title: Macrolides and viral infections: focus on azithromycin in COVID-19 pathology

text: The emergence of the new disease COVID-19, is posing the challenge of seeking effective therapies. Since the most severe clinical manifestation of COVID-19 appeared to be a severe acute respiratory syndrome, azithromycin has been proposed as a potential treatment. Azithromycin is known to have immunomodulating and antiviral properties. In vitro studies have demonstrated the capacity of azithromycin to reduce production of pro-inflammatory cytokines such as IL-8, IL-6, TNF alpha, reduce oxidative stress and modulate T-helper functions. At the same time there are multiple clinical evidences of the role of azithromycin in acute respiratory distress syndrome and against MERS. Some preliminary evidences have demonstrated controversial results regarding efficacy of azithromycin in combination with hydroxychloroquine in COVID-19. Firstly, a French trial demonstrated 100% of virological negativization of six patients treated with azithromycin plus hydroxychloroquine vs 57.1% of patients treated with only hydroxychloroquine and 12.5% of the control group (p<0.05). On the other hand, another case series revealed no efficacy at all on eleven patients treated with same combination and doses. Furthermore, there are some concerns regarding the association of azithromycin and hydroxychloroquine because of the potential Qt prolongation. In fact, both drugs have this as potential side effect and evidences regarding the safety use of this combination are controversial. Despite the necessity to quickly find solutions for COVID-19, extreme caution must be used in evaluating the risk-benefit balance. However, based on preclinical and clinical evidences and some preliminary results in COVID-19, azithromycin could have a potential in the fight against this new disease.


title: Adapting vascular surgery practice to the current COVID-19 era at a tertiary academic center in Madrid.

text: INTRODUCTION: The epidemic potential of Coronavirus infection is now a reality. Since the first case detected in late 2019 in China a fast-world-wide expansion confirms it. The vascular patient is at a higher risk of developing a severe form of the disease due to its nature associating several comorbid states and thus, some Vascular Surgery communities from many countries have tried to stratify patients into those requiring care during these uncertain times. METHODS: Observational study describing the current daily vascular surgery practice at one tertiary academic hospital in Madrid region, Spain; one of the most affected regions worldwide due to the COVID-19 outbreak. We analyzed our surgical practice since March 14(th) when the lockdown was declared up to date, May 14(th) (2 months). Procedural surgical practice, organizational issues, early outcomes and all the troubles encountered during this new situation are described. RESULTS: Our department is composed of 10 vascular surgeons and 4 trainees. Surgical practice has been reduced to only urgent care, totaling 50 repairs on 45 patients during the time period. Five surgeries were performed on 3 COVID-19 positive patients. Sixty percent were due to CLI, 45% of them performed by complete endovascular approach; whereas less than 10% of repairs were aorta related. We were allocated to use a total of 5 surgical rooms in different locations, none our usual, as it was converted into an ICU room while performing 50% of those repairs with unusual nursery staff. CONCLUSIONS: The COVID-19 outbreak has dramatically changed our organization and practice in favor of urgent or semi-urgent surgical care alone. The lack for in-hospital/ICU beds and changing nursery staff changed the whole availability organization at our hospital and was a key factor in surgical decision making in some cases.


title: Pregnancy and postpartum outcomes in a universally tested population for SARS‐CoV‐2 in New York City: A prospective cohort study

text: OBJECTIVE: To describe differences in outcomes between pregnant women with and without COVID‐19 DESIGN: Prospective cohort study of pregnant women consecutively admitted for delivery, and universally tested via nasopharyngeal (NP) swab for SARS‐CoV‐2 using reverse transcriptase polymerase chain reaction (RT‐PCR). All infants of mothers with COVID‐19 underwent SARS‐CoV‐2 testing. SETTING: Three New York City hospitals POPULATION: Pregnant women > 20 weeks’ gestation admitted for delivery METHODS: Data were stratified by SARS‐CoV‐2 result and symptomatic status, and summarized using parametric and nonparametric tests. MAIN OUTCOME MEASURES: Prevalence and outcomes of maternal COVID‐19; obstetric outcomes; neonatal SARS‐CoV‐2; placental pathology. RESULTS: Of 675 women admitted for delivery, 10.4% were positive for SARS‐CoV‐2, of whom 78.6% were asymptomatic. We observed differences in sociodemographics and comorbidities between women with symptomatic vs. asymptomatic vs. no COVID‐19. Cesarean delivery rates were 46.7% in symptomatic COVID‐19, 45.5% in asymptomatic COVID‐19, and 30.9% without COVID‐19 (p=0.044). Postpartum complications (fever, hypoxia, readmission) occurred in 12.9% of women with COVID‐19 vs 4.5% of women without COVID‐19 (p<0.001). No woman required mechanical ventilation, and no maternal deaths occurred. Among 71 infants tested, none were positive for SARS‐CoV‐2. Placental pathology demonstrated increased frequency of fetal vascular malperfusion, indicative of thrombi in fetal vessels, in women with vs. without COVID‐19 (48.3% vs 11.3%, p <0.001). CONCLUSION: Among pregnant women with COVID‐19 at delivery, we observed increased cesarean delivery rates and increased frequency of maternal complications in the postpartum period. Additionally, intraplacental thrombi may have maternal and fetal implications for COVID‐19 infections remote from delivery.


title: A framework for open tracheostomy in COVID‐19 patients

text: The COVID-19 pandemic is causing untold disruption across the globe and all countries irrespective of the strength and resilience of their health systems are feeling the burden. Intensive care units are facing a surge of patients requiring invasive ventilation.It is likely that requests for a tracheostomy in COVID-19 ventilated patients will soon come our way. It is difficult to predict the burden, but it would be remiss not to be prepared.


title: Magnetic Lateral Flow Immunoassays

text: A new generation of magnetic lateral flow immunoassays is emerging as powerful tool for diagnostics. They rely on the use of magnetic nanoparticles (MNP) as detecting label, replacing conventional gold or latex beads. MNPs can be sensed and quantified by means of external devices, allowing the development of immunochromatographic tests with a quantitative capability. Moreover, they have an added advantage because they can be used for immunomagnetic separation (IMS), with improvements in selectivity and sensitivity. In this paper, we have reviewed the current knowledge on magnetic-lateral flow immunoassay (LFIA), coupled with both research and commercially available instruments. The work in the literature has been classified in two categories: optical and magnetic sensing. We have analysed the type of magnetic nanoparticles used in each case, their size, coating, crystal structure and the functional groups for their conjugation with biomolecules. We have also taken into account the analytical characteristics and the type of transduction. Magnetic LFIA have been used for the determination of biomarkers, pathogens, toxins, allergens and drugs. Nanocomposites have been developed as alternative to MNP with the purpose of sensitivity enhancement. Moreover, IMS in combination with other detection principles could also improve sensitivity and limit of detection. The critical analysis in this review could have an impact for the future development of magnetic LFIA in fields requiring both rapid separation and quantification.


title: The 5′-end sequence of the murine coronavirus genome: Implications for multiple fusion sites in leader-primed transcription

text: Abstract The coronavirus leader-primed transcription model proposes that free leader RNA species derived from the 5′-end of the genomic RNA are utilized as a primer for the transcription of subgenomic mRNAs. To elucidate the precise mechanism of leader-priming, we cloned and sequenced the 5′-end of the mouse hepatitis virus genomic RNA. The 5′-terminal sequences are identical to the leader sequences present at the 5′-end of the subgenomic mRNAs. Two possible hairpin loop structures and an AU-rich region around the 3′-end of the leader sequence may provide the termination site for leader RNA synthesis. The comparison of 5′-end genomic sequences and the intergenic start sites for mRNA transcription revealed that there are homologous regions of 7–18 nucleotides at the putative leader/body junction sites. Some intergenic regions contain a mismatching nucleotide within this homologous region. We propose that free leader RNA binds to the intergenic region due to this homology and is cleaved at the mismatching nucleotide before serving as a primer. Thus, the free leader RNA species may be longer than the leader sequences in the subgenomic mRNAs and different mRNAs may have different leader/body junction sites.


title: Antibody-dependent infection of human macrophages by severe acute respiratory syndrome coronavirus

text: BACKGROUND: Public health risks associated to infection by human coronaviruses remain considerable and vaccination is a key option for preventing the resurgence of severe acute respiratory syndrome coronavirus (SARS-CoV). We have previously reported that antibodies elicited by a SARS-CoV vaccine candidate based on recombinant, full-length SARS-CoV Spike-protein trimers, trigger infection of immune cell lines. These observations prompted us to investigate the molecular mechanisms and responses to antibody-mediated infection in human macrophages. METHODS: We have used primary human immune cells to evaluate their susceptibility to infection by SARS-CoV in the presence of anti-Spike antibodies. Fluorescence microscopy and real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) were utilized to assess occurrence and consequences of infection. To gain insight into the underlying molecular mechanism, we performed mutational analysis with a series of truncated and chimeric constructs of fragment crystallizable γ receptors (FcγR), which bind antibody-coated pathogens. RESULTS: We show here that anti-Spike immune serum increased infection of human monocyte-derived macrophages by replication-competent SARS-CoV as well as Spike-pseudotyped lentiviral particles (SARS-CoVpp). Macrophages infected with SARS-CoV, however, did not support productive replication of the virus. Purified anti-viral IgGs, but not other soluble factor(s) from heat-inactivated mouse immune serum, were sufficient to enhance infection. Antibody-mediated infection was dependent on signaling-competent members of the human FcγRII family, which were shown to confer susceptibility to otherwise naïve ST486 cells, as binding of immune complexes to cell surface FcγRII was necessary but not sufficient to trigger antibody-dependent enhancement (ADE) of infection. Furthermore, only FcγRII with intact cytoplasmic signaling domains were competent to sustain ADE of SARS-CoVpp infection, thus providing additional information on the role of downstream signaling by FcγRII. CONCLUSIONS: These results demonstrate that human macrophages can be infected by SARS-CoV as a result of IgG-mediated ADE and indicate that this infection route requires signaling pathways activated downstream of binding to FcγRII receptors.


title: Influenza early warning model based on Yunqi theory

text: OBJECTIVE: To establish an early warning model to simulate the outbreak of influenza based on weather conditions and Yunqi theory, an ancient calendar theory of Chinese medicine (CM). METHODS: Tianjin, a northeastern city in China, was chosen as the region of research and applied the influenza-like illness attack rate (ILI)% as the baseline and warning line to determine the severity of influenza epidemic. Then, an influenza early warning model was constructed based on the theory of rough set and support vector machines (RS-SVM), and the relationship between influenza and meteorology was explored through analyzing the monitoring data. RESULTS: The predictive performance of the model was good, which had achieved 81.8% accuracy when grouping the obtained data into three levels that represent no danger, danger of a light epidemic, and danger of a severe epidemic. The test results showed that if the host qi and guest qi were not balanced, this kind of situation was more likely to cause influenza outbreaks. CONCLUSIONS: The outbreak of influenza closely relates to temperature, humidity, visibility, and wind speed and is consistent with some part of CM doctrine. The result also indicates that there is some reasonable evidence in the Yunqi theory.


Impact of the Covid-19 Pandemic and Lung Transplantation Program in France


title: Contribution of the FilmArray Respiratory Panel in the management of adult and pediatric patients attending the emergency room during 2015–2016 influenza epidemics: An interventional study

text: Abstract Aim To evaluate the contribution of a multiplex PCR for respiratory viruses on antibiotic and antiviral prescription, ancillary test prescription, admission and length of stay of patients. Methods Two hundred ninety-one adult and pediatric patients visiting the emergency department during the 2015–2016 influenza epidemic were prospectively included and immediately tested 24/7 using the FilmArray Respiratory Panel. The results were communicated to the practitioner in charge as soon as they became available. Clinical and biological data were gathered and analyzed. Findings Results from the FilmArray Respiratory Panel do not appear to impact admission or antibiotic prescription, with the exception of a lower admission rate for children who tested positive for influenza B. Parameters that account for the clinical decisions evaluated are CRP level, white blood cell count, suspected or proven bacterial infection and, for adult patients only, signs of respiratory distress. Length of stay is also not significantly different between patients with a positive and a negative result. A rapid influenza test result permits a more appropriate prescription of oseltamivir.


title: Addressing the Gaps in Preparation for Quarantine

text: INTRODUCTION: In the event of an outbreak of a communicable respiratory illness, quarantine may become necessary. The New York Institute for All Hazard Preparedness (NYIAHP) of the State University of New York (SUNY) Downstate Medical Center, in cooperation with the New York City Department of Health and Mental Hygiene's Healthcare Emergency Preparedness Program, (NYC DOHMH-HEPP) quarantine working group, has developed a series of clinical protocols to help health care facilities respond to such an event. PROBLEM: Two full-scale exercises (FSEs) were designed and conducted a year apart in the quarantine unit at Kings County Hospital Center (KCHC) to test the efficacy and feasibility of these quarantine protocols. The goal of these exercises was to identify the gaps in preparedness for quarantine and increase hospital readiness for such an event. METHODS: Evaluators monitored for efficient management of critical physical plants, personnel and material resources. Players were expected to integrate and practice emergency response plans and protocols specific to quarantine. In developing the exercise objectives, five activities were selected for evaluation: Activation of the Unit, Staffing, Charting/Admission, Symptom Monitoring and Infection Control, and Client Management. RESULTS: The results of the initial FSE found that there were incomplete critical tasks within all five protocols: These deficiencies were detailed in an After Action Report and an Improvement Plan was presented to the KCHC Disaster Preparedness Committee a month after the initial FSE. In the second FSE a year later, all critical tasks for Activation of the unit, Staffing and Charting/Admission were achieved. Completion of critical tasks related to Symptom Monitoring and Infection Control and Client Management was improved in the second FSE, but some tasks were still not performed appropriately. CONCLUSION: In short, these exercises identified critical needs in disaster preparedness of the KCHC Quarantine Unit. The lessons learned from this logistical exercise enabled the planning group to have a better understanding of leadership needs, communication capabilities, and infection control procedures. Kings County Hospital Center performed well during these exercises. It was clear that performance in the second exercise was improved, and many problems noted in the first exercise were corrected. Staff also felt better prepared the second time. This supports the idea that frequent exercises are vital to maintain disaster readiness. R Nathawad, PM Roblin, D Pruitt, B Arquilla. Addressing the gaps in preparation for quarantine. Prehosp Disaster Med. 2013;28(2):1-7 23158909.


title: Exploration of alternative supply chains and distributed manufacturing in response to COVID-19; a case study of medical face shields

text: Abstract Quarantine conditions arising as a result of the coronavirus (COVID-19) have had a significant impact on global production-rates and supply chains. This has coincided with increased demands for medical and personal protective equipment such as face shields. Shortages have been particularly prevalent in western countries which typically rely upon global supply chains to obtain these types of device from low-cost economies. National calls for the repurposing of domestic mass-production facilities have the potential to meet medical requirements in coming weeks, however the immediate demand associated with the virus has led to the mobilisation of a diverse distributed workforce. Selection of appropriate manufacturing processes and underused supply chains is paramount to the success of these operations. A simplified medical face shield design is presented which repurposes an assortment of existing alternative supply chains. The device is easy to produce with minimal equipment and training. It is hoped that the methodology and approach presented is of use to the wider community at this critical time.


title: Identification of α-fodrin as an autoantigen in experimental coronavirus retinopathy (ECOR)

text: Abstract The coronavirus, mouse hepatitis virus (MHV), JHM strain induces a biphasic disease in BALB/c mice that consists of an acute retinitis followed by progression to a chronic retinal degeneration with autoimmune reactivity. Retinal degeneration resistant CD-1 mice do not develop either the late phase or autoimmune reactivity. A mouse RPE/choroid DNA expression library was screened using sera from virus infected BALB/c mice. Two clones were identified, villin-2 protein and α-fodrin protein. α-Fodrin protein was used for further analysis and western blot reactivity was seen only in sera from virus infected BALB/c mice. CD4 T cells were shown to specifically react with MHV antigens and with α-fodrin protein. These studies clearly identified both antibody and CD4 T cell reactivities to α-fodrin in sera from virus infected, retinal degenerative susceptible BALB/c mice.


title: The Role of the Laboratory and Transfusion Service in the Management of Ebola Virus Disease

text: Abstract The Ebola outbreak that began in 2013 infected and killed record numbers of individuals and created unprecedented challenges, including containment and treatment of the virus in resource-strained West Africa as well as the repatriation and treatment for patients in the United States and Europe. Valuable lessons were learned, especially the important role that the laboratory and transfusion service plays in the treatment for patients with Ebola virus disease (EVD) by providing data for supportive care and fluid resuscitation as well as the generation of investigational therapies such as convalescent plasma (CP). To provide treatment support, laboratories had to evaluate and update procedures to ensure the safety of laboratory personnel. Because there is no licensed EVD-specific treatment, CP was used in more than 99 patients with only 1 possible severe adverse event reported. However, given the biologic variability inherent in CP as well as the small number of patient treated in a nonrandomized fashion, the efficacy of CP in the treatment of EVD remains unknown.


title: Use of personal protective equipment to protect against respiratory infections in Pakistan: A systematic review

text: Abstract Like other low-income countries, limited data are available on the use of personal protective equipment (PPE) in Pakistan. We conducted a systematic review of studies on PPE use for respiratory infections in healthcare settings in Pakistan. MEDLINE, Embase and Goggle Scholar were searched for clinical, epidemiological and laboratory-based studies in English, and 13 studies were included; all were observational/cross-sectional studies. The studies examined PPE use in hospital (n=7), dental (n=4) or laboratory (n=2) settings. Policies and practices on PPE use were inconsistent. Face masks and gloves were the most commonly used PPE to protect from respiratory and other infections. PPE was not available in many facilities and its use was limited to high-risk situations. Compliance with PPE use was low among healthcare workers, and reuse of PPE was reported. Clear policies on the use of PPE and available PPE are needed to avoid inappropriate practices that could result in the spread of infection. Large, multimethod studies are recommended on PPE use to inform national infection-control guidelines.


title: Clinical Characteristics of Patients With Coronavirus Disease 2019 (COVID-19) Receiving Emergency Medical Services in King County, Washington

text: IMPORTANCE: The ability to identify patients with coronavirus disease 2019 (COVID-19) in the prehospital emergency setting could inform strategies for infection control and use of personal protective equipment. However, little is known about the presentation of patients with COVID-19 requiring emergency care, particularly those who used 911 emergency medical services (EMS). OBJECTIVE: To describe patient characteristics and prehospital presentation of patients with COVID-19 cared for by EMS. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included 124 patients who required 911 EMS care for COVID-19 in King County, Washington, a large metropolitan region covering 2300 square miles with 2.2 million residents in urban, suburban, and rural areas, between February 1, 2020, and March 18, 2020. EXPOSURES: COVID-19 was diagnosed by reverse transcription–polymerase chain reaction detection of severe acute respiratory syndrome coronavirus 2 from nasopharyngeal swabs. Test results were available a median (interquartile range) of 5 (3-9) days after the EMS encounter. MAIN OUTCOMES AND MEASURES: Prevalence of clinical characteristics, symptoms, examination signs, and EMS impression and care. RESULTS: Of the 775 confirmed COVID-19 cases in King County, EMS responded to 124 (16.0%), with a total of 147 unique 911 encounters. The mean (SD) age was 75.7 (13.2) years, 66 patients (53.2%) were women, 47 patients (37.9%) had 3 or more chronic health conditions, and 57 patients (46.0%) resided in a long-term care facility. Based on EMS evaluation, 43 of 147 encounters (29.3%) had no symptoms of fever, cough, or shortness of breath. Based on individual examination findings, fever, tachypnea, or hypoxia were only present in a limited portion of cases, as follows: 43 of 84 encounters (51.2%), 42 of 131 (32.1%), and 60 of 112 (53.6%), respectively. Advanced care was typically not required, although in 24 encounters (16.3%), patients received care associated with aerosol-generating procedures. As of June 1, 2020, mortality among the study cohort was 52.4% (65 patients). CONCLUSIONS AND RELEVANCE: The findings of this cohort study suggest that screening based on conventional COVID-19 symptoms or corresponding examination findings of febrile respiratory illness may not possess the necessary sensitivity for early diagnostic suspicion, at least in the prehospital emergency setting. The findings have potential implications for early identification of COVID-19 and effective strategies to mitigate infectious risk during emergency care.


title: Nucleotide composition of the Zika virus RNA genome and its codon usage

text: BACKGROUND: RNA viruses have genomes with a distinct nucleotide composition and codon usage. We present the global characteristics of the RNA genome of Zika virus (ZIKV), an emerging pathogen within the Flavivirus genus. ZIKV was first isolated in 1947 in Uganda, caused a widespread epidemic in South and Central America and the Caribbean in 2015 and has recently been associated with microcephaly in newborns. METHODS: The nearly 11 kb positive-stranded RNA genome of ZIKV was analyzed for its nucleotide composition, also in the context of the folded RNA molecule. Nucleotide trends were investigated along the genome length by skew analyses and we analyzed the codons used for translation of the ZIKV proteins. RESULTS: ZIKV RNA has a biased nucleotide composition in being purine-rich and pyrimidine-poor. This preference for purines is a general characteristic of the mosquito-borne and tick-borne flaviviruses. The virus-specific nucleotide bias is further enriched in the unpaired, single-stranded regions of the structured ZIKV RNA genome, thus further imposing this ZIKV-specific signature. The codons used for translation of the ZIKV proteins is also unusual, but we show that it is the underlying bias in nucleotide composition of the viral RNA that largely dictates these codon preferences. CONCLUSIONS: The ZIKV RNA genome has a biased nucleotide composition that dictates the codon usage of this flavivirus. We discuss the evolutionary scenarios and molecular mechanisms that may be responsible for these distinctive ZIKV RNA genome features.


title: The use of non-invasive ventilation during acute respiratory failure due to pneumonia

text: Abstract The use of non-invasive ventilation in patients with community-acquired pneumonia is controversial since this is associated with high rates of treatment failure, compared with other causes of severe acute respiratory failure. The populations of patients with community-acquired pneumonia who have demonstrated better response to non-invasive ventilation are those with previous cardiac or respiratory disease, particularly chronic obstructive pulmonary disease. By contrast, the use of non-invasive ventilation in patients with community-acquired pneumonia without these pre-existing diseases should be very cautious and under strict monitoring conditions, since there are increasing evidences that the unnecessary delay in intubation of those patients who fail treatment with non-invasive ventilation is associated with lower survival. Pulmonary complications of immunosuppressed patients are associated with high rates of intubation and mortality. The use of non-invasive ventilation in these patients may decrease the need for intubation and improve the poor outcome associated with these complications. Continuous positive airway pressure has been used to treat acute respiratory failure in several conditions characterised by alveolar collapse. While this is extremely useful in patients with acute cardiogenic pulmonary oedema, the efficacy in pneumonia seems limited to immunosuppressed patients with pulmonary complications. Conversely, there are no sufficient evidences on the efficacy of continuous positive airway pressure in immunocompetent patients with pneumonia and severe acute respiratory failure.


PROPOSED USE OF THALIDOMIDE FOR THE CYTOKINE STORM OF COVID-19


title: What can vaccines learn from aviation?

text: • The global pharmaceutical industry is a highly regulated sector. • Stark absence of global harmony in these regulatory processes. • Efforts taken to bring global uniformity, but is far from successful. • Highly regulated aviation industry enjoys globally harmonized regulatory processes. • Shout out to international authorities to take a cue from aviation sector. • This will ensure introduction of best vaccines and timely availability for patients.


title: Repurposing of chloroquine and some clinically approved antiviral drugs as effective therapeutics to prevent cellular entry and replication of coronavirus

text: The reemergence of coronavirus prompts the need for the development of effective therapeutics to prevent the cellular entry and replication of coronavirus. This study demonstrated the putative inhibitory potential of lopinavir, remdesivir, oseltamir, azithromycin, ribavirin, and chloroquine towards V-ATPase, protein kinase A, SARS-CoV spike glycoprotein/ACE-2 complex and viral proteases. The pharmacodynamic and pharmacokinetic properties were predicted through the pkCSM server while the corresponding binding affinity of the selected drugs towards the proteins was computed using AutodockVina Screening tool. The ADMET properties revealed all the drugs possess drug-like properties. Lopinavir has the highest binding affinities to the pocket site of SARS-CoV spike glycoprotein/ACE-2 complex, cyclic AMP-dependent protein kinase A and 3-Chymotrypsin like protease while redemsivir has the highest binding affinities for vacuolar proton-translocating ATPase (V-ATPase) and papain-like proteins. The amino acids Asp269, Leu370, His374, and His345 were predicted as the key residues for lopinavir binding to human SARS-CoV spike glycoprotein/ACE-2 complex while His378, Tyr515, Leu73, Leu100, Phe32 and Phe40 for remdesivir and Tyr510, Phe504, Met62, Tyr50, and His378 were predicted for azithromycin as the key residues for binding to SARS-CoV spike glycoprotein/ACE-2 complex. Moreover, it was also observed that chloroquine has appreciable binding affinities for 3-Chymotrpsin- like protease and cyclic AMP-dependent protein kinase A when compared to Oseltamivir and ribavirin. The study provided evidence suggesting putative repurposing of the selected drugs for the development of valuable drugs for the prevention of cellular entry and replication of coronavirus. Communicated by Ramaswamy H. Sarma


title: Interpreting whole genome sequencing for investigating tuberculosis transmission: a systematic review

text: BACKGROUND: Whole genome sequencing (WGS) is becoming an important part of epidemiological investigations of infectious diseases due to greater resolution and cost reductions compared to traditional typing approaches. Many public health and clinical teams will increasingly use WGS to investigate clusters of potential pathogen transmission, making it crucial to understand the benefits and assumptions of the analytical methods for investigating the data. We aimed to understand how different approaches affect inferences of transmission dynamics and outline limitations of the methods. METHODS: We comprehensively searched electronic databases for studies that presented methods used to interpret WGS data for investigating tuberculosis (TB) transmission. Two authors independently selected studies for inclusion and extracted data. Due to considerable methodological heterogeneity between studies, we present summary data with accompanying narrative synthesis rather than pooled analyses. RESULTS: Twenty-five studies met our inclusion criteria. Despite the range of interpretation tools, the usefulness of WGS data in understanding TB transmission often depends on the amount of genetic diversity in the setting. Where diversity is small, distinguishing re-infections from relapses may be impossible; interpretation may be aided by the use of epidemiological data, examining minor variants and deep sequencing. Conversely, when within-host diversity is large, due to genetic hitchhiking or co-infection of two dissimilar strains, it is critical to understand how it arose. Greater understanding of microevolution and mixed infection will enhance interpretation of WGS data. CONCLUSIONS: As sequencing studies have sampled more intensely and integrated multiple sources of information, the understanding of TB transmission and diversity has grown, but there is still much to be learnt about the origins of diversity that will affect inferences from these data. Public health teams and researchers should combine epidemiological, clinical and WGS data to strengthen investigations of transmission. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-016-0566-x) contains supplementary material, which is available to authorized users.


title: Serological and molecular evidence that canine respiratory coronavirus is circulating in Italy

text: Abstract Canine respiratory coronavirus (CRCoV) is a group II coronavirus that was firstly identified in lung samples of dogs with canine infectious respiratory disease (CIRD) in UK in 2003. We report for the first time the identification of CRCoV in Italy, together with serological evidence that the virus has been circulating in the Italian dog population as from 2005. Serological investigations on 216 dog sera, carried out by an ELISA test using the strictly related bovine coronavirus (BCoV) as antigen, revealed an overall CRCoV seroprevalence of 32.06% in the last 2 years. RT-PCR targeting the S-gene of CRCoV was carried out on 109 lung samples collected from carcasses of dogs submitted for diagnostic investigations. Positive results were obtained from the lungs of a dog of the Apulia region that was co-infected with canine parvovirus type 2. Sequence analysis of the S-gene fragment amplified by RT-PCR (595bp) showed similarity to group II coronaviruses, with the highest nucleotide identity (98%) to the only CRCoV strain currently available in the GenBank database (strain T101). The results of the present study show that CRCoV is present also in continental Europe, although further studies are required to determine the real pathogenic potential of the virus.


title: Lupus-Induced Vasculitis and Multiple Organ Dysfunction Syndrome as the First Presentation of Systemic Lupus Erythematosus (SLE) in Pregnancy

text: Patient: Female, 21-year-old Final Diagnosis: Diffuse alveolar hemorrhage Symptoms: Cough • dyspnea • fever • rash • sore throat Medication: — Clinical Procedure: — Specialty: Rheumatology OBJECTIVE: Rare disease Background: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production leading to inflammation in multiple organs; it commonly affects young women in their child-bearing years. Clinical manifestations are diverse and range from mild arthritis to diffuse alveolar hemorrhage (DAH). DAH is a rare and devastating complication of SLE that carries a mortality rate of up to 50%, despite aggressive therapy. CASE REPORT: A 21-year-old primigravida at 16 weeks gestation presents with a productive cough, rash, sore throat, and high-grade fever. Chest x-ray suggested multifocal pneumonia. Patient deteriorated despite antibiotics and intravenous (IV) fluids. She developed worsening anemia, leukopenia, and thrombocytopenia. Autoimmune work-up was positive for Coombs, antinuclear antibody, anti-smith antibody, and hypocomplementemia. Skin biopsy was consistent with SLE. SLE vasculitis was suspected. She required mechanical intubation for rapid respiratory deterioration, with CT thorax suggesting ARDS. Bronchoscopy was done and confirmed DAH. Her course was further complicated with retinopathy and acute pancreatitis associated with SLE. She was treated with IV steroids, IV cyclophosphamide, and plasmapheresis, with significant clinical improvement and successful extubation. She delivered a healthy baby at 32 weeks gestation. CONCLUSIONS: Early recognition and initiation of treatment is critical to survival in DAH and requires a high index of clinical suspicion. Treatment includes high-dose steroids, cyclophosphamide, and plasma exchange. Pregnancy increases the risk of adverse outcome in SLE. Seven cases of DAH in pregnant patients with SLE have been reported. Here, we report a catastrophic presentation of DAH, acute pancreatitis, and retinopathy in a pregnant patient with newly diagnosed SLE.


title: Budded baculovirus particle structure revisited

text: Abstract Baculoviruses are a group of enveloped, double-stranded DNA insect viruses with budded (BV) and occlusion-derived (ODV) virions produced during their infection cycle. BVs are commonly described as rod shaped particles with a high apical density of protein extensions (spikes) on the lipid envelope surface. However, due to the fragility of BVs the conventional purification and electron microscopy (EM) staining methods considerably distort the native viral structure. Here, we use cryo-EM analysis to reveal the near-native morphology of two intensively studied baculoviruses, Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) and Spodoptera exigua MNPV (SeMNPV), as models for BVs carrying GP64 and F as envelope fusion protein on the surface. The now well-preserved AcMNPV and SeMNPV BV particles have a remarkable elongated, ovoid shape leaving a large, lateral space between nucleocapsid (NC) and envelope. Consistent with previous findings the NC has a distinctive cap and base structure interacting tightly with the envelope. This tight interaction may explain the partial retaining of the envelope on both ends of the NC and the disappearance of the remainder of the BV envelope in the negative-staining EM images. Cryo-EM also reveals that the viral envelope contains two layers with a total thickness of ≈6–7nm, which is significantly thicker than a usual biological membrane (<4nm) as measured by X-ray scanning. Most spikes are densely clustered at the two apical ends of the virion although some envelope proteins are also found more sparsely on the lateral regions. The spikes on the surface of AcMNPV BVs appear distinctly different from those of SeMNPV. Based on our observations we propose a new near-native structural model of baculovirus BVs.


title: Outbreak dynamics of COVID-19 in China and the United States

text: On March 11, 2020, the World Health Organization declared the coronavirus disease 2019, COVID-19, a global pandemic. In an unprecedented collective effort, massive amounts of data are now being collected worldwide to estimate the immediate and long-term impact of this pandemic on the health system and the global economy. However, the precise timeline of the disease, its transmissibility, and the effect of mitigation strategies remain incompletely understood. Here we integrate a global network model with a local epidemic SEIR model to quantify the outbreak dynamics of COVID-19 in China and the United States. For the outbreak in China, in [Formula: see text] provinces, we found a latent period of 2.56 ± 0.72 days, a contact period of 1.47 ± 0.32 days, and an infectious period of 17.82 ± 2.95 days. We postulate that the latent and infectious periods are disease-specific, whereas the contact period is behavior-specific and can vary between different provinces, states, or countries. For the early stages of the outbreak in the United States, in [Formula: see text] states, we adopted the disease-specific values from China and found a contact period of 3.38 ± 0.69 days. Our network model predicts that—without the massive political mitigation strategies that are in place today—the United States would have faced a basic reproduction number of 5.30 ± 0.95 and a nationwide peak of the outbreak on May 10, 2020 with 3 million infections. Our results demonstrate how mathematical modeling can help estimate outbreak dynamics and provide decision guidelines for successful outbreak control. We anticipate that our model will become a valuable tool to estimate the potential of vaccination and quantify the effect of relaxing political measures including total lockdown, shelter in place, and travel restrictions for low-risk subgroups of the population or for the population as a whole.


Reply (by Kevin Welch) to Zara Patel Correspondence


title: In focus: molecular and cell biology research in China

text: An interactive, intellectual environment with good funding opportunities is essential for the development and success of basic research. The fast-growing economy and investment in science, together with a visionary plan, have attracted foreign scholars to work in China, motivated world-class Chinese scientists to return and strengthened the country's international collaborations. As a result, molecular and cell biology research in China has evolved rapidly over the past decade. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrm3638) contains supplementary material, which is available to authorized users.


title: The Molecular Genetics of Feline Coronaviruses: Comparative Sequence Analysis of the ORF7a/7b Transcription Unit of Different Biotypes

text: Abstract Feline coronaviruses (FCoVs) have been subdivided into feline enteric coronaviruses (FECVs) and feline infectious peritonitis viruses (FIPVs) on the basis of pathogenic properties. Serologically, a distinction has been made between type I and II FCoVs, the latter of which more closely resemble canine coronavirus (CCV). To gain more insight into the genetic relationships between different FCoV biotypes, we determined the nucleotide sequences of the ORF7a/7b transcription unit of nine strains. The following observations were made: (i) The sequences are 87-100% identical. In this part of the genome, type I and II FCoVs are more closely related to each other than to CCV. To explain the genetic and antigenic differences between the spike genes of type I and II FCoVs, we postulate that type II FCoVs have arisen by an RNA recombination event between a type I FCoV and CCV. (ii) The avirulent "FECV" strains UCD and 79-1683 are more similar to virulent "FIPV" strains than to each other. Our findings thus support the notion that FECV and FIPV are not different species but merely virulence variants. (iii) In contrast to FECV 79-1683, FECV UCD contains an intact ORF7b, indicating that ORF7b deletions are not a universal distinguishing property of FECVs. (iv) ORF7b deletions readily occur in vitro, correlating with loss of virulence. By reverse transcription polymerase chain reaction analysis, we show that in naturally occurring FCoVs ORF7b is maintained Thus, ORF7b seems to provide a distinct selective advantage during natural infection.


title: Structural basis of SARS-CoV-2 3CLpro and anti-COVID-19 drug discovery from medicinal plants †

text: Abstract The recent outbreak of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 in December 2019 raised global health concerns. The viral 3-chymotrypsin-like cysteine protease (3CLpro) enzyme controls coronavirus replication and is essential for its life cycle. 3CLpro is a proven drug discovery target in the case of severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV). Recent studies revealed that the genome sequence of SARS-CoV-2 is very similar to that of SARS-CoV. Therefore, herein, we analysed the 3CLpro sequence, constructed its 3D homology model, and screened it against a medicinal plant library containing 32,297 potential anti-viral phytochemicals/traditional Chinese medicinal compounds. Our analyses revealed that the top nine hits might serve as potential anti- SARS-CoV-2 lead molecules for further optimisation and drug development process to combat COVID-19.


Correlating Cell Line Studies With Tissue Distribution of DPP4/TMPRSS2 and Human Biological Samples May Better Define the Viral Tropism of MERS-CoV


title: Neuroleptic malignant syndrome in patients with COVID-19

text: We report the first two cases of Coronavirus Disease 2019 (COVID-19) who were receiving intensive care including favipiravir, and were clinically diagnosed with neuroleptic malignant syndrome (NMS) to focus attention on NMS in COVID-19 management. Case 1: A 46-year-old-man with acute respiratory distress syndrome (ARDS) caused by COVID-19 infection was being administered favipiravir. Fentanyl, propofol, and rocuronium were also given. On day 3, midazolam administration was initiated for deep sedation. On day 5, his high body temperature increased to 41.2 °C, creatine kinase level elevated, and he developed tachycardia, tachypnea, altered consciousness, and diaphoresis. NMS was suspected, and supportive therapy was initiated. High-grade fever persisted for 4 days and subsided on day 9. Case 2: A 44-year-old-man with ARDS caused by COVID-19 infection was being treated with favipiravir. On day 5, risperidone was started for delirium. On day 7, his body temperature suddenly increased to 40.8 °C, his CK level elevated, and he developed tachycardia, tachypnea, altered consciousness, and diaphoresis. NMS diagnosis was confirmed, and both, favipiravir and risperidone were discontinued on day 8. On the same day, his CK levels decreased, and his body temperature normalized on day 9. Patients with COVID-19 infection frequently require deep sedation and develop delirium; therefore, more attention should be paid to the development of NMS in patients who are being administered such causative agents. The mechanism underlying the occurrence of NMS in COVID-19 patients treated with favipiravir remains unknown. Therefore, careful consideration of NMS development is necessary in the management of COVID-19 patients.


title: COVID‐19 Interconnectedness: Health Inequity, the Climate Crisis, and Collective Trauma

text: The COVID‐19 pandemic brings to the forefront the complex interconnected dilemmas of globalization, health equity, economic security, environmental justice, and collective trauma, severely impacting the marginalized and people of color in the United States. This lack of access to and the quality of healthcare, affordable housing, and lack of financial resources also continue to have a more significant impact on documented and undocumented immigrants. This paper aims at examining these critical issues and developing a framework for family therapists to address these challenges by focusing on four interrelated dimensions: cultural values, social determinants of health, collective trauma, and the ethical and moral responsibility of family therapists. Given the fact that family therapists may unwittingly function as the best ally of an economic and political system that perpetuates institutionalized racism and class discrimination, we need to utilize a set of principles, values, and practices that are not just palliative or after the fact but bring forth into the psychotherapeutic and policy work a politics of care. Therefore, a strong call to promote and advocate for the broader continuum of health and critical thinking preparing professionals to meet the challenges of health equity, as well as economic and environmental justice, are needed. The issues discussed in this paper are specific to the United States despite their relevance to family therapy as a field. We are mindful not to generalize the United States' reality to the rest of the world, recognizing that issues discussed in this paper could potentially contribute to international discourse.


title: Genetic characteristics, pathogenicity, and immunogenicity associated with cell adaptation of a virulent genotype 2b porcine epidemic diarrhea virus

text: Abstract Porcine epidemic diarrhea virus (PEDV) has emerged or re-emerged worldwide, posing a significant financial threat to major pig-producing countries. In the present study, a virulent Korean pandemic PEDV strain, KNU-141112, was serially propagated in Vero cells for up to 100 passages. Through cell culture adaptation, we obtained four distinct deletion (DEL) mutants by plaque purification followed by nucleotide sequencing of the spike (S)/ORF3 gene-coding region, which were designated KNU-141112-S DEL2, −S DEL5, −S DEL2/ORF3, and −S DEL5/ORF3. Further whole genome sequencing identified 12 or 14 amino acid changes in the cell-adapted DEL strains. Animal inoculation studies revealed that the virulence of both S DEL2/ORF3 and S DEL5/ORF3 viruses with a large 46-nt deletion in the intergenic portion of S and ORF3 was remarkably diminished, indicating viral attenuation in the natural host. Furthermore, these cell-adapted strains elicited potent neutralizing antibody responses in immunized pigs. Taken together, our data indicate that the cell-attenuated S DEL2/ORF3 and S DEL5/ORF3 strains are promising candidates for the development of a safe and effective live PEDV vaccine.


14 Fever Without Localizing Signs


title: Metallo-aminopeptidase inhibitors

text: Aminopeptidases are enzymes that selectively hydrolyze an amino acid residue from the N-terminus of proteins and peptides. They are important for the proper functioning of prokaryotic and eukaryotic cells, but very often are central players in the devastating human diseases like cancer, malaria and diabetes. The largest aminopeptidase group include enzymes containing metal ion(s) in their active centers, which often determines the type of inhibitors that are the most suitable for them. Effective ligands mostly bind in a non-covalent mode by forming complexes with the metal ion(s). Here, we present several approaches for the design of inhibitors for metallo-aminopeptidases. The optimized structures should be considered as potential leads in the drug discovery process against endogenous and infectious diseases.


title: Post-Traumatic Stress Disorder Among Health Care Providers Following the Israeli Attacks Against Gaza Strip in 2014: A Call for Immediate Policy Actions

text: Abstract Purpose This study aimed to assess the level of posttraumatic stress disorder and to examine the relationship between exposure to war stress and posttraumatic symptoms among health care providers following Israeli offensives against Gaza Strip in 2014. Methodology A cross-sectional design was used for this study. We targeted all nurses and doctors working in three governmental hospitals in the Gaza Strip and worked with victims of the last war, more specifically, those who were working in emergency departments, intensive care units, operating rooms, surgical departments, and burn units. A demographic sheet and Impact Event Scale–Revised were used in this study. The Impact Event Scale–Revised has three sub-scales; intrusion, avoidance, and hyper-arousal. Results The results showed that 291 (89.8%) of 324 participants had scores more than 35 (threshold cut-off point) on the Impact Event Scale–Revised. Scores ranged from zero to 80 with a mean of 52.13. Females had higher levels of stress (55.79) than males (51.63) and nurses (54.85) had more stress than physicians (47.38). The most frequent symptoms of trauma subscales was “avoidance” (mean=20.04), followed by “intrusion” (mean=17.83), and then “hyper-arousal” (mean=14.27). Levels of trauma symptoms were not affected by place of living, hospital of work, while level of education had impacted level of trauma. Conclusion The findings showed that health care providers suffered from severe posttraumatic symptoms after exposure to prolonged war stress. This level of trauma among health care providers warrants intervention programs to reduce stress and trauma among Gaza health care providers after the war.


title: Genomic characteristics and pathogenicity of natural recombinant porcine reproductive and respiratory syndrome virus 2 harboring genes of a Korean field strain and VR-2332-like strain

text: Abstract Porcine reproductive and respiratory syndrome (PRRS), an economically-important disease caused by PRRS virus (PRRSV), has become endemic to most pig-producing countries. Point mutation and recombination are responsible for genetic heterogeneity, resulting in circulation of genetically-diverse strains. However, no natural recombinant PRRSV has yet been identified in Korea. Here, we successfully isolated natural recombinant PRRSV-2 (KU-N1202) using cell culture, investigated its genomic characteristics, and further evaluated its pathogenicity. KU-N1202 is a recombinant strain between Korean MN184-like and VR-2332-like strains. Specifically, ORF5 to partial ORF7 of the VR-2332-like strain was inserted into the backbone of a CP07-626-2-like strain. KU-N1202 induced mild-to-moderate clinical signs and mild histopathological changes with low viral loads in challenged pigs. Contact pigs showed minimal clinical signs and lower viral loads than those in the challenge group. This study demonstrates the genomic characteristics and pathogenicity of natural recombinant PRRSV-2, illustrating the potential importance of recombination in the field.


title: Traditional Chinese Medicine Diagnosis “Yang-Xu Zheng”: Significant Prognostic Predictor for Patients with Severe Sepsis and Septic Shock

text: Pathogenesis of sepsis includes complex interaction between pathogen activities and host response, manifesting highly variable signs and symptoms, possibly delaying diagnosis and timely life-saving interventions. This study applies traditional Chinese medicine (TCM) Zheng diagnosis in patients with severe sepsis and septic shock to evaluate its adaptability and use as an early predictor of sepsis mortality. Three-year prospective observational study enrolled 126 septic patients. TCM Zheng diagnosis, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and blood samples for host response cytokines measurement (tumor necrosis factor-α, Interleukin-6, Interleukin-8, Interleukin-10, Interleukin-18) were collected within 24 hours after admission to Intensive Care Unit. Main outcome was 28-day mortality; multivariate logistic regression analysis served to determine predictive variables of the sepsis mortality. APACHE II score, frequency of Nutrient-phase heat, and Qi-Xu and Yang-Xu Zhengs were significantly higher in nonsurvivors. The multivariate logistic regression analysis identified Yang-Xu Zheng as the outcome predictor. APACHE II score and levels of five host response cytokines between patients with and without Yang-Xu Zheng revealed significant differences. Furthermore, cool extremities and weak pulse, both diagnostic signs of Yang-Xu Zheng, were also proven independent predictors of sepsis mortality. TCM diagnosis “Yang-Xu Zheng” may provide a new mortality predictor for septic patients.


title: Fecal transmission in COVID‐19: A potential shedding route

text: We read with interest recent article by Zhang et al 1 on the diagnosis of Coronavirus disease 2019 (COVID-19) by fecal specimen test. Following the recent outbreak of pneumonia with unknown pathogen in Hubei province in China, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolated from human airway epithelial cells and the disease was named COVID-19.2 It is a public health emergency of international concern and rapidly spearing all over the world.3 This article is protected by copyright. All rights reserved.


title: Spatial and space-time clustering and demographic characteristics of human nontyphoidal Salmonella infections with major serotypes in Toronto, Canada

text: Nontyphoidal Salmonella enterica (NTS) causes a substantial health burden to human populations in Canada and worldwide. Exposure sources and demographic factors vary by location and can therefore have a major impact on salmonellosis clustering. We evaluated major NTS serotypes: S. Enteritidis (n = 620), S. Typhimurium (n = 150), S. Thompson (n = 138), and S. Heidelberg (n = 136) reported in the city of Toronto, Canada, between January 1, 2015, and December 31, 2017. Cases were analyzed at the forward sortation area (FSA)—level (an area indicated by the first three characters of the postal code). Serotype-specific global and local clustering of infections were evaluated using the Moran's I method. Spatial and space-time clusters were investigated using Poisson and multinomial scan statistic models. Case-case analyses using a multinomial logistic regression model was conducted to compare seasonal and demographic factors among the different serotypes. High infection rate FSAs clustered in the central region of Toronto for S. Enteritidis, in the south-central region for S. Typhimurium, in north-west region for S. Thompson, and in the south-east region for S. Heidelberg. The relative risk ratio of S. Enteritidis infections was significantly higher in cases who reported travel outside of Ontario. The relative risk ratio of infections was significantly higher in summer for S. Typhimurium, and in fall for S. Thompson. The relative risk ratio of infection was highest for the 0–9 age group for S. Typhimurium, and the 20–39 age group for S. Heidelberg. Our study will aid public health stakeholders in designing serotype-specific geographically targeted disease prevention programs.


title: Preventing transmission among operating room staff during COVID-19 pandemic: the role of the Aerosol Box and other personal protective equipment

text: The COVID-19 pandemic is highly challenging for the operating room staff and healthcare workers in emergency departments. SARS-CoV-2 is a positive-sense single-stranded RNA beta-coronavirus that primarily targets the human respiratory system, with fever, cough, myalgia, and pneumonia as the most common manifestations. However, since SARS-CoV-2 RNA was detected in stool specimens much more attention has been paid to gastrointestinal symptoms such as loss of appetite, nausea, and diarrhea. Furthermore, the expression of ACE-2 receptors in absorptive enterocytes from ileum and colon suggests that these organs should also be considered as a potential high risk for SARS-CoV-2 infection. During aerosol-generating medical procedures (AGMP; e.g. intubating and extubating patients or any surgical procedures), the production of both airborne particles and droplets may increase the risk of infection. In this situation, the surgical staff is strongly recommended to wear personal protective equipment (PPE). A transparent plastic cube, the so-called “Aerosol Box” (AB), has been recently designed to lend further protection against droplets and aerosol exposure during the AGMP.


title: Mouse thymic virus (MTLV; Murid Herpesvirus 3) infection in athymic nude mice: Evidence for a T lymphocyte requirement

text: Abstract Mouse thymic virus (MTLV; murid herpesvirus 3) is a lymphotropic herpesvirus that cytolytically infects developing T lineage lymphocytes in the thymus of neonatal mice. MTLV establishes a persistent infection and can be recovered indefinitely from infected mice, but nothing is known about requirements for this persistent infection. In order to determine whether T lineage lymphocytes are required for infection, young adult athymic nude (nulnu) mice and euthymic littermates were infected with MTLV and tested for virus shedding. Although euthymic littermates regularly shed virus, in the nude mice only about 20% of isolation attempts up to 100 days postinfection were positive. Blind passage yielded an additional three isolations out of 14 samples (21 %). In addition, unlike many other herpesviruses, the virus did not replicate in a number of epithelial and fibroblastic cell lines that were tested. These data confirm that the virus is preferentially T lymphotropic and suggest that infection may require T lineage lymphocytes.


title: The Socio-Economic Implications of the Coronavirus and COVID-19 Pandemic: A Review

text: Abstract The COVID-19 pandemic has resulted in over 1.4 million confirmed cases and over 83,000 deaths globally. It has also sparked fears of an impending economic crisis and recession. Social distancing, self-isolation and travel restrictions forced a decrease in the workforce across all economic sectors and caused many jobs to be lost. Schools have closed down, and the need of commodities and manufactured products has decreased. In contrast, the need for medical supplies has significantly increased. The food sector has also seen a great demand due to panic-buying and stockpiling of food products. In response to this global outbreak, we summarise the socio-economic effects of COVID-19 on individual aspects of the world economy.


title: Pneumovirus-like characteristics of the mRNA and proteins of turkey rhinotracheitis virus

text: Abstract Electronmicroscopy has indicated that turkey rhinotracheitis virus (TRTV), the causative agent of an acute repiratory disease in turkeys, is a member of the Paramyxoviridae family. To determine if TRTV belongs to one of the three defined genera of this family (Paramyxovirus, Morbillivirus and Pneumovirus) we have analysed the RNA and proteins induced during replication of TRTV in Vero cells. Following replication in the presence of actinomycin D 10 polyadenylated RNA bands, ranging in M r from 0.22 to 2.0 × 106, were detected in infected cells; some bands probably contained 2 or more RNA species. Viral proteins were studied after radiolabelling in the presence of [35S]methionine and [3H]glucosamine. Comparison of the polypeptides in mock-infected and infected cells, virions and nucleocapsids and after lentil-lectin chromatography and immunoprecipitation revealed seven virus-specific polypeptides (p), some of which were glycosylated (gp): gp82 (M r 82K), gp68, gp53, gp15, p43, p40 and p35. These are considered to be analogous to the large glycopolypeptide (HN, H and G), fusion protein precursor F0, the F protein cleavage products F1 and F2, nucleocapsid (N), phosphorylated (P) and matrix (M) polypeptides, respectively, of the Paramyxoviridae. Two other polypeptides (M r 200K and 22K) were also detected, as was a glycopolypeptide of M r 97K, probably related to gp82. Tunicamycin inhibited glycosylation of gp53 and gp15 but gp82 was little affected, most glycans still being present on a glycopolypeptide of approximately 79K. This finding, indicating that gp82 has mostly O-linked glycans, considered with the mRNA profile and the molecular weight of the N protein shows that of the three genera in this family, TRTV most closely resembles the Pneumovirus genus.


title: Clinical severity of human infection with avian influenza A(H7N9) virus

text: BACKGROUND: Characterizing the severity profile of human infections with influenza viruses of animal origin is a part of pandemic risk assessment, and an important part of the assessment of disease epidemiology. Our objective was to assess the clinical severity of human infections with the avian influenza A(H7N9) virus that has recently emerged in China. METHODS: Among laboratory-confirmed cases of A(H7N9) who were hospitalised, we estimated the risk of fatality, mechanical ventilation, and admission to the intensive care unit based on censored data during the currently ongoing outbreak. We also used information on laboratory-confirmed cases detected through sentinel influenza-like illness (ILI) surveillance to estimate the number of symptomatic A(H7N9) virus infections to date and the symptomatic case fatality risk. FINDINGS: Among 123 hospitalised cases, 37 cases had died and 69 had recovered by May 28, 2013. Hospitalised cases had high risks of mortality (36%; 95% confidence interval (CI): 26%–45%), mechanical ventilation or mortality (69%; 95% CI: 60%–77%), and ICU admission or mechanical ventilation or mortality (83%; 95% CI: 76%–90%), and the risk of these severe outcomes increased with age. Depending on assumptions about the coverage of the sentinel ILI network and health-care seeking behavior for cases of ILI associated with A(H7N9) virus infection, we estimated that the symptomatic case fatality risk could be between 160 and 2,800 per 100,000 symptomatic cases. INTERPRETATION: We estimated that the severity of A(H7N9) is somewhat lower than A(H5N1) but higher than seasonal influenza viruses and influenza A(H1N1)pdm09 virus. The estimated risks of fatality among hospitalised cases and symptomatic cases are measures of severity that should not be affected by shifts over time in the probability of laboratory-confirmation of mild cases and should inform risk assessment. FUNDING: Ministry of Science and Technology, China; Research Fund for the Control of Infectious Disease and University Grants Committee, Hong Kong Special Administrative Region, China; and the US National Institutes of Health.


title: First Mildly Ill, Non-Hospitalized Case of Coronavirus Disease 2019 (COVID-19) Without Viral Transmission in the United States — Maricopa County, Arizona, 2020

text: BACKGROUND: Coronavirus disease 2019 (COVID-19) causes a range of illness severity. Mild illness has been reported, but whether illness severity correlates with infectivity is unknown. We describe the public health investigation of a mildly ill, non-hospitalized COVID-19 case who traveled to China. METHODS: The case was a Maricopa County resident with multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive specimens collected on January 22, 2020. Contacts were persons exposed to the case on or after the day before case diagnostic specimen collection. Contacts were monitored for 14 days after last known exposure. High-risk contacts had close, prolonged case contact (≥10 minutes within 2 meters). Medium-risk contacts wore all U.S. Centers for Disease Control and Prevention (CDC)-recommended personal protective equipment during interactions. Nasopharyngeal and oropharyngeal (NP/OP) specimens were collected from the case and high-risk contacts and tested for SARS-CoV-2. RESULTS: Paired case NP/OP specimens were collected for SARS-CoV-2 testing at 11 time points. In 8 pairs (73%), ≥1 specimen tested positive or indeterminate, and in 3 pairs (27%) both tested negative. Specimens collected 18 days after diagnosis tested positive. Sixteen contacts were identified; 11 (69%) had high-risk exposure, including 1 intimate contact, and 5 (31%) had medium-risk exposure. In total, 35 high-risk contact NP/OP specimens were collected for SARS-CoV-2 testing; all 35 pairs (100%) tested negative. CONCLUSIONS: This report demonstrates that SARS-CoV-2 infection can cause mild illness and result in positive tests for up to 18 days after diagnosis, without evidence of transmission to close contacts. These data might inform public health strategies to manage individuals with asymptomatic infection or mild illness.


title: Information theory applications for biological sequence analysis

text: Information theory (IT) addresses the analysis of communication systems and has been widely applied in molecular biology. In particular, alignment-free sequence analysis and comparison greatly benefited from concepts derived from IT, such as entropy and mutual information. This review covers several aspects of IT applications, ranging from genome global analysis and comparison, including block-entropy estimation and resolution-free metrics based on iterative maps, to local analysis, comprising the classification of motifs, prediction of transcription factor binding sites and sequence characterization based on linguistic complexity and entropic profiles. IT has also been applied to high-level correlations that combine DNA, RNA or protein features with sequence-independent properties, such as gene mapping and phenotype analysis, and has also provided models based on communication systems theory to describe information transmission channels at the cell level and also during evolutionary processes. While not exhaustive, this review attempts to categorize existing methods and to indicate their relation with broader transversal topics such as genomic signatures, data compression and complexity, time series analysis and phylogenetic classification, providing a resource for future developments in this promising area.


title: Infectious Bronchitis Virus Generates Spherules from Zippered Endoplasmic Reticulum Membranes

text: Replication of positive-sense RNA viruses is associated with the rearrangement of cellular membranes. Previous work on the infection of tissue culture cell lines with the betacoronaviruses mouse hepatitis virus and severe acute respiratory syndrome coronavirus (SARS-CoV) showed that they generate double-membrane vesicles (DMVs) and convoluted membranes as part of a reticular membrane network. Here we describe a detailed study of the membrane rearrangements induced by the avian gammacoronavirus infectious bronchitis virus (IBV) in a mammalian cell line but also in primary avian cells and in epithelial cells of ex vivo tracheal organ cultures. In all cell types, structures novel to IBV infection were identified that we have termed zippered endoplasmic reticulum (ER) and spherules. Zippered ER lacked luminal space, suggesting zippering of ER cisternae, while spherules appeared as uniform invaginations of zippered ER. Electron tomography showed that IBV-induced spherules are tethered to the zippered ER and that there is a channel connecting the interior of the spherule with the cytoplasm, a feature thought to be necessary for sites of RNA synthesis but not seen previously for membrane rearrangements induced by coronaviruses. We also identified DMVs in IBV-infected cells that were observed as single individual DMVs or were connected to the ER via their outer membrane but not to the zippered ER. Interestingly, IBV-induced spherules strongly resemble confirmed sites of RNA synthesis for alphaviruses, nodaviruses, and bromoviruses, which may indicate similar strategies of IBV and these diverse viruses for the assembly of RNA replication complexes. IMPORTANCE All positive-sense single-stranded RNA viruses induce rearranged cellular membranes, providing a platform for viral replication complex assembly and protecting viral RNA from cellular defenses. We have studied the membrane rearrangements induced by an important poultry pathogen, the gammacoronavirus infectious bronchitis virus (IBV). Previous work studying closely related betacoronaviruses identified double-membrane vesicles (DMVs) and convoluted membranes (CMs) derived from the endoplasmic reticulum (ER) in infected cells. However, the role of DMVs and CMs in viral RNA synthesis remains unclear because these sealed vesicles lack a means of delivering viral RNA to the cytoplasm. Here, we characterized structures novel to IBV infection: zippered ER and small vesicles tethered to the zippered ER termed spherules. Significantly, spherules contain a channel connecting their interior to the cytoplasm and strongly resemble confirmed sites of RNA synthesis for other positive-sense RNA viruses, making them ideal candidates for the site of IBV RNA synthesis.


title: Effects of limited medical resource on a Filippov infectious disease model induced by selection pressure

text: Abstract In reality, the outbreak of emerging infectious diseases including SARS, A/H1N1 and Ebola are accompanied by the common cold and flu. The selective treatment measure for mitigating and controlling the emerging infectious diseases should be implemented due to limited medical resources. However, how to determine the threshold infected cases and when to implement the selective treatment tactics are crucial for disease control. To address this, we derive a non-smooth Filippov system induced by selective treatment measure. The dynamic behaviors of two subsystems have been discussed completely, and the existence conditions for sliding segment, sliding mode dynamics and different types of equilibria such as regular equilibrium, pseudo-equilibrium, boundary equilibrium and tangent point have been provided. Further, numerical sliding bifurcation analyses show that the proposed Filippov system has rich sliding bifurcations. Especially, the most interesting results are those for the fixed parameter set as the bifurcation parameter varies, the sliding bifurcations occur sequentially: crossing → buckling → real/virtual equilibrium → buckling → crossing. The key factors which affect the selective treatment measures and the threshold value of infected cases for emerging infectious disease have been discussed in more detail.


title: Chapter 5 The Value of the Tree of Life

text: Abstract The value of the Tree of Life to human well-being and survival is enormous—our species simply cannot thrive without a biodiverse planet; that is, a healthy Tree of Life. The vast importance of the Tree of Life falls into several general categories. First, the immense overall importance of biodiversity not only involves providing food, medicines, and ecosystem services such as clean air and water, but also a second major theme of this chapter is the importance to human well-being of knowledge of how species are related. Knowledge of how organisms are related has predictive value. We all know from our own family trees that relationships matter. For example, if a close relative has a disease or cancer that is genetically inherited, we realize that there is a chance we may have inherited that trait. Similarly, broad knowledge of relationships is fundamental, providing crucial new information regarding the discovery of medicines, combatting disease, crop improvement, while also providing insight into the study of ecosystem function and services (clean air and water). Knowledge of species relationships and the Tree of Life can help in the discovery of new medicines—closely related organisms produce similar chemicals; similarly, that knowledge of relationships is essential to improve crops by identifying close wild relatives that may have important traits (disease resistance, drought tolerance). Knowledge of the Tree of Life can also aid in the study of ecology and conservation efforts. As closely related species will often respond in similar ways to environmental factors such as temperature and moisture availability, the Tree of Life can also provide critical information in predicting how species may respond to climate change.


title: Coronavirus Disease 2019 (COVID-19) CT Findings: A Systematic Review and Meta-analysis

text: Abstract Purpose To date, considerable knowledge gaps remain regarding the chest CT imaging features of COVID-19. We performed a systematic review and meta-analysis of results from published studies to date to provide a summary of evidence on detection of COVID-19 by chest CT and the expected CT imaging manifestations. Methods Studies were identified by searching PubMed database for articles published between December 2019 and February 2020. Pooled CT positive rate of COVID-19 and pooled incidence of CT imaging findings were estimated using a random-effect model. Results A total of 13 studies met inclusion criteria. The pooled positive rate of the CT imaging was 89.76% and 90.35% when only including thin-section chest CT. Typical CT signs were ground glass opacities (83.31%), ground glass opacities with mixed consolidation (58.42%), adjacent pleura thickening (52.46%), interlobular septal thickening (48.46%), and air bronchograms (46.46%). Other CT signs included crazy paving pattern (14.81%), pleural effusion (5.88%), bronchiectasis (5.42%), pericardial effusion (4.55%), and lymphadenopathy (3.38%). The most anatomic distributions were bilateral lung infection (78.2%) and peripheral distribution (76.95%). The incidences were highest in the right lower lobe (87.21%), left lower lobe (81.41%), and bilateral lower lobes (65.22%). The right upper lobe (65.22%), right middle lobe (54.95%), and left upper lobe (69.43%) were also commonly involved. The incidence of bilateral upper lobes was 60.87%. A considerable proportion of patients had three or more lobes involved (70.81%). Conclusions The detection of COVID-19 chest CT imaging is very high among symptomatic individuals at high risk, especially using thin-section chest CT. The most common CT features in patients affected by COVID-19 included ground glass opacities and consolidation involving the bilateral lungs in a peripheral distribution.


title: Viral respiratory diseases (ILT, aMPV infections, IB): are they ever under control?(1)

text: 1. The use of vaccines is the main approach to control of the economically important poultry viral respiratory diseases infectious laryngotracheitis (ILT), avian metapneumovirus (aMPV) infections and infectious bronchitis (IB). This paper appraises the current methods of vaccine control in the light of the nature of each virus and epidemiological factors associated with each disease. 2. Infectious laryngotracheitis virus (ILTV) exists as a single type with a wide range of disease severity. It is a serious disease in certain regions of the world. Recent work has distinguished molecular differences between vaccine and field strains and vaccine virus can be a cause of disease. Vaccines have remained unaltered for many years but new ones are being developed to counter vaccine side effects and reversion and reactivation of latent virus. 3. Avian metapneumoviruses, the cause of turkey rhinotracheitis and respiratory disease in chickens exists as 4 subtypes, A, B, C and D. A and B are widespread and vaccines work well provided that accurate doses are given. Newer vaccine developments are designed to eliminate reversion and possibly counter the appearance of newer field strains which may break through established vaccine coverage. 4. IB presents the biggest problem of the three. Being an unstable RNA virus, part of the viral genome that codes for the S1 spike gene can undergo mutation and recombination so that important antigenic variants can appear irregularly which may evade existing vaccine protection. While conventional vaccines work well against homologous types, new strategies are needed to counter this instability. Molecular approaches involving tailoring viruses to suit field challenges are in progress. However, the simple use of two genetically different vaccines to protect against a wide range of heterologous types is now a widespread practice that is very effective. 5. None of the three diseases described can claim to be satisfactorily controlled and it remains to be seen whether the newer generations of vaccines will be more efficacious and cost effective. The importance of constant surveillance is emphasised and the testing of novel vaccines cannot be achieved without the use of vaccine-challenge experiments in poultry.


title: Full-Length Genome Characterization of Chinese Porcine Deltacoronavirus Strain CH/SXD1/2015

text: A porcine deltacoronavirus (PDCoV) was identified in the Chinese mainland and found to be closely related to Hong Kong strain HKU15-155 but differed from PDCoV strains in the United States and South Korea. The complete genome of PDCoV strain CH/SXD1/201 was sequenced and analyzed to further characterize PDCoV in Chinese swine.


¿Es la hiporrespuesta inmune de la uremia un factor de protección contra la neumonía grave por COVID-19?


title: Feline coronavirus antibody titer in cerebrospinal fluid from cats with neurological signs

text: To investigate the utility of cerebrospinal fluid (CSF) anti-feline coronavirus (FCoV) antibody test for diagnosis of feline infectious peritonitis (FIP), the antibody titers were tested in CSF and sera from 271 FIP-suspected neurological cats. CSF antibody was detected in 28 cats, which were divided into 2 groups; 15 with CSF titer of 1:80 or lower and 13 with CSF titer of 1:640 or higher. In the latter group, reciprocal serum titer/reciprocal CSF titer was 8 or lower, which is extremely lower than normal range (256-2048), and FCoV RNA was detected in all of 11 CSF samples assayed by RT-PCR. Our findings indicate that CSF titer of 1:640 or higher may be served as a candidate for the index for diagnosing FIP.


title: Effect of temperature on the infectivity of COVID-19

text: Abstract Objectives To evaluate the influence of temperature on the infectivity of COVID-19 in Japan. Methods We evaluated the relationship between the accumulated number of patients per 1,000,000 population and the average temperature in February 2020 in each prefecture by Poisson regression analysis. We introduced the monthly number of inbound visitors from China in January 2020 in each prefecture as an additional explanatory variable in the model. Results Both monthly inbound visitors from China in January 2020 and mean temperature in February 2020 are associated with the cumulative number of COVID-19 case on March 16, 2020. Conclusions Our analysis showed a possible association between low temperature and increased risk of COVID-19 infection. Further evaluation would be desirable at a global level.


title: Estimated effect of COVID‐19 lockdown on melanoma thickness and prognosis: a rate of growth model

text: The coronavirus COVID‐19 pandemic, which emerged in Wuhan, China several months ago,(1) has led to large‐scale lockdown in many countries around the world, including Spain. Uncertainty about the duration of these measures led us to consider the potential impact of diagnostic delays due to the paralyzation of certain health procedures and services on the prognosis of patients with melanoma.


Caring for persons in detention suffering with mental illness during the Covid-19 outbreak


title: Management of maternal resuscitation and category 1 cesarean delivery in a Covid-19 suspect parturient

text: • Hospital guidelines for management of Covid-19 suspect parturient; • Maternal resuscitation in Covid-19 suspect parturient; • Category 1 cesarean delivery in Covid-19 suspect parturient.


title: Influenza A(H1N1)pdm09 and Cystic Fibrosis Lung Disease: A Systematic Meta-Analysis

text: BACKGROUND: To systematically assess the literature published on the clinical impact of Influenza A(H1N1)pdm09 on cystic fibrosis (CF) patients. METHODS: An online search in PUBMED database was conducted. Original articles on CF patients with Influenza A(H1N1)pdm09 infection were included. We analyzed incidence, symptoms, clinical course and treatment. RESULTS: Four surveys with a total of 202 CF patients infected by Influenza A(H1N1)pdm09 were included. The meta-analysis showed that hospitalisation rates were higher in CF patients compared to the general population. While general disease symptoms were comparable, the clinical course was more severe and case fatality rate (CFR) was higher in CF patients compared to asthmatics and the general population. CONCLUSIONS: Evidence so far suggests that CF patients infected with Influenza A(H1N1)pdm09 show increased morbidity and a higher CFR compared to patients with other chronic respiratory diseases and healthy controls. Particularly, CF patients with advanced stage disease seem to be more susceptible to severe lung disease. Accordingly, early antiviral and antibiotic treatment strategies are essential in CF patients. Preventive measures, including vaccination as well as hygiene measures during the influenza season, should be reinforced and improved in CF patients.


title: Signal transduction in the type I interferon system and viral countermeasures

text: Type I interferons (IFN) including IFNα/β are cytokines of the immune system with critical functions in innate and adaptive immune response. Secreted IFN acts via JAK/STAT signaling pathways to direct a huge gene expression program, including antiviral, apoptotic, survival and immune genes. Only recently, the molecular patterns and their receptors as well as the connected signaling pathways leading to transcriptional activation of IFN genes have been elucidated. Ubiquitous cytosolic RNA helicases like RIG‐I which sense intracellular triphosphate RNAs and activate the IFN‐controlling transcription factors IRF3 and IRF7 seem to play a major role in antiviral defense and immunity. Recognition of extracellular nucleic acids by a subset of Toll‐like receptors in addition contributes to a generalized host IFN response. During co‐evolution with the host, viruses have learned to counteract every piece of the IFN network. Learning from viruses how to target the IFN system may lead us to novel strategies for therapeutic intervention.


title: Bispecific antibodies: design, therapy, perspectives

text: Antibodies (Abs) containing two different antigen-binding sites in one molecule are called bispecific. Bispecific Abs (BsAbs) were first described in the 1960s, the first monoclonal BsAbs were generated in the 1980s by hybridoma technology, and the first article describing the therapeutic use of BsAbs was published in 1992, but the number of papers devoted to BsAbs has increased significantly in the last 10 years. Particular interest in BsAbs is due to their therapeutic use. In the last decade, two BsAbs – catumaxomab in 2009 and blinatumomab in 2014, were approved for therapeutic use. Papers published in recent years have been devoted to various methods of BsAb generation by genetic engineering and chemical conjugation, and describe preclinical and clinical trials of these drugs in a variety of diseases. This review considers diverse BsAb-production methods, describes features of therapeutic BsAbs approved for medical use, and summarizes the prospects of practical application of promising new BsAbs.


title: Re-emergence of fatal human influenza A subtype H5N1 disease

text: Summary Human disease associated with influenza A subtype H5N1 reemerged in January, 2003, for the first time since an outbreak in Hong Kong in 1997. Patients with H5N1 disease had unusually high serum concentrations of chemokines (eg, interferon induced protein-10 [IP-10] and monokine induced by interferon γ [MIG]). Taken together with a previous report that H5N1 influenza viruses induce large amounts of proinflam-matory cytokines from macrophage cultures in vitro, our findings suggest that cytokine dysfunction contributes to the pathogenesis of H5N1 disease. Development of vaccines against influenza A (H5N1) virus should be made a priority.


title: Definitive Care for the Critically Ill During a Disaster: Medical Resources for Surge Capacity From a Task Force for Mass Critical Care Summit Meeting, January 26–27, 2007, Chicago, IL

text: Background Mass numbers of critically ill disaster victims will stress the abilities of health-care systems to maintain usual critical care services for all in need. To enhance the number of patients who can receive life-sustaining interventions, the Task Force on Mass Critical Care (hereafter termed the Task Force) has suggested a framework for providing limited, essential critical care, termed emergency mass critical care (EMCC). This article suggests medical equipment, concepts to expand treatment spaces, and staffing models for EMCC. Methods Consensus suggestions for EMCC were derived from published clinical practice guidelines and medical resource utilization data for the everyday critical care conditions that are anticipated to predominate during mass critical care events. When necessary, expert opinion was used. Task Force major suggestions The Task Force makes the following suggestions: (1) one mechanical ventilator that meets specific characteristics, as well as a set of consumable and durable medical equipment, should be provided for each EMCC patient; (2) EMCC should be provided in hospitals or similarly equipped structures; after ICUs, postanesthesia care units, and emergency departments all reach capacity, hospital locations should be repurposed for EMCC in the following order: (A) step-down units and large procedure suites, (B) telemetry units, and (C) hospital wards; and (3) hospitals can extend the provision of critical care using non-critical care personnel via a deliberate model of delegation to match staff competencies with patient needs. Discussion By using the Task Force suggestions for adequate supplies of medical equipment, appropriate treatment space, and trained staff, communities may better prepare to deliver augmented essential critical care in response to disasters.


title: Up-Regulation of Mcl-1 and Bak by Coronavirus Infection of Human, Avian and Animal Cells Modulates Apoptosis and Viral Replication

text: Virus-induced apoptosis and viral mechanisms that regulate this cell death program are key issues in understanding virus-host interactions and viral pathogenesis. Like many other human and animal viruses, coronavirus infection of mammalian cells induces apoptosis. In this study, the global gene expression profiles are first determined in IBV-infected Vero cells at 24 hours post-infection by Affymetrix array, using avian coronavirus infectious bronchitis virus (IBV) as a model system. It reveals an up-regulation at the transcriptional level of both pro-apoptotic Bak and pro-survival myeloid cell leukemia-1 (Mcl-1). These results were further confirmed both in vivo and in vitro, in IBV-infected embryonated chicken eggs, chicken fibroblast cells and mammalian cells at transcriptional and translational levels, respectively. Interestingly, the onset of apoptosis occurred earlier in IBV-infected mammalian cells silenced with short interfering RNA targeting Mcl-1 (siMcl-1), and was delayed in cells silenced with siBak. IBV progeny production and release were increased in infected Mcl-1 knockdown cells compared to similarly infected control cells, while the contrary was observed in infected Bak knockdown cells. Furthermore, IBV infection-induced up-regulation of GADD153 regulated the expression of Mcl-1. Inhibition of the mitogen-activated protein/extracellular signal-regulated kinase (MEK/ERK) and phosphoinositide 3-kinase (PI3K/Akt) signaling pathways by chemical inhibitors and knockdown of GADD153 by siRNA demonstrated the involvement of ER-stress response in regulation of IBV-induced Mcl-1 expression. These results illustrate the sophisticated regulatory strategies evolved by a coronavirus to modulate both virus-induced apoptosis and viral replication during its replication cycle.


Chapter 16 Global Health


COVID‐19 and the personal protection debate: An exposition on transmission


title: Humoral Innate Immunity at the Crossroad Between Microbe and Matrix Recognition: The Role of PTX3 in Tissue Damage

text: Innate immunity is involved in regulating inflammatory and tissue repair responses to injury. In particular, humoral innate immunity plays functions related to wound clearance from tissue debris, and regulation of macrophage and stromal cell activities. PTX3, a component of humoral innate immunity, orchestrates tissue repair by interacting with plasminogen and fibrin. Fluid-phase molecules of innate immunity interact with elements of the extracellular matrix, and some of the latter display opsonic activity against certain bacterial species. Thus, recognition of extracellular matrix and microbial components is a recurrent theme in the humoral arm of the innate immune system.


title: Evaluation of Protection Level, Respiratory Safety, and Practical Aspects of Commercially Available Snorkel Masks as Personal Protection Devices Against Aerosolized Contaminants and SARS-CoV2

text: Introduction: The “Severe Acute Respiratory Syndrome Coronavirus 2″ (SARS-CoV2) pandemic has led to a worldwide shortage of personal protection devices (PPD) for medical and paramedical personnel. Adaptation of commercially available snorkel masks to serve as full face masks has been proposed. Even not formally approved as PPD, they are publicized on social media as suitable for this use. Concerns about actual protection levels and risk of carbon dioxide (CO(2)) accumulation while wearing them for extended periods made us perform a systematic testing of various brands, in order to verify whether they are as safe and effective as claimed. Methods: A ‘fit’ test was performed, analogous to gas mask testing. Respiratory safety was evaluated by measuring end-tidal CO(2) and oxygen saturation while wearing the masks in rest and during physical exercise. Masks were tested with 3D adaptors to mount regular bacterial-viral ventilator filters when available, or with snorkel openings covered with N95/FFP2 cloth. Results: Modified masks performed reasonably well on the fit test, comparable to regular N95/FFP2 masks. Not all ventilator filters are equally protective. For all masks, a small initial increase in end-tidal CO(2) was noted, remaining within physiological limits. 3D printed adaptors are safer, have more flexibility and reliability than makeshift adaptations. Conclusions: These masks can offer benefit as a substitute for complete protective gear as they are easier to don and remove and offer full-face protection. They may be more comfortable to wear for extended periods. Proper selection of mask size, fit testing, quality of 3D printed parts, and choice of filter are important.


title: SARS-CoV Infection in a Restaurant from Palm Civet

text: Epidemiologic investigations showed that 2 of 4 patients with severe acute respiratory syndrome (SARS) identified in the winter of 2003–2004 were a waitress at a restaurant in Guangzhou, China, that served palm civets as food and a customer who ate in the restaurant a short distance from animal cages. All 6 palm civets at the restaurant were positive for SARS-associated coronavirus (SARS-CoV). Partial spike (S) gene sequences of SARS-CoV from the 2 patients were identical to 4 of 5 S gene viral sequences from palm civets. Phylogenetic analysis showed that SARS-CoV from palm civets in the restaurant was most closely related to animal isolates. SARS cases at the restaurant were the result of recent interspecies transfer from the putative palm civet reservoir, and not the result of continued circulation of SARS-CoV in the human population.


title: Monoclonal antibody specific to HA2 glycopeptide protects mice from H3N2 influenza virus infection

text: Canine influenza virus (CIV) subtype H3N2 is a newly identified, highly contagious respiratory pathogen that causes cough, pneumonia and other respiratory symptoms in dogs. Data indicate that the virus is responsible for recent clinical cases of dog disease in China. However, therapeutic options for this disease are very limited. In this study, seven monoclonal antibodies (mAbs) against CIV JS/10 (an H3N2 subtype virus) were produced and characterized. Among them, mAb D7, which is specific for the HA2 glycopeptide (gp), induced the highest neutralization titers. The protection provided by mAb D7 was evaluated in BALB/c mice challenged with homologous or heterologous strains of H3N2 influenza virus, including two strains of CIV and one strain of swine influenza virus (SIV). The data show that mAb D7 protected the mice from infection with the three viral strains, especially the homologous strain, which was indicated by the recovery of body weight, reduction of viral load, and reduction of tissue damage. Moreover, the levels of IFN-γ and TNF-α in the lungs, as detected by ELISA, were reduced in the infected mice treated with the mAb D7 compared with those without mAb D7 treatment. Thus, our findings demonstrate, for the first time, that a mAb could reduce the release of IFN-γ and TNF-α associated with tissue damage by CIV infection and that the mAb might be of great therapeutic value for CIV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-015-0146-7) contains supplementary material, which is available to authorized users.


title: Lab-Attenuated Rabies Virus Causes Abortive Infection and Induces Cytokine Expression in Astrocytes by Activating Mitochondrial Antiviral-Signaling Protein Signaling Pathway

text: Rabies is an ancient disease but remains endemic in most parts of the world and causes approximately 59,000 deaths annually. The mechanism through which the causative agent, rabies virus (RABV), evades the host immune response and infects the host central nervous system (CNS) has not been completely elucidated thus far. Our previous studies have shown that lab-attenuated, but not wild-type (wt), RABV activates the innate immune response in the mouse and dog models. In this present study, we demonstrate that lab-attenuated RABV causes abortive infection in astrocytes, the most abundant glial cells in the CNS. Furthermore, we found that lab-attenuated RABV produces more double-stranded RNA (dsRNA) than wt RABV, which is recognized by retinoic acid-inducible gene I (RIG-I) or melanoma differentiation-associated protein 5 (MDA5). Activation of mitochondrial antiviral-signaling protein (MAVS), the common adaptor molecule for RIG-I and MDA5, results in the production of type I interferon (IFN) and the expression of hundreds of IFN-stimulated genes, which suppress RABV replication and spread in astrocytes. Notably, lab-attenuated RABV replicates in a manner identical to that of wt RABV in MAVS−/− astrocytes. It was also found that lab-attenuated, but not wt, RABV induces the expression of inflammatory cytokines via the MAVS- p38/NF-κB signaling pathway. These inflammatory cytokines increase the blood–brain barrier permeability and thus enable immune cells and antibodies infiltrate the CNS parenchyma, resulting in RABV control and elimination. In contrast, wt RABV restricts dsRNA production and thus evades innate recognition by RIG-I/MDA5 in astrocytes, which could be one of the mechanisms by which wt RABV evades the host immune response in resident CNS cells. Our findings suggest that astrocytes play a critical role in limiting the replication of lab-attenuated RABV in the CNS.


The Outbreak of COVID-19 and Diabetes in Korea: “We Will Find a Way as We Have Always Done”


title: Rapid telepsychology deployment during the COVID‐19 pandemic: A special issue commentary and lessons from primary care psychology training

text: OBJECTIVE: This article positions the special issue on telepsychology amidst the COVID‐19 pandemic, which has dramatically accelerated the adoption and dissemination of telepsychology. METHOD: The article makes general observations about the themes emerging in the special issue with considerations for application, training, theory‐driven research, and policy. It then presents as a case example the rapid deployment during the pandemic of telepsychology doctoral training and services at the Virginia Commonwealth University (VCU) Primary Care Psychology Collaborative. RESULTS: Facilitators to VCU telepsychology deployment included trainee and supervisor resources, strong telepsychology training, and prior experience. Barriers to overcome included limited clinic capacity, scheduling, technology, and accessibility and diversity issues. Lessons learned involved presenting clinical issues, supervision, and working with children and adolescents. CONCLUSIONS: Telepsychology is crucial for psychological service provision, during the COVID‐19 pandemic more than ever, and that is unlikely to change as psychologists and patients increasingly continue to appreciate its value.