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1.
Critical Care Conference: 42nd International Symposium on Intensive Care and Emergency Medicine Brussels Belgium ; 27(Supplement 1), 2023.
Article in English | EMBASE | ID: covidwho-2318203

ABSTRACT

Introduction: COVID-19 infection is associated with marked inflammatory response and the patients who are admitted to the hospital are at increased risk of developing venous thromboembolism. sRAGE (soluble receptor for advanced glycation end-products) are acutely elevated in host inflammatory response to infections [1]. Fractal dimension ( df), the biomarker of clot microstructure that measures thrombogenicity has shown to be elevated in acute inflammatory conditions such as sepsis and severe sepsis. The aim of the study was to analyse these biomarkers in COVID-19 infection and whether these biomarkers help to predict mortality. Method(s): 120 suspected COVID-19 patients were recruited from the Emergency Department of a tertiary teaching hospital. One patient was excluded because they were anticoagulated, blood samples were taken to perform fractal dimension ( df) and sRAGE. Result(s): When compared to PCR -ve group, 95 patients in the PCR + ve group had significantly elevated sRAGE (p < 0.001), but not df (p = 0.43). When compared to those who survived, sRAGE was significantly elevated (p = 0.01) in 14 patients who died in PCR + ve group, but not df (p = 0.08). No significant correlation existed between sRAGE levels and df in those patients who survived (p = 0.72) or died (p = 0.92). Logistic regression analysis showed that sRAGE and df in combination acted as highly significant predictors of mortality in COVID-19 (p = 0.009) in PCR + ve group. Conclusion(s): COVID-19 patients had a profound inflammatory response as evidenced by significantly elevated sRAGE levels. This inflammatory process was more profound in those who died. The thrombogenicity in COVID-19 patients and those who died with COVID-19 appears to be not significant as measured by df. sRAGE in combination with df can be utilised as significant predictors of mortality in COVID-19 patients.

2.
Topics in Antiviral Medicine ; 31(2):215-216, 2023.
Article in English | EMBASE | ID: covidwho-2314219

ABSTRACT

Background: The rapid emergence of the SARS-CoV-2 Omicron variant that evades many therapies illustrates the need for antiviral treatments with high genetic barriers to resistance. The small molecule PAV-104, identified through a moderate-throughput screen involving cell-free protein synthesis, was recently shown to target a subset of host protein assembly machinery in a manner specific to viral assembly with minimal host toxicity. The chemotype shows broad activity against respiratory viral pathogens, including Orthomyxoviridae, Paramyxoviridae, Adenoviridae, Herpesviridae, and Picornaviridae, with low susceptibility to evolutionary escape. Here, we investigated the capacity of PAV-104 to inhibit SARS-CoV-2 replication in human airway epithelial cells (AECs). Method(s): Dose-dependent cytotoxicity of PAV-104 in Calu-3 cells was determined by MTT assay. Calu-3 cells were infected with SARS-CoV-2 isolate USA-WA1/2020 (MOI=0.01). Primary AECs were isolated from healthy donor lung transplant tissue, cultured at air liquid interface (ALI), and infected with SARS-CoV-2 Gamma, Delta, and Omicron variants (MOI=0.1). SARS-CoV-2 replication was assessed by RT-PCR quantitation of the N gene, immunofluorescence assay (IFA) of nucleocapsid (N) protein, and titration of supernatant (TCID50). Transient co-expression of four SARS-CoV-2 structural proteins (N, M, S, E) to produce virus-like particles (VLPs) was used to study the effect of PAV-104 on viral assembly. Drug resin affinity chromatography was performed to study the interaction between PAV-104 and N. Glycerol gradient sedimentation was used to assess N oligomerization. Total RNA-seq and the REACTOME database were used to evaluate PAV-104 effects on the host transcriptome. Result(s): PAV-104 reached 50% cytotoxicity in Calu-3 cells at 3732 nM (Fig.1A). 50 nM PAV-104 inhibited >99% of SARS-CoV-2 infection in Calu-3 cells (p< 0.01) and in primary AECs (p< 0.01) (Fig.1B-E). PAV-104 specifically inhibited SARS-CoV-2 post entry, and suppressed production of SARS-CoV-2 VLPs without affecting viral protein synthesis. PAV-104 interacted with SARS-CoV-2 N and interfered with N oligomerization. Transcriptome analysis revealed that PAV-104 treatment reversed SARS-CoV-2 induction of the interferon and maturation of nucleoprotein signaling pathways. Conclusion(s): PAV-104 is a pan-respiratory virus small molecule inhibitor with promising activity against SARS-CoV-2 in human airway epithelial cells that should be explored in animal models and clinical studies.

3.
Critical Care Conference: 42nd International Symposium on Intensive Care and Emergency Medicine Brussels Belgium ; 27(Supplement 1), 2023.
Article in English | EMBASE | ID: covidwho-2312261

ABSTRACT

Introduction: COVID-19 pandemic infection has affected over 650 million people with over 6 million deaths. Critically unwell patients are at increased risk of developing invasive fungal infections [1]. The aim of this study was to identify the number of patients admitted to ICU with COVID-19 who developed fungal infections and to compare these patients (fungal group) with those without fungal infections (non-fungal group) to investigate which factors may have contributed to increased risk of infection. Method(s): Retrospective study undertaken in a tertiary teaching hospital ICU. 174 patients admitted with severe COVID-19 infection during March 2020 until May 2021 were included. Result(s): 81(47%) patients developed fungal infections of which 94% had Candida and 6% had Aspergillus infection. Age and smoking history did not appear to be a contributing factor. The nonfungal group had significantly higher body mass index (33 +/- 8 vs 31 +/- 7, p = 0.01). ICU length of stay [23(1-116) vs 8(1-60), p < 0.001], hospital length of stay [30(3-183) vs 15(1-174) +/- 7, p < 0.001], steroid days [10(1-116) vs 4(0-28), p = 0.02] and ventilation days [18(0-120) vs 2(0-55), p < 0.001] were significantly higher in the fungal group. The mortality rate in both groups were similar (51% vs 51.6%). Conclusion(s): Fungal infections are extremely common in COVID- 19 patients admitted to ICU, seen in almost half of patients in this cohort (47%). Longer treatment with corticosteroids appears to increase the risk of developing fungal infections. Increased length of ICU stay, and a greater length of mechanical ventilation significantly increase the risk of fungal infections in COVID-19 patients in intensive care. Fungal infection, however was not associated with increase in mortality.

4.
Journal of the American College of Cardiology ; 81(16 Supplement):S71-S73, 2023.
Article in English | EMBASE | ID: covidwho-2301828

ABSTRACT

Clinical Information Patient Initials or Identifier Number: A Relevant Clinical History and Physical Exam: 47yr old man, suffered a blast injury at the workplace after an O2 tank exploded while he was transferring liquid gas into a tank for welding purposes. The impact has caused him to temporary loss of consciousness. Upon awakening, he had severe chest pain associated with shortness of breath. On examination, superficial partial thickness injury on the chest wall, and lungs: reduced breath sound bi-basally, no murmur heard. BP:106/77mmHg, HR:100/min, SPO2 100% on HFM 15L/min. [Formula presented] [Formula presented] [Formula presented] Relevant Test Results Prior to Catheterization: Serial ECGs were done and showed dynamic changes in the anterior leads Bedside echo before invasive coronary angiograms shows mild LVSD, normal valves, and no pericardial effusion [Formula presented] [Formula presented] Relevant Catheterization Findings: Right radial approach 6F system Opitorque catheter for diagnostic angiogram LMS: smooth LAD: ATO mid LAD, DG1 prox ATO LCx: smooth RCA: smooth Impression: ATO to LAD and Diagonal 1 ( Dual ATO) [Formula presented] [Formula presented] [Formula presented] Interventional Management Procedural Step: Right radial coronary angiogram via 6F system EBU 3.0 engaged with good support Sion blue wired into LAD, export catheter delivered, and aspirated red thrombus Pre-dilated with Sapphire 3 SC 2.5x15mm @ 6-10ATM Flow established in LAD, however, decided to interrogate DG1 as it shows ATO BMW wired into the DG1 and pre-dilated with Sapphire 3 SC 2.0x15mm Noted nonflow limiting dissection and decided to stent DG1 with 2.25x34mm@12ATM, dissection sealed and TIMI III flow established Stented mid LAD with 2.5x30mm @12ATM just before LAD/DG1 bifurcation, then stented proximal LAD with 2.5x 26mm@ 12ATM. Post-dilated LAD with 2.75x15mm@ 14-20ATM TIMI II-III flow IV Tirofiban has been given a loading dose due to a high thrombus burden and sluggish flow [Formula presented] [Formula presented] [Formula presented] Conclusion(s): Myocardial infarction is a rare complication of blunt chest trauma. This case demonstrates how blast shock waves result in the dissection of the coronary vessel leading to total occlusion of the two vessels. It also promotes red thrombus within the coronary vessels. Percutaneous coronary intervention is the most suitable way to treat this condition. Intravascular imaging such as IVUS or OCT would be beneficial to demonstrate the physiology behind this MI and would also be helpful in planning and optimizing the lesions. Unfortunately, intravascular imaging was not used for this patient to reduce procedural time as he was treated during the height of the COVID pandemic.Copyright © 2023

5.
Journal of the Indian Medical Association ; 120(11):29-36, 2022.
Article in English | EMBASE | ID: covidwho-2252082

ABSTRACT

Mucormycosis has emerged as an important fungal infection with high associated mortality rates. Mucormycosis causes devastating angio-invasive fungal infections, primarily in patients with underlying risk factors. The prevalence of mortality associated with invasive Mucormycosis is high (>30-50%), with 90% mortality contributed by disseminated disease. Sudden rise in Mucormycosis cases during the COVID-19 pandemic came as a surprise to all. Lowered immunity due to COVID and associated conditions like diabetes, made the population susceptible to this dreaded disease. This disease led to both increase in morbidity and mortality among the general population. Aim of the Study: To interpret in detail the causes of mortality of patients presenting with COVID Associated Mucormycosis (CAM-19) at AIIMS Patna between May-November, 2021. Material(s) and Method(s): An observational study of all patients who were treated for mucormycosis during the period of May 2021-Nov 2021 in ENT Department, AIIMS, Patna. During the period of study, 219 patients of Rhino-Orbital-Cerebral Mucormycosis (ROCM) were admitted for treatment. Five patients had gone on Leave Against Medical Advice (LAMA). So, 214 patients were included in the study. Result(s): Among the 214 patients, 165 patients were treated surgically through both endoscopic and open approaches along with antifungal therapy management. 41 patients died during the hospital course of the treatment. The mortality rate of ROCM stood at 19.15% in our series. Pulmonary Mucormycosis had high mortality (100%). Diabetes is the most common risk factor. Multiple co-morbidities and extensive intracranial involvement had a strong association with mortality. Conclusion(s): The advanced stage of ROCM was associated with more deaths. Our series mortality rate of 19.15% is lower than most of the other documented mortality rates. Our results support that early aggressive surgical approach, antifungal therapy and multidisciplinary approach has reduced the mortality.Copyright © 2022 Indian Medical Association. All rights reserved.

6.
Journal of Clinical and Diagnostic Research ; 17(2):SC08-SC12, 2023.
Article in English | EMBASE | ID: covidwho-2264845

ABSTRACT

Introduction: The prevalence of obesity among school children in Kerala is on a steady rise. Consumption of food with high glycaemic index, change in sleep patterns, reduced physical activity and the use of screen has been linked to obesity in children. Published literature on this association is scarce from urban Thiruvananthapuram, hence, the present study. Aim(s): To identify the association of various risk factors such as frequency of junk food consumption, dietary preferences, physical activity and daily screen time and weight related disorders among school going children (8-10 years) in Thiruvananthapuram. Material(s) and Method(s): The present cross-sectional case-control study was conducted in one Rural Government School (Venjaramoodu Government Upper Primary School) and one Urban Private School (S.N. Public School, Chenkottukonam) of Thiruvananthapuram, Kerala, India, and enrolled school going children aged 8-10 years with higher than recommended Body Mass Index (BMI) for age as cases, age and gender-matched children with normal BMI as controls. Participants with BMI above 23rd and below 27th adult equivalent for age and gender were considered overweight and those above 27th adult equivalent for age and gender were considered as obese. A structured questionnaire was sent home with the children, and the parents were requested to answer the questions along with written informed consent. Socio-demographic parameters, anthropometric measurements were obtained by trained staff, dietary habits, and details regarding physical activity and screen usage were collected. Variables were categorised according to the standard recommendations by World Health Organisation (WHO) and Indian Association of Paediatrics (IAP). Variables were expressed as frequencies and the tests of significance used were Chi-square test and Odds ratio, to express the strength of association between parameters. A p-value <0.05 was considered statistically significant. Result(s): The mean age of cases and controls was nine years. A total of 708 school children were screened and 352 participants (175 cases and 177 controls) were enrolled in the present study. The BMI of cases was 29.3 kg/m2 and of controls was 20.2 kg/m2. Higher than recommended screen time (p<0.001), more frequent junk food consumption (p<0.001) and lack of physical activity (p<0.001) were found to be significantly associated with obesity and overweight. Dietary preference was not associated with obesity or overweight and obesity and overweight was more common in children studying in private schools (p<0.001). Conclusion(s): Reducing screen time, reducing junk food consumption and increasing physical activity will help in reducing the prevalence of life style diseases among school children. Further evaluation is necessary to determine the factors contributing to the increased prevalence of these disorders in private schools.Copyright © 2023 Journal of Clinical and Diagnostic Research. All rights reserved.

7.
Cardiometry ; - (25):697-702, 2022.
Article in English | Web of Science | ID: covidwho-2226412

ABSTRACT

The world witnessed the biggest pandemic in almost 100 years, the impact of which is felt in all walks of life. It will be early days to predict too many things. But it is essential to foresee the economic impact of COVID-19. In India, which was already in economic turmoil, it remains to be seen how this new blow will affect the economic cycle. The paper attempts to do this in various sectors like agriculture, tourism, and industrial sectors. Secondary data is reviewed for the study. The paper also discusses innovations in this reference, and it also discusses the steps that the country is taking to sustain this situation. It uses estimation techniques for predicting the economic impact in the various sectors. The paper identifies and analyses the various factors that led to the significant disturbance of farming systems and the agricultural sector as a whole following the lockout, using quantitative and qualitative sources of knowledge with an emphasis on the Indian state of Uttar Pradesh, including expert elicitation and a farmer survey. Our research found that a shortage of migrant labor in some regions and a surplus of jobs in others had a significant impact on the April crop, resulting in a decrease in agricultural wages in some communities and an increase in others, as well as significant production losses.

8.
Cardiometry ; - (25):685-696, 2022.
Article in English | Web of Science | ID: covidwho-2226411

ABSTRACT

Objectives: To find the impact of COVID-19 on the sports industry and how the industry will adapt to the changes. Methodology: Secondary data was collected from several websites related to various sports' revenues, broadcasting, and sponsorships. Primary data was collected in the form of public opinion to analyze the change in the coming years. A qualitative method was used for the analysis. Findings: After analyzing the data following results are indicated concerning the changes in the sports industry: a) Sports industry is set to take a massive loss in terms of revenue, b) The public would not attend any sports event until early next year or until a vaccine is developed, whichever is the earliest. Limitations: The limitations of the research could be the revenue data which is likely to change with the resumption of sporting activities. Public opinion might vary as the situation improves, and the idea will differ from one country to another. Application: The study will be helpful for all sports enthusiasts as they would get to know the overall industry scenario and for students who would want to explore the sports industry from the outside.

9.
Cardiometry ; - (25):667-677, 2022.
Article in English | Web of Science | ID: covidwho-2226410

ABSTRACT

The outbreak of the Covid-19 pandemic has created a profound impact on every sector of our life. The most significant effect of this global pandemic is "global lockdown.>> The lockdown has brought many changes in our lifestyle. One of the substantial changes in the usage of network connectivity. Many people have started to work from home, the number of online learning other uses like the OTT, social media, etc., have increased. It's observed that internet traffic has significantly increased by 25%-30%. In this paper, the authors have analyzed the global network connectivity performance concerning the changes in usage. They examined various service providers' or companies' feedback to these unprecedented conditions. The authors used secondary research methodology for quantitative analysis to understand the increase in usage. Also, this pandemic is opening up new opportunities for the service provider as this pandemic is accelerating remote working, so the service provider is going for more and more automation which reduces the field headcount and the cost. Also, operators have started to offer new collaboration apps, video conferencing tools, and learning platforms which open up new business opportunities. Many new businesses have begun to transform their business in digital, which also opens up a unique opportunity.

10.
European Journal of Molecular and Clinical Medicine ; 10(1):3014-3038, 2023.
Article in English | EMBASE | ID: covidwho-2207374

ABSTRACT

Efforts to prevent the transmission of the SARS-CoV-2 infection are critical in light of the ongoing worldwide spread of COVID-19. Recently developed diagnostic tools include CRISPR, IgG tests, spike protein detection, and artificial intelligence. RT-PCR has been replaced with point-of-care assays, which may be performed at the patient's bedside (RT-PCR). All of these options are available to treat the disease: antivirals and other antiparasitic agents, anti-inflammatory medications like interferon or convalescent plasma, monoclonal antibodies like gamma-globulin, and RNAi treatments like mesenchymal stem cell therapy are among the options (ECMO). More than a dozen different types of vaccines are now being tested in clinical studies. Furthermore, breakthrough technologies that are easily deployable and transportable.In addition, vaccination delivery technologies are being developed. The threat of a second wave of infection needs strict and reasonable control mechanisms to keep mortality to a minimal when governments begin to loosen their lockdown tactics. Research into COVID-19's advances in diagnostics and treatment may serve as a platform for future research that can lead to improved containment strategies. Copyright © 2023 Ubiquity Press. All rights reserved.

11.
Journal of Immunology ; 208(1), 2022.
Article in English | Web of Science | ID: covidwho-2201413
12.
2022 IEEE International Conference on Electro Information Technology, eIT 2022 ; 2022-May:242-247, 2022.
Article in English | Scopus | ID: covidwho-1961373

ABSTRACT

Misinformation is always a serious problem for the general public, especially during pandemic. People constantly receive text messages of related coronavirus news and its cures from their smartphones. These health text messages help people update their coronavirus knowledge repeatedly and better manage their health, but some of the messages may mislead people and may even cause a fatal result. This research tries to identify mobile health text misinformation by proposing a self-reconfigurable system, which includes the preprocessing functions (involving lexical analysis, stopword removal, and stemming), a dataflow graph from TensorFlow, and a reconfiguration method for self-improvement. Experiment results show the proposed method significantly improves the accuracy of the mobile health text misinformation detection compared to the one without using self-reconfiguration. However, the results also show the accuracy still has room for improvement. More refinements need to be done before the method could be put into an effective use. © 2022 IEEE.

13.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927906

ABSTRACT

Introduction: The rapid emergence of the SARS-CoV-2 Omicron variant that evades many monoclonal antibody therapies illustrates the need for anti-viral treatments with low susceptibility to evolutionary escape. The small molecule PAV-104, identified through a moderate-throughput screen involving cell-free protein synthesis, was recently shown to target a subset of host protein assembly machinery in a manner specific to viral assembly. This compound has minimal host toxicity, including once daily oral dosing in rats that achieves >200-fold of the 90% effective concentration (EC90) in blood. The chemotype shows broad activity against respiratory viral pathogens, including Orthomyxoviridae, Paramyxoviridae, Adenoviridae, Herpesviridae, and Picornaviridae, with low suceptability to evolutionary escape. We hypothesized that PAV-104 would be active against SARSCoV- 2 variants in human airway epithelial cells. Methods: Airway epithelial cells were differentiated from lung transplant tissue at air-liquid interface (ALI) for four weeks prior to challenge with Alpha (Pango lineage designation B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) SARS-CoV-2 variants. Viral replication was determined by quantitative PCR measurement of the SARS-CoV-2 nucleocapsid (N) gene. Dose-dependent virus inhibition and cytotoxicity of PAV-104 in the Calu-3 airway epithelial cell line was determined by PCR and MTT assay. Student's t-tests were used to evaluate statistical significance. Results: Alpha, Beta, Gamma, and Delta variants of SARS-CoV-2 showed comparable infectivity in human primary airway epithelial cells at ALI (N=3 donors), 47- to 550-fold higher than the parent (USA-WA1/2020) strain. PAV-104 reached 50% cytotoxicity in Calu-3 cells at 240 nM (Fig. 1A). Dose-response studies in Calu-3 cells demonstrated PAV-104 has a 6 nM 50% inhibitory concentration (IC50) for blocking replication of SARS-CoV-2 (USA-WA1/2020) (Fig.1B). In primary cells at ALI from 3 donors tested, there was >99% inhibition of infection by SARS-CoV-2 Gamma variant (N=3, MOI 0.1, P <0.01) with 100 nM PAV-104 (Fig. 1C). Addition of 100 nM PAV-104 2-hours post-infection, but not pre-infection, resulted in >99% suppression of viral replication, indicating a post-entry drug mechanism. PAV-104 bound a small subset of the known allosteric modulator 14-3-3, itself implicated in the interactome of SARS-CoV-2. Conclusion: PAV-104 is a host-targeted, orally bioavailable, pan-viral small molecule inhibitor with promising activity against SARS-CoV-2 variants in human primary airway epithelial cells. (Figure Presented).

14.
Topics in Antiviral Medicine ; 30(1 SUPPL):72, 2022.
Article in English | EMBASE | ID: covidwho-1881043

ABSTRACT

Background: Coronavirus disease 2019 (COVID19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) remains a global health emergency even with effective vaccines and limited FDA-approved therapies. To limit mortality and morbidity across the spectrum of disease, the need for therapeutics remains critical. Galectin9 (gal9) is a beta-galactoside binding protein that modulates cell-cell and cell-matrix interactions. In response to SARS-CoV2 infection, it has been shown that circulating gal9 levels are elevated in patient sera with moderate to severe disease. Additionally, it has been reported that gal9 unexpectedly may competitively bind the host ACE2 receptor, potentially impeding viral entry. Therefore, we hypothesized that early recombinant gal-9 treatment post infection may prevent binding of the virus to susceptible host cells resulting in decreased severity of SARS-CoV2-associated disease. Methods: To determine the therapeutic potential of gal9 for treating COVID19, we infected K18-hACE2 transgenic mice intranasally with 104 particle forming units (PFU) of SARS-CoV2. 6 hours post infection (hpi), mice were treated with a single dose of 30 ug of recombinant human gal9 (rhgal9) or PBS intraperitoneally and subsequently monitored 12 days for morbidity. Subgroups of mice were humanely euthanized at 2 and 5 days pi (dpi) for viral plaque assay, flow cytometry, and protein analysis from lung tissue and bronchial alveolar lavage (BAL). Results: We found that mice treated with rhgal9 during the acute phase of infection exhibit improved survival compared to PBS treated animals (25%, p<0.0001). We found that at 5 dpi, rhgal9 treated mice exhibited enhanced viral clearance in the BAL but not in the lung parenchyma. Additionally, we found increased CD8 T cell (p<0.001) and decreased neutrophil (p<0.05) frequencies in the lung at 5 dpi. Finally, we found that BAL fluid had elevated levels of Type 1 Interferon [IFNa (p<0.01) and IFNb (p<0.01)] at 2 dpi and increased MyD88 proinflammatory cytokines [IL1a (p<0.05), IL1b (p<0.01), TNFa (p<0.05), and MIP1a (p<0.05) at 5 dpi. Conclusion: Our study suggests that rhgal9 treatment may be potentially therapeutic for treating acute COVID19. Our data suggest that rhgal9 treatment in combination with other anti-inflammatory mediators may curtail damaging inflammation associated with SARS-CoV2 disease. Further studies are required to determine the optimal time, combination and duration of treatment pi to effectively target the gal9 pathways.

16.
Topics in Antiviral Medicine ; 30(1 SUPPL):65, 2022.
Article in English | EMBASE | ID: covidwho-1880180

ABSTRACT

Background: Galectin-9 (Gal-9) is a β-galactoside-binding lectin involved in immune regulation and viral immunopathogenesis. Multiple recent reports demonstrate that plasma levels of Gal-9 are elevated in the setting of severe COVID-19 disease. However, a causal role of Gal-9 in SARS-CoV-2 pathology remains to be elucidated. Here, we determined the impact of Gal-9 on SARS-CoV-2 replication and pro-inflammatory signaling in immortalized and primary human airway epithelial cells (AECs). Methods: Dose-dependent cytotoxicity of recombinant human Gal-9 in the Calu-3 AEC line was determined by MTT assay. Calu-3 cells were infected with SARS-CoV-2 isolate USA-WA1/2020 (MOI=0.01). Primary AECs were isolated from healthy donor lung transplant tissue, cultured at air liquid interface (ALI), and infected with SARS-CoV-2 lineage P.1 (MOI=0.1). SARS-CoV-2 replication was assessed by RT-PCR quantitation of the nucleocapsid (N) gene, immunofluorescence assay (IFA) of N protein, and titration of supernatant (TCID50). Viral entry was measured using luciferase activity of VSV-SARS-CoV-2 S-ΔG-Luciferase reporter pseudovirus. ACE2 and TMPRSS2 cell-surface expression were measured by flow cytometry. Pro-inflammatory factors (IL-6, IL-8, and TNFα) were detected by RT-PCR. Total RNA-seq was used to evaluate Gal-9 effects on the host transcriptome. Groups were compared by Student's t-test, and differential expression analyses were performed using DESeq2. Results: Gal-9 reached 50% cytotoxicity in Calu-3 cells at 597 nM. Gal-9 significantly increased SARS-CoV-2 expression (8.1 to 25.5 fold;p<0.0001) and infectious virus release (1.9 to 17.8 fold;p<0.038) in a dose-dependent manner in Calu-3 cells. Pseudovirus entry into Calu-3 cells was enhanced by Gal-9 (2.4 to 5.6 fold;p<0.0016), and the enhanced entry was inhibited by anti-ACE2 antibody (p<0.0027). Cell surface ACE2 and TMPRSS2 expression were unaffected by Gal-9. Gal-9 treatment accelerated virus-induced expression of IL-6, IL-8, and TNFα (p<0.018) in Calu-3 cells. Gal-9 increased SARS-CoV-2 production (p=0.03) and pro-inflammatory factor expression (p<0.05) in primary AECs (N=5 donors). RNA-seq data revealed that Gal-9 significantly induced IL-17, EIF2, IL-8 and IL-6 signaling pathways in the setting of SARS-CoV-2 infection. Conclusion: Gal-9 facilitates SARS-CoV-2 entry, replication, and virus-induced pro-inflammatory signaling in AECs ex vivo. Our data suggest that pharmacologic manipulation of Gal-9 should be explored as a SARS-CoV-2 therapeutic strategy.

17.
2022 International Conference on Decision Aid Sciences and Applications, DASA 2022 ; : 42-46, 2022.
Article in English | Scopus | ID: covidwho-1874176

ABSTRACT

Technological advancements have the potential to help every surgeon to enhance the quality of world-wide surgical care. Robotic surgery is currently at its inception stage but is expected to bloom with parallel advancements in computer science and artificial intelligence. The objective of this paper would be to understand the present and future scope of robotic surgery utilizing AI/ML techniques. The study will revolve around how next-generation surgical robots will be inherent in optimizing a surgeon's skills productively, to achieve the pinnacle of precision during complicated surgical procedures. It will focus on how AI/ML helps in Robotic Spine Surgery, Minimally Invasive Surgery techniques, and ophthalmic surgeries. It will talk about the current limitations of robotic surgery and how with latest technological advancements it will be possible to overcome the shortcomings. © 2022 IEEE.

18.
19.
Critical Care ; 26(SUPPL 1), 2022.
Article in English | EMBASE | ID: covidwho-1793883

ABSTRACT

Introduction: COVID-19 is a severe respiratory disease associated with a marked inflammatory response. Clinical methods of assessing severity of disease, including National Early Warning Score 2 (NEWS2), have been shown to predict severity in COVID-19 [1]. However, little research has been undertaken comparing NEWS2 to underlying inflammatory processes. In this study, we assessed whether inflammatory markers taken at presentation to the Emergency Department could predict and mortality in COVID-19 patients. Methods: Whole blood samples were taken at admission to the emergency department for procalcitonin, fibrinogen, CRP, von Willebrand Factor (vWF), IL-6 and TNFα. NEWS2 was also recorded on admission. Levels of inflammatory markers were retrospectively compared to NEWS2 scores and mortality outcomes. Results: A total of 95 patients positive for COVID-19 were included. NEWS2 values > 5 were associated with higher CRP (131.5 ± 87.9 vs 86.4 ± 106.5, p = 0.03), IL-6 (71.9 ± 111 vs 43.4 ± 99, p = 0.007), and vWF (334.1 ± 83.3 vs 296.3 ± 93.4, p = 0.04). The trend of increasing inflammatory markers was also shown in patients who died, significantly so for IL-6 (44.4 ± 54.97 vs 18.8 ± 48.36, p = 0.035). NEWS2 was also shown to be significantly higher in patients who died (7.8 ± 2.2 vs 4.3 ± 2.8, p = < 0.01). Conclusions: NEWS2 predicted the severity of underlying inflammatory response. All inflammatory markers showed a marked increase with severity and mortality, most significant with IL-6. This suggests NEWS2 and inflammatory markers may predict severity and mortality in COVID-19 patients. Further research is required to evaluate these mechanistic changes in inflammatory response.

20.
Critical Care ; 26(SUPPL 1), 2022.
Article in English | EMBASE | ID: covidwho-1793842

ABSTRACT

Introduction: A significant degree of mortality and morbidity in COVID-19 is due to thromboembolic disease. Changes in coagulation markers have been well described in critically unwell patients on ICU. There is less clear evidence regarding these changes at the time of presentation to the Emergency Department and the progression of disease over time. We sought to investigate how coagulation markers change over the course of COVID-19 infection and whether they might predict disease severity. Methods: Patients were recruited from a single University Teaching Hospital ED at the time of presentation. Those with a positive PCR test were followed up throughout their stay. Rotational thromboelastometry (ROTEM) was performed on arrival, after 24 h, 3-5 days and 7 days, alongside routine haematological and biochemical testing. ROTEM values at each of these time points were analysed, and compared. Length of stay and patient outcome were also recorded for subgroup analysis. The ROTEM parameters selected for analysis were both EXTEM and INTEM Clotting Time (CT), Clot Formation Time (CFT), Maximal Clot Firmness (MCF), Alpha Angle (Alpha) and Maximum Lysis Percentage (ML). This reflects clot formation kinetics, mechanical strength and clot breakdown via both extrinsic and intrinsic pathways. Results: EXTEM (7.64 ± 5.53 vs 11.83 ± 6.30) and INTEM ML (4.69 ± 3.55 vs 9.95 ± 5.22) were significantly reduced in those who died vs patients with a prolonged hospital stay. Over time there were no patterns of change to ROTEM values in any outcome group. Conclusions: Comparisons between groups demonstrated that one distinguishing feature between those who require ICU admission or die of COVID-19 compared with those who survive a prolonged hospital stay to discharge was the extent to which fibrinolysis could occur. Failure to break clots down could be a significant mechanism in the mortality and morbidity of COVID-19.

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