Association studies between COVID-19 and SSc-ILD

Severe COVID-19 patients may develop pulmonary fibrosis, similar to SSc-ILD disease, suggesting a potential link between the two diseases. However, there are limited treatment options for SSc-ILD-type diseases. Therefore, investigating pathological markers of the two diseases can provide valuable insights for treating related conditions. RNA sequencing technology offers high throughput and precision. However, the bimodal nature of RNA-Seq data cannot be accurately captured by commonly used algorithms such as DESeq2. To address this issue, the Beta-Poisson model has been developed to identify differentially expressed genes. Unlike the classical DESeq2 algorithm, the Beta-Poisson model introduces a Beta distribution to construct a new hybrid distribution in place of the Gamma distribution of the Gamma-Poisson distribution, effectively characterizing the bimodal features of RNA-Seq data. The transcriptomes of SARS-CoV infection and SSc-ILD disease in the lung epithelial cell dataset were analyzed to identify common differentially expressed genes of SARS-CoV and SSc-ILD disease. Gene function and signaling pathway enrichment analysis and protein-protein interaction (PPI) network were used to identify common pathways and drug targets for SSc-ILD with COVID-19 infection. The results show that there are 50 differentially expressed genes in common between COVID-19 and SSC-ILD. The functions of these genes are mainly enriched in immune system response, interferon signaling pathway and other related signaling pathways, and enriched in biological processes such as cell defense response to virus and interferon regulation. Based on the detection of hub genes based on PPIs network, it is predicted that STAT1, ISG15, IRF7, MX1, EIF2AK2, DDX58, OAS1, OAS2, IFIT1 and IFIT3 are the key genes involved in the pathological phenotype of the two diseases. Based on the key genes, the interaction of transcription factor (TF) and miRNA with common differentially expressed genes is also identified. The possible pathological markers of the two diseases and related molecular regulatory mechanisms of disease treatment are revealed to provide theoretical basis for the treatment of the two diseases. © 2023 Editorial Office of Journal of Shenzhen University. All rights reserved.

Clinical analysis of liver dysfunction in pregnant patients with mild SARS CoV-2 infection

Objective: The current study aimed to describe the clinical characteristics of mild SARS-CoV-2 infected pregnant women with abnormal liver function (ALF), explore the association between ALF with maternal and fetal outcomes. Method(s): This retrospective analysis included 87 pregnant patients with mild SARS-CoV-2 infection admitted and treated from December 1, 2022, to 31, 2022 in the department of Obestircs at Beijing Obstetrics and Gynecology Hospital. We evaluated patients for demographic and clinical features, laboratory parameters and pregnancy complications. Result(s): 27 Patients in this cohort had clinical presentations of ALF. Compared with the control group, the peripheral blood platelet (PLT), D-dimer quantitative determination (D-Dimer), lactate dehydrogenase (LDH), total protein (TP), albumin (ALB), indirect bilirubin (DBIL), gamma- glutamyltranspeptidase (GGT) and total bile acid (TBA) showed significantly differences (p<0.05). 12 cases (44.44%) complicated with pregnancy induced hypertension (PIH), 14 cases (51.85%) complicated with intrahepatic cholestasis of pregnancy (ICP), 2 cases (7.4%) complicated with acute fatty liver during pregnancy (AFLP) and 5 cases (14.81%) complicated with postpartum hemorrhage in patients with abnormal LFT were significantly higher than those in the control group (p<0.05). Compared with the control group, the incidence of premature delivery (22.22%) and fetal distress (37.04%) in the experiment group were significantly higher (p<0.05), and the incidence of neonatal asphyxia was not significantly different (p>0.05). Conclusion(s): Pregnant women are generally susceptible to mild SARS-CoV-2 and may induce ALF. ALF is associated with increased risk of mother and infant. The maternal and infant outcomes of those who terminated pregnancy in time are acceptable. Therefore, pregnant women with COVID-19 who received antiviral treatment should be closely monitored for evaluating liver function and relevant indicators. The long-term outcomes in the future are worth to further study.Copyright © 2023

COVID-19 virus: the immune reaction to vaccines

The immune system is developed to preserve its hosts from an ever-expanding cluster of pathogenic microbes. The elimination of toxic substances, allergens, or any other harmful existences that come in, passing the mucosal surfaces, is as well the responsibility of this special system. Its ability to distinguish self (our bodies' functioning cells and tissues) from non-self is the key aspect to its ability to mobilize some reaction to an invasion initiated by the stranger substances listed above. To identify and kill unsafe microorganisms, the host applies both natural and versatile systems, our innate and adaptive immune systems. Vaccines are used to combat the current SARS-CoV-2 strain by utilizing immune system mechanisms, specifically the adaptive immune system. Vectored vaccines, protein vaccines, genetic vaccine, and monoclonal antibody for passive vaccination are among the vaccine platforms under consideration for SARS-CoV-2. Each vaccine has its own benefits and drawbacks. This paper is written to describe the three major forms of COVID-19 vaccines, as well as the unique mechanisms of elements of the immune system associated with the virus. © 2023 SPIE.

The Reduction of SARS-CoV-2 RNA Concentration in the Presence of Sewer Biofilms

Wastewater surveillance has been widely used to track the prevalence of SARS-CoV-2 in communities. Although some studies have investigated the decay of SARS-CoV-2 RNA in wastewater, understanding about its fate during wastewater transport in real sewers is still limited. This study aims to assess the impact of sewer biofilms on the dynamics of SARS-CoV-2 RNA concentration in naturally contaminated real wastewater (raw influent wastewater without extra SARS-CoV-2 virus/gene seeding) using a simulated laboratory-scale sewer system. The results indicated that, with the sewer biofilms, a 90% concentration reduction of the SARS-CoV-2 RNA was observed within 2 h both in wastewater of gravity (GS, gravity-driven sewers) and rising main (RM, pressurized sewers) sewer reactors. In contrast, the 90% reduction time was 8–26 h in control reactors without biofilms. The concentration reduction of SARS-CoV-2 RNA in wastewater was significantly more in the presence of sewer biofilms. In addition, an accumulation of c.a. 260 and 110 genome copies/cm2 of the SARS-CoV-2 E gene was observed in the sewer biofilm samples from RM and GS reactors within 12 h, respectively. These results confirmed that the in-sewer concentration reduction of SARS-CoV-2 RNA in wastewater was likely caused by the partition to sewer biofilms. The need to investigate the in-sewer dynamic of SARS-CoV-2 RNA, such as the variation of RNA concentration in influent wastewater caused by biofilm attachment and detachment, was highlighted by the significantly enhanced reduction rate of SARS-CoV-2 RNA in wastewater of sewer biofilm reactors and the accumulation of SARS-CoV-2 RNA in sewer biofilms. Further research should be conducted to investigate the in-sewer transportation of SARS-CoV-2 and their RNA and evaluate the role of sewer biofilms in leading to underestimates of COVID-19 prevalence in communities.

COVID-19: comparison lung CT signs and biochemical parameters in the groups of patients with three-time positive RT-PCR and with triple negative RT-PCR test during the period of hospitalization.

Research goal. Comparative characteristics of the dynamics of CT semiotics and biochemical parameters of two groups of patients: with positive RT-PCR and with triple negative RT-PCR. Reflection of the results by comparing them with the data already available in the literature. The aim of the study is to compare the dynamics of CT semiotics and biochemical parameters of blood tests in two groups of patients: with positive RT-PCR and with triple negative RT-PCR. We also reflect the results by comparing them with the data already available in the literature. Materials and methods. We have performed a retrospective analysis of CT images of 66 patients: group I (n1 = 33) consists of patients who had three- time negative RT-PCR (nasopharyngeal swab for SARS-CoV-2 RNA) during hospitalization, and group II (n2 = 33) includes patients with triple positive RT-PCR. An important selection criterion is the presence of three CT examinations (primary, 1st CT and two dynamic examinations - 2nd CT and 3rd CT) and at least two results of biochemistry (C-reactive protein (CRP), fibrinogen, prothrombin time, procalcitonin) performed in a single time interval of +/- 5 days from 1st CT, upon admission, and +/- 5 days from 3st CT. A total of 198 CT examinations of the lungs were analyzed (3 examinations per patient). Results. The average age of patients in the first group was 58 +/- 14.4 years, in the second - 64.9 +/- 15.7 years. The number of days from the moment of illness to the primary CT scan 6.21 +/- 3.74 in group I, 7.0 (5.0-8.0) in group II, until the 2nd CT scan - 12.5 +/- 4, 87 and 12.0 (10.0-15.0), before the 3rd CT scan - 22.0 (19.0-26.0) and 22.0 (16.0-26.0), respectively. In both groups, all 66 patients (100%), the primary study identified the double-sided ground-glass opacity symptom and 36 of 66 (55%) patients showed consolidation of the lung tissue. Later on, a first follow-up CT defined GGO not in all the cases: it was presented in 22 of 33 (67%) patients with negative RT-PCR (group I) and in 28 of 33 (85%) patients with the positive one (group II). The percentage of studies showing consolidation increased significantly: up to 30 of 33 (91%) patients in group I, and up to 32 of 33 (97%) patients in group II. For the first time, radiological symptoms of "involutional changes" appeared: in 17 (52%) patients of the first group and in 5 (15%) patients of the second one. On second follow-up CT, GGO and consolidations were detected less often than on previous CT: in 1 and 27 patients of group I (3% and 82%, respectively) and in 6 and 30 patients of group II (18% and 91%, respectively), although the consolidation symptom still prevailed significantly . The peak of "involutional changes" occurred on last CT: 31 (94%) and 25 (76%) patients of groups I and II, respectively.So, in the groups studied, the dynamics of changes in lung CT were almost equal. After analyzing the biochemistry parameters, we found out that CRP significantly decreased in 93% of patients (p < 0.001) in group I;in group II, there was a statistically significant decrease in the values of C-reactive protein in 81% of patients (p = 0.005). With an increase in CT severity of coronavirus infection by one degree, an increase in CRP by 41.8 mg/ml should be expected. In group I, a statistically significant (p = 0.001) decrease in fibrinogen was recorded in 77% of patients;and a similar dynamic of this indicator was observed in group II: fibrinogen values decreased in 66% of patients (p = 0.002). Such parameters as procalcitonin and prothrombin time did not significantly change during inpatient treatment of the patients of the studied groups (p = 0.879 and p = 0.135), which may indicate that it is inappropriate to use these parameters in assessing dynamics of patients with a similar course of the disease. When comparing the outcomes of the studied groups, there was a statistically significant higher mortality in group II - 30.3%, in group I - 21.2% (p = 0.043). Conclusion. According to our data, a course of the disease does not significantly differ in the groups o patients with positive RT-PCR and three-time negative RT-PCR. A negative RT-PCR analysis may be associated with an individual peculiarity of a patient such as a low viral load of SARS-CoV-2 in the upper respiratory tract. Therefore, with repeated negative results on the RNA of the virus in the oro- and nasopharynx, one should take into account the clinic, the X-ray picture and biochemical indicators in dynamics and not be afraid to make a diagnosis of COVID-19.Copyright © 2021 ALIES. All rights reserved.

Could platelet mass index (PMI) be a new prognostic biomarker for COVID-19?

Aim: Although most patients with COVID-19 experience respiratory tract infections, severe reactions to the virus may cause coagulation abnormalities that mimic other systemic coagulopathies associated with severe infections, such as disseminated intravascular coagulation and thrombotic microangiopathy. Fluctuations in platelet markers, which are an indicator of the acute phase response for COVID-19, are of clinical importance. The aim of this study is to evaluate the relationship between disease severity and Platelet Mass Index (MPI) parameters in COVID-19 patients. Material(s) and Method(s): This retrospective observational study was conducted with patients who were diagnosed with COVID-19 in a tertiary hospital. The study was continued with the remaining 280 patients. All laboratory data were scanned retrospectively from patient files and hospital information system. Result(s): A very high positive correlation was found between PMI and PLT. The PMI value in women was significantly higher than in men. It was observed that PMI did not differ significantly in terms of mortality, intubation, CPAP and comorbidity. PMI vs. Pneumonia Ct Severity Score, biochemistry parameters (AST, CRP), hemogram parameters (WBC, HGB, HCT, MCV, LYM, MPV EO) and coagulation factors (aPTT and FIB) at various levels of positive/negative, weak and strong, and significant relationship was found. There was no significant relationship between hormone and D-dimer when compared with PMI. Discussion(s): Although platelet count alone does not provide information about the prognosis of the disease, PMI may guide the clinician as an indicator of lung damage in seriously ill patients.Copyright © 2022, Derman Medical Publishing. All rights reserved.

Correlations of interleukin levels with the severity of SARS-CoV-2 coronavirus infection.

A new coronavirus infection caused by the SARS-CoV-2 virus is characterized by a systemic hyperinflammatory response with a pronounced increase in the content of pro-inflammatory cytokines. Materials and methods. The study was conducted on the basis of the Samara Regional Children's Infectious Diseases Hospital from 2021 to 2022. 40 patients with moderate (n = 20, group I) and severe forms (n = 20, group II) COVID-19 were studied, the comparison group consisted of patients with viral pneumonia of another etiology (n = 35, group III). Results. The infectious agent SARS-CoV-2 induces high levels of cytokines IL-6 (p < 0.005), IL-8 (p < 0.05) and a slight increase in TNF-alpha (p < 0.05). IL-8 was significantly associated with disease duration (p < 0.01). We assume that the value of this interleukin will increase in the post-COVID period. Conclusions. Changes in IL-6 and IL-8 levels in patients with COVID-19, along with clinical features, are important biomarkers for predicting the severity and duration of the disease.Copyright © Children Infections.All rights reserved

Mid-density Gene Expression profiling of SARSCOV-2 infected samples using Applied BiosystemsTM TaqManTM Flexible Array Panels

Background/Objectives: The broad spectrum of clinical manifestations from SARS-COV-2 infection and observed risk factors for severe disease highlight the importance of understanding molecular mechanisms underlying SARS-CoV-2 associated disease pathogenesis. Research studies have identified a large number of host proteins that play roles in viral entry, innate immune response, or immune signalling during infection. The ability to interrogate subsets of these genes simultaneously within SARSCOV-2 infected samples is critical to understanding how their expression contribute to phenotypic variability of the disease caused by the pathogen. Method(s): 30 Nasopharyngeal swab were obtained and included SARS-CoV-2 infected and control samples. RNA was extracted, reverse transcribed and loaded onto flexible TaqMan array panels designed specifically for targeting the most cited genes related to SARS-COV-2 entry and restriction factors as well as cytokines, chemokines, and growth factors involved in the pathogenesis. Result(s): Our data indicated that not only were the levels of several of these host factors differentially modulated between the two study groups, but also that SARS-CoV-2 infected subjects presented with greater frequency of several important inflammatory cytokines and chemokines such as CCL2, CCL3, IFNG, entry receptors such as ACE2, TMRPS11A, and host restriction factors including LY6E and ZBP1. Conclusion(s): TaqMan array plates provide a fast, midthroughput solution to determine the levels of several virus and host-associated factors in various cell types and add to our understanding of how the pathogenesis may vary depending on gender, age, infection site etc.

Echocardiographic features of COVID-19 patients without significant baseline cardiovascular disease.

Objective. To assess the relationship between the severity of COVID-19 in patients without significant baseline cardiovascular pathology and various echocardiographic parameters of myocardial dysfunction. Material and methods. 46 patients with COVID-19 were included in our study: 33 patients of moderate severity and 13 - with severe disease. On days 1 and 9 upon admission, all patients underwent an echocardiographic study with standard assessment of the both ventricles function, as well as an assessment of their global longitudinal strain (GLS). Comparison of the studied parameters was carried out both between groups of patients and within each group in dynamics. Results. On day 1patients in the severe group had higher values of the systolic gradient on the tricuspid valve (22.0 [21.0;26.0] vs 30.0 [24.0;34.5] mm Hg, p = 0.02), systolic excursion of the plane of the tricuspid ring (2.3 [2.1;2.4] vs 2.0 [1.9;2.2] mm, p = 0.016), E/e' ratio (9.5 [7.7;8.9] vs 7.5 [6.8;9.3], p = 0.03). At day 9 among patients in the severe group, there was a decrease in end-diastolic (111.0 [100.0;120.0] vs 100.0 [89.0;105.0] ml, p = 0.03) and of end-systolic (35.5 [32.0;41, 2] vs 28.0 [25.0;31.8] ml, p < 0.01) volumes of the left ventricle. There was a decrease in GLS of the both ventricles compared to general accepted values. In dynamics, there was an increase in the GLS of the right ventricle in both groups, but it was more pronounced among severe group of patients (day 1 -18.5 [-15.2;-21.1] vs -20.2 [-15.8.1;-21.1] %, p = 0.03). The troponin levels were in the normal range. Conclusion. In COVID-19 patients without significant baseline cardiovascular pathology, there is a transient decrease in longitudinal strain of both ventricles, even in the absence of clinical and laboratory signs of acute myocardial injury.Copyright © Creative Cardiology 2021.

The SARS-CoV-2 Antibody and Drug Research Based on the Structure of the Spike Protein and the Mechanism of Cell Entry.

COVID-19 is a severe acute respiratory syndrome caused by a novel coronavirus, SARS-CoV- 2.COVID-19 is now a pandemic, and is not yet fully under control.As the surface spike protein (S) mediates the recognition between the virus and cell membrane and the process of cell entry, it plays an important role in the course of disease transmission.The study on the S protein not only elucidates the structure and function of virus-related proteins and explains their cellular entry mechanism, but also provides valuable information for the prevention, diagnosis and treatment of COVII)-19.Concentrated on the S protein of SARS-CoV-2, this review covers four aspects: (1 ) The structure of the S protein and its binding with angiotensin converting enzyme II (ACE2) , the specific receptor of SARS-CoV-2, is introduced in detail.Compared with SARS-CoV, the receptor binding domain (RBD) of the SARS-CoV- 2 S protein has a higher affinity with ACE2, while the affinity of the entire S protein is on the contrary.(2) Currently, the cell entry mechanism of SARS-CoV-2 meditated by the S protein is proposed to include endosomal and non-endosomal pathways.With the recognition and binding between the S protein and ACE2 or after cell entry, transmembrane protease serine 2(TMPRSS2) , lysosomal cathepsin or the furin enzyme can cleave S protein at S1/S2 cleavage site, facilitating the fusion between the virus and target membrane.(3) For the progress in SARS-CoV-2 S protein antibodies, a collection of significant antibodies are introduced and compared in the fields of the target, source and type.(4) Mechanisms of therapeutic treatments for SARS-CoV-2 varied.Though the antibody and medicine treatments related to the SARS-CoV-2 S protein are of high specificity and great efficacy, the mechanism, safety, applicability and stability of some agents are still unclear and need further assessment.Therefore, to curb the pandemic, researchers in all fields need more cooperation in the development of SARS-CoV-2 antibodies and medicines to face the great challenge.Copyright © Palaeogeography (Chinese Edition).All right reserved.

Long-term support of COVID-19 patients with veno-venous extracorporeal membrane oxygenation: Complications, predictors of mortality and long-term outcome

Objectives: Treatment of severe respiratory distress syndrome (ARDS) due to COVID-19 by veno-venous extracorporeal membrane oxygenation (VV-ECMO) had a mortality of up to 70% in Germany. Many patients with COVID-19 need VV-ECMO support longer than 28 days (long-term VV-ECMO). Evidence on mortality, complications during intensive care, functional status after discharge and mortality-predictors for patients supported with long-term VV-ECMO is lacking. Method(s): Retrospective study of 137 consecutive patients treated with VV-ECMO for ARDS due to COVID-19 at University Hospital Regensburg from March 2020 to March 2022. Result(s): 38% (n=52;87% male) of patients needed longterm VV-ECMO support. In these, SOFA score (median [IQR]) at ECMO initiation was 9 [8-11], age 58.2 [50.6- 62.5] years, PaO2/FiO2-ratio 67 [52-88] mmHg, pCO262 [52-74] mmHg, Murray-Score 3.3 [3.0-3.6] and PEEP 15 [13 - 16] cmH2O. Duration of long-term support was 45 [35-65] days. 26 (50%) patients were discharged from the ICU. Only one patient died after hospital discharge. At VVECMO initiation, baseline characteristics did not differ between deceased and survivors. Complications were frequent (acute kidney injury: 31/52, renal replacement therapy: 14/52, pulmonary embolism: 21/52, intracranial hemorrhage 8/52, major bleeding 34/52 and secondary sclerosing cholangitis: 5/52) and more frequent in the deceased. Karnofsky index (normal 100) after rehabilitation was 70 [57.5-82.5]. Twelve of the 18 patients discharged from rehabilitation had a satisfactory quality of life according to their own subjective assessment. Four patients required nursing support. Mortality-predictors within the first 30 days on VV-ECMO only observed in those who deceased later, were: Bilirubin >5mg/dl for > 7 days, pulmonary compliance <10ml/mbar for >14 days, and repeated serum concentrations of interleukin 8 >150ng/L. Conclusion(s): Long-term extracorporeal lung support in patients with COVID-19 resulted in 50 % survival and subsequently lead to a satisfactory quality of life and functionality in the majority of patients. It should preferably be performed in experienced centers because of a high incidence of complications. Several findings during the early course were associated with late mortality but need validation in large prospective studies.

Surface enhanced Raman spectroscopy based analysis of SARS-CoV-2 spike protein binding to ACE2 receptor

The SARS-CoV-2 virus is still a challenge because of its diversity and mutations. The binding interactions of the angiotensin converting enzyme 2 (ACE2) receptor and the spike protein are relevant for the SARS-CoV-2 virus to enter the cell. Consequently, it is important and helpful to analyze binding activities and the changes in the structure of the ACE2 receptor and the spike protein. Surface enhanced Raman spectroscopy is able to analyze small concentrations of the proteins without contact, non-invasively and label-free. In this work, we present a SERS based approach in the visible wavelength range to analyze and study the binding interactions of the ACE2 receptor and the spike protein. SERS measurements of the ACE2 receptor, the spike protein and the ACE2-spike complex were performed. Additionally, an inhibitor was used to prevent the spike protein from binding to ACE2 and to compare the results. The analysis of the measured SERS spectra reveals structural differences and changes due to binding activities. Thus, we show that the performed SERS based approach can help for rapid and non-invasive analysis of binding interactions of the ACE2-spike complex and also of protein binding in general. © 2023 SPIE.

Persistent Topological Laplacian Analysis of SARS-CoV-2 Variants

Topological data analysis (TDA) is an emerging field in mathematics and data science. Its central technique, persistent homology, has had tremendous success in many science and engineering disciplines. However, persistent homology has limitations, including its inability to handle heterogeneous information, such as multiple types of geometric objects;being qualitative rather than quantitative, e.g., counting a 5-member ring the same as a 6-member ring, and a failure to describe nontopological changes, such as homotopic changes in protein–protein binding. Persistent topological Laplacians (PTLs), such as persistent Laplacian and persistent sheaf Laplacian, were proposed to overcome the limitations of persistent homology. In this work, we examine the modeling and analysis power of PTLs in the study of the protein structures of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor binding domain (RBD). First, we employ PTLs to study how the RBD mutation-induced structural changes of RBD-angiotensin-converting enzyme 2 (ACE2) binding complexes are captured in the changes of spectra of the PTLs among SARS-CoV-2 variants. Additionally, we use PTLs to analyze the binding of RBD and ACE2-induced structural changes of various SARS-CoV-2 variants. Finally, we explore the impacts of computationally generated RBD structures on a topological deep learning paradigm and predictions of deep mutational scanning datasets for the SARS-CoV-2 Omicron BA.2 variant. Our results indicate that PTLs have advantages over persistent homology in analyzing protein structural changes and provide a powerful new TDA tool for data science. [ FROM AUTHOR] Copyright of Journal of Computational Biophysics & Chemistry is the property of World Scientific Publishing Company and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Fast de novo antibody structure prediction with atomic accuracy

Background: In the field of antibody engineering, an essential task is to design a novel antibody whose paratopes bind to a specific antigen with correct epitopes. Understanding antibody structure and its paratope can facilitate a mechanistic understanding of its function. Therefore, antibody structure prediction from its sequence alone has always been a highly valuable problem for de novo antibody design. AlphaFold2 (AF2), a breakthrough in the field of structural biology, provides a solution to this protein structure prediction problem by learning a deep learning model. However, the computational efficiency and undesirable prediction accuracy on antibody, especially on the complementarity-determining regions limit its applications in de novo antibody design. Method(s): To learn informative representation of antibodies, we trained a deep antibody language model (ALM) on curated sequences from observed antibody space database via a well-designed transformer model. We also developed a novel model named xTrimoABFold++ to predict antibody structure from antibody sequence only based on the pretrained ALM as well as efficient evoformers and structural modules. The model was trained end-to-end on the antibody structures in PDB by minimizing the ensemble loss of domain-specific focal loss on CDR and the frame aligned point loss. Result(s): xTrimoABFold++ outperforms AF2 and OmegaFold, HelixFold-Single with 30+% improvement on RMSD. Also, it is 151 times faster than AF2 and predicts antibody structure in atomic accuracy within 20 seconds. In recently released antibodies, for example, cemiplimab of PD1 (PDB: 7WVM) and cross-neutralizing antibody 6D6 of SARS-CoV-2 (PDB: 7EAN), the RMSD of xTrimoABFold++ are 0.344 and 0.389 respectively. Conclusion(s): To the best of our knowledge, xTrimoABFold++ achieved the state-of-the-art in antibody structure prediction. Its improvement on both accuracy and efficiency makes it a valuable tool for de novo antibody design, and could make further improvement in immuno-theory.

The preventive effect and mechanism of Dayuanyin in hypoxic pulmonary hypertension through NF-kappaB signaling pathway.

Dayuanyin (DYY) has been shown to reduce lung inflammation in both coronavirus disease 2019 (COVID-19) and lung injury. This experiment was designed to investigate the efficacy and mechanism of action of DYY against hypoxic pulmonary hypertension (HPH) and to evaluate the effect of DYY on the protection of lung function. Animal welfare and experimental procedures are approved and in accordance with the provision of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Science. Male C57/BL6J mice were randomly divided into 4 groups: control group, model group, DYY group (800 mg.kg-1), and positive control sildenafil group (100 mg.kg-1). The animals were given control solvents or drugs by gavage three days in advance. On day 4, the animals in the model group, DYY group and sildenafil group were kept in a hypoxic chamber containing 10% +/- 0.5% oxygen, and the animals in the control group were kept in a normal environment, and the control solvent or drugs continued to be given continuously for 14 days. The right ventricular systolic pressure, right ventricular hypertrophy index, organ indices and other metrics were measured in the experimental endpoints. Meantime, the expression levels of the inflammatory factors in mice lung tissues were measured. The potential therapeutic targets of DYY on pulmonary hypertension were predicted using network pharmacology, the expression of nuclear factor kappa B (NF- kappaB) signaling pathway-related proteins were measured by Western blot assay. It was found that DYY significantly reduced the right ventricular systolic pressure, attenuated lung injury and decreased the expression of inflammatory factors in mice. It can also inhibit hypoxia-induced activation of NF- kappaB signaling pathway. DYY has a protective effect on lung function, as demonstrated by DYY has good efficacy in HPH, and preventive administration can slow down the disease progression, and its mechanism may be related to inhibit the activation of NF-kappaB and signal transducer and activator of transcription 3 (STAT3) by DYY.Copyright © 2023, Chinese Pharmaceutical Association. All rights reserved.

Study on potential common action and mechanism of Reduning Injection against SARS, MERS and COVID-19 based on network pharmacology and molecular docking technology.

Objective To explore the potential common mechanism and active ingredients of Reduning Injection against SARS, MERS and COVID-19 through network pharmacology and molecular docking technology. Methods The TCMSP database was used to retrieve the chemical components and targets of Artemisiae Annuae Herba, Lonicerae Japonicae Flos and Gardeniae Fructus in Reduning Injection. The gene corresponding to the target was searched by UniProt database, and Cytoscape 3.8.2 was used to build a medicinal material-compound-target (gene) network. Three coronavirus-related targets were collected in the Gene Cards database with the key words of "SARS""MERS" and "COVID-19", and common target of three coronavirus infection diseases were screened out through Venny 2.1.0 database. The common targets of SARS, MERS and COVID-19 were intersected with the targets of Reduning Injection, and the common targets were selected as research targets. Protein-protein interaction (PPI) network map were constructed by Cytoscape3.8.2 software after importing the common targets into the STRING database to obtain data. R language was used to carry out GO biological function enrichment analysis and KEGG signaling pathway enrichment analysis, histograms and bubble charts were drew, and component-target-pathway network diagrams was constructed. The key compounds in the component-target-pathway network were selected for molecular docking with important target proteins, novel coronavirus (SARS-CoV-2) 3CL hydrolase, and angiotensin-converting enzyme II (ACE2). Results 31 active compounds and 207 corresponding targets were obtained from Reduning Injection. 2 453 SARS-related targets, 805 MERS-related targets, 2 571 COVID-19-related targets, and 786 targets for the three diseases. 11 common targets with Reduning Injection: HSPA5, CRP, MAPK1, HMOX1, TGFB1, HSP90AA1, TP53, DPP4, CXCL10, PLAT, PRKACA. GO function enrichment analysis revealed 995 biological processes (BP), 71 molecular functions (MF), and 31 cellular components (CC). KEGG pathway enrichment analysis screened 99 signal pathways (P < 0.05), mainly related to prostate cancer, fluid shear stress and atherosclerosis, hepatocellular carcinoma, proteoglycans in cancer, lipid and atherosclerosis, human T-cell leukemia virus 1 infection, MAPK signaling pathway, etc. The molecular docking results showed that the three core active flavonoids of quercetin, luteolin, and kaempferol in Reduning Injection had good affinity with key targets MAPK1, PRKACA, and HSP90AA1, and the combination of the three active compounds with SARS-CoV-2 3CL hydrolase and ACE2 was less than the recommended chemical drugs. Conclusion Reduning Injection has potential common effects on the three diseases of SARS, MERS and COVID-19. This effect may be related to those active compounds such as quercetin, luteolin, and kaempferol acting on targets such as MAPK1, PRKACA, HSP90AA1 to regulate multiple signal pathways and exert anti-virus, suppression of inflammatory storm, and regulation of immune function.Copyright © 2022 Drug Evaluation Research. All rights reserved.

Fulminant varicella infection complicated by disseminated intravascular coagulation following influenza-A case report

Objectives: Varicella is common infectious disease mainly in childhood, usually is a mild, self-limited illness and complications are usually rare. The incubation period for this disease is generally 14- 16 days but may vary from 7 to 21 days. Varicella in the adults with comorbidities or immunosuppressed children may be severe and prolonged with complications. Method(s): A case report of a 6-year-old girl hospitalized for new-onset manifestations of disseminated vesicular exanthema, the manifestations of which occurred mainly on the chest, back, capillitium, oral cavity, and genital area. The child was suffering from abdominal, knee and lumbosacral pain at that time. The patient's history revealed that 10 days prior to the cutaneous manifestations, she had influenza with bronchopneumonia requiring oxygen therapy, steroids and antibiotics. Result(s): The condition progressed within 48 h, complicated by the development of multi-organ failure, coagulopathy with the development of disseminated intravascular coagulopathy over the course of antiviral, antibiotic and antifungal therapy. Laboratory parameters included high elevation of C-reactive protein, il-6, leukocytosis, neutrophilia and highly elevated liver enzymes. Varicella infection was confirmed by detection of herpes zoster virus - polymerase chain reaction (PCR) from vesicles. The patient received intravenous immunoglobulin therapy at a dose of 2 g/L and fresh frozen plasma, thrombocyte concentrate. The girl was intubated with analogization. Laboratory parameters subsequently revealed high anti CoV-2 positivity, high CoV-2 IgG positivity and negative CoV-2 IgM. The patient's condition did not preclude the course of multisystem inflammatory syndrome in children (MIS-C) corticosteroids were added to the treatment at a dose of 1 mg/kg weight. Patient's condition stabilized after 1 month. Discussion(s): Our case report presents an example of fulminant complicated life-threatening course of varicella. Even in common respiratory infections, we must think about the risk and consequences of coinfections and post-infectious complications such as in our case especially influenza and COVID-19.

SARS-COV-2 Infection in Children and Young People in Bulgaria - A Prospective, Single-Center, Cohort Study

Compared to other respiratory viruses, the proportion of hospitalizations due to SARS-CoV-2 among children is relatively low. While severe illness is not common among children and young individuals, a particular type of severe condition called multisystem inflammatory syndrome in children (MIS-C) has been reported. The aim of this prospective cohort study, which followed a group of individuals under the age of 19, was to examine the characteristics of patients who had contracted SARS-CoV-2, including their coexisting medical conditions, clinical symptoms, laboratory findings, and outcomes. The study also aimed to investigate the features of children who met the WHO case definition of MIS-C, as well as those who required intensive care. A total of 270 patients were included between March 2020 and December 2021. The eligible criteria were individuals between 0-18 with a confirmed SARS-CoV-2 infection at the Infectious Disease Hospital "Prof. Ivan Kirov"in Sofia, Bulgaria. Nearly 76% of the patients were <= 12 years old. In our study, at least one comorbidity was reported in 28.1% of the cases, with obesity being the most common one (8.9%). Less than 5% of children were transferred to an intensive care unit. We observed a statistically significant difference in the age groups, with children between 5 and 12 years old having a higher likelihood of requiring intensive care compared to other age groups. The median values of PaO2 and SatO2 were higher among patients admitted to the standard ward, while the values of granulocytes and C-reactive protein were higher among those transferred to the intensive care unit. Additionally, we identified 26 children who met the WHO case definition for MIS-C. Our study data supports the evidence of milder COVID-19 in children and young individuals as compared to adults. Older age groups were associated with higher incidence of both MIS-C and ICU admissions.Copyright © 2023 P. Velikov et al., published by Sciendo.