Correlation between glycocalyx and diseases, and progress in its degradation mechanism

With the burgeoning development of glycobiology, a growing body of research shows a significant relationship between the development of various diseases and polysaccharides. Glycocalyx, an important component of the vascular endothelium, has a villi-like structure and plays a highly crucial role in maintaining vascular homeostasis. In-depth multidisciplinary studies have further revealed that the biological functions of glycocalyx are not only limited to vascular homeostasis, but are also closely related to various diseases in vivo. Foundations of glycocalyx composition and biological function, this paper reviews the latest research of glycocalyx biodegradation mechanism from the perspective of biological relevance of glycocalyx main components [heparan sulfate (HS), chondroitin sulfate (CS), hyaluronic acid (HA) and core protein] to cancer, corona virus disease 2019 (COVID-19), trauma surgery and other diseases by visualization and molecular biology experimental methods, and intends to provide new thoughts for clinical development of novel diagnostic methods and therapeutic targets.

`Development of a rapid neutralizing antibody test for SARS-CoV-2 and its application for neutralizing antibody screening and vaccinated serum testing

Background : Since the outbreak of coronavirus disease (COVID-19), the high infection rate and mutation frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent, have contributed to the ongoing global pandemic. Vaccination has become the most effective means of controlling COVID-19. Traditional neutralizing tests of sera are complex and labor-intensive, therefore, a rapid test for detecting neutralizing antibodies and antibody status post-immunization is needed. Methods : Based on the fact that antibodies exhibit neutralizing activity by blocking the binding of the S protein receptor-binding domain (S-RBD) to ACE2, we developed a rapid neutralizing antibody test, ACE2-Block-ELISA. To evaluate the sensitivity and specificity, we used 54 positive and 84 negative serum samples. We also tested the neutralizing activities of monoclonal antibodies (mAbs) and 214 sera samples from healthy individuals immunized with the inactivated SARS-CoV-2 vaccine. Results : The sensitivity and specificity of the ACE2-Block ELISA were 96.3% and 100%, respectively. For neutralizing mAb screening, ch-2C5 was selected for its ability to block the ACE2–S-RBD interaction. A plaque assay confirmed that ch-2C5 neutralized SARS-CoV-2, with NT50 values of 4.19, 10.63, and 1.074 μg/mL against the SARS-CoV-2 original strain, and the Beta and Delta variants, respectively. For the immunized sera samples, the neutralizing positive rate dropped from 82.14% to 32.16% within 4 months post-vaccination. Conclusions : This study developed and validated an ACE2-Block-ELISA to test the neutralizing activities of antibodies. As a rapid, inexpensive and easy-to-perform method, this ACE2-Block-ELISA has potential applications in rapid neutralizing mAb screening and SARS-CoV-2 vaccine evaluation.

An integrated interval type-2 fuzzy technique for democratic-autocratic multi-criteria decision making

This paper develops an integrated trapezoidal interval type-2 fuzzy (TrIT2F) technique for democratic-autocratic multi-criteria group decision making based on best-worst method (BWM) and VIKOR (VIsekriterijumska optimizacija i KOm-promisno Resenje), which is called TrIT2F-BW-VIKOR. In this technique, the pairwise comparisons and evaluations are represented by trapezoidal interval type-2 fuzzy sets (TrIT2FSs). The existing definition of TrIT2FS is perfected by adding two rational constraints proposed in this paper. A weight-normalizing theorem is initiated to normalize the TrIT2F weights. To determine the TrIT2F weights of junior decision makers (JDMs) and criteria, the classical BWM is extended into TrIT2F environment, which is called TrIT2F-BWM. In this TrIT2F-BWM, the weight-normalizing theorem is applied to normalize the TrIT2F weights, a consistency ratio is designed to check the reliability of the obtained TrIT2F weights. Based on the determined weights of JDMs and criteria, an extended VIKOR is developed to rank alternatives. The proposed technique can not only effectively retain the inherent fuzzy information of TrIT2FSs, but also flexibly handle different decision situations. The validity of the proposed technique is demonstrated with a makeshift (fangcang) hospital selection example on COVID-19. Some sensitivity and comparison analyses are provided to show the stability, flexibility, and superiorities of the proposed technique.

Cardiac Troponin T as the Underlying Risk Factor Associated With Disease Severity and Mortality in Patients With Coronavirus Disease 2019 (preprint)

Backgrounds: To describe the clinical characteristics of coronavirus disease 2019 hospitalized patients and further analyze the potential risk factors related to the severity of the disease and 28-day mortality of patients.Methods: A total of 122 coronavirus disease 2019 patients hospitalized in Wuhan Third Hospital from 26 January 2020 to 16 March 2020 were included in this retrospective study. Clinical data of patients were retrospectively analyzed, and the risk factors associated with disease severity and 28-day mortality were screened by cox regression analysis.Results: Of all 122 patients, the median age was 64 years old (interquartile range, 57- 71 years old).Compared with non-severe patients, severe patients had higher indices like cardiac troponin T and respiratory rate. In cox regression analysis, cardiac troponin T correlated with 28-day mortality most.Conclusions: Abnormal cardiac troponin T value after admission were in strong correlation with 28-day survival status.

Risk Factors Related to Weight Gain for Chines During Home Confinement in COVID-19 Pandemic: An Observational Retrospective Study (preprint)

Objective: The observational study was intended to explore the weight changes and risk factors of weight gain during the self-quarantine and find available methods to lose weight. Method: This was an online retrospective observational study investigating the weight changes before and after home confinement. A total of 530 participants completed the online questionnaire. diet, sleep, self-reported depression, disease history and exercise information possibly relating to weight changes were incorporated into the questionnaire. The differences among four groups (underweight, normal weight, overweight and obesity) in BMI change and weight change were compared, and the risk factors of weight gain was also analyzed by multiple linear regression analysis. Result: Participants were mostly between 21-50 years old, getting an average weight change of 0.82±3.31kg, and an average BMI change of 0.35 [-0.37, 1.00]. 43.77% of them gained weight by 2.99±2.29kg averagely. People with normal weight were easier to gain weight than obese group (p=0.001). There were differences in food intake (p<0.001), eating habits(p<0.001), taste preference (p=0.047), daily exercise step change(p=0.007), exercise (p=0.02) between non-weight gain group and weight gain group. The multiple linear regression revealed that weight gains were associated with sex (p=0.002), food intake (p=0.004), current daily exercise step (p=0.009) and self-reported depression (p=0.002) and weight loss was related to food intake (p=0.004) and pre-BMI (p=0.001). Conclusion: Eating irregularly, increasing food intake, self-reported depression and decreased daily steps were risk factors of weight gain, yet weight loss was related to decreased food intake and pre-BMI.

CT scores predict mortality in 2019-nCoV pneumonia (preprint)

Background: While 2019-nCoV nucleic acid swab tests has high false positives rate, How to diagnose 2019-nCoV pneumonia and predict prognosis by CT is very important. Methods: In this retrospective single-center study, we consecutively included suspected 2019-nCoV pneumonia critical cases in the intensive care unit of Wuhan third hospital from January 31, 2020 to February 16, 2020. The cases were confirmed by real-time RT-PCR, and all patients were evaluated with CT, cutoff values were obtained according to the Yoden index, and were divided into high CT score group and low CT score group. Epidemiological, demographic, clinical, and laboratory data were collected. Results: The major imaging feature of 2019-nCoV pneumonia is the ground glass opacity (GGO). Multivariate regression analysis found that CT score and absolute count of lymphocytes were independent risk factor for death, and CT score predicted mortality AUC-ROC =0.7, cutoff=1.45. When the absolute count of lymphocytes decreased, the patient's CT also deteriorated. Conclusion: CT score and absolute count of lymphocytes were independent risk factor for death, and patients with high CT score may have a worse prognosis. Lower absolute count of lymphocytes may indicated the patient's CT also deteriorated.

Correlation Analysis Between Disease Severity and Inflammation-related Parameters in Patients with COVID-19 Pneumonia (preprint)

Aim: The new coronavirus pneumonia (COVID-19) outbreaking at the end of 2019 is highly contagious. Crude mortality rate reached 49% in critical patients. Inflammation matters on disease progression. This study analyzed blood inflammation indicators among mild, severe and critical patients, helping to identify severe or critical patients early. Methods: In this cross-sectional study, 100 patients were included and divided to mild, severe or critical groups. Correlation of peripheral blood inflammation-related indicators with disease criticality was analyzed. Cut-off values for critically ill patients were speculated through the ROC curve. ResultsSignificantly, disease severity were associated with age (R=-0.564, P<0.001), interleukin-2 receptor (IL2R) (R=-0.534, P<0.001), interleukin-6 (IL-6) (R=-0.535, P<0.001), interleukin-8 (IL-8) (R=-0.308, P<0.001), interleukin-10 (IL-10) (R=-0.422, P<0.001), tumor necrosis factor (TNF) (R=-0.322, P<0.001), C-reactive protein (CRP) (R=-0.604, P<0.001), ferroprotein (R=-0.508, P<0.001), procalcitonin (R=-0.650, P<0.001), white cell counts (WBC) (R=-0.54, P<0.001), lymphocyte counts (LC) (R=-0.56, P<0.001), neutrophil count (NC) (R=-0.585, P<0.001) and eosinophil counts (EC) (R=-0.299, P=0.01). ConclusionWith following parameters such as age >67.5 years, IL2R >793.5U/mL, CRP >30.7ng/mL, ferroprotein >2252g/L, WBC>9.5*10^9/L or NC >7.305*10^9/L, the progress of COVID-19 to critical stage should be closely observed and possibly prevented. Inflammation is closely related to severity of COVID-19, and IL-6, TNF and IL-8 might be promising therapeutic targets.

A pneumonia outbreak associated with a new coronavirus of probable bat origin.

Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats^1-4. Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans^5-7. Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor-angiotensin converting enzyme II (ACE2)-as SARS-CoV.

Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin (preprint)

Since the SARS outbreak 18 years ago, a large number of severe acute respiratory syndrome related coronaviruses (SARSr-CoV) have been discovered in their natural reservoir host, bats1-4. Previous studies indicated that some of those bat SARSr-CoVs have the potential to infect humans5-7. Here we report the identification and characterization of a novel coronavirus (nCoV-2019) which caused an epidemic of acute respiratory syndrome in humans, in Wuhan, China. The epidemic, started from December 12th, 2019, has caused 198 laboratory confirmed infections with three fatal cases by January 20th, 2020. Full-length genome sequences were obtained from five patients at the early stage of the outbreak. They are almost identical to each other and share 79.5% sequence identify to SARS-CoV. Furthermore, it was found that nCoV-2019 is 96% identical at the whole genome level to a bat coronavirus. The pairwise protein sequence analysis of seven conserved non-structural proteins show that this virus belongs to the species of SARSr-CoV. The nCoV-2019 virus was then isolated from the bronchoalveolar lavage fluid of a critically ill patient, which can be neutralized by sera from several patients. Importantly, we have confirmed that this novel CoV uses the same cell entry receptor, ACE2, as SARS-CoV.