Training infectious diseases senior residents during COVID-19: The impact and the lessons learnt.

BACKGROUND: The COVID-19 pandemic had major impact on the training of Infectious Diseases (ID) residents across the globe. They were part of the frontline staff, while at the same time training to be ID physicians. This study focused on identifying their capability, i.e. the ability to adapt existing competencies to new situations, which is now recognised as an essential element of professional practice. AIM: This study explored what ID residents learnt and how they learnt as they adapted to working in this unpredictable and challenging COVID-19 pandemic. METHODS: This qualitative explorative study was based in the Infectious Diseases Senior Residency Programme across three training institutions in Singapore. Individual semi-structured interviews were conducted. Data were analysed using a template analysis technique. RESULTS: Nine ID residents participated in this study. They learnt to engage with uncertainty in a meaningful way by relying on prior training and rapidly learning how to most effectively learn (metacognition). Learning was enhanced by collaboration between multidisciplinary health professionals, strong leadership and intrinsic motivation from personal interest in ID. They learnt through observing how senior faculty approached and managed the COVID-19 situation. CONCLUSION: When learning for future capability in a rapidly evolving situation, role-modelling and mentoring are essential as available information resources may still not provide the learning from skilled doctors with actual experiences managing complex, uncertain situations.

Modeling Kaempferol as a Potential Pharmacological Agent for COVID-19/PF Co-Occurrence Based on Bioinformatics and System Pharmacological Tools.

Objective: People suffering from coronavirus disease 2019 (COVID-19) are prone to develop pulmonary fibrosis (PF), but there is currently no definitive treatment for COVID-19/PF co-occurrence. Kaempferol with promising antiviral and anti-fibrotic effects is expected to become a potential treatment for COVID-19 and PF comorbidities. Therefore, this study explored the targets and molecular mechanisms of kaempferol against COVID-19/PF co-occurrence by bioinformatics and network pharmacology. Methods: Various open-source databases and Venn Diagram tool were applied to confirm the targets of kaempferol against COVID-19/PF co-occurrence. Protein-protein interaction (PPI), MCODE, key transcription factors, tissue-specific enrichment, molecular docking, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to clarify the influential molecular mechanisms of kaempferol against COVID-19 and PF comorbidities. Results: 290 targets and 203 transcription factors of kaempferol against COVID-19/PF co-occurrence were captured. Epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase SRC (SRC), mitogen-activated protein kinase 3 (MAPK3), mitogen-activated protein kinase 1 (MAPK1), mitogen-activated protein kinase 8 (MAPK8), RAC-alpha serine/threonine-protein kinase (AKT1), transcription factor p65 (RELA) and phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) were identified as the most critical targets, and kaempferol showed effective binding activities with the above critical eight targets. Further, anti-COVID-19/PF co-occurrence effects of kaempferol were associated with the regulation of inflammation, oxidative stress, immunity, virus infection, cell growth process and metabolism. EGFR, interleukin 17 (IL-17), tumor necrosis factor (TNF), hypoxia inducible factor 1 (HIF-1), phosphoinositide 3-kinase/AKT serine/threonine kinase (PI3K/AKT) and Toll-like receptor signaling pathways were identified as the key anti-COVID-19/PF co-occurrence pathways. Conclusion: Kaempferol is a candidate treatment for COVID-19/PF co-occurrence. The underlying mechanisms may be related to the regulation of critical targets (EGFR, SRC, MAPK3, MAPK1, MAPK8, AKT1, RELA, PIK3CA and so on) and EGFR, IL-17, TNF, HIF-1, PI3K/AKT and Toll-like receptor signaling pathways. This study contributes to guiding development of new drugs for COVID-19 and PF comorbidities.

Efficacy and Safety of Dapagliflozin versus Liraglutide in Patients with Overweight or Obesity and Type 2 Diabetes Mellitus: A Randomised Controlled Clinical Trial in Tianjin, China

Objective We aimed to clarify the efficacy of dapagliflozin versus liraglutide in patients with overweight or obesity and type 2 diabetes mellitus (T2DM) at the beginning of the coronavirus disease 2019 (COVID-19) pandemic. Methods T2DM patients with overweight or obesity who visited the Metabolic Disease Management Center at Tianjin Fourth Central Hospital from October 2019 to January 2020 were recruited and randomised to receive dapagliflozin or liraglutide for 24 weeks. Changes in blood glucose and lipid levels, blood pressure, and body weight, as well as the occurrence of hypoglycaemia and other adverse events, were compared. Results 309 patients completed the study (143 in liraglutide group and 166 in dapagliflozin group). After 24 weeks, HbA1c, fasting blood glucose (FPG), and 2 h postprandial blood glucose (2hPG) levels significantly decreased from 8.80% ± 1.41% to 7.02% ± 1.05%, 10.41 ± 3.13 to 7.59 ± 2.16 mmol/L, and 17.90 ± 4.39 to 10.12 ± 2.47 mmol/L, respectively, in the dapagliflozin group, and from 8.92% ± 1.49% to 6.78% ± 1.00%, 10.04 ± 2.99 to 7.20 ± 1.63 mmol/L, and 17.30 ± 4.39 to 10.13 ± 4.15 mmol/L, respectively, in the liraglutide group. Changes in HbA1c, FPG, and 2hPG levels between groups were not significantly different. Systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C) level significantly decreased from 144.1 ± 19.1 to 139.7 ± 16.2 mmHg (p = 0.001) and from 3.21 ± 0.94 to 2.98 ± 0.89 mmol/L (p = 0.014), respectively, in the dapagliflozin group. After COVID-19 outbreak, the number of patients taking sleep-promoting drugs increased from 4.9% to 9.4% (p = 0.029). Conclusions Liraglutide and dapagliflozin had strong hypoglycaemic effects in patients with overweight or obesity and T2DM at the beginning of the COVID-19 pandemic. Dapagliflozin may be beneficial in improving SBP and LDL-C levels;however, further research is warranted.

Modeling Kaempferol as a Potential Pharmacological Agent for COVID-19/PF Co-Occurrence Based on Bioinformatics and System Pharmacological Tools

Objective: People suffering from coronavirus disease 2019 (COVID-19) are prone to develop pulmonary fibrosis (PF), but there is currently no definitive treatment for COVID-19/PF co-occurrence. Kaempferol with promising antiviral and anti-fibrotic effects is expected to become a potential treatment for COVID-19 and PF comorbidities. Therefore, this study explored the targets and molecular mechanisms of kaempferol against COVID-19/PF co-occurrence by bioinformatics and network pharmacology. Methods: Various open-source databases and Venn Diagram tool were applied to confirm the targets of kaempferol against COVID-19/PF co-occurrence. Protein-protein interaction (PPI), MCODE, key transcription factors, tissue-specific enrichment, molecular docking, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to clarify the influential molecular mechanisms of kaempferol against COVID-19 and PF comorbidities. Results: 290 targets and 203 transcription factors of kaempferol against COVID-19/PF co-occurrence were captured. Epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase SRC (SRC), mitogen-activated protein kinase 3 (MAPK3), mitogen-activated protein kinase 1 (MAPK1), mitogen-activated protein kinase 8 (MAPK8), RAC-alpha serine/threonine-protein kinase (AKT1), transcription factor p65 (RELA) and phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) were identified as the most critical targets, and kaempferol showed effective binding activities with the above critical eight targets. Further, anti-COVID-19/PF co-occurrence effects of kaempferol were associated with the regulation of inflammation, oxidative stress, immunity, virus infection, cell growth process and metabolism. EGFR, interleukin 17 (IL-17), tumor necrosis factor (TNF), hypoxia inducible factor 1 (HIF-1), phosphoinositide 3-kinase/AKT serine/threonine kinase (PI3K/AKT) and Toll-like receptor signaling pathways were identified as the key anti-COVID-19/PF co-occurrence pathways. Conclusion: Kaempferol is a candidate treatment for COVID-19/PF co-occurrence. The underlying mechanisms may be related to the regulation of critical targets (EGFR, SRC, MAPK3, MAPK1, MAPK8, AKT1, RELA, PIK3CA and so on) and EGFR, IL-17, TNF, HIF-1, PI3K/AKT and Toll-like receptor signaling pathways. This study contributes to guiding development of new drugs for COVID-19 and PF comorbidities.

Insights into potential mechanisms of asthma patients with COVID-19: A study based on the gene expression profiling of bronchoalveolar lavage fluid.

BACKGROUND: The 2019 novel coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently a major challenge threatening the global healthcare system. Respiratory virus infection is the most common cause of asthma attacks, and thus COVID-19 may contribute to an increase in asthma exacerbations. However, the mechanisms of COVID-19/asthma comorbidity remain unclear. METHODS: The "Limma" package or "DESeq2" package was used to screen differentially expressed genes (DEGs). Alveolar lavage fluid datasets of COVID-19 and asthma were obtained from the GEO and GSV database. A series of analyses of common host factors for COVID-19 and asthma were conducted, including PPI network construction, module analysis, enrichment analysis, inference of the upstream pathway activity of host factors, tissue-specific analysis and drug candidate prediction. Finally, the key host factors were verified in the GSE152418 and GSE164805 datasets. RESULTS: 192 overlapping host factors were obtained by analyzing the intersection of asthma and COVID-19. FN1, UBA52, EEF1A1, ITGB1, XPO1, NPM1, EGR1, EIF4E, SRSF1, CCR5, PXN, IRF8 and DDX5 as host factors were tightly connected in the PPI network. Module analysis identified five modules with different biological functions and pathways. According to the degree values ranking in the PPI network, EEF1A1, EGR1, UBA52, DDX5 and IRF8 were considered as the key cohost factors for COVID-19 and asthma. The H2O2, VEGF, IL-1 and Wnt signaling pathways had the strongest activities in the upstream pathways. Tissue-specific enrichment analysis revealed the different expression levels of the five critical host factors. LY294002, wortmannin, PD98059 and heparin might have great potential to evolve into therapeutic drugs for COVID-19 and asthma comorbidity. Finally, the validation dataset confirmed that the expression of five key host factors were statistically significant among COVID-19 groups with different severity and healthy control subjects. CONCLUSIONS: This study constructed a network of common host factors between asthma and COVID-19 and predicted several drugs with therapeutic potential. Therefore, this study is likely to provide a reference for the management and treatment for COVID-19/asthma comorbidity.

A Practical Strategy for Exploring the Pharmacological Mechanism of Luteolin Against COVID-19/Asthma Comorbidity: Findings of System Pharmacology and Bioinformatics Analysis.

Asthma patients may increase their susceptibility to SARS-CoV-2 infection and the poor prognosis of coronavirus disease 2019 (COVID-19). However, anti-COVID-19/asthma comorbidity approaches are restricted on condition. Existing evidence indicates that luteolin has antiviral, anti-inflammatory, and immune regulation capabilities. We aimed to evaluate the possibility of luteolin evolving into an ideal drug and explore the underlying molecular mechanisms of luteolin against COVID-19/asthma comorbidity. We used system pharmacology and bioinformatics analysis to assess the physicochemical properties and biological activities of luteolin and further analyze the binding activities, targets, biological functions, and mechanisms of luteolin against COVID-19/asthma comorbidity. We found that luteolin may exert ideal physicochemical properties and bioactivity, and molecular docking analysis confirmed that luteolin performed effective binding activities in COVID-19/asthma comorbidity. Furthermore, a protein-protein interaction network of 538 common targets between drug and disease was constructed and 264 hub targets were obtained. Then, the top 6 hub targets of luteolin against COVID-19/asthma comorbidity were identified, namely, TP53, AKT1, ALB, IL-6, TNF, and VEGFA. Furthermore, the enrichment analysis suggested that luteolin may exert effects on virus defense, regulation of inflammation, cell growth and cell replication, and immune responses, reducing oxidative stress and regulating blood circulation through the Toll-like receptor; MAPK, TNF, AGE/RAGE, EGFR, ErbB, HIF-1, and PI3K-AKT signaling pathways; PD-L1 expression; and PD-1 checkpoint pathway in cancer. The possible "dangerous liaison" between COVID-19 and asthma is still a potential threat to world health. This research is the first to explore whether luteolin could evolve into a drug candidate for COVID-19/asthma comorbidity. This study indicated that luteolin with superior drug likeness and bioactivity has great potential to be used for treating COVID-19/asthma comorbidity, but the predicted results still need to be rigorously verified by experiments.

Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients.

Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC50 between 1.2 and 4.3 µM, depending on viruses or cells, and selective index (SI) in 15-83 range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with FNC triphosphate (the active form) concentrated in the thymus and peripheral blood mononuclear cells (PBMC). Treating SARS-CoV-2 infected rhesus macaques with FNC (0.07 mg/kg, qd, orally) reduced viral load, recuperated the thymus, improved lymphocyte profiles, alleviated inflammation and organ damage, and lessened ground-glass opacities in chest X-ray. Single-cell sequencing suggested the promotion of thymus function by FNC. A randomized, single-arm clinical trial of FNC on compassionate use (n = 31) showed that oral FNC (5 mg, qd) cured all COVID-19 patients, with 100% viral ribonucleic acid negative conversion in 3.29 ± 2.22 days (range: 1-9 days) and 100% hospital discharge rate in 9.00 ± 4.93 days (range: 2-25 days). The side-effect of FNC is minor and transient dizziness and nausea in 16.12% (5/31) patients. Thus, FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus, followed by promoted immunity.

Clinical manifestations of blood cell parameters and inflammatory factors in 92 patients with COVID-19.

BACKGROUND: Although there are many COVID-19 case series studies, few studies report the relationship between variations in blood cell parameters and inflammatory factors and disease severity. This study aims to describe the dynamic trends in COVID-19 blood cell parameters and inflammatory factors. METHODS: Ninety-two patients with confirmed COVID-19 at Jingzhou Central Hospital, Hubei Province, China, between January 23, 2020, and April 10, 2020, were enrolled. Epidemiological data, clinical information, and laboratory test results were collected and analyzed. RESULTS: As patient age increased, disease severity increased (P<0.0001). The inflammatory factor C-reactive protein (CRP) showed a gradual increasing trend with disease aggravation. Based on dynamic change graphs, CRP in all patients with severe and critical COVID-19 initially increased and then decreased; however, CRP in patients with a good prognosis did not increase again after the initial decline (<20 mg/L). CRP in patients with a poor prognosis returned to a high level (>50 mg/L) 1 week after the initial decrease and continued to fluctuate at a high level. Lymphocyte count (LYM#) in patients with severe and critical disease was significantly lower (<1×109/L) than that in patients with moderate disease; LYM# was significantly increased 3 weeks after disease onset in patients with a good prognosis (>1×109/L), but patients with a poor prognosis continued to have a low LYM#. CONCLUSIONS: CRP and LYM# showed strong correlation with disease progression, suggesting that these parameters could be used to monitor changes in patient condition.

Clinical characteristics and risk factors for symptomatic venous thromboembolism in hospitalized COVID-19 patients: A multicenter retrospective study.

BACKGROUND: High incidence of asymptomatic venous thromboembolism (VTE) has been observed in severe COVID-19 patients, but the characteristics of symptomatic VTE in general COVID-19 patients have not been described. OBJECTIVES: To comprehensively explore the prevalence and reliable risk prediction for VTE in COVID-19 patients. METHODS/RESULTS: This retrospective study enrolled all COVID-19 patients with a subsequent VTE in 16 centers in China from January 1 to March 31, 2020. A total of 2779 patients were confirmed with COVID-19. In comparison to 23,434 non-COVID-19 medical inpatients, the odds ratios (ORs) for developing symptomatic VTE in severe and non-severe hospitalized COVID-19 patients were 5.94 (95% confidence interval [CI] 3.91-10.09) and 2.79 (95% CI 1.43-5.60), respectively. When 104 VTE cases and 208 non-VTE cases were compared, pulmonary embolism cases had a higher rate for in-hospital death (OR 6.74, 95% CI 2.18-20.81). VTE developed at a median of 21 days (interquartile range 13.25-31) since onset. Independent factors for VTE were advancing age, cancer, longer interval from symptom onset to admission, lower fibrinogen and higher D-dimer on admission, and D-dimer increment (DI) ≥1.5-fold; of these, DI ≥1.5-fold had the most significant association (OR 14.18, 95% CI 6.25-32.18, p = 2.23 × 10-10 ). A novel model consisting of three simple coagulation variables (fibrinogen and D-dimer levels on admission, and DI ≥1.5-fold) showed good prediction for symptomatic VTE (area under the curve 0.865, 95% CI 0.822-0.907, sensitivity 0.930, specificity 0.710). CONCLUSIONS: There is an excess risk of VTE in hospitalized COVID-19 patients. This novel model can aid early identification of patients who are at high risk for VTE.

From COVID-19 to the Common Cold: Novel Host-Targeted, Pan-Respiratory Antiviral Small Molecule Therapeutics (preprint)

Antiviral compounds displaying remarkable features have been identified by an unconventional drug screen and advanced through animal validation. Efficacy is observed against the six viral families causing most human respiratory viral disease, irrespective of strain, including both influenza (FLUV) and SARS-CoV-2, with cell culture EC50 at or below 100 nM. Survival benefit is demonstrated in pigs against another member of family Coronaviridae, porcine epidemic diarrhea virus (PEDV), and shown equally effective in mild and severe disease. Respiratory syncytial virus (RSV) titer is reduced by drug treatment in cotton rats. A substantial barrier to viral resistance is demonstrated for FLUV. Drug resin affinity chromatography (DRAC) reveals a novel drug target: a multi-protein complex (MPC) formed transiently, in an energy-dependent fashion, and composed of host proteins implicated in both viral lifecycles and manipulation of innate immunity. The protein composition of this host MPC is modified upon viral infection, with increase or decrease of some proteins and appearance or complete loss of others. Valosin-containing protein, also known as Transitional endoplasmatic reticulum ATPase (VCP/p97), is present in the target MPC of uninfected cells and significantly increased in both FLUV and CoV infection. SQSTM1/p62, a key regulator of the autophagy pathway of innate immunity whose dysfunction is implicated in cytokine storm, is i) found in the target MPC from uninfected cells, ii) diminished in DRAC eluates by infection, and iii) restored by drug treatment of infected cells. 14-3-3 is one of likely several proteins that comprise the drug-binding site. Advanced compounds with improved pharmacokinetic (PK) properties and lung exposure are approaching criteria for a Target Product Profile. We propose these novel drug targets to comprise a previously unappreciated molecular basis for homeostasis that is modified by viruses to allow exploitation for viral propagation and is restored by treatment with the therapeutic compounds presented. This discovery has transformative implications for treatment of respiratory viral-related disease, applicable to everything from seasonal FLUV to COVID-19 and future novel respiratory viruses, due to the pan-family nature of drug activity and barrier to resistance development.

Red cell distribution width (RDW): a prognostic indicator of severe COVID-19.

BACKGROUND: The global mortality rate for coronavirus disease 2019 (COVID-19) is 3.68%, but the mortality rate for critically ill patients is as high as 50%. Therefore, the exploration of prognostic predictors for patients with COVID-19 is vital for prompt clinical intervention. Our study aims to explore the predictive value of hematological parameters in the prognosis of patients with severe COVID-19. METHODS: Ninety-eight patients who were diagnosed with COVID-19 at Jingzhou Central Hospital and Central Hospital of Wuhan, Hubei Province, were included in this study. RESULTS: The median age of the patients was 59 [28-80] years; the median age of patients with a good prognosis was 56 [28-79] years, and the median age of patients with a poor outcome was 67 [35-80] years. The patients in the poor outcome group were older than the patients in the good outcome group (P<0.05). The comparison of hematological parameters showed that lymphocyte count (Lym#), red blood cells (RBCs), hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) were significantly lower in the poor outcome group than in the good outcome group (P<0.05). Further, the red cell volume distribution width-CV (RDW-CV) and red cell volume distribution width-SD (RDW-SD) were significantly higher in the poor outcome group than in the good outcome group (P<0.0001). Receiver operating characteristic (ROC) curves showed RDW-SD, with an area under the ROC curve (AUC) of 0.870 [95% confidence interval (CI) 0.796-0.943], was the most significant single parameter for predicting the prognosis of severe patients. When the cut-off value was 42.15, the sensitivity and specificity of RDW-SD for predicting the prognosis of severe patients were 73.1% and 80.2%, respectively. Reticulocyte (RET) channel results showed the RET level was significantly higher in critical patients than in moderate patients and severe patients (P<0.05), which may be one cause of the elevated RDW in patients with a poor outcome. CONCLUSIONS: In this study, the hematological parameters of COVID-19 patients were statistically analyzed. RDW was found to be a prognostic predictor for patients with severe COVID-19, and the increase in RET may contribute to elevated RDW.

Examining the effector mechanisms of Xuebijing injection on COVID-19 based on network pharmacology.

BACKGROUND: Chinese medicine Xuebijing (XBJ) has proven to be effective in the treatment of mild coronavirus disease 2019 (COVID-19) cases. But the bioactive compounds and potential mechanisms of XBJ for COVID-19 prevention and treatment are unclear. This study aimed to examine the potential effector mechanisms of XBJ on COVID-19 based on network pharmacology. METHODS: We searched Chinese and international papers to obtain the active ingredients of XBJ. Then, we compiled COVID-19 disease targets from the GeneCards gene database and via literature searches. Next, we used the SwissTargetPrediction database to predict XBJ's effector targets and map them to the abovementioned COVID-19 disease targets in order to obtain potential therapeutic targets of XBJ. Cytoscape software version 3.7.0 was used to construct a "XBJ active-compound-potential-effector target" network and protein-protein interaction (PPI) network, and then to carry out network topology analysis of potential targets. We used the ClueGO and CluePedia plugins in Cytoscape to conduct gene ontology (GO) biological process (BP) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis of XBJ's effector targets. We used AutoDock vina and PyMOL software for molecular docking. RESULTS: We obtained 144 potential COVID-19 effector targets of XBJ. Fourteen of these targets-glyceraldehyde 3-phosphate dehydrogenase (GAPDH), albumin (ALB), tumor necrosis factor (TNF), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 1 (MAPK1), Caspase-3 (CASP3), signal transducer and activator of transcription 3 (STAT3), MAPK8, prostaglandin-endoperoxide synthase 2 (PTGS2), JUN, interleukin-2 (IL-2), estrogen receptor 1 (ESR1), and MAPK14 had degree values > 40 and therefore could be considered key targets. They participated in extracellular signal-regulated kinase 1 and 2 (ERK1, ERK2) cascade, the T-cell receptor signaling pathway, activation of MAPK activity, cellular response to lipopolysaccharide, and other inflammation- and immune-related BPs. XBJ exerted its therapeutic effects through the renin-angiotensin system (RAS), nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), MAPK, phosphatidylinositol-4, 5-bisphosphate 3-kinase (PI3K)-protein kinase B (Akt)-vascular endothelial growth factor (VEGF), toll-like receptor (TLR), TNF, and inflammatory-mediator regulation of transient receptor potential (TRP) signaling pathways to ultimately construct a "drug-ingredient-target-pathway" effector network. The molecular docking results showed that the core 18 effective ingredients had a docking score of less than - 4.0 with those top 10 targets. CONCLUSION: The active ingredients of XBJ regulated different genes, acted on different pathways, and synergistically produced anti-inflammatory and immune-regulatory effects, which fully demonstrated the synergistic effects of different components on multiple targets and pathways. Our study demonstrated that key ingredients and their targets have potential binding activity, the existing studies on the pharmacological mechanisms of XBJ in the treatment of sepsis and severe pneumonia, could explain the effector mechanism of XBJ in COVID-19 treatment, and those provided a preliminary examination of the potential effector mechanism in this disease.

Preliminary study to identify severe from moderate cases of COVID-19 using combined hematology parameters.

BACKGROUND: The third fatal coronavirus is the novel coronavirus (SARS-CoV-2) that causes novel coronavirus pneumonia (COVID-19) which first broke out in December 2019. Patients will develop rapidly if there is no any intervention, so the risk identification of severe patients is critical. The aim of this study was to investigate the characteristics and rules of hematology changes in patients with COVID-19, and to explore the possibility differentiating moderate and severe patients using conventional hematology parameters or combined parameters. METHODS: The clinical data of 45 moderate and severe type patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in Jingzhou Central Hospital from January 23 to February 13, 2020 were collected. The epidemiological indexes, clinical symptoms, and laboratory test results of the patients were retrospectively analyzed. Those parameters with significant differences between moderate and severe cases were analyzed, and the combination parameters with the best diagnostic performance were selected using the linear discriminant analysis (LDA) method. RESULTS: Of the 45 patients with the novel 2019 corona virus (COVID-19) (35 moderate and 10 severe cases), 23 were male and 22 were female, with ages ranging from 16 to 62 years. The most common clinical symptoms were fever (89%) and dry cough (60%). As the disease progressed, white blood cell count (WBC), neutrophil count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), red blood cell distribution width-coefficient of variation (RDW-CV), and red cell volume distribution width-standard deviation (RDW-SD) parameters in the severe group were significantly higher than those in the moderate group (P<0.05); meanwhile, lymphocyte count (Lym#), eosinophil count (Eos#), high fluorescent cell percentage (HFC%), red blood cell count (RBC), hemoglobin (HGB), and hematocrit (HCT) parameters in the severe group were significantly lower than those in the moderate group (P<0.05). For NLR parameter, it's area under the curve (AUC), cutoff, sensitivity and specificity were 0.890, 13.39, 83.3% and 82.4% respectively; meanwhile, for PLR parameter, it's AUC, cutoff, sensitivity and specificity were 0.842, 267.03, 83.3% and 74.0% respectively. The combined parameters of NLR and RDW-SD had the best diagnostic efficiency (AUC =0.938), and when the cutoff value was 1.046, the sensitivity and the specificity were 90.0% and 84.7% respectively, followed by the combined parameter NLR&RDW-CV (AUC =0.923). When the cut-off value was 0.62, the sensitivity and the specificity for distinguishing severe type from moderate cases of COVID-19 were 90.0% and 82.4% respectively. CONCLUSIONS: The combined NLR and RDW-SD parameter is the best hematology index. It may help clinicians to predict the severity of COVID-19 patients and can be used as a useful indicator to help prevent and control the epidemic.

Epidemiological survey on a family aggregation COVID-19 in Y County, Chenzhou City, Hunan / 上海预防医学

Objective To investigate epidemic characteristics of a family aggregation COVID-19, and to provide scientific basis for prevention and control of family aggregation epidemic. Methods] Field epidemiological methods were used to investigate the cases and close contacts of a family aggregation COVID-19 in Y County, Chenzhou City, Hunan Province. Descriptive statistical analysis was used on epidemiological data . The 2019-nCoV nucleic acid was detected by real-time fluorescence quantitative RT-PCR. Results It was found that Ms. Deng was infected with COVID-19 and became the infectious source of the family aggregation epidemic , who had lived in Wuhan Hubei Province. Her boyfriend Mr. Cao became a second-generation case of COVID-19..Another two asymptomatic but infected persons were family members living with Ms.Deng . Conclusion COVID-19 easily spreads within families. The awareness of family members' protection, the education of new coronavirus pneumonia prevention and control in key groups should be strengthened to avoid the occurrence and spread of family aggregation epidemic.