Investigation on the binding behavior of human α1-acid glycoprotein with Janus Kinase inhibitor baricitinib: Multi-spectroscopic and molecular simulation methodologies.

Baricitinib is a Janus Kinase (JAK) inhibitor that is primarily used to treat moderately to severely active rheumatoid arthritis in adults and has recently been reported for the treatment of patients with severe COVID-19. This paper describes the investigation of the binding behavior of baricitinib to human α1-acid glycoprotein (HAG) employing a variety of spectroscopic techniques, molecular docking and dynamics simulations. Baricitinib can quench the fluorescence from amino acids in HAG through a mix of dynamic and static quenching, according to steady-state fluorescence and UV spectra observations, but it is mainly static quenching at low concentration. The binding constant (Kb) of baricitinib to HAG at 298 K was at the level of 104 M-1, indicating a moderate affinity of baricitinib to HAG. Hydrogen bonding and hydrophobic interactions conducted the main effect, according to thermodynamic characteristics, competition studies between ANS and sucrose, and molecular dynamics simulations. For the change in HAG conformation, the results of multiple spectra showed that baricitinib was able to alter the secondary structure of HAG as well as increase the polarity of the microenvironment around the Trp amino acid. Furthermore, the binding behavior of baricitinib to HAG was investigated by molecular docking and molecular dynamics simulations, which validated experimental results. Also explored is the influence of K+, Co2+, Ni2+, Ca2+, Fe3+, Zn2+, Mg2+ and Cu2+plasma on binding affinity.

Post-marketing safety concerns with nirmatrelvir: A disproportionality analysis of spontaneous reports submitted to the FDA Adverse Event Reporting System.

AIMS: Nirmatrelvir is an antiviral drug with a novel mechanism of action, targeting the 3-CL protease, and is used in the treatment of COVID-19. However, the potential side effects have not yet been fully studied. The aim of this study was to identify potential safety signals of nirmatrelvir by analysing post-marketing safety data based on the largest publicly available worldwide pharmacovigilance database. METHODS: We analysed nirmatrelvir adverse events to identify and characterize relevant safety signals based on the FDA Adverse Event Reporting System database in 2022. The case/non-case approach was used to estimate the reporting odds ratio (ROR) and information component (IC) with relevant confidence intervals (95% CI) for adverse events (AEs) that numbered 4 or more. RESULTS: A total of 26 846 cases were included. Disease recurrence (ROR [95% CI] = 413.2 [395.6-431.59]), dysgeusia (ROR [95% CI] = 110.84 [106.04-115.85]), anosmia (ROR [95% CI] = 15.21 [12.76-18.11]), ageusia (ROR [95% CI] = 9.80 [8.50-11.3]) and urticaria (ROR [95% CI] = 1.91 [1.69-2.17]) were the main safety signals. In addition, abdominal pain upper and skin toxicity were two specific safety signals of nirmatrelvir. In the pregnant population, there was a significant increased ROR for life-threatening conditions (ROR [95% CI] = 8.00 [1.77-36.20]). CONCLUSIONS: Our study identified that the main and specific safety signals of nirmatrelvir were disease recurrence, dysgeusia, abdominal pain upper and skin toxicity. Clinicians and pharmacists should be vigilant of these AEs, although differentiating between COVID-19 symptoms and AEs can be challenging. Notably, a potential safety concern of nirmatrelvir should be a warning based on a small number of events in the pregnant population. However, the available data are insufficient, and further continued pharmacovigilance and surveillance is needed to fully understand this issue.

Proteomic and phosphoproteomic characteristics of the cortex, hippocampus, thalamus, lung, and kidney in COVID-19-infected female K18-hACE2 mice

Background Neurological damage caused by coronavirus disease 2019 (COVID-19) has attracted increasing attention. Recently, through autopsies of patients with COVID-19, the direct identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in their central nervous system (CNS) has been reported, indicating that SARS-CoV-2 might directly attack the CNS. The need to prevent COVID-19-induced severe injuries and potential sequelae is urgent, requiring the elucidation of large-scale molecular mechanisms in vivo. Methods In this study, we performed liquid chromatography-mass spectrometry-based proteomic and phosphoproteomic analyses of the cortex, hippocampus, thalamus, lungs, and kidneys of SARS-CoV-2-infected K18-hACE2 female mice. We then performed comprehensive bioinformatic analyses, including differential analyses, functional enrichment, and kinase prediction, to identify key molecules involved in COVID-19. Findings We found that the cortex had higher viral loads than did the lungs, and the kidneys did not have SARS-COV-2. After SARS-CoV-2 infection, RIG-I-associated virus recognition, antigen processing and presentation, and complement and coagulation cascades were activated to different degrees in all five organs, especially the lungs. The infected cortex exhibited disorders of multiple organelles and biological processes, including dysregulated spliceosome, ribosome, peroxisome, proteasome, endosome, and mitochondrial oxidative respiratory chain. The hippocampus and thalamus had fewer disorders than did the cortex;however, hyperphosphorylation of Mapt/Tau, which may contribute to neurodegenerative diseases, such as Alzheimer's disease, was found in all three brain regions. Moreover, SARS-CoV-2-induced elevation of human angiotensin-converting enzyme 2 (hACE2) was observed in the lungs and kidneys, but not in the three brain regions. Although the virus was not detected, the kidneys expressed high levels of hACE2 and exhibited obvious functional dysregulation after infection. This indicates that SARS-CoV-2 can cause tissue infections or damage via complicated routes. Thus, the treatment of COVID-19 requires a multipronged approach. Interpretation This study provides observations and in vivo datasets for COVID-19-associated proteomic and phosphoproteomic alterations in multiple organs, especially cerebral tissues, of K18-hACE2 mice. In mature drug databases, the differentially expressed proteins and predicted kinases in this study can be used as baits to identify candidate therapeutic drugs for COVID-19. This study can serve as a solid resource for the scientific community. The data in this manuscript will serve as a starting point for future research on COVID-19-associated encephalopathy. Funding This study was supported by grants from the 10.13039/501100005150Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the 10.13039/501100001809National Natural Science Foundation of China, and the 10.13039/501100004826Natural Science Foundation of Beijing.

Proteomic and phosphoproteomic characteristics of the cortex, hippocampus, thalamus, lung, and kidney in COVID-19-infected female K18-hACE2 mice.

BACKGROUND: Neurological damage caused by coronavirus disease 2019 (COVID-19) has attracted increasing attention. Recently, through autopsies of patients with COVID-19, the direct identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in their central nervous system (CNS) has been reported, indicating that SARS-CoV-2 might directly attack the CNS. The need to prevent COVID-19-induced severe injuries and potential sequelae is urgent, requiring the elucidation of large-scale molecular mechanisms in vivo. METHODS: In this study, we performed liquid chromatography-mass spectrometry-based proteomic and phosphoproteomic analyses of the cortex, hippocampus, thalamus, lungs, and kidneys of SARS-CoV-2-infected K18-hACE2 female mice. We then performed comprehensive bioinformatic analyses, including differential analyses, functional enrichment, and kinase prediction, to identify key molecules involved in COVID-19. FINDINGS: We found that the cortex had higher viral loads than did the lungs, and the kidneys did not have SARS-COV-2. After SARS-CoV-2 infection, RIG-I-associated virus recognition, antigen processing and presentation, and complement and coagulation cascades were activated to different degrees in all five organs, especially the lungs. The infected cortex exhibited disorders of multiple organelles and biological processes, including dysregulated spliceosome, ribosome, peroxisome, proteasome, endosome, and mitochondrial oxidative respiratory chain. The hippocampus and thalamus had fewer disorders than did the cortex; however, hyperphosphorylation of Mapt/Tau, which may contribute to neurodegenerative diseases, such as Alzheimer's disease, was found in all three brain regions. Moreover, SARS-CoV-2-induced elevation of human angiotensin-converting enzyme 2 (hACE2) was observed in the lungs and kidneys, but not in the three brain regions. Although the virus was not detected, the kidneys expressed high levels of hACE2 and exhibited obvious functional dysregulation after infection. This indicates that SARS-CoV-2 can cause tissue infections or damage via complicated routes. Thus, the treatment of COVID-19 requires a multipronged approach. INTERPRETATION: This study provides observations and in vivo datasets for COVID-19-associated proteomic and phosphoproteomic alterations in multiple organs, especially cerebral tissues, of K18-hACE2 mice. In mature drug databases, the differentially expressed proteins and predicted kinases in this study can be used as baits to identify candidate therapeutic drugs for COVID-19. This study can serve as a solid resource for the scientific community. The data in this manuscript will serve as a starting point for future research on COVID-19-associated encephalopathy. FUNDING: This study was supported by grants from the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, and the Natural Science Foundation of Beijing.

Evaluation of RT-LAMP Assay for Rapid Detection of SARS-CoV-2.

OBJECTIVE: To evaluate the accuracy of the reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in community or primary-care settings. METHOD: We systematically searched the Web of Science, Embase, PubMed, and Cochrane Library databases. We conducted quality evaluation using ReviewManager software (version 5.0). We then used MetaDisc software (version 1.4) and Stata software (version 12.0) to build forest plots, along with a Deeks funnel plot and a bivariate boxplot for analysis. RESULT: Overall, the sensitivity, specificity, and diagnostic odds ratio were 0.79, 0.97, and 328.18, respectively. The sensitivity for the subgroup with RNA extraction appeared to be higher, at 0.88 (0.86-0.90), compared to the subgroup without RNA extraction, at 0.50 (0.45-0.55), with no significant difference in specificity. CONCLUSION: RT-LAMP assay exhibited high specificity regarding current SARS-CoV-2 infection. However, its overall sensitivity was relatively moderate. Extracting RNA was found to be beneficial in improving sensitivity.

How Did the Pandemic Affect Our Perception of Sustainability? Enlightening the Major Positive Impact on Health and the Environment

Since the World Health Organization (WHO) declared the outbreak of severe acute respiratory syndrome COVID-19 virus 2 (COVID-19) virus disease 2 (SARS-CoV-2) on 9 January 2020, the entire world has been exceptionally interested in examining the impact of this pandemic on people and the environment. The pandemic led to unprecedented measures to halt air traffic and close factories due to lockdowns, economic closures, and the stopping of transportation of all kinds. The decline in the use of coal by power plants, oil refining, and steel manufacturing had a beneficial effect on air pollution and caused a decrease in carbon dioxide emissions. Moreover, the concept of sustainability has become more prevalent, reflecting the increasing awareness of the responsibility placed on every member of society. Sustainability is the quality and quantity of change that meets our needs without destroying the giving planet, which is the hope for the survival of future generations. We summarized and discussed the studies and research documenting these effects on the environment and health worldwide to come up with objective conclusions, and to draw some recommendations and concepts about the importance of sustainability. The significance of this article lies in that it aims to briefly review some of the positive and negative impacts observed and reported during the SARS-CoV-2 pandemic on health and the planet's environment for the duration of April 2020-October 2022, and finally discuss the challenges and prospects to endorse planet sustainability. While COVID-19 had many beneficial effects on the planet's recovery, there were also profound effects on health due to the disease itself. Government and policymakers must take measures to prevent this environmental healing process from being transient.

Assessment of the Effect on Thromboprophylaxis with Multifaceted Quality Improvement Intervention based on Clinical Decision Support System in Hospitalized Patients: A Pilot Study.

BACKGROUND: To explore the feasibility and effectiveness of multifaceted quality improvement intervention based on the clinical decision support system (CDSS) in VTE prophylaxis in hospitalized patients. METHODS: A randomized, department-based clinical trial was conducted in the department of respiratory and critical care medicine, orthopedic, and general surgery wards. Patients aged ≥18 years, without VTE in admission, were allocated to the intervention group and received regular care combined with multifaceted quality improvement intervention based on CDSS during hospitalization. VTE prophylaxis rate and the occurrence of hospital-associated VTE events were analyzed as primary and secondary outcomes. RESULTS: A total of 3644 eligible residents were enrolled in this trial. With the implementation of the multifaceted quality improvement intervention based on the CDSS, the VTE prophylaxis rate of the intervention group increased from 22.93% to 34.56% (p < 0.001), and the incidence of HA-VTE events increased from 0.49% to 1.00% (p = 0.366). In the nonintervention group, the VTE prophylaxis rate increased from 24.49% to 27.90% (p = 0.091), and the incidence of HA-VTE events increased from 0.47% to 2.02% (p = 0.001). CONCLUSIONS: Multifaceted quality improvement intervention based on the CDSS strategy is feasible and expected to facilitate implementation of the recommended VTE prophylaxis strategies and reduce the incidence of HA-VTE in hospital. However, it is necessary to conduct more multicenter clinical trials in the future to provide more reliable real-world evidence.

Fatality assessment and variant risk monitoring for COVID-19 using three new hospital occupancy related metrics.

BACKGROUND: Though case fatality rate (CFR) is widely used to reflect COVID-19 fatality risk, its use is limited by large temporal and spatial variation. Hospital mortality rate (HMR) is also used to assess the severity of COVID-19, but HMR data is not directly available globally. Alternative metrics are needed for COVID-19 severity and fatality assessment. METHODS: We introduce new metrics for COVID-19 fatality risk measurements/monitoring and a new mathematical model to estimate average hospital length of stay for deaths (Ldead) and discharges (Ldis). Multiple data sources were used for our analyses. FINDINGS: We propose three, new metrics: hospital occupancy mortality rate (HOMR), ratio of total deaths to hospital occupancy (TDHOR), and ratio of hospital occupancy to cases (HOCR), for dynamic assessment of COVID-19 fatality risk. Estimated Ldead and Ldis for 501,079 COVID-19 hospitalizations in 34 US states between 7 August 2020 and 1 March 2021 were 18·2(95%CI:17·9-18·5) and 14·0(95%CI:13·9-14·0) days, respectively. We found the dramatic changes in COVID-19 CFR observed in 27 countries during early stages of the pandemic were mostly caused by undiagnosed cases. Compared to the first week of November 2021, the week mean HOCRs (mimics hospitalization-to-case ratio) for Omicron variant (58·6% of US new cases as of 25 December 2021) decreased 65·16% in the US as of 16 January 2022. INTERPRETATION: The new and reliable measurements described here could be useful for COVID-19 fatality risk and variant-associated risk monitoring. FUNDING: No specific funding was associated with the present study.

Advanced Functions Embedded in the Second Version of Database, Global Evaluation of SARS-CoV-2/hCoV-19 Sequences 2.

The Global Evaluation of SARS-CoV-2/hCoV-19 Sequences 2 (GESS v2 https://shiny.ph.iu.edu/GESS_v2/) is an updated version of GESS, which has offered a handy query platform to analyze single-nucleotide variants (SNVs) on millions of high coverages and high-quality severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) complete genomes provided by the Global Initiative on Sharing Avian Influenza Data (GISAID). Including the tools in the first version, the GESS v2 is embedded with new functions, which allow users to search SNVs, given the viral nucleotide or amino acid sequence. The GESS v2 helps users to identify SNVs or SARS-CoV-2 lineages enriched in countries of user's interest and show the migration path of a selected lineage on a world map during specific time periods chosen by the users. In addition, the GESS v2 can recognize the dynamic variations of newly emerging SNVs in each month to help users monitor SNVs, which will potentially become dominant soon. More importantly, multiple sets of analyzed results about SNVs can be downloaded directly from the GESS v2 by which users can conduct their own independent research. With these significant updates, the GESS v2 will continue to serve as a public open platform for researchers to explore SARS-CoV-2 evolutionary patterns from the perspectives of the prevalence and impact of SNVs.

Genome-wide analyses reveal the detrimental impacts of SARS-CoV-2 viral gene Orf9c on human pluripotent stem cell-derived cardiomyocytes.

Patients with coronavirus disease 2019 (COVID-19) commonly have manifestations of heart disease. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome encodes 27 proteins. Currently, SARS-CoV-2 gene-induced abnormalities of human heart muscle cells remain elusive. Here, we comprehensively characterized the detrimental effects of a SARS-CoV-2 gene, Orf9c, on human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) by preforming multi-omic analyses. Transcriptomic analyses of hPSC-CMs infected by SARS-CoV-2 with Orf9c overexpression (Orf9cOE) identified concordantly up-regulated genes enriched into stress-related apoptosis and inflammation signaling pathways, and down-regulated CM functional genes. Proteomic analysis revealed enhanced expressions of apoptotic factors, whereas reduced protein factors for ATP synthesis by Orf9cOE. Orf9cOE significantly reduced cellular ATP level, induced apoptosis, and caused electrical dysfunctions of hPSC-CMs. Finally, drugs approved by the U.S. Food and Drug Administration, namely, ivermectin and meclizine, restored ATP levels and ameliorated CM death and functional abnormalities of Orf9cOE hPSC-CMs. Overall, we defined the molecular mechanisms underlying the detrimental impacts of Orf9c on hPSC-CMs and explored potentially therapeutic approaches to ameliorate Orf9c-induced cardiac injury and abnormalities.

Updated SARS-CoV-2 single nucleotide variants and mortality association.

By analyzing newly collected SARS-CoV-2 genomes and comparing them with our previous study about SARS-CoV-2 single nucleotide variants (SNVs) before June 2020, we found that the SNV clustering had changed remarkably since June 2020. Apart from that the group of SNVs became dominant, which is represented by two nonsynonymous mutations A23403G (S:D614G) and C14408T (ORF1ab:P4715L), a few emerging groups of SNVs were recognized with sharply increased monthly incidence ratios of up to 70% in November 2020. Further investigation revealed sets of SNVs specific to patients' ages and/or gender, or strongly associated with mortality. Our logistic regression model explored features contributing to mortality status, including three critical SNVs, G25088T(S:V1176F), T27484C (ORF7a:L31L), and T25A (upstream of ORF1ab), ages above 40 years old, and the male gender. The protein structure analysis indicated that the emerging subgroups of nonsynonymous SNVs and the mortality-related ones were located on the protein surface area. The clashes in protein structure introduced by these mutations might in turn affect the viral pathogenesis through the alteration of protein conformation, leading to a difference in transmission and virulence. Particularly, we explored the fact that nonsynonymous SNVs tended to occur in intrinsic disordered regions of Spike and ORF1ab to significantly increase hydrophobicity, suggesting a potential role in the change of protein folding related to immune evasion.

Cover Image, Volume 93, Number 12, December 2021

Front Cover Caption: The cover image is based on the Research Article Updated SARS-CoV-2 single nucleotide variants and mortality association by Shuyi Fang et al., https://doi.org/10.1002/jmv.27191.

A survey on computational methods in discovering protein inhibitors of SARS-CoV-2.

The outbreak of acute respiratory disease in 2019, namely Coronavirus Disease-2019 (COVID-19), has become an unprecedented healthcare crisis. To mitigate the pandemic, there are a lot of collective and multidisciplinary efforts in facilitating the rapid discovery of protein inhibitors or drugs against COVID-19. Although many computational methods to predict protein inhibitors have been developed [ 1- 5], few systematic reviews on these methods have been published. Here, we provide a comprehensive overview of the existing methods to discover potential inhibitors of COVID-19 virus, so-called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). First, we briefly categorize and describe computational approaches by the basic algorithms involved in. Then we review the related biological datasets used in such predictions. Furthermore, we emphatically discuss current knowledge on SARS-CoV-2 inhibitors with the latest findings and development of computational methods in uncovering protein inhibitors against COVID-19.

COVID-19 or treatment associated immunosuppression may trigger hepatitis B virus reactivation: A case report.

BACKGROUND: Since the initial recognition of coronavirus disease 2019 (COVID-19) in Wuhan, this infectious disease has spread to most areas of the world. The pathogenesis of COVID-19 is yet unclear. Hepatitis B virus (HBV) reactivation occurring in COVID-19 patients has not yet been reported. CASE SUMMARY: A 45-year-old hepatitis B man with long-term use of adefovir dipivoxil and entecavir for antiviral therapy had HBV reactivation after being treated with methylprednisolone for COVID-19 for 6 d. CONCLUSION: COVID-19 or treatment associated immunosuppression may trigger HBV reactivation.

Multicenter analysis and a rapid screening model to predict early novel coronavirus pneumonia using a random forest algorithm.

ABSTRACT: Early determination of coronavirus disease 2019 (COVID-19) pneumonia from numerous suspected cases is critical for the early isolation and treatment of patients.The purpose of the study was to develop and validate a rapid screening model to predict early COVID-19 pneumonia from suspected cases using a random forest algorithm in China.A total of 914 initially suspected COVID-19 pneumonia in multiple centers were prospectively included. The computer-assisted embedding method was used to screen the variables. The random forest algorithm was adopted to build a rapid screening model based on the training set. The screening model was evaluated by the confusion matrix and receiver operating characteristic (ROC) analysis in the validation.The rapid screening model was set up based on 4 epidemiological features, 3 clinical manifestations, decreased white blood cell count and lymphocytes, and imaging changes on chest X-ray or computed tomography. The area under the ROC curve was 0.956, and the model had a sensitivity of 83.82% and a specificity of 89.57%. The confusion matrix revealed that the prospective screening model had an accuracy of 87.0% for predicting early COVID-19 pneumonia.Here, we developed and validated a rapid screening model that could predict early COVID-19 pneumonia with high sensitivity and specificity. The use of this model to screen for COVID-19 pneumonia have epidemiological and clinical significance.

Decreased Low-Density Lipoprotein Cholesterol Level Indicates Poor Prognosis of Severe and Critical COVID-19 Patients: A Retrospective, Single-Center Study.

Coronavirus disease 2019 (COVID-19) has become a global public health crisis. Reduced low-density lipoprotein cholesterol (LDL-C) levels were observed in COVID-19 patients. The present study aimed to explore the relationship between LDL-C levels and the prognosis of severe and critical COVID-19 patients. A total of 211 severe and critical COVID-19 patients were enrolled and divided into four groups according to the LDL-C levels, including 53 patients in Group A (LDL-C ≥ 2.71 mmol/L), 53 patients in Group B (2.28 ≤ LDL-C < 2.71 mmol/L), 53 patients in Group C (1.83 ≤ LDL-C < 2.28 mmol/L) and 52 patients in Group D (LDL-C < 1.83 mmol/L). LDL-C levels were lower in critically ill patients than in severe patients. The main symptoms before admission, characteristics on admission and comorbidities of enrolled patients did not differ among the four groups. Compared with patients with high LDL-C levels, patients with low LDL-C levels were more likely to have immune and inflammation dysfunction, renal dysfunction, liver dysfunction and cardiac dysfunction on admission. The proportions of patients with shock and acute cardiac injury, of those admitted to intensive care unit (ICU) and of those treated with mechanical ventilation were inversely related to LDL-C level. The mortality of COVID-19 patients increased with LDL-C reduction. Serum LDL-C levels of COVID-19 patients was negatively correlated with CRP level, but positively correlated with lymphocyte count, as shown by Pearson correlation analysis. Proportional hazard models showed that low LDL-C levels were associated with increased risk of hospitalization death, cardiac injury and admission to the ICU. Taken together, these results suggest that decreased LDL-C levels indicate poor prognosis of severe and critical COVID-19 patients.

[Bioinformatics Analysis of the Influence of Coronavirus Infection on Hematopoietic System and Potential Intervention Drugs and Their Significance for COVID-19].

OBJECTIVE: To analyze and predict the effect of coronavirus infection on hematopoietic system and potential intervention drugs, and explore their significance for coronavirus disease 2019 (COVID-19). METHODS: The gene expression omnibus (GEO) database was used to screen the whole genome expression data related with coronavirus infection. The R language package was used for differential expression analysis and KEGG/GO enrichment analysis. The core genes were screened by PPI network analysis using STRING online analysis website. Then the self-developed apparent precision therapy prediction platform (EpiMed) was used to analyze diseases, drugs and related target genes. RESULTS: A database in accordance with the criteria was found, which was derived from SARS coronavirus. A total of 3606 differential genes were screened, including 2148 expression up-regulated genes and 1458 expression down-regulated genes. GO enrichment mainly related with viral infection, hematopoietic regulation, cell chemotaxis, platelet granule content secretion, immune activation, acute inflammation, etc. KEGG enrichment mainly related with hematopoietic function, coagulation cascade reaction, acute inflammation, immune reaction, etc. Ten core genes such as PTPRC, ICAM1, TIMP1, CXCR5, IL-1B, MYC, CR2, FSTL1, SOX1 and COL3A1 were screened by protein interaction network analysis. Ten drugs with potential intervention effects, including glucocorticoid, TNF-α inhibitor, salvia miltiorrhiza, sirolimus, licorice, red peony, famciclovir, cyclosporine A, houttuynia cordata, fluvastatin, etc. were screened by EpiMed plotform. CONCLUSION: SARS coronavirus infection can affect the hematopoietic system by changing the expression of a series of genes. The potential intervention drugs screened on these grounds are of useful reference significance for the basic and clinical research of COVID-19.

The COSMIC Bubble Helmet: A Non-Invasive Positive Pressure Ventilation System for COVID-19.

Goal: COSMIC Medical, a Vancouver-based open-source volunteer initiative, has designed an accessible, affordable, and aerosol-confining non-invasive positive-pressure ventilator (NIPPV) device, known as the COSMIC Bubble Helmet (CBH). This device is intended for COVID-19 patients with mild-to-moderate acute respiratory distress syndrome. System Design: CBH is composed of thermoplastic polyurethane, which creates a flexible neck seal and transparent hood. This device can be connected to wall oxygen, NIPPVs including Continuous Positive Airway Pressure and Bi-level Positive Airway Pressure, and mechanical ventilators. Discussion: Justification of CBH design components relied on several factors, predominantly the safety and comfort of patients and healthcare providers. Conclusion: CBH has implications within and outside of the pandemic, as an alternative to invasive mechanical ventilation methods. We have experimentally verified that CBH is effective in minimizing aerosolization risks and performs at specified clinical requirements.

The Association between Obesity and Severity in Patients with Coronavirus Disease 2019: a Retrospective, Single-center Study, Wuhan.

Aim: In other respiratory infectious diseases, obesity may be associated with a poor outcome. For coronavirus disease 2019 (COVID-19), the association between obesity and severity or prognosis requires further analysis. Methods: This was a retrospective, single-center study. Hospitalized patients were recruited in Renmin Hospital of Wuhan University from January 2, 2020 to February 20, 2020. The data of body mass index (BMI) was obtained from follow-up of surviving patients. According to BMI, normal weight was defined as 18.5-23.9 kg/m2, overweight as 24.0-27.9 kg/m2 and obesity as > 28.0 kg/m2. Results: A total of 463 patients were enrolled, of which 242 (52.3%) patients were in the normal weight group; 179 (38.7%) were in the overweight group; and 42 (9.1%) were in the obesity group. Compared to the normal group, obese patients were more likely to have a higher heart rate; lower finger oxygen saturation; higher levels of white blood cells, neutrophil counts, basophil counts, intravenous glucose, triacylglycerol, uric acid, alanine aminotransferase, creatine kinase-MB, CD19+ cell counts and percentage; and lower levels of monocyte percentage, high density lipoprotein and CD3+ cell percentage. In addition, the proportions of hypertension (21.5% vs. 42.6%) and severe+critical illness (47.8 vs. 81.0 %) were significantly higher in the obesity group than those in normal group. However, no significant differences were observed between the normal and obesity groups in critical illness, organ damage and defined endpoint (mechanical ventilation or intensive care unit). Multiple logistic regression showed that obesity increased the risk of developing severe+critical illness (Odd ratio 3.586, 95% CI 1.550-8.298, P=0.003) in patients with COVID-19, and did not affect the risk of critical illness, organ damage and endpoints. Overweight did not affect the risk of severity, organ damage or endpoint in patients with COVID-19. Conclusion: Obesity may be a risk factor for developing severity in patients with COVID-19.