Interaction between target peptide and complementary peptide by bimolecular fluorescence complementary technology

[Objective] Using the bimolecular fluorescence complementation (BiFC) technology, the present experiment aimed to study the interaction relationship and localization of the target peptide and the complementary peptide based on the porcine epidemic diarrhea virus (PEDV) S protein receptor binding site peptide in living cells, so as to provide the foundation and theoretical support for the further use of the peptide in the detection of porcine epidemic diarrhea virus. [Method] The target peptide was designed according to the physical and chemical characteristics of the target protein, such as the amino acid composition, the type of charge, the ability to form intennolecular hydrogen bonds, the strength of polarity, and hydrophobicity;According to the amino acid composition of the target protein, a complementary peptide that interacted with it in theory was designed, and the target peptide and complementary peptide were predicted and analyzed by using bioinfonnatics tools;The target peptide and complementary peptide were inserted into the pBiFC-VC155 and pBiFC-VN173 vector, which was double digested by the EcoRI/XhoI and NotI/SalI, respectively, verified by enzyme digestion and sequencing, and then transfected into Vero cells to study the interaction between the target peptide and the complementary peptide, and the precise localization of BiFC complex in cells. [Result] Bioinfonnatics analysis showed that the target peptide and complementary peptide had hydrophilic and hydrophobic domains, respectively, and the hydrophilic domains were both positively and negatively charged, which could generate electrostatic attraction. The results of enzyme digestion and sequencing showed that the pBiFC-VC155-target peptide and pBiFC-VNI73-complementary peptide plasmids were successfully constructed;Cell transfection experiments showed that the target peptide and complementary peptide could form BiFC complexes in Vcro cells after co-transfection of recombinant plasmids, indicating that they could interact with each other;Indirect immuttolluorescence assay confirmed that the BiFC complex was mainly distributed in the nucleus. [Conclusion] It was confirmed that the peptide designed based on the PEW/ S protein receptor binding site can interact with each other in living cells, demonstrating the feasibility of the peptide for detection.

Using CONTAM to Design Ventilation Strategy of Negative Pressure Isolation Ward considering Different Height of Door Gaps

Infectious disease departments in hospitals require pressure gradient to create unidirectional airflow to prevent the spread of contaminants, typically by creating active air infiltration through the difference between supply and exhaust air volumes. The door gap is the channel of air flow between rooms, so its height has an important influence on the pressure difference and infiltration air volume of the room. There is still a lack of research on setting reasonable ventilation strategies according to the different height of door gaps at different positions in the building. In this study, model of a set of isolation ward was established and analyzed using the multi-zone simulation software CONTAM, and the ventilation strategies with different height of door gaps were applied to the actual infection diseases department. The results show that in a building with ventilation system divided by functional area, the difference in the height of the door gaps requires different active infiltration air volumes. Pressure fluctuations in the medical and patient corridors are greater than in other rooms. The significance of this study is to understand the active infiltration of air to guide the design and operation of ventilation systems in infectious disease hospitals or building remodeled to isolate close contacts of Covid-19 patients. It is also instructive for the design of pressure gradients in clean workshops, biological laboratories, and other similar buildings.

Relationship Between Platelet Count and In-hospital Mortality in Adult Patients With COVID-19: A Retrospective Cohort Study.

Background: The coronavirus disease 2019 (COVID-19) has become a global pandemic. Systemic inflammation in COVID-19 patients has been associated with poor clinical outcome. This study aims to determine the relationship between platelet count and in-hospital mortality. Methods: The original data of this study were from article development and validation of a predictive model of in-hospital mortality in COVID-19 patients. In this secondary analysis, we adopted multi-variable logistic regression analyses and smooth curve fitting to assess the independent association between platelet count and in-hospital mortality. We further applied a two-piecewise linear regression model to examine the nonlinear association between platelet count and in-hospital mortality. Results: Of the 2006 patients, the average age of the participants was 65.9 ± 16.5 years and 42.6% were women. We observed a U-shaped relationship between platelet count and in-hospital mortality. We found two different slopes, the correlations between platelet count and in-hospital mortality of COVID-19 patients were totally different below and above the inflection point which was around 370 × 109/L. On the left side of the inflection point, the OR was 0.996 (OR: 0.996, 95%CI: 0.994-0.998, p < 0.001). On the right side of the inflection point, the OR was 1.011 (OR: 1.011, 95%CI: 1.001-1.021, p = 0.029). Conclusions: A U-shaped association between platelet count and in-hospital mortality was found in the patients with COVID-19. The optimal of platelet count associated with the lowest risk of in-hospital mortality was around 370 × 109/L.

DNA Based Vaccine Expressing SARS-CoV-2 Spike-CD40L Fusion Protein Confers Protection Against Challenge in a Syrian Hamster Model.

SARS-CoV-2 infections present a tremendous threat to public health. Safe and efficacious vaccines are the most effective means in preventing the infections. A variety of vaccines have demonstrated excellent efficacy and safety around the globe. Yet, development of alternative forms of vaccines remains beneficial, particularly those with simpler production processes, less stringent storage conditions, and the capability of being used in heterologous prime/boost regimens which have shown improved efficacy against many diseases. Here we reported a novel DNA vaccine comprised of the SARS-CoV-2 spike protein fused with CD40 ligand (CD40L) serving as both a targeting ligand and molecular adjuvant. A single intramuscular injection in Syrian hamsters induced significant neutralizing antibodies 3-weeks after vaccination, with a boost substantially improving immune responses. Moreover, the vaccine also reduced weight loss and suppressed viral replication in the lungs and nasal turbinates of challenged animals. Finally, the incorporation of CD40L into the DNA vaccine was shown to reduce lung pathology more effectively than the DNA vaccine devoid of CD40L. These results collectively indicate that this DNA vaccine candidate could be further explored because of its efficacy and known safety profile.

Atrial Fibrillation Detection and Atrial Fibrillation Burden Estimation via Wearables.

Atrial Fibrillation (AF) is an important cardiac rhythm disorder, which if left untreated can lead to serious complications such as a stroke. AF can remain asymptomatic, and it can progressively worsen over time; it is thus a disorder that would benefit from detection and continuous monitoring with a wearable sensor. We develop an AF detection algorithm, deploy it on a smartwatch, and prospectively and comprehensively validate its performance on a real-world population that included patients diagnosed with AF. The algorithm showed a sensitivity of 87.8% and a specificity of 97.4% over every 5-minute segment of PPG evaluated. Furthermore, we introduce novel algorithm blocks and system designs to increase the time of coverage and monitor for AF even during periods of motion noise and other artifacts that would be encountered in daily-living scenarios. An average of 67.8% of the entire duration the patients wore the smartwatch produced a valid decision. Finally, we present the ability of our algorithm to function throughout the day and estimate the AF burden, a first-of-this-kind measure using a wearable sensor, showing 98% correlation with the ground truth and an average error of 6.2%.

DNA Based Vaccine Expressing SARS-CoV-2 Spike-CD40L Fusion Protein Confers Protection Against Challenge in a Syrian Hamster Model

SARS-CoV-2 infections present a tremendous threat to public health. Safe and efficacious vaccines are the most effective means in preventing the infections. A variety of vaccines have demonstrated excellent efficacy and safety around the globe. Yet, development of alternative forms of vaccines remains beneficial, particularly those with simpler production processes, less stringent storage conditions, and the capability of being used in heterologous prime/boost regimens which have shown improved efficacy against many diseases. Here we reported a novel DNA vaccine comprised of the SARS-CoV-2 spike protein fused with CD40 ligand (CD40L) serving as both a targeting ligand and molecular adjuvant. A single intramuscular injection in Syrian hamsters induced significant neutralizing antibodies 3-weeks after vaccination, with a boost substantially improving immune responses. Moreover, the vaccine also reduced weight loss and suppressed viral replication in the lungs and nasal turbinates of challenged animals. Finally, the incorporation of CD40L into the DNA vaccine was shown to reduce lung pathology more effectively than the DNA vaccine devoid of CD40L. These results collectively indicate that this DNA vaccine candidate could be further explored because of its efficacy and known safety profile.

Structural Insights into the Cofactor Role of Heparin/Heparan Sulfate in Binding between the SARS-CoV-2 Spike Protein and Host Angiotensin-Converting Enzyme II.

The viral entry process of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires heparin and heparan sulfates from the cell surface, functioning as a cofactor for human angiotensin-converting enzyme 2 (ACE2) for recognizing the receptor-binding domain (RBD) of the spike (S) protein on the surface of the virion. In the present study, the binding poses of an oligosaccharide with four repeating units of GlcNS6S-IdoA2S (octa) predicted by Vina-Carb in the RBD binding site were employed in molecular dynamics (MD) simulations to provide atomic details for studying the cofactor mechanism. The molecular model in the MD simulations reproduced the length- and sequence-dependent behavior observed from the microarray experiments and revealed an important planar U-turn shape for HP/HS binding to RBD. The model for octa with this shape in the ACE2-RBD complex enhanced the interactions in the binding interface. The comparisons with the ACE2-RBD complex suggested that the presence of octa in the RBD binding site blocked the movements in a loop region at the distal end of the RBD binding interface and promoted the contacts of this loop region with the ACE2 N-terminus helix. This study shed light on the atomic and dynamic details for HP/HS interacting with RBD and provided insights into their cofactor role in the ACE2-RBD interactions.

SpeechSpiro: Lung Function Assessment from Speech Pattern as an Alternative to Spirometry for Mobile Health Tracking.

Respiratory illnesses are common in the United States and globally; people deal with these illnesses in various forms, such as asthma, chronic obstructive pulmonary diseases, or infectious respiratory diseases (e.g., coronavirus). The lung function of subjects affected by these illnesses degrades due to infection or inflammation in their respiratory airways. Typically, lung function is assessed using in-clinic medical equipment, and quite recently, via portable spirometry devices. Research has shown that the obstruction and restriction in the respiratory airways affect individuals' voice characteristics. Hence, audio features could play a role in predicting the lung function and severity of the obstruction. In this paper, we go beyond well-known voice audio features and create a hybrid deep learning model using CNN-LSTM to discover spatiotemporal patterns in speech and predict the lung function parameters with accuracy comparable to conventional devices. We validate the performance and generalizability of our method using the data collected from 201 subjects enrolled in two studies internally and in collaboration with a pulmonary hospital. SpeechSpiro measures lung function parameters (e.g., forced vital capacity) with a mean normalized RMSE of 12% and R2 score of up to 76% using 60-second phone audio recordings of individuals reading a passage.Clinical relevance - Speech-based spirometry has the potential to eliminate the need for an additional device to carry out the lung function assessment outside clinical settings; hence, it can enable continuous and mobile track of the individual's condition, healthy or with a respiratory illness, using a smartphone.

Venous thromboembolism in non-COVID-19 population during the pandemic: a nationwide multicenter retrospective survey.

Impact of pandemic on the incidence of venous thromboembolism (VTE) in non-COVID-19 patients is undetermined. Thus, a nationwide multicenter retrospective survey was conducted to evaluate the disease burden in non-COVID-19 population. This multi-center survey involved 94 hospitals from 24 provinces in the mainland of China, and collected data on non-COVID-19 patients admitted to the radiology departments due to VTE between January 24 and April 16, 2020. Baseline characteristics, VTE risk factors, clinical manifestations and the treatments were compared with those in the same period of 2019. 3,358 patients with VTE from 74 hospitals were included in this study (1,458 in 2020, 1,900 in 2019). Most aged ≥ 50 years (80.6% in the pandemic, 81.2% in 2019). The number of patients aged 30-39 years increased from 3.9% in 2019 period to 5.8% in the pandemic (p = 0.009). Among the VTE risk factors, the rate of decreased activity increased significantly in the pandemic, and was much higher than that in 2019 (30.7% vs 22.6%, p < 0.0001). Under the risk of decreased activity, patients with comorbidities chronic diseases, especially diabetes, showed significantly a higher incidence of VTE (30.4% vs 22.0%, p < 0.0001). In the pandemic period, fewer patients were treated with anticoagulation alone (33.5% vs 36.7%, p = 0.05), and more underwent inferior vena cava filter (IVCF) implantation, compared with those in 2019 (66.5% vs 63.2%, p = 0.046). The pandemic increased the VTE risk of decreased activity among the non-COVID-19 population. Patients with comorbidities, especially diabetes, have a significant higher risk of VTE during the pandemic.

Ace2 and Tmprss2 Expressions Are Regulated by Dhx32 and Influence the Gastrointestinal Symptoms Caused by SARS-CoV-2.

Studies showed that the gastrointestinal (GI) tract is one of the most important pathways for SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19). As SARS-CoV-2 cellular entry depends on the ACE2 receptor and TMPRSS2 priming of the spike protein, it is important to understand the molecular mechanisms through which these two proteins and their cognate transcripts interact and influence the pathogenesis of COVID-19. In this study, we quantified the expression, associations, genetic modulators, and molecular pathways for Tmprss2 and Ace2 mRNA expressions in GI tissues using a systems genetics approach and the expanded family of highly diverse BXD mouse strains. The results showed that both Tmprss2 and Ace2 are highly expressed in GI tissues with significant covariation. We identified a significant expression quantitative trait locus on chromosome 7 that controls the expression of both Tmprss2 and Ace2. Dhx32 was found to be the strongest candidate in this interval. Co-expression network analysis demonstrated that both Tmprss2 and Ace2 were located at the same module that is significantly associated with other GI-related traits. Protein-protein interaction analysis indicated that hub genes in this module are linked to circadian rhythms. Collectively, our data suggested that genes with circadian rhythms of expression may have an impact on COVID-19 disease, with implications related to the timing and treatment of COVID-19.

RNA helicases required for viral propagation in humans.

RNA viruses cause many routine illnesses, such as the common cold and the flu. Recently, more deadly diseases have emerged from this family of viruses. The hepatitis C virus has had a devastating impact worldwide. Despite the cures developed in the U.S. and Europe, economically disadvantaged countries remain afflicted by HCV infection due to the high cost of these medications. More recently, COVID-19 has swept across the world, killing millions and disrupting economies and lifestyles; the virus responsible for this pandemic is a coronavirus. Our understanding of HCV and SARS CoV-2 replication is still in its infancy. Helicases play a critical role in the replication, transcription and translation of viruses. These key enzymes need extensive study not only as an essential player in the viral lifecycle, but also as targets for antiviral therapeutics. In this review, we highlight the current knowledge for RNA helicases of high importance to human health.

Genetic Dissection of the Regulatory Mechanisms of Ace2 in the Infected Mouse Lung.

Acute lung injury (ALI) is an important cause of morbidity and mortality after viral infections, including influenza A virus H1N1, SARS-CoV, MERS-CoV, and SARS-CoV-2. The angiotensin I converting enzyme 2 (ACE2) is a key host membrane-bound protein that modulates ALI induced by viral infection, pulmonary acid aspiration, and sepsis. However, the contributions of ACE2 sequence variants to individual differences in disease risk and severity after viral infection are not understood. In this study, we quantified H1N1 influenza-infected lung transcriptomes across a family of 41 BXD recombinant inbred strains of mice and both parents-C57BL/6J and DBA/2J. In response to infection Ace2 mRNA levels decreased significantly for both parental strains and the expression levels was associated with disease severity (body weight loss) and viral load (expression levels of viral NA segment) across the BXD family members. Pulmonary RNA-seq for 43 lines was analyzed using weighted gene co-expression network analysis (WGCNA) and Bayesian network approaches. Ace2 not only participated in virus-induced ALI by interacting with TNF, MAPK, and NOTCH signaling pathways, but was also linked with high confidence to gene products that have important functions in the pulmonary epithelium, including Rnf128, Muc5b, and Tmprss2. Comparable sets of transcripts were also highlighted in parallel studies of human SARS-CoV-infected primary human airway epithelial cells. Using conventional mapping methods, we determined that weight loss at two and three days after viral infection maps to chromosome X-the location of Ace2. This finding motivated the hierarchical Bayesian network analysis, which defined molecular endophenotypes of lung infection linked to Ace2 expression and to a key disease outcome. Core members of this Bayesian network include Ace2, Atf4, Csf2, Cxcl2, Lif, Maml3, Muc5b, Reg3g, Ripk3, and Traf3. Collectively, these findings define a causally-rooted Ace2 modulatory network relevant to host response to viral infection and identify potential therapeutic targets for virus-induced respiratory diseases, including those caused by influenza and coronaviruses.

Analysis and optimization of 15-minute community life circle based on supply and demand matching: A case study of Shanghai.

The 15-minute community life circle (15min-CLC) strategy is one of Shanghai's important methods for building a global city and facing a society with a more diverse population structure in the future. In the existing research, the balance between the construction of the life circle and the needs of the people in the life circle still needs to be further fulfilled. This paper is based on the city's multi-source large data set including 2018 AutoNavi POI (Point of Interests), OSM (OpenStreetMap) road network data and LandScan population data set, and evaluates the current status of Shanghai's 15min-CLC through the fusion of kernel density estimation, service area analysis and other statistical models and proposes relevant optimization suggestions. The results show that there are the following shortcomings: (1) From the perspective of different types of infrastructure service facilities, the spatial construction of Shanghai's overall life service facilities and shopping service facilities needs to be optimized. (2) From the perspective of comprehensive evaluation, the comprehensive service convenience of infrastructure service facilities in the downtown area is relatively high, while the comprehensive service convenience of urban infrastructure service facilities in the suburbs and outer suburbs is relatively low; The diversity of basic service facilities in the 15min-CLC in the downtown area is more consistent with the population distribution; However, in the peripheral areas of the urban area, too many infrastructure service facilities have been constructed. Based on the above shortcomings and the perspective of supply and demand matching, relevant optimization strategies are proposed in different regions and different types of infrastructure service facilities: (1) focus on the construction of basic service facilities in the urban fringe and urban-rural areas, improve the full coverage of the basic service facilities, and appropriately reduce the number of basic service facilities in the downtown area. (2) The development of community business models can be used to promote the development of new life service facilities and shopping service facilities. (3) Improve community medical institutions through facility function conversion, merger and reconstruction, etc. (4) Optimize the hierarchical basic service facility system and improve the population supporting facilities of basic service facilities in the 15min-CLC. This paper incorporates people's needs and concerns on the living environment into the 15min-CLC evaluation model, and uses Shanghai as an example to conduct research, summarizes the existing shortcomings, and proposes corresponding optimization strategies based on the matching of supply and demand. This article attempts to explore a replicable 15min-CLC planning model, so that it can be extended to the Yangtze River Delta urban agglomeration, to provide reference for further research on the 15min-CLC, and to promote urban construction under the concept of sustainable development.

Correction: Antiviral drug design based on the opening mechanism of spike glycoprotein in SARS-CoV-2.

Correction for 'Antiviral drug design based on the opening mechanism of spike glycoprotein in SARS-CoV-2' by Ruichao Mao et al., Phys. Chem. Chem. Phys., 2021, DOI: 10.1039/d1cp01045j.

Impact of COVID-19 Pandemic on Intervals and Outcomes of Repeated Transarterial Chemoembolization in Patients With Hepatocellular Carcinoma.

PURPOSE: Given that the novel coronavirus disease (COVID-19) pandemic has disrupted operations globally, an institution's ability to repeat transarterial chemoembolization (TACE) for patients with hepatocellular carcinoma (HCC) has also been affected. The aim of this study was to evaluate the impact of the COVID-19 on the intervals and outcomes of TACE in HCC patients. MATERIALS AND METHODS: This retrospective study included 154 HCC patients who underwent follow-up after TACE treatment from January 2020 to March 2020 (n = 71, study group) and January 2019 to March 2019 (n = 83, control group) at two institutions in China. The endpoints included the follow-up interval and overall response rate (ORR). Multivariate logistic regression analyses were performed to identify independent risk factors for a worse ORR. The cut-off point was determined to divide follow-up durations into long- and short-intervals. RESULTS: The median follow-up interval was 82.0 days (IQR, 61-109) in the study group, which was significantly longer than 66.0 days (IQR, 51-94) in the control group (P = 0.004). The ORR was 23.9 and 39.8% in the study and control group, respectively (P = 0.037). The cut-off value was 95 days. The grouping (OR, 2.402; 95% CI, 1.040-5.546; P = 0.040), long interval (OR, 2.573; 95% CI, 1.022-6.478; P = 0.045), and China liver cancer staging system (OR, 2.500; 95% CI, 1.797-3.480; P <0.001) were independent predictors for the efficacy of TACE treatment. CONCLUSIONS: The COVID-19 pandemic causes a longer follow-up interval in general, which may further lead to a lower ORR in HCC patients. Those with a follow-up interval of >95 days tend to have a worse prognosis.

Antiviral drug design based on the opening mechanism of spike glycoprotein in SARS-CoV-2.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the host cell after the receptor binding domain (RBD) of the virus spike (S) glycoprotein binds to the human angiotensin-converting enzyme 2 (hACE2). This binding requires the RBD to undergo a conformational change from a closed to an open state. In the present study, a key pair of salt bridges formed by the side chains of K537 and E619, residues at the interfaces of SD1 and SD2, respectively, was identified to promote the opening of the RBD. Mutations of K537Q and E619D reduced their side chain lengths and eliminated this pair of salt bridges; as a result, the opening of the RBD was not observed in the MD simulations. Thus, blocking the formation of this pair of salt bridges is a promising approach for treating novel coronavirus disease 2019 (COVID-19). FDA approved drug molecules were screened by their capabilities of blocking the formation of the key pair of salt bridges, achieved by their positional stabilities in the cavity containing the side chains of K537 and E619 formed in the interface between SD1 and SD2. Simeprevir, imatinib, and naldemedine were identified to possess the desired capability with the most favorable interaction energies.

Clinical diagnosis of severe COVID-19: A derivation and validation of a prediction rule.

BACKGROUND: The widespread coronavirus disease 2019 (COVID-19) has led to high morbidity and mortality. Therefore, early risk identification of critically ill patients remains crucial. AIM: To develop predictive rules at the time of admission to identify COVID-19 patients who might require intensive care unit (ICU) care. METHODS: This retrospective study included a total of 361 patients with confirmed COVID-19 by reverse transcription-polymerase chain reaction between January 19, 2020, and March 14, 2020 in Shenzhen Third People's Hospital. Multivariate logistic regression was applied to develop the predictive model. The performance of the predictive model was externally validated and evaluated based on a dataset involving 126 patients from the Wuhan Asia General Hospital between December 2019 and March 2020, by area under the receiver operating curve (AUROC), goodness-of-fit and the performance matrix including the sensitivity, specificity, and precision. A nomogram was also used to visualize the model. RESULTS: Among the patients in the derivation and validation datasets, 38 and 9 participants (10.5% and 2.54%, respectively) developed severe COVID-19, respectively. In univariate analysis, 21 parameters such as age, sex (male), smoker, body mass index (BMI), time from onset to admission (> 5 d), asthenia, dry cough, expectoration, shortness of breath, asthenia, and Rox index < 18 (pulse oxygen saturation, SpO2)/(FiO2 × respiratory rate, RR) showed positive correlations with severe COVID-19. In multivariate logistic regression analysis, only six parameters including BMI [odds ratio (OR) 3.939; 95% confidence interval (CI): 1.409-11.015; P = 0.009], time from onset to admission (≥ 5 d) (OR 7.107; 95%CI: 1.449-34.849; P = 0.016), fever (OR 6.794; 95%CI: 1.401-32.951; P = 0.017), Charlson index (OR 2.917; 95%CI: 1.279-6.654; P = 0.011), PaO2/FiO2 ratio (OR 17.570; 95%CI: 1.117-276.383; P = 0.041), and neutrophil/lymphocyte ratio (OR 3.574; 95%CI: 1.048-12.191; P = 0.042) were found to be independent predictors of COVID-19. These factors were found to be significant risk factors for severe patients confirmed with COVID-19. The AUROC was 0.941 (95%CI: 0.901-0.981) and 0.936 (95%CI: 0.886-0.987) in both datasets. The calibration properties were good. CONCLUSION: The proposed predictive model had great potential in severity prediction of COVID-19 in the ICU. It assisted the ICU clinicians in making timely decisions for the target population.

Thermal and humid environment improvement of the protective clothing for medical use with a portable cooling device: Analysis of air supply parameters.

COVID-19 has caused a huge impact on people's daily life and has made great damage on national economy. All the epidemic situation not only require the improvement of medical science, but also the corresponding auxiliary research field, e.g. the improve of protective clothing for medical use (MUPC). Developing a new kind of MUPC with portable cooling devices to improve medical workers' thermal comfort and protection performance of MUPC is imminent. In this paper, an integrated MUPC with a portable vortex tube cooling device was studied with experimental method. In a phytotron, a manikin wearing the MUPC was experimentally studied in terms of the influence of environment temperature and cool air supply conditions. On the basis of experiments, the MUPC inside air temperature and relative humidity, skin temperature of human body was studied with simulation method. Overall thermal sensation vote (TSV) and local TSV of human body were calculated, based on simulation results, to evaluate human thermal sensation. The results showed that, first, 50 L/min cool air flowrate with 18-20 °C supply temperature can create a good MUPC inside thermal sensation environment, for both head supply and body supply conditions. Both body supply condition and head supply condition cannot create a uniform MUPC inside thermal sensation environment. Second, MUPC inside air relative humidity is around or lower than 60% for most body parts, except for air supply position and body parts that air is difficult to reach. Thirdly, with cool air supplied into MUPC, a micro-positive pressure environment can be obtained, and the protection performance of MUPC can be improved.

Prognostic Nomogram on Admission Predicting Progression for Patients with Nonsevere COVID-19

The present study aimed to establish a prognostic nomogram to stratify high-risk patients with Coronavirus Disease 2019 (COVID-19) who progressed from the nonsevere condition on admission to severe during hospitalization. This multicenter retrospective study included patients with nonsevere COVID-19 on admission from Jan 10, 2020 to Feb 7, 2020. In the training cohort, independent risk factors associated with disease progression were identified by univariate and multivariate analyses. The prognostic nomogram was established and then validated externally using C-index. The study included 351 patients (293 and 58 in the training and validation cohorts, respectively), with 27 (9.2%) and 5 (8.6%) patients progressed, respectively. In the training cohort, older age (OR 1.036, 95% CI 1.000-1.073), more lobes involved on chest CT (OR 1.841, 95% CI 1.117-3.035), comorbidity present (OR 2.478, 95% CI 1.020-6.018), and lower lymphocyte count (OR 0.081, 95% CI 0.019-0.349) were identified as independent risk factors. The prognostic nomogram was established in the training cohort with satisfied external prognostic performance (C-index 0.906, 95% CI 0.806-1.000). In conclusion, older age, comorbidity present, more lobes involved on chest CT, and lower lymphocyte count are independent risk factors associated with disease progression during hospitalization for patients with nonsevere COVID-19.

Virus load and virus shedding of SARS-CoV-2 and their impact on patient outcomes.

BACKGROUND: Understanding a virus shedding patterns in body fluids/secretions is important to determine the samples to be used for diagnosis and to formulate infection control measures. AIM: To investigate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding patterns and its risk factors. METHODS: All laboratory-confirmed coronavirus disease 2019 patients with complete medical records admitted to the Shenzhen Third People's Hospital from January 28, 2020 to March 8, 2020 were included. Among 145 patients (54.5% males; median age, 46.1 years), three (2.1%) died. The bronco-alveolar lavage fluid (BALF) had the highest virus load compared with the other samples. The viral load peaked at admission (3.3 × 108 copies) and sharply decreased 10 d after admission. RESULTS: The viral load was associated with prolonged intensive care unit (ICU) duration. Patients in the ICU had significantly longer shedding time compared to those in the wards (P < 0.0001). Age > 60 years [hazard ratio (HR) = 0.6; 95% confidence interval (CI): 0.4-0.9] was an independent risk factor for SARS-CoV-2 shedding, while chloroquine (HR = 22.8; 95%CI: 2.3-224.6) was a protective factor. CONCLUSION: BALF had the highest SARS-CoV-2 load. Elderly patients had higher virus loads, which was associated with a prolonged ICU stay. Chloroquine was associated with shorter shedding duration and increased the chance of viral negativity.