title: Use of the human colorectal adenocarcinoma (Caco‐2) cell line for isolating respiratory viruses from nasopharyngeal aspirates

text: The human colorectal adenocarcinoma‐derived Caco‐2 cell line was evaluated as a means isolating common respiratory viruses from nasopharyngeal aspirates for the diagnosis of respiratory diseases. One hundred eighty‐nine direct immunofluorescence positive nasopharyngeal aspirates obtained from patients with various viral respiratory diseases were cultured in the presence of Caco‐2 cells or the following conventional cell lines: LLC‐MK2, MDCK, HEp‐2, and A549. Caco‐2 cell cultures effectively propagated the majority (84%) of the viruses present in nasopharyngeal aspirate samples compared with any positive cultures obtained using the panel cells (78%) or individual cell line MDCK (38%), HEp‐2 (21%), LLC‐MK2 (27%), or A549 (37%) cell lines. The differences against individual cell line were statistically significant (P = < 0.000001). Culture in Caco‐2 cells resulted in the isolation of 85% (36/42) of viruses which were not cultivated in conventional cell lines. By contrast, 80% (24/30) of viruses not cultivated in Caco‐2 cells were isolated using the conventional panel. The findings indicated that Caco‐2 cells were sensitive to a wide range of viruses and can be used to culture a broad range of respiratory viruses. J. Med. Virol. 85:874–879, 2013. © 2013 Wiley Periodicals, Inc.


title: Comparison of human metapneumovirus, respiratory syncytial virus and Rhinovirus respiratory tract infections in young children admitted to hospital

text: Respiratory Syncytial Virus (RSV), Human metapneumovirus (HMPV), and Rhinoviruses (RV) are frequent causes of respiratory tract infections in young children. We compared laboratory and clinical findings in children with comparable age distribution and hospitalized due to RSV, HMPV or RV infections. Viral pathogens were detected by a quantitative real time PCR from nasopharyngeal aspirates. No significant differences in the admission diagnosis, laboratory parameters, patient demographics and treatment measures between the three viral causes of respiratory illness were found. No correlation between viral load and disease severity was observed however, there was a significantly lower concentration of the nasopharyngeal interleukin 8 (IL‐8) in children with RV compared to HMPV and RSV, indicating a milder proinflammatory reaction. Moreover, RV‐infected children had significantly lower body temperature, higher leucocyte counts in peripheral blood, and a tendency to have a shorter stay in hospital than children with either HMPV or RSV infection. Taken together, clinical presentation of the infections with RSV, HMPV, and RV is similar among children of the same age group and not clearly distinguishable by standard clinical or laboratory findings. Therefore, virus specific testing should be included regularly for routine diagnosis of children with respiratory tract infections. J. Med. Virol. 87:275–280, 2015. © 2014 Wiley Periodicals, Inc.


title: Rational Vaccine Design in the Time of COVID-19

text: As scientists consider SARS-CoV-2 vaccine design, we discuss problems that may be encountered and how to tackle them by what we term “rational vaccine design.” We further discuss approaches to pan-coronavirus vaccines. We draw on experiences from recent research on several viruses including HIV and influenza, as well as coronaviruses.


title: Continuous intravenous anaesthesia with sufentanil and midazolam in medetomidine premedicated New Zealand White rabbits

text: BACKGROUND: Anaesthesia in rabbits is associated with a high mortality rate, compared to that in cats and dogs. Total intravenous anaesthesia (TIVA) with drugs that provide cardiovascular stability and are rapidly metabolised could be of benefit for use in rabbits. The aim was to evaluate cardiorespiratory effects of TIVA with sufentanil-midazolam in eight New Zealand White rabbits. Subcutaneous premedication with medetomidine (0.1 mg/kg BW) was followed by IV administration of a mixture of 2.5 μg/mL sufentanil and 0.45 mg/mL midazolam at a rate of 0.3 mL/kg BW/h for anaesthetic induction. Additionally, intravenous boluses of 0.1 mL of the mixture were administered every 20 s until the righting reflex was lost. Following endotracheal intubation, anaesthesia was maintained for 60 min with an infusion rate adjusted to supress the pedal withdrawal reflex. Air and oxygen (1:2) were delivered at 3 L/min. Physiological variables were recorded before induction and at predefined time points during and after anaesthesia. RESULTS: Righting and pedal withdrawal reflexes were lost within 3 and 5 min, respectively. Doses of sufentanil and midazolam were 0.48 μg/kg BW and 0.09 mg/kg BW for induction, and 0.72 μg/kg BW/h and 0.13 mg/kg BW/h for maintenance. Apnoea occurred in two rabbits. Induction of anaesthesia caused a significant increase in heart rate, cardiac output and arterial CO(2) partial pressure and a decrease in mean arterial pressure, respiratory rate and pH. Mean time from stopping the infusion to endotracheal extubation was 5 min, and to return of the righting reflex 7 min. Anaesthesia was characterized by induction and recovery without excitation, with muscle relaxation, and absence of the pedal withdrawal reflex. CONCLUSIONS: TIVA with sufentanil-midazolam provided smooth induction and recovery of anaesthesia in rabbits but with marked hypotension and respiratory depression, requiring mechanical ventilation. Further evaluation is needed to establish if the protocol is useful for rabbits undergoing surgery.


title: Laboratory Diagnosis of Four Recent Sporadic Cases of Community-acquired SARS, Guangdong Province, China

text: Four cases of severe acute respiratory syndrome (SARS) that occurred from December 16, 2003, to January 8, 2004, in the city of Guangzhou, Guangdong Province, China, were investigated. Clinical specimens collected from these patients were tested by provincial and national laboratories in China as well as members of the World Health Organization SARS Reference and Verification Laboratory Network in a collaborative effort to identify and confirm SARS-associated coronavirus (SARS-CoV) infection. Although SARS-CoV was not isolated from any patient, specimens from three patients were positive for viral RNA by reverse transcription–polymerase chain reaction assay, and all patients had detectable rises in SARS-CoV–specific antibodies. This study shows the effectiveness of a collaborative, multilaboratory response to diagnose SARS.


title: Epithelial cell lines of the cotton rat (Sigmodon hispidus) are highly susceptible in vitro models to zoonotic Bunya-, Rhabdo-, and Flaviviruses

text: BACKGROUND: Small mammals such as bats and rodents have been increasingly recognized as reservoirs of novel potentially zoonotic pathogens. However, few in vitro model systems to date allow assessment of zoonotic viruses in a relevant host context. The cotton rat (Sigmodon hispidus) is a New World rodent species that has a long-standing history as an experimental animal model due to its unique susceptibility to human viruses. Furthermore, wild cotton rats are associated with a large variety of known or potentially zoonotic pathogens. METHODS: A method for the isolation and culture of airway epithelial cell lines recently developed for bats was applied for the generation of rodent airway and renal epithelial cell lines from the cotton rat. Continuous cell lines were characterized for their epithelial properties as well as for their interferon competence. Susceptibility to members of zoonotic Bunya-, Rhabdo-, and Flaviviridae, in particular Rift Valley fever virus (RVFV), vesicular stomatitis virus (VSV), West Nile virus (WNV), and tick-borne encephalitis virus (TBEV) was tested. Furthermore, novel arthropod-derived viruses belonging to the families Bunya-, Rhabdo-, and Mesoniviridae were tested. RESULTS: We successfully established airway and kidney epithelial cell lines from the cotton rat, and characterized their epithelial properties. Cells were shown to be interferon-competent. Viral infection assays showed high-titre viral replication of RVFV, VSV, WNV, and TBEV, as well as production of infectious virus particles. No viral replication was observed for novel arthropod-derived members of the Bunya-, Rhabdo-, and Mesoniviridae families in these cell lines. CONCLUSION: In the current study, we showed that newly established cell lines from the cotton rat can serve as host-specific in vitro models for viral infection experiments. These cell lines may also serve as novel tools for virus isolation, as well as for the investigation of virus-host interactions in a relevant host species.


title: To investigate the association between the health literacy and hand hygiene practices of the older adults to help them fight against infectious diseases in Hong Kong

text: BACKGROUND: Proper hand hygiene helps prevent infectious diseases, while health literacy plays a critical role in preventive health behaviors. It remains unclear as to why proper hand hygiene practices cannot be sustained and what role health literacy plays in older adults fight against infectious diseases. METHODS: A convenience sample of 433 old adults aged 65 and above was recruited. Their hygiene practices and health literacy were evaluated using a structured questionnaire adopted from the Centre for Health Protection and the Chinese version of the HLS-Asia-Q questionnaire. RESULTS: The percentage distribution of the hand hygiene performance, from always to never, was 18%-10%. A majority 63.28% (274) of them were classified as having inadequate health literacy (0-25), while a meager 1.62% (7) of them as having excellent health literacy (42.01-50). The Spearman correlation showed a significant positive relationship (P < 0.05) between the participants’ health literacy and their hand hygiene practices. CONCLUSIONS: Health literacy and hand hygiene are positively related in helping the older adults fight against infectious diseases. To sustain proper hand hygiene practices is to provide frequent hand hygiene training to the older adults.


title: Geminivirus protein structure and function

text: Geminiviruses are a family of plant viruses that cause economically important plant diseases worldwide. These viruses have circular single‐stranded DNA genomes and four to eight genes that are expressed from both strands of the double‐stranded DNA replicative intermediate. The transcription of these genes occurs under the control of two bidirectional promoters and one monodirectional promoter. The viral proteins function to facilitate virus replication, virus movement, the assembly of virus‐specific nucleoprotein particles, vector transmission and to counteract plant host defence responses. Recent research findings have provided new insights into the structure and function of these proteins and have identified numerous host interacting partners. Most of the viral proteins have been shown to be multifunctional, participating in multiple events during the infection cycle and have, indeed, evolved coordinated interactions with host proteins to ensure a successful infection. Here, an up‐to‐date review of viral protein structure and function is presented, and some areas requiring further research are identified.


Pseudotyped Vesicular Stomatitis Virus for Functional Analysis of Sars Coronavirus Spike Protein


Age, “Life-Cycles,” and the Allocation of Scarce Medical Resources∗


title: Assessing spread risk of Wuhan novel coronavirus within and beyond China, January-April 2020: a travel network-based modelling study

text: BACKGROUND: A novel coronavirus (2019-nCoV) emerged in Wuhan City, China, at the end of 2019 and has caused an outbreak of human-to-human transmission with a Public Health Emergency of International Concern declared by the World Health Organization on January 30, 2020. AIM: We aimed to estimate the potential risk and geographic range of Wuhan novel coronavirus (2019-nCoV) spread within and beyond China from January through to April, 2020. METHODS: A series of domestic and international travel network-based connectivity and risk analyses were performed, by using de-identified and aggregated mobile phone data, air passenger itinerary data, and case reports. RESULTS: The cordon sanitaire of Wuhan is likely to have occurred during the latter stages of peak population numbers leaving the city before Lunar New Year (LNY), with travellers departing into neighbouring cities and other megacities in China. We estimated that 59,912 air passengers, of which 834 (95% UI: 478 – 1349) had 2019-nCoV infection, travelled from Wuhan to 382 cities outside of mainland China during the two weeks prior to Wuhan’s lockdown. The majority of these cities were in Asia, but major hubs in Europe, the US and Australia were also prominent, with strong correlation seen between predicted importation risks and reported cases. Because significant spread has already occurred, a large number of airline travellers (3.3 million under the scenario of 75% travel reduction from normal volumes) may be required to be screened at origin high-risk cities in China and destinations across the globe for the following three months of February to April, 2020 to effectively limit spread beyond its current extent. CONCLUSION: Further spread of 2019-nCoV within China and international exportation is likely to occur. All countries, especially vulnerable regions, should be prepared for efforts to contain the 2019-nCoV infection.


title: Epidemiology of respiratory viruses in bronchoalveolar lavage samples in a tertiary hospital

text: Abstract Background The prevalence of respiratory viruses in adults is largely underexplored, as most studies focus on children. Additionally, in severely ill or immunocompromised adults, where respiratory infections are mostly attributed to bacteria and fungi; respiratory viruses can lead to severe complications. Objectives To evaluate the epidemiology of respiratory viruses in bronchoalveolar lavage fluid (BAL) specimens from patients with lower respiratory tract disease. The study population consisted of different groups including immunocompetent patients (control patients), solid organ transplant recipients, patients with haematological malignancies and other immunocompromised adults. Study design A total of 134 BAL fluid specimens collected during 2009–2011 were retrospectively assessed with the new commercial multiplex real-time PCR FTD Respiratory 21 Plus®, targeting 18 different viruses and 2 atypical bacterial pathogens. Results Viral or atypical bacterial pathogens were detected in 29.1% of BAL fluid specimens. Coronaviruses were most prevalent (13.4%), followed by rhinoviruses (5.2%), RSV (4.5%) and bocaviruses (3.7%). Comparing the total number of viruses detected, a statistically significant difference was observed between the control group and patients with haematological malignancies (27.5% vs. 57.1%, p <0.05). Conclusion In conclusion, our study highlights the high prevalence of respiratory viruses in BAL fluid specimens from adult patients with lower respiratory tract disease. The methods to be used should be sensitive and cover a wide range of potential pathogens. The specific patient population can also influence the detection rates of respiratory viruses.


title: Beet yellows virus replicase and replicative compartments: parallels with other RNA viruses

text: In eukaryotic virus systems, infection leads to induction of membranous compartments in which replication occurs. Virus-encoded subunits of the replication complex mediate its interaction with membranes. As replication platforms, RNA viruses use the cytoplasmic surfaces of different membrane compartments, e.g., endoplasmic reticulum (ER), Golgi, endo/lysosomes, mitochondria, chloroplasts, and peroxisomes. Closterovirus infections are accompanied by formation of multivesicular complexes from cell membranes of ER or mitochondrial origin. So far the mechanisms for vesicles formation have been obscure. In the replication-associated 1a polyprotein of Beet yellows virus (BYV) and other closteroviruses, the region between the methyltransferase and helicase domains (1a central region (CR), 1a CR) is marginally conserved. Computer-assisted analysis predicts several putative membrane-binding domains in the BYV 1a CR. Transient expression of a hydrophobic segment (referred to here as CR-2) of the BYV 1a in Nicotiana benthamiana led to reorganization of the ER and formation of ~1-μm mobile globules. We propose that the CR-2 may be involved in the formation of multivesicular complexes in BYV-infected cells. This provides analogy with membrane-associated proteins mediating the build-up of “virus factories” in cells infected with diverse positive-strand RNA viruses (alpha-like viruses, picorna-like viruses, flaviviruses, and nidoviruses) and negative-strand RNA viruses (bunyaviruses).


title: Efectos de la infección viral en el paciente trasplantado

text: Las infecciones virales continúan siendo una importante causa de morbimortalidad en los pacientes trasplantados. En estos pacientes, el riesgo de infección viral depende de varios factores como el tipo de trasplante, la intensidad de la inmunosupresión y la susceptibilidad del receptor. Además de efectos directos, la infección viral puede causar efectos indirectos derivados del efecto inmunomodulador de algunos virus como citomegalovirus o herpesvirus 6. Entre estos efectos se encuentran un mayor riesgo de replicación de otros virus, de rechazo, de otras infecciones oportunistas y de otras entidades específicas en cada tipo de trasplante. Los tests moleculares cuantitativos han reemplazado en la mayoría de las ocasiones a los métodos serológicos y al cultivo para el diagnóstico de estas infecciones, especialmente en el caso de citomegalovirus, virus de Epstein-Barr, y los virus de la hepatitis B y C. Sin embargo, estos avances diagnósticos no se han acompañado del desarrollo de antivirales específicos o de vacunas eficaces, por lo que las medidas de prevención continúan siendo fundamentales en estos pacientes. Viral infection remains an important cause of morbidity and mortality in transplant recipients. The risk of viral infection in these patients depends on several factors, such as the type of organ transplanted, the intensity of immunosuppression, and the recipient's susceptibility. In additional to direct effects, viral infection cause indirect effects, including greater risk of replication of other viruses, graft rejection, opportunistic infections and other specific entities for each type of transplant. These indirect effects result from the immunomodulatory activity of some viruses, such as cytomegalovirus and human herpes virus-6. For the most part, quantitative molecular tests have replaced serologic testing and in vitro culture for diagnosing infection. This approach is particularly prominent for cytomegalovirus, Epstein-Barr virus, hepatitis B virus, and hepatitis C virus. Despite these diagnostic advances, the development of specific antiviral agents and effective antiviral vaccines is limited. Thus, prophylactic strategies are still essential in transplant recipients.


title: Synthesis and biological activity of new glycyrrhizic acid conjugates with amino acids and dipeptides

text: New glycyrrhizic acid (GA) conjugates were synthesized with the use of tert-butyl esters of amino acids or benzyl esters of dipeptides; they contained two residues of L-amino acids (Met, Phe, Pro, and Ile or dipeptides Gly-Leu and Gly-Phe). Activation of GA carboxy groups was carried out with the help of N-hydroxysuccinimide, N,N′-dicyclohexylcarbodiimide, or N-hydroxybenzotriazole with dicyclohexylcarbodiimide. A proline-containing GA derivative is a low-toxic substance; it raises the level of agglutinins by 3.7 times in the blood of mice and 3 times that of hemolysins compared with the control. Dipeptide GA derivatives possess an expressed anti-HIV-1 activity in cultures of MT-4 cells and are 90-70 times less cytotoxic than azidothymidine. The selectivity index of the compounds exceeds those of GA by 110 and 34 times, respectively.


title: Microbial Cleaning for Removal of Surface Contamination

text: Microbial cleaning takes advantage of naturally occurring microbes to remove a wide variety of contaminants from various surfaces. The method is based on the affinity of microbes for hydrocarbons which are digested, producing harmless carbon dioxide, water and soluble fatty acids. The microbes are nonpathogenic and are safe to handle and dispose. The process is environmentally friendly and is less expensive than solvent cleaning, but it is not applicable to high precision cleaning applications. Typical applications include parts washing; oil and grease removal from concrete and other floor surfaces, and from drains and grease traps; cleaning and disinfection in healthcare facilities; cleaning of historical artworks and structures; and household and institutional cleaning applications.


title: Structural comparison strengthens the higher-order classification of proteases related to chymotrypsin

text: Specific cleavage of proteins by proteases is essential for several cellular, physiological, and viral processes. Chymotrypsin-related proteases that form the PA clan in the MEROPS classification of proteases is one of the largest and most diverse group of proteases. The PA clan comprises serine proteases from bacteria, eukaryotes, archaea, and viruses and chymotrypsin-related cysteine proteases from positive-strand RNA viruses. Despite low amino acid sequence identity, all PA clan proteases share a conserved double β-barrel structure. Using an automated structure-based hierarchical clustering method, we identified a common structural core of 72 amino acid residues for 143 PA clan proteases that represent 12 protein families and 11 subfamilies. The identified core is located around the catalytic site between the two β-barrels and resembles the structures of the smallest PA clan proteases. We constructed a structure-based distance tree derived from the properties of the identified common core. Our structure-based analyses support the current classification of these proteases at the subfamily level and largely at the family level. Structural alignment and structure-based distance trees could thus be used for directing objective classification of PA clan proteases and to strengthen their higher order classification. Our results also indicate that the PA clan proteases of positive-strand RNA viruses are related to cellular heat-shock proteases, which suggests that the exchange of protease genes between viruses and cells might have occurred more than once.


Neurotoxicosis in 4 Cats Receiving Ronidazole


title: Viral Evasion Strategies in Type I IFN Signaling – A Summary of Recent Developments

text: The immune system protects the organism against infections and the damage associated with them. The first line of defense against pathogens is the innate immune response. In the case of a viral infection, it induces the interferon (IFN) signaling cascade and eventually the expression of type I IFN, which then causes an antiviral state in the cells. However, many viruses have developed strategies to counteract this mechanism and prevent the production of IFN. In order to modulate or inhibit the IFN signaling cascade in their favor, viruses have found ways to interfere at every single step of the cascade, for example, by inducing protein degradation or cleavage, or by mediate protein polyubiquitination. In this article, we will review examples of viruses that modulate the IFN response and describe the mechanisms they use.


title: Pre-spillover Prevention of Emerging Zoonotic Diseases: What Are the Targets and What Are the Tools?

text: The uneven standards of surveillance, human- or animal-based, for zoonotic diseases or pathogens maintained and transmitted by wildlife H R s, or even domestic species, is a global problem, readily apparent even within the United States, where investment in public health, including surveillance systems, has a long and enviable history. As of 2006, there appears to be little scientific, social, or political consensus that animalbased surveillance for zoonoses merits investment in international infrastructure, other than the fledgling efforts with avian influenza, or targeted nontraditional avenues of surveillance and research.


title: Clinical Features of Critical Coronavirus Disease 2019 in Children

text: We sought to describe the presentation, course, and outcomes of hospitalized pediatric coronavirus disease 2019 patients, with detailed description of those requiring mechanical ventilation, and comparisons between critically ill and noncritical hospitalized pediatric patients. DESIGN: Observational cohort study. SETTING: Riley Hospital for Children at Indiana University Health in Indianapolis in the early weeks of the coronavirus disease 2019 pandemic. PATIENTS: All hospitalized pediatric patients with confirmed coronavirus disease 2019 as of May 4, 2020, were included. INTERVENTIONS: Patients received therapies including hydroxychloroquine, remdesivir, tocilizumab, and convalescent serum and were managed according to an institutional algorithm based on evidence available at the time of presentation. MEASUREMENTS AND MAIN RESULTS: Of 407 children tested for severe acute respiratory syndrome-coronavirus 2 at our hospital, 24 were positive, and 19 required hospitalization. Seven (36.8%) were critically ill in ICU, and four (21%) required mechanical ventilation. Hospitalized children were predominantly male (14, 74%) and African-American or Hispanic (14, 74%), with a bimodal distribution of ages among young children less than or equal to 2 years old (8, 42%) and older adolescents ages 15–18 (6, 32%). Five of seven (71.4%) of critically ill patients were African-American (n = 3) or Hispanic (n = 2). Critical illness was associated with older age (p = 0.017), longer duration of symptoms (p = 0.036), and lower oxygen saturation on presentation (p = 0.016); with more thrombocytopenia (p = 0.015); higher C-reactive protein (p = 0.031); and lower WBC count (p = 0.039). Duration of mechanical ventilation averaged 14.1 days. One patient died. CONCLUSIONS: Severe, protracted coronavirus disease 2019 is seen in pediatric patients, including those without significant comorbidities. We observed a greater proportion of hospitalized children requiring mechanical ventilation than has been reported to date. Older children, African-American or Hispanic children, and males may be at risk for severe coronavirus disease 2019 requiring hospitalization. Hypoxia, thrombocytopenia, and elevated C-reactive protein may be useful markers of critical illness. Data regarding optimal management and therapies for pediatric coronavirus disease 2019 are urgently needed.


title: Health workers' safety during tracheostomy in COVID‐19 patients: Homemade protective screen

text: As an aerosol and droplets generating procedure, tracheostomy increases contamination risks for health workers in the coronavirus disease context. To preserve the health care system capacity and to limit virus cross‐transmission, protecting caregivers against coronavirus infection is of critical importance. We report the use of external fixator equipment to set up a physical interface between the patient's neck and the caregiver performing a tracheostomy in COVID‐19 patients. Once the metal frame set in place, it is wrapped with a single‐use clear and sterile cover for surgical C‐arm. This installation is simple, easy, and fast to achieve and can be carried out with inexpensive material available in every hospital. This physical interface is an additional safety measure that prevents the direct projection of secretions or droplets. It should, of course, only be considered as a complement to strict compliance with barrier precautions and personal protective equipment.


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title: A dual-centre observational review of hospital based palliative care in patients dying with COVID-19

text: Abstract The current Covid-19 pandemic has put significant strain on all aspects of healthcare delivery, including palliative care services. Given the high mortality from this disease, particularly in the more vulnerable members of society, it is important to examine how best to deliver a high standard of end of life care during this crisis. This case series collected data from two acute hospitals examining the management of patients diagnosed with Covid-19 who subsequently died (n=36) and compared this to national and local end of life audit data for all other deaths. Our results demonstrated a shorter dying phase (38.25 hours vs 74 hours) and higher rates of syringe driver use (72% vs 33% in local audits), although with similar average mediation doses. Of note was the significant heterogeneity in the phenotype of deterioration in the dying phase, two distinct patterns emerged, with one group demonstrating severe illness with a short interval between symptom onset and death and another group presenting with a more protracted deterioration. This brief report suggests a spectrum of mode of dying. Over all the cohort reflects previously described experiences, with increased frailty (median Clinical Frailty Scale score of 5) and extensive comorbidity burden. This brief report provides clinicians with a contemporaneous overview of our experience, knowledge and pattern recognition when caring for people with Covid-19 and highlights the value of proactive identification of patients and risk of deterioration and palliation.


title: HVAC filtration for controlling infectious airborne disease transmission in indoor environments: Predicting risk reductions and operational costs

text: Abstract This work describes and applies a methodology for estimating the impact of recirculating heating, ventilating, and air-conditioning (HVAC) particle filters on the control of size-resolved infectious aerosols in indoor environments using a modified version of the Wells-Riley model for predicting risks of infectious disease transmission. Estimates of risk reductions and associated operational costs of both HVAC filtration and equivalent outdoor air ventilation are modeled and compared using a case study of airborne transmission of influenza in a hypothetical office space. Overall, recirculating HVAC filtration was predicted to achieve risk reductions at lower costs of operation than equivalent levels of outdoor air ventilation, particularly for MERV 13–16 filters. Medium efficiency filtration products (MERV 7–11) are also inexpensive to operate but appear less effective in reducing infectious disease risks.


title: MERS-CoV spillover at the camel-human interface

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus originating in camels that has been causing significant mortality and morbidity in humans in the Arabian Peninsula. The epidemiology of the virus remains poorly understood, with hospital outbreaks, isolated cases with known exposure to camels and apparent community transmission occurring simultaneously. While traditional and seroepidemiological studies have been employed extensively throughout the epidemic, viral sequence data have not been utilised to their full potential in understanding transmission patterns within the outbreak. Here we use existing MERS-CoV sequence data to explore the phylodynamics of the virus in two of its known major hosts, humans and camels. We employ structured coalescent models to show that long-term MERS-CoV evolution occurs exclusively in camels, whereas humans act as a transient, and ultimately terminal host. By analysing the distribution of human outbreak cluster sizes and zoonotic introduction times we show that human outbreaks in the Arabian peninsula are driven by seasonally varying zoonotic transfer of viruses from camels. Without heretofore unseen evolution of host tropism, MERS-CoV is unlikely to become endemic in humans.


The importance of a “socially responsible” approach during COVID-19: the invisible heroes of science in Italy


title: Expression profiling meta-analysis of ACE2 and TMPRSS2, the putative anti-inflammatory receptor and priming protease of SARS-CoV-2 in human cells, and identification of putative modulators

text: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in hundreds of thousands of deaths worldwide. While the majority of people with COVID-19 won’t require hospitalization, those who do may experience severe life-threatening complications, including acute respiratory distress syndrome. SARS-CoV-2 infects human cells by binding to the cellular surface protein angiotensin-converting enzyme 2 (ACE2); in addition, the cellular transmembrane serine protease 2 (TMPRSS2) is needed for priming of the spike (S) protein of the virus. Virus entry may also depend on the activity of the endosomal/lysosomal cysteine proteases cathepsin B, L (CTSB, CTSL) although their activity is likely dispensable. Given that the uncertainty of how COVID-19 kills, hampers doctors’ ability to choose treatments the need for a deep understanding of COVID-19 biology is urgent. Herein, we performed an expression profiling meta-analysis of ACE2, TMPRSS2 and CTSB/L genes (and proteins) in public repository databases and found that all are widely expressed in human tissues; also, the ACE2 and TMPRSS2 genes tend to be co-regulated. The ACE2 and TMPRSS genes expression is (among others) suppressed by TNF, and is induced by pro-inflammatory conditions including obesity, Barrett's esophagus, stomach infection by helicobacter pylori, diabetes, autoimmune diseases and oxidized LDL; by exercise, as well as by growth factors, viruses’ infections, cigarette smoke, interferons and androgens. Regarding currently investigated therapies interferon-beta induced ACE2 gene expression in bronchial epithelial cells, while chloroquine tends to upregulate CTSB/L genes. Finally, we analyzed KEGG pathways modulated by ACE2, TMPRSS2 and CTSB/L and probed DrugBank for drugs that target modules of the affected pathways. Our data indicate possible novel high-risk groups for COVID-19; provide a rich resource for future investigations of its pathogenesis and highlight the therapeutic challenges we face.


title: Severe Acute Respiratory Syndrome Epidemic in Asia

text: We analyzed the dynamics of cumulative severe acute respiratory syndrome (SARS) cases in Singapore, Hong Kong, and Beijing using the Richards model. The predicted total SARS incidence was close to the actual number of cases; the predicted cessation date was close to the lower limit of the 95% confidence interval.


title: Diferencias en función de la edad y la autopercepción del envejecimiento en ansiedad, tristeza, soledad y sintomatología comórbida ansioso-depresiva durante el confinamiento por el COVID-19

text: Resumen Objetivos: Analizar si existen diferencias en función de la edad en ansiedad, tristeza, soledad y comorbilidad ansioso-depresiva en personas jóvenes, de mediana edad y mayores confinadas debido a la pandemia del COVID-19, y explorar la relación entre la autopercepción negativa del envejecimiento y nivel de sintomatología psicológica en función del grupo de edad. Método: Participan 1501 personas (rango de edad: 18 a 88 años). Se evaluó el grado de ansiedad, tristeza y soledad, y autopercepción del envejecimiento. Se dividió a la muestra en función del grupo de edad y por cuartiles (bajo, intermedios y alto) en ansiedad, tristeza, soledad y autopercepción del envejecimiento. Resultados: Las personas mayores informan de menor ansiedad y tristeza que los de mediana edad y jóvenes, y los de mediana edad de menores niveles que los jóvenes. Los de mediana edad informan de menor soledad, seguidos de los mayores y los jóvenes. Para cada grupo de edad, aquellos con una alta autopercepción negativa del envejecimiento informan de mayor ansiedad, tristeza y soledad. Hay más comorbilidad ansioso-depresiva en jóvenes y menos en mayores; más personas deprimidas en mediana edad, menos mayores con ansiedad, y más mayores y menos jóvenes sin sintomatología ansiosa y depresiva. Para todos los grupos de edad, las personas con comorbilidad ansioso-depresiva son las que tienen puntuaciones altas en autopercepción negativa del envejecimiento. Conclusiones: Las personas mayores informan de menos malestar psicológico que otros grupos de edad. Tener una alta autopercepción negativa del envejecimiento perjudica a la salud psicológica independientemente de la edad. Abstract Objectives: To analyze differences by age group in anxiety, depression, loneliness and comorbid anxiety and depression in young people, middle aged adults and older adults during the lock-down period at home due to the COVID-19 pandemic, and to explore the association between negative self-perceptions of aging and psychological symptoms controlling by age group. Method: Participants are 1501 people (age range 18 to 88 years). Anxiety, sadness, loneliness and self-perceptions of aging were assessed. The sample was divided according to the age group and quartiles (lower, intermediate levels, and higher) of anxiety, sadness, loneliness and self-perceptions of aging. Results: Older adults reported lower levels of anxiety and sadness than middle aged adults, and middle aged adults reported lower levels than younger participants. Middle aged adults reported the lowest loneliness, followed by older adults and younger participants. For each age group, those with more negative self-perceptions of aging reported higher anxiety, sadness and loneliness. More comorbid anxiety and sadness was found in younger adults and less in older adults; more depressed participants in the middle aged group, and more older adults and less younger participants were found in the group with the lowest levels of anxiety and sadness. For all the age groups, participants with high levels of comorbid anxiety and sadness are those who report the highest scores in negative self-perceptions of aging. Conclusions: Older adults reported lower psychological anxiety, sadness and loneliness than the other age groups. Having negative self-perceptions of aging damage psychological health irrespective of the chronological age.


title: Cellular response to influenza virus infection: a potential role for autophagy in CXCL10 and interferon-alpha induction

text: Historically, influenza pandemics have arisen from avian influenza viruses. Avian influenza viruses H5N1 and H9N2 are potential pandemic candidates. Infection of humans with the highly pathogenic avian influenza H5N1 virus is associated with a mortality in excess of 60%, which has been attributed to dysregulation of the cytokine system. Human macrophages and epithelial cells infected with some genotypes of H5N1 and H9N2 viruses express markedly elevated cytokine and chemokine levels when compared with seasonal influenza A subtype H1N1 virus. The mechanisms underlying this cytokine and chemokine hyperinduction are not fully elucidated. In the present study, we demonstrate that autophagy, a tightly regulated homeostatic process for self-digestion of unwanted cellular subcomponents, plays a role in cytokine induction. Autophagy is induced to a greater extent by H9N2/G1, in association with cytokine hyperinduction, compared with H1N1 and the novel pandemic swine-origin influenza A/H1N1 viruses. Using 3-methyladenine to inhibit autophagy and small interfering RNA to silence the autophagy gene, Atg5, we further show that autophagic responses play a role in influenza virus-induced CXCL10 and interferon-α expression in primary human blood macrophages. Our results provide new insights into the pathogenic mechanisms of avian influenza viruses.


docid: knheqmbj

title: The protective role of microRNA-21 against coxsackievirus B3 infection through targeting the MAP2K3/P38 MAPK signaling pathway

text: BACKGROUND: The P38 mitogen-activated protein kinase (MAPK) pathway plays an essential role in CVB3-induced diseases. We previously demonstrated microRNA-21 has potential inhibitory effect on the MAP2K3 which locates upstream of P38 MAPK and was upregulated in mouse hearts upon CVB3 infection. However, the effect and underlying mechanism of miRNA-21 on CVB3 infection remain unclear. METHODS: We detected continuous changes of cellular miRNA-21 and P38 MAPK proteins expression profiling post CVB3 infection in vitro within 12 h. P38 MAPK signaling was inhibited by the specific inhibitor, small interfering RNA and miRNA-21 mimic in vitro, CVB3 replication, cell apoptosis rate and proliferation were detected. Viral load in the mice heart, cardiomyocyte apoptosis rate and histological of the heart were also detected in the mice model of viral myocarditis pretreated with miRNA-21-lentivirus. RESULTS: We observed significant upregulation of miRNA-21 expression followed by suppression of the MAP2K3/P38 MAPK signaling in CVB3-infected Hela cells. The inactivation of the MAP2K3/P38 MAPK signaling by P38 MAPK specific inhibitor, small interfering RNA against MAP2K3, or miRNA-21 overexpression significantly inhibited viral progeny release from CVB3-infected cells. Mechanistically, when compared with control miRNA, miRNA-21 showed no effect on capsid protein VP1 expression and viral load within host cells, while significantly reversing CVB3-induced caspase-3 activation and cell apoptosis rate, further promoting proliferation of infected cells, which indicates the inhibitory effect of miRNA-21 on CVB3 progeny release. In the in vivo study, when compared with control miRNA, miRNA-21 pretreatment remarkably inactivated the MAP2K3/P38 MAPK signaling in mice and protected them against CVB3 infection as evidenced by significantly alleviated cell apoptosis rate, reduced viral titers, necrosis in the heart as well as by remarkably prolonged survival time. CONCLUSIONS: miRNA-21 were reverse correlated with P38 MAPK activation post CVB3 infection, miRNA-21 overexpression significantly inhibited viral progeny release and decreased myocytes apoptosis rate in vitro and in vivo, suggesting that miRNA-21 may serve as a potential therapeutic agent against CVB3 infection through targeting the MAP2K3/P38 MAPK signaling.


title: Mask is the possible key for self‐isolation in COVID‐19 pandemic

text: Ma's research shows N95 masks, medical masks, even homemade masks could block at least 90% of the virus in aerosols(1). This study puts the debate on whether the public wear masks back on the table. Recently Science interviewed Dr. Gao, director‐general of Chinese Center for Disease Control and Prevention (CDC). This article is protected by copyright. All rights reserved.


title: Inflection point: The future of subcontracting in the petroleum industry

text: Abstract Oil prices have been in the downtrend since the recession of 2008. Since then, companies have struggled to survive as factors of production are being driven by external influences. International efforts to create a sustainable environment further intricates the supply and demand curve as countries develop policies and strategies to phase out fossil fuels. There has been a myriad of researches conducted by both public and private organisations that seem to agree and disagree on certain factors of a peak oil forecast. There is lack of research however, on finding common ground to determine the central tendencies if multiple predictions are accounted, which creates bias in decision making. The findings of this research provide a practical outlook for businesses and governments to better position their financial and policy decisions with regard to fossil fuels which could affect the lives of many. This research uses a novel prediction combination approach to determine an earliest-case peak oil occurrence through qualitative and quantitative methods for bias minimisation. The predictions are sourced from a balance of reputable private and public international agencies. The result interestingly finds commonality of reaching an earliest-case of peak oil in the year 2025 with feasible factors considered. The research discusses the inflection point forecast and financial risk mitigation recommendations for private entities and governments gathered from expert reports and articles in the field of oil supply and demand.


title: Bureaucratic Accountability and Disaster Response: Why Did the Korea Coast Guard Fail in Its Rescue Mission During the Sewol Ferry Accident?

text: The Sewol ferry accident, occurring in the ocean in South Korea on April 16, 2014, resulted in the loss of 304 lives. Some argue that one of the primary reasons for such an excessive death toll was because the post‐disaster rescue operations led by the Korea Coast Guard (KCG) were neither timely nor efficient and effective. In this study, we attempt to understand whether there was any systemic cause behind such an unsuccessful disaster response on the part of the KCG. In doing so, we analyze the KCG's aptitudes, attitudes, and behaviors vis‐à‐vis its rescue operations in the broader context of Sewol ferry disaster management, while utilizing the classic theories of bureaucratic accountability. We conclude this research by arguing that the KCG was more concerned about hierarchical, political, and legal accountability than professional accountability in the midst of the accident, and discuss theoretical and practical ramifications of our findings.


ACE/ACE2 Ratio: A Key Also in 2019 Coronavirus Disease (Covid-19)?


title: Estimation of COVID-19 prevalence in Italy, Spain, and France

text: Abstract At the end of December 2019, coronavirus disease 2019 (COVID-19) appeared in Wuhan city, China. As of April 15, 2020, >1.9 million COVID-19 cases were confirmed worldwide, including >120,000 deaths. There is an urgent need to monitor and predict COVID-19 prevalence to control this spread more effectively. Time series models are significant in predicting the impact of the COVID-19 outbreak and taking the necessary measures to respond to this crisis. In this study, Auto-Regressive Integrated Moving Average (ARIMA) models were developed to predict the epidemiological trend of COVID-19 prevalence of Italy, Spain, and France, the most affected countries of Europe. The daily prevalence data of COVID-19 from 21 February 2020 to 15 April 2020 were collected from the WHO website. Several ARIMA models were formulated with different ARIMA parameters. ARIMA (0,2,1), ARIMA (1,2,0), and ARIMA (0,2,1) models with the lowest MAPE values (4.7520, 5.8486, and 5.6335) were selected as the best models for Italy, Spain, and France, respectively. This study shows that ARIMA models are suitable for predicting the prevalence of COVID-19 in the future. The results of the analysis can shed light on understanding the trends of the outbreak and give an idea of the epidemiological stage of these regions. Besides, the prediction of COVID-19 prevalence trends of Italy, Spain, and France can help take precautions and policy formulation for this epidemic in other countries.


title: An anti-Gn glycoprotein antibody from a convalescent patient potently inhibits the infection of severe fever with thrombocytopenia syndrome virus

text: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease localized to China, Japan, and Korea that is characterized by severe hemorrhage and a high fatality rate. Currently, no specific vaccine or treatment has been approved for this disease. To develop a therapeutic agent for SFTS, we isolated antibodies from a phage-displayed antibody library that was constructed from a patient who recovered from SFTS virus (SFTSV) infection. One antibody, designated as Ab10, was reactive to the Gn envelope glycoprotein of SFTSV and protected host cells and A129 mice from infection in both in vitro and in vivo experiments. Notably, Ab10 protected 80% of mice, even when injected 5 days after inoculation with a lethal dose of SFTSV. Using cross-linker assisted mass spectrometry and alanine scanning, we located the non-linear epitope of Ab10 on the Gn glycoprotein domain II and an unstructured stem region, suggesting that Ab10 may inhibit a conformational alteration that is critical for cell membrane fusion between the virus and host cell. Ab10 reacted to recombinant Gn glycoprotein in Gangwon/Korea/2012, HB28, and SD4 strains. Additionally, based on its epitope, we predict that Ab10 binds the Gn glycoprotein in 247 of 272 SFTSV isolates previously reported. Together, these data suggest that Ab10 has potential to be developed into a therapeutic agent that could protect against more than 90% of reported SFTSV isolates.


title: Alphavirus Nucleocapsid Packaging and Assembly

text: Alphavirus nucleocapsids are assembled in the cytoplasm of infected cells from 240 copies of the capsid protein and the approximately 11 kb positive strand genomic RNA. However, the challenge of how the capsid specifically selects its RNA package and assembles around it has remained an elusive one to solve. In this review, we will summarize what is known about the alphavirus capsid protein, the packaging signal, and their roles in the mechanism of packaging and assembly. We will review the discovery of the packaging signal and how there is as much evidence for, as well as against, its requirement to specify packaging of the genomic RNA. Finally, we will compare this model with those of other viral systems including particular reference to a relatively new idea of RNA packaging based on the presence of multiple minimal packaging signals throughout the genome known as the two stage mechanism. This review will provide a basis for further investigating the fundamental ways of how RNA viruses are able to select their own cargo from the relative chaos that is the cytoplasm.


docid: eizypepg

title: Mucosal Immunogenicity of Genetically Modified Lactobacillus acidophilus Expressing an HIV-1 Epitope within the Surface Layer Protein

text: Surface layer proteins of probiotic lactobacilli are theoretically efficient epitope-displaying scaffolds for oral vaccine delivery due to their high expression levels and surface localization. In this study, we constructed genetically modified Lactobacillus acidophilus strains expressing the membrane proximal external region (MPER) from human immunodeficiency virus type 1 (HIV-1) within the context of the major S-layer protein, SlpA. Intragastric immunization of mice with the recombinants induced MPER-specific and S-layer protein-specific antibodies in serum and mucosal secretions. Moreover, analysis of systemic SlpA-specific cytokines revealed that the responses appeared to be Th1 and Th17 dominant. These findings demonstrated the potential use of the Lactobacillus S-layer protein for development of oral vaccines targeting specific peptides.


title: An iterative and automated computational pipeline for untargeted strain-level identification using MS/MS spectra from pathogenic samples

text: Untargeted accurate strain-level classification of a priori unidentified organisms using tandem mass spectrometry is a challenging task. Reference databases often lack taxonomic depth, limiting peptide assignments to the species level. However, the extension with detailed strain information increases runtime and decreases statistical power. In addition, larger databases contain a higher number of similar proteomes. We present TaxIt, an iterative workflow to address the increasing search space required for MS/MS-based strain-level classification of samples with unknown taxonomic origin. TaxIt first applies reference sequence data for initial identification of species candidates, followed by automated acquisition of relevant strain sequences for low level classification. Furthermore, proteome similarities resulting in ambiguous taxonomic assignments are addressed with an abundance weighting strategy to improve candidate confidence. We apply our iterative workflow on several samples of bacterial and viral origin. In comparison to non-iterative approaches using unique peptides or advanced abundance correction, TaxIt identifies microbial strains correctly in all examples presented (with one tie), thereby demonstrating the potential for untargeted and deeper taxonomic classification. TaxIt makes extensive use of public, unrestricted and continuously growing sequence resources such as the NCBI databases and is available under open-source license at https://gitlab.com/rki_bioinformatics.


docid: zolwoedn

title: North Carolina frees up $30 million for BH during COVID‐19 crisis

text: North Carolina's seven regional managed care agencies for behavioral health are receiving $30 million so they can keep a variety of programs running during the COVID‐19 crisis, Carolina Public Press reported March 31. The money, which an N.C. Department of Health and Human Services (DHHS) spokesperson said represented unused Medicaid funds, has been shifted to the state's seven local management entities/managed care organizations, commonly called LME/MCOs. The LME/MCOs manage care for beneficiaries receiving mental health, developmental disabilities and substance abuse services who are on Medicaid, uninsured or underinsured. The letter also gave the LME/MCOs authority to use up to 15% of risk reserves to support contracted providers, but with a significant qualifier. The agencies, the DHHS said, would be able to use their reserves to support providers that are “maintaining consumers in their existing residential placements, utilizing telehealth capabilities to the maximum extent possible, providing services that keep consumers from needing access to emergency departments and inpatient services, and otherwise making efforts to deliver high‐quality services during this crisis.” The department's caveat that local providers make every effort to keep their clients out of hospitals is part of a concerted campaign to maintain as much bed space and equipment as possible as the number of COVID‐19 cases rises.


title: Managing the R0 of Covid‐19: mathematics fights back

text: Perhaps for the first time in history, a single statistical measure is now dictating the entirety of UK government policy. The ‘basic reproduction number’, R0 value for Covid‐19 is more directly determining economic and social policy than has ever the inflation rate, interest rate, or exchange rate. It is encouraging to see political policy for once ‘rational’ but disappointing it took a pandemic to make it so. However, is R0 an appropriate and significant measure? Like many mathematics/statistical parameters, R0 is relatively easy to explain, more complicated to understand (even graphically), and very difficult to calculate, or use for modelling. Given its significance for all our lives, it is important to understand a little of its background. This article seeks to explain the issues in a non‐technical way, relegating all equations (used sparingly) to appendices.


title: A Multi-Tier Fog Content Orchestrator Mechanism with Quality of Experience Support

text: Abstract Video-on-Demand (VoD) services create a demand for content orchestrator mechanisms to support Quality of Experience (QoE). Fog computing brings benefits for enhancing the QoE for VoD services by caching the content closer to the user in a multi-tier fog architecture, considering their available resources to improve QoE. In this context, it is mandatory to consider network, fog node, and user metrics to choose an appropriate fog node to distribute videos with QoE support properly. In this article, we introduce a content orchestrator mechanism, called of Fog4Video, which chooses an appropriate fog node to download video content. The mechanism considers the available bandwidth, delay, and cost, besides the QoE metrics for VoD, namely number of stalls and stalls duration, to deploy VoD services in the opportune fog node. Decision-making acknowledges periodical reports of QoE from the clients to assess the video streaming from each fog node. These values serve as inputs for a real-time Analytic Hierarchy Process method to compute the influence factor for each parameter and compute the QoE improvement potential of the fog node. Fog4Video is executed in fog nodes organized in multiple tiers, having different characteristics to provide VoD services. Simulation results demonstrate that Fog4Video transmits adapted videos with 30% higher QoE and reduced monetary cost up to 24% than other content request mechanisms.


title: The double burden of diabetes and global infection in low and middle-income countries

text: Four out of five people in the world with diabetes now live in low- and middle-income countries (LMIC), and the incidence of diabetes is accelerating in poorer communities. Diabetes increases susceptibility to infection and worsens outcomes for some of the world’s major infectious diseases such as tuberculosis, melioidosis and dengue, but the relationship between diabetes and many neglected tropical diseases is yet to be accurately characterised. There is some evidence that chronic viral infections such as hepatitis B and HIV may predispose to the development of type 2 diabetes by chronic inflammatory and immunometabolic mechanisms. Helminth infections such as schistosomiasis may be protective against the development of diabetes, and this finding opens up new territory for discovery of novel therapeutics for the prevention and treatment of diabetes. A greater understanding of the impact of diabetes on risks and outcomes for infections causing significant diseases in LMIC is essential in order to develop vaccines and therapies for the growing number of people with diabetes at risk of infection, and to prioritise research agendas, public health interventions and policy. This review seeks to give an overview of the current international diabetes burden, the evidence for interactions between diabetes and infection, immune mechanisms for the interaction, and potential interventions to tackle the dual burden of diabetes and infection.


title: Infección Y Trombosis Asociada Al Covid-19: Posible Papel Del Grupo Sanguineo Abo

text: Resumen Introducción: La infección por SARS-CoV-2, presenta gran heterogeneidad clínica, desde asintomática hasta cuadros clínicos graves con un desenlace fatal. Algunos autores refieren el grupo sanguíneo ABO como posible marcador biológico de susceptibilidad para la enfermedad. Pacientes Y Métodos: Se han recogido los pacientes ingresados con infección por COVID-19 y se ha analizado la incidencia por grupos en relación con la base poblacional de la Comunidad Foral de Navarra, así como sus principales complicaciones y evolución. Resultados: Los pacientes de grupo O ingresados con infección por COVID-19 son proporcionalmente menos respecto a la base poblacional sin ser la diferencia estadísticamente significativa. Los grupos AB y B son un 38% más en el grupo de infectados que en la población. El grupo B ha presentado significación estadística en cuanto al número de complicaciones trombóticas junto con mayor tasa de ingreso en unidades de cuidados intensivos. Conclusión: El estudio sugiere menor susceptibilidad a la infección de los pacientes de grupos O y mayor riesgo de complicaciones en el grupo B. Hacen falta estudios con mayor tamaño muestral para poder obtener resultados significativos. Abstract Background: SARS-CoV-2 infection is clinically very heterogeneous, varying from asymptomatic to severe clinical conditions with a fatal outcome. Some studies suggests that the ABO blood group could be a biological marker of susceptibility for the development of the disease. Material And Methods: We collected data from patients admitted with COVID-19 infection who had ABO blood group recorded, and analyzed the incidence by groups, compared with the global population in Navarre, as well as their main complications and evolution. Results: Group O was proportionally less represented in the hospitalized patients with respect to the global population, although the difference was not statistically significant. Group B had significantly higher rates of thrombotic complications and required more admissions in intensive care units. Conclusion: The study suggests a lower susceptibility to infection in group O and a higher risk of complications in group B. Studies with a larger sample size are required in order to obtain significant results.


title: Systematic profiling of ACE2 expression in diverse physiological and pathological conditions for COVID‐19/SARS‐CoV‐2

text: Recent retrospective studies of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) disease (COVID‐19) revealed that the patients with common comorbidities of cancers and chronic diseases face significantly poorer clinical outcomes than those without. Since the expression profile of ACE2, a crucial cell entry receptor for SARS‐CoV‐2, could indicate the susceptibility to SARS‐CoV‐2 infection, here we systematically dissected ACE2 expression using large‐scale multi‐omics data from 30 organs/tissues, 33 cancer types and some common chronic diseases involving >28 000 samples. It was found that sex and age could be correlated with the susceptibility of SARS‐CoV‐2 infection for certain tissues. Strikingly, ACE2 was up‐regulated in cervical squamous cell carcinoma and endocervical adenocarcinoma, colon adenocarcinoma, oesophageal carcinoma, kidney renal papillary cell carcinoma, lung adenocarcinoma and uterine corpus endometrial carcinoma compared to controls. Furthermore, the patients with common chronic diseases regarding angiocardiopathy, type 2 diabetes, liver, pneumonia and hypertension were also with higher ACE2 expression compared to related controls, which were validated using independent data sets. Collectively, our study may reveal a novel important mechanism that the patients with certain cancers and chronic diseases may express higher ACE2 expression compared to the individuals without diseases, which could lead to their higher susceptibility to multi‐organ injury of SARS‐CoV‐2 infection.


title: Treating Respiratory Viral Diseases with Chemically Modified, Second Generation Intranasal siRNAs

text: Chemically synthesized short interfering RNA (siRNA) of pre-determined sequence has ushered a new era in the application of RNA interference (RNAi) against viral genes. We have paid particular attention to respiratory viruses that wreak heavy morbidity and mortality worldwide. The clinically significant ones include respiratory syncytial virus (RSV), parainfluenza virus (PIV) and influenza virus. As the infection by these viruses is clinically restricted to the respiratory tissues, mainly the lungs, the logical route for the application of the siRNA was also the same, i.e., via the nasal route. Following the initial success of intranasal siRNA against RSV, second-generation siRNAs were made against the viral polymerase large subunit (L) that were chemically modified and screened for improved stability, activity and pharmacokinetics. 2′-O-methyl (2′-O-Me) and 2′-deoxy-2′-fluoro (2′-F) substitutions in the ribose ring were incorporated in different positions of the sense and antisense strands and the resultant siRNAs were tested with various transfection reagents intranasally against RSV. Based on these results, we propose the following consensus for designing intranasal antiviral siRNAs: (i) modified 19–27 nt long double-stranded siRNAs are functional in the lung, (ii) excessive 2′-OMe and 2′-F modifications in either or both strands of these siRNAs reduce efficacy, and (iii) limited modifications in the sense strand are beneficial, although their precise efficacy may be position-dependent.


title: Teaching Adequate Prehospital Use of Personal Protective Equipment During the COVID-19 Pandemic: Development of a Gamified e-Learning Module

text: BACKGROUND: The coronavirus disease (COVID-19) pandemic has led to increased use of personal protective equipment (PPE). Adequate use of this equipment is more critical than ever because the risk of shortages must be balanced against the need to effectively protect health care workers, including prehospital personnel. Specific training is therefore necessary; however, the need for social distancing has markedly disrupted the delivery of continuing education courses. Electronic learning (e-learning) may provide significant advantages because it requires neither the physical presence of learners nor the repetitive use of equipment for demonstration. OBJECTIVE: Inclusion of game mechanics, or “gamification,” has been shown to increase knowledge and skill acquisition. The objective of this research was to develop a gamified e-learning module to interactively deliver concepts and information regarding the correct choice and handling of PPE. METHODS: The SERES framework was used to define and describe the development process, including scientific and design foundations. After we defined the target audience and learning objectives by interviewing the stakeholders, we searched the scientific literature to establish relevant theoretical bases. The learning contents were validated by infection control and prehospital experts. Learning mechanics were then determined according to the learning objectives, and the content that could benefit from the inclusion of game mechanics was identified. RESULTS: The literature search resulted in the selection and inclusion of 12 articles. In addition to gamification, pretesting, feedback, avoiding content skipping, and demonstrations using embedded videos were used as learning mechanics. Gamification was used to enhance the interactivity of the PPE donning and doffing sequences, which presented the greatest learning challenges. The module was developed with Articulate Storyline 3 to ensure that it would be compatible with a wide array of devices, as this software generates HTML5-compatible output that can be accessed on smartphones, tablets, and regular computers as long as a recent browser is available. CONCLUSIONS: A gamified e-learning module designed to promote better knowledge and understanding of PPE use among prehospital health care workers was created by following the SERES framework. The impact of this module should now be assessed by means of a randomized controlled trial.


title: Mice lacking α1,3‐fucosyltransferase 9 exhibit modulation of in vivo immune responses against pathogens

text: Carbohydrate structures, including Lewis X (Le(x)), which is not synthesized in mutant mice that lack α1,3‐fucosyltransferase 9 (Fut9(−/−)), are involved in cell–cell recognition and inflammation. However, immunological alteration in Fut9(−/−) mice has not been studied. Thus, the inflammatory response of Fut9(−/−) mice was examined using the highly neurovirulent mouse hepatitis virus (MHV) JHMV srr7 strain. Pathological study revealed that inflammation induced in the brains of Fut9(−/−) mice after infection was more extensive compared with that of wild‐type mice, although viral titers obtained from the brains of mutant mice were lower than those of wild‐type mice. Furthermore, the reduction in cell numbers in the spleens of wild‐type mice after infection was not observed in the infected Fut9(−/−) mice. Although there were no clear differences in the levels of cytokines examined in the brains between Fut9(−/−) and wild‐type mice except for interferon‐β (IFN‐β) expression, some of those in the spleens, including interferon‐γ (IFN‐γ), interleukin‐6 (IL‐6), and monocyte chemoattractant protein‐1 (MCP‐1), showed higher levels in Fut9(−/−) than in wild‐type mice. Furthermore, Fut9(−/−) mice were refractory to the in vivo inoculation of endotoxin (LPS) compared with wild‐type mice. These results indicate that Le(x) structures are involved in host responses against viral or bacterial challenges.


XXIIIe Congrès de la société de réanimation de langue française. Sessions orales encadrées


title: If not now, when?

text: The editor of the BJPsych Bulletin reflects on the extraordinary recent events triggered by the COVID-19 pandemic. Mental health professionals are at the front line of managing the pandemic and emergency changes should lead to a much needed refocus on what is really vital. In these unsettling times we ought to review how we manage the crisis, and its aftermath, both personally and professionally.


title: Lessons Never Learned: Crisis and gender‐based violence

text: The COVID‐19 pandemic exposes underlying inequalities in our socio‐economic and health systems, such as gender‐based violence (GBV). In emergencies, particularly ones that involve quarantine, GBV often increases. Policymakers must utilize community expertise, technology and existing global guidelines to disrupt these trends in the early stages of the COVID‐19 epidemic. Gender norms and roles relegating women to the realm of care work puts them on the frontlines in an epidemic, while often excluding them from developing the response. It is critical to value women’s roles in society and include their voices in the decision‐making process to avoid unintended consequences and ensure a comprehensive response that caters to the needs of the most vulnerable groups.


title: Coronavirus as a Catalyst to Transform Consumer Policy and Enforcement

text: A review of the unfair commercial practices (including price gouging) that have emerged in the context of the pandemic lead us to reflect on how effective consumer law enforcement is at this juncture. This article calls for the pandemic to act as a catalyst to review the way consumer law has so far approached markets and their regulation. It argues that now, more than ever, consumer law needs to protect the vulnerable and public enforcement mechanisms must be able to prevent harm as much as possible rather than repair it. Fairness should be by design and not something that is offered to consumers simply as a remedy. The article explores some viable solutions to effect this transformation of consumer policy and enforcement beyond the pandemic.


title: MassTag Polymerase-Chain-Reaction Detection of Respiratory Pathogens, Including a New Rhinovirus Genotype, That Caused Influenza-Like Illness in New York State during 2004–2005

text: In New York State during winter 2004, there was a high incidence of influenza-like illness that tested negative both for influenza virus, by molecular methods, and for other respiratory viruses, by virus culture. Concern that a novel pathogen might be implicated led us to implement a new multiplex diagnostic tool. MassTag polymerase chain reaction resolved 26 of 79 previously negative samples, revealing the presence of rhinoviruses in a large proportion of samples, half of which belonged to a previously uncharacterized genetic clade. In some instances, knowledge of the detected viral and/or bacterial (co)infection could have altered clinical management


An infectious disease pandemic and increased suicide risk


docid: rsmhyjin

title: Clinical characteristics of COVID‐19 patients combined with allergy


title: Advances in MERS-CoV Vaccines and Therapeutics Based on the Receptor-Binding Domain

text: Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) is an infectious virus that was first reported in 2012. The MERS-CoV genome encodes four major structural proteins, among which the spike (S) protein has a key role in viral infection and pathogenesis. The receptor-binding domain (RBD) of the S protein contains a critical neutralizing domain and is an important target for development of MERS vaccines and therapeutics. In this review, we describe the relevant features of the MERS-CoV S-protein RBD, summarize recent advances in the development of MERS-CoV RBD-based vaccines and therapeutic antibodies, and illustrate potential challenges and strategies to further improve their efficacy.


title: Crise sanitaire liée au COVID-19 : modalités du traitement de l’appendicite aiguë non compliquée de l’adulte par antibiothérapie seule comme alternative à l’appendicectomie

text: Summary The massive inflow of patients with COVID-19 requiring urgent care has overloaded hospitals in France and impacts the management of other patients. Deferring hospitalization and non-urgent surgeries has become a priority for surgeons today in order to relieve the health care system.It is obviously not simple to reduce emergency surgery without altering the quality of care or leading to a loss of chance for the patient. Acute appendicitis is a very specific situation and the prevalence of this disease leads us to reconsider this particular disease in the context of the COVID-19 crisis. Indeed, while the currently recommended treatment for uncomplicated acute appendicitis is surgical appendectomy, the non-surgical alternative of medical management by antibiotic therapy alone has been widely evaluated by high-quality studies in the literature. Insofar as the main limitation of exclusively medical treatment of uncomplicated acute appendicitis is the risk of recurrent appendicitis, this treatment option represents an alternative of choice to reduce the intra-hospital overload in this context of health crisis.The aim of this work is therefore to provide physicians and surgeons with a practical guide based on a review of the literature on the medical treatment of uncomplicated acute appendicitis in adults, to offer this alternative treatment to the right patients and under good conditions, especially when access to the operating room is limited or impossible.


title: On biological evolution and environmental solutions

text: Abstract Drawing insights from multiple disciplines is essential for finding integrative solutions that are required to tackle complex environmental problems. Human activities are causing unprecedented influence on global ecosystems, culminating in the loss of species and fundamental changes in the selective environments of organisms across the tree of life. Our collective understanding about biological evolution can help identify and mitigate many of the environmental problems in the Anthropocene. To this end, we propose a stronger integration of environmental sciences with evolutionary biology.


title: Equine proliferative enteropathy caused by Lawsonia intracellularis

text: Equine proliferative enteropathy (EPE) is a disease of foals caused by the obligate intracellular organism Lawsonia intracellularis. This emerging disease affects mainly weanling foals and causes fever, lethargy, peripheral oedema, diarrhoea, colic and weight loss. The diagnosis of EPE may be challenging and relies on the presence of hypoproteinaemia, thickening of segments of the small intestinal wall observed on abdominal ultrasonography, positive serology and molecular detection of L. intracellularis in faeces. Although the clinical entity, diagnostic work‐up and treatment of EPE are well established and described, the epidemiology for this disease has remained largely unaddressed. This article reviews the aetiology, epidemiology, clinical signs, diagnosis, treatment and prevention of EPE.


title: COVID-19 - Enacting a ‘new normal’ for people who use drugs

text: The COVID-19 crisis has magnified existing social, economic and political inequities. People who use drugs are particularly vulnerable due to criminalisation and stigma and often experience underlying health conditions, higher rates of poverty, unemployment and homelessness, as well as a lack of access to vital resources – putting them at greater risk of infection. On the other hand, COVID-19 presents an opportunity to confront the mistakes of the past and re-negotiate a new social contract. The International Network of People who use Drugs (INPUD) believe that this crisis must be an occasion to rethink the function of punishment, to reform the system and to work towards ending the war on drugs. This commentary presents a set of recommendations to UN agencies, governments, donor agencies, academics and researchers and civil society, challenging these actors to work alongside people who use drugs to enact a new reality based on solidarity and cooperation, protection of health and restoration of rights and dignity and most importantly to mobilise to win the peace.


title: Formation of fibroblastic reticular network in the brain after infection with neurovirulent murine coronavirus

text: cl‐2 virus is an extremely neurovirulent murine coronavirus. However, during the initial phase of infection between 12 and 24 h post‐inoculation (hpi), the viral antigens are detected only in the meninges, followed by viral spread into the ventricular wall before invasion into the brain parenchyma, indicating that the viruses employ a passage between the meninges and ventricular wall as an entry route into the brain parenchyma. At 48 hpi, the passage was found to be constructed by ER‐TR7 antigen (ERag)‐positive fibers (ERfibs) associated with laminin and collagen III between the fourth ventricle and meninges at the cerebellopontine angle. The construct of the fibers mimics the reticular fibers of the fibroblastic reticular network, which comprises a conduit system in the lymphoid organs. In the meninges, ERfibs together with collagen fibers, lining in a striped pattern, made up a pile of thin sheets. In the brain parenchyma, mature ERfibs associated with laminin were found around blood vessels. Besides mature ERfibs, immature Erfibs without associations with other extracellular matrix components like laminin and collagen appeared after infection, suggesting that the CNS creates a unique conduit system for immune communication triggered by viral invasion.


title: Novel Corona virus Disease infection in Tunisia: Mathematical model and the impact of the quarantine strategy

text: Corona virus disease (COVID-19) is an extremely serious infection with an extremely high death rate worldwide. In March, the disease was declared a ”global pandemic” by the World Health Organization (WHO). Until now, there is no known vaccine or drug, since the unknown things related to the disease are more important than our theoretical and empirical knowledge. However, mathematical modeling and the estimation of the basic number of reproductions can provide clarifications in order to determine the potential and severity of this epidemic and therefore provide essential information to identify the type of measures and interventions to be taken to control the intensity of the spread of the disease. Hence, in this paper, we propose a new deterministic compartmental model based on the clinical progression of the disease, the epidemiological state of the individuals and the intervention for the dynamics of COVID-19 infections. Our approach consists of seven phenotypes: the susceptible humans, exposed humans, infectious humans, the recovered humans, the quarantine population, there recovered-exposed and deceased population. We proved first through mathematical approach the positivity, boundness and existence of a solution to the considered model. We also studied the existence of the disease free equilibrium and corresponding stability. Our work shows, in particular, that the disease will decrease if the number of reproduction R(0) was less than one. Moreover, the impact of the quarantine strategies to reduce the spread of this disease is discussed. The theoretical results are validated by some numerical simulations of the system of the epidemic’s differential equations. It should be mentioned that, the error between the considered model and the official data curve is quite small.


title: Assessment of the Wearability of Facemasks against Air Pollution in Primary School-Aged Children in London

text: Air pollution is a major health problem and children are particularly vulnerable to the adverse effects. Facemasks are one form of protection but, to be effective, they need to filter out airborne pollutants, fit the face well and be wearable. In this pilot study, we assess the perceived wearability of three facemasks (Vogmask, TuHao and ReSpimask) marketed in the UK as being designed to protect children against exposure to air pollution. Twenty-four primary school children wore each facemask during a standardised walking and running activity. After each activity, the children were asked to rate facemask wearability in terms of parameters, such as perceived comfort, hotness, breathability and fit. At the end of the trial, the children compared and identified their preferred facemask. The main complaint about the facemasks was the children’s faces being too hot. The ReSpimask was most frequently reported as being perceived to be the hardest to breathe through. The TuHao facemask was the only adjustable strap mask assessed but was reported to be difficult to adjust. Facemasks with a nose clip were frequently rated highest for fit (TuHao and Vogmask). The patterned, cloth fabric Vogmask had significantly higher ratings for appearance and perceived fit. The results show children’s perceptions of facemasks are highly affected by the facemask’s design, hotness and perceived breathability. By making children’s facemasks more appealing, breathable, cooler and improving their fit, wearability may be improved.


title: COVID-19: Pandemic Risk, Resilience and Possibilities for Aging Research

text: The COVID-19 global crisis is reshaping Canadian society in unexpected and profound ways. The significantly higher morbidity and mortality risks by age suggest that this is largely a “gero-pandemic,” which has thrust the field of aging onto center stage. This editorial emphasizes that vulnerable older adults are also those most affected by COVID-19 in terms of infection risk, negative health effects, and the potential deleterious outcomes on a range of social, psychological, and economic contexts – from ageism to social isolation. We also contend that the pathogenic analysis of this pandemic needs to be balanced with a salutogenic approach that examines the positive adaptation of people, systems and society, termed COVID-19 resilience. This begs the question: how and why do some older adults and communities adapt and thrive better than others? This examination will lead to the identification and response to research and data gaps, challenges, and innovative opportunities as we plan for a future in which COVID-19 has become another endemic infection in the growing list of emerging and re-emerging pathogens.


title: First case of COVID‐19 in a kidney transplant recipient treated with belatacept

text: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing public health emergency of international concern. Acute respiratory distress syndrome (ARDS) develops in 3-30% of patients with COVID-19 (1,2), because of direct virus-induced cytopathic effects in the respiratory tract or cytokine storms triggered by the host's immune response. Comorbidities are known to increase the risk of ARDS in SARS-CoV-2-infected patients (1).


title: Polyhydroxyalkanoate chip for the specific immobilization of recombinant proteins and its applications in immunodiagnostics

text: In this study, a novel strategy was developed for the highly selective immobilization of proteins, using the polyhydroxyalkanoate (PHA) depolymerase substrate binding domain (SBD) as an active binding domain. In order to determine the appropriacy of this method for immunodiagnostic assays, the single-chain antibody (ScFv) against the hepatitis B virus (HBV) preS2 surface protein and the severe acute respiratory syndrome coronavirus (SARS-CoV) envelope protein (SCVe) were fused to the SBD, then directly immobilized on PHA-coated slides via microspotting. The fluorescence-labeled HBV antigen and the antibody against SCVe were then utilized to examine specific interactions on the PHA-coated surfaces. Fluorescence signals were detected only at the spotted positions, thereby indicating a high degree of affinity and selectivity for their corresponding antigens/antibodies. Furthermore, we detected small amounts of ScFv-SBD (2.7 ng/mL) and SCVe-SBD fusion proteins (0.6 ng/mL). Therefore, this microarray platform technology, using PHA and SBD, appears generally appropriate for immunodiagnosis, with no special requirements with regard to synthetic or chemical modification of the biomolecules or the solid surface.


title: Use of systematic epidemiological methods in outbreak investigations from India, 2008–2016: A systematic review

text: Abstract Background In the absence of a comprehensive review, we conducted a systematic review on the use of systematic approach in outbreak investigation using reports from India. Objectives The primary objective was to estimate the proportion of outbreak reports from India during 2008–16, that reported the steps in outbreak investigation. The secondary objectives were to (1) describe the outbreak reports by selected characteristics (source, investigating agency, disease, time, place and person) (2) estimate the proportion of outbreaks that conducted analytical and additional studies. Methods We searched eight electronic databases and grey literature for outbreak investigation reports among humans at community settings from India during 2008–2016. We developed a check-list based on the 10-steps approach used by Field Epidemiology Training Programme (FETP) of ICMR-National Institute of Epidemiology (ICMR-NIE), Chennai, India. This checklist was used to independently screen and extract data on general characteristics of the outbreak investigation reports and the steps completed. We adopted The Joanna Briggs Institute (JBI) check list for prevalence studies to examine the credibility and consistency. The protocol was registered at Prospero (CRD42017065038). We calculated proportion of reports that followed the steps in their investigation and descriptive statistics on selected characteristics. Results Of 10,657 articles screened, 136 articles were included for the review. Completion of the ten steps in the outbreak investigations was seen in 16% of reports. The highest level of completion was for drawing conclusion in outbreak investigation (98%) and the lowest completion (29%) was for developing a case definition by time, place and person followed by conducting an analytic study (24%). Conclusions Outbreak reports from India either lacked application of systematic steps for investigation or failed to report the actual procedures followed. We recommend improving systematic investigation of outbreaks through training and supervision of outbreak response teams and encouraging publications.


title: Association of renin-angiotensin-aldosterone system inhibitors with COVID-19-related outcomes in Korea: a nationwide population-based cohort study

text: BACKGROUND: Renin-angiotensin-aldosterone system (RAAS) inhibitors may facilitate host cell entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or attenuate organ injury via RAAS blockade. We aimed to assess the associations between prior use of RAAS inhibitors and clinical outcomes among Korean patients with coronavirus 2019 (COVID-19). METHODS: We performed a nationwide population-based cohort study using the Korean Health Insurance Review and Assessment database. Claim records were screened for 66793 individuals who were tested for COVID-19 until April 8, 2020. Adjusted odds ratios (ORs) were used to compare the clinical outcomes between RAAS inhibitor users and nonusers. RESULTS: Among 5179 confirmed COVID-19 cases, 762 patients were RAAS inhibitor users and 4417 patients were nonusers. Relative to nonusers, RAAS inhibitor users were more likely to be older, male, and have comorbidities. Among 1954 hospitalized patients with COVID-19, 377 patients were RAAS inhibitor users and 1577 patients were nonusers. In-hospital mortality was observed for 33 RAAS inhibitor users (9%) and 51 nonusers (3%) (p<0.001). However, after adjustment for age, sex, Charlson Comorbidity Index, immunosuppression, and hospital type, the use of RAAS inhibitors was not associated with a higher risk of mortality (adjusted OR, 0.88; 95% confidence interval, 0.53–1.44; p=0.60). No significant differences were observed between RAAS inhibitor users and nonusers in terms of vasopressor use, modes of ventilation, extracorporeal membrane oxygenation, renal replacement therapy, and acute cardiac events. CONCLUSIONS: Our findings suggest that prior use of RAAS inhibitors was not independently associated with mortality among COVID-19 patients in Korea.


China shares experience and supports the world during the COVID-19 outbreak


docid: joacrild

title: Developing a supervised learning-based social media business sentiment index

text: The fast-growing digital data generation leads to the emergence of the era of big data, which become particularly more valuable because approximately 70% of the collected data in the world comes from social media. Thus, the investigation of online social network services is of paramount importance. In this paper, we use the sentiment analysis, which detects attitudes and emotions toward issues of society posted in social media, to understand the actual economic situation. To this end, two steps are suggested. In the first step, after training the sentiment classifiers with several big data sources of social media datasets, we consider three types of feature sets: feature vector, sequence vector and a combination of dictionary-based feature and sequence vectors. Then, the performance of six classifiers is assessed: MaxEnt-L1, C4.5 decision tree, SVM-kernel, Ada-boost, Naïve Bayes and MaxEnt. In the second step, we collect datasets that are relevant to several economic words that the public use to explicitly express their opinions. Finally, we use a vector auto-regression analysis to confirm our hypothesis. The results show the statistically significant relationship between public sentiment and economic performance. That is, “depression” and “unemployment” lead to KOSPI. Also, it shows that the extracted keywords from the sentiment analysis, such as “price,” “year-end-tax” and “budget deficit,” cause the exchange rates.


title: Human metapneumovirus in adults: a short case series

text: This study was carried out to further the available information on adult cases of human metapneumovirus (hMPV), a recently described cause of respiratory infection. Among a cohort of 741 symptomatic patients tested since 2003, the virus was diagnosed in six adults using reverse transcriptase polymerase chain reaction. Of the six, two were from the community, two were hospital inpatients with chronic obstructive pulmonary disease and two were immunocompromised patients, both of whom required ventilation and later died. This report discusses the clinical features, epidemiology and diagnosis of hMPV, highlighting that this infection may be associated with death in high-risk adults. For adults presenting with respiratory symptoms and a background of pre-existing respiratory disease or who are immunocompromised, nucleic acid-based techniques are a cost-effective means of making the viral diagnosis in a clinically relevant time frame.


title: Mimivirus: leading the way in the discovery of giant viruses of amoebae

text: The accidental discovery of the giant virus of amoeba — Acanthamoeba polyphaga mimivirus (APMV; more commonly known as mimivirus) — in 2003 changed the field of virology. Viruses were previously defined by their submicroscopic size, which probably prevented the search for giant viruses, which are visible by light microscopy. Extended studies of giant viruses of amoebae revealed that they have genetic, proteomic and structural complexities that were not thought to exist among viruses and that are comparable to those of bacteria, archaea and small eukaryotes. The giant virus particles contain mRNA and more than 100 proteins, they have gene repertoires that are broader than those of other viruses and, notably, some encode translation components. The infection cycles of giant viruses of amoebae involve virus entry by amoebal phagocytosis and replication in viral factories. In addition, mimiviruses are infected by virophages, defend against them through the mimivirus virophage resistance element (MIMIVIRE) system and have a unique mobilome. Overall, giant viruses of amoebae, including mimiviruses, marseilleviruses, pandoraviruses, pithoviruses, faustoviruses and molliviruses, challenge the definition and classification of viruses, and have increasingly been detected in humans. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrmicro.2016.197) contains supplementary material, which is available to authorized users.


title: Human bocavirus infection in hospitalized children in Italy

text: Background Human bocavirus (HBoV) was first discovered in Sweden in 2005 and has now been found worldwide; however its role in clinically relevant diseases has not yet been clearly defined. Objectives To gain new insight into HBoV infection among children hospitalized with acute respiratory infections in Rome. Methods Between November 2004 and May 2007, 415 nasal washings were tested for the presence of an extensive range of respiratory viruses using molecular methods. Results Viral pathogens were detected in 214 children (51·6%), 28·9% being respiratory syncytial virus (RSV) and 9·6% being rhinovirus positive. Of the 34 children (8·2%) who tested positive for HBoV, 21 (61·8%) were co‐infected with another respiratory virus, mainly RSV. Human bocavirus was the only pathogen identified in four pneumonia and six bronchiolitis cases in March 2005 and January 2007, respectively. Human bocavirus was also detected in one child hospitalized with gastroenteritis and in another with erythema. Conclusions In the examined population, HBoV was the third most common virus detected but with a high rate of co‐infection with other respiratory viruses. Human bocavirus appeared to be the etiological agent in some pneumonia and bronchiolitis cases in which tests for all likely respiratory pathogens were negative.


title: Enteric viral infections in lambs or kids

text: Abstract Diarrhoea in lambs and kids is often a complex, multi-factorial syndrome. Common infectious causes of diarrhoea in lambs and kids during the first month of life are of bacterial or parasite nature. However, despite appreciable improvements in management practices and prevention and treatment strategies over the last decades, diarrhoea is still a common and costly syndrome affecting newborn small ruminants. Recent advances in the diagnostics and metagenomic investigations of the enteric environment have allowed discovering a number of novel viruses, although their pathobiological properties remain largely unknown. Assessing more in depth the impact of these viruses on the health and productions of these livestock animals is necessary and requires the development of accurate diagnostic tools and updating of the diagnostic algorithms of enteric pathological conditions.


title: What Is Required to Prevent a Second Major Outbreak of SARS-CoV-2 upon Lifting Quarantine in Wuhan City, China

text: Summary Background The Chinese government implemented a metropolitan-wide quarantine of Wuhan city on 23rd January 2020 to curb the epidemic of the coronavirus COVID-19. Lifting of this quarantine is imminent. We modelled the effects of two key health interventions on the epidemic when the quarantine is lifted. Methods We constructed a compartmental dynamic model to forecast the trend of the COVID-19 epidemic at different quarantine lifting dates and investigated the impact of different rates of public contact and facial mask usage on the epidemic. Results We projected a declining trend of the COVID-19 epidemic if the current quarantine strategy continues, and Wuhan would record the last new confirmed cases in late April 2020. At the end of the epidemic, 65,733 (45,722-99,015) individuals would be infected by the virus, among which 16,166 (11,238-24,603, 24.6%) were through public contacts, 45,996 (31,892-69,565, 69.7%) through household contact, and 3,571 (2,521-5,879, 5.5%) through hospital contacts (including 778 (553-1,154) non-COVID-19 patients and 2,786 (1,969-4,791) medical staff). A total of 2,821 (1,634-6,361) would die of COVID-19 related pneumonia in Wuhan. Early quarantine lifting on 21st March is viable only if Wuhan residents sustain a high facial mask usage of ≥85% and a pre-quarantine level public contact rate. Delaying city resumption to mid/late April would relax the requirement of facial mask usage to ≥75% at the same contact rate. Conclusions The prevention of a second epidemic is viable after the metropolitan-wide quarantine is lifted but requires a sustaining high facial mask usage and a low public contact rate.


title: Lopinavir/ritonavir is associated with pneumonia resolution in COVID‐19 patients with influenza coinfection: a retrospective matched‐pair cohort study

text: BACKGROUND: During the early stages of the pandemic, some coronavirus disease (COVID‐19)patients were misdiagnosed as having influenza, which aroused the concern that some deaths attributed to influenza were actually COVID‐19‐related. Howerver, little is known about whether coinfection with influenza contributes to severity of COVID‐19 pneumonia, and the optimal therapeutic strategy for these patients. METHODS: We retrospectively studied 128 hospitalized patients with COVID‐19 pneumonia. All patients were positive severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)positive by nucleic acid detection. 64 cases were co‐infected with influenza A/B and the other 64 were influenza negative, matched by age, sex, and days from onset of symptoms. RESULTS: Among the 64 co‐infected patients, 54 (84.4%) were co‐infected with influenza A, and 10 (15.6%) with influenza B. The median duration of viral shedding time from admission was longer for patients with influenza coinfection (17.0 days) than for those without influenza coinfection (12.0 days) (P<0.001). The multivariable Cox proportional hazards model showed that the hazard ratio HR of resolution in lung involvement was 1.878 (P=0.020) for patients administered lopinavir/ritonavir, compared with those not administered lopinavir/ritonavir (95% confidence interval (CI) 1.103, 3.196). Among influenza co‐infected patients, those treated with lopinavir/ritonavir exhibited faster pneumonia resolution within two weeks after symptom onset (37% vs 1%, P=0.001). CONCLUSIONS: There was no difference in lung involvement between influenza co‐infected and non‐infected groups. Lopinavir/ritonavir eliminated the difference of lung involvement between influenza co‐infected and non‐infected groups, indicating that lopinavir/ritonavir is associated with pneumonia resolution in COVID‐19. This article is protected by copyright. All rights reserved.


title: Comments on Zhang et al: Clinical trial analysis of 2019‐nCoV therapy registered in China

text: We have read the article by Zhang et al. published in the recent issue of the Journal of Medical Virology1 . Zhang and his colleagues have made a cross-sectional survey of currently registered clinical trials concerning 2019-nCoV, including the published literature. As such, they have given a preliminary assessment on the prospects of therapy for 2019-nCoV. This article is protected by copyright. All rights reserved.