Human Clinical Data Research Articles

Edge prior guided dictionary learning for quantitative susceptibility mapping reconstruction.

Compared with conventional magnetic resonance imaging methods, the quantitative magnetic susceptibility mapping (QSM) technique can quantitatively measure the magnetic susceptibility distribution of tissues, which has an important clinical application value in the investigations of brain micro-bleeds, Parkinson's, and liver iron deposition, etc. However, the quantitative susceptibility mapping algorithm is an ill-posed inverse problem due to the near-zero value in the dipole kernel, and high-quality QSM reconstruction with effective streaking artifact suppression remains a challenge. In recent years, the performance of sparse representation has been well validated in improving magnetic resonance image (MRI) reconstruction. In this study, by incorporating feature learning into sparse representation, we propose an edge prior guided dictionary learning-based reconstruction method for the dipole inversion in quantitative susceptibility mapping reconstruction. The structure feature dictionary relies on magnitude images for susceptibility maps have similar structures with magnitude images, and this structure feature dictionary and edge prior information are used in the dipole inversion step. The performance of the proposed algorithm is assessed through in vivo human brain clinical data, leading to high-quality susceptibility maps with improved streaking artifact suppression, structural recovery, and quantitative metrics. The proposed edge prior guided dictionary learning method for dipole inversion in QSM achieves improved performance in streaking artifacts suppression, structural recovery and deep gray matter reconstruction.

150. Updated Clinical Guidelines for Treatment and Prophylaxis of Plague

BackgroundPlague still occurs naturally in the western United States, Latin America, Asia, and Africa. Yersinia pestis, the causative agent of plague, is a Tier 1 bioterrorism agent due to its potential for aerosol release and high fatality rates. Recommendations for treatment and post-exposure prophylaxis (PEP) of plague were published in 2000 and included limited first-line options for treating plague, namely streptomycin or gentamicin. Doxycycline or ciprofloxacin were recommended for PEP. However, since 2000 new human clinical data and animal data have become available, and the FDA has approved additional antimicrobials for plague. MethodsCDC developed updated, evidence-based guidelines for treatment and prophylaxis of plague using a comprehensive process. To collect evidence on relative efficacy of various antimicrobials for treatment of plague, the guidelines team conducted systematic literature reviews and analyzed U.S. surveillance data. Results of these investigations were published in Clinical Infectious Diseases in 2020. We also hosted several meetings with subject matter experts and clinical organizations (IDSA, AAP, etc.), federal agencies, and others to review relevant data and gather individual input on treatment and prophylaxis of plague. ResultsThe forthcoming plague guidelines will include several important updates. First-line treatment options have been expanded to include ciprofloxacin, levofloxacin, and moxifloxacin in addition to streptomycin and gentamicin. For PEP, levofloxacin and moxifloxacin are now first-line options in addition to doxycycline and ciprofloxacin. Trimethoprim-sulfamethoxazole is now one of several new alternative options for PEP. The updated guidelines also include recommendations for treatment of clinical forms of plague other than pneumonic. Additional special populations such as immunocompromised persons and neonates are also covered. ConclusionPlague remains a threat, both as a naturally occurring disease and as a potential bioterrorism weapon, and preparedness and early recognition are key to effective response. The updated clinical guidelines will be a useful tool for clinicians to manage antimicrobial treatment and PEP for plague. Disclosures All Authors: No reported disclosures

MEF2 is a key regulator of cognitive potential and confers resilience to neurodegeneration.

Recent increases in human longevity have been accompanied by a rise in the incidence of dementia, highlighting the need to preserve cognitive function in an aging population. A small percentage of individuals with pathological hallmarks of neurodegenerative disease are able to maintain normal cognition. Although the molecular mechanisms that govern this neuroprotection remain unknown, individuals that exhibit cognitive resilience (CgR) represent a unique source of therapeutic insight. For both humans and animal models, living in an enriched, cognitively stimulating environment is the most effective known inducer of CgR. To understand potential drivers of this phenomenon, we began by profiling the molecular changes that arise from environmental enrichment in mice, which led to the identification of MEF2 transcription factors (TFs). We next turned to repositories of human clinical and brain transcriptomic data, where we found that the MEF2 transcriptional network was overrepresented among genes that are most predictive of end-stage cognition. Through single-nucleus RNA sequencing of cortical tissue from resilient and nonresilient individuals, we further confirmed up-regulation of MEF2C in resilient individuals to a subpopulation of excitatory neurons. Last, to determine the causal impact of MEF2 on cognition in the context of neurodegeneration, we overexpressed Mef2a/c in the PS19 mouse model of tauopathy and found that this was sufficient to improve cognitive flexibility and reduce hyperexcitability. Overall, our findings reveal a previously unappreciated role for MEF2 TFs in promoting CgR, highlighting their potential as biomarkers or therapeutic targets for neurodegeneration and healthy aging.

Unraveling the Gordian knot: genetics and the troubled road to effective therapeutics for Alzheimer's disease.

In the late 20th century, identification of the major protein components of amyloid plaques and neurofibrillary tangles provided a window into the molecular pathology of Alzheimer’s disease, ushering in an era of optimism that targeted therapeutics would soon follow. The amyloid-cascade hypothesis took hold very early, supported by discoveries that dominant mutations in APP, PSEN1, and PSEN2 cause the very rare, early-onset, familial forms of the disease. However, in the past decade, a stunning series of failed Phase-3 clinical trials, testing anti-amyloid antibodies or processing-enzyme inhibitors, prompts the question, What went wrong? The FDA’s recent controversial approval of aducanumab, despite widespread concerns about efficacy and safety, only amplifies the question. The assumption that common, late-onset Alzheimer’s is a milder form of familial disease was not adequately questioned. The differential timing of discoveries, including blood–brain–barrier-penetrant tracers for imaging of plaques and tangles, made it easy to focus on amyloid. Furthermore, the neuropathology community initially implemented Alzheimer’s diagnostic criteria based on plaques only. The discovery that MAPT mutations cause frontotemporal dementia with tauopathy made it even easier to overlook the tangles in Alzheimer’s. Many important findings were simply ignored. The accepted mouse models did not predict the human clinical trials data. Given this lack of pharmacological validity, input from geneticists in collaboration with neuroscientists is needed to establish criteria for valid models of Alzheimer’s disease. More generally, scientists using genetic model organisms as whole-animal bioassays can contribute to building the pathogenesis network map of Alzheimer’s disease.

Therapeutic Outcome of Burn Patients Treated With Hyperbaric Oxygen.

Amongst various interventions for burns and inhalation injuries, hyperbaric oxygen therapy (HBOT) has recently been widely integrated as an adjunctive management of care due to its therapeutic properties in reducing tissue hypoxia, pathological inflammation, and augmenting neovascularization. However, the limitation of human clinical trials and data undermines its efficacy to be implemented as an adjunctive therapeutic modality in burns. The purpose of the literature review is to determine the efficacy of HBOT as an adjunct to standard management in burns. A review of the literature was done by searching PubMed, Cochrane, Medline, EMBASE, and Google Scholar for papers addressing the comparison of therapeutic outcomes between HBOT and non-HBOT in burns. Current research findings are conflicting, and the use of HBOT as an adjunct in burns management is still controversial. Therefore there is still a need for more data and research on the therapeutic benefits of HBOT in burn management.

Linking immune-mediated damage to neurodegeneration in multiple sclerosis: could network-based MRI help?

Inflammatory demyelination characterizes the initial stages of multiple sclerosis, while progressive axonal and neuronal loss are coexisting and significantly contribute to the long-term physical and cognitive impairment. There is an unmet need for a conceptual shift from a dualistic view of multiple sclerosis pathology, involving either inflammatory demyelination or neurodegeneration, to integrative dynamic models of brain reorganization, where, glia-neuron interactions, synaptic alterations and grey matter pathology are longitudinally envisaged at the whole-brain level. Functional and structural MRI can delineate network hallmarks for relapses, remissions or disease progression, which can be linked to the pathophysiology behind inflammatory attacks, repair and neurodegeneration. Here, we aim to unify recent findings of grey matter circuits dynamics in multiple sclerosis within the framework of molecular and pathophysiological hallmarks combined with disease-related network reorganization, while highlighting advances from animal models (in vivo and ex vivo) and human clinical data (imaging and histological). We propose that MRI-based brain networks characterization is essential for better delineating ongoing pathology and elaboration of particular mechanisms that may serve for accurate modelling and prediction of disease courses throughout disease stages.

Injection pressure levels for creating blebs during subretinal gene therapy.

Retinal damage has been associated with increased injection pressure during subretinal gene therapy delivery in various animal models, yet there are no human clinical data regarding the pressures required to initiate and propagate subretinal blebs. This study characterized the intraoperative pressure levels for subretinal gene therapy delivery across eight retinal conditions. A total of 116 patients with retinal degenerative diseases have been treated with subretinal gene therapy at OHSU-Casey Eye Institute as of June 2020; seventy patients (60.3%) were treated using a pneumatic-assisted subretinal delivery system. All retinal blebs were performed using a 41-gauge injection cannula, and use of a balanced salt solution (BSS) "pre-bleb" prior to gene therapy delivery was performed at the discretion of the surgeon. Patient age and intraoperative data for BSS and vector injections were analyzed in a masked fashion for all patients who received pneumatic-assisted subretinal gene therapy. The median age of the patients was 35 years (range 4-70). No significant differences in injection pressures were found across the eight retinal conditions. In this study, patient age was shown to affect maximum injection pressures required for bleb propagation, and the relationship between age and pressure varied based on retinal condition. These data have important implications in optimizing surgical protocols for subretinal injections.

Overview on toxicity of nanoparticles, it's mechanism, models used in toxicity studies and disposal methods – A review

The usage of nanoparticles in the recent years have gained a huge importance in various fields due to their unique properties such as electrical, optical, magnetic abilities that contribute to the growth of science and technology. Therefore, it has become vital to understand the impact of nanoparticles on the human health and environment as they are expected to impose a negative threat in the environment due to its exploitation and improper disposal. As a result, nanotoxicology has been emerged as new realm of toxicology that mainly deals with understanding of the interaction between the nanoparticles with the environment. Due to the increased exposure of nanoparticles to the environment, a better assessment of nanotoxicity is required along with imposing methods for a more efficient use of nanoparticles and with proper disposal methods to help reduce the adverse effects. Therefore, this review paper provides a detailed understanding of the mechanism that is responsible for nanoparticles toxicity and its interaction with the environment along with the factors that contribute to its toxic effects with specific information of metal nanoparticles such as gold, silver, superparamagnetic iron oxide, platinum and zinc nanoparticles. It also provides a detailed explanation on adverse effects on human cell lines and clinical data derived from studies conducted on various in-vitro and in-vivo models utilized to assess the toxic impacts of the nano-sized particles. • There is a need of studying the impact of nanoparticles on the environment. • It is essential to understand the mechanism of nanoparticles’ toxicity and possible disposal methods.

The Dilemma of perfluorooctanoate (PFOA) human half-life

Disparity in the results from human observational and clinical studies is not uncommon, but risk assessment efforts often judge one set of data more relevant with the loss of valuable information. The assessment for perfluorooctanoate (PFOA) is a good example of this problem. The estimation of its safe dose is disparate among government groups due in part to differences in understanding of its half-life in humans. These differences are due in part to incomplete information on sources of exposure in the human observational half-life studies, which have been routinely acknowledged, but until recently not well understood. Exposure information is thus critical in understanding, and possibly resolving, this disparity in PFOA safe dose, and potentially for disparities with similar chemistries when both human observational and clinical findings are available. We explore several hypotheses to explain this disparity in PFOA half-life from human observational studies in light of findings of a clinical study in humans and relevant exposure information from a recent international meeting of the Society of Toxicology and Environmental Chemistry (SETAC). Based on information from both human observational studies and clinical data, we proposed a range for the half-life for PFOA of 0.5–1.5 years, which would likely raise many existing regulatory safe levels if all other parameters stayed the same.

Emerging pharmacologic mechanisms of buprenorphine to explain experience of analgesia versus adverse effects.

Buprenorphine's unique pharmacologic mechanisms of action lend itself to a higher level of complexity than its typical characterization as a partial agonist at µ-opioid receptors. It is well-documented that its additional activity at Δ- and κ-opioid receptors, and opioid receptor ligand 1 may be associated with varying degrees of analgesia and usual opioid-related adverse effects. However, novel downstream molecular and cellular mechanisms from µ-opioid receptor activation contain potential new insights into its overall unique effects. These include buprenorphine's peculiar ability to induce analgesia at escalating doses, while exhibiting a plateaued effect on respiratory depression, euphoria, gastrointestinal (GI) motility, depression, anxiety, and addictive potential. Thus, this review aims to discuss several of these emerging mechanisms to gain a better understanding of these curious actions, as well as support much of this in vitro evidence with various human clinical trial data to further support buprenorphine's place on the analgesic ladder.

DNA Methylation of Biliary Tract Cancer Identifies Subtypes with Different Immune Characteristics and Clinical Outcomes

DNA methylation-associated studies on biliary tract cancer (BTC), including cholangiocarcinoma (CCA) and gallbladder cancer (GBC), may improve the BTC classification scheme. In our cohort including 57 CCAs and 48 GBCs, lower level of methylation changes were associated with fewer copy number variations, fewer mutations of cell cycle pathway, CCND/E1, FGF/FGFR family, and NOTCH pathway, and remarkably longer overall survival (OS, HR=0.07, 95% CI 0.01-0.65, P =0.017). Additionally, we constructed a 12-feature prognostic prediction model that effectively predicted OS (HR=0.21, 95% CI 0.10-0.43, P <0.001). Moreover, the BTCs with minimal methylation changes exhibited higher immune-related signatures, infiltration of CD8+ lymphocytes, and PD-L1 expression, indicating an inflamed tumor immune microenvironment (TIME) with PD-L1 expression elicited by immune attack, potentially suggesting better immunotherapy efficacy. In BTCs, DNA methylation is a powerful tool for molecular classification, serving as a robust indicator of genomic aberrations, survival outcomes, and tumor immune microenvironment. Our integrative analysis provides insights into prognostication after curative surgery and patient selection for immunotherapy. Funding Statement: This work was supported by the Innovation Group Project of Shanghai Municipal Health Commission (2019CXJQ03) and the Shanghai Municipal Health Commission (202040045). Declaration of Interests: Y. Xu, G. Wang, C. Li, Y. Zhang, J. Zhao, C. Wang, X. Wen, Z. Zhang, B. Li, H. Zhang, Z. Zhang, and S. Cai are employees of Burning Rock Biotech. Other authors declare no potential conflicts of interest. Ethics Approval Statement: All collection and usage of human samples and clinical data were in accordance with the principles of the Declaration of Helsinki and approved by the Ethics Committee of Eastern Hepatobiliary Surgery Hospital (EHBHKY2018-02-014). The written consents were received from all the participated patients.

Antimicrobial Treatment and Prophylaxis of Plague: Recommendations for Naturally Acquired Infections and Bioterrorism Response.

SummaryThis report provides CDC recommendations to U.S. health care providers regarding treatment, pre-exposure prophylaxis, and postexposure prophylaxis of plague. Yersinia pestis, the bacterium that causes plague, leads to naturally occurring disease in the United States and other regions worldwide and is recognized as a potential bioterrorism weapon. A bioweapon attack with Y. pestis could potentially infect thousands, requiring rapid and informed decision making by clinicians and public health agencies. The U.S. government stockpiles a variety of medical countermeasures to mitigate the effects of a bioterrorism attack (e.g., antimicrobials, antitoxins, and vaccines) for which the 21st Century Cures Act mandates the development of evidence-based guidelines on appropriate use. Guidelines for treatment and postexposure prophylaxis of plague were published in 2000 by a nongovernmental work group; since then, new human clinical data, animal study data, and U.S. Food and Drug Administration approvals of additional countermeasures have become available. To develop a comprehensive set of updated guidelines, CDC conducted a series of systematic literature reviews on human treatment of plague and other relevant topics to collect a broad evidence base for the recommendations in this report. Evidence from CDC reviews and additional sources were presented to subject matter experts during a series of forums. CDC considered individual expert input while developing these guidelines, which provide recommended best practices for treatment and prophylaxis of human plague for both naturally occurring disease and following a bioterrorism attack. The guidelines do not include information on diagnostic testing, triage decisions, or logistics involved in dispensing medical countermeasures. Clinicians and public health officials can use these guidelines to prepare their organizations, hospitals, and communities to respond to a plague mass-casualty event and as a guide for treating patients affected by plague.

Comparison of hemagglutination inhibition and hemagglutinin pseudovirus neutralization titres in relation to protection against influenza in a mouse model.

The hemagglutination inhibition (HI) test has long been used as a standard measure of antibody response for inactivated influenza vaccines. However, the HI test has limitations, such as insensitivity when using some H3N2 virus strains and failure to detect neutralizing antibodies that target regions distant from the receptor binding site. We therefore examined a hemagglutinin pseudovirus neutralization (PVN) test as a possible supplement or alternative to the HI test. We evaluated the association of HI or PVN titres with protection against influenza infection in mice based on morbidity (where the illness was defined as 25% body weight loss). We assessed this relationship using dose-response models incorporating HI or PVN titres as a variable. The morbidity was correlated with the pre-exposure titres, and such a correlation was well described by a modified dose-response model. The mathematical modelling suggests that PVN titres consistently show a stronger association with invivo protection as compared to HI titres in mice. Given our findings, the PVN test warrants further investigation as a tool for evaluating antibody responses to influenza vaccines containing hemagglutinin. The resulting models may also be useful for analyzing human clinical data to identify potentially protective antibody titres against influenza illness.

Circulating Tumor DNA Methylation Markers for Differential Diagnosis of Hepatocellular Carcinoma

Background: An effective blood-based method for hepatocellular carcinoma (HCC) early detection has not yet been developed. Aberrant DNA methylation may offer opportunities in revolutionizing cancer screening and diagnosis. We sought to identified a non-invasive DNA methylation-based diagnostic approach using cell-free DNA for HCC early detection in high risk population. Methods: Differentially methylated DNA methylation blocks were determined by comparing methylation profiles of biopsy-proven HCC, cirrhotic and healthy liver tissues using targeted bisulfite sequencing. A multi-layer HCC screening model was subsequently constructed based on tissue-derived differentially methylated makers using plasma samples from 120 HCC patients, 92 cirrhotic patients and 290 healthy individuals. This model was independently validated in a cohort consisting of 67 HCC patients, 115 cirrhotic patients and 242 healthy individuals. The clinical parameters of misclassified samples were also investigated. Findings: Based on methylation profiling of tissue samples, a total of 2,321 DNA methylation markers were derived, which were subsequently used to construct a cfDNA-based HCC screening model, achieving a sensitivity of 86% and specificity of 97% in the training cohort and a sensitivity of 82% and specificity of 96% in the independent validation cohort. The HCC screening model can effectively discriminate HCC patients from non-HCC patients, including patients with cirrhosis, HBV infection and healthy individuals, achieving an AUC of 0.956; whereas serum alpha-fetoprotein (AFP) achieved an AUC of 0.803. Interpretation: We have developed and validated an HCC screening model which can effectively distinguish early stage HCC patients from cirrhotic patients and symptomatic HBsAg-seropositive individuals. Funding: Key Research and Development Program of Hunan Province, Natural Science Foundation of Hunan Province, China. Declaration of Interest: None to declare. Ethical Approval: The study was approved by the ethic committee of The Second Xiangya Hospital of Central South University (KYLL2018072) and Chongqing University Cancer Hospital (2019167). All collection and usage of human sample and clinical data were in accordance with the principles of the Declaration of Helsinki. Written informed content was obtained from every participant for the use of their tissue or plasma samples.

Single session per oral endoscopic myotomy and trans oral incisionless fundoplication – can we prevent reflux in patients with achalasia?

Background and study aims The rate of gastroesophageal reflux disease (GERD) after per oral endoscopic myotomy (POEM) is concerning. Endoscopic anti-reflux methods, such as Trans Oral Incisionless Fundoplication (TIF), are crucial for the long-term success of POEM, especially if they can be performed in the same session. Methods We completed a proof-of-concept canine pilot study (n = 6) to assess safety and feasibility of POEM and TIF in a single session (POEM-TIF). Subsequently, POEM-TIF was also performed in patients with achalasia (n = 5). Herein, we report on the safety, technical and clinical success of the first-in-human cases with symptom follow-up at 1, 3 and 6 months and pH testing at 6 months. Results POEM was completed successfully in six canines (3 anterior and 3 posterior myotomies), followed by TIF in the same session. Necropsy and extensive testing demonstrated no evidence of mucosal injury and no leaks. The reconstructed valve was 220 to 240 degrees, 3 to 4 cm in length, and resulted in concomitant esophageal lengthening (2–5 cm). Using similar principles, the first-in-human cases were performed without intraprocedural or delayed adverse events. pH testing at 6 months showed that four of five patients had no evidence of GERD (DeMeester > 14.72), and in one case, there was evidence of esophagitis. Conclusions Single session POEM-TIF appears to be safe and feasible. Early clinical human data suggests that it may be able to reduce post POEM GERD, however the additional secondary benefits such as lengthening and straightening of the esophagus, may prove to be equally important for the long-term success of POEM.

Invitro modeling accurately predicts cardiac lead fracture at 10 years.

Development of a cardiac lead fracture model has the potential to differentiate well-performing lead designs from poor performing ones and could aid in future lead development. The purpose of this study was to demonstrate a predictive model for lead fracture and validate the results generated by the model by comparing them to observed 10-year implantable cardioverter-defibrillator lead fracture-free survival. The model presented here uses a combination of invivo patient data, invitro conductor fatigue test data, and statistical simulation to predict the fracture-free survival of cardiac leads. The model was validated by comparing the results to human clinical performance data from the Medtronic Sprint Fidelis (Minneapolis, MN) models 6931 (single coil, active fixation) and 6949 (dual coil, active fixation), as well as the Quattro model 6947 (dual coil, active fixation). Median patient age in the single coil Fidelis 6931 population (64 years) was less than in the dual coil Fidelis 6949 and Quattro populations (68 years). Modeled and observed fracture-free survival for Quattro (>97%) was superior to that for Fidelis (<94%). The modeled survival agreed with the observed fracture-free survival data. The average model error was 0.3% (SD 1.2%). This model for cardiac lead fracture-free survival using invivo lead bending measurements and invitro bench testing can be used to predict lead performance as observed by alignment with field survival data.

Functional Connectivity of the Cognitive Cerebellum.

Anatomical tracing, human clinical data, and stimulation functional imaging have firmly established the major role of the (neo-)cerebellum in cognition and emotion. Telencephalization characterized by the great expansion of associative cortices, especially the prefrontal one, has been associated with parallel expansion of the neocerebellar cortex, especially the lobule VII, and by an increased number of interconnections between these two cortical structures. These anatomical modifications underlie the implication of the neocerebellum in cognitive control of complex motor and non-motor tasks. In humans, resting state functional connectivity has been used to determine a thorough anatomo-functional parcellation of the neocerebellum. This technique has identified central networks involving the neocerebellum and subserving its cognitive function. Neocerebellum participates in all intrinsic connected networks such as central executive, default mode, salience, dorsal and ventral attentional, and language-dedicated networks. The central executive network constitutes the main circuit represented within the neocerebellar cortex. Cerebellar zones devoted to these intrinsic networks appear multiple, interdigitated, and spatially ordered in three gradients. Such complex neocerebellar organization enables the neocerebellum to monitor and synchronize the main networks involved in cognition and emotion, likely by computing internal models.

The parallels between particle induced lung overload and particle induced periprosthetic osteolysis (PPOL)

Background: When particles deposit for instance in the lung after inhalation or in the hip joint after local release from a hip implant material they can initiate a defense response. Even though these particles originate from inert materials such as polyethylene (PE) or titanium, they may cause harm when reaching high local doses and overwhelming local defense mechanisms. Main body: This paper describes the parallels between adverse outcome pathways (AOP) and particle properties in lung overload and periprosthetic osteolysis (PPOL). It is noted that in both outcomes in different organs , the macrophage and cytokine orchestrated persistent inflammation is the common driver of events, in the bone leading to loss of bone density and structure, and in the lung leading to fibrosis and cancer. Most evidence on lung overload and its AOP is derived from chronic inhalation studies in rats, and the relevance to man is questioned. In PPOL, the paradigms and metrics are based on human clinical data, with additional insights generated from in vitro and animal studies. In both organ pathologies the total volume of particle deposition has been used to set threshold values for the onset of pathological alterations. The estimated clinical threshold for PPOL of 130 mg/ml is much higher than the amount to cause lung overload in the rat (10 mg/ml). Conclusions: The paradigms developed in two very different areas of particle response in the human body have major similarities in their AOP. Connecting the clinical evidence in PPOL to lung overload challenges current paradigms and the human relevance of rat inhalation studies.

Immunopathological Changes in SARS-CoV-2 Critical and Non-critical Pneumonia Patients: A Systematic Review to Determine the Cause of Co-infection.

The ongoing COVID-19 pandemic originating from Wuhan, China is causing major fatalities across the world. Viral pneumonia is commonly observed in COVID-19 pandemic. The number of deaths caused by viral pneumonia is mainly due to secondary bacterial or fungal infection. The immunopathology of SARS-CoV-2 viral pneumonia is poorly understood with reference to human clinical data collected from patients infected by virus and secondary bacterial or fungal infection occurring simultaneously. The co-infection inside the lungs caused by pneumonia has direct impact on the changing lymphocyte and neutrophil counts. Understanding the attribution of these two immunological cells triggered by cytokines level change is of great importance to identify the progression of pneumonia from non-severe to severe state in hospitalized patients. This review elaborates the cytokines imbalance observed in SARS-CoV-1 (2003 epidemic), SARS-CoV-2 (2019 pandemic) viral pneumonia and community acquired pneumonia (CAP), respectively, in patients to determine the potential reason of co-infection. In this review the epidemiology, virology, clinical symptoms, and immunopathology of SARS-CoV-2 pneumonia are narrated. The immune activation during SARS-CoV-1 pneumonia, bacterial, and fungal pneumonia is discussed. Here it is further analyzed with the available literatures to predict the potential internal medicines, prognosis and monitoring suggesting better treatment strategy for SARS-CoV-2 pneumonia patients.

A review on viral data sources and search systems for perspective mitigation of COVID-19.

With the outbreak of the COVID-19 disease, the research community is producing unprecedented efforts dedicated to better understand and mitigate the effects of the pandemic. In this context, we review the data integration efforts required for accessing and searching genome sequences and metadata of SARS-CoV2, the virus responsible for the COVID-19 disease, which have been deposited into the most important repositories of viral sequences. Organizations that were already present in the virus domain are now dedicating special interest to the emergence of COVID-19 pandemics, by emphasizing specific SARS-CoV2 data and services. At the same time, novel organizations and resources were born in this critical period to serve specifically the purposes of COVID-19 mitigation while setting the research ground for contrasting possible future pandemics. Accessibility and integration of viral sequence data, possibly in conjunction with the human host genotype and clinical data, are paramount to better understand the COVID-19 disease and mitigate its effects. Few examples of host-pathogen integrated datasets exist so far, but we expect them to grow together with the knowledge of COVID-19 disease; once such datasets will be available, useful integrative surveillance mechanisms can be put in place by observing how common variants distribute in time and space, relating them to the phenotypic impact evidenced in the literature.