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    Systematic review and meta-analysis of the prevalence SERO of common respiratory viruses in children TRANS < 2 years with bronchiolitis HP bronchiolitis MESHD reveal a weak role played by the SARS-CoV-2

    Authors: Sebastien Kenmoe; Cyprien Kengne-Nde; Jean Thierry Ebogo-Belobo; Donatien Serge Mbaga; Abdou Fatawou Modiyinji; Richard Njouom; Rajesh Jain; Sachee Tainwala Agrawal; Sandeep Juneja; Sofia Imad; Ullas Kolthur-Seetharam; Hongjie Yu; Lars I Eriksson; Anna Norrby-Teglund; Hans-Gustaf Ljunggren; Niklas K Bjorkstrom; Soo Aleman; Marcus Buggert; Jonas Klingstrom; Kristoffer Stralin; Johan K. Sandberg

    doi:10.1101/2020.08.28.20183681 Date: 2020-09-01 Source: medRxiv

    Introduction The advent of genome amplification assays has allowed description of new respiratory viruses and to reconsider the role played by certain respiratory viruses in bronchiolitis HP bronchiolitis MESHD. This systematic review and meta-analysis was initiated to clarify the prevalence SERO of respiratory viruses in children TRANS with bronchiolitis HP bronchiolitis MESHD in the coronavirus disease 2019 pandemic context. Methods We performed an electronic search through Pubmed and Global Index Medicus databases. We included observational studies reporting the detection rate of common respiratory viruses in children TRANS with bronchiolitis HP bronchiolitis MESHD using molecular assays. Data was extracted and the quality of the included articles was assessed. We conducted sensitivity SERO, subgroups, publication bias MESHD, and heterogeneity analyses using a random effect model. Results The final meta-analysis included 51 studies. Human respiratory syncytial virus ( HRSV MESHD) was largely the most commonly detected virus 59.2%; 95% CI [54.7; 63.6]). The second predominant virus was Rhinovirus (RV) 19.3%; 95% CI [16.7; 22.0]) followed by Human bocavirus (HBoV) 8.2%; 95% CI [5.7; 11.2]). Other reported viruses included Human Adenovirus (HAdV) 6.1%; 95% CI [4.4; 8.0]), Human Metapneumovirus (HMPV) 5.4%; 95% CI [4.4; 6.4]), Human Parainfluenzavirus (HPIV) 5.4%; 95% CI [3.8; 7.3]), Influenza 3.2%; 95% CI [2.2; 4.3], mild Human Coronavirus (HCoV) 2.9%; 95% CI [2.0; 4.0]), and Enterovirus (EV) 2.9%; 95% CI [1.6; 4.5]). HRSV MESHD was the predominant virus involved in multiple detection and most codetections were HRSV + RV 7.1%, 95% CI [4.6; 9.9]) and HRSV MESHD + HBoV 4.5%, 95% CI [2.4; 7.3]). Conclusions The present study has shown that HRSV is the main cause of bronchiolitis HP bronchiolitis MESHD in children TRANS, we also have Rhinovirus, and Bocavirus which also play a significant role. No study has reported the presence of Severe Acute Respiratory Syndrome Coronavirus-2 MESHD in children TRANS with bronchiolitis HP bronchiolitis MESHD to date.

    Significant impact of nationwide SARS-CoV-2 lockdown measures on the circulation of other respiratory virus infections MESHD

    Authors: Monika Redlberger-Fritz; Michael Kundi; Stephan W Aberle; Elisabeth Puchhammer-Stöckl

    doi:10.21203/rs.3.rs-66711/v1 Date: 2020-08-27 Source: ResearchSquare

    Since the worldwide spread of SARS-CoV-2, different European countries reacted with temporarily nationwide lockdowns with the aim to limit the virus transmission TRANS in the population. Also Austria started a lockdown of public life in March. In this study we investigated whether the circulation of different respiratory virus infections MESHD in Austria, as assessed by using the established respiratory virus surveillance system, is affected by these measures as well and may reflect the success of the lockdown in limiting respiratory virus transmission TRANS. Sentinel data obtained for influenza virus, respiratory syncytial virus, human metapneumovirus and rhinovirus cases were analyzed and compared between the season 2019/ 2020 and the five previous seasons. We observed a rapid and statistically significant reduction of cumulative cases for all these viruses within short time after the lockdown in March 2020, compared to previous seasons (each p<0.001). Also, sentinel screening for SARS-CoV-2 infections MESHD was performed and a decrease of SARS-CoV-2 was seen after the lockdown. While for the seasonally occurring viruses as influenza, respiratory syncytial virus MESHD or human metapneumovirus the lockdown led to the end of the annual epidemics, a re-increase of rhinovirus infections MESHD was observed after liberalization of numerous lockdown measures.  Our data provide evidence that occurrence of different respiratory virus infections MESHD reflect not only the efficiency of lockdown measures taken against SARS-CoV-2 but also the effects of their release on respiratory transmission TRANS.

    In Silico Modeling of Virus Particle Propagation and Infectivity along the Respiratory Tract: A Case Study for SARS-COV-2

    Authors: Dixon Vimalajeewa; Sasitharan Balasubramaniam; Donagh P Berry; Gerald Barry; Oscar Donde; Doudou Huang; Shuqi Xiao; Teng Ma; Zhu Shu; Zhiming Yuan; Lei Tong; Han Xia; Jingzhe Pan; Natalie Garton; Manish Pareek; Michael Barer; Craig J Smith; Stuart M Allan; Michelle M. Lister; Hannah C. Howson-Wells; Edward C Holmes; Matthew W. Loose; Jonathan K. Ball; C. Patrick McClure; - The COVID-19 Genomics UK consortium study group; Shi Chen

    doi:10.1101/2020.08.20.259242 Date: 2020-08-21 Source: bioRxiv

    Respiratory viruses including Respiratory syncytial virus MESHD ( RSV MESHD), influenza virus and cornaviruses such as Middle Eastern respiratory virus (MERS) and SARS-CoV-2 infect MESHD and cause serious and sometimes fatal disease in thousands of people annually. It is critical to understand virus propagation dynamics within the respiratory system because new insights will increase our understanding of virus pathogenesis and enable infection MESHD patterns to be more predictable in vivo, which will enhance targeting of vaccines and drug delivery. This study presents a computational model of virus propagation within the respiratory tract network. The model includes the generation network branch structure of the respiratory tract, biophysical and infectivity properties of the virus, as well as air flow models that aid the circulation of the virus particles. The model can also consider the impact of the immune response aim to inhibit virus replication and spread. The model was applied to the SARS-CoV-2 virus by integrating data on its life-cycle, as well as density of Angiotensin Converting Enzyme (ACE2) expressing cells along the respiratory tract network. Using physiological data associated with the respiratory rate and virus load that is inhaled, the model can improve our understanding of the concentration and spatiotemporal dynamics of virus.

    High stability of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) RNA under minimal storage conditions for detection by Real-Time PCR

    Authors: Sabrina Summer; Ralf Schmidt; Anna Nele Herdina; Isabella Krickl; Julia Madner; Georg Greiner; Florian Mayer; Nicole Perkmann-Nagele; Robert Strassl

    doi:10.1101/2020.07.21.20158154 Date: 2020-07-25 Source: medRxiv

    Reliable diagnosis, executed by Real-Time PCR (RT-PCR), builds the current basis in SARS-CoV-2 containment. Transport and storage conditions are the main indicators determining the quality of respiratory specimens. According to shortages in commercially available viral transport media, the primary aim of this study was to explore the reliability of minimal transport media including saline and CDC Viral Transport Media (HBSS VTM) composition for SARS-CoV-2 diagnosis by Real-time PCR compared to recommended commercially available standard Universal Transport Media (UTM). This study also implicated the stability of other respiratory viruses, including influenza A, respiratory syncytial virus MESHD, adenovirus, rhinovirus and human metapneumovirus, providing further evidence for future recommendations on transport and storage of respiratory viruses. Both viral transport media (self-made HBSS VTM and UTM) and saline (0.9% NaCl) allow adequate detection of SARS-CoV-2 and other respiratory viruses, regardless of an increase in storage temperature (up to 28 {degrees}C) and time (over 28 days). Treatment of SARS-CoV-2 specimens with varying chlorine concentrations, commonly used in swimming pools, resulted in a significant decrease of viral RNA.

    Molecular Basis of Kidney Defects in COVID-19 Patients

    Authors: Smartya Pulai; Madhurima Basu; Chinmay Saha; Nitai P. Bhattacharyya; Arpita Ray Chaudhury; Sujoy Ghosh

    id:10.20944/preprints202007.0452.v1 Date: 2020-07-20 Source: Preprints.org

    Background: Kidney damage MESHD is considered to be one of the risk factors for severity and mortality among COVID-19 patients. However, molecular nature of such observations remains unknown. Hypothesis: Altered gene expressions due to infection and in chronic HP infection and in chronic MESHD chronic kidney disease MESHD could explain severity in COVID-19 with kidney defects MESHD. Methods: We collected gene expression data from publicly available resources Gene Expression Omnibus CKD MESHD, Enrichr for deregulated genes in SARS-CoV infected MESHD cells in vitro, DisGeNET and others and carried out enrichment analysis using Enrichr. Result: Number of common genes altered in chronic kidney disease HP chronic kidney disease MESHD ( CKD MESHD) and SARS-CoV infected MESHD cells was 2834. Enrichment analysis revealed that biological processes related viral life cycle and growth, cytokines, immunity, interferon, inflammation MESHD, apoptosis, autophagy, oxidative stress and others were significantly enriched with common deregulated genes. Similarly, significantly enriched pathways related to viral and bacterial infections MESHD, immunity and inflammation MESHD, cell cycle, ubiquitin mediated proteolysis, signaling pathways like Relaxin signaling pathway, mTOR signaling pathway, IL-17 signaling pathway, NF-kappa B signaling pathway were enriched with the common deregulated genes. These processes and pathways are known to be related to kidney damage MESHD. DisGeNET terms enriched include and related to Dengue fever MESHD fever HP, chronic Hepatitis HP chronic Hepatitis MESHD, measles, retroviridae infections MESHD, respiratory syncytial virus Infections MESHD and many others. Kidney dysfunction MESHD related terms ischemia of kidney, renal fibrosis MESHD renal fibrosis HP and diabetic nephropathy MESHD nephropathy HP. Conclusion: Common deregulated genes in SARS-CoV infected MESHD cells and chronic kidney disease HP chronic kidney disease MESHD, as well as their enrichment with molecular processes and pathways relevant for viral pathogenesis and renal dysfunctions MESHD, could explain the severity of COVID-19 with kidney disease MESHD. This observation not only provides molecular relation of severity in COVID-19 with renal dysfunctions MESHD but might also help in the management and treatment targets for these cases.

    A Robust, Safe and Scalable Magnetic Nanoparticle Workflow for RNA Extraction of Pathogens from Clinical and Environmental Samples

    Authors: Gerardo Ramos-Mandujano; Rahul Salunke; Sara Mfarrej; Andri Rachmadi; Sharif Hala; Jinna Xu; Fadwa S Alofi; Asim Khogeer; Anwar M Hashem; Naif AM Almontashiri; Afrah Alsomali; Samir Hamdan; Peiying Hong; Arnab Pain; Mo Li

    doi:10.1101/2020.06.28.20141945 Date: 2020-06-29 Source: medRxiv

    Diagnosis and surveillance of emerging pathogens such as SARS-CoV-2 depend on nucleic acid isolation from clinical and environmental samples. Under normal circumstances, samples would be processed using commercial proprietary reagents in Biosafety 2 (BSL-2) or higher facilities. A pandemic at the scale of COVID-19 has caused a global shortage of proprietary reagents and BSL-2 laboratories to safely perform testing. Therefore, alternative solutions are urgently needed to address these challenges. We developed an open-source method called Magnetic- nanoparticle-Aided Viral RNA Isolation of Contagious Samples (MAVRICS) that is built upon reagents that are either readily available or can be synthesized in any molecular biology laboratory with basic equipment. Unlike conventional methods, MAVRICS works directly in samples inactivated in acid guanidinium thiocyanate-phenol-chloroform (e.g., TRIzol), thus allowing infectious samples to be handled safely without biocontainment facilities. Using 36 COVID-19 patient samples, 2 wastewater samples and 1 human pathogens control sample, we showed that MAVRICS rivals commercial kits in validated diagnostic tests of SARS-CoV-2, influenza viruses, and respiratory syncytial virus MESHD. MAVRICS is scalable and thus could become an enabling technology for widespread community testing and wastewater monitoring in the current and future pandemics.

    The impact of COVID-19 non-pharmaceutical interventions on the future dynamics of endemic infections

    Authors: Rachel E. Baker; Sang Woo Park; Wenchang Yang; Gabriel A. Vecchi; C. Jessica E. Metcalf; Bryan T. Grenfell

    doi:10.1101/2020.06.22.20137588 Date: 2020-06-23 Source: medRxiv

    Non-pharmaceutical interventions (NPIs) have been employed to reduce the transmission TRANS of SARS-CoV-2, yet these measures are already having similar effects on other directly-transmitted, endemic diseases. Disruptions to the seasonal transmission TRANS patterns of these diseases may have consequences for the timing and severity of future outbreaks. Here we consider the implications of SARS-CoV-2 NPIs for two endemic infections circulating in the United States of America (USA): respiratory syncytial virus (RSV) and seasonal influenza. Using laboratory surveillance data from 2020, we estimate that RSV transmission TRANS declined by at least 20% in the USA at the start of the NPI period. We simulate future trajectories of both RSV MESHD and influenza, using an epidemic model. As susceptibility increases over the NPI period, we find that substantial outbreaks of RSV MESHD may occur in future years, with peak outbreaks likely occurring in the winter of 2021-2022. Results for influenza broadly echo this picture, but are more uncertain; future outbreaks are likely dependent on the transmissibility TRANS and evolutionary dynamics of circulating strains.

    COVID-19: disease pathways and gene expression changes predict methylprednisolone can improve outcome in severe cases

    Authors: Sorin Draghici; Tuan-Minh Nguyen; Larry A Sonna; Cordelia Ziraldo; Radu L Vanciu; Raef Fadel; Austin Morrison; Mayur Ramesh; Gil Mor

    doi:10.1101/2020.05.06.20076687 Date: 2020-05-19 Source: medRxiv

    Background. Current management efforts of COVID-19 include: early diagnosis, use of antivirals and immune modulation. After the initial viral phase of the illness, identification of the patients developing cytokine storm syndrome is critical. Treatment of this hyper-inflammation MESHD in these patients using existing, approved therapies with proven safety profiles could address the immediate need to reduce the rising mortality. Methods. Using data from an A549 cell line, primary human bronchial epithelial (NBHE), as well as from COVID-19-infected lung, we compare the changes in the gene expression, pathways and mechanisms between SARS-CoV2, influenza A, and respiratory syncytial virus MESHD. Results. We identified FDA-approved drugs that could be repurposed to help COVID-19 patients with severe symptoms related to hyper-inflammation MESHD. An important finding is that drugs in the same class will not achieve similar effects. For instance methylprednisolone and prednisolone were predicted to be effective in reverting many of the changes triggered by COVID-19, while other closely related steroids, such as prednisone or dexamethasone, were not. An independent clinical study evaluated 213 subjects, 81 (38%) and 132 (62%) in pre-and post-methylprednisolone groups, respectively. The composite end point was composed of escalation to intensive care units, need for mechanical ventilation, and death MESHD. The composite endpoint occurred at a significantly lower rate in post-methylprednisolone group compared to pre-methylprednisolone group (34.9% vs. 54.3%, p=0.005). Conclusion. Clinical results confirmed the efficacy of the in silico prediction that indicated methyl- prednisolone could improve outcomes in severe COVID-19. These findings are important for any future pandemic regardless of the virus.

    A Transcriptome Analysis Identifies Potential Preventive and Therapeutic Approaches Towards COVID-19

    Authors: Md Rezaul Islam; Andre Fischer

    id:10.20944/preprints202004.0399.v1 Date: 2020-04-22 Source: Preprints.org

    The recent outbreak of Coronavirus Disease MESHD 2019 (COVID-19) is a major threat to human health and the global economy. In addition to the development of vaccines there is an urgent need for preventive and therapeutic strategies towards severe COVID-19. Key to this would be a better understanding of the molecular mechanismsoiuuuu affected by SARS-COV-2. To address this, we performed a systems biology approach by integrating available RNA-seq datasets from post-mortem lung tissue of COVID-19 patients and cell culture models infected with SARS-COV-2, Respiratory Syncytial virus MESHD or influenza virus. We identified two gene-expression modules that are commonly regulated by the three viral diseases MESHD and one that is specific to COVID-19. All 3 gene-expression modules represent key inflammatory processes. We identified several proteins within these networks that can be targeted by FDA approved drugs. Key examples are TNF, NFkB, INTERLEUKIN-1 and ALOX5 signaling pathways. Our data also suggest that Vitamin D supplementation and a ketogenic diet should be further analyzed as preventive strategies. In conclusion, our data highlights the potential of transcriptomics to unravel the pathological processes related to COVID-19 and guide the initiation of clinical trials.

    Influenza Viral Infection is a High-Risk Factor for Developing Coronavirus Disease MESHD 2019 (COVID-19)

    Authors: Lei Zhang; Youwei Zhang

    id:10.20944/preprints202003.0307.v1 Date: 2020-03-20 Source: Preprints.org

    Coronavirus disease MESHD 2019 (COVID-19) is caused by infection with the 2019 novel coronavirus 2 (2019-nCoV, now referred to as SARS-CoV-2). COVID-19 has become a global pandemic since its outbreak at the end of Dec 2019. COVID-19 could lead to severe acute respiratory disease MESHD, especially to those who have reduced immunity. Binding of the viral Spike protein (S) to its receptor ACE2 (Angiotensin Converting Enzyme 2) on the surface of target cells has been proven to be key for virus entry and infection MESHD. Although ACE2 expression in the respiratory system is necessary for pneumonia HP pneumonia MESHD infection by SARS-CoV-2, the regulation of ACE2 gene expression remains poorly investigated, especially for patients that are in pre-pathological conditions. Here, by analyzing The Gene Expression Omnibus (GEO) database, we investigated the expression regulation of ACE2 in various kinds of primary epithelial cells from the respiratory system after influenza A or respiratory Syncytial Virus (RSV) infection MESHD. Our analyses reveal that infection of influenza A, RSV MESHD or influenza vaccines greatly increased ACE2 expression, suggesting that influenza viral infection MESHD could represent a high risk factor for developing COVID-19. We also found that the regulatory effect of influenza A virus on ACE2 expression is associated with activation of the interferon beta-induced pathway and viral RNA-activated host response. Together, our data provide a theoretical framework for clinical classification for SARS-CoV-2 infection MESHD susceptibility and could be used for future prevention and therapy treatment for COVID-19.

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