title: Comparison of commercial systems for extraction of nucleic acids from DNA/RNA respiratory pathogens

text: Abstract This study compared six automated nucleic acid extraction systems and one manual kit for their ability to recover nucleic acids from human nasal wash specimens spiked with five respiratory pathogens, representing Gram-positive bacteria (Streptococcus pyogenes), Gram-negative bacteria (Legionella pneumophila), DNA viruses (adenovirus), segmented RNA viruses (human influenza virus A), and non-segmented RNA viruses (respiratory syncytial virus). The robots and kit evaluated represent major commercially available methods that are capable of simultaneous extraction of DNA and RNA from respiratory specimens, and included platforms based on magnetic-bead technology (KingFisher mL, Biorobot EZ1, easyMAG, KingFisher Flex, and MagNA Pure Compact) or glass fiber filter technology (Biorobot MDX and the manual kit Allprep). All methods yielded extracts free of cross-contamination and RT-PCR inhibition. All automated systems recovered L. pneumophila and adenovirus DNA equivalently. However, the MagNA Pure protocol demonstrated more than 4-fold higher DNA recovery from the S. pyogenes than other methods. The KingFisher mL and easyMAG protocols provided 1- to 3-log wider linearity and extracted 3- to 4-fold more RNA from the human influenza virus and respiratory syncytial virus. These findings suggest that systems differed in nucleic acid recovery, reproducibility, and linearity in a pathogen specific manner.


Globalization of Chikungunya: 10 years to invade the world


title: From guidance to practice: Promoting risk communication and community engagement for prevention and control of coronavirus disease (COVID‐19) outbreak in China

text: Integrating risk communication and community engagement into the national public health emergency response is crucial. Considering the difficulties and challenges faced by China in the prevention and control of coronavirus disease (COVID‐19) and based on interim guidelines from the World Health Organization, this article makes several recommendations addressing the outbreak in China. These include improvements in the internal governmental risk communication systems, enhancing the coordination between internal and partner governmental emergency management, and promoting public communication in response to societal concerns. Regarding these recommendations, we emphasize community engagement in joint prevention and control, confronting uncertainty and countering rumors effectively, and strengthening international cooperation and evidence‐based decision making for prevention and control measures.


title: A novel low virulent respiratory infectious bronchitis virus originating from the recombination of QX, TW and 4/91 genotype strains in China

text: Abstract In China, variants of infectious bronchitis virus (IBV) evolve continually and diverse recombinant strains have been reported. Here, an IBV strain, designated as ck/CH/LJX/2017/07 (referred as JX17) was isolated from chicken vaccinated with H120 and 4/91 in Jiangxi, China, in 2017. Sequence analysis reveals of the S1 gene of JX17 the highest nucleotide identity of 98.15% with that of GI-7 genotype TW2575/98 strain. Furthermore, whole genome analysis among JX17 and other 18 IBV strains demonstrates that JX17 has the highest nucleotide identity of 95.94% with GI-19 genotype YX10 strain. Among all genes of JX17 except the S1 gene, the N gene and 3’ UTR have the highest identity to GI-13 genotype 4/91 strain and the rest genes are the most identical to GI-19 genotype YX10 strain. Analyzed by the RDP and SimPlot, the recombination of JX17 strain was shown to occur in regions which include 5’-terminal S1 gene (20,344 to 22,447 nt), most N gene and 3’ UTR (26,163 to 27,648 nt). The pathogenicity study shows that JX17 is a natural low virulent IBV variant which caused respiratory symptoms but no death. Taken together, these results indicate that IBV strains continue to evolve through genetic recombination and three prevalent genotypes in China including QX, TW and 4/91 have started to recombine.


title: Progression of CXR features on a COVID-19 survivor

text: COVID-19 causes consolidations or ground glass opacities that are predominantly peripheral, basal, and bilateral on chest x-ray (CXR). There are no published case reports that present over ten serial CXRs on the same patient. We present a case report of a 68-year-old patient with confirmed COVID-19 and a prolonged course of admission, receiving nasal and humidified oxygen, non-invasive and then mechanical ventilation. She self-extubated, but remained stable on nasal oxygen only and was transferred for rehabilitation. We present 12 of her serial CXRs over six weeks, showing progression from subtle changes to overt widespread pneumonitis to slow resolution. She is also an example of a rare case of COVID-19 pneumonitis causing persistent hypoxia for over six weeks.


title: Localization of major neutralizing epitopes on the S1 polypeptide of the murine coronavirus peplomer glycoprotein

text: Abstract A recombinant baculovirus system has been used to express the amino terminal half of the murine coronavirus (JHMV) peplomer glycoprotein in insect cells. The expressed polypeptide is glycosylated and is recognized by a set of monoclonal antibodies (mAbs) specific for JHMV S protein. Three of these mAbs have a very high neutralizing activity for JHMV but not for other MHV strains. These results indicate that JHMV-specific, major neutralizing epitopes reside in the amino terminal S1 subunit of the peplomer glycoprotein.


title: Influenza Virus Infections

text: Abstract Influenza, commonly known as flu, is a contagious, febrile viral disease. Common symptoms are chills, fever, sore throat, coughing, sneezing, muscle pains, headache, myalgia, etc. Influenza viruses (IVs) belonging to orthomyxovirus group are of three types (types A, B, and C). IVs are enveloped, segmented, negative-stranded RNA viruses containing eight distinct RNA segments (types A and B) and seven RNA segments (type C). Only type A viruses exhibit different subtypes. Currently, 18 hemagglutination (HA) subtypes (H1 to H18) and 11 neuraminidase (NA) subtypes (N1 to N11) are known in humans and other warm-blooded animals. Flu outbreaks occur as annual epidemics in fall and winter and infrequently, as worldwide pandemics. Annual epidemics are caused by antigenic drift due to mutations in HA and NA antigens, whereas pandemics are caused by antigenic shift due to genetic reassortment among different subtype viruses. The first pandemic of the twenty-first century, declared by the World Health Organization (WHO) in 2009, was caused by an H1N1 virus, derived from quadruple reassortment among swine, avian, and human IVs. Currently, two types of antiinfluenza drugs, based on either blocking the M2 proton channel (amantadine and rimantadine) or inhibiting NA (oseltamivir or Tamiflu by Roche and zanamivir or Relanza by GlaxoSmithKline) are available. The virus is commonly spread by aerosol droplets and by fingertips. Therefore, washing hands and avoiding contact with infected persons are the first lines of defense. Indoor living and closeness of people in an enclosed environment in winter facilitate virus transmission leading to epidemics. Annual vaccination is the best preventative measure. Currently, two types of vaccines (subunit vaccine by injection and live attenuated vaccine by nasal spray) are available and recommended by WHO and Centers for Disease Control.


title: Production of a monoclonal antibody against SARS-CoV spike protein with single intrasplenic immunization of plasmid DNA

text: Abstract Severe acute respiratory syndrome (SARS) is a highly infectious disease caused by a novel coronavirus (SARS-CoV). Specific monoclonal antibodies (mAbs) against the SARS-CoV are vital for early diagnosis and pathological studies of SARS. Direct intrasplenic inoculation of plasmid DNA encoding antigen is an effective and fast approach to generate specific mAb when the protein antigen is difficult to prepare or dangerous in use. In this study, we selected one fragment of SARS-CoV spike protein (S1-3) as antigenic determinant by immunoinformatics. Single intrasplenic immunization of plasmid DNA encoding S1-3 induced anti-spike protein antibodies. We established one hybridoma cell line secreting specific mAb and evaluated this mAb with murine leukemia virus pseudotyped with SARS-CoV spike protein (MLV/SARS-CoV). The mAb could recognize the spike protein on the MLV/SARS-CoV-infected Vero E6 cells albeit with no neutralizing effect on the infectivity of the pseudotype virus. Our results show that a single-shot intrasplenic DNA immunization is efficient for the production of specific mAb against SARS spike protein, and a linear epitope of the spike protein is recognized in this study.


Lack of Mimivirus Detection in Patients with Respiratory Disease, China


title: High-resolution Chest CT Features and Clinical Characteristics of Patients Infected with COVID-19 in Jiangsu, China

text: Abstract Background A pneumonia associated with the coronavirus disease 2019 (COVID-19) recently emerged in China. It was recognized as a global health hazard. Methods 234 inpatients with COVID-19 were included. Detailed clinical data, chest HRCT basic performances and certain signs were recorded, and ground-glass opacity (GGO), consolidation, fibrosis and air trapping were quantified. Both clinical types and CT stages were evaluated. Results Most patients (approximately 90%) were classified as common type and with epidemiologic history. Fever and cough were main symptoms. Chest CT showed abnormal attenuation in bilateral multiple lung lobes, distributed in the lower and/or periphery of the lungs (94.98%), with multiple shapes. GGO and vascular enhancement sign were most frequent seen, followed by interlobular septal thickening and air bronchus sign as well as consolidation, fibrosis and air trapping. There were significant differences in most of CT signs between different stage groups. The SpO2 and OI were decreased in stage IV, and the CT score of consolidation, fibrosis and air trapping was significantly lower in stage I (P <0.05). A weak relevance was between the fibrosis score and the value of PaO2 and SpO2 (P <0.05). Conclusions Clinical performances of patients with COVID-19, mostly with epidemiologic history and typical symptoms, were critical valuable in the diagnosis of the COVID-19. While chest HRCT provided the distribution, shape, attenuation and extent of lung lesions, as well as some typical CT signs of COVID-19 pneumonia.


title: Performances of different diagnostic tests for feline infectious peritonitis in challenging clinical cases

text: Objectives: Feline infectious peritonitis (FIP) can be difficult to diagnose. Histopathology is considered the gold standard test but immunohistochemistry (IHC) is mandatory to confirm/exclude the disease. This study aimed to assess the performances of tests carried out in vivo or at postmortem examination in challenging cases in which FIP was confirmed or excluded based on IHC or on adequate follow‐up. Methods: Twelve cases (four without FIP, eight with FIP) were retrospectively studied. Clinical findings, serum protein electrophoresis (SPE), analysis of the effusions (AE), antifeline coronavirus serology, serum concentration of α1‐acid glycoprotein (AGP) and histopathology were classified as consistent, doubtful or non‐consistent with FIP. Sensitivity, specificity and concordance (κ) with the final diagnosis were calculated. Results: Concordance was absent for serology (κ=−0·08) and AE (κ=−0·52), poor for histopathology (κ=0·09), fair for SPE (κ=0·25) and perfect for AGP (κ=1·00). Sensitivity was high for AGP (100%) and low for AE (50%), SPE (37·5%) and histopathology (37·5%). Specificity was high for AGP or histopathology (100%) and low for SPE (50%) and AE (0%). Clinical Significance: IHC must always be performed to confirm FIP. If this is not possible, when histopathology is controversial, elevated AGP concentrations may support the diagnosis of FIP.


title: Spatial–temporal transmission of influenza and its health risks in an urbanized area

text: Cities and urban areas play an important role in fostering influenza transmission, often leading to epidemics and even pandemics. Although there is growing literature on influenza transmission at national and international scales, little attention has been paid to a city scale. This article aims to understand the spatial–temporal transmission of influenza and identify its health risks in the urbanized area of Buffalo, New York. An individual-based spatially explicit model is established to replicate an urban contact network, and simulate influenza epidemics. The resulting epidemic curves and infection intensity maps are used to analyze the transmission dynamics, possible contributing factors, and high-risk places and times. The results indicate that the city-wide transmission of influenza can be described by five stages: local growth, expansion, fast city-wide growth, slow city-wide growth, and fade-out. The places and times associated with higher risk are closely related to spatial heterogeneity in the population, and travel behaviors of individuals. Interestingly, these high-risk places and times are insensitive to where infection sources are introduced. This research suggests that high-risk places can be pre-identified as control targets using census and land use data. In addition, a better understanding on the city-wide travel of individuals is critical for designing proper timelines for influenza control. These suggestions will be valuable for local health agencies as they prepare to combat new waves of H1N1 influenza.


title: Apoptosis induced by a cytopathic hepatitis A virus is dependent on caspase activation following ribosomal RNA degradation but occurs in the absence of 2′–5′ oligoadenylate synthetase

text: Abstract We have presented previously evidence that the cytopathogenic 18f strain of hepatitis A virus (HAV) induced degradation of ribosomal RNA (rRNA) in infected cells [Arch. Virol. 148 (2003) 1275–1300]. In contrast, the non-cytopathogenic parent virus HM175 clone 1 had no effect on rRNA integrity. We present here data showing that rRNA degradation is followed by apoptosis accompanied by characteristic DNA laddering in the cytoplasm of 18f infected cells. The DNA laddering coincided with the detection of caspase 3 and PARP-1 cleavage and was dependent upon activation of the caspase pathway, since treatment with Z-VAD-FMK, a pan-caspase inhibitor, inhibited both events. RNase L mRNA was present in both virus-infected and uninfected cells. Messenger RNA for the interferon inducible enzyme 2′–5′ oligoadenylate synthetase (2′–5′ OAS), which polymerizes ATP into 2′–5′ oligo adenylate (2–5A, the activator of RNase L) in the presence of double-stranded RNA, was not detected following virus infection. 2′–5′ OAS mRNA was induced by treatment of the cells with interferon-β (IFN-β). IFN-β mRNA was marginally induced following infection. However, phosphorylated STAT 1, a key regulator of interferon-stimulated gene transcription was not detected in virus infected cells. STAT 1 phosphorylation in response to IFN treatment was lower in virus-infected cells, compared to uninfected cells treated with interferon, suggesting that 18f virus infection interferes with interferon signaling. The results suggest that 18f infection causes the induction of a 2–5A independent RNase L like activity.


title: Which Melbourne metropolitan areas are vulnerable to COVID-19 based on age, disability and access to health services? Using spatial analysis to identify service gaps and inform delivery

text: Abstract Ageing adults (65+) with disability are especially vulnerable to COVID-19 and upon contracting, are a cohort most likely to require palliative care. Therefore, it is very important that health services - particularly health services providing palliative care - are proximately available. Treating the Melbourne metropolitan area as a case-study, a spatial analysis was conducted to clarify priority areas with a significantly high percentage and number of ageing adults (65+) with disability, and high barriers to accessing primary health services. After, travel times from priority areas to (i) palliative medicine, and (ii) hospital services were calculated. The geographic dispersion of areas with people vulnerable to COVID-19 with poor access to palliative care and health services are clarified. Unique methods of health service delivery are required to ensure that vulnerable populations in under-serviced metropolitan areas receive prompt and adequate care. The spatial methodology employed can be implemented in different contexts to support evidence-based COVID-19 and pandemic palliative care service decisions.


title: Respiratory Flows As A Method For Safely Preventing The Coronavirus Transmission (Covid-19)

text: SUMMARY The spread of CoV-2 occurs mainly by respiratory droplets. Its dispersion depends on several factors: viscoelasticity of fluid, ventilation, evaporation rate, exhalations, sneeze or cough. At moment, the preventive distance to avoid the contamination has been established in 1-2 m. We believe that it is necessary to review this aspect, because the respiratory flows change with the intensity of physical activity.The ventilatory response can be evaluated in terms of ventilatory demand or ventilatory efficiency. During maximal effort tests, athletes mobilize an extraordinary amount of air arriving to 150/200 L/min. The respiratory volume follows increase in linear progression during the test in function of power developed. When the air volume is increased 10 times, we think that the distance should be around 6-7 m.


title: Combination of RT‐qPCR testing and clinical features for diagnosis of COVID‐19 facilitates management of SARS‐CoV‐2 outbreak

text: In December 2019, a cluster of acute respiratory illness occurred in Wuhan, Hubei Province, China. This disease is now officially known as 2019 novel coronavirus disease (COVID-19) from WHO, novel coronavirus pneumonia This article is protected by copyright. All rights reserved.


title: Initial emergency department mechanical ventilation strategies for COVID-19 hypoxemic respiratory failure and ARDS

text: INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging viral pathogen that causes the novel coronavirus disease of 2019 (COVID-19) and may result in hypoxemic respiratory failure necessitating invasive mechanical ventilation in the most severe cases. OBJECTIVE: This narrative review provides evidence-based recommendations for the treatment of COVID-19 related respiratory failure requiring invasive mechanical ventilation. DISCUSSION: In severe cases, COVID-19 leads to hypoxemic respiratory failure that may meet criteria for acute respiratory distress syndrome (ARDS). The mainstay of treatment for ARDS includes a lung protective ventilation strategy with low tidal volumes (4–8 mL/kg predicted body weight), adequate positive end-expiratory pressure (PEEP), and maintaining a plateau pressure of < 30 cm H(2)O. While further COVID-19 specific studies are needed, current management should focus on supportive care, preventing further lung injury from mechanical ventilation, and treating the underlying cause. CONCLUSIONS: This review provides evidence-based recommendations for the treatment of COVID-19 related respiratory failure requiring invasive mechanical ventilation.


title: Chronic Obstructive Pulmonary Disease Inpatient Management

text: This article outlines the management of patients with acute exacerbations of chronic obstructive pulmonary disease (COPD), which are common in the course of chronic COPD and are associated with substantial morbidity. There are numerous guidelines, but literature suggests that there is substantial variation in care in patients with acute exacerbations of COPD. Key components of acute therapy for most patients include oral steroids, antibiotics, nebulizers, oxygen, and early consideration of noninvasive ventilation. Adjuvant components of care include venous thromboembolism prophylaxis, appropriate immunizations, counseling for smoking cessation, and consideration of pulmonary rehabilitation.


title: Heart University: a new online educational forum in paediatric and adult congenital cardiac care. The future of virtual learning in a post-pandemic world?

text: Online learning has become an increasingly expected and popular component for education of the modern-day adult learner, including the medical provider. In light of the recent coronavirus pandemic, there has never been more urgency to establish opportunities for supplemental online learning. Heart University aims to be “the go-to online resource” for e-learning in CHD and paediatric-acquired heart disease. It is a carefully curated open access library of paedagogical material for all providers of care to children and adults with CHD or children with acquired heart disease, whether a trainee or a practising provider. In this manuscript, we review the aims, development, current offerings and standing, and future goals of Heart University.


title: Sinus Infections, Inflammation, and Asthma

text: There is an important link between the upper and lower respiratory tracts whereby inflammation in one environment can influence the other. In acute rhinosinusitis, pathogen exposures are the primary driver for inflammation in the nose, which can exacerbate asthma. In chronic rhinosinusitis, a disease clinically associated with asthma, the inflammation observed is likely from a combination of an impaired epithelial barrier, dysregulated immune response, and potentially infection (or colonization) by specific pathogens. This review explores the associations between rhinosinusitis and asthma, with particular emphasis placed on the role of infections and inflammation.


title: Experimental infection of United States swine with a Chinese highly pathogenic strain of porcine reproductive and respiratory syndrome virus

text: Abstract The pathogenesis of Type 2 highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) in 10-week old swine in the United States was investigated. rJXwn06, rescued from an infectious clone of Chinese HP-PRRSV, replicated in swine with at least 100-fold increased kinetics over U.S. strain VR-2332. rJXwn06 caused significant weight loss, exacerbated disease due to bacterial sepsis and more severe histopathological lung lesions in pigs exposed to HP-PRRSV than to those infected with VR-2332. Novel findings include identification of bacterial species present, the degree of thymic atrophy seen, and the inclusion of contact animals that highlighted the ability of HP-PRRSV to rapidly transmit between animals. Furthermore, comprehensive detailed cytokine analysis of serum, bronchoalveolar lavage fluid, and tracheobronchial lymph node tissue homogenate revealed a striking elevation in levels of cytokines associated with both innate and adaptive immunity in HP-PRRSV infected swine, and showed that contact swine differed in the degree of cytokine response.


title: Protecting children from iatrogenic harm during COVID19 pandemic

text: Critical care management of patients with COVID‐19 has been influenced by a mixture of public, media and societal pressure, as well as clinical and anecdotal observations from many prominent researchers and key opinion leaders. These factors may have affected the principles of evidence‐based medicine and encouraged the widespread use of non‐tested pharmacological and aggressive respiratory support therapies, even in intensive care units (ICUs). The COVID‐19 pandemic has predominantly affected adult populations, while children appear to be relatively spared of severe disease. Notwithstanding, paediatric intensive care (PICU) clinicians may already have been influenced by changes in practices of adult ICUs, and these changes may pose unintended consequences to the vulnerable population in the PICU. In this article, we analyse several potential iatrogenic causes of the detrimental effects of the current pandemic to children and highlight the risks underlying a sudden change of clinical practice.


title: High mannose-specific lectin (KAA-2) from the red alga Kappaphycus alvarezii potently inhibits influenza virus infection in a strain-independent manner

text: Abstract The carbohydrate binding profile of the red algal lectin KAA-2 from Kappaphycus alvarezii was evaluated by a centrifugal ultrafiltration–HPLC method using pyridylaminated oligosaccharides. KAA-2 bound exclusively to high mannose type N-glycans, but not to other glycans such as complex type, hybrid type, or the pentasaccharide core of N-glycans. This lectin exhibited a preference for an exposed α1–3 Man on a D2 arm in a similar manner to Eucheuma serra agglutinin (ESA-2), which shows various biological activities, such as anti-HIV and anti-carcinogenic activity. We tested the anti-influenza virus activity of KAA-2 against various strains including the recent pandemic H1N1-2009 influenza virus. KAA-2 inhibited infection of various influenza strains with EC50s of low nanomolar levels. Immunofluorescence microscopy using an anti-influenza antibody demonstrated that the antiviral activity of KAA-2 was exerted by interference with virus entry into host cells. This mechanism was further confirmed by the evidence of direct binding of KAA-2 to a viral envelope protein, hemagglutinin (HA), using an ELISA assay. These results indicate that this lectin would be useful as a novel antiviral reagent for the prevention of infection.


title: Clinical guidance for navigating the QTc-prolonging and arrhythmogenic potential of pharmacotherapy during the COVID-19 pandemic

text: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for coronavirus disease 19 (COVID-19), has rapidly spread since December 2019 to become the focus of healthcare systems worldwide. Its highly contagious nature and significant mortality has led to its prioritization as a public health issue. The race to prevent and treat this disease has led to “off-label” prescribing of medications such as hydroxychloroquine, azithromycin, and Kaletra (lopinavir/ritonavir). Currently, there is no robust clinical evidence for the use of these drugs in the treatment of COVID-19, with most, if not all of these medications associated with the potential for QT interval prolongation, torsades de pointes, and resultant drug-induced sudden cardiac death. The aim of this document is to help healthcare providers mitigate the potential deleterious effects of drug-induced QTc prolongation.


title: Human genetics and genomics meetings going virtual: practical lessons learned from two international meetings in early 2020

text: The recent coronavirus disease 2019 (COVID-19) pandemic has caused worldwide disruption which also extends to the arena of scientific meetings around the world. Here, we explore the lessons learned from moving two human genetics and genomics meetings quickly to an online format in early 2020. The tips presented herein may be useful not only for future virtual meetings but may also enrich future physical if not hybrid meetings once they resume.


Reproductive health and human rights


title: Identification of the nucleotide substitutions in 62 SARS-CoV-2 sequences from Turkey

text: A previously unknown coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been shown to cause coronavirus disease 2019 (COVID-19) pandemic. The first case of COVID-19 in Turkey has been declared in March 11th, 2020 and from there on, more than 150,000 people in the country have been diagnosed with the disease. In this study, 62 viral sequences from Turkey, which have been uploaded to GISAID database, were analyzed by means of their nucleotide substitutions in comparison to the reference SARS-CoV-2 genome from Wuhan. Our results indicate that the viral isolates from Turkey harbor some common mutations with the viral strains from Europe, Oceania, North America and Asia. When the mutations were evaluated, C3037T, C14408T and A23403G were found to be the most common nucleotide substitutions among the viral isolates in Turkey, which are mostly seen as linked mutations and are part of a haplotype observed high in Europe.


title: Clinical and epidemiological features of respiratory virus infections in preschool children over two consecutive influenza seasons in southern Brazil

text: This study reports the results of a systematic screening for respiratory viruses in pediatric outpatients from an emergency department (ED) in southern Brazil during two consecutive influenza seasons. Children eligible for enrollment in this study were aged 24–59 months and presented with acute respiratory symptoms and fever. Naso‐ and oropharyngeal swabs were collected and multiplex reverse transcription PCR (RT‐PCR) was performed to identify the respiratory viruses involved. In total, 492 children were included in this study: 248 in 2010 and 244 in 2011. In 2010, 136 samples (55%) were found to be positive for at least one virus and the most frequently detected viruses were human rhinovirus (HRV) (18%), adenovirus (AdV) (13%), and human coronavirus (CoV) (5%). In 2011, 158 samples (65%) were found to be positive for at least one virus, and the most frequently detected were HRV (29%), AdV (12%), and enterovirus (9%). Further, the presence of asthma (OR, 3.17; 95% CI, 1.86–5.46) was independently associated with HRV infection, whereas fever was associated with AdV (OR, 3.86; 95% CI, 1.31–16.52) and influenza infections (OR, 3.74; 95% CI, 1.26–16.06). Ten patients (2%) were diagnosed with pneumonia, and six of these tested positive for viral infection (4 HRV, 1 RSV, and 1 AdV). Thus, this study identified the most common respiratory viruses found in preschool children in the study region and demonstrated their high frequency, highlighting the need for improved data collection, and case management in order to stimulate preventive measures against these infections. J. Med. Virol. 88:1325–1333, 2016. © 2016 Wiley Periodicals, Inc.


title: Putative probiotic Lactobacillus spp. from porcine gastrointestinal tract inhibit transmissible gastroenteritis coronavirus and enteric bacterial pathogens

text: A total of 310 bacterial strains isolated from the porcine gastrointestinal tract were tested for their activity against transmissible gastroenteritis (TGE) coronavirus and other enteric pathogens. Based on activity, the strains Probio-38 and Probio-37 were selected as potential probiotics and identified as Lactobacillus plantarum Probio-38 and Lactobacillus salivarius Probio-37 respectively by 16S rRNA gene sequencing. Supernatants of these strains inhibited TGE coronavirus in vitro in ST cells, without any cytopathic effect even after 72 h of incubation. Both the strains exhibited high survival in synthetic gastric juice. The strains were resistant to 5% porcine bile and exhibited antimicrobial activity against all the 13 enteric bacterial pathogens tested. These strains also exhibited resistance to most of the antibiotics analyzed. The inhibition of transmissible gastroenteritis coronavirus and enteric bacterial pathogens as well as the bile tolerance, high survival in gastric juice, and the antibiotic resistance indicate that the two isolated bacterial strains are ideal probiotic candidates for animal application after proper in vivo experiments.


title: Antivirals against animal viruses

text: Abstract Antivirals are compounds used since the 1960s that can interfere with viral development. Some of these antivirals can be isolated from a variety of sources, such as animals, plants, bacteria or fungi, while others must be obtained by chemical synthesis, either designed or random. Antivirals display a variety of mechanisms of action, and while some of them enhance the animal immune system, others block a specific enzyme or a particular step in the viral replication cycle. As viruses are mandatory intracellular parasites that use the host’s cellular machinery to survive and multiply, it is essential that antivirals do not harm the host. In addition, viruses are continually developing new antiviral resistant strains, due to their high mutation rate, which makes it mandatory to continually search for, or develop, new antiviral compounds. This review describes natural and synthetic antivirals in chronological order, with an emphasis on natural compounds, even when their mechanisms of action are not completely understood, that could serve as the basis for future development of novel and/or complementary antiviral treatments.


title: Antiviral Potential of Selected Starter Cultures, Bacteriocins and d,l-Lactic Acid

text: The antiviral potential of selected bacteria species [lactic acid bacteria (LAB) and micrococcaceae] was examined. By this, the effect of their cell-free supernatants as well as of certain species-related metabolites (sakacin A, nisin, and lactic acid) was investigated on different viruses after exposure at 24 °C for 3 days. Viruses were incubated with supernatants and metabolites in a dilution ratio of 1:10. Data for antiviral effects towards murine norovirus S99 (MNV), influenza A virus A/WSN/33 (H1N1), Newcastle disease virus Montana (NDV) and feline herpesvirus KS 285 (FHV) were generated in vitro simulating pH and temperature conditions according to raw sausage fermentations. Investigations showed no antiviral effect of sakacin A and nisin on MNV, H1N1, FHV and NDV. Furthermore, the antiviral potential of d,l-lactic acid was determined for MNV and H1N1. At raw sausage-related pH values (5.0–6.2) it could be shown that the virus titre for MNV and H1N1 was reduced by a maximum of 3.25 log and 2.5 log units, respectively. In addition, 29 culture supernatants of different bacteria species, mainly LAB and staphylococci, were tested for their antiviral activity against MNV. Only the cell-free supernatant of a Lb. curvatus strain showed a higher virus titre reduction of MNV by 1.25 log units compared to the control. Further studies on the characterisation of this cell-free supernatant were carried out, however, the antiviral substance could not be identified so far.


title: Interest of designed cyclodextrin-tools in gene delivery

text: Summary Cyclodextrins (CyDs) currently displays even today the image of a natural macrocyclic compound largely dominant in the formation of inclusion complexes with small hydrophobic molecules. During the past 10years, advances in this field allowed to achieve more and more sophisticated CyDs derivatives opening a simple access in scale-up quantities to original and better CyD-based gene delivery systems. In addition, possibility to combine covalent and supramolecular approaches offers new venues for the design of tailor-made CyD-based nanovehicles to improve their transfection ability and gene transfer in cells. In this account, we describe our recent progress in the construction of a novel CyD-based G0 (generation number) core dendrimer, scalable to CyD oligomers by a strategy using protonable guanidine tethers and whose concept can be generalized for the assembly of CyD pre-coated dendrimers. The synthetic strategy based on an original Staudinger-Aza-Wittig tandem coupling reaction. We present an outline of the different analytical strategies to characterize CyD-ODN (cyclodextrin-oligodeoxynucleotide) complexes. Among them, Capillary electrophoresis (CE) was used to perfectly characterize our CyD-siRNA and CyD-DNA complexes and shown to be a very attractive method with advantages of low sample consumption, rapid analysis speed, and high efficiency that make this technology a major tool for association constant measurement. Finally, we present the different biological methods that can be used, in vitro, to study gene delivery, and more precisely ones we have performed to evaluate the capability of our original model bis-guanidinium-tetrakis-β-cyclodextrin dendrimeric tetrapod, to deliver efficiently DNA or siRNA in eukaryotic cells.


title: A molecular epidemiological investigation of PEDV in China: Characterization of co‐infection and genetic diversity of S1‐based genes

text: Porcine epidemic diarrhoea virus (PEDV) is an emerging and re‐emerging epizootic virus of swine that causes substantial economic losses to the pig industry in China and other countries. The variations in the virus, and its co‐infections with other enteric viruses, have contributed to the poor control of PEDV infection. In the current study, a broad epidemiological investigation of PEDV was carried out in 22 provinces or municipalities of China during 2015–2018. The enteric viruses causing co‐infection with PEDV and the genetic diversity of the PEDV S1 gene were also analysed. The results indicated that, of the 543 diarrhoea samples, 66.85% (363/543) were positive for PEDV, and co‐infection rates of PEDV with 13 enteric viruses ranged from 3.58% (13/363) to 81.55% (296/363). Among these enteric viruses, the signs of diarrhoea induced by PEDV were potentially associated with co‐infections with porcine enterovirus 9/10 (PEV) and torque teno sus virus 2 (TTSuV‐2) (p < .05). The 147 PEDV strains identified in our study belong to Chinese pandemic strains and exhibited genetic diversity. The virulence‐determining S1 proteins of PEDV pandemic strains were undergoing amino acid mutations, in which S58_S58insQGVN–N135dup–D158_I159del‐like mutations were common patterns (97.28%, 143/147). When compared with 2011–2014 PEDV strains, the amino acid mutations of PEDV pandemic strains were mainly located in the N‐terminal domain of S1 (S1‐NTD), and 21 novel mutations occurred in 2017 and 2018. Furthermore, protein homology modelling showed that the mutations in pattern of insertion and deletion mutations of the S1 protein of PEDV pandemic strains may have caused structural changes on the surface of the S1 protein. These data provide a better understanding of the co‐infection and genetic evolution of PEDV in China.


title: Virome of a Feline Outbreak of Diarrhea and Vomiting Includes Bocaviruses and a Novel Chapparvovirus

text: An unexplained outbreak of feline diarrhea and vomiting, negative for common enteric viral and bacterial pathogens, was subjected to viral metagenomics and PCR. We characterized from fecal samples the genome of a novel chapparvovirus we named fechavirus that was shed by 8/17 affected cats and identified three different feline bocaviruses shed by 9/17 cats. Also detected were nucleic acids from attenuated vaccine viruses, members of the normal feline virome, viruses found in only one or two cases, and viruses likely derived from ingested food products. Epidemiological investigation of disease signs, time of onset, and transfers of affected cats between three facilities support a possible role for this new chapparvovirus in a highly contagious feline diarrhea and vomiting disease.


title: Stably expressed FIPV peplomer protein induces cell fusion and elicits neutralizing antibodies in mice

text: Abstract We have established bovine papilloma virus (BPV)-transformed mouse C127 cell lines that synthesize the peplomer protein of the feline infectious peritonitis virus (FIPV) strain 79-1146. For this purpose, a new cassette expression vector pHSL, which carries the Drosophila HSp70 promotor and the polyadenylation signal of the Moloney murine leukemia virus long terminal repeat, was constructed. Cocultivation of the BPV-transformed cell lines with FIPV-permissive feline fcwf-D cells resulted in polykaryocyte formation. Since it depended on the presence of fcwf-D cells, binding of E2 to the cell receptor may be required for membrane fusion. E2 was synthesized as a core-glycosylated protein of 180K which was only slowly transported from the endoplasmic reticulum to the medial Golgi: of the E2-molecules labeled during a 1-hr pulse about half was still completely sensitive to endoglycosidase H after a 2-hr chase, while the remaining E2 had been chased into multiple, partially endoglycosidase H-resistant forms. Immunofluorescence studies also indicated that most E2 was retained intracellularly. Mice immunized with whole lysates of the transformed cells produced FIPV-neutralizing antibodies as shown by plaque reduction.


title: Failure of Fluid Absorption in the Endolymphatic Sac Initiates Cochlear Enlargement that Leads to Deafness in Mice Lacking Pendrin Expression

text: Mutations of SLC26A4 are among the most prevalent causes of hereditary deafness. Deafness in the corresponding mouse model, Slc26a4(−/−), results from an abnormally enlarged cochlear lumen. The goal of this study was to determine whether the cochlear enlargement originates with defective cochlear fluid transport or with a malfunction of fluid transport in the connected compartments, which are the vestibular labyrinth and the endolymphatic sac. Embryonic inner ears from Slc26a4(+/−) and Slc26a4(−/−) mice were examined by confocal microscopy ex vivo or after 2 days of organ culture. Culture allowed observations of intact, ligated or partially resected inner ears. Cochlear lumen formation was found to begin at the base of the cochlea between embryonic day (E) 13.5 and 14.5. Enlargement was immediately evident in Slc26a4(−/−) compared to Slc26a4(+/−) mice. In Slc26a4(+/−) and Slc26a4(−/−) mice, separation of the cochlea from the vestibular labyrinth by ligation at E14.5 resulted in a reduced cochlear lumen. Resection of the endolymphatic sacs at E14.5 led to an enlarged cochlear lumen in Slc26a4(+/−) mice but caused no further enlargement of the already enlarged cochlear lumen in Slc26a4(−/−) mice. Ligation or resection performed later, at E17.5, did not alter the cochlea lumen. In conclusion, the data suggest that cochlear lumen formation is initiated by fluid secretion in the vestibular labyrinth and temporarily controlled by fluid absorption in the endolymphatic sac. Failure of fluid absorption in the endolymphatic sac due to lack of Slc26a4 expression appears to initiate cochlear enlargement in mice, and possibly humans, lacking functional Slc26a4 expression.


title: Neuraminidase activity and specificity of influenza A virus are influenced by haemagglutinin-receptor binding

text: Influenza virus haemagglutinin (HA) and neuraminidase (NA) are involved in the recognition and modulation of sialic acids on the cell surface as the virus receptor. Although the balance between two proteins functions has been found to be crucial for viral fitness, the interplay between the proteins has not been well established. Herein we present evidence for interplay between influenza HA and NA, which may affect the balance between two glycoprotein functions. NA enzymatic activities against sialoglycans were promoted by the presence of HA, which is in accordance with the level of co-existing HA. Such activity enhancement was lost when the HA-receptor binding properties were abolished by low-pH treatment or by mutations at the HA receptor binding domain. Sialidase activities of NA-containing virus-like particles and native influenza viruses were detected using different NA-assays and sialic acid substrates. Most pronounced HA-mediated NA enhancement was found when intact virions were confronted with multivalent surface-anchored substrates, which mimics the physiological conditions on cell membranes. Using recombinant viruses with altered HA bindings preference between α2,3- and α2,6-linked sialic acids, we also found that NA function against different substrates is correlated with the HA-receptor specificity. The effect of HA-receptor specificities on NA functions, together with the HA-mediated NA enhancement, may play a role in virus evasion of the mucus barrier, as well as in cross-species adaptation. Our data also indicate the importance of using multivalent substrates in future studies of NA functions.


title: Expression and Purification of Human Keratinocyte Growth Factor 2 by Fusion with SUMO

text: Small ubiquitin-related modifier (SUMO) fusion system has been shown to be efficient for enhancing expression and preventing degradation of the target protein. We showed herein that SUMO fusion to human keratinocyte growth factor 2 (hKGF-2) gene was feasible and it significantly enhanced protein expression and its efficiency. The fusion DNA fragment composed of SUMO gene, which was fused to hexahistidine tag, and hKGF-2 gene was amplified by PCR and inserted into the expression vector pET28a to construct the recombinant plasmid, pET28a-SUMO-hKGF-2. The plasmid was then transformed into Escherichia coli Rosetta(TM)2(DE3), and the recombinant fusion protein SUMO-hKGF-2 was expressed at 30°C for 6 h, with the induction of IPTG at the final concentration of 0.4 mM. The expression level of the fusion protein was up to 30% of the total cellular protein. The fusion protein was purified by Ni-NTA affinity chromatography. After desalting by Sephadex G-25 size exclusion chromatography, the hexahistidine-SUMO-hKGF-2 was digested by SUMO proteases. The recombinant hKGF-2 was purified again with Ni-NTA column and the purity was about 95% with a total yield of 13.9 mg/l culture. The result of mitogenicity assay suggests that the recombinant hKGF-2 can significantly promote the proliferation of normal rat kidney epithelial (NRK-52E) cells.


title: Potential inhibitors of the interaction between ACE2 and SARS-CoV-2 (RBD), to develop a drug

text: AIMS: The COVID-19 disease caused by the SARS-CoV-2 has become a pandemic and there are no effective treatments that reduce the contagion. It is urgent to propose new treatment options, which are more effective in the interaction between viruses and cells. In this study was to develop a search for new pharmacological compounds against the angiotensin-converting enzyme 2 (ACE2), to inhibit the interaction with SARS-CoV-2. MATERIALS AND METHODS: Docking, virtual screening using almost 500,000 compounds directed to interact in the region between the residues (Gln24, Asp30, His34, Tyr41, Gln42, Met82, Lys353, and Arg357) in ACE2. The average of ΔG(binding), the standard deviation value and the theoretical toxicity from compounds were analyzed. KEY FINDINGS: 20 best compounds directed to interact in ACE2 with a high probability to be safe in humans, validated by web servers of prediction of ADME and toxicity (ProTox-II and PreADMET), to difficult the interaction between ACE2 and region binding domain (RBD) of SARS-CoV-2. SIGNIFICANCE: In this study, 20 compounds were determined by docking focused on the region of interaction between ACE2 and RBD of SARS-CoV-2 was carried out. The compounds are publicly available to validate the effect in in vitro tests.


title: Recent advances involving the renin–angiotensin system

text: The renin–angiotensin system (RAS) exercises fundamental control over sodium and water handling in the kidney. Accordingly, dysregulation of the RAS leads to blood pressure elevation with ensuing renal and cardiovascular damage. Recent studies have revealed that the RAS hormonal cascade is more complex than initially posited with multiple enzymes, effector molecules, and receptors that coordinately regulate the effects of the RAS on the kidney and vasculature. Moreover, recently identified tissue-specific RAS components have pleomorphic effects independent of the circulating RAS that influence critical homeostatic mechanisms including the immune response and fetal development. Further characterization of the diverse interactions between the RAS and other signaling pathways within specific tissues should lead to novel treatments for renal and cardiovascular disease.


title: RNAi Therapeutic Platforms for Lung Diseases

text: RNA interference (RNAi) is rapidly becoming an important method for analyzing gene functions in many eukaryotes and holds promise for the development of therapeutic gene silencing. The induction of RNAi relies on small silencing RNAs, which affect specific messenger RNA (mRNA) degradation. Two types of small RNA molecules, i.e. small interfering RNAs (siRNAs) and microRNAs (miRNAs), are central to RNAi. Drug discovery studies and novel treatments of siRNAs are currently targeting a wide range of diseases, including various viral infections and cancers. Lung diseases in general are attractive targets for siRNA therapeutics because of their lethality and prevalence. In addition, the lung is anatomically accessible to therapeutic agents via the intrapulmonary route. Recently, increasing evidence indicates that miRNAs play an important role in lung abnormalities, such as inflammation and oncogenesis. Therefore, miRNAs are being targeted for therapeutic purposes. In this review, we present strategies for RNAi delivery and discuss the current state-of-the-art RNAi-based therapeutics for various lung diseases.


title: COVID19 during pregnancy: a systematic review of reported cases.

text: Abstract Objective to conduct a systematic review of the outcomes reported for pregnant patients with COVID 19. Data sources we searched electronically Pubmed, Cinahl, Scopus using combination of keywords “Coronavirus and/ or pregnancy”; “COVID and/or pregnancy”; “COVID disease and/or pregnancy”; “COVID pneumonia and/or pregnancy. There were no restriction of languages in order to collect as much cases as possible. Study eligibility criteria all pregnant women, with a COVID19 diagnosed with acid nucleic test, with reported data about pregnancy and, in case of delivery, reported outcomes. Study appraisal and synthesis methods all the studies included have been evaluated according the tool for evaluating the methodological quality of case reports and case series described by Murad et al. Results 6 studies including 51 women were eligible for the systematic review. Three pregnancies were ongoing at the time of the report; of the remaining 48, 46 were delivered with a cesarean section and 2 vaginally; there was 1 stillbirth and 1 neonatal death. Conclusions although vertical transmission of SARS-Cov2 has been excluded thus far and the outcome for mothers and fetuses has been generally good, the high rate of preterm cesarean delivery is a reason for concern. These interventions were typically elective, and it is reasonable to question whether they were warranted or not. COVID-19 associated with respiratory insufficiency in late pregnancies certainly creates a complex clinical scenario.


title: The 2009 H1N1 Pandemic Adds to Our Knowledge of Influenza Pathogenesis

text: This commentary discusses the pathology and pathogenesis of the 2009 H1N1 influenza A pandemic.


title: Bayesian inference of transmission chains using timing of symptoms, pathogen genomes and contact data

text: There exists significant interest in developing statistical and computational tools for inferring ‘who infected whom’ in an infectious disease outbreak from densely sampled case data, with most recent studies focusing on the analysis of whole genome sequence data. However, genomic data can be poorly informative of transmission events if mutations accumulate too slowly to resolve individual transmission pairs or if there exist multiple pathogens lineages within-host, and there has been little focus on incorporating other types of outbreak data. We present here a methodology that uses contact data for the inference of transmission trees in a statistically rigorous manner, alongside genomic data and temporal data. Contact data is frequently collected in outbreaks of pathogens spread by close contact, including Ebola virus (EBOV), severe acute respiratory syndrome coronavirus (SARS-CoV) and Mycobacterium tuberculosis (TB), and routinely used to reconstruct transmission chains. As an improvement over previous, ad-hoc approaches, we developed a probabilistic model that relates a set of contact data to an underlying transmission tree and integrated this in the outbreaker2 inference framework. By analyzing simulated outbreaks under various contact tracing scenarios, we demonstrate that contact data significantly improves our ability to reconstruct transmission trees, even under realistic limitations on the coverage of the contact tracing effort and the amount of non-infectious mixing between cases. Indeed, contact data is equally or more informative than fully sampled whole genome sequence data in certain scenarios. We then use our method to analyze the early stages of the 2003 SARS outbreak in Singapore and describe the range of transmission scenarios consistent with contact data and genetic sequence in a probabilistic manner for the first time. This simple yet flexible model can easily be incorporated into existing tools for outbreak reconstruction and should permit a better integration of genomic and epidemiological data for inferring transmission chains.


title: Considerations for the treatment of pancreatic cancer during the COVID-19 pandemic: the UK consensus position

text: The coronavirus disease 2019 (COVID-19) pandemic epicentre has moved to the USA and Europe, where it is placing unprecedented demands on healthcare resources and staff availability. These service constraints, coupled with concerns relating to an increased incidence and severity of COVID-19 among patients with cancer, should lead to re-consideration of the risk–benefit balance for standard treatment pathways. This is of particular importance to pancreatic cancer, given that standard diagnostic modalities such as endoscopy may be restricted, and that disease biology precludes significant delays in treatment. In light of this, we sought consensus from UK clinicians with an interest in pancreatic cancer for management approaches that would minimise patient risk and accommodate for healthcare service restrictions. The outcomes are described here and include recommendations for treatment prioritisation, strategies to bridge to later surgical resection in resectable disease and factors that modify the risk–benefit balance for treatment in the resectable through to the metastatic settings. Priority is given to strategies that limit hospital visits, including through the use of hypofractionated precision radiotherapy and chemoradiotherapy treatment approaches.


title: Neutralizing antiviral antibody responses

text: Publisher Summary Neutralizing antibodies are evolutionarily important effectors of immunity against viruses. Their evaluation has revealed a number of basic insights into specificity, rules of reactivity (tolerance), and memory—namely, (1) Specificity of neutralizing antibodies is defined by their capacity to distinguish between virus serotypes; (2) B cell reactivity is determined by antigen structure, concentration, and time of availability in secondary lymphoid organs; and (3) B cell memory is provided by elevated protective antibody titers in serum that are depending on antigen stimulation. These perhaps slightly overstated rules are simple, correlate with in vivo evidence as well as clinical observations, and appear to largely demystify many speculations about antibodies and B cell physiology. The chapter also considers successful vaccines and compares them with those infectious diseases where efficient protective vaccines are lacking, it is striking to note that all successful vaccines induce high levels of neutralizing antibodies (nAbs) that are both necessary and sufficient to protect the host from disease. Successful vaccination against infectious diseases such as tuberculosis, leprosy, or HIV would require induction of additional long-lasting T cell responses to control infection.


title: Serosurvey of selected viruses in captive giant pandas (Ailuropoda melanoleuca) in China

text: Abstract Serum samples from 92 giant pandas in three captive facilities were tested for antibodies against five viruses of carnivores. Antibody titers against canine distemper virus (CDV) in two facilities in which giant pandas were vaccinated were variable. The canine adenovirus (CAV-1) and canine parvovirus (CPV) titers in vaccinated group were both positive, but titers were not high and varied among individual except one vaccinated panda had extremely high CAV-1 titer, indicating infection with the field virus following vaccination. Our results suggest that the vaccines used for these giant pandas do not elicit consistent antibody titers. Antibody titers against CDV, CPV and CAV-1 in unvaccinated giant pandas were highly variable, especially CPV titer. Almost half of sera were CPV antibody positive, and CPV titers were high enough to suggest infection with the virus. Canine coronavirus (CCV) and canine parainfluenza virus (CPIV) titers were not detected in all serum samples. The results of this study emphasize the need for research on infectious diseases of giant pandas and development of suitable vaccines for the species.


title: Potential Benefits and Harms of Novel Antidiabetic Drugs during COVID-19 Crisis

text: Patients with diabetes have been reported to have enhanced susceptibility to severe or fatal COVID-19 infections, including a high risk of being admitted to intensive care units with respiratory failure and septic complications. Given the global prevalence of diabetes, affecting over 450 million people worldwide and still on the rise, the emerging COVID-19 crisis poses a serious threat to an extremely large vulnerable population. However, the broad heterogeneity and complexity of this dysmetabolic condition, with reference to etiologic mechanisms, degree of glycemic derangement and comorbid associations, along with the extensive sexual dimorphism in immune responses, can hamper any patient generalization. Even more relevant, and irrespective of glucose-lowering activities, DPP4 inhibitors and GLP1 receptor agonists may have a favorable impact on the modulation of viral entry and overproduction of inflammatory cytokines during COVID-19 infection, although current evidence is limited and not univocal. Conversely, SGLT2 inhibitors may increase the likelihood of COVID-19-related ketoacidosis decompensation among patients with severe insulin deficiency. Mindful of their widespread popularity in the management of diabetes, addressing potential benefits and harms of novel antidiabetic drugs to clinical prognosis at the time of a COVID-19 pandemic deserves careful consideration.


title: The impact of the Covid‐19 pandemic on Italian mobility

text: Francesco Finazzi and Alessandro Fassò use location data collected by an earthquake‐monitoring app to gauge compliance with lockdown measures in Italy


title: 2019 novel coronavirus (COVID-19) pneumonia complications: the importance of lung ultrasound

text: In December 2019, a novel coronavirus (SARS-Cov-2) was first reported in Wuhan, China, and rapidly spread around the world, leading to an international emerging public health emergency. As reported from Chinese experiences, approximately 20% of patients had a severe course, requiring intensive care, with an overall case fatality rate of 2.3%. In diagnosis, chest computed tomography most commonly showed ground-glass opacity with or without consolidative patterns. Herein, we report a case of a patient affected by COVID-19 pneumonia referred in the emergency department of our institution on April 4, 2020, with peculiar lung ultrasound findings.


title: Inflammation induced by influenza virus impairs human innate immune control of pneumococcus

text: Colonization of the upper respiratory tract by pneumococcus is important both as a determinant of disease and for transmission into the population. The immunological mechanisms that contain pneumococcus during colonization are well studied in mice but remain unclear in humans. Loss of this control of pneumococcus following infection with influenza virus is associated with secondary bacterial pneumonia. We used a human challenge model with type 6B pneumococcus to show that acquisition of pneumococcus induced early degranulation of resident neutrophils and recruitment of monocytes to the nose. Monocyte function was associated with the clearance of pneumococcus. Prior nasal infection with live attenuated influenza virus induced inflammation, impaired innate immune function and altered genome-wide nasal gene responses to the carriage of pneumococcus. Levels of the cytokine CXCL10, promoted by viral infection, at the time pneumococcus was encountered were positively associated with bacterial load.


title: Lockdown for CoViD-2019 in Milan: What are the effects on air quality?

text: Abstract Based on the rapid spread of the CoViD-2019, a lockdown was declared in the whole Northern Italy by the Government. The application of increasingly rigorous containment measures allowed to reduce the impact of the CoViD-2019 pandemic on the Italian National Health System but at the same time these restriction measures gave also the opportunity to assess the effect of anthropogenic activities on air pollutants in an unprecedented way. This paper aims to study the impact of the partial and total lockdown (PL and TL, respectively) on air quality in the Metropolitan City of Milan. As results, the severe limitation of people movements following the PL and the subsequent TL determined a significant reduction of pollutants concentration mainly due to vehicular traffic (PM10, PM2.5, BC, benzene, CO, and NOx). The lockdown led to an appreciable drop in SO2 only in the city of Milan while it remained unchanged in the adjacent areas. Despite the significant decrease in NO2 in the TL, the O3 exhibited a significant increase, probably, due to the minor NO concentration. In Milan and SaA the increase was more accentuated, probably, due to the higher average concentrations of benzene in Milan than the adjacent areas that might have promoted the formation of O3 in a more significant way.


title: Synthesis of hybrid hydrophobic composite air filtration membranes for antibacterial activity and chemical detoxification with high particulate filtration efficiency (PFE)

text: Abstract Hybrid hydrophobic composite PVDF–Ag–Al2O3 nanofibrous air filtration membranes are synthesized by the electrospinning method with different concentrations of Al2O3 and fixed concentration of Ag to study their antibacterial, particulate filtration efficiencies, and their detoxification ability. All the membranes were characterized for their physical and chemical properties before being tested. It was also found that at Al2O3 concentrations higher than 8%, nanofibers could not be formed by the pure blending and electrospinning technique. The antibacterial activity of the membranes proved that silver incorporation provided suitable disinfection with greater than 99.5% antibacterial efficiency for all membranes. The antibacterial efficiency of the membranes was maintained even as the concentration of Al2O3 was increased. The hydrolysis of paraoxon, a nerve agent simulant, for the prepared membranes was also studied. The removal of paraoxon was found to increase as the loaded concentration of Al2O3 in the membrane increased. The particulate filtration efficiency of the prepared membranes was tested using particles of diameter 0.36μm. Compared to the nascent PVDF nanofiber membranes with particle filtration efficiency of 94%, the Ag and Al2O3 loaded membranes all had a higher particle filtration efficiency. Interestingly, it was found that as the concentration of Al2O3 loaded in the membranes increased so did the particle filtration efficiency. Membrane characterization data revealed that as the concentration of the Al2O3 was increased, the average pore size of the membrane was reduced and the thickness of the filter mat increased. This would explain the higher retention of the particles by these filters. Correspondingly, the resistance of the filters also increased as more Al2O3 was loaded in the nanofiber membranes. The synthesized nanofibrous membranes have the potential to be used as 3 in 1 highly efficient air filters.


title: Respiratory and gastrointestinal infections at the 2017 Grand Magal de Touba, Senegal: A prospective cohort survey

text: Abstract Background The Grand Magal of Touba is the largest Muslim pilgrimage in Senegal with a potential for infectious disease transmission. Methods Clinical follow-up, adherence to preventive measures and qPCR-based respiratory and gastrointestinal pathogens carriage pre- and post-Magal, were assessed. Results 110 pilgrims from South Senegal were included. The duration of stay in Touba was 3 days. 41.8% and 14.5% pilgrims reported respiratory and gastrointestinal symptoms. Most individuals having the onset of symptoms during their stay in Touba, or soon after returning. The acquisition of rhinoviruses, coronaviruses and adenovirus was 13.0, 16.7 and 4.6% respectively and that of Streptococcus pneumoniae and Haemophilus influenzae was 3.7% and 26.9%. Acquisition of gastrointestinal viruses and parasites was low, while bacterial acquisition ranged from 2.2% for Campylobacter jejuni to 33.0% for enteropathogenic Escherichia coli. Conclusion This preliminary study confirms that Grand Magal pilgrims are likely to be exposed to communicable disease risk as observed in other pilgrimage settings. Further study including larger numbers of pilgrims are needed to investigate potential risk factors for respiratory and gastrointestinal infections at the Grand Magal.


title: Fully Human Monoclonal Antibody Directed to Proteolytic Cleavage Site in Severe Acute Respiratory Syndrome (SARS) Coronavirus S Protein Neutralizes the Virus in a Rhesus Macaque SARS Model

text: Background. There is still no effective method to prevent or treat severe acute respiratory syndrome (SARS), which is caused by SARS coronavirus (CoV). In the present study, we evaluated the efficacy of a fully human monoclonal antibody capable of neutralizing SARS-CoV in vitro in a Rhesus macaque model of SARS. Methods. The antibody 5H10 was obtained by vaccination of KM mice bearing human immunoglobulin genes with Escherichiacoli–producing recombinant peptide containing the dominant epitope of the viral spike protein found in convalescent serum samples from patients with SARS. Results. 5H10, which recognized the same epitope that is also a cleavage site critical for the entry of SARS-CoV into host cells, inhibited propagation of the virus and pathological changes found in Rhesus macaques infected with the virus through the nasal route. In addition, we analyzed the mode of action of 5H10, and the results suggested that 5H10 inhibited fusion between the virus envelope and host cell membrane. 5H10 has potential for use in prevention and treatment of SARS if it reemerges. Conclusions. This study represents a platform to produce fully human antibodies against emerging infectious diseases in a timely and safe manner.


title: Complete genome comparison of porcine reproductive and respiratory syndrome virus parental and attenuated strains

text: Abstract Two full-length porcine reproductive and respiratory syndrome virus (PRRSV) genomes, strain VR-2332 and its cell culture passaged descendent RespPRRS vaccine strain, were compared and analyzed in order to identify possible sites of attenuation. Of the 44 nucleotide changes, 13 resulted in conservative changes and 18 produced non-conservative changes. The results suggest that key amino acids in ORF1 may contribute to the phenotype of RespPRRS, which includes increased growth rate on MA-104 cells and decreased virulence in swine. The results provide a genetic basis for future manipulation of a PRRSV reverse genetics system.


title: Evolutionary analysis of the dynamics of viral infectious disease

text: Many organisms that cause infectious diseases, particularly RNA viruses, mutate so rapidly that their evolutionary and ecological behaviours are inextricably linked. Consequently, aspects of the transmission and epidemiology of these pathogens are imprinted on the genetic diversity of their genomes. Large-scale empirical analyses of the evolutionary dynamics of important pathogens are now feasible owing to the increasing availability of pathogen sequence data and the development of new computational and statistical methods of analysis. In this Review, we outline the questions that can be answered using viral evolutionary analysis across a wide range of biological scales.


Cerebrovascular Disease in COVID-19: Is There a Higher Risk of Stroke?


title: Palladium-Catalyzed Aryl Amination Reactions of 6-Bromo- and 6-Chloropurine Nucleosides

text: Palladium-catalyzed C–N bond forming reactions of 6-bromo- as well as 6-chloropurine ribonucleosides and the 2’-deoxy analogues with aryl amines are described. Efficient conversions were observed with Pd(OAc)(2)/Xantphos/Cs(2)CO(3), in PhMe at 100 °C. Reactions of the bromo nucleoside derivatives could be conducted at a lowered catalytic loading (5 mol % Pd(OAc)(2)/7.5 mol % Xantphos), whereas good product yields were obtained with a higher catalyst load (10 mol % Pd(OAc)(2)/15 mol % Xantphos) when the chloro analogue was employed. Among the examples evaluated, silyl protection for the hydroxyls appears better as compared to acetyl. The methodology has been evaluated via reactions with a variety of aryl amines and by synthesis of biologically relevant deoxyadenosine and adenosine dimers. This is the first detailed analysis of aryl amination reactions of 6-chloropurine nucleosides, and comparison of the two halogenated nucleoside substrates.


title: Replicative Capacity of MERS Coronavirus in Livestock Cell Lines

text: Replicative capacity of Middle East respiratory syndrome coronavirus (MERS-CoV) was assessed in cell lines derived from livestock and peridomestic small mammals on the Arabian Peninsula. Only cell lines originating from goats and camels showed efficient replication of MERS-CoV. These results provide direction in the search for the intermediate host of MERS-CoV.


title: Multi-Stage Group Testing Improves Efficiency of Large-Scale COVID-19 Screening

text: Abstract Background SARS-CoV-2 test kits are in critical shortage in many countries. This limits large-scale population testing and hinders the effort to identify and isolate infected individuals. Objective Herein, we developed and evaluated multi-stage group testing schemes that test samples in groups of various pool sizes in multiple stages. Through this approach, groups of negative samples can be eliminated with a single test, avoiding the need for individual testing and achieving considerable savings of resources. Study design We designed and parameterized various multi-stage testing schemes and compared their efficiency at different prevalence rates using computer simulations. Results We found that three-stage testing schemes with pool sizes of maximum 16 samples can test up to three and seven times as many individuals with the same number of test kits for prevalence rates of around 5% and 1%, respectively. We propose an adaptive approach, where the optimal testing scheme is selected based on the expected prevalence rate. Conclusion These group testing schemes could lead to a major reduction in the number of testing kits required and help improve large-scale population testing in general and in the context of the current COVID-19 pandemic.


title: Experimental infection of IS/885/00-like infectious bronchitis virus in specific pathogen free and commercial broiler chicks

text: Abstract Pathogenesis of an IS/885/00-like (IS/885) strain of variant infectious bronchitis virus (IBV) was examined in one day old specific pathogen free (SPF) and commercial broiler chicks. Chicks were humanely euthanized at 3, 6, 9, 12, 15, 21 and 28days post infection (dpi) for necropsy examination, and tissues were collected for histopathology and virus detection by reverse transcription polymerase chain reaction (RT-PCR). Respiratory clinical signs and gross lesions consisting of tracheal caseous exudate and plugs, and swollen kidneys (with or without) urate deposits were observed in SPF and broiler chicks. The onset of disease developed more slowly and were of lesser severity in broiler compared to SPF chicks, reflecting the inhibitory effects of the IBV maternal-antibodies in the broiler chicks or genetic/strain susceptibility, or both. Head swelling was observed in one infected broiler chick at 15dpi and the virus was recovered by RT-PCR and isolation. In the IS/885-infected SPF chicks, cystic oviducts were found in two female chicks. IS/885 was isolated from the cystic fluid. Using ELISA, low to moderate levels of the antibodies to IBV was detected in the SPF compared to broiler infected chicks.


title: Rapid prototyping and clinical testing of a reusable face shield for health care workers responding to the COVID-19 pandemic

text: Due to supply chain disruption, the COVID-19 pandemic has caused severe shortages in personal protective equipment (PPE) for health care professionals. Local fabrication based on 3D printing is one way to address this challenge, particularly in the case of simple products such as protective face shields. As a consequence, many public domain designs for face shields have become available. No clear path exists, however, for introducing a locally fabricated and unapproved product into a clinical setting. In a US health care setting, face shields are regulated by the Food and Drug Administration (FDA); similar policies exist in other countries. We describe a research protocol under which rapid iteration on an existing design, coupled with clinical feedback and real-world testing in an emergency department, allowed a face shield to be implemented by the members of the incident command team at a major academic medical center. We describe our design and testing process and provide an overview of regulatory considerations associated with fabrication and testing of face shields and related products. All designs, materials used, testing protocols, and survey results are reported in full to facilitate the execution of similar face shield efforts in other clinical settings. Our work serves as a case study for development of a robust local response to pandemics and other health care emergencies, with implications for healthcare professionals, hospital administrators, regulatory agencies and concerned citizens.


title: Five decades of research on foreign direct investment by MNEs: An overview and research agenda

text: Abstract Despite the significance attached to foreign direct investment (FDI) by Multinational enterprises (MNEs), there are is no comprehensive review of the FDI literature. Moreover, those that have been published, focus on subsets of FDI. This review systematically examines the empirical as well as theoretical research on FDI through an analysis of 500 articles published during the last five decades. Theoretical models, methods, context, and contributions to scholarship were reviewed. We strive to highlight the key theories, paradigms, and articles and provide directions for future research. We conclude that FDI has evolved as the most significant area of international business.


title: Detection of a novel gammaherpesvirus (genus Rhadinovirus) in wild muntjac deer in Northern Ireland

text: This study represents the initial part of an investigation into the potential for non-native, wild, free-living muntjac deer (Muntiacus reevesi) to carry viruses that could be a threat to livestock. A degenerate PCR assay was used to screen a range of tissues from muntjac deer culled in Northern Ireland for the presence of herpesviral nucleic acids. This was followed by sequencing of PCR amplicons and phylogenetic analysis. We report the detection of a novel gammaherpesvirus most closely related to a type 2 ruminant rhadinovirus from mule deer. It remains to be determined if this new virus is pathogenic to deer or presents a risk to food security through the susceptibility of domestic livestock.


AMD Management During the COVID‐19 Pandemic


title: The Impact of Viral Infections in Children with Community-Acquired Pneumonia

text: For many years viral causes of community-acquired pneumonia were often been given limited attention. The number of published studies on influenza alone increased fivefold from 2001 to 2010. Specifically several studies have underlined that the involvement of viruses in community-acquired pneumonia has been underestimated, and this underestimation has been attributed to a lack of appropriate diagnostic methods. Now, with the advent of modern molecular assays, it is well recognized that viruses account for the largest proportion of community-acquired pneumonia in preschool children in both developed and developing countries. Respiratory syncytial virus, influenza virus, adenovirus, and parainfluenza virus are the major pathogens involved, but the relative importance of additional viruses (rhinoviruses, bocavirus, human metapneumovirus) is increasing and will be better defined by future research.


title: Estimating the impact of violent events on transmission in Ebola virus disease outbreak, Democratic Republic of the Congo, 2018–2019

text: INTRODUCTION: As of April 2019, the current Ebola virus disease (EVD) outbreak in the Democratic Republic of the Congo (DRC) is occurring in a longstanding conflict zone and has become the second largest EVD outbreak in history. It is suspected that after violent events occur, EVD transmission will increase; however, empirical studies to understand the impact of violence on transmission are lacking. Here, we use spatial and temporal trends of EVD case counts to compare transmission rates between health zones that have versus have not experienced recent violent events during the outbreak. METHODS: We collected daily EVD case counts from DRC Ministry of Health. A time-varying indicator of recent violence in each health zone was derived from events documented in the WHO situation reports. We used the Wallinga-Teunis technique to estimate the reproduction number R for each case by day per zone in the 2018–2019 outbreak. We fit an exponentially decaying curve to estimates of R overall and by health zone, for comparison to past outbreaks. RESULTS: As of 16 April 2019, the mean overall R for the entire outbreak was 1.11. We found evidence of an increase in the estimated transmission rates in health zones with recently reported violent events versus those without (p = 0.008). The average R was estimated as between 0.61 and 0.86 in regions not affected by recent violent events, and between 1.01 and 1.07 in zones affected by violent events within the last 21 days, leading to an increase in R between 0.17 and 0.53. Within zones with recent violent events, the mean estimated quenching rate was lower than for all past outbreaks except the 2013–2016 West African outbreak. CONCLUSION: The difference in the estimated transmission rates between zones affected by recent violent events suggests that violent events are contributing to increased transmission and the ongoing nature of this outbreak.


title: Biosecurity and Equine Infectious Diseases

text: Abstract The article provides an overview of biosecurity measures that apply to all potential pathogens in the horse exemplified by the control and management of equine herpesvirus myeloencephalopathy (an emergent disease), methicillin-resistant Staphylococcus aureus (a zoonotoc disease), and strangles in horses, an ancient disease that remains a scourge of susceptible Equidae. The emphasis is on infectious disease within the United States, although the principles of biosecurity in limiting infectious disease spread are not restricted by boundaries.


title: Validation of a commercially available SARS-CoV-2 serological immunoassay

text: OBJECTIVES: To validate the diagnostic accuracy of a Euroimmun SARS-CoV-2 IgG and IgA immunoassay for COVID-19. METHODS: In this unmatched (1:2) case-control validation study, we used sera of 181 laboratory-confirmed SARS-CoV-2 cases and 326 controls collected before SARS-CoV-2 emergence. Diagnostic accuracy of the immunoassay was assessed against a whole spike protein-based recombinant immunofluorescence assay (rIFA) by receiver operating characteristic (ROC) analyses. Discrepant cases between ELISA and rIFA were further tested by pseudo-neutralization assay. RESULTS: COVID-19 patients were more likely to be male and older than controls, and 50.3% were hospitalized. ROC curve analyses indicated that IgG and IgA had high diagnostic accuracies with AUCs of 0.990 (95% Confidence Interval [95%CI]: 0.983-0.996) and 0.978 (95%CI: 0.967-0.989), respectively. IgG assays outperformed IgA assays (p=0.01). Taking an assessed 15% inter-assay imprecision into account, an optimized IgG ratio cut-off > 2.5 displayed a 100% specificity (95%CI: 99-100) and a 100% positive predictive value (95%CI: 96-100). A 0.8 cut-off displayed a 94% sensitivity (95%CI: 88-97) and a 97% negative predictive value (95%CI: 95-99). Substituting the upper threshold for the manufacturer’s, improved assay performance, leaving 8.9% of IgG ratios indeterminate between 0.8-2.5. CONCLUSIONS: The Euroimmun assay displays a nearly optimal diagnostic accuracy using IgG against SARS-CoV-2 in patient samples, with no obvious gains from IgA serology. The optimized cut-offs are fit for rule-in and rule-out purposes, allowing determination of whether individuals in our study population have been exposed to SARS-CoV-2 or not. IgG serology should however not be considered as a surrogate of protection at this stage.


Cardiology training in times of COVID-19: Beyond the present


title: Pathology and Tissue Distribution of Turkey Coronavirus in Experimentally Infected Chicks and Turkey Poults

text: Summary Twenty 1-day-old specific pathogen free chicks and 20 1-day-old commercially derived turkey poults were inoculated with a Brazilian strain of turkey coronavirus (TCoV) to study the pathogenicity and virus distribution up to 14 days post-inoculation by histopathology, immunohistochemistry, reverse transcriptase polymerase chain reaction and sequencing. At 2–14 dpi, TCoV antigens were detected in the paranasal sinus and lachrymal accessory gland (Harderian gland) of infected chicks and in the ileum, ileocaecal junction and caecum of infected poults. Lymphocytic inflammation was present in these tissues. TCoV was re-isolated from pooled tissue suspensions of nasal concha, Harderian gland and paranasal sinus from chicks, as well as from the ileum, ileocaecal junction and caecum of poults, after three consecutive passages in 28-day-old embryonated turkey eggs. Viral RNA corresponding to the spike gene region (1178–2073 genome position) was amplified from the upper respiratory tract of chickens and from the intestinal tract of poults and phylogenetic analysis confirmed the identity as TCoV. This is the first description of TCoV antigens and mRNA in upper respiratory tissues in experimentally infected chickens.


title: The Molecular Biology of Coronaviruses

text: Publisher Summary This chapter discusses the manipulation of clones of coronavirus and of complementary DNAs (cDNAs) of defective-interfering (DI) RNAs to study coronavirus RNA replication, transcription, recombination, processing and transport of proteins, virion assembly, identification of cell receptors for coronaviruses, and processing of the polymerase. The nature of the coronavirus genome is nonsegmented, single-stranded, and positive-sense RNA. Its size ranges from 27 to 32 kb, which is significantly larger when compared with other RNA viruses. The gene encoding the large surface glycoprotein is up to 4.4 kb, encoding an imposing trimeric, highly glycosylated protein. This soars some 20 nm above the virion envelope, giving the virus the appearance-with a little imagination-of a crown or coronet. Coronavirus research has contributed to the understanding of many aspects of molecular biology in general, such as the mechanism of RNA synthesis, translational control, and protein transport and processing. It remains a treasure capable of generating unexpected insights.


title: Risk Factors for Repeat Adverse Asthma Events in Children After Visiting an Emergency Department

text: Objective The aim of this study was to identify risk factors for long-term adverse outcomes in children with asthma after visiting the emergency department (ED). Methods A prospective observational study was conducted at the ED of a pediatric tertiary hospital in Ontario, Canada. Patient outcomes (ie, acute asthma episodes and ED visits) were measured at baseline and at 1- and 6-months post-ED discharge. Time trends in outcomes were assessed using the generalized estimating equations method. Multiple conditional logistic regressions were used to model outcomes at 6 months and examine the impact of drug insurance coverage while adjusting for confounders. Results Of the 269 children recruited, 81.8% completed both follow-ups. ED use significantly reduced from 39.4% at baseline to 26.8% at 6 months (P < .001), whereas the level of acute asthma episodes remained unchanged. Children with drug insurance coverage were less likely to have acute asthma episodes (adjusted odds ratio [AOR] = 0.36; 95% CI, 0.15–0.85; P < .02) or repeat ED visits (AOR = 0.45; 95% CI, 0.20–0.99; P < .05) at 6 months. Other risk factors for adverse outcomes included previous adverse asthma events and certain asthma triggers (eg, cold/sinus infection). Washing bed linens in hot water weekly was protective against subsequent acute asthma episodes. Conclusions Our study demonstrated significant improvements in long-term outcomes in children seeking acute care for asthma in the ED. Future efforts remain in targeting the sustainability of improved outcomes beyond 6 months. Risk factors identified can help target vulnerable populations for proper interventions, which may include efforts to maximize insurance coverage for asthma medications and strategies to improve asthma self-management through patient and provider education.


title: Chapter 5 Salivary Glands

text: Abstract The anatomical development and primary functions of the major and minor salivary glands and their associated lesions found in rats are discussed in this chapter.


title: The SARS-Coronavirus papain-like protease: Structure, function and inhibition by designed antiviral compounds

text: Over ten years have passed since the deadly human coronavirus that causes severe acute respiratory syndrome (SARS-CoV) emerged from the Guangdong Province of China. Despite the fact that the SARS-CoV pandemic infected over 8,500 individuals, claimed over 800 lives and cost billions of dollars in economic loss worldwide, there still are no clinically approved antiviral drugs, vaccines or monoclonal antibody therapies to treat SARS-CoV infections. The recent emergence of the deadly human coronavirus that causes Middle East respiratory syndrome (MERS-CoV) is a sobering reminder that new and deadly coronaviruses can emerge at any time with the potential to become pandemics. Therefore, the continued development of therapeutic and prophylactic countermeasures to potentially deadly coronaviruses is warranted. The coronaviral proteases, papain-like protease (PLpro) and 3C-like protease (3CLpro), are attractive antiviral drug targets because they are essential for coronaviral replication. Although the primary function of PLpro and 3CLpro are to process the viral polyprotein in a coordinated manner, PLpro has the additional function of stripping ubiquitin and ISG15 from host-cell proteins to aid coronaviruses in their evasion of the host innate immune responses. Therefore, targeting PLpro with antiviral drugs may have an advantage in not only inhibiting viral replication but also inhibiting the dysregulation of signaling cascades in infected cells that may lead to cell death in surrounding, uninfected cells. This review provides an up-to-date discussion on the SARS-CoV papain-like protease including a brief overview of the SARS-CoV genome and replication followed by a more in-depth discussion on the structure and catalytic mechanism of SARS-CoV PLpro, the multiple cellular functions of SARS-CoV PLpro, the inhibition of SARS-CoV PLpro by small molecule inhibitors, and the prospect of inhibiting papain-like protease from other coronaviruses. This paper forms part of a series of invited articles in Antiviral Research on “ From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses.”


title: Plant virus proteins involved in natural vector transmission

text: Abstract Plant viruses transmitted by invertebrate vectors either reversibly bind to vector mouthparts or are internalized by the vector and later secreted. Viral proteins mediate the binding of plant viruses to vector mouthparts and the transport of virus across vector-cell membranes. Both mechanisms probably involve conformational changes of virus proteins during their association with the vector.


title: Multivariate Analyses of Codon Usage of SARS-CoV-2 and other betacoronaviruses

text: Coronavirus disease 2019 (COVID-19) is a global health concern as it continues to spread within China and beyond. The causative agent of this disease, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), belongs to the genus Betacoronavirus which also includes severe acute respiratory syndrome related coronavirus (SARSr-CoV) and Middle East respiratory syndrome related coronavirus (MERSr-CoV). Codon usage of viral genes are believed to be subjected to different selection pressures in different host environments. Previous studies on codon usage of influenza A viruses can help identify viral host origins and evolution trends, however, similar studies on coronaviruses are lacking. In this study, global correspondence analysis (CA), within-group correspondence analysis (WCA) and between-group correspondence analysis (BCA) were performed among different genes in coronavirus viral sequences. The amino acid usage pattern of SARS-CoV-2 was generally found similar to bat and human SARSr-CoVs. However, we found greater synonymous codon usage differences between SARS-CoV-2 and its phylogenetic relatives on spike and membrane genes, suggesting these two genes of SARS-CoV-2 are subjected to different evolutionary pressures.


title: Full-Genome Sequence of Pantropic Canine Coronavirus

text: Pantropic canine coronavirus (CCoV) was first detected in young dogs in Italy in 2005, but the complete genome sequence of this virus had not yet been determined. Here, we report the full-length genome sequence of the prototype strain CB/05, which showed that this virus is genetically similar to CCoV-IIa viruses.


title: Signatures of malaria-associated pathology revealed by high-resolution whole-blood transcriptomics in a rodent model of malaria

text: The influence of parasite genetic factors on immune responses and development of severe pathology of malaria is largely unknown. In this study, we performed genome-wide transcriptomic profiling of mouse whole blood during blood-stage infections of two strains of the rodent malaria parasite Plasmodium chabaudi that differ in virulence. We identified several transcriptomic signatures associated with the virulent infection, including signatures for platelet aggregation, stronger and prolonged anemia and lung inflammation. The first two signatures were detected prior to pathology. The anemia signature indicated deregulation of host erythropoiesis, and the lung inflammation signature was linked to increased neutrophil infiltration, more cell death and greater parasite sequestration in the lungs. This comparative whole-blood transcriptomics profiling of virulent and avirulent malaria shows the validity of this approach to inform severity of the infection and provide insight into pathogenic mechanisms.


title: Violence against women during covid-19 pandemic restrictions

text: Protections for women and girls must be built into response plans


title: Mental distress in orthodontic patients during the COVID-19 epidemic

text: Introduction The ongoing coronavirus disease 2019 (COVID-19) outbreak impacts the mental health of patients, health workers and the public. The level of impact on the mental health of orthodontic patients in treatment is unknown. The objective of the study was to evaluate the mental health of orthodontic patients in China during the early stage of the pandemic. Methods An online questionnaire type of survey was conducted on a convenien ce sample of anonymous participants. The questionnaire, in Chinese (Mandarin), comprised 5 sections. Sections 1 to 3 included demographic, epidemical, and orthodontic status of the patients. Section 4 assessed the mental health related to orthodontics. Section 5 was the Kessler-10 mental distress scale. A total of 48 orthodontists were invited to distribute the questionnaires to their patients. Descriptive statistics, principle component analysis, k-means cluster analysis and bivariate logistics regression analysis were performed with statistical significance set at P<0.05. Result s: Questionnaires were collected from 558 patients (104 males, 354 females; age 24.78 ± 6.33 years [mean ± standard deviation]). The prevalence of mental distress was 38% (174/458). Higher odds ratios were associated with female participants, missed appointments and Hubei residence. Types of orthodontic appliance were associated with anxiety of prolonged treatment duration. The manner of communication with patients regarding the postponement of appointments was associated with patients' concern of prolonged treatment duration. Frequency of contact from dentists was associated with patients' independence. Conclusion s: Over one third of orthodontic patients experienced mental distress during the pandemic. Multiple factors affected the level of anxiety of orthodontic patients, such as the type of orthodontic appliance, interval from the last dental visit, manner of communication with the orthodontist, and the localities of the pandemic progression.


title: The most important challenges ahead of microbiome pattern in the post era of the COVID-19 pandemic

text: As the ongoing COVID-19 pandemic posed a huge challenge to global public health, emphasis on personal hygiene caused extraordinary daily use of detergents and household cleaning products. Since antibacterial cleaning products have the capacity to change the environmental microbiome, increased exposure to household disinfectants could be associated with alterations in human microbiota composition and function. Moreover, the emerging links between household cleaning products and occurrence of non-communicable diseases and antibiotic resistance may involve the gut microbiome. The mediating effects of disturbed gut microbiota on associations between home use of cleaning products and life-long health consequences have been documented in some observational studies. Regarding the evidence associated reduction in exposure to non-pathogenic commensal bacteria and gut dysbiosis, further study is required to assess the effect of massive use of cleaning products during COVID-19 pandemic on long-term host health mediated by the altered microbiota. In this context, recommendations to consume probiotics and fermented foods might reverse the consequences by alleviating dysbiosis.


title: Cross-sectional evaluation of humoral responses against SARS-CoV-2 Spike

text: The SARS-CoV-2 virus is responsible for the current worldwide coronavirus disease 2019 (COVID-19) pandemic, infecting millions of people and causing hundreds of thousands of deaths. The Spike glycoprotein of SARS-CoV-2 mediates viral entry and is the main target for neutralizing antibodies. Understanding the antibody response directed against SARS-CoV-2 is crucial for the development of vaccine, therapeutic and public health interventions. Here we performed a cross-sectional study on 98 SARS-CoV-2-infected individuals to evaluate humoral responses against the SARS-CoV-2 Spike. The vast majority of infected individuals elicited anti-Spike antibodies within 2 weeks after the onset of symptoms. The levels of receptor-binding domain (RBD)-specific IgG persisted overtime, while the levels of anti-RBD IgM decreased after symptoms resolution. Some of the elicited antibodies cross-reacted with other human coronaviruses in a genus-restrictive manner. While most of individuals developed neutralizing antibodies within the first two weeks of infection, the level of neutralizing activity was significantly decreased over time. Our results highlight the importance of studying the persistence of neutralizing activity upon natural SARS-CoV-2 infection.


Importance of MHV-CoV A59 Nucleocapsid Protein COOH-Terminal Negative Charges


title: Do COVID-19 and SARS Gene Complexities and Variations Help Overcome the Knowledge Gap?

text: A whole new pathogen, to which humans have virtually no pre-existing immunity, has caused fear all over the world. Severe acute respiratory syndrome coronavirus (SARS CoV-2) is one of the types of human novel-coronavirus of the family coronavirus. The nature of transmission of the virus makes it one of the most infectious pathogenic diseases that has ever existed. Though the human coronaviruses have existed since the discovery of the human coronavirus 229E (HCoV-229E) and human coronavirus OC43 (HCoV-OC43) in 1960, it has been a challenge to develop an effective cure as well as vaccine for the diseases associated with coronaviruses. Commonly, human coronaviruses cause illnesses such as intestinal and respiratory tract illnesses. Nevertheless, the symptoms reflected after infection from the coronaviruses take some time before being identified. Thus, viruses can replicate and cause more harm to the human body before being detected. Moreover, research continues to explain why some gene variations in some individuals increase the risk of some infectious diseases, while others are not affected. Looking at gene variations in people infected with Coronavirus Disease 2019 (COVID-19) and studying how genes influence people's response to infection will help to develop a vaccine that will help strengthen the immune system. Knowing how the human genes respond to the virus COVID-19 will help to cure people more effectively.