hazards models, TCM treatment was associated with 45 improved survival [multivariate HR, 0.13; 95% confidence interval (CI), 0.06–0.24; P < 0.001]. 46 Furthermore, we found that TCM treatment could partially improve the inflammation status by 47 reducing the levels of proinflammatory cytokines and recovering multiple organic functions. TCM 48 treatment may decrease inflammation status by reducing the level of proinflammatory cytokines and 49 allowing the recovery of multiple organic functions, which could improve the survival rate of critically 50 ill COVID-19 patients.

Accurate Lung Nodules Segmentation with Detailed Representation Transfer and Soft Mask Supervision (preprint)

Accurate lung nodules segmentation from Computed Tomography (CT) images is crucial to the analysis and diagnosis of lung diseases such as COVID-19 and lung cancer. However, due to the smallness and variety of lung nodules and the lack of high-quality labeling, accurate lung nodule segmentation is still a challenging problem. To address these issues, we propose a complete paradigm for accurate lung nodules segmentation. First, we introduce a new segmentation mask named Soft Mask which has richer and more accurate edge details description and better visualization. Correspondingly, we develop a universal semi-automatic Soft Mask annotation pipeline to deal with different datasets. Second, a novel Network with Detailed representation transfer and Soft Mask supervision (DSNet) is proposed to process the input low-resolution images of lung nodules into high-quality segmentation results. In our DSNet, we design a novel Selective Detailed Representation Fusion Module to reconstruct the detailed representation to alleviate the small size of lung nodules images. In addition, the adversarial training framework with Soft Mask is proposed to further improve the accuracy of segmentation. Extensive experiments validate that our DSNet outperforms the state-of-the-art methods for accurate lung nodules segmentation. And our method also demonstrates competitive results in other accurate medical segmentation tasks. Besides, we provide a new challenging lung nodules segmentation dataset for further studies.

Heparin-induced thrombocytopenia is associated with a high risk of mortality in critical COVID-19 patients receiving heparin-involved treatment (preprint)

Background Coronavirus infectious disease 2019 (COVID-19) has developed into a global pandemic. It is essential to investigate the clinical characteristics of COVID-19 and uncover potential risk factors for severe disease to reduce the overall mortality rate of COVID-19. Methods Sixty-one critical COVID-19 patients admitted to the intensive care unit (ICU) and 93 severe non-ICU patients at Huoshenshan Hospital (Wuhan, China) were included in this study. Medical records, including demographic, platelet counts, heparin-involved treatments, heparin-induced thrombocytopenia-(HIT) related laboratory tests, and fatal outcomes of COVID-19 patients were analyzed and compared between survivors and nonsurvivors. Findings Sixty-one critical COVID-19 patients treated in ICU included 15 survivors and 46 nonsurvivors. Forty-one percent of them (25/61) had severe thrombocytopenia, with a platelet count (PLT) less than 50x109/L, of whom 76% (19/25) had a platelet decrease of >50% compared to baseline; 96% of these patients (24/25) had a fatal outcome. Among the 46 nonsurvivors, 52.2% (24/46) had severe thrombocytopenia, compared to 6.7% (1/15) among survivors. Moreover, continuous renal replacement therapy (CRRT) could induce a significant decrease in PLT in 81.3% of critical CRRT patients (13/16), resulting in a fatal outcome. In addition, a high level of anti-heparin-PF4 antibodies, a marker of HIT, was observed in most ICU patients. Surprisingly, HIT occurred not only in patients with heparin exposure, such as CRRT, but also in heparin-naive patients, suggesting that spontaneous HIT may occur in COVID-19. Interpretation Anti-heparin-PF4 antibodies are induced in critical COVID-19 patients, resulting in a progressive platelet decrease. Exposure to a high dose of heparin may trigger further severe thrombocytopenia with a fatal outcome. An alternative anticoagulant other than heparin should be used to treat COVID-19 patients in critical condition.

Detection of Coronavirus in Simultaneously Collected Tear and Throat Swab Samples from the Patients with 2019- new Coronavirus Infection Disease: A Single Center Cross-sectional Study (preprint)

Objecive: This study aimed to evaluate whether the coronavirus can be detected in the tears in the eyes of 2019- novel coronavirus (2019-nCoV) infected patients and compa re the detection consistency of two simultaneously collected samples, from the tears and throat swabs, of these patients.Methods: A total of 35 diagnosis confirmed patients with 2019-nCoV infection disease,from January 26 to February 19, 2020, at central theater Wuhan general hospital of PLA, were included in this cross-sectional case series study. The diagnosis was confirmed by both clinical and laboratory ways. Throat samples from all enrolled patients were collected with sampling swab, and simultaneously ,tear samples were collected w ith sampling swab from 9 patients (No.1-9) and with Schirmer's strip from the remaining patients (No.10-35) (bilateral eyes for all patients). Sample collecting and testing were performed in three separate time points: first from patients No.1-9,second from p atients No.10-29,and third from patients No.30-35. Reverse-transcriptase-polymerase-chai n-reaction (RT-PCR) assay was performed by the same technician(Researcher Zhang), who was blind to the patients profile, within 4 hours after each collection.Results: Among enrolled patients, 29 (No.1-29) had mild or moderate clinical symptoms and 6 (No.30-35) had severe symptoms. The mean time interval from the sample collection day to diagnosis confirmation day was 9.71±6.50 days (ranged from 3 to 29 days). None of the patients had conjunctivitis. Nineteen out of 35 (54.3%) throat samples presented positive Rt-PCR results. Three (no.13,21,31) out of 35 (8.6%) tear samples presented positive RT-PCR results. Two(no.21, 31) of these three patients   were throat swab positive and one (No. 13) was negative. The consistency analysis indicated that tears and throat samples showed poor consistency ( Kappa=-0.009, P=0.9 ).The cycle threshold value (Ct-value) of tears samples collected by sampling swab was significantly higher than that by Schirmer's strip(t=2.288, P=0.03).Conclusion: In spite of the low 2019-nCoV positive detection rate of tear samples from 2019-nCoV infected patients, we cannot fully rule out the transmission by ocular surface. Whether tear testing can be used as an aid in judging of 2019-nCoV infection need further investigation.Authors Ying Yan and Bo Zeng contributed equally to this study

Highly pathogenic coronavirus N protein aggravates lung injury by MASP-2-mediated complement over-activation (preprint)

An excessive immune response contributes to SARS-CoV, MERS-CoV and SARS-CoV-2 pathogenesis and lethality, but the mechanism remains unclear. In this study, the N proteins of SARS-CoV, MERS-CoV and SARS-CoV-2 were found to bind to MASP-2, the key serine protease in the lectin pathway of complement activation, resulting in aberrant complement activation and aggravated inflammatory lung injury. Either blocking the N protein:MASP-2 interaction or suppressing complement activation can significantly alleviate N protein-induced complement hyper-activation and lung injury in vitro and in vivo. Complement hyper-activation was also observed in COVID-19 patients, and a promising suppressive effect was observed when the deteriorating patients were treated with anti-C5a monoclonal antibody. Complement suppression may represent a common therapeutic approach for pneumonia induced by these highly pathogenic coronaviruses.

Immune Cell Profiling of COVID-19 Patients in the Recovery Stage by Single-Cell Sequencing (preprint)

COVID-19 caused by SARS-CoV-2 has recently affected over 200,000 people and killed more than 8000. Immune system dysregulation such as lymphopenia and inflammatory cytokine storm has been observed in COVID-19 patients, but it remains unclear for the change of key immune cell subsets and their states during COVID-19. Here, we applied single-cell technology to comprehensively characterize transcriptional changes of peripheral blood mononuclear cells in ten patients recovered from COVID-19. Compared with healthy control, COVID-19 induced a unique signature of immune cells in humans, especially in the early recovery stage (ERS). In ERS patients, T cells were decreased remarkably, while monocytes were increased. A detailed analysis of monocytes showed that there was an increased ratio of classical CD14++ monocytes with highly inflammatory genes expression, as well as a greater abundance of CD14++IL1B+ monocytes. For nature killer (NK) cells and T cells, CD4+ T cells were significantly decreased and expressed high level of inflammatory markers, while NK cells were increased. In addition, T cells were highly expanded clone, especially in CD4+ T memory cells and CD8+ T cells. Among B cells, plasma cells were increased remarkably, and naive B cells were reduced. Our study also identified several novel B cell receptor (BCR) changes (such as IGHV1-8 and IGHV3-7), and confirmed isotypes (IGKV3-11 and IGHV3-21) previously used for virus vaccine development. The strongest pairing frequencies, IGHV3-23+IGHJ4, indicated a monoclonal state associated with SARS-CoV-2 specificity. Furthermore, integrated analysis predicated that IL-1B and M-CSF may be novel candidate target gene for inflammatory storm, and TNFSF13, IL-18 and IL-4 may be benefit for the recovery of COVID-19 patients. Our study provides the first evidence of inflammatory immune signature in early recovery stage, suggesting that the COVID-19 patients are still vulnerable after hospital discharge. Our identification of novel BCR signaling may lead to the development of vaccine and antibodies for the treatment of COVID-19.