Pan-cancer landscape of CENPO and its underlying mechanism in LUAD.

BACKGROUND: Centromere protein O (CENPO) is a newly discovered constitutive centromeric protein, associated with cell death. However, little is known about how CENPO expression is associated with human cancers or immune infiltration. Here, we assessed the function of CENPO in pan-cancer and further verified the results in lung adenocarcinoma (LUAD) through in vitro and in vivo experiments. METHODS: Sangerbox and TCGA databases were used to evaluate the CENPO expression level in different human cancer types. A subsequent evaluation of the potential role of CENPO as a diagnostic and prognostic biomarker in pancancer was conducted. The CENPO mutations were analyzed using the cBioPortal database and its function was analyzed using the LinkedOmics and CancerSEA databases. The TIMER2 and TISIDB websites were used to find out how CENPO affects immune infiltration. The expression level of CENPO in LUAD was revealed by TCGA database and immunohistochemical (IHC) staining. Targetscan, miRWalk, miRDB, miRabel, LncBase databases, and Cytoscape tool were used to identify microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) that regulate expression and construct ceRNA network. Subsequently, loss-of-function assays were performed to identify the functions of CENPO on the malignant behavior and tumor growth of LUAD in vitro and in vivo experiments. RESULTS: In most cancers, CENPO was upregulated and mutated, which predicted a poorer prognosis. Furthermore, infiltration of CENPO and myeloid-derived suppressor cells (MDSC) showed a significant positive correlation, while T-cell NK infiltration showed a significant negative correlation in most cancers. CENPO was expressed at high levels in LUAD and was correlated with p-TNM stage. Furthermore, CENPO knockdown suppressed the malignant phenotypes of LUAD cells, manifested by slower proliferation, cycle in G2, increased apoptosis, decreased migration, and attenuated tumorigenesis. Furthermore, CENPO knockdown decreased CDK1/6, PIK3CA, and inhibited mTOR phosphorylation, suggesting that the mTOR signaling pathway may be involved in CENPO-mediated regulation of LUAD development. CONCLUSIONS: In pan-cancer, especially LUAD, CENPO may be a potential biomarker and oncogene. Furthermore, CENPO has been implicated in immune cell infiltration in pan-cancer and represents a potential immunotherapeutic target for tumor therapy.

Newest perspectives of glycopeptide antibiotics: biosynthetic cascades, novel derivatives, and new appealing antimicrobial applications.

Glycopeptide antibiotics (GPAs) are a family of non-ribosomal peptide natural products with polypeptide skeleton characteristics, which are considered the last resort for treating severe infections caused by multidrug-resistant Gram-positive pathogens. Over the past few years, an increasing prevalence of Gram-positive resistant strain "superbugs" has emerged. Therefore, more efforts are needed to study and modify the GPAs to overcome the challenge of superbugs. In this mini-review, we provide an overview of the complex biosynthetic gene clusters (BGCs), the ingenious crosslinking and tailoring modifications, the new GPA derivatives, the discoveries of new natural GPAs, and the new applications of GPAs in antivirus and anti-Gram-negative bacteria. With the development and interdisciplinary integration of synthetic biology, next-generation sequencing (NGS), and artificial intelligence (AI), more GPAs with new chemical structures and action mechanisms will constantly be emerging.

The rapid and efficient strategy for SARS-CoV-2 Omicron transmission control: analysis of outbreaks at the city level.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron (B.1.1.529) variant is highly transmissible with potential immune escape. Hence, control measures are continuously being optimized to guard against large-scale coronavirus disease 2019 (COVID-19) outbreaks. This study aimed to explore the relationship between the intensity of control measures in response to different SARS-CoV-2 variants and the degree of outbreak control at city level. METHODS: A retrospective study was conducted in 49 cities with COVID-19 outbreaks between January 2020 and June 2022. Epidemiological data on COVID-19 were extracted from the National Health Commission, People's Republic of China, and the population flow data were sourced from the Baidu migration data provided by the Baidu platform. Outbreak control was quantified by calculating the degree of infection growth and the time-varying reproduction number ([Formula: see text]). The intensity of the outbreak response was quantified by calculating the reduction in population mobility during the outbreak period. Correlation and regression analyses of the intensity of the control measures and the degree of outbreak control for the Omicron variant and non-Omicron mutants were conducted, respectively. RESULTS: Overall, 65 outbreaks occurred in 49 cities in China from January 2020 to June 2022. Of them, 66.2% were Omicron outbreaks and 33.8% were non-Omicron outbreaks. The intensity of the control measures was positively correlated with the degree of outbreak control (r = 0.351, P = 0.03). The degree of reduction in population mobility was negatively correlated with the Rt value (r = - 0.612, P < 0.01). Therefore, under the same control measure intensity, the number of new daily Omicron infections was 6.04 times higher than those attributed to non-Omicron variants, and the Rt value of Omicron outbreaks was 2.6 times higher than that of non-Omicron variants. In addition, the duration of non-Omicron variant outbreaks was shorter than that of the outbreaks caused by the Omicron variant (23.0 ± 10.7, 32.9 ± 16.3, t = 2.243, P = 0.031). CONCLUSIONS: Greater intensity of control measures was associated with more effective outbreak control. Thus, in response to the Omicron variant, the management to restrict population movement should be used to control its spread quickly, especially in the case of community transmission occurs widely. Faster than is needed for non-Omicron variants, and decisive control measures should be imposed and dynamically adjusted in accordance with the evolving epidemic situation.

Expedient Synthesis of Ubiquitin‐like Protein ISG15 Tools through Chemo‐Enzymatic Ligation Catalyzed by a Viral Protease Lbpro

Ubiquitin (Ub)‐like protein ISG15 (interferon‐stimulated gene 15) regulates innate immunity and links with the evasion of host response by viruses such as SARS‐CoV‐2. Dissecting ISGylation pathways recently received increasing attention which can inform related disease interventions, but such studies necessitate the preparation and development of various ISG15 protein tools. Here, we find that the leader protease (Lbpro) encoded by foot‐and‐mouth disease virus can promote ligation reactions between recombinant ISG15 and synthetic glycyl compounds, generating protein tools such as ISG15‐propargylamide and ISG15‐rhodamine110, which are needed for cellular proteomic studies of deISGylases, and the screening and evaluation of inhibitors against SARS‐CoV‐2 papain‐like protease (PLpro). Furthermore, this strategy can be also used to load ISG15 onto the lysine of a synthetic peptide through an isopeptide bond, and prepare Ub and NEDD8 (ubiquitin‐like protein Nedd8) protein tools.

Sex-Specific Microglial Activation and SARS-CoV-2 Receptor Expression Induced by Chronic Unpredictable Stress.

The coronavirus disease 2019 (COVID-19) pandemic has generated a lot of stress and anxiety among not only infected patients but also the general population across the globe, which disturbs cerebral immune homeostasis and potentially exacerbates the SARS-CoV-2 virus-induced neuroinflammation, especially among people susceptible to neuropsychiatric disorders. Here, we used a chronic unpredictable mild stress (CUMS) mouse model to study its effects on glia-mediated neuroinflammation and expression of SARS-CoV2 viral receptors. We observed that female mice showed depressive-like behavior after CUMS, whereas male mice showed enhanced anxiety and social withdrawal. Interestingly, CUMS led to increased amounts of total and MHCII+ microglia in the hippocampi of female mice but not male mice. mRNA levels of SARS-CoV-2 viral receptors angiotensin-converting enzyme 2 (Ace2) and basigin (Bsg) were also upregulated in the prefrontal cortices of stressed female mice but not male mice. Similarly, sex-specific changes in SARS-CoV-2 viral receptors FURIN and neuropilin-1 (NRP1) were also observed in monocytes of human caregivers enduring chronic stress. Our findings provided evidence on detrimental effects of chronic stress on the brain and behavior and implied potential sex-dependent susceptibility to SARS-CoV-2 infection after chronic stress.

Sibling Jealousy and Temperament: The Mediating Effect of Emotion Regulation in China During COVID-19 Pandemic.

This study aimed to examine first-born children's sibling jealousy and explore the relationships among first-born children's sibling jealousy, temperament, and emotion regulation in China during COVID-19 pandemic. The research hypotheses of this study are empirically examined through online and offline surveys. A sample of 304 two-child families from China participated in the study; the first-born children were aged between 1.17 and 7 years. The results indicated the following: (1) the older the first-born children and the greater the age difference between siblings, the lower the sibling jealousy. (2) Difficult temperament of first-born children could predict sibling jealousy significantly and positively, and emotion regulation could predict sibling jealousy negatively. (3) There was a partially mediating effect of emotion regulation between temperament and sibling jealousy. Compared with intermediate temperament, first-born children with difficult temperament had weaker emotion regulation and higher sibling jealousy. Overall, findings have important implications for psychological interventions for families of first-born children with difficult temperament.

Human Mesenchymal Stem Cells Treatment for Severe COVID-19: 1-Year Follow-Up Results of a Randomized, Double-Blind, Placebo-Controlled Trial (preprint)

Background The long-term consequences of human umbilical cord-derived mesenchymal stem cell (UC-MSC) treatment for COVID-19 patients are yet to be reported. This study assessed the 1-year outcomes in patients with severe COVID-19, who were recruited in our previous UC-MSC clinical trial.Methods: In this prospective, longitudinal, cohort study, 100 patients enrolled in our phase 2 trial were prospectively followed up at 3-month intervals for 1 year to evaluate the long-term safety and effectiveness of UC-MSC treatment. The primary endpoint was an altered proportion of whole-lung lesion volumes measured by high-resolution CT. Other imaging outcomes, 6-minute walking distance (6-MWD), lung function, plasma biomarkers, and adverse events were also recorded and analyzed. This trial was registered with ClinicalTrials.gov (NCT04288102).Findings: Within 3 months, MSC administration exerted numerical improvement in whole-lung lesion volume compared with the placebo, leading to a significant difference of −10.82% (95% CI: −20.69%, −1.46%, P=0.030) on day 10. MSC also reduced the proportion of solid component lesion volume compared with the placebo at each follow-up point, with a significant difference of − 9.02% (95%CI: − 17.44%, − 0.10%, P=0.045) at month 9. More interestingly, 17.86% (10/56) of patients in the MSC group had normal CT images at month 12 ( P= 0.013), but none in the placebo group. The incidence of symptoms was lower in the MSC group than in the placebo group at each follow-up time, particularly sleep difficulties at month 3 (OR 0.19, 95% CI 0.07,0.50; P=0.001), and usual activity at month 12 (OR 0.15, 95% CI 0.03,0.79; P=0.018). Neutralizing antibodies were all positive, with a similar median inhibition rate (61.6% vs. 67.55%) in both groups at month 12. No difference in adverse events at the 1-year follow-up and tumor markers at month 12 were observed between the two groups.Interpretation: UC-MSC administration achieves a long-term benefit in the recovery of lung lesions and symptoms in COVID-19 patients.Trial Registration: This trial was registered with ClinicalTrials.gov (NCT04288102).Funding The National Key R&D Program of China, the Innovation Groups of the National Natural Science Foundation of China, and the National Science and Technology Major Project.Declaration of Interest: None to declare. Ethical Approval: This study was approved by the Ethics Committee of the Fifth Medical Center, Chinese PLA General Hospital (2020-013-D).

Potent neutralizing RBD-specific antibody cocktail against SARS-CoV-2 and its mutant.

The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants has posed a serious global public health emergency. Therapeutic interventions or vaccines are urgently needed to treat and prevent the further dissemination of this contagious virus. This study described the identification of neutralizing receptor-binding domain (RBD)-specific antibodies from mice through vaccination with a recombinant SARS-CoV-2 RBD. RBD-targeted monoclonal antibodies (mAbs) with distinct function and epitope recognition were selected to understand SARS-CoV-2 neutralization. High-affinity RBD-specific antibodies exhibited high potency in neutralizing both live and pseudotype SARS-CoV-2 viruses and the SARS-CoV-2 pseudovirus particle containing the spike protein S-RBDV367F mutant (SARS-CoV-2(V367F)). These results demonstrated that these antibodies recognize four distinct groups (I-IV) of epitopes on the RBD and that mAbs targeting group I epitope can be used in combination with mAbs recognizing groups II and/or IV epitope to make mAb cocktails against SARS-CoV-2 and its mutants. Moreover, structural characterization reveals that groups I, III, and IV epitopes are closely located to an RBD hotspot. The identification of RBD-specific antibodies and cocktails may provide an effective therapeutic and prophylactic intervention against SARS-CoV-2 and its isolates.

Intravenous immunoglobulin-based adjuvant therapy for severe COVID-19: a single-center retrospective cohort study.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a major challenge facing the world. Certain guidelines issued by National Health Commission of the People's Repubilic of China recommend intravenous immunoglobulin (IVIG) for adjuvant treatment of COVID-19. However, there is a lack of clinical evidence to support the use of IVIG. METHODS: This single-center retrospective cohort study included all adult patients with laboratory-confirmed severe COVID-19 in the Respiratory and Critical Care Unit of Dabie Mountain Regional Medical Center, China. Patient information, including demographic data, laboratory indicators, the use of glucocorticoids and IVIG, hospital mortality, the application of mechanical ventilation, and the length of hospital stay was collected. The primary outcome was the composite end point, including death and the use of mechanical ventilation. The secondary outcome was the length of hospital stay. RESULTS: Of the 285 patients with confirmed COVID-19, 113 severely ill patients were included in this study. Compared to the non-IVIG group, more patients in the IVIG group reached the composite end point [12 (25.5%) vs 5 (7.6%), P = 0.008] and had longer hospital stay periods [23.0 (19.0-31.0) vs 16.0 (13.8-22.0), P < 0.001]. After adjusting for confounding factors, differences in primary outcomes between the two groups were not statistically significant (P = 0.167), however, patients in the IVIG group had longer hospital stay periods (P = 0.041). CONCLUSION: Adjuvant therapy with IVIG did not improve in-hospital mortality rates or the need for mechanical ventilation in severe COVID-19 patients. Our study does not support the use of immunoglobulin in patients with severe COVID-19 patients.

Predictive analysis and countermeasures in response to COVID-19 epidemic in 2020-2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a natural emerging virus, with rapid virus replication, wide cell tropism, and strong survival ability. Its epidemic characteristics are similar to those of influenza virus. Asymptomatic infections are widespread in a covert way, and the virus has adapted to human population, making it difficult to control the transmission. The global epidemic in 2020/2021 may further deteriorate before the SARS-CoV-2 vaccines are widely applied and show protective effectiveness, and China will still face the risk of continuous overseas multi-channel import and local outbreaks or recurrence of the epidemic. Therefore, it is necessary to carry out further surveillance about the prevalence and infection of SARS-CoV-2 in the population and the corresponding environment of the high-risk areas in China, and establish a national super mobile SARS-CoV-2 detection network laboratory for performing ultra-large-scale testing tasks;implement differentiated vaccination strategies and closely follow up and monitor the effectiveness and efficiency of vaccination;and continue to strengthen effective public health measures such as wearing masks, washing hands frequently, keeping social distances, opening windows frequently, and reducing gatherings. The coronavirus disease 2019 (COVID-19) epidemic warns us once again that the continuous emergence of new infectious diseases caused by unknown pathogens of wild animal origin has become the new normal status. It is necessary to systematically carry out unknown microbial discovery and reverse pathogenic etiology research in a prospective manner, and actively defend against emerging infectious diseases in the future.

Efficacy of the combination of modern medicine and traditional Chinese medicine in pulmonary fibrosis arising as a sequelae in convalescent COVID-19 patients: a randomized multicenter trial.

BACKGROUND: The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to a significant number of mortalities worldwide. COVID-19 poses a serious threat to human life. The clinical manifestations of COVID-19 are diverse and severe and 20% of infected patients are reported to be in a critical condition. A loss in lung function and pulmonary fibrosis are the main manifestations of patients with the severe form of the disease. The lung function is affected, even after recovery, thereby greatly affecting the psychology and well-being of patients, and significantly reducing their quality of life. METHODS: Participants must meet the following simultaneous inclusion criteria: over 18 years of age, should have recovered from severe or critical COVID-19 cases, should exhibit pulmonary fibrosis after recovery, and should exhibit Qi-Yin deficiency syndrome as indicated in the system of traditional Chinese medicine (TCM). The eligible candidates will be randomized into treatment or control groups. The treatment group will receive modern medicine (pirfenidone) plus TCM whereas the control group will be administered modern medicine plus TCM placebo. The lung function index will be continuously surveyed and recorded. By comparing the treatment effect between the two groups, the study intend to explore whether TCM can improve the effectiveness of modern medicine in patients with pulmonary fibrosis arising as a sequelae after SARS-CoV-2 infection. DISCUSSION: Pulmonary fibrosis is one of fatal sequelae for some severe or critical COVID-19 cases, some studies reveal that pirfenidone lead to a delay in the decline of forced expiratory vital capacity, thereby reducing the mortality partly. Additionally, although TCM has been proven to be efficacious in treating pulmonary fibrosis, its role in treating pulmonary fibrosis related COVID-19 has not been explored. Hence, a multicenter, parallel-group, randomized controlled, interventional, prospective clinical trial has been designed and will be conducted to determine if a new comprehensive treatment for pulmonary fibrosis related to COVID-19 is feasible and if it can improve the quality of life of patients. TRIAL REGISTRATION: This multicenter, parallel-group, randomized controlled, interventional, prospective trial was registered at the Chinese Clinical Trial Registry (ChiCTR2000033284) on 26th May 2020 (prospective registered).

Heparin-binding protein levels correlate with aggravation and multiorgan damage in severe COVID-19.

BACKGROUND: Critically ill coronavirus disease 2019 (COVID-19) patients may suffer persistent systemic inflammation and multiple organ failure, leading to a poor prognosis. RESEARCH QUESTION: To examine the relevance of the novel inflammatory factor heparin-binding protein (HBP) in critically ill COVID-19 patients, and evaluate the correlation of the biomarker with disease progression. STUDY DESIGN AND METHODS: 18 critically ill COVID-19 patients who suffered from respiratory failure and sepsis, including 12 cases who experienced a rapidly deteriorating clinical condition and six cases without deterioration, were investigated. They were compared with 15 age- and sex- matched COVID-19-negative patients with respiratory failure. Clinical data were collected and HBP levels were investigated. RESULTS: HBP was significantly increased in critically ill COVID-19 patients following disease aggravation and tracked with disease progression. HBP elevation preceded the clinical manifestations for up to 5 days and was closely correlated with patients' pulmonary ventilation and perfusion status. INTERPRETATION: HBP levels are associated with COVID-19 disease progression in critically ill patients. As a potential mediator of disease aggravation and multiple organ injuries that are triggered by continuing inflammation and oxygen deficits, HBP warrants further study as a disease biomarker and potential therapeutic target.

Axial Chiral Binaphthoquinone and Perylenequinones from the Stromata of Hypocrella bambusae Are SARS-CoV-2 Entry Inhibitors.

A new axial chiral binaphtoquinone, hypocrellone (1), and a new perylenequinone, hypomycin F (2), were isolated from the stromata of Hypocrella bambusae, together with five known compounds, 3-7. The structures of 1 and 2 were assigned by spectroscopic and HRESIMS data analyses. The axial chirality of 1 was determined by electronic circular dichroism data analysis, and the absolute configurations of 2 and 3 were determined by X-ray crystallography. The axial chirality of 7 was determined by UV-induced photooxidation from 4. Compounds 1, 4, and 5 showed inhibitory activity against pseudotyped SARS-CoV-2 infection in 293T-ACE2 cells with IC50 values of 0.17, 0.038, and 0.12 µM. Compounds 4 and 5 were also active against live SARS-CoV-2 infection with EC50 values of 0.22 and 0.21 µM, respectively. Further cell-cell fusion assays, surface plasmon resonance assays, and molecular docking studies revealed that 4 and 5 could bind with the receptor-binding domain of SARS-CoV-2 S protein to prevent its interaction with human angiotensin-converting enzyme II receptor. Our results revealed that 4 and 5 are potential SARS-CoV-2 entry inhibitors.

A more secure and effective method for throat swab collection: The importance of adequate exposure of oral cavity in COVID-19 specimen collection.

OBJECTIVES: This study aims to propose a novel and effective throat swab collection method for coronavirus disease 2019 (COVID-19). METHODS: The subjects were randomly divided into two groups. The subjects were asked to open their mouth to make "ah" sound (traditional method) or simulate yawn (improved method) for throat swab collection. The usage of tongue depressor, collection time, adverse reactions and subjective discomfort (VAS score) were compared. The collection time, comprehensive indicators of adverse reactions and VAS score were also compared among three collectors. RESULTS: The tongue depressor was less used in the improved group (χ2 = 40.186, P < 0.01). The average collection time of the traditional group was 5.44 ± 2.97 and that of the improved group was 4.00 ± 2.31 (P < 0.01). The subjects in the improved group had fewer and milder adverse reactions. The VAS score of subjects in the improved group was lower than that in the traditional group (P < 0.01). Among different collectors, the collection time, comprehensive indicators of adverse reactions and VAS were the same as the overall trend. CONCLUSION: Simulating yawn is a safer and faster throat swab collection method.

Intracity Pandemic Risk Evaluation Using Mobile Phone Data: The Case of Shanghai during COVID-19

The coronavirus disease 2019 (COVID-19) pandemic has provided an opportunity to rethink the development of a sustainable and resilient city. A framework for comprehensive intracity pandemic risk evaluation using mobile phone data is proposed in this study. Four steps were included in the framework: identification of high-risk groups, calculation of dynamic population flow and construction of a human mobility network, exposure and transmission risk assessment, and pandemic prevention guidelines. First, high-risk groups were extracted from mobile phone data based on multi-day activity chains. Second, daily human mobility networks were created by aggregating population and origin-destination (OD) flows. Third, clustering analysis, time series analysis, and network analysis were employed to evaluate pandemic risk. Finally, several solutions are proposed to control the pandemic. The outbreak period of COVID-19 in Shanghai was used to verify the proposed framework and methodology. The results show that the evaluation method is able to reflect the different spatiotemporal patterns of pandemic risk. The proposed framework and methodology may help prevent future public health emergencies and localized epidemics from evolving into global pandemics.

A Retrospective Study on the Effects of Convalescent Plasma Therapy in 24 Patients Diagnosed with COVID-19 Pneumonia in February and March 2020 at 2 Centers in Wuhan, China.

BACKGROUND This retrospective study aimed to describe the effects of convalescent plasma therapy in 24 patients diagnosed with coronavirus disease 2019 (COVID-19) pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during February and March 2020 in Wuhan, China. MATERIAL AND METHODS The confirmation of SARS-CoV-2 infection was made by the reverse transcription-polymerase chain reaction test. We retrospectively analyzed the clinical data and laboratory test reports of patients with severe COVID-19 pneumonia who received a convalescent plasma transfusion. RESULTS A total of 24 patients with COVID-19 pneumonia who were transfused with ABO-compatible convalescent plasma were enrolled in the study. Convalescent plasma transfusion showed an effective clinical outcome in 14 of 24 patients (an effective rate of 58.3%). No patients had an adverse reaction to the transfusion. Compared with before convalescent plasma transfusion, the lymphocyte count after convalescent plasma transfusion increased to a normal level (median: 0.80×109/L vs. 1.12×109/L, P=0.004). Other laboratory indicators such as white blood cells, high-sensitivity C-reactive protein, procalcitonin, alanine aminotransferase, and aspartate transaminase showed a decreasing trend after transfusion. CONCLUSIONS This retrospective observational clinical study showed that convalescent plasma therapy could have beneficial effects on patient outcomes. Recently, regulatory authorization has been given for the use of convalescent plasma therapy, and clinical guidelines have been developed for the collection and use of convalescent plasma and hyperimmune immunoglobulin in patients with COVID-19.

Risk factors related to the severity of COVID-19 in Wuhan.

Objective: To evaluate the characteristics at admission of patients with moderate COVID-19 in Wuhan and to explore risk factors associated with the severe prognosis of the disease for prognostic prediction. Methods: In this retrospective study, moderate and severe disease was defined according to the report of the WHO-China Joint Mission on COVID-19. Clinical characteristics and laboratory findings of 172 patients with laboratory-confirmed moderate COVID-19 were collected when they were admitted to the Cancer Center of Wuhan Union Hospital between February 13, 2020 and February 25, 2020. This cohort was followed to March 14, 2020. The outcomes, being discharged as mild cases or developing into severe cases, were categorized into two groups. The data were compared and analyzed with univariate logistic regression to identify the features that differed significantly between the two groups. Based on machine learning algorithms, a further feature selection procedure was performed to identify the features that can contribute the most to the prediction of disease severity. Results: Of the 172 patients, 112 were discharged as mild cases, and 60 developed into severe cases. Four clinical characteristics and 18 laboratory findings showed significant differences between the two groups in the statistical test (P<0.01) and univariate logistic regression analysis (P<0.01). In the further feature selection procedure, six features were chosen to obtain the best performance in discriminating the two groups with a linear kernel support vector machine. The mean accuracy was 91.38%, with a sensitivity of 0.90 and a specificity of 0.94. The six features included interleukin-6, high-sensitivity cardiac troponin I, procalcitonin, high-sensitivity C-reactive protein, chest distress and calcium level. Conclusions: With the data collected at admission, the combination of one clinical characteristic and five laboratory findings contributed the most to the discrimination between the two groups with a linear kernel support vector machine classifier. These factors may be risk factors that can be used to perform a prognostic prediction regarding the severity of the disease for patients with moderate COVID-19 in the early stage of the disease.

Neuropathobiology of COVID-19: The Role for Glia.

SARS-CoV-2, which causes the Coronavirus Disease 2019 (COVID-19) pandemic, has a brain neurotropism through binding to the receptor angiotensin-converting enzyme 2 expressed by neurones and glial cells, including astrocytes and microglia. Systemic infection which accompanies severe cases of COVID-19 also triggers substantial increase in circulating levels of chemokines and interleukins that compromise the blood-brain barrier, enter the brain parenchyma and affect its defensive systems, astrocytes and microglia. Brain areas devoid of a blood-brain barrier such as the circumventricular organs are particularly vulnerable to circulating inflammatory mediators. The performance of astrocytes and microglia, as well as of immune cells required for brain health, is considered critical in defining the neurological damage and neurological outcome of COVID-19. In this review, we discuss the neurotropism of SARS-CoV-2, the implication of neuroinflammation, adaptive and innate immunity, autoimmunity, as well as astrocytic and microglial immune and homeostatic functions in the neurological and psychiatric aspects of COVID-19. The consequences of SARS-CoV-2 infection during ageing, in the presence of systemic comorbidities, and for the exposed pregnant mother and foetus are also covered.