From Bench Side to Bed-Travelling on a Road to Get a Safe and Effective Vaccine Against COVID-19, Day to Save the Life

: Coronavirus Disease 2019 (COVID-19) is caused by a new strain of coronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). It is the most challenging pandemic of this century. The growing COVID-19 pandemic has triggered extraordinary efforts to restrict the virus in numerous ways, owing to the emergence of SARS-CoV-2. Immunotherapy, which includes artificially stimulating the immune system to generate an immunological response, is regarded as an effective strategy for preventing and treating several infectious illnesses and malignancies. Given the pandemic's high fatality rate and quick expansion, an effective vaccination is urgently needed to keep it under control. The basic goal of all COVID-19 vaccine programs is to develop a vaccine that causes the generation of surface protein neutralizing antibodies in subjects. The epitope discovery for the SARS-CoV-2 vaccine candidates is likewise made using an immuno-informatics methodology. It can be used to find the epitopes in viral proteins important for cytotoxic T cells and B cells. A safe and effective COVID-19 vaccine that can elicit the necessary immune response is necessary to end the epidemic. The global search for a safe and effective COVID-19 vaccine is yielding results. More than a dozen vaccines have already been approved around the world, with many more in the clinical trials. Patents can cover the underlying technology used to generate a vaccine, whereas trade secrets can cover manufacturing methods and procedures.

Parallel extreme gradient boosting classifier for lung cancer detection

Most lung cancers do not cause symptoms until the disease is in its later stage. That led the lung cancer having a high fatality rate compared to other cancer types. Many scientists try to use artificial intelligence algorithms to produce accurate lung cancer detection. This paper used extreme gradient boosting (XGBoost) models as a base model for its effectiveness. It enhanced lung cancer detection performance by suggesting three stages model; feature stage, XGBooste parallel stage and selection stage. This study used two types of gene expression datasets; RNA-sequence and microarray profiles. The results presented the effectiveness of the proposed model, especially in dealing with imbalanced datasets, by having 100% each of sensitivity, specificity, precision, F1_score, area under curve (AUC), and accuracy metrics when it applied on all of the datasets used in this study.

Epidemiological Characterization and the Impact of Healthcare-Associated Pneumonia in Patients Admitted in a Northern Portuguese Hospital

Pneumonia is one of the main causes of hospitalization and mortality. It’s the fourth leading cause of death worldwide. Healthcare-associated infections are the most frequent complication of healthcare and affect hundreds of millions of patients around the world, although the actual number of patients affected is unknown due to the difficulty of reliable data. The main goal of this manuscript is to describe the epidemiological characteristics of patients admitted with pneumonia and the impact of healthcare-associated pneumonia (HCAP) in those patients. It is a quantitative descriptive study with retrospective analysis of the clinical processes of 2436 individuals for 1 year (2018) with the diagnosis of pneumonia. The individuals with ≤5 years old represented 10.4% (n = 253) and ≥65 were 72.6% (n = 1769). 369 cases resulted in death, which gives a sample lethality rate of 15.2%. The severity and mortality index were not sensitive to the death event. We found 30.2% (n = 735) individuals with HCAP and 0.41% (n = 59) with ventilator-associated pneumonia (VAP). In only 59 individuals (2.4%) the agent causing pneumonia was isolated. The high fatality rate obtained shows that pneumonia is a major cause of death in vulnerable populations. Moreover, HCAP is one of the main causes of hospital admissions from pneumonia and death and the most pneumonias are treated empirically. Knowledge of the epidemiology characterization of pneumonia, especially associated with healthcare, is essential to increase the skills of health professionals for the prevention and efficient treatment of pneumonia.

Nucleoside-modified mRNA vaccines protect IFNAR -/- mice against Crimean Congo hemorrhagic fever virus infection

Crimean-Congo hemorrhagic fever (CCHF), caused by Crimean-Congo hemorrhagic fever virus (CCHFV), is on the World Health Organizations’ list of prioritized diseases and pathogens. With global distribution, high fatality rate and no approved vaccine or effective treatment, CCHF constitutes a threat against global health. In the current study, we demonstrate that vaccination with nucleoside-modified mRNA-lipid nanoparticles (mRNA-LNP), encoding for the CCHFV nucleoprotein (N) or glycoproteins (GcGn) protect IFNAR -/- mice against lethal CCHFV infection. In addition, we found that both mRNA-LNP induced strong humoral and cellular immune responses in IFNAR -/- and immunocompetent mice and that neutralizing antibodies are not necessary for protection. When evaluating immune responses induced by immunization including CCHFV Gc and Gn antigens, we found the Gc protein to be more immunogenic compared to the Gn protein. Hepatic injury is prevalent in CCHF and contributes to the severity and mortality of the disease in humans. Thus, to understand the immune response in the liver after infection and the potential effect of the vaccine, we performed a proteomic analysis on liver samples from vaccinated and control mice after CCHFV infection. Similar to observations in humans, vaccination affected the metabolic pathways. In conclusion, this study shows that a CCHFV mRNA-LNP vaccine, based on viral nucleo- or glycoproteins, mediate protection against CCHFV induced disease. Consequently, genetic immunization is an attractive approach to prevent disease caused by CCHFV and we believe we have necessary evidence to bring this vaccine platform to the next step in the development of a vaccine against CCHFV infection. Importance Crimean-Congo hemorrhagic fever virus (CCHFV) is a zoonotic pathogen causing Crimean-Congo hemorrhagic fever (CCHF), a severe fever disease. CCHFV have a wide distribution and are endemic in several areas around the world. Cases of CCHF are also being reported in new areas, indicating an expansion of the disease, which is of high concern. Dispersion of the disease, high fatality rate and no approved vaccine makes CCHF a threat to global health. The development of a vaccine is thus of great importance. Here we show 100% protection against lethal CCHFV infection in mice immunized with mRNA-LNP encoding for different CCHFV proteins. The vaccination showed both robust humoral and cellular immunity. mRNA-LNP vaccines combine the ability to induce an effective immune response, the safety of a transient carrier and the flexibility of genetic vaccines. This and our results from the current study support the development of a mRNA-LNP based vaccine against CCHFV.

SAFA initiates innate immunity against cytoplasmic RNA virus SFTSV infection

Nuclear scaffold attachment factor A (SAFA) is a novel RNA sensor involved in sensing viral RNA in the nucleus and mediating antiviral immunity. Severe fever with thrombocytopenia syndrome virus (SFTSV) is a bunyavirus that causes SFTS with a high fatality rate of up to 30%. It remains elusive whether and how cytoplasmic SFTSV can be sensed by the RNA sensor SAFA. Here, we demonstrated that SAFA was able to detect SFTSV infection and mediate antiviral interferon and inflammatory responses. Transcription and expression levels of SAFA were strikingly upregulated under SFTSV infection. SAFA was retained in the cytoplasm by interaction with SFTSV nucleocapsid protein (NP). Importantly, SFTSV genomic RNA was recognized by cytoplasmic SAFA, which recruited and promoted activation of the STING-TBK1 signaling axis against SFTSV infection. Of note, the nuclear localization signal (NLS) domain of SAFA was important for interaction with SFTSV NP and recognition of SFTSV RNA in the cytoplasm. In conclusion, our study reveals a novel antiviral mechanism in which SAFA functions as a novel cytoplasmic RNA sensor that directly recognizes RNA virus SFTSV and mediates an antiviral response.

COVID-19 and CAR-T cells: current challenges and future directions-a report from the EPICOVIDEHA survey by EHA-IDWP

Patients receiving chimeric antigen receptor T cells (CAR-T cells) therapy may be particularly susceptible to coronavirus disease 2019 (COVID-19) because of several factors including the immunosuppression associated to the underlying disease and delayed cytopenias. Regrettably, data on outcomes of CAR-T recipients with COVID-19 are extremely scarce. The aim of this study was to investigate the characteristics and outcomes of COVID-19 in patients treated with CAR-T therapy. The European Hematology Association - Scientific Working Group Infection in Hematology endorsed a survey to collect and analyze data from patients developing COVID-19 after CAR-T therapy. Overall, 459 patients treated with CAR-T cells were reported from 18 European centers. The prevalence of COVID-19 cases was 4.8%. Median time from CAR-T therapy and COVID-19 diagnosis was 169 days. Severe infection occurred in 66.7% of patients and 43.3% of the subjects required admission to ICU. The COVID-19 mortality was 33%. In multivariable analysis, the disease status at the time of COVID-19 trended marginally towards adverse outcome (P=0.075). In conclusion, we documented a high fatality rate for CAR-T patients with COVID-19, supporting the need to design successful interventions to mitigate the risk of infection in this vulnerable group of patients.

High D-dimer Level in Fracture Patient with Asymptomatic Covid-19: Dilemmatic Surgery Decision - A Serial Case Report

Introduction: SARS-CoV-2 is highly transmittable virus. D-dimer associated with high fatality rate in COVID-19 with pneumonia and fractures. COVID-19 make surgical decision more challenging. Thrombosis plays an important mechanism in severity of COVID-19 and could be measured through D-dimer level. Case illustrations: We report 4 fracture cases with asymptomatic COVID-19. 1st case diagnosed close fracture in right 1/3 distal cruris without pneumonia, D-dimer 2420 ng/dl. Surgery 20 days after trauma with decreased D-dimer level. 2nd case, was diagnosed with close fracture in the left cruris and right 1/3 middle of clavicle with pneumonia, D-dimer level 6670 ng/dl, decision obtained in 27 days after hospitalization with decreased D-dimer. 3rd case diagnosed open fracture in left 1/3 distal humerus with pneumonia, D-dimer level 1020 ng/dl. Surgery 32 days after trauma with decreased D-dimer. 4th case diagnosed open fracture in left 1/3 proximal humeral and left medial phalanx index finger with pneumonia. The D-dimer level 2830 ng/dl. Surgery was obtained 17 days after trauma with decreased D-dimer. Discussion: Pandemic creates gray zone in orthopedic surgery. D-dimer found increased in COVID-19 and fracture patients. Asymptomatic case can be operated on 10th day post positive result as long as the general condition is optimal. D-dimer also important in making the decision to perform surgery. D-dimer over 2500 ng/mL have greater risk for being VTE in fracture patients. Conclusion: The pandemic has creates a large gray zone. The strategies for decision making includes general condition and severity COVID-19 also D-dimer level. Keywords: D-dimer, COVID-19, Fracture, Surgery.

Factors Related to Survival in Intensive Care Unit Patients with Covid-19: A study from a Single Center in Brazil.

Introduction: The aim of this study is to the present an original research which describes the outcome in 268 ICU consecutive patients in a single center, as well analyzing the effects of viral infection on preexisting medical conditions such as hypertension, diabetes, obesity, chronic obstructive pulmonary disease, and how these factors affected survival and hospital stay.Material and methods: We retrospectively analyzed patients included in this study who were admitted to ICU between March 18th 2020 until August 30th 2020. All patients were analyzed under the same protocol at Hospital Alemão Oswaldo Cruz, São Paulo, Brazil. Several factors were considered, such as: age, gender, symptoms before hospitalization, comorbidities, vasopressors use, radiological findings and use of high flow nasal catheter. The results were presented using the hazard ratio and its respective 95% confidence intervals. For statistical inferences, p <0.05 was adopted for all analysis.Results: The median age was 72 years, 64,2 years (53-74) for patients who were discharged, and 79.9 years (71.4-88.4) for those deceased (p<0.001). The most common comorbidities associated were: systemic arterial hypertension, diabetes, thyroid disease, cardiovascular and kidney disease. The univariate analysis showed the following factors as predictors of survival: myalgia (p=0.001), cerebrovascular disease (p=0.002), COPD (p=0.003), dementia (p=0.000), the need for mechanical ventilation (p=0.000), dialysis (0.000), vasopressors use (0.000), SAPS3 (0.000), lymphopenia (p=0.004), elevated D-dimer (P=0.011), time in ICU before tracheostomy (p=0.002), and performing a tracheostomy (p=0.000). The independent predictors of mortality were: advanced age (p=0.003); the non-use of vasopressor in the ICU was protective factor (p=0.001); tracheostomy performed in ICU was a mortality predictor (p=0.002).Discussion: COVID-19 affects more older adults and there is also a high fatality rate in this subset of patients. Acute respiratory distress syndrome (ARDS) is the primary cause of death in and around < 5% of patients were reported as experiencing bacterial/fungal coinfection at admission. Our findings support the observations of earlier studies, which found a high percentage of hospitalized patients of advanced age with preexisting conditions, hypertension being the most common.Conclusion: In our analysis, age, the need for vasopressors medications patients who underwent tracheostomy and underlying comorbidities, such as systemic coronary disease, heart failure, neoplasia, COPD, were found to be significantly associated with COVID-19 severity.

Speed Management in Iran: A Review Process

The level of road trauma is high in the Eastern Mediterranean Region with the Islamic Republic of Iran having a particularly high fatality rate at 20.5 per 100,000 population. The Government, assisted by the World Health Organisation (WHO), committed to implementing demonstration projects in three provinces that will form the basis of road safety actions to be advanced by the WHO across the Region. In recognition that speed management is a pivotal factor in achieving a safer road and traffic system, and as a component of the project, a review was carried out in 2019 by a team of international experts in the field in collaboration with national consultants. This review was undertaken in consideration of the Safe System Approach and the Results-Based Management Approach. The findings of this review and their implications for future actions in Iran are discussed in this paper.

Vaccine Induced Immune Thrombotic Thrombocytopenia Causing a Severe Form of Cerebral Venous Thrombosis With High Fatality Rate: A Case Series

During a 2-week period, we have encountered five cases presenting with the combination of cerebral venous thrombosis (CVT), intracerebral hemorrhage and thrombocytopenia. A clinical hallmark was the rapid and severe progression of disease in spite of maximum treatment efforts, resulting in fatal outcome in for 4 out of 5 patients. All cases had received ChAdOx1 nCov-19 vaccine 1–2 weeks earlier and developed a characteristic syndrome thereafter. The rapid progressive clinical course and high fatality rate of CVT in combination with thrombocytopenia in such a cluster and in otherwise healthy adults is a recent phenomenon. Cerebral autopsy findings were those of venous hemorrhagic infarctions and thrombi in dural venous sinuses, including thrombus material apparently rich in thrombocytes, leukocytes and fibrin. Vessel walls were free of inflammation. Extra-cerebral manifestations included leech-like thrombi in large veins, fibrin clots in small venules and scattered hemorrhages on skin and membranes. CVT with thrombocytopenia after adenovirus vectored COVID-19 vaccination is a new clinical syndrome that needs to be recognized by clinicians, is challenging to treat and seems associated with a high mortality rate.