title: Evaluating the massive underreporting and undertesting of COVID-19 cases in multiple global epicenters

text: Abstract Background With continuous global COVID-19 outbreak, differing case numbers and mortality rates are observed. While actual case numbers appear vague, mortality numbers related to COVID-19 seem more precise. In this study, we used the mortality rate as the main indicator to evaluate the extent of underreporting and underdetection of COVID-19 cases. Methods We have analyzed all available data provided by the World Health Organization on the development of international COVID-19 cases and mortality numbers on March 17th, 2020. A crude case-fatality risk (cCFR) and adjusted case-fatality risk (aCFR) was calculated for China, South Korea, Japan, Italy, France, Spain, Germany, Iran and the United States. Additionally, a fold-change (FC) was derived for each country. Results The highest aCFR and FC were detected for Spain. Based on their FC values, an extremely high number of undetected COVID-19 cases was displayed in France, the United States, Italy and Spain. For these countries, our findings indicate a detection rate of only 1-2% of total actual COVID-19 cases. Conclusions Due to limited testing capacities, mortality numbers may serve as a better indicator for COVID-19 case spread in many countries. Our data indicate that countries like France, Italy, the United States, Iran and Spain have extremely high numbers of undetected and underreported cases. Differences in testing availability and capacity, containment as well as overall health care and medical infrastructure result in significantly different mortality rates and COVID-19 case numbers for each respective country.


title: Viral and bacterial infections associated with camel (Camelus dromedarius) calf diarrhea in North Province, Saudi Arabia

text: Diarrhea and deaths in new-born camel calves were noticed by veterinary investigators and pastoralist in Saudi Arabia to be very high. Hence, it is thought to be necessary to investigate this problem from the virological and bacteriological point of view. The role of pathogenic bacteria and viruses in six different towns of North Province (Al-Assafia, Arar, Domat Aljandal, Hail, Skaka and Khoa) in Saudi Arabia was studied. Survey was conducted in diarrheic camel calves aged 12 months or younger. In our study calf diarrhea was reported in 184 out of 2308 camels examined clinically during one year, the prevalence of diarrhea was found to be 8.0% in calves ranging from one month to one year. In the present study group A rotavirus and Brucella abortus were detected in 14.7% and 8.98%, respectively, using ELISA technique. Escherichia coli was isolated from diarrheic calf camel (58.2%) 99/170 samples during dry and wet season. Salmonella spp. and Enterococcus spp. were detected in 12% and 8.8% of the specimens, respectively. In this study enterotoxogenic E. coli (ET E. coli) was isolated from 7% of diarrheic camel, which indicates the strong correlation between the camel calf diarrhea and the detection of enterotoxogenic E. coli. This study represented the first report for the detection of group A rotavirus and B. abortus antigen and antibodies in calf camels in Saudi Arabia. It is recommended that the disease should be controlled by vaccination in calf camels.


title: Variations in the Nucleocapsid Protein Gene of Infectious Bronchitis Viruses Isolated in Korea

text: Fourteen infectious bronchitis viruses (IBVs) were isolated in Korea between 2001 and 2003 from chickens suspected to be infected with IBVs. The nucleocapsid (N) protein genes of the various IBVs were amplified by reverse transcriptase-polymerase chain reaction (RT-PCR) and were cloned and sequenced, and the nucleotide and deduced amino acid sequences were compared with published sequences for non-Korean IBV strains. The Korean IBV isolates shared amino acid sequence similarity of between 89.2% (K203-02 and K1255-03) and 98.3% (K434-01 and K281-01) with each other and exhibited amino acid sequence similarity between 57.0% (K774-01 and V18/91) and 96.6% (K507-01 and JP8147) with non-Korean IBV strains. Phylogenetic analysis of the deduced N protein amino acid sequences resulted in the segregation of Korean IBV isolates into three different clusters, with cluster assignments differing for some of the isolates from those obtained with analysis of the S1 glycoprotein. Korean IBV isolates K069-01, K281-01, K434-01, K504-01, K774-01, K748-01, K044-02, K058-02, K161-02, K203-02, and K234-02 formed an independent cluster comprised only of Korean IBV isolates. Another Korean IBV isolate, K210-02, belonged to a cluster that included IBV strains isolated in USA, the Netherlands and China. Recent Korean IBV isolates K514-03 and K1255-03 grouped into a third distinct cluster related to a Chinese IBV strain. As deduced from phylogenetic analysis, some IBV isolates appear to have arisen from the recombination of IBV strains with different origins.


title: Multiple Genome Segments Determine Virulence of Bluetongue Virus Serotype 8

text: Bluetongue virus (BTV) causes bluetongue, a major hemorrhagic disease of ruminants. In order to investigate the molecular determinants of BTV virulence, we used a BTV8 strain minimally passaged in tissue culture (termed BTV8(L) in this study) and a derivative strain passaged extensively in tissue culture (BTV8(H)) in in vitro and in vivo studies. BTV8(L) was pathogenic in both IFNAR(−/−) mice and in sheep, while BTV8(H) was attenuated in both species. To identify genetic changes which led to BTV8(H) attenuation, we generated 34 reassortants between BTV8(L) and BTV8(H). We found that partial attenuation of BTV8(L) in IFNAR(−/−) mice was achieved by simply replacing genomic segment 2 (Seg2, encoding VP2) or Seg10 (encoding NS3) with the BTV8(H) homologous segments. Fully attenuated viruses required at least two genome segments from BTV8(H), including Seg2 with either Seg1 (encoding VP1), Seg6 (encoding VP6 and NS4), or Seg10 (encoding NS3). Conversely, full reversion of virulence of BTV8(H) required at least five genomic segments of BTV8(L). We also demonstrated that BTV8(H) acquired an increased affinity for glycosaminoglycan receptors during passaging in cell culture due to mutations in its VP2 protein. Replication of BTV8(H) was relatively poor in interferon (IFN)-competent primary ovine endothelial cells compared to replication of BTV8(L), and this phenotype was determined by several viral genomic segments, including Seg4 and Seg9. This study demonstrated that multiple viral proteins contribute to BTV8 virulence. VP2 and NS3 are primary determinants of BTV pathogenesis, but VP1, VP5, VP4, VP6, and VP7 also contribute to virulence. IMPORTANCE Bluetongue is one of the major infectious diseases of ruminants, and it is listed as a notifiable disease by the World Organization for Animal Health (OIE). The clinical outcome of BTV infection varies considerably and depends on environmental and host- and virus-specific factors. Over the years, BTV serotypes/strains with various degrees of virulence (including nonpathogenic strains) have been described in different geographical locations. However, no data are available to correlate the BTV genotype to virulence. This study shows that BTV virulence is determined by different viral genomic segments. The data obtained will help to characterize thoroughly the pathogenesis of bluetongue. The possibility to determine the pathogenicity of virus isolates on the basis of their genome sequences will help in the design of control strategies that fit the risk posed by new emerging BTV strains.


title: CRISPR/dCas9-mediated biosensor for detection of tick-borne diseases

text: Abstract Rapid and highly sensitive detection of biomolecules is greatly needed for pathogen diagnosis in clinical samples, but the method needs to be significantly improved in terms of sensitivity and specificity for actual use in clinical settings. Here, we report the development of an improved molecular diagnostics tool that utilizes CRISPR/dCas9-mediated biosensor that couples a nuclease inactivated Cas9 (dCas9) and single microring resonator biosensor, enables label-free and real-time detection of pathogenic DNA and RNA. We addressed the clinical utility of this CRISPR/dCas9-mediated biosensor in tick-borne illnesses including scrub typhus (ST) and severe fever with thrombocytopenia syndrome (SFTS), whose clinical presentations are too similar to be easily differentiated. By using CRISPR/dCas9-mediated biosensor, we achieved single molecule sensitivity for the detection of ST (0.54 aM) and SFTS (0.63 aM); this detection sensitivity is 100 times more sensitive than that of RT-PCR assay. Finally, CRISPR/dCas9-mediated biosensor was able to clearly distinguish between ST and SFTS in serum samples within 20 min. We believe that CRISPR/dCas9-mediated biosensor will be useful for rapid and accurate molecular diagnostic tool that is suitable for immediate clinical applications.


title: High prevalence and diversity of viruses of the subfamily Gammaherpesvirinae, family Herpesviridae, in fecal specimens from bats of different species in southern China

text: Several studies have reported the detection of herpesviruses (HVs) in bats. However, the prevalence and phylogenetic characteristics of HVs in bats are still poorly understood. To elucidate the epidemiological characteristics of bat HVs in southern China, 520 fecal samples from eight bat species were collected in four geographic regions of southern China. Of these samples, 73 (14.0 %) tested positive for HVs using nested polymerase chain reaction assay. Phylogenetic analysis revealed a high degree of molecular diversity of HVs in bats of different species from different geographic regions. Our study provides evidence for co-evolution of bats and HVs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-015-2614-9) contains supplementary material, which is available to authorized users.


title: Chapter 9 Clinical Manifestations and Laboratory Diagnosis of Ebola Virus Infection

text: Abstract This chapter highlights the clinical features of Ebola virus disease and findings on laboratory tests. The steps required to differentiate Ebola virus disease from other endemic infectious diseases are presented. The chapter also describes the precautionary guidelines set up by Center for Disease Control and Prevention in regards to proper usage of personal protective gear and handling of biological specimens of Ebola virus disease patients.


title: The Study of Viral RNA Diversity in Bird Samples Using De Novo Designed Multiplex Genus-Specific Primer Panels

text: Advances in the next generation sequencing (NGS) technologies have significantly increased our ability to detect new viral pathogens and systematically determine the spectrum of viruses prevalent in various biological samples. In addition, this approach has also helped in establishing the associations of viromes with many diseases. However, unlike the metagenomic studies using 16S rRNA for the detection of bacteria, it is impossible to create universal oligonucleotides to target all known and novel viruses, owing to their genomic diversity and variability. On the other hand, sequencing the entire genome is still expensive and has relatively low sensitivity for such applications. The existing approaches for the design of oligonucleotides for targeted enrichment are usually involved in the development of primers for the PCR-based detection of particular viral species or genera, but not for families or higher taxonomic orders. In this study, we have developed a computational pipeline for designing the oligonucleotides capable of covering a significant number of known viruses within various taxonomic orders, as well as their novel variants. We have subsequently designed a genus-specific oligonucleotide panel for targeted enrichment of viral nucleic acids in biological material and demonstrated the possibility of its application for virus detection in bird samples. We have tested our panel using a number of collected samples and have observed superior efficiency in the detection and identification of viral pathogens. Since a reliable, bioinformatics-based analytical method for the rapid identification of the sequences was crucial, an NGS-based data analysis module was developed in this study, and its functionality in the detection of novel viruses and analysis of virome diversity was demonstrated.


title: A case-crossover analysis of the impact of weather on primary cases of Middle East respiratory syndrome

text: BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) is endemic in dromedary camels in the Arabian Peninsula, and zoonotic transmission to people is a sporadic event. In the absence of epidemiological data on the reservoir species, patterns of zoonotic transmission have largely been approximated from primary human cases. This study aimed to identify meteorological factors that may increase the risk of primary MERS infections in humans. METHODS: A case-crossover design was used to identify associations between primary MERS cases and preceding weather conditions within the 2-week incubation period in Saudi Arabia using univariable conditional logistic regression. Cases with symptom onset between January 2015 – December 2017 were obtained from a publicly available line list of human MERS cases maintained by the World Health Organization. The complete case dataset (N = 1191) was reduced to approximate the cases most likely to represent spillover transmission from camels (N = 446). Data from meteorological stations closest to the largest city in each province were used to calculate the daily mean, minimum, and maximum temperature ((ο)C), relative humidity (%), wind speed (m/s), and visibility (m). Weather variables were categorized according to strata; temperature and humidity into tertiles, and visibility and wind speed into halves. RESULTS: Lowest temperature (Odds Ratio = 1.27; 95% Confidence Interval = 1.04–1.56) and humidity (OR = 1.35; 95% CI = 1.10–1.65) were associated with increased cases 8–10 days later. High visibility was associated with an increased number of cases 7 days later (OR = 1.26; 95% CI = 1.01–1.57), while wind speed also showed statistically significant associations with cases 5–6 days later. CONCLUSIONS: Results suggest that primary MERS human cases in Saudi Arabia are more likely to occur when conditions are relatively cold and dry. This is similar to seasonal patterns that have been described for other respiratory diseases in temperate climates. It was hypothesized that low visibility would be positively associated with primary cases of MERS, however the opposite relationship was seen. This may reflect behavioural changes in different weather conditions. This analysis provides key initial evidence of an environmental component contributing to the development of primary MERS-CoV infections.


title: Opportunistic Infections with Coronavirus-Like Particles in Patients Infected with the Human Immunodeficiency Virus?

text: Summary From 35 patients infected with Human Immunodeficiency Virus (HIV) and belonging to various risk groups, 60 stool specimens were examined for the presence of Coronavirus-like particles (CVLP) using electron microscopy. CVLP were detected in 5 (8%) stool samples from 5 different patients (14%). Only one of the patients had diarrhoea. The five patients with CVLP-positive stools were all at advanced stages of HIV infection. The remarkable discrepancy between our data and another study, reporting a rate of 50% CVLP-positive HIV patients, most of them persistently shedding the virus, is discussed.


title: Caring for Critically Ill Adults With Coronavirus Disease 2019 in a PICU: Recommendations by Dual Trained Intensivists*

text: In the midst of the severe acute respiratory syndrome coronavirus 2 pandemic, which causes coronavirus disease 2019, there is a recognized need to expand critical care services and beds beyond the traditional boundaries. There is considerable concern that widespread infection will result in a surge of critically ill patients that will overwhelm our present adult ICU capacity. In this setting, one proposal to add “surge capacity” has been the use of PICU beds and physicians to care for these critically ill adults. DESIGN: Narrative review/perspective. SETTING: Not applicable. PATIENTS: Not applicable. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The virus’s high infectivity and prolonged asymptomatic shedding have resulted in an exponential growth in the number of cases in the United States within the past weeks with many (up to 6%) developing acute respiratory distress syndrome mandating critical care services. Coronavirus disease 2019 critical illness appears to be primarily occurring in adults. Although pediatric intensivists are well versed in the care of acute respiratory distress syndrome from viral pneumonia, the care of differing aged adult populations presents some unique challenges. In this statement, a team of adult and pediatric-trained critical care physicians provides guidance on common “adult” issues that may be encountered in the care of these patients and how they can best be managed in a PICU. CONCLUSIONS: This concise scientific statement includes references to the most recent and relevant guidelines and clinical trials that shape management decisions. The intention is to assist PICUs and intensivists in rapidly preparing for care of adult coronavirus disease 2019 patients should the need arise.


title: Chapter 12 Procyonidae, Viverridae, Hyenidae, Herpestidae, Eupleridae, and Prionodontidae

text: Abstract This chapter covers the diseases and pathology of multiple taxonomic groups within the order Carnivora including Procyonidae several of the Feliformia carnivores. The overwhelming majority of knowledge about disease pathogenesis for these species is biased toward raccoons and concern for disease spread to humans and companion animals. Procyonids and feliform carnivores are ubiquitous in their environments and share habitat and environmental resources with other nondomestic and domestic carnivores and humans. As reservoirs for a number of important multispecies or zoonotic pathogens, surveys for pathogens that may be harbored or vectored by several of the species in this chapter, for example, raccoons (e.g., canine distemper virus, rabies, and leptospirosis) and civets (e.g., SARS coronavirus), have been active areas of investigation. Unfortunately, less research has focused on the potential effects of these pathogens on their hosts.


title: Respiratory and pulmonary complications in head and neck cancer patients: Evidence‐based review for the COVID‐19 era

text: BACKGROUND: Pulmonary complications and infections frequently affect patients with head and neck squamous cell carcinoma (HNSCC). Common characteristics can predispose these patients to the development of severe respiratory illness, which may be particularly relevant during the 2019 coronavirus disease (COVID‐19) pandemic. METHODS: A scoping review was performed to assess the impact of pulmonary comorbidities and adverse respiratory outcomes in HNSCC patients. RESULTS: Advanced age, history of tobacco and alcohol abuse, and cardiopulmonary comorbidities are significant risk factors for the development of adverse respiratory outcomes. Treatment toxicities from radiation or chemoradiation therapy significantly increase these risks. CONCLUSION: Respiratory complications are a frequent cause of morbidity and mortality among HNSCC patients, and the COVID‐19 pandemic may disproportionately affect this population. Interventions designed to decrease smoking and alcohol use, improve oral hygiene, and aggressively manage medical comorbidities are important to the long‐term management and health of these patients.


Response to four comments on ‘Can angiotensin receptor-blocking drugs perhaps be harmful in the COVID-19 pandemic?’


Maintaining Our Humanity Through the Mask: Mindful Communication During COVID‐19


À propos de chirurgie et COVID-19 : quelques précautions complémentaires. Réponse à : « Stratégie pour la pratique de la chirurgie digestive et oncologique en situation d’épidémie de COVID-19 »()


title: Effects of operational decisions on the diffusion of epidemic disease: A system dynamics modeling of the MERS-CoV outbreak in South Korea

text: Abstract We evaluated the nosocomial outbreak of Middle East Respiratory Syndrome (MERS) Coronavirus (CoV) in the Republic of Korea, 2015, from a healthcare operations management perspective. Establishment of healthcare policy in South Korea provides patients’ freedom to select and visit multiple hospitals. Current policy enforces hospitals preference for multi-patient rooms to single-patient rooms, to lower financial burden. Existing healthcare systems tragically contributed to 186 MERS outbreak cases, starting from single “index patient” into three generations of secondary infections. By developing a macro-level health system dynamics model, we provide empirical knowledge to examining the case from both operational and financial perspectives. In our simulation, under base infectivity scenario, high emergency room occupancy circumstance contributed to an estimated average of 101 (917%) more infected patients, compared to when in low occupancy circumstance. Economic patient room design showed an estimated 702% increase in the number of infected patients, despite the overall 98% savings in total expected costs compared to optimal room design. This study provides first time, system dynamics model, performance measurements from an operational perspective. Importantly, the intent of this study was to provide evidence to motivate public, private, and government healthcare administrators’ recognition of current shortcomings, to optimize performance as a whole system, rather than mere individual aspects.


title: Lung Infections

text: A review of pulmonary infections of all types with diagnostic and morphological features.


Update of Practice Guidelines for the Management of Community-Acquired Pneumonia in Immunocompetent Adults


title: Multiplex Degenerate Primer Design for Targeted Whole Genome Amplification of Many Viral Genomes

text: Background. Targeted enrichment improves coverage of highly mutable viruses at low concentration in complex samples. Degenerate primers that anneal to conserved regions can facilitate amplification of divergent, low concentration variants, even when the strain present is unknown. Results. A tool for designing multiplex sets of degenerate sequencing primers to tile overlapping amplicons across multiple whole genomes is described. The new script, run_tiled_primers, is part of the PriMux software. Primers were designed for each segment of South American hemorrhagic fever viruses, tick-borne encephalitis, Henipaviruses, Arenaviruses, Filoviruses, Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus, and Japanese encephalitis virus. Each group is highly diverse with as little as 5% genome consensus. Primer sets were computationally checked for nontarget cross reactions against the NCBI nucleotide sequence database. Primers for murine hepatitis virus were demonstrated in the lab to specifically amplify selected genes from a laboratory cultured strain that had undergone extensive passage in vitro and in vivo. Conclusions. This software should help researchers design multiplex sets of primers for targeted whole genome enrichment prior to sequencing to obtain better coverage of low titer, divergent viruses. Applications include viral discovery from a complex background and improved sensitivity and coverage of rapidly evolving strains or variants in a gene family.


title: Generation of therapeutic antisera for emerging viral infections

text: The recent Ebola virus outbreak has highlighted the therapeutic potential of antisera and renewed interest in this treatment approach. While human convalescent sera may not be readily available in the early stages of an outbreak, antisera of animal origin can be produced in a short time frame. Here, we compared adjuvanted virus-like particles (VLP) with recombinant modified vaccinia virus Ankara and vesicular stomatitis virus (VSV), both expressing the Ebola virus antigens. The neutralizing antibody titers of rabbits immunized with adjuvanted VLPs were similar to those immunized with the replication-competent VSV, indicating that presentation of the antigen in its native conformation rather than de novo antigen expression is essential for production of functional antibodies. This approach also yielded high-titer antisera against Nipah virus glycoproteins, illustrating that it is transferable to other virus families. Multiple-step immunoglobulin G purification using a two-step 20–40% ammonium sulfate precipitation followed by protein A affinity chromatography resulted in 90% recovery of functionality and sustained in vivo stability. Adjuvanted VLP-based immunization strategies are thus a promising approach for the rapid generation of therapeutic antisera against emerging infections.


title: Emerging Viral Infections in India

text: Despite an elaborate armamentarium to tackle microbes, emerging infectious diseases remain a crucial global challenge. Emerging infections can be defined as “infections that have newly appeared in a population or have existed previously but are rapidly increasing in incidence or geographic range.” Several factors like increase in international travel and trade, human encroachment on wild-life habitats, changes in agricultural practices and wild-life trade have contributed to the emergence of pathogens. Emergence/re-emergence of several viral infections has been reported from India in the past few decades; some of the important emerging viral infections are discussed in this review. They include infection due to Nipah, Hantaviruses, Chikungunya, Human Enterovirus-71, Influenza, Chandipura, Crimean Congo, SARS Coronavirus, Buffalopox, Dengue and Japanese Encephalitis viruses. Creating increased awareness and training of clinical microbiologists/virologists for identification of new/emerging pathogens, and prompt reporting and management of outbreaks is essential to tackle the threat posed by emerging/re-emerging infections.


title: Pathologies attribuables à la consommation de coquillages

text: Résumé Une revue de la littérature a permis de dégager la longue liste de germes et polluants rencontrés dans les coquillages et potentiellement pathogènes pour le consommateur. Il s'agit d'agents microbiens qui, véhiculés par les effluents issus des collectivités humaines ou animales, vont gagner les étangs littoraux et les sites ostréicoles. Par le jeu de la transmission fécale-orale, les coquillages sont à l'origine de manifestations cliniques très variées: états septicémiques, typhoïdes, hépatite virale A, syndromes neurologiques, gastro-entérites d'étiologie bactérienne, parasitaire ou virale. D'autres tableaux cliniques sont associés à des agents spécifiques résidants des milieux aquatiques: vibrions et algues toxiques dont le développement est conditionné par l'apport nutritif des eaux insuffisamment traitées et dépendant des conditions climatiques et écologiques. L'assainissement des collectivités et la protection des sites d'ostréiculture constituent l'unique prévention à mettre en regard d'une consommation paradoxale dans notre société hypersécuritaire: celle d'un coquillage, vivant et cru, directement extrait de son milieu naturel de production. Toute consommation festive a ses risques; pour qu'ils soient acceptables, les producteurs et les instances de contrôle doivent œuvrer, ensemble, à les réduire. Abstract From a literature survey, a long list of germs and pollutants found in shellfish has been drawn up, which are potential pathogens when eaten. These consist of microbes, which, carried by the effluent from human or animal communities, reach shoreline ponds and oyster production sites. Transmission from faecal material to the eaten seafood is the origin of a variety of clinical conditions: septicaemia, typhoid, viral hepatitis A, neurological syndromes, and gastro-enteritis induced by bacteria, parasites or viruses. Other illnesses are associated with specific agents coming from the water environment: vibrios and toxic seaweeds, whose growth has been affected by nutrients in the untreated, surrounding waters, and depends on climatic and ecological conditions. The treatment of waste water from communities, and the protection of production sites are the sole means of illness prevention, since the case of shellfish, eaten alive and raw, and having been taken directly from the natural production environment, is a paradox in our ⪡hyper-secure⪢ food system. All food intake in the festive season has risks: for these to be acceptable, producers and control mechanisms must work together to reduce them.


title: Role of Severe Acute Respiratory Syndrome Coronavirus Viroporins E, 3a, and 8a in Replication and Pathogenesis

text: Viroporins are viral proteins with ion channel (IC) activity that play an important role in several processes, including virus replication and pathogenesis. While many coronaviruses (CoVs) encode two viroporins, severe acute respiratory syndrome CoV (SARS-CoV) encodes three: proteins 3a, E, and 8a. Additionally, proteins 3a and E have a PDZ-binding motif (PBM), which can potentially bind over 400 cellular proteins which contain a PDZ domain, making them potentially important for the control of cell function. In the present work, a comparative study of the functional motifs included within the SARS-CoV viroporins was performed, mostly focusing on the roles of the IC and PBM of E and 3a proteins. Our results showed that the full-length E and 3a proteins were required for maximal SARS-CoV replication and virulence, whereas viroporin 8a had only a minor impact on these activities. A virus missing both the E and 3a proteins was not viable, whereas the presence of either protein with a functional PBM restored virus viability. E protein IC activity and the presence of its PBM were necessary for virulence in mice. In contrast, the presence or absence of the homologous motifs in protein 3a did not influence virus pathogenicity. Therefore, dominance of the IC and PBM of protein E over those of protein 3a was demonstrated in the induction of pathogenesis in mice.


Critical care journals during the COVID-19 pandemic: challenges and responsibilities


title: Towards our understanding of SARS-CoV, an emerging and devastating but quickly conquered virus

text: Abstract Severe acute respiratory syndrome (SARS) is a newly emerging infectious disease caused by a novel coronavirus (SARS-CoV), which has overwhelmed more than 30 countries claiming nearly 8400 cases with over 800 fatalities. Thanks to the unprecedented international collaboration, the whole-genomes of SARS-CoVs were successfully deciphered shortly after the identification of the causative pathogen for outbreak of SARS in southern China, in 2003. Hitherto, the SARS-CoV, as a viral paradigm of emerging infectious entities, has been extensively studied that has ranged from epidemiology, molecular virology/immunology to structural genomics. Also, several lines of breakthroughs have been record-brokenly obtained, that included the finding of ACE2, a functional receptor for the SARS-CoV, solution of the 3CLpro structure, a first crystal structure of SARS-related macromolecules, revealing of bats as natural reservoirs for SARS-like viruses and the possible involvement of civet cats in the SARS emergence. This review intends to outline the major progress in the journey of SARS-related exploration, by emphasizing those inaugurated studies with milestone-like significance contributed by Chinese research groups.


title: Survival After In-Hospital Cardiac Arrest In Critically Ill Patients: Implications For The Covid-19 Pandemic?

text: The coronavirus disease 2019 (COVID-19) outbreak is placing a considerable strain on U.S. healthcare systems. Due to presumptions of poor outcomes in such critically ill patients, many hospitals have started considering a universal do-not-resuscitate order in patients with confirmed Covid-19 given a limited supply of intensive care unit (ICU) beds and the potential risk of transmission of infection to healthcare workers during resuscitation. However, empirical data on survival of cardiac arrest in Covid-19 patients are unavailable at this time. To inform this debate, we report survival outcomes following cardiopulmonary resuscitation in a cohort of similar critically ill patients with pneumonia or sepsis who were receiving mechanical ventilation in an ICU at the time of arrest. The probability of survival without severe neurological disability (CPC of 1 or 2) ranged from less than 3% to over 22% across key patient subgroups, For patients with an initial rhythm of asystole or PEA, who were also receiving vasopressors at the time of arrest, fewer than 10% were discharged without severe neurological disability (CPC of 1 or 2), and this number dropped to less than 3% in patients over 80 years old. In contrast, survival rates were much higher in younger patients, patients with an initial rhythm of VF or pulseless VT, and in patients receiving ventilatory support without vasopressors. Our findings suggest caution in universal resuscitation policies. Even in a cohort of critically ill patients on mechanical ventilation, survival outcomes following in-hospital resuscitation were not uniformly poor and varied markedly depending on age, co-morbidities and illness severity. We believe that these data can help inform discussions among patients, providers and hospital leaders regarding resuscitation policies and goals of care in the context of the COVID-19 pandemic.


title: Direct trafficking pathways from the Golgi apparatus to the plasma membrane

text: Abstract In eukaryotic cells, protein sorting is a highly regulated mechanism important for many physiological events. After synthesis in the endoplasmic reticulum and trafficking to the Golgi apparatus, proteins sort to many different cellular destinations including the endolysosomal system and the extracellular space. Secreted proteins need to be delivered directly to the cell surface. Sorting of secreted proteins from the Golgi apparatus has been a topic of interest for over thirty years, yet there is still no clear understanding of the machinery that forms the post-Golgi carriers. Most evidence points to these post-Golgi carriers being tubular pleomorphic structures that bud from the trans-face of the Golgi. In this review, we present the background studies and highlight the key components of this pathway, we then discuss the machinery implicated in the formation of these carriers, their translocation across the cytosol, and their fusion at the plasma membrane.


title: A truncated fragment of Ov-ASP-1 consisting of the core pathogenesis-related-1 (PR-1) domain maintains adjuvanticity as the full-length protein

text: Abstract The Onchocerca volvulus activation-associated secreted protein-1 (Ov-ASP-1) has good adjuvanticity for a variety of antigens and vaccines, probably due to its ability activate antigen-processing cells (APCs). However, the functional domain of Ov-ASP-1 as an adjuvant is not clearly defined. Based on the structural prediction of this protein family, we constructed a 16-kDa recombinant protein of Ov-ASP-1 that contains only the core pathogenesis-related-1 (PR-1) domain (residues 10–153), designated ASPPR. We found that ASPPR exhibits adjuvanticity similar to that of the full-length Ov-ASP-1 (residues 10–220) for various antigens, including ovalbumin (OVA), HBsAg protein antigen, and the HIV peptide 5 (Pep5) antigen, but it is more suitable for vaccine design in ASPPR-antigen fusion proteins, and more stable in PBS than Ov-ASP-1 stored at −70°C. These results suggest that ASPPR might be the functional region of Ov-ASP-1 as an adjuvant, and therefore could be developed as an adjuvant for human use.


title: Type I Interferons as Regulators of Lung Inflammation

text: Immune responses to lung infections must be tightly regulated in order to permit pathogen eradication while maintaining organ function. Exuberant or dysregulated inflammation can impair gas exchange and underlies many instances of lung disease. An important driver of inflammation in the lung is the interferon (IFN) response. Type I IFNs are antiviral cytokines that induce a large range of proteins that impair viral replication in infected cells. This cell-intrinsic action plays a crucial role in protecting the lungs from spread of respiratory viruses. However, type I IFNs have also recently been found to be central to the initiation of lung inflammatory responses, by inducing recruitment and activation of immune cells. This helps control virus burden but can cause detrimental immunopathology and contribute to disease severity. Furthermore, there is now increasing evidence that type I IFNs are not only induced after viral infections but also after infection with bacteria and fungi. The pro-inflammatory function of type I IFNs in the lung opens up the possibility of immune modulation directed against this antiviral cytokine family. In this review, the initiation and signaling of type I IFNs as well as their role in driving and maintaining lung inflammation will be discussed.


title: Identification of the immunodominant neutralizing regions in the spike glycoprotein of porcine deltacoronavirus

text: Abstract Porcine deltacoronavirus (PDCoV), is an emerging enteropathogenic coronavirus in pigs, that poses a novel threat to swine husbandry worldwide. Crucial to halting PDCoV transmission and infection is the development of effective therapies and vaccines. The spike (S) protein of coronavirus is the major target of host neutralizing antibodies, however the immunodominant neutralizing region in the S protein of PDCoV has not been defined. Here, three truncations of the PDCoV S protein were generated, the N-terminal domain of the S1 subunit (NTD, amino acids (aa) 50–286), the C-terminal domain of the S1 subunit (CTD, aa 278–616), and S2 subunit (aa 601–1087). The proteins were expressed using an E. coli expression system. Polyclonal antisera against the three recombinant proteins were produced in rabbits and mice. All three antisera were able to inhibit PDCoV infection in vitro, as determined by virus neutralization assay, fluorescent focus neutralization assay, and plaque-reduction neutralization. The CTD-specific antisera had the most potent PDCoV-neutralizing effect, indicating that the CTD region may contain the major neutralizing epitope(s) in the PDCoV S protein. Based on these findings, CTD may be a promising target for development of an effective vaccine against PDCoV infection in pigs.


title: ARIMA modelling and forecasting of irregularly patterned COVID-19 outbreaks using Japanese and South Korean data

text: Abstract The World Health Organization (WHO) upgraded the status of the coronavirus disease 2019 (COVID-19) outbreak from epidemic to global pandemic on March 11, 2020. Various mathematical and statistical models have been proposed to predict the spread of COVID-2019[1]. We collated data on daily new confirmed cases of the COVID-19 outbreaks in Japan and South Korea from January 20, 2020 to April 26, 2020. Auto Regressive Integrated Moving Average (ARIMA) model were introduced to analyze two data sets and predict the daily new confirmed cases for the 7-day period from April 27, 2020 to May 3, 2020. Also, the forecasting results and both data sets are provided.


title: Outcome of Coronavirus spectrum infections (SARS, MERS, COVID 1 -19) during pregnancy: a systematic review and meta-analysis

text: ABSTRACT Objective The aim of this systematic review was to report pregnancy and perinatal outcomes of Coronavirus (CoV) spectrum infections, and particularly COVID-19 disease due to SARS-COV-2 infection during pregnancy. Data sources Medline, Embase, Cinahl and Clinicaltrials.gov databases were searched electronically utilizing combinations of word variants for “coronavirus” or “severe acute respiratory syndrome” or “SARS” or “Middle East respiratory syndrome” or “MERS” or “COVID-19” and “pregnancy”. The search and selection criteria were restricted to English language. Study eligibility criteria Inclusion criteria were pregnant women with a confirmed Coronavirus related illness, defined as either SARS, MERS or COVID-19. Study appraisal and synthesis methods We used meta-analyses of proportions to combine data and reported pooled proportions. The pregnancy outcomes observed included miscarriage, preterm birth, pre-eclampsia, preterm prelabor rupture of membranes, fetal growth restriction, and mode of delivery. The perinatal outcomes observed were fetal distress, Apgar score < 7 at five minutes, neonatal asphyxia, admission to neonatal intensive care unit, perinatal death, and evidence of vertical transmission. Results 19 studies including 79 women were eligible for this systematic review: 41 pregnancies (51.9%) affected by COVID-19, 12 (15.2%) by MERS, and 26 (32.9%) by SARS. An overt diagnosis of pneumonia was made in 91.8% and the most common symptoms were fever (82.6%), cough (57.1%) and dyspnea (27.0%). For all CoV infections, the rate of miscarriage was 39.1% (95% CI 20.2-59.8); the rate of preterm birth < 37 weeks was 24.3% (95% CI 12.5-38.6); premature prelabor rupture of membranes occurred in 20.7% (95% CI 9.5-34.9), preeclampsia in 16.2% (95% CI 4.2-34.1), and fetal growth restriction in 11.7% (95% CI 3.2-24.4); 84% were delivered by cesarean; the rate of perinatal death was 11.1% (95% CI 84.8-19.6) and 57.2% (95% CI 3.6-99.8) of newborns were admitted to the neonatal intensive care unit. When focusing on COVID-19, the most common adverse pregnancy outcome was preterm birth < 37 weeks, occurring in 41.1% (95% CI 25.6-57.6) of cases, while the rate of perinatal death was 7.0% (95% CI 1.4-16.3). None of the 41 newborns assessed showed clinical signs of vertical transmission. Conclusion In mothers infected with coronavirus infections, including COVID-19, >90% of whom also had pneumonia, PTB is the most common adverse pregnancy outcome. Miscarriage, preeclampsia, cesarean, and perinatal death (7-11%) were also more common than in the general population. There have been no published cases of clinical evidence of vertical transmission. Evidence is accumulating rapidly, so these data may need to be updated soon. The findings from this study can guide and enhance prenatal counseling of women with COVID-19 infection occurring during pregnancy.


title: Characterization of paneth cells in alpacas (Vicugna pacos, Mammalia, Camelidae)

text: Abstract Paneth cells are secretory epithelial cells of the innate immune system of the intestine of several mammals, including alpacas. Little is known about the latter; thus, in the present study we described the morphology and histochemical characteristics of Paneth cells in healthy fetuses, and young and adult alpacas. For this purpose, samples of duodenum, jejunum and ileum were taken from 6 fetuses at different days of pregnancy (between days 221–330), 66 offsprings (between 0 and 45-days-old) and 5 adult alpacas (>2-years-old). Samples were fixed in 10% buffered formalin and processed for histological and morphometrical analysis using HE and Masson Trichomićs technique. Immunohistochemistry was used to identify Paneth cells using anti-lysozyme antibody. In addition, the lectinhistochemichal binding-pattern of Paneth celĺs granules was evaluated. Lyzozyme was immunohistochemically detected in the granules of Paneth cells from day 283 of pregnancy in all the small intestinal sections of the studied fetuses. In newborn alpacas Paneth cells were initially found in the duodenum, but the following days (days 18–21 after birth) they were also found in the ileum. Their size gradually increased after birth, but then no significant differences were found. In adult alpacas the number was lower than offsprings. We suggest that Paneth cells early differentiate in the small intestine of alpacas, and the increase in their number during the first two weeks of life strongly support their possible involvement in the intestinal defensive functions against the enteric diseases that occur during the lactancy stage.


title: Newcastle disease vaccines—A solved problem or a continuous challenge?

text: Abstract Newcastle disease (ND) has been defined by the World Organisation for Animal Health as infection of poultry with virulent strains of Newcastle disease virus (NDV). Lesions affecting the neurological, gastrointestinal, respiratory, and reproductive systems are most often observed. The control of ND must include strict biosecurity that prevents virulent NDV from contacting poultry, and also proper administration of efficacious vaccines. When administered correctly to healthy birds, ND vaccines formulated with NDV of low virulence or viral-vectored vaccines that express the NDV fusion protein are able to prevent clinical disease and mortality in chickens upon infection with virulent NDV. Live and inactivated vaccines have been widely used since the 1950’s. Recombinant and antigenically matched vaccines have been adopted recently in some countries, and many other vaccine approaches have been only evaluated experimentally. Despite decades of research and development towards formulation of an optimal ND vaccine, improvements are still needed. Impediments to prevent outbreaks include uneven vaccine application when using mass administration techniques in larger commercial settings, the difficulties associated with vaccinating free-roaming, multi-age birds of village flocks, and difficulties maintaining the cold chain to preserve the thermo-labile antigens in the vaccines. Incomplete or improper immunization often results in the disease and death of poultry after infection with virulent NDV. Another cause of decreased vaccine efficacy is the existence of antibodies (including maternal) in birds, which can neutralize the vaccine and thereby reduce the effectiveness of ND vaccines. In this review, a historical perspective, summary of the current situation for ND and NDV strains, and a review of traditional and experimental ND vaccines are presented.


title: The potential impact of COVID-19 in refugee camps in Bangladesh and beyond: A modeling study

text: BACKGROUND: COVID-19 could have even more dire consequences in refugees camps than in general populations. Bangladesh has confirmed COVID-19 cases and hosts almost 1 million Rohingya refugees from Myanmar, with 600,000 concentrated in the Kutupalong-Balukhali Expansion Site (mean age, 21 years; standard deviation [SD], 18 years; 52% female). Projections of the potential COVID-19 burden, epidemic speed, and healthcare needs in such settings are critical for preparedness planning. METHODS AND FINDINGS: To explore the potential impact of the introduction of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the Kutupalong-Balukhali Expansion Site, we used a stochastic Susceptible Exposed Infectious Recovered (SEIR) transmission model with parameters derived from emerging literature and age as the primary determinant of infection severity. We considered three scenarios with different assumptions about the transmission potential of SARS-CoV-2. From the simulated infections, we estimated hospitalizations, deaths, and healthcare needs expected, age-adjusted for the Kutupalong-Balukhali Expansion Site age distribution. Our findings suggest that a large-scale outbreak is likely after a single introduction of the virus into the camp, with 61%–92% of simulations leading to at least 1,000 people infected across scenarios. On average, in the first 30 days of the outbreak, we expect 18 (95% prediction interval [PI], 2–65), 54 (95% PI, 3–223), and 370 (95% PI, 4–1,850) people infected in the low, moderate, and high transmission scenarios, respectively. These reach 421,500 (95% PI, 376,300–463,500), 546,800 (95% PI, 499,300–567,000), and 589,800 (95% PI, 578,800–595,600) people infected in 12 months, respectively. Hospitalization needs exceeded the existing hospitalization capacity of 340 beds after 55–136 days, between the low and high transmission scenarios. We estimate 2,040 (95% PI, 1,660–2,500), 2,650 (95% PI, 2,030–3,380), and 2,880 (95% PI, 2,090–3,830) deaths in the low, moderate, and high transmission scenarios, respectively. Due to limited data at the time of analyses, we assumed that age was the primary determinant of infection severity and hospitalization. We expect that comorbidities, limited hospitalization, and intensive care capacity may increase this risk; thus, we may be underestimating the potential burden. CONCLUSIONS: Our findings suggest that a COVID-19 epidemic in a refugee settlement may have profound consequences, requiring large increases in healthcare capacity and infrastructure that may exceed what is currently feasible in these settings. Detailed and realistic planning for the worst case in Kutupalong-Balukhali and all refugee camps worldwide must begin now. Plans should consider novel and radical strategies to reduce infectious contacts and fill health worker gaps while recognizing that refugees may not have access to national health systems.


title: A seroepidemiologic study of Reston ebolavirus in swine in the Philippines

text: BACKGROUND: Ebola viruses cause viral hemorrhagic fever in humans and non-human primates and are endemic in Africa. Reston ebolavirus (REBOV) has caused several epizootics in cynomolgus monkeys (Macaca fascicularis) but is not associated with any human disease. In late 2008, REBOV infections were identified in swine for the first time in the Philippines. METHODS: A total of 215 swine sera collected at two REBOV-affected farms in 2008, in Pangasinan and Bulacan, were tested for the presence of REBOV-specific antibodies using multiple serodiagnosis systems. A total of 98 swine sera collected in a non-epizootic region, Tarlac, were also tested to clarify the prevalence of REBOV infection in the general swine population in the Philippines. RESULTS: Some 70 % of swine sera at the affected farms were positive for REBOV antibodies in the multiple serodiagnosis systems. On the other hand, none of the swine sera collected in Tarlac showed positive reactions in any of the diagnosis systems. CONCLUSIONS: The high prevalence of REBOV infection in swine in the affected farms in 2008 suggests that swine is susceptible for REBOV infection. The multiple serological assays used in the study are thought to be useful for future surveillance of REOBV infection in swine in the Philippines.


title: Low Circulation of Subclade A1 Enterovirus D68 Strains in Senegal during 2014 North America Outbreak

text: To retrospectively investigate enterovirus D68 circulation in Senegal during the 2014 US outbreak, we retrieved specimens from 708 persons, mostly children, who had acute respiratory symptoms during September–December 2014. Enterovirus D68 was detected in 14 children (2.1%); most cases occurred in October. Phylogenetic analysis revealed that all strains clustered within subclade A1.


Donor Infection: An Opinion on Lung Donor Utilization


title: HIV-1 mutates to evade IFITM1 restriction

text: Abstract Interferon-induced transmembrane (IFITM) proteins inhibit the infection of a wide range of viruses including human immunodeficiency virus type 1 (HIV-1). At present, little is known about how viruses overcome IFITM restriction. In this study, we have utilized HIV-1 as a model and selected IFITM1-resistant viruses after multiple passages of HIV-1 in IFITM1-expressing SupT1 cells. Sequencing the entire viral genome revealed several mutations in the vpu and envelope genes, among which mutations Vpu34 and EnvG367E together enable efficient HIV-1 replication in IFITM1-expressing cells. Vpu34 introduces a stop codon at amino acid position 35 of Vpu, whereas EnvG367E changes the G367 residue at the CD4-binding site of gp120. These two mutations do not appear to overcome the downregulation of viral p24 expression caused by IFITM1, but rather enhance HIV-1 replication by promoting cell-to-cell virus transmission. Altogether, our data demonstrate that HIV-1 can mutate to evade IFITM1 restriction by increasing cell-to-cell transmission.


title: Antibody prevalence to human enteric coronavirus-like particles and indications of antigenic differences between particles from different areas

text: Antibody to human enteric coronavirus-like particles was detected in Australian Aborigines, but at lower levels or not at all in Europeans. There were indications of antigenic differences between particles from different areas. Support was provided for consideration of such particles as infectious agents.


title: The benevolent health worm: comparing Western human rights-based ethics and Confucian duty-based moral philosophy

text: Censorship in the area of public health has become increasingly important in many parts of the world for a number of reasons. Groups with vested interest in public health policy are motivated to censor material. As governments, corporations, and organizations champion competing visions of public health issues, the more incentive there may be to censor. This is true in a number of circumstances: curtailing access to information regarding the health and welfare of soldiers in the Kuwait and Iraq wars, poor health conditions in Aboriginal communities, downplaying epidemics to bolster economies, and so forth. This paper will look at the use of a computer worm (the benevolent health worm) to disseminate vital information in␣situations where public health is threatened by government censorship and where there is great risk for those who ‹speak out’. The discussion of the benevolent health worm is focused on the Peoples’ Republic of China (China) drawing on three public health crises: HIV/AIDS, SARS and Avian Influenza. Ethical issues are examined first in a general fashion and then in a specific manner which uses the duty-based moral philosophy of Confucianism and a Western human rights-based analysis. Technical, political and legal issues will also be examined to the extent that they better inform the ethical debate.


title: Mental health problems and social media exposure during COVID-19 outbreak

text: Huge citizens expose to social media during a novel coronavirus disease (COVID-19) outbroke in Wuhan, China. We assess the prevalence of mental health problems and examine their association with social media exposure. A cross-sectional study among Chinese citizens aged≥18 years old was conducted during Jan 31 to Feb 2, 2020. Online survey was used to do rapid assessment. Total of 4872 participants from 31 provinces and autonomous regions were involved in the current study. Besides demographics and social media exposure (SME), depression was assessed by The Chinese version of WHO-Five Well-Being Index (WHO-5) and anxiety was assessed by Chinese version of generalized anxiety disorder scale (GAD-7). multivariable logistic regressions were used to identify associations between social media exposure with mental health problems after controlling for covariates. The prevalence of depression, anxiety and combination of depression and anxiety (CDA) was 48.3% (95%CI: 46.9%-49.7%), 22.6% (95%CI: 21.4%-23.8%) and 19.4% (95%CI: 18.3%-20.6%) during COVID-19 outbroke in Wuhan, China. More than 80% (95%CI:80.9%-83.1%) of participants reported frequently exposed to social media. After controlling for covariates, frequently SME was positively associated with high odds of anxiety (OR = 1.72, 95%CI: 1.31–2.26) and CDA (OR = 1.91, 95%CI: 1.52–2.41) compared with less SME. Our findings show there are high prevalence of mental health problems, which positively associated with frequently SME during the COVID-19 outbreak. These findings implicated the government need pay more attention to mental health problems, especially depression and anxiety among general population and combating with “infodemic” while combating during public health emergency.


title: Phytochemical profile of Paulownia tomentosa (Thunb). Steud.

text: Paulownia tomentosa, a member of the plant family Paulowniaceae and a rich source of biologically active secondary metabolites, is traditionally used in Chinese herbal medicine. Flavonoids, lignans, phenolic glycosides, quinones, terpenoids, glycerides, phenolic acids, and miscellaneous other compounds have been isolated from different parts of P. tomentosa plant. Recent interest in this species has focused on isolating and identifying of prenylated flavonoids, that exhibit potent antioxidant, antibacterial, and antiphlogistic activities and inhibit severe acute respiratory syndrome coronavirus papain-like protease. They show cytotoxic activity against various human cancer cell lines and inhibit the effects of human cholinesterase, butyrylcholinesterase, and bacterial neuraminidases. Most of the compounds considered here have never been isolated from any other species of plant. This review summarizes the information about the isolated compounds that are active, their bioactivities, and the structure–activity relationships that have been worked out for them.


Introduction: Progress towards meeting the challenges in clinical microbiology and infectious diseases


title: Gastroenteritis, Hepatitis, Encephalopathy, and Human Herpesvirus 6 Detection in an Immunocompetent Child: Benefits and Risks of Syndromic Multiplex Molecular Panel Testing

text: An immunocompetent toddler came to medication attention with gastroenteritis, complicated by encephalopathy and hepatitis. Multiplexed testing using a polymerase chain reaction meningitis panel was positive for human herpesvirus 6 (HHV-6). Clinical correlation, quantitative HHV-6 polymerase chain reaction, and metagenomic next-generation sequencing supported a likely diagnosis of primary HHV-6B infection.


title: PCR-based diagnostics for infectious diseases: uses, limitations, and future applications in acute-care settings

text: Summary Molecular diagnostics are revolutionising the clinical practice of infectious disease. Their effects will be significant in acute-care settings where timely and accurate diagnostic tools are critical for patient treatment decisions and outcomes. PCR is the most well-developed molecular technique up to now, and has a wide range of already fulfilled, and potential, clinical applications, including specific or broad-spectrum pathogen detection, evaluation of emerging novel infections, surveillance, early detection of biothreat agents, and antimicrobial resistance profiling. PCR-based methods may also be cost effective relative to traditional testing procedures. Further advancement of technology is needed to improve automation, optimise detection sensitivity and specificity, and expand the capacity to detect multiple targets simultaneously (multiplexing). This review provides an up-to-date look at the general principles, diagnostic value, and limitations of the most current PCR-based platforms as they evolve from bench to bedside.


title: Covid-19 goes global

text: Our chance to limit international outbreaks may be over as the virus spreads in Italy and the Middle East, reports Debora MacKenzie


title: Profiling infectious diseases in Turkey after the influx of 3.5 million Syrian refugees

text: Abstract Background Since 2011, the conflict in Syria has led to over five million refugees. Turkey hosts the highest number of Syrian refugees in the world. By February 2019 over 3.6 million people had fled to Turkey to seek safety. Only 6.1% of Syrian refugees live in temporary shelters. Owing to the disrupted healthcare services, many children coming from the conflict zones are less likely to have received vaccination. In temporary shelters immunization coverage is >95% and the refugee population is receptive to vaccination. Aims The objective of this study was to review the infectious diseases situation among Syrian refugees in Turkey. Sources We have reviewed the reports and studies provided by the governmental and non-governmental organizations and obtained more detailed data from the Ministry of Health in Turkey. Content Between 2012 and 2016, 1 299 209 cases of respiratory tract infection and 158 058 episodes of diarrhoea with 59 bloody diarrhoeas were reported; 1354 hepatitis A cases and 108 active tuberculosis cases were detected and treated in the temporary shelters for Syrian refugees. Overall in Turkey, 7794 cutaneous leishmaniasis have been reported. Implications Since the influx of Syrian refugees, there has been an increase in cases of leishmaniasis and measles. No significant increase was detected for tuberculosis, other vector-borne infections, and healthcare associated or sexually transmitted infections. The Syrian refugees can be considered as a vulnerable group in Turkey due to their living and working conditions. Based on available data and our detailed analysis, the numbers show a stable situation regarding infectious diseases.


title: Face ID firms battle Covid-19 as users shun fingerprinting

text: Facial recognition firms have launched a slew of new products to combat the global Covid-19 virus. But users worldwide are also discarding touch-based fingerprinting systems – prompting fears the pandemic could trigger a business slump among ‘contact’ biometric technology vendors.


title: Analysis of Psychological and Sleep Status and Exercise Rehabilitation of Front-Line Clinical Staff in the Fight Against COVID-19 in China

text: BACKGROUND: The aim of this study was to understand the changes in psychological factors and sleep status of front-line medical staff in the fight against COVID-19 and provide evidence of exercise interventions to relieve psychological stress and improve sleep status for medical staff. MATERIAL/METHODS: A survey study was conducted among 120 front-line medical staff in the fight against COVID-19, of which 60 medical staff worked at the designated hospital (experimental group) and 60 medical staff worked at the non-designated hospital (control group). The Symptom Checklist 90 (SCL-90), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), and PTSD Checklist-Civilian Version (PCL-C) were used to assess mental status. Sleep status was assessed using the Pittsburgh Sleep Quality Index (PSQI). RESULTS: SCL-90 scores of somatization, depression, anxiety, and terror were higher than normal in front-line medical staff at the designated hospital. The SAS (45.89±1.117), SDS (50.13±1.813), and PCL-C (50.13±1.813) scores in the experimental group were higher than the normal control group, and were significantly different from those in the control group on SDS and PCL-C scales (P<0.05). The total average PSQI of the experimental group was 16.07±3.761, indicating that the sleep quality was poor. Among them, participants with moderate insomnia reached 61.67%, and participants with severe insomnia reached 26.67%. CONCLUSIONS: There are psychological symptoms and sleep symptoms in front-line medical staff who participate in the fight against COVID-19, and they affect each other. Hospitals should improve emergency management measures, strengthen psychological counseling for clinical front-line medical staff, strengthen exercise intervention, and improve their sleep quality and mental health.


title: Glycerol Monolaurate, an Analogue to a Factor Secreted by Lactobacillus, Is Virucidal against Enveloped Viruses, Including HIV-1

text: The vaginal microbiota influences sexual transmission of human immunodeficiency virus type 1 (HIV-1). Colonization of the vaginal tract is normally dominated by Lactobacillus species. Both Lactobacillus and Enterococcus faecalis may secrete reutericyclin, which inhibits the growth of a variety of pathogenic bacteria. Increasing evidence suggests a potential therapeutic role for an analogue of reutericyclin, glycerol monolaurate (GML), against microbial pathogens. Previous studies using a macaque vaginal simian immunodeficiency virus (SIV) transmission model demonstrated that GML reduces transmission and alters immune responses to infection in vitro. Previous studies showed that structural analogues of GML negatively impact other enveloped viruses. We sought to expand understanding of how GML inhibits HIV-1 and other enveloped viruses and show that GML restricts HIV-1 entry post-CD4 engagement at the step of coreceptor binding. Further, HIV-1 and yellow fever virus (YFV) particles were more sensitive to GML interference than particles “matured” by proteolytic processing. We show that high-pressure-liquid-chromatography (HPLC)-purified reutericyclin and reutericyclin secreted by Lactobacillus inhibit HIV-1. These data emphasize the importance and protective nature of the normal vaginal flora during viral infections and provide insights into the antiviral mechanism of GML during HIV-1 infection and, more broadly, to other enveloped viruses.


title: The SARS-CoV heptad repeat 2 exhibits pH-induced helix formation

text: Abstract The heptad repeats 1 and 2 of SARS-CoV spike, termed HR1 and HR2, play critical roles in viral entry. Moreover, HR1 and HR2 derived free peptides are inhibitors of SARS-CoV entry. In this work we used circular dichroism to show that HR2 helix formation is induced at pH 5, the pH of the endosome. In addition, we demonstrate that the HR2 helix is further stabilized at physiological ionic strengths. Together, these observations provide new insight into the mechanism of SARS-CoV entry and suggest that HR2 may be an attractive target for therapeutic intervention.


Clinical characteristics and risk factors for mortality among inpatients with COVID‐19 in Wuhan, China


title: Functional variants regulating LGALS1 (Galectin 1) expression affect human susceptibility to influenza A(H7N9)

text: The fatality of avian influenza A(H7N9) infection in humans was over 30%. To identify human genetic susceptibility to A(H7N9) infection, we performed a genome-wide association study (GWAS) involving 102 A(H7N9) patients and 106 heavily-exposed healthy poultry workers, a sample size critically restricted by the small number of human A(H7N9) cases. To tackle the stringent significance cutoff of GWAS, we utilized an artificial imputation program SnipSnip to improve the association signals. In single-SNP analysis, one of the top SNPs was rs13057866 of LGALS1. The artificial imputation (AI) identified three non-genotyped causal variants, which can be represented by three anchor/partner SNP pairs rs13057866/rs9622682 (AI P = 1.81 × 10(−7)), rs4820294/rs2899292 (2.13 × 10(−7)) and rs62236673/rs2899292 (4.25 × 10(−7)) respectively. Haplotype analysis of rs4820294 and rs2899292 could simulate the signal of a causal variant. The rs4820294/rs2899292 haplotype GG, in association with protection from A(H7N9) infection (OR = 0.26, P = 5.92 × 10(−7)) correlated to significantly higher levels of LGALS1 mRNA (P = 0.050) and protein expression (P = 0.025) in lymphoblast cell lines. Additionally, rs4820294 was mapped as an eQTL in human primary monocytes and lung tissues. In conclusion, functional variants of LGALS1 causing the expression variations are contributable to the differential susceptibility to influenza A(H7N9).


title: Toll-like receptors in antiviral innate immunity

text: Toll-like receptors (TLRs) are fundamental sensor molecules of the host innate immune system, which detect conserved molecular signatures of a wide range of microbial pathogens and initiate innate immune responses via distinct signaling pathways. Various TLRs are implicated in the early interplay of host cells with invading viruses, which regulates viral replication and/or host responses, ultimately impacting on viral pathogenesis. To survive the host innate defense mechanisms, many viruses have developed strategies to evade or counteract signaling through the TLR pathways, creating an advantageous environment for their propagation. Here we review the current knowledge of the roles TLRs play in antiviral innate immune responses, discuss examples of TLR-mediated viral recognition, and describe strategies used by viruses to antagonize the host antiviral innate immune responses.


title: Aryl methylene ketones and fluorinated methylene ketones as reversible inhibitors for severe acute respiratory syndrome (SARS) 3C-like proteinase

text: Abstract The severe acute respiratory syndrome (SARS) virus depends on a chymotrypsin-like cysteine proteinase (3CLpro) to process the translated polyproteins to functional viral proteins. This enzyme is a target for the design of potential anti-SARS drugs. A series of ketones and corresponding mono- and di-fluoro ketones having two or three aromatic rings were synthesized as possible reversible inhibitors of SARS 3CLpro. The design was based on previously established potent inhibition of the enzyme by oxa analogues (esters), which also act as substrates. Structure–activity relationships and modeling studies indicate that three aromatic rings, including a 5-bromopyridin-3-yl moiety, are key features for good inhibition of SARS 3CLpro. Compound 11d, 2-(5-bromopyridin-3-yl)-1-(5-(4-chlorophenyl)furan-2-yl)ethanone and its α-monofluorinated analogue 12d, gave the best reversible inhibition with IC50 values of 13μM and 28μM, respectively. In contrast to inhibitors having two aromatic rings, α-fluorination of compounds with three rings unexpectedly decreased the inhibitory activity.


Data Protection and Research: A vital challenge in the era of Covid-19 Pandemic


title: A novel mosquito ubiquitin targets viral envelope protein for degradation and reduces virion production during dengue virus infection

text: BACKGROUND: Dengue virus (DENV) is a mosquito-borne flavivirus that causes significant human disease and mortality in the tropics and subtropics. By examining the effects of virus infection on gene expression, and interactions between virus and vector, new targets for prevention of infection and novel treatments may be identified in mosquitoes. We previously performed a microarray analysis of the Ae. aegypti transcriptome during infection with DENV and found that mosquito ubiquitin protein Ub3881 (AAEL003881) was specifically and highly down-regulated. Ubiquitin proteins have multiple functions in insects, including marking proteins for proteasomal degradation, regulating apoptosis and mediating innate immune signaling. METHODS: We used qRT-PCR to quantify gene expression and infection, and RNAi to reduce Ub3881 expression. Mosquitoes were infected with DENV through blood feeding. We transfected DENV protein expression constructs to examine the effect of Ub3881 on protein degradation. We used site-directed mutagenesis and transfection to determine what amino acids are involved in Ub3881-mediated protein degradation. Immunofluorescence, Co-immunoprecipitation and Western blotting were used to examine protein interactions and co-localization. RESULTS: The overexpression of Ub3881, but not related ubiquitin proteins, decreased DENV infection in mosquito cells and live Ae. aegypti. The Ub3881 protein was demonstrated to be involved in DENV envelope protein degradation and reduce the number of infectious virions released. CONCLUSIONS: We conclude that Ub3881 has several antiviral functions in the mosquito, including specific viral protein degradation. GENERAL SIGNIFICANCE: Our data highlights Ub3881 as a target for future DENV prevention strategies in the mosquito transmission vector.


title: Is restoring an ecosystem good for your health?

text: Abstract It is well known that the degradation of ecosystems can have serious impacts on human health. There is currently a knowledge gap on what impact restoring ecosystems has on human health. In restoring ecosystems there is a drive to restore the functionality of ecosystems rather than restoring ecosystems to ‘pristine’ condition. Even so, the complete restoration of all ecosystem functions is not necessarily possible. Given the uncertain trajectory of the ecosystem during the ecosystem restoration process the impact of the restoration on human health is also uncertain. Even with this uncertainty, the restoration of ecosystems for human health is still a necessity.


title: COVID-19: Clinical course and outcomes of 36 maintenance hemodialysis patients from a single center in Spain.

text: SARS-CoV-2-pneumonia emerged in Wuhan, China in December 2019. Unfortunately, there is lack of evidence about the optimal management of novel coronavirus disease 2019 (COVID-19), even less in patients on maintenance hemodialysis (MHD) therapy than in the general population. In this retrospective observational single-center study we analyzed the clinical course and outcomes of all MHD patients hospitalized with COVID-19 from March 12(th) to April 10(th), 2020 as confirmed by real time polymerase chain reaction. Baseline features, clinical course, laboratory data, and different therapies were compared between survivors and non-survivors to identify risk factors associated with mortality. Among the 36 patients, 11 (30.5%) died and 7 could be discharged within the observation period. Clinical and radiological evolution during the first week of admission were predictive of mortality. Among the 36 patients, 18 had worsening of their clinical status, as defined by severe hypoxia with oxygen therapy requirements greater than 4 Liters/minute and radiological worsening. Significantly 11 out of those 18 patients (61.1%) died. None of the classical cardiovascular risk factors in the general population were associated with higher mortality. However, a longer time on hemodialysis (hazard ratio 1.008(95% confidence interval 1.001-1.015) per year), increased LDH levels (1.006(1.001-1.011), and lower lymphocyte count (0.996 (0.992-1.000) one week after clinical onset were all significantly associated with higher mortality risk. Thus, the mortality among hospitalized hemodialysis patients diagnosed with COVID-19 is high. Lymphopenia and increased LDH levels were associated with poor prognosis.


title: Integrated Disease Surveillance and Response (IDSR) in Malawi: Implementation gaps and challenges for timely alert

text: OBJECTIVE: The recent 2014 Ebola Virus Disease (EVD) outbreaks rang the bell to call upon global efforts to assist resource-constrained countries to strengthen public health surveillance system for early response. Malawi adopted the Integrated Disease Surveillance and Response (IDSR) strategy to develop its national surveillance system since 2002 and revised its guideline to fulfill the International Health Regulation (IHR) requirements in 2014. This study aimed to understand the state of IDSR implementation and differences between guideline and practice for future disease surveillance system strengthening. METHODS: This was a mixed-method research study. Quantitative data were to analyze completeness and timeliness of surveillance system performance from national District Health Information System 2 (DHIS2) during October 2014 to September 2016. Qualitative data were collected through interviews with 29 frontline health service providers from the selected district and 7 key informants of the IDSR system implementation and administration at district and national levels. FINDINGS: The current IDSR system showed relatively good completeness (73.1%) but poor timeliness (40.2%) of total expected monthly reports nationwide and zero weekly reports during the study period. Major implementation gaps were lack of weekly report and trainings. The challenges of IDSR implementation revealed through qualitative data included case identification, compiling reports for timely submission and inadequate resources. CONCLUSIONS: The differences between IDSR technical guideline and actual practice were huge. The developing information technology infrastructure in Malawi and emerging mobile health (mHealth) technology can be opportunities for the country to overcome these challenges and improve surveillance system to have better timeliness for the outbreaks and unusual events detection.


CARS 2020—Computer Assisted Radiology and Surgery Proceedings of the 34th International Congress and Exhibition, Munich, Germany, June 23–27, 2020


title: Positive detection of SARS‐CoV‐2 combined HSV1 and HHV6B virus nucleic acid in tear and conjunctival secretions of a non‐conjunctivitis COVID‐19 patient with obstruction of common lacrimal duct

text: BACKGROUND: The current outbreak of COVID‐19 has spread rapidly all over the world. Respiratory droplets and contaction with infected patients are the two major transmission routes. However, the value of tear virus nucleic acid is still not clear. We dynamic detected the SARS‐CoV‐2 in eye sample of one COVID‐19 patient with obstruction of common lacrimal ducts. METHODS: Besides the routine examination, nasopharyngeal and eye swab were continuously measured by polymerase chain reaction assay and next‐generation sequencing (NGS). Gene detection was performed for drug use guidance, and flow cytometry was performed to analyse the lymphocyte subsets. RESULTS: Nasopharyngeal swabs were positive for 22 days, but eye swabs were still continuously positive for 2 weeks after nasopharyngeal swabs turned negative. The low level of lymphocyte and the high level IL‐6 lasted for almost 4 weeks, then became near normal. Next‐generation sequencing (NGS) confirmed the existing of SARS‐CoV‐2, HSV1 and HHV6B virus nucleic acid. The gene detection for drug use guidance showed the genetic locus ABCB1 (3435T>C) rs1045642 belonged to type CC and it mean the efficiency of lopinavir–ritonavir would be significantly decreased. The flow cytometry of lymphocyte subsets showed PD‐1(+) CD95(+) cells was accounting for 94.8% in CD3(+) CD8(+) T subset and for 94.8% in CD3(+) TCRγδ(+) T subset. CONCLUSIONS: As obstruction of common lacrimal duct, positively detection in one eye for 2 weeks more after nasopharyngeal swab became negative. More eye swabs should be collected from COVID‐19 patients, especially from those immunocompromised, those with eye symptoms and those had a history of ocular diseases.


Letter to the Editor in response to the article “Lack of type 1 diabetes involvement in the SARS-CoV-2 population: Only a particular coincidence?


title: Suppression of MHV3 virus-activated macrophages by dieldrin

text: Abstract Dieldrin (36 mg/kg body weight) administered intraperitoneally prolonged recovery from infection with mouse hepatitis virus 3 (MHV3) in the genetically-resistant A/J strain, affected the humoral anti-MHV3 IgG immune response, and inhibited the intrinsic antiviral activity of peritoneal macrophages upon in vitro rechallenge with the virus. Infection of untreated A/J animals and vehicle controls with MHV3 resulted in marked and reproducible activation of peritoneal macrophages, observed in vitro as resistance to MHV3-cytopathic effects 48 hr after rechallenge with the virus, whereas exposure to dieldrin resulted in apparent loss of the intrinsic capacity of cells to restrict replication of MHV3 and to protect them from cytolysis. In addition, in vitro treatment of MHV3 virus-activated macrophages with dieldrin, mitomycin C and X-irradiation, inhibited the intrinsic capacity of cells to restrict MHV3 replication. This mechanism of cellular restriction of the virus by MHV3-activated macrophages from the resistant A/J strain appeared to be one of the sensitive targets for the suppressive action of dieldrin on host resistance, as (i) no major changes in macrophage cellular parameters were observed in in vitro studies of cell viability, adherence to plastic, and Superoxide anion generation; (ii) the increased cell yield in the peritoneal exudates during MHV3 virus infection was not affected by dieldrin exposure; and (iii) the attachment and uptake of [3H]MHV3 by virus-activated macophages was shown to be unchanged by dieldrin exposure.


title: Engineering self-assembled materials to study and direct immune function

text: Abstract The immune system is an awe-inspiring control structure that maintains a delicate and constantly changing balance between pro-immune functions that fight infection and cancer, regulatory or suppressive functions involved in immune tolerance, and homeostatic resting states. These activities are determined by integrating signals in space and time; thus, improving control over the densities, combinations, and durations with which immune signals are delivered is a central goal to better combat infectious disease, cancer, and autoimmunity. Self-assembly presents a unique opportunity to synthesize materials with well-defined compositions and controlled physical arrangement of molecular building blocks. This review highlights strategies exploiting these capabilities to improve the understanding of how precisely-displayed cues interact with immune cells and tissues. We present work centered on fundamental properties that regulate the nature and magnitude of immune response, highlight pre-clinical and clinical applications of self-assembled technologies in vaccines, cancer, and autoimmunity, and describe some of the key manufacturing and regulatory hurdles facing these areas.


title: Structural and functional analysis of the hemagglutinin-esterase of infectious salmon anaemia virus

text: Abstract Infectious salmon anaemia virus (ISAV) is a piscine orthomyxovirus causing a serious disease in farmed Atlantic salmon (Salmo salar L.). The virus surface glycoprotein hemagglutinin-esterase (HE) is responsible for both viral attachment and release. Similarity to bovine and porcine torovirus hemagglutinin-esterase (BToV HE, PToV HE), bovine coronavirus HE (BCoV HE) and influenza C hemagglutinin-esterase-fusion (InfC HEF) proteins were exploited in a computational homology-based structure analysis of ISAV HE. The analysis resolved structural aspects of the protein and identified important features of relevance to ISAV HE activity. By recombinant expression and purification of secretory HE (recHE) proteins, receptor-binding and quantitative analyses of enzymatic activities displayed by ISAV HE molecules are presented for the first time. Three different recHE molecules were constructed: one representing a high virulent isolate, one a low virulent, while in the third a Ser32 to Ala32 amino acid substitution was introduced in the enzymatic catalytic site as inferred from the model. The three amino acid differences between the high and low virulent variants, of which two localized to the putative receptor-binding domain and one in the esterase domain, had no impact on receptor-binding or -release activities. In contrast, the Ser32 amino acid substitution totally abolished enzymatic activity while receptor binding increased, as observed by agglutination of Atlantic salmon red blood cells. This demonstrates the essential role of a serine in the enzyme's catalytic site. In conclusion, structural analysis of ISAV HE in combination with selected recHE proteins gave insights into structure–function relationships and opens up for further studies aiming at dissecting molecular determinants of ISAV virulence.


title: The energy crises revealed by COVID: Intersections of Indigeneity, inequity, and health

text: The global COVID-19 pandemic is a health crisis, an economic crisis, and a justice crisis. It also brings to light multiple ongoing, underlying social crises. The COVID-19 crisis is actively revealing crises of energy sovereignty in at least four ways. First, there are many whose access to basic health services is compromised because of the lack of energy services necessary to provide these services. Second, some people are more vulnerable to COVID-19 because of exposure to environmental pollution associated with energy production. Third, energy services are vital to human wellbeing, yet access to energy services is largely organized as a consumer good. The loss of stable income precipitated by COVID-19 may therefore mean that many lose reliable access to essential energy services. Fourth, the COVID-19 crisis has created a window of opportunity for corporate interests to engage in aggressive pursuit of energy agendas that perpetuate carbon intensive and corporate controlled energy systems, which illuminates the ongoing procedural injustices of energy decision making. These four related crises demonstrate why energy sovereignty is essential for a just energy future. Energy sovereignty is defined as the right for communities, rather than corporate interests, to control access to and decision making regarding the sources, scales, and forms of ownership characterizing access to energy services. Energy sovereignty is a critical component in the design of a post-COVID-19 energy system that is capable of being resilient to future shocks without exacerbating injustices that are killing the most vulnerable among us.


title: Chloroquine use improves dengue-related symptoms

text: Dengue is the most important arboviral disease in the world. As chloroquine, an antimalarial agent, has shown some antiviral effects, this study evaluated its effect in patients with dengue. A randomised, double-blind study was performed by administering chloroquine or placebo for three days to 129 patients with dengue-related symptoms. Of these patients, 37 were confirmed as having dengue and completed the study; in total, 19 dengue patients received chloroquine and 18 received placebo. There was no significant difference in the duration of the disease or the degree and days of fever. However, 12 patients (63%) with confirmed dengue reported a substantial decrease in pain intensity and a great improvement in their ability to perform daily activities (p = 0.0004) while on the medication and the symptoms returned immediately after these patients stopped taking the medication. The same effect was not observed in patients with diseases other than dengue. Therefore, this study shows that patients with dengue treated with chloroquine had an improvement in their quality of life and were able to resume their daily activities. However, as chloroquine did not alter the duration of the disease or the intensity and days of fever, further studies are necessary to confirm the clinical effects and to assess the side effects of chloroquine in dengue patients.


XXII(e) actualités du Pharo — Urgences et crises sanitaires dans les pays à ressources limitées: 5–7 octobre 2016, Marseille


title: Safe and effective management of tracheostomy in COVID‐19 patients

text: BACKGROUND: An increasing number of COVID‐19 patients worldwide will probably need tracheostomy in an emergency or at the recovering stage of COVID‐19. We explored the safe and effective management of tracheostomy in COVID‐19 patients, to benefit patients and protect health care workers at the same time. METHODS: We retrospectively analyzed 11 hospitalized COVID‐19 patients undergoing tracheostomy. Clinical features of patients, ventilator withdrawal after tracheostomy, surgical complications, and nosocomial infection of the health care workers associated with the tracheostomy were analyzed. RESULTS: The tracheostomy of all the 11 cases (100%) was performed successfully, including percutaneous tracheostomy of 6 cases (54.5%) and conventional open tracheostomy of 5 cases (45.5%). No severe postoperative complications occurred, and no health care workers associated with the tracheostomy are confirmed to be infected by SARS‐CoV‐2. CONCLUSION: Comprehensive evaluation before tracheostomy, optimized procedures during tracheostomy, and special care after tracheostomy can make the tracheostomy safe and beneficial in COVID‐19 patients.


Síndrome de Guillain Barré asociado a infección por SARS-CoV-2


title: In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds

text: Abstract Effective antiviral agents are urgently needed to combat the possible return of severe acute respiratory syndrome (SARS). Commercial antiviral agents and pure chemical compounds extracted from traditional Chinese medicinal herbs were screened against 10 clinical isolates of SARS coronavirus by neutralisation tests with confirmation by plaque reduction assays. Interferon-beta-1a, leukocytic interferon-alpha, ribavirin, lopinavir, rimantadine, baicalin and glycyrrhizin showed antiviral activity. The two interferons were only active if the cell lines were pre-incubated with the drugs 16h before viral inoculation. Results were confirmed by plaque reduction assays. Antiviral activity varied with the use of different cell lines. Checkerboard assays for synergy were performed showing combinations of interferon beta-1a or leukocytic interferon-alpha with ribavirin are synergistic. Since the clinical and toxicity profiles of these agents are well known, they should be considered either singly or in combination for prophylaxis or treatment of SARS in randomised placebo controlled trials in future epidemics.


Co‐infection of SARS‐CoV‐2 and HIV in a patient in Wuhan city, China


title: The healthcare worker at risk during the COVID-19 pandemic: a Jewish ethical perspective

text: The current COVID-19 pandemic has raised many questions and dilemmas for modern day ethicists and healthcare providers. Are physicians, nurses and other healthcare workers morally obligated to put themselves in harm’s way and treat patients during a pandemic, occurring a great risk to themselves, their families and potentially to other patients? The issue was relevant during the 1918 influenza epidemic and more recently severe acute respiratory syndrome epidemic in 2003. Since the risk to the healthcare workers was great, there was tension between the ethical duty and responsibility to treat and the risk to one’s own life. This tension was further noted during the 2014 Ebola outbreak in West Africa that left hundreds of healthcare workers dead. The AMA Code of Ethics states that physicians are to ‘provide urgent medical care during disasters…even in the face of greater than usual risk to physicians’ own safety, health or life.’1 Classic Jewish sources have dealt with this question as well. There is an obligation ‘to not stand by idly when your friends life is in danger’; however, the question arises as to whether there are limits to this obligation? Is one required to risk one’s own life to save another’s? There is a consensus that one is not required but the question open to debate is whether it is praiseworthy to do so. However, regarding healthcare workers, there is agreement for ethical, professional and societal reasons that they are required to put themselves in harm’s way to care for their patients.


title: Orthopaedic patient workflow in CoViD-19 pandemic in Italy

text: Abstract CoViD-19 epidemic started in China in late December 2019, and soon spread, turning into a pandemic. All medical specialties have soon been involved in the management of CoViD-19 patients; the daily Orthopaedic activity has been affected profoundly by this dramatic health emergency. The present paper aims to summarize all the measures and changes that had to be made in order to avoid the healthcare system collapse in the most affected areas, and provides an operative flowchart.


JOINT SOCIETY STATEMENT ON ELECTIVE SURGERY DURING COVID-19 PANDEMIC


title: Changing radiotherapy review practice in response to COVID-19 in a radiotherapy satellite centre

text: BACKGROUND: The COVID-19 pandemic has required a rapid and evolving response in order to enable the continued delivery of radiotherapy, whilst effectively managing the risk of infection to patients and staff. In early March 2020, we were presented with the challenge of achieving safe delivery of care in clinical practice for a group of patients that are already at higher risk of morbidity from COVID-19 with only limited guidance. PURPOSE: This article outlines the adjustments made at The Christie at Oldham satellite centre in order to promote optimal care to our patients receiving radiotherapy, and to mitigate infection risk at the department for both patients and staff. MATERIALS AND METHODS: We share insight into some of the evolving processes that our team have developed since March 2020 in promoting optimal care to patients receiving radiotherapy at The Christie at Oldham satellite centre. These include changes to the department floor, paper flow, supportive care and staffing. RESULTS AND CONCLUSIONS: As we continue to progress through this pandemic, we accept that there will be an ongoing journey of learning with adjustments to practice and evolving ‘new norm’, thereby ensuring we keep our patients and team safe and well. We also hoped that our experience would support radiotherapy-related practices in surges of the pandemic in other parts of the world or in case of the second wave.


title: Re-starting Travel in the Era of COVID-19: Preparing Anew

text: Teaser: Travel, a major contributor to global economy, needs to adapt to the COVID-19 pandemic. Restarting business and travel share convergent considerations. Travel health preparation will require detailed assessment to specifically address COVID-19: the individual’s personal risk stratification, elements of travel, and policies imposed on each traveler and itinerary. Precise details of the trip will help to formulate beneficial recommendations.


title: Pandemic and Macho Organizations: Wakeup Call or Business as Usual?

text: The COVID‐19 pandemic is one of the greatest challenges for our generation. The global spread of the virus is affecting societies’ gender dynamics in general and in organizations in particular. Based on ethnographic research being carried out in a police organization in Brazil, this piece discusses how COVID‐19 is impacting hegemonic masculinity in organizations. Police organizations are prototypical hegemonic masculinity organizations. I argue that the COVID‐19 pandemic at first encourages the performance of the police typical macho masculinity, but as the disease progresses, it creates a situation that challenges it. I explore that even though the pandemic threatens macho masculinity in organizations, it is still unclear if an alternative gender dynamic will emerge from this crisis in macho organizations.


title: Stress and sleep: a survey based on wearable sleep trackers among medical and nursing staff in Wuhan during the COVID-19 pandemic

text: BACKGROUD: COVID-19 pandemic has significantly affected the sleep health of local medical and nursing staff. AIM: We used wearable pulse oximeters to monitor and screen the medical and nursing staff working in hospitals designated for COVID-19 in the Wuhan area. This study aimed to establish a reliable basis to provide sleep intervention for the medical and nursing staff. METHODS: Thirty medical and nursing staff members with symptoms of insomnia were instructed to wear medical ring-shaped pulse oximeters to monitor their sleep overnight. We also used the Insomnia Severity Index (ISI) and the Chinese version of the Self-Reporting Questionnaire (SRQ-20) to evaluate the severity of insomnia and mental health status, respectively, for each participant. RESULTS: Among the 30 participants, only 26 completed the screening. Ten cases (38.5%) demonstrated moderate to severe sleep apnoea–hypopnea syndrome (SAHS) when using an oxygen desaturation index ≥15 times/hour as the cut-off value. Participants with comorbid moderate to severe SAHS had significantly higher ISI and SRQ scores (p values 0.034 and 0.016, respectively) than those in the insomnia group. Correlation analysis revealed that ISI was positively correlated with total sleep time (TST) (r=0.435, p=0.026), and negatively correlated with deep sleep (r=−0.495, p=0.010); furthermore, patient SRQ scores were positively correlated with TST, sleep efficiency (SE) and REM (rapid eyes movement) sleep % (r=0.454 and 0.389, 0.512; p=0.020, 0.050 and 0.008, respectively). Stepwise logistic regression indicated that SRQ-20 and sex were risk factors for insomnia with comorbid SAHS, and their OR values were 1.516 and 11.56 (95% CI 1.053 to 2.180 and 1.037 to 128.9), respectively. CONCLUSION: Medical and nursing staff with insomnia showed clear signs of comorbid sleep apnoea attributable to stress. The wearable pulse oximeters accurately monitored the participants’ breathing when asleep.


title: Insights from nanomedicine into chloroquine efficacy against COVID-19

text: Chloroquine — an approved malaria drug — is known in nanomedicine research for the investigation of nanoparticle uptake in cells, and may have potential for the treatment of COVID-19.


title: Effect of interferon alpha and cyclosporine treatment separately and in combination on Middle East Respiratory Syndrome Coronavirus (MERS-CoV) replication in a human in-vitro and ex-vivo culture model

text: Abstract Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has emerged as a coronavirus infection of humans in the past 5 years. Though confined to certain geographical regions of the world, infection has been associated with a case fatality rate of 35%, and this mortality may be higher in ventilated patients. As there are few readily available animal models that accurately mimic human disease, it has been a challenge to ethically determine what optimum treatment strategies can be used for this disease. We used in-vitro and human ex-vivo explant cultures to investigate the effect of two immunomodulatory agents, interferon alpha and cyclosporine, singly and in combination, on MERS-CoV replication. In both culture systems the combined treatment was more effective than either agent used alone in reducing MERS-CoV replication. PCR SuperArray analysis showed that the reduction of virus replication was associated with a greater induction of interferon stimulated genes. As these therapeutic agents are already licensed for clinical use, it may be relevant to investigate their use for therapy of human MERS-CoV infection.


title: BCX4430 – A broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease

text: Summary The adenosine nucleoside analog BCX4430 is a direct-acting antiviral drug under investigation for the treatment of serious and life-threatening infections from highly pathogenic viruses, such as the Ebola virus. Cellular kinases phosphorylate BCX4430 to a triphosphate that mimics ATP; viral RNA polymerases incorporate the drug's monophosphate nucleotide into the growing RNA chain, causing premature chain termination. BCX4430 is active in vitro against many RNA viral pathogens, including the filoviruses and emerging infectious agents such as MERS-CoV and SARS-CoV. In vivo, BCX4430 is active after intramuscular, intraperitoneal, and oral administration in a variety of experimental infections. In nonclinical studies involving lethal infections with Ebola virus, Marburg virus, Rift Valley fever virus, and Yellow Fever virus, BCX4430 has demonstrated pronounced efficacy. In experiments conducted in several models, both a reduction in the viral load and an improvement in survival were found to be related to the dose of BCX4430. A Phase 1 clinical trial of intramuscular administration of BCX4430 in healthy subjects is currently ongoing.