title: Identification of Oxidative Stress and Toll-like Receptor 4 Signaling as a Key Pathway of Acute Lung Injury

text: Multiple lung pathogens such as chemical agents, H5N1 avian flu, or SARS cause high lethality due to acute respiratory distress syndrome. Here we report that Toll-like receptor 4 (TLR4) mutant mice display natural resistance to acid-induced acute lung injury (ALI). We show that TLR4-TRIF-TRAF6 signaling is a key disease pathway that controls the severity of ALI. The oxidized phospholipid (OxPL) OxPAPC was identified to induce lung injury and cytokine production by lung macrophages via TLR4-TRIF. We observed OxPL production in the lungs of humans and animals infected with SARS, Anthrax, or H5N1. Pulmonary challenge with an inactivated H5N1 avian influenza virus rapidly induces ALI and OxPL formation in mice. Loss of TLR4 or TRIF expression protects mice from H5N1-induced ALI. Moreover, deletion of ncf1, which controls ROS production, improves the severity of H5N1-mediated ALI. Our data identify oxidative stress and innate immunity as key lung injury pathways that control the severity of ALI.


title: The Socio-economic and Psychosocial Impact of Covid-19 Pandemic on Urban Refugees in Uganda

text: Abstract Considering the COVID-19 global public health crisis, this paper examines the socio-cultural, economic and psychosocial impact of the pandemic on urban refugees in Uganda. We analyse the living conditions of urban refugees that make it problematic for them to adhere to public health measures. Since COVID-19 is perceived as “imported”, refugees are assumed as its potential transmitters, consequently experiencing heightened stigma and isolation. Lack of culturally and linguistically accessible information and services excludes them from on-going efforts to prevent the pandemic. The lockdown has affected refugee livelihoods and increased income insecurity, sexual and gender-based violence and anxiety. Given the paucity of Government-led services to contain the epidemic, we argue that contingency planning must involve refugees and their communities to access accurate and relevant information in appropriate languages. It is also important to build the capacity of frontline workers to understand the specific needs of refugees to deliver appropriate protection in the context of the pandemic.


title: QT prolongation, torsades de pointes and sudden death with short courses of chloroquine or hydroxychloroquine as used in COVID-19: a systematic review

text: Chloroquine and hydroxychloroquine are now being widely used as treatments for COVID-19. Both medications prolong the QT interval and accordingly may put patients at increased risk of torsades de pointes and sudden death. Published guidance documents vary in their recommendations for monitoring and managing these potential adverse effects. Accordingly, we set out to conduct a systematic review of the arrhythmogenic effect of short courses of chloroquine or hydroxychloroquine. We searched in MEDLINE and Embase, as well as grey literature up to April 17, 2020, on the risk of QT prolongation, torsades, ventricular arrhythmia, and sudden death with short-term chloroquine and hydroxychloroquine usage. This resulted in 390 unique records, of which fourteen were ultimately selected for qualitative synthesis and which included data on 1515 COVID-19 patients. Approximately 10% of COVID-19 patients treated with these drugs developed QT prolongation. We found evidence of ventricular arrhythmia in two COVID-19 patients out of a group of 28 treated with high-dose chloroquine. A limitation of these results is unclear follow-up and possible publication/reporting bias, but there is compelling evidence that chloroquine and hydroxychloroquine induce significant QT interval prolongation and potentially increase the risk of arrhythmia. Daily ECG monitoring and other risk mitigation strategies should be considered in order to prevent possible harms from what is currently an unproven therapy.


title: Outbreak of febrile illness caused by coxsackievirus A4 in a nursery school in Beijing, China

text: BACKGROUND: Coxsackievirus A4 (CV-A4) is classified as human enterovirus A according to its serotype. CV-A4, an etiological agent of hand, foot, and mouth disease, affects children worldwide and can circulate in closed environments such as schools and hospitals for long periods. FINDINGS: An outbreak of febrile illness at a nursery school in Beijing, China, was confirmed to be caused by CV-A4. Phylogenetic analysis of the complete genome of the isolated strain showed that the virus belongs to the same cluster as the predominant CV-A4 strain in China. This outbreak was controlled by effective measures. CONCLUSIONS: The early identification of the pathogen and timely intervention may be the most critical factors in controlling an outbreak caused by CV-A4 in a preschool.


title: Clinical evaluation of commercial nucleic acid amplification tests in patients with suspected sepsis

text: BACKGROUND: Sepsis is a serious medical condition requiring timely administered, appropriate antibiotic therapy. Blood culture is regarded as the gold standard for aetiological diagnosis of sepsis, but it suffers from low sensitivity and long turnaround time. Thus, nucleic acid amplification tests (NAATs) have emerged to shorten the time to identification of causative microbes. The aim of the present study was to evaluate the clinical utility in everyday practice in the emergency department of two commercial NAATs in patients suspected with sepsis. METHODS: During a six-week period, blood samples were collected consecutively from all adult patients admitted to the general emergency department for suspicion of a community-onset sepsis and treated with intravenous antibiotics. Along with conventional blood cultures, multiplex PCR (Magicplex™) was performed on whole blood specimens whereas portions from blood culture bottles were used for analysis by microarray-based assay (Prove-it™). The aetiological significance of identified organisms was determined by two infectious disease physicians based on clinical presentation and expected pathogenicity. RESULTS: Among 382 episodes of suspected sepsis, clinically relevant microbes were detected by blood culture in 42 episodes (11%), by multiplex PCR in 37 episodes (9.7%), and by microarray in 32 episodes (8.4%). Although moderate agreement with blood culture (kappa 0.50), the multiplex PCR added diagnostic value by timely detection of 15 clinically relevant findings in blood culture-negative specimens. Results of the microarray corresponded very well to those of blood culture (kappa 0.90), but were available just marginally prior to blood culture results. CONCLUSIONS: The use of NAATs on whole blood specimens in adjunct to current culture-based methods provides a clinical add-on value by allowing for detection of organisms missed by blood culture. However, the aetiological significance of findings detected by NAATs should be interpreted with caution as the high analytical sensitivity may add findings that do not necessarily corroborate with the clinical diagnosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-0938-4) contains supplementary material, which is available to authorized users.


Is there a Link between endocrine disruptors and COVID-19 severe pneumonia?


title: Acute phase protein response to viral infection and vaccination

text: Abstract Organisms respond in multiple ways to microbial infections. Pathogen invasion tipically triggers an inflammatory response where acute phase proteins (APP) have a key role. Pentraxins (PTX) are a family of highly conserved APP that play a part in the host defense against infection. The larger proteins of the family are simply named pentraxins, while c-reactive proteins (CRP) and serum amyloid proteins (SAA, SAP) are known as short pentraxins. Although high APP levels have been broadly associated with bacterial infections, there is a growing body of evidence revealing increased PTX, CRP and SAP expression upon viral infection. Furthermore, CRP, PTX and SAP have shown their potential as diagnostic markers and predictors of disease outcome. Likewise, the measurement of APP levels can be valuable to determine the efficacy of antiviral therapies and vaccines. From the practical point of view, the ability of APP to reduce viral infectivity has been observed in several virus-host models. This has prompted investigation efforts to assess the role of acute phase response proteins as immunoregulatory molecules and their potential as therapeutic reagents. This work aims to present an overview of the APP response to viral infections reviewing the current knowledge in the field.


title: Oral Mutian®X stopped faecal feline coronavirus shedding by naturally infected cats

text: Abstract Feline coronavirus (FCoV) is common among cats living indoors in groups. In about 10% of infected cats, a potentially lethal disease, feline infectious peritonitis (FIP) occurs. Virus transmission is faecal-oral. Mutian® Xraphconn (Mutian X) is a product marketed to treat cats with FIP but is also being used to stop virus shedding, although no clear guidelines exist for its use for this purpose. The aim of this study was to establish the minimum dose and treatment duration required to ensure viral clearance from the faeces of asymptomatic virus-shedding cats. In five multicat households, 29 cats naturally infected with FCoV and actively shedding virus in the faeces were given Mutian X pills. Virus shedding was monitored using reverse-transcription quantitative polymerase chain reaction (RT-qPCR) controlled for faecal inhibitors to ensure sensitivity. Mutian X given orally cleared the virus in 29 cats; although four cats required a repeated course to finally stop virus shedding. A dose of 4 mg/kg q24 h for four days was found to be the optimal treatment protocol: 2 mg/kg cleared only 80% of cats. Post-treatment using a sensitive RT-qPCR test was essential to ensure that virus clearance had been achieved, since failure to clear even one cat can result in re-infection of the others. Records of virus shedding by cats before treatment provided a retrospective control: significantly more cats stopped shedding virus after Mutian X than recovered from infection during the control period (p < .00001). This is the first report of the successful elimination of faecal FCoV shedding in chronically infected cats.


title: Characterization of novel monoclonal antibodies against MERS-coronavirus spike protein

text: Abstract Middle East Respiratory Syndrome coronavirus (MERS-CoV) causes severe pulmonary infection, with ∼35 % mortality. Spike glycoprotein (S) of MERS-CoV is a key target for vaccines and therapeutics because S mediates viral entry and membrane-fusion to host cells. Here, four different S subunit proteins, receptor-binding domain (RBD; 358–606 aa), S1 (1–751 aa), S2 (752–1296 aa), and SΔTM (1–1296 aa), were generated using the baculoviral system and immunized in mice to develop neutralizing antibodies. We developed 77 hybridomas and selected five neutralizing mAbs by immunization with SΔTM against MERS-CoV EMC/2012 strain S-pseudotyped lentivirus. However, all five monoclonal antibodies (mAb) did not neutralize the pseudotyped V534A mutation. Additionally, one mAb RBD-14F8 did not show neutralizing activity against pseudoviruses with amino acid substitution of L506 F or D509 G (England1 strain, EMC/2012 L506 F, and EMC/2012 D509 G), and RBD-43E4 mAb could not neutralize the pseudotyped I529 T mutation, while three other neutralizing mAbs showed broad neutralizing activity. This implies that the mutation in residue 506–509, 529, and 534 of S is critical to generate neutralization escape variants of MERS-CoV. Interestingly, all five neutralizing mAbs have binding affinity to RBD, although most mAbs generated by RBD did not have neutralizing activity. Additionally, chimeric antibodies of RBD-14F8 and RBD-43E4 with human Fc and light chain showed neutralizing effect against wild type MERS-CoV KOR/KNIH/002, similar to the original mouse mAbs. Thus, our mAbs can be utilized for the identification of specific mutations of MERS-CoV.


title: Coronavirus 3CL(pro )proteinase cleavage sites: Possible relevance to SARS virus pathology

text: BACKGROUND: Despite the passing of more than a year since the first outbreak of Severe Acute Respiratory Syndrome (SARS), efficient counter-measures are still few and many believe that reappearance of SARS, or a similar disease caused by a coronavirus, is not unlikely. For other virus families like the picornaviruses it is known that pathology is related to proteolytic cleavage of host proteins by viral proteinases. Furthermore, several studies indicate that virus proliferation can be arrested using specific proteinase inhibitors supporting the belief that proteinases are indeed important during infection. Prompted by this, we set out to analyse and predict cleavage by the coronavirus main proteinase using computational methods. RESULTS: We retrieved sequence data on seven fully sequenced coronaviruses and identified the main 3CL proteinase cleavage sites in polyproteins using alignments. A neural network was trained to recognise the cleavage sites in the genomes obtaining a sensitivity of 87.0% and a specificity of 99.0%. Several proteins known to be cleaved by other viruses were submitted to prediction as well as proteins suspected relevant in coronavirus pathology. Cleavage sites were predicted in proteins such as the cystic fibrosis transmembrane conductance regulator (CFTR), transcription factors CREB-RP and OCT-1, and components of the ubiquitin pathway. CONCLUSIONS: Our prediction method NetCorona predicts coronavirus cleavage sites with high specificity and several potential cleavage candidates were identified which might be important to elucidate coronavirus pathology. Furthermore, the method might assist in design of proteinase inhibitors for treatment of SARS and possible future diseases caused by coronaviruses. It is made available for public use at our website: .


title: Ribavirin and interferon-β synergistically inhibit SARS-associated coronavirus replication in animal and human cell lines

text: Abstract Initial in vitro investigations demonstrated type I interferons (IFNs: IFN-α, IFN-β) to inhibit replication of SARS coronavirus (SARS-CoV), but found the nucleoside analogue ribavirin ineffective in Vero cells. In this report, ribavirin was shown to inhibit SARS-CoV replication in five different cell types of animal or human origin at therapeutically achievable concentrations. Since clinical anti-SARS-CoV activity of type I interferons or ribavirin is limited, we investigated the combination of IFN-β and ribavirin. Determination of the virus yield indicated highly synergistic anti-SARS-CoV action of the combination suggesting the consideration of ribavirin plus IFN-β for the treatment of SARS.


title: Massive peptide sharing between viral and human proteomes

text: Thirty viral proteomes were examined for amino acid sequence similarity to the human proteome, and, in parallel, a control of 30 sets of human proteins was analyzed for internal human overlapping. We find that all of the analyzed 30 viral proteomes, independently of their structural or pathogenic characteristics, present a high number of pentapeptide overlaps to the human proteome. Among the examined viruses, human T-lymphotropic virus 1, Rubella virus, and hepatitis C virus present the highest number of viral overlaps to the human proteome. The widespread and ample distribution of viral amino acid sequences through the human proteome indicates that viral and human proteins are formed of common peptide backbone units and suggests a fluid compositional chimerism in phylogenetic entities canonically classified distantly as viruses and Homo sapiens. Importantly, the massive viral to human peptide overlapping calls into question the possibility of a direct causal association between virus–host sharing of amino acid sequences and incitement to autoimmune reactions through molecular recognition of common motifs.


title: Reply to: Neurological, Cognitive and Behavioral Disorders During COVID‐19: The Nitric Oxide Track

text: This letter comments on the letter by Cedric Annweiler


title: Phage display in the study of infectious diseases

text: Microbial infections are dependent on the panoply of interactions between pathogen and host and identifying the molecular basis of such interactions is necessary to understand and control infection. Phage display is a simple functional genomic methodology for screening and identifying protein–ligand interactions and is widely used in epitope mapping, antibody engineering and screening for receptor agonists or antagonists. Phage display is also used widely in various forms, including the use of fragment libraries of whole microbial genomes, to identify peptide–ligand and protein–ligand interactions that are of importance in infection. In particular, this technique has proved successful in identifying microbial adhesins that are vital for colonization.


title: Plagues in the ICU: A Brief History of Community-Acquired Epidemic and Endemic Transmissible Infections Leading to Intensive Care Admission

text: The ability to diagnose and treat infectious diseases and handle infectious disease outbreaks continues to improve. For the most part, the major plagues of antiquity remain historical footnotes, yet, despite many advances, there is clear evidence that major pandemic illness is always just one outbreak away. In addition to the HIV pandemic, the smaller epidemic outbreaks of Legionnaire's disease, hantavirus pulmonary syndrome, and severe acute respiratory syndrome, among many others, points out the potential risk associated with a lack of preplanning and preparedness. Although pandemic influenza is at the top of the list when discussing possible future major infectious disease outbreaks, the truth is that the identity of the next major pandemic pathogen cannot be predicted with any accuracy. We can only hope that general preparedness and the lessons learned from previous outbreaks suffice.


title: Traditional Chinese Medicine: an effective treatment for 2019 novel coronavirus pneumonia (NCP)

text: ABSTRACT The novel coronavirus pneumonia broke out in 2019 and spread rapidly. In 30 different countries, there are over seventy thousand patients have been diagnosed in total. Therefore, it is urgent to develop the effective program to prevent and treat for the novel coronavirus pneumonia. In view of Traditional Chinese Medicine has accumulated a solid theoretical foundation of plague in ancient and recent decades. Meanwhile, Traditional Chinese Medicine can provide the more effective and personalized treatment via adjusting the specific medicine for each patient based on the different syndromes. In addition, TCM often has different effect on the distinct stages of diseases, contributing to the prevention, treatment and rehabilitation. Nowadays, TCM has exhibited decent effect in the in the fight against NCP. Therefore, it is convinced that Traditional Chinese Medicine is an effective treatment for 2019 novel coronavirus pneumonia.


title: Current knowledge of COVID-19 and infection prevention and control strategies in healthcare settings: A global analysis

text: OBJECTIVE: In the current absence of a vaccine for COVID-19, public health responses aim to break the chain of infection by focusing on the mode of transmission. We reviewed the current evidence on the transmission dynamics and on pathogenic and clinical features of COVID-19 to critically identify any gaps in the current infection prevention and control (IPC) guidelines. METHODS: In this study, we reviewed global COVID-19 IPC guidelines by organizations such as the World Health Organization (WHO), the US Centers for Disease Control and Prevention (CDC), and the European Centre for Disease Prevention and Control (ECDC). Guidelines from 2 high-income countries (Australia and United Kingdom) and from 1 middle-income country (China) were also reviewed. We searched publications in English on ‘PubMed’ and Google Scholar. We extracted information related to COVID-19 transmission dynamics, clinical presentations, and exposures that may facilitate transmission. We then compared these findings with the recommended IPC measures. RESULTS: Nosocomial transmission of SARS-CoV-2 in healthcare settings occurs through droplets, aerosols, and the oral–fecal or fecal–droplet route. However, the IPC guidelines fail to cover all transmission modes, and the recommendations also conflict with each other. Most guidelines recommend surgical masks for healthcare providers during routine care and N95 respirators for aerosol-generating procedures. However, recommendations regarding the type of face mask varied, and the CDC recommends cloth masks when surgical masks are unavailable. CONCLUSION: IPC strategies should consider all the possible routes of transmission and should target all patient care activities involving risk of person-to-person transmission. This review may assist international health agencies in updating their guidelines.


title: Valosin-containing protein (VCP/p97) plays a role in the replication of West Nile virus

text: Abstract Valosin-containing protein (VCP) is classified as a member of the type II AAA+ ATPase protein family. VCP functions in several cellular processes, including protein degradation, membrane fusion, vesicular trafficking and disassembly of stress granules. Moreover, VCP is considered to play a role in the replication of several viruses, albeit through different mechanisms. In the present study, we have investigated the role of VCP in West Nile virus (WNV) infection. Endogenous VCP expression was inhibited using either VCP inhibitors or by siRNA knockdown. It could be shown that the inhibition of endogenous VCP expression significantly inhibited WNV infection. The entry assay revealed that silencing of endogenous VCP caused a significant reduction in the expression levels of WNV-RNA compared to control siRNA-treated cells. This indicates that VCP may play a role in early steps either the binding or entry steps of the WNV life cycle. Using WNV virus like particles and WNV-DNA-based replicon, it could be demonstrated that perturbation of VCP expression decreased levels of newly synthesized WNV genomic RNA. These findings suggest that VCP is involved in early steps and during genome replication of the WNV life cycle.


title: Identification of two antiviral inhibitors targeting 3C-like serine/3C-like protease of porcine reproductive and respiratory syndrome virus and porcine epidemic diarrhea virus

text: Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) and porcine epidemic diarrhea virus (PEDV) are highly virulent and contagious porcine pathogens that cause tremendous economic losses to the swine industry worldwide. Currently, there is no effective treatment for PRRSV and PEDV, and commercial vaccines do not induce sterilizing immunity. In this study, we screened a library of 1000 compounds and identified two specific inhibitors, designated compounds 2 and 3, which target the PRRSV 3C-like serine protease (3CLSP). First, we evaluated the inhibitory effects of compounds 2 and 3 on PRRSV 3CLSP activity. Next, we determined the anti-PRRSV capacity of compounds 2 and 3 in MARC-145 cells and obtained EC50 and CC50 values of 57μM (CC50 =479.9μM) and 56.8μM (CC50 =482.8μM), respectively. Importantly, compounds 2 and 3 also targeted the PEDV 3C-like protease (3CL protease) and inhibited PEDV replication, showing EC50 and CC50 values of 100μM (CC50 =533.8μM) and 57.9μM (CC50 =522.3μM), respectively. Finally, our results indicated that the active sites (His39 in 3CLSP and His41 in 3CL protease) were conservative, and contacted compounds 2 and 3 via hydrogen bonds and hydrophobic forces in the putative substrate-binding models. In summary, compounds 2 and 3 exhibit broad-spectrum antiviral activity and may facilitate the development of antiviral drugs against PRRSV and PEDV.


title: Treatment-Refractory Headache in the Setting of COVID-19 Pneumonia: Migraine or Meningoencephalitis? Case Report

text: The coronavirus responsible for the COVID-19 pandemic, SARS-2-CoV, most commonly involves the respiratory tract; however, more severe cases have been found to have multi-organ involvement, including the central nervous system. Headache has been documented as a presenting symptom of COVID-19, which may prompt neurology consultation. To date, few cases of COVID-19 meningitis have been confirmed, but it must remain in the differential diagnosis for patients with headache and fever. A 58-year-old female with multiple sclerosis on fingolimod, chronic migraine well-controlled on fremanezumab, and cerebrovascular disease presented with fevers and respiratory symptoms, as well as acute treatment-refractory headache with associated neck stiffness and transient behavioral abnormalities. Although not confirmed with cerebrospinal fluid testing, we suspect this patient had COVID-19 meningoencephalitis, highlighting the need to consider secondary headaches in patients with coronavirus infection, even in the setting of chronic migraine. We offer anecdotal treatment recommendations for acutely refractory secondary headache and guidance for the consulting neurologist during the COVID-19 pandemic.


title: Extensive coronavirus-induced membrane rearrangements are not a determinant of pathogenicity

text: Positive-strand RNA (+RNA) viruses rearrange cellular membranes during replication, possibly in order to concentrate and arrange viral replication machinery for efficient viral RNA synthesis. Our previous work showed that in addition to the conserved coronavirus double membrane vesicles (DMVs), Beau-R, an apathogenic strain of avian Gammacoronavirus infectious bronchitis virus (IBV), induces regions of ER that are zippered together and tethered open-necked double membrane spherules that resemble replication organelles induced by other +RNA viruses. Here we compared structures induced by Beau-R with the pathogenic lab strain M41 to determine whether membrane rearrangements are strain dependent. Interestingly, M41 was found to have a low spherule phenotype. We then compared a panel of pathogenic, mild and attenuated IBV strains in ex vivo tracheal organ culture (TOC). Although the low spherule phenotype of M41 was conserved in TOCs, each of the other tested IBV strains produced DMVs, zippered ER and spherules. Furthermore, there was a significant correlation for the presence of DMVs with spherules, suggesting that these structures are spatially and temporally linked. Our data indicate that virus induced membrane rearrangements are fundamentally linked to the viral replicative machinery. However, coronavirus replicative apparatus clearly has the plasticity to function in different structural contexts.


Test ARN para SARS-CoV-2 positivos recurrentes en pacientes recuperados y dados de alta hospitalaria


title: SAA is a biomarker to distinguish the severity and prognosis of Coronavirus Disease 2019 (COVID-19)

text: Abstract Background To explore the significance of SAA in evaluating the severity and prognosis of COVID-19. Methods A total of 132 patients with confirmed COVID-19 who were admitted to a designated COVID-19 hospital in Wuhan, China from January 18, 2020 to February 26, 2020 were collected. The dynamic changes of blood SAA, CRP, PCT, WBC, Lymphocyte (L), PLT, CT imaging, and disease progression were studied. All patients completed at least twice laboratory data collection and clinical condition assessment at three time points indicated for this study; The length of hospital stay was longer than 14 days prior to February 26, 2020. Results COVID-19 patients had significantly increased SAA and CRP levels, while L count decreased, and PCT, WBC, and PLT were in the normal range. As disease progressed from mild to critically severe, SAA and CRP gradually increased, while L decreased, and PLT, WBC, and PCT had no significant changes; ROC curve analysis suggests that SAA/L, CRP, SAA, and L count are valuable in evaluating the severity of COVID-19 and distinguishing critically ill patients from mild ones; Patients with SAA consistently trending down during the course of disease have better prognosis, compared with the patients with SAA continuously rising; The initial SAA level is positively correlated with the dynamic changes of the serial CT scans. Patient with higher initial SAA level are more likely to have poor CT imaging. Conclusions SAA and L are sensitive indicators in evaluating the severity and prognosis of COVID-19. Monitoring dynamic changes of SAA, combined with CT imaging could be valuable in diagnosis and treatment of COVID-19.


title: Epidemic spreading in metapopulation networks with heterogeneous infection rates

text: Abstract In this paper, we study epidemic spreading in metapopulation networks wherein each node represents a subpopulation symbolizing a city or an urban area and links connecting nodes correspond to the human traveling routes among cities. Differently from previous studies, we introduce a heterogeneous infection rate to characterize the effect of nodes’ local properties, such as population density, individual health habits, and social conditions, on epidemic infectivity. By means of a mean-field approach and Monte Carlo simulations, we explore how the heterogeneity of the infection rate affects the epidemic dynamics, and find that large fluctuations of the infection rate have a profound impact on the epidemic threshold as well as the temporal behavior of the prevalence above the epidemic threshold. This work can refine our understanding of epidemic spreading in metapopulation networks with the effect of nodes’ local properties.


Risk-stratifying COVID-19 Patients the Right Way


title: Strategy of using personal protective equipment during aerosol generating medical procedures with COVID-19

text: • Compared the effectiveness and cost-effectiveness between masks and respirators for the COVID-19 transmission; • Discussed the strategy to avoid severe nosocomial infection through aerosol-generating medical procedures; • Suggestions for healthcare workers to choose proper personal protective equipment.


title: Using predicted imports of 2019-nCoV cases to determine locations that may not be identifying all imported cases

text: Cases from the ongoing outbreak of atypical pneumonia caused by the 2019 novel coronavirus (2019-nCoV) exported from mainland China can lead to self-sustained outbreaks in other populations. Internationally imported cases are currently being reported in several different locations. Early detection of imported cases is critical for containment of the virus. Based on air travel volume estimates from Wuhan to international destinations and using a generalized linear regression model we identify locations which may potentially have undetected internationally imported cases.


COVID-19 - Where have all the STEMIs gone?


title: Respiratory viral infection in exacerbations of COPD

text: Summary Background Patients with COPD have frequent exacerbations. The role of respiratory viral infection is just emerging. We wished to determine prospectively the incidence of viral infection in exacerbated and stable COPD patients as well as smokers who do not have airways obstruction. Methods Stable and exacerbated COPD patients were recruited along with a group of patients who had smoked but who did not have any airways obstruction. Spirometry was performed and sputum specimens were tested for a range of 12 different respiratory viruses using PCR. Results One hundred and thirty-six patients with exacerbations of COPD, 68 stable COPD patients and 16 non-obstructed smokers were recruited. A respiratory virus was detected in 37% of exacerbations, 12% of stable COPD patients and 12% of non-obstructed smokers, p <0.0005. Rhinovirus was most frequently detected. The symptom of fever was associated with virus detection, p <0.05. Infection with more than one virus was only found in the exacerbated COPD patients. Conclusion Respiratory viral infection is associated with exacerbations of COPD. Rhinovirus was the most common infecting agent identified and in two cases human metapneumovirus was also detected. Dual infections were only seen amongst those patients admitted to hospital with acute exacerbations of COPD. Viruses were more commonly detected in those with more severe airways disease.


title: Avian infectious bronchitis and deep pectoral myopathy—A case control study

text: Abstract Infectious bronchitis is caused by a coronavirus, infectious bronchitis virus (IBV). Infectious bronchitis is an acute and highly contagious disease of economic importance due to the reduction in weight gain observed with infected broilers and the drop in egg quality and production associated with infected laying hens. The presence of deep pectoral myopathy has been associated with IBV variants. This lesion is detected at slaughterhouses and is characterized by paleness and atrophy of the deep pectoral muscle, including necrosis of the region, leading to condemnations of the breast muscle, a valuable meat cut in the market. This work aimed to study the relationship between deep pectoral myopathy and IBV by describing tracheal and muscle lesions and comparing the frequency of IBV detection via reverse-transcription (RT) PCR in muscle, tracheal, and cecal tonsil samples from broilers with and without myopathy. A case-control study was conducted in 40 broiler flocks vaccinated with the Massachusetts strain. The case group consisted of 23 flocks that presented myopathic lesions under sanitary inspection and a control group of 17 flocks without myopathic lesions. The tracheal, cecal tonsil, and supracoracoid muscle (with and without lesions) samples from the 40 broiler flocks were screened by RT-PCR to detect IBV. Histopathology of muscle and tracheal tissue was carried out. Upon microscopic examination, the muscle samples from the case group presented extensive necrosis, intense mononuclear inflammatory infiltration, muscle fiber fragmentation, and fibrotic tissue, confirming myopathy, whereas muscles from the control group showed no alterations. The tracheal samples presented a large number of infiltrated mononuclear inflammatory cells that in some areas formed submucosal nodules. A total of 25 flocks tested IBV positive by RT-PCR: 14 from the case group and 11 from the control group. The IBV was detected by RT-PCR directly in muscle samples. Despite that, the relationship between deep pectoral myopathy and IBV was not established. The higher positive IBV RT-PCR percentage noted in the cecal tonsil samples demonstrates how important the choice of organs is for diagnostic purposes.


title: ACE2 Expression is Increased in the Lungs of Patients with Comorbidities Associated with Severe COVID-19

text: The pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has resulted in several thousand deaths worldwide in just a few months. Patients who died from Coronavirus disease 2019 (COVID-19) often had comorbidities, such as hypertension, diabetes, and chronic obstructive lung disease. The angiotensin-converting enzyme 2 (ACE2) was identified as a crucial factor that facilitates SARS-CoV2 to bind and enter host cells. To date, no study has assessed the ACE2 expression in the lungs of patients with these diseases. Here, we analyzed over 700 lung transcriptome samples of patients with comorbidities associated with severe COVID-19 and found that ACE2 was highly expressed in these patients, compared to control individuals. This finding suggests that patients with such comorbidities may have higher chances of developing severe COVID-19. We also found other genes, such as RAB1A, that can be important for SARS-CoV-2 infection in the lung. Correlation and network analyses revealed many potential regulators of ACE2 in the human lung, including genes related to histone modifications, such as HAT1, HDAC2, and KDM5B. In fact, epigenetic marks found in ACE2 locus were compatible to with those promoted by KDM5B. Our systems biology approach offers a possible explanation for increase of COVID-19 severity in patients with certain comorbidities.


title: Plant lectins are potent inhibitors of coronaviruses by interfering with two targets in the viral replication cycle

text: Abstract We describe the antiviral activity of plant lectins with specificity for different glycan structures against the severe acute respiratory syndrome coronavirus (SARS-CoV) and the feline infectious peritonitis virus (FIPV) in vitro. The SARS-CoV emerged in 2002 as an important cause of severe lower respiratory tract infection in humans, and FIPV infection causes a chronic and often fatal peritonitis in cats. A unique collection of 33 plant lectins with different specificities were evaluated. The plant lectins possessed marked antiviral properties against both coronaviruses with EC50 values in the lower microgram/ml range (middle nanomolar range), being non-toxic (CC50) at 50–100μg/ml. The strongest anti-coronavirus activity was found predominantly among the mannose-binding lectins. In addition, a number of galactose-, N-acetylgalactosamine-, glucose-, and N-acetylglucosamine-specific plant agglutinines exhibited anti-coronaviral activity. A significant correlation (with an r-value of 0.70) between the EC50 values of the 10 mannose-specific plant lectins effective against the two coronaviruses was found. In contrast, little correlation was seen between the activity of other types of lectins. Two targets of possible antiviral intervention were identified in the replication cycle of SARS-CoV. The first target is located early in the replication cycle, most probably viral attachment, and the second target is located at the end of the infectious virus cycle.


title: Clinical characteristics and cytokine profiles of children with acute lower respiratory tract infections caused by human rhinovirus

text: The clinical profile of human rhinovirus (HRV) with regard to lower respiratory infections remains unclear. We analyzed the clinical features and cytokine responses of HRV isolates in children with respiratory infections. Quantitative analysis and genotyping of the HRV-positive samples from 601 nasopharyngeal aspirates (NPAs) were performed using VP4/VP2 sequencing. To compare T-helper1 (Th1) type (IFN-γ, TNF-α) and Th2 type (IL-4, IL-10) cytokine responses between HRV-A, B and C, the levels of the four cytokines were measured. The HRV-positive children had shorter fever duration (P = 0.018), and higher frequencies of chest retraction (P = 0.002) and wheezing (P = 0.022) than did the HRV-negative group. HRV-A was identified in 55 cases (58.5%), HRV-B in 8 (8.5%), and HRV-C in 31 (33.0%). There were no significant differences in the clinical data or NPA cytokines levels between patients with HRV-A and HRV-C infections. HRV is an important pathogen of the lower respiratory tract in young children. HRV-A and HRV-C are the dominant species that cause respiratory difficulty in young children.


title: Commonly circulating human coronaviruses do not have a significant role in the etiology of gastrointestinal infections in hospitalized children

text: Abstract Background Human coronaviruses (HCoVs) OC43, 229E, NL63 and HKU1 are common causes of respiratory infections. Over the years, it has been proposed that HCoVs play a possible role in gastrointestinal infections. Objectives To assess the role of HCoVs in acute gastroenteritis (AGE) in children. Study design Study was conducted at Tampere University Hospital over 2 years. Both stool and nasal swab samples were collected from 172 children with AGE, 545 with acute respiratory tract infection (ARTI) and 238 with symptoms of both. The samples were tested for HCoVs by RT-PCR. Results HCoVs were detected in 52 (5.4%) children: in 6.4% of those with AGE, 4.4% with ARTI and 7.1% with symptoms of both. HCoVs OC43, HKU1, 229E and NL63 were encountered in 13, 11, 13 and 15 cases, respectively. HCoVs were detected simultaneously in stool and nasal swab samples in 17 children, in nasal swabs alone in 33 children, and in the stools alone in two children. HCoVs were present in the stools of eight (4.7%) of the 172 children with AGE; in six of these cases, the nasal swab sample was also positive for the respective HCoV. Additionally, in six of the eight cases, the stool sample contained either rotavirus or calicivirus. Conclusions HCoVs can be detected in the stools of children with AGE, but usually together with well-known gastroenteritis viruses, and concomitantly in the respiratory tract. It appears that commonly circulating HCoVs do not have a significant role in the AGE of children admitted to hospital.


title: Bovine respiratory syncytial virus infection enhances Pasteurella multocida adherence on respiratory epithelial cells

text: Abstract Primary infection with bovine respiratory syncytial virus (BRSV) predisposes cattle to secondary infection with bacteria that cause bovine respiratory disease complex (BRDC). However, the interaction between BRSV and bacteria is unclear. This in vitro study examined the adherence of Pasteurella multocida (PM) to BRSV-infected cells was assessed in colony forming unit assays, by flow cytometry analysis, and by indirect immunofluorescence analysis (IFA) of epithelial cells (A549, HEp-2, and MDBK). An in vitro model based on infection of BRSV-infected epithelial cells revealed that PM adherence to BRSV-infected cells was 2- to 8-fold higher than uninfected cells. This was confirmed by flow cytometry analysis and IFA. Epithelial cell expression of mRNA encoding cytokines and chemokines increased after exposure to PM, but increased further after co-infection with BRSV and PM. BRSV-mediated adherence of PM to epithelial cells may underlie the serious symptoms of BRDC.


title: Structural characterization of the HCoV-229E fusion core

text: Abstract HCoV-229E spike (S) protein mediates virion attachment to cells and subsequent fusion of the viral and cellular membranes. This protein is composed of an N-terminal receptor-binding domain (S1) and a C-terminal trans-membrane fusion domain (S2). S2 contains a highly conserved heptad repeat 1 and 2 (HR1 and HR2). In this study, the HRs sequences were designed and connected with a flexible linker. The recombinant fusion core protein was crystallized and its structure was solved at a resolution of 2.45 Å. Then we characterized the binding of HR1s and HR2s via both sequence alignment and structural analysis. The overall structures, especially the residues in some positions of HR2 are highly conserved. Fourteen hydrophobic and three polar residues from each HR1 peptide are packed in layers at the coiled-coil interface. These core amino acids can be grouped into seven heptad repeats. Analysis of hydrophobic and hydrophilic interactions between HR2 helix and HR1 helices, shows that the HR1 and HR2 polypeptides are highly complementary in both shape and chemical properties. Furthermore, the available knowledge concerning HCoV-229E fusion core may make it possible to design small molecule or polypeptide drugs targeting membrane fusion, a crucial step of HCoV-229E infection.


title: Efficacy and safety of current therapeutic options for COVID-19 - lessons to be learnt from SARS and MERS epidemic: A systematic review and meta-analysis

text: Abstract The rapidly progressing of coronavirus disease 2019 (COVID-19) pandemic has become a global concern. This meta-analysis aimed at evaluating the efficacy and safety of current option of therapies for severe acute respiratory syndrome (SARS), Middle Eastern respiratory syndrome (MERS) besides COVID-19, in an attempt to identify promising therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients. We searched PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and WANFANG DATA for randomized controlled trials (RCTs), prospective cohort, and retrospective cohort studies that evaluated therapies (hydroxychloroquine, lopinavir/ritonavir-based therapy, and ribavirin-based therapy, etc.) for SARS, MERS, and COVID-19. The primary outcomes were mortality, virological eradication and clinical improvement, and secondary outcomes were improvement of symptoms and chest radiography results, incidence of acute respiratory disease syndrome (ARDS), utilization of mechanical ventilation, and adverse events (AEs). Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effects models, and the quality of evidence was appraised using GRADEpro. Eighteen articles (5 RCTs, 2 prospective cohort studies, and 11 retrospective cohort studies) involving 4,941 patients were included. Compared with control treatment, anti-coronary virus interventions significantly reduced mortality (RR 0.65, 95% CI 0.44-0.96; I 2 = 81.3%), remarkably ameliorate clinical improvement (RR 1.52, 95% CI 1.05-2.19) and radiographical improvement (RR 1.62, 95% CI 1.11-2.36, I 2 = 11.0 %), without manifesting clear effect on virological eradication, incidence of ARDS, intubation, and AEs. Subgroup analyses demonstrated that the combination of ribavirin and corticosteroids remarkably decreased mortality (RR 0.43, 95% CI 0.27-0.68). The lopinavir/ritonavir-based combination showed superior virological eradication and radiographical improvement with reduced rate of ARDS. Likewise, hydroxychloroquine improved radiographical result. For safety, ribavirin could induce more bradycardia, anemia and transaminitis. Meanwhile, hydroxychloroquine could increase AEs rate especially diarrhea. Overall, the quality of evidence on most outcomes were very low. In conclusion, although we could not draw a clear conclusion for the recommendation of potential therapies for COVID-19 considering the very low quality of evidence and wide heterogeneity of interventions and indications, our results may help clinicians to comprehensively understand the advantages and drawbacks of each anti-coronavirus agents on efficacy and safety profiles. Lopinavir/ritonavir combinations might observe better virological eradication capability than other anti-coronavirus agents. Conversely, ribavirin might cause more safety concerns especially bradycardia. Thus, large RCTs objectively assessing the efficacy of antiviral therapies for SARS-CoV-2 infections should be conducted with high priority.


title: Ethnic and socioeconomic differences in SARS-CoV-2 infection: prospective cohort study using UK Biobank

text: BACKGROUND: Understanding of the role of ethnicity and socioeconomic position in the risk of developing SARS-CoV-2 infection is limited. We investigated this in the UK Biobank study. METHODS: The UK Biobank study recruited 40–70-year-olds in 2006–2010 from the general population, collecting information about self-defined ethnicity and socioeconomic variables (including area-level socioeconomic deprivation and educational attainment). SARS-CoV-2 test results from Public Health England were linked to baseline UK Biobank data. Poisson regression with robust standard errors was used to assess risk ratios (RRs) between the exposures and dichotomous variables for being tested, having a positive test and testing positive in hospital. We also investigated whether ethnicity and socioeconomic position were associated with having a positive test amongst those tested. We adjusted for covariates including age, sex, social variables (including healthcare work and household size), behavioural risk factors and baseline health. RESULTS: Amongst 392,116 participants in England, 2658 had been tested for SARS-CoV-2 and 948 tested positive (726 in hospital) between 16 March and 3 May 2020. Black and south Asian groups were more likely to test positive (RR 3.35 (95% CI 2.48–4.53) and RR 2.42 (95% CI 1.75–3.36) respectively), with Pakistani ethnicity at highest risk within the south Asian group (RR 3.24 (95% CI 1.73–6.07)). These ethnic groups were more likely to be hospital cases compared to the white British. Adjustment for baseline health and behavioural risk factors led to little change, with only modest attenuation when accounting for socioeconomic variables. Socioeconomic deprivation and having no qualifications were consistently associated with a higher risk of confirmed infection (RR 2.19 for most deprived quartile vs least (95% CI 1.80–2.66) and RR 2.00 for no qualifications vs degree (95% CI 1.66–2.42)). CONCLUSIONS: Some minority ethnic groups have a higher risk of confirmed SARS-CoV-2 infection in the UK Biobank study, which was not accounted for by differences in socioeconomic conditions, baseline self-reported health or behavioural risk factors. An urgent response to addressing these elevated risks is required.


Transporting Patient with Suspected SARS


title: Recommendations for Cardiopulmonary Resuscitation (CPR) of patients with suspected or confirmed COVID-19

text: Abstract The care for patients suffering from cardiopulmonary arrest in a context of a COVID-19 pandemic has particularities that should be highlighted. The following recommendations from the Brazilian Association of Emergency Medicine (ABRAMEDE), the Brazilian Society of Cardiology (SBC) and the Brazilian Association of Intensive Medicine (AMIB) and the Brazilian Society of Anesthesiology (SBA), associations and societies official representatives of specialties affiliated to the Brazilian Medical Association (AMB), aim to guide the various assistant teams, in a context of little solid evidence, maximizing the protection of teams and patients. It is essential to wear full Personal Protective Equipment (PPE) for aerosols during the care of Cardiopulmonary Resuscitation (CPR) and it is imperative to consider and treat the potential causes in these patients, especially hypoxia and arrhythmias caused by changes in the QT interval or myocarditis. The installation of an advanced invasive airway must be obtained early and the use of High Efficiency Particulate Arrestance (HEPA) filters at the interface with the valve bag is mandatory; situations of occurrence of CPR during mechanical ventilation and in a prone position demand peculiarities that are different from the conventional CPR pattern. Faced with the care of a patient diagnosed or suspected of COVID-19, the care follows the national and international protocols and guidelines 2015 ILCOR (International Alliance of Resuscitation Committees), AHA 2019 Guidelines (American Heart Association) and the Update of the Cardiopulmonary Resuscitation and Emergency Care Directive of the Brazilian Society of Cardiology 2019.


title: Virological and Epidemiological Situation in the Influenza Epidemic Seasons 2016/2017 and 2017/2018 in Poland

text: The World Health Organization estimates that influenza virus infects 3–5 million people worldwide every year, of whom 290,000 to 650,000 die. In the 2016/2017 epidemic season in Poland, the incidence of influenza was 1,692 per 100,000 population. The influenza A virus, subtype A/H3N2/, was the predominant one in that season. However, in the most recent 2017/2018 epidemic season, the incidence exceeded 1,782 per 100,000 already by August of 2018. In this season, influenza B virus predominated, while the A/H1N1/pdm09 strain was most frequent among the influenza A subtypes. The peak incidence, based on the number of clinical specimens tested, was in weeks 4–5 of 2017 and week 8 of 2018 in the 2016/2017 and 2017/2018 epidemic seasons, respectively. As of the 2017/2018 season, a quadrivalent vaccine, consisting of two antigens of influenza A subtypes and another two of influenza B virus, was available in Poland. Nonetheless, the vaccination rate remained at one of the lowest level in Europe, fluctuating between 3% and 4% of the general Polish population.


title: Fact-finding survey of nosocomial infection control in hospitals in Vietnam and application to training programs

text: Abstract Nosocomial infection control is crucial for improving the quality of medical care. It is also indispensable for implementing effective control measures for severe acute respiratory syndrome (SARS) and the possible occurrence of a human influenza pandemic. The present authors, in collaboration with Vietnamese hospital staff, performed a fact-finding survey of nosocomial infection control in hospitals in northern Vietnam and compared the results with those of a survey conducted 4 years previously. Remarkable improvement was recognized in this period, although there were considerable differences between the central hospitals in Hanoi and local hospitals. In the local hospitals, basic techniques and the systems for infection control were regarded as insufficient, and it is necessary to improve these techniques and systems under the guidance of hospitals in the central area. Based on the results of the survey, programs were prepared and training courses were organized in local hospitals. Evaluation conducted after the training courses showed a high degree of satisfaction among the trainees. The results of the survey and the training courses conducted during the study period are expected to contribute to the improvement of nosocomial infection control in remote areas of Vietnam


title: Cellular Nanosponges Inhibit SARS-CoV-2 Infectivity

text: [Image: see text] We report cellular nanosponges as an effective medical countermeasure to the SARS-CoV-2 virus. Two types of cellular nanosponges are made of the plasma membranes derived from human lung epithelial type II cells or human macrophages. These nanosponges display the same protein receptors, both identified and unidentified, required by SARS-CoV-2 for cellular entry. It is shown that, following incubation with the nanosponges, SARS-CoV-2 is neutralized and unable to infect cells. Crucially, the nanosponge platform is agnostic to viral mutations and potentially viral species, as well. As long as the target of the virus remains the identified host cell, the nanosponges will be able to neutralize the virus.


title: Armillifer-Infected Snakes Sold at Congolese Bushmeat Markets Represent an Emerging Zoonotic Threat

text: African pythons (Pythonidae) and large vipers (Bitis spp.) act as definitive hosts for Armillifer armillatus and Armillifer grandis parasites (Crustacea: Pentastomida) in the Congo Basin. Since the proportion of snakes in bushmeat gradually increases, human pentastomiasis is an emerging zoonotic disease. To substantiate the significance of this threat, we surveyed snakes offered for human consumption at bushmeat markets in the Kole district, Democratic Republic of the Congo, for the presence of adult pentastomids. In Bitis vipers (n = 40), Armillifer spp. infestations exhibited an 87.5% prevalence and 6.0 median intensity. Parasite abundance covaried positively with viper length, but not with body mass. In pythons (n = 13), Armillifer spp. exhibited a 92.3% prevalence and 3.5 median intensity. The positive correlations between parasite abundance and python length or mass were statistically nonsignificant. Ninety-one percent of A. grandis were discovered in vipers and 97% of infected vipers hosted A. grandis, whereas 81% of A. armillatus specimens were found in pythons and 63% of infected pythons hosted A. armillatus. Thus, challenging the widespread notion of strict host specificity, we found ‘reversed’ infections and even a case of coinfection. In this study, we also gathered information about the snake consumption habits of different tribal cultures in the area. Infective parasite ova likely transmit to humans directly by consumption of uncooked meat, or indirectly through contaminated hands, kitchen tools or washing water.


title: Coronavirus Disease 2019 (Covid-19) presenting as purulent fulminant myopericarditis and cardiac tamponade: a case report and literature review.

text: The vast majority of patients in the ongoing coronavirus Disease 2019 (Covid-19) pandemic primarily present with severe respiratory illness. We report a Covid-19 patient who presented with findings of acute coronary syndrome and was found to have purulent fulminant myopericarditis and cardiac tamponade. We compare our case to the previously reported instances of Covid-19-associated myocarditis. Through review of the available literature, we also highlight the potential mechanisms of cardiac injury in Covid-19. We hope to increase awareness amongst clinicians about this unusual presentation of Covid-19.


title: Paramyxovirus F1 protein has two fusion peptides: implications for the mechanism of membrane fusion 1 1 Edited by A. R.Fersht

text: Abstract Viral fusion proteins contain a highly hydrophobic segment, named the fusion peptide, which is thought to be responsible for the merging of the cellular and viral membranes. Paramyxoviruses are believed to contain a single fusion peptide at the N terminus of the F1 protein. However, here we identified an additional internal segment in the Sendai virus F1 protein (amino acids 214–226) highly homologous to the fusion peptides of HIV-1 and RSV. A synthetic peptide, which includes this region, was found to induce membrane fusion of large unilamellar vesicles, at concentrations where the known N-terminal fusion peptide is not effective. A scrambled peptide as well as several peptides from other regions of the F1 protein, which strongly bind to membranes, are not fusogenic. The functional and structural characterization of this active segment suggest that the F1 protein has an additional internal fusion peptide that could participate in the actual fusion event. The presence of homologous regions in other members of the same family suggests that the concerted action of two fusion peptides, one N-terminal and the other internal, is a general feature of paramyxoviruses.


title: Characterization of San Miguel Sea Lion Virus populations using pyrosequencing-based methods

text: Abstract San Miguel Sea Lion Virus (SMSV) is a small RNA virus in the genus Vesivirus with an unusually broad host range. Three populations of SMSV were examined by PCR amplification of the capsid precursor and putative helicase genes, followed by pyrosequencing. The populations were nasal swabs from two SMSV infected California sea lions (Zalophus californianus) from two different years, and a virus isolate from the earlier swab that was passaged in cell culture five times. In the capsid precursor, extensive deletions were prevalent in the passaged virus but uncommon in the clinical samples. A greater prevalence of point mutations was seen in the capsid precursor gene than in the putative helicase gene. In culture, the minority sequence in the capsid precursor at nucleotide position 5826 rapidly shifted after five passages to become the majority sequence. Levels of diversity at individual sites showed much more similarity between the two clinical samples than between the earlier clinical sample and the passaged culture from the same sample. SMSV appears to behave as a quasispecies. Assessment of original patient samples is preferable for understanding clinical SMSV populations.


title: Essential Role of Patient Blood Management in a Pandemic: A Call for Action

text: The World Health Organization (WHO) has declared Coronavirus Disease 2019 (COVID-19), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a pandemic. Global health care now faces unprecedented challenges with widespread and rapid human-to-human transmission of SARS-CoV-2 and high morbidity and mortality with COVID-19 worldwide. Across the world, medical care is hampered by a critical shortage of not only hand sanitizers, personal protective equipment, ventilators, and hospital beds, but also impediments to the blood supply. Blood donation centers in many areas around the globe have mostly closed. Donors, practicing social distancing, some either with illness or undergoing self-quarantine, are quickly diminishing. Drastic public health initiatives have focused on containment and “flattening the curve” while invaluable resources are being depleted. In some countries, the point has been reached at which the demand for such resources, including donor blood, outstrips the supply. Questions as to the safety of blood persist. Although it does not appear very likely that the virus can be transmitted through allogeneic blood transfusion, this still remains to be fully determined. As options dwindle, we must enact regional and national shortage plans worldwide and more vitally disseminate the knowledge of and immediately implement patient blood management (PBM). PBM is an evidence-based bundle of care to optimize medical and surgical patient outcomes by clinically managing and preserving a patient’s own blood. This multinational and diverse group of authors issue this “Call to Action” underscoring “The Essential Role of Patient Blood Management in the Management of Pandemics” and urging all stakeholders and providers to implement the practical and commonsense principles of PBM and its multiprofessional and multimodality approaches.


title: Molecular survey of enteric viruses in commercial chicken farms in Korea with a history of enteritis

text: Abstract Several enteric viruses have increasingly received attention as potential causative agents of runting-stunting syndrome (RSS) in chickens. A molecular survey was performed to determine the presence of a broad range of enteric viruses, namely chicken astrovirus (CAstV), avian nephritis virus (ANV), chicken parvovirus (ChPV), infectious bronchitis virus (IBV), avian rotavirus (AvRV), avian reovirus (ARV), and fowl adenovirus (FAdV), in intestinal samples derived from 34 commercial chicken flocks that experienced enteritis outbreaks between 2010 and 2012. Using techniques such as PCR and reverse-transcription PCR, enteric viruses were identified in a total of 85.3% of investigated commercial chicken flocks in Korea. Furthermore, diverse combinations of 2 or more enteric viruses were simultaneously identified in 51.7% of chicken farms positive for enteric viruses. The rank order of positivity for enteric viruses was as follows: ANV (44.1%), CAstV (38.2%), ChPV (26.5%), IBV (20.6%), ARV (8.8%), AvRV (5.9%), and FAdV (2.9%). Additionally, other pathogens such as Escherichia coli, Salmonella spp., Eimeria spp., and FAdV were detected in 79% of chicken flocks positive for enteric viruses using PCR, bacterial isolation, and microscopic examination. The results of our study indicate the presence of several enteric viruses with various combinations in commercial chicken farms that experienced enteritis outbreaks. Experimental studies are required to further understand the roles of enteric viruses in RSS in commercial chickens.


Infectious disease trends in China since the SARS outbreak


Educación Remota En Médicos Residentes En Tiempos Del Covid-19


title: The Effect of The COVID-19 Pandemic On Electively Scheduled HIP and KNEE Arthroplasty Patients in THE United States

text: Abstract In response to the COVID-19 pandemic, US hospitals stopped performing elective procedures. This led to cancellation of a large number of hip and knee arthroplasty cases. We aimed to assess the effect this had on our elective primary arthroplasty patients by distributing a specifically designed survey to patients across six institutions identified through the AAHKS Research Committee. Surveys were completed by 360 patients over the course of one week. Patients were most anxious about the uncertainty of when their operation could be rescheduled. Although 85% of patients understood and agreed with the cancellation of elective surgeries as part of public health measures to curb the spread of pandemic, almost 90% of patients plan to reschedule as soon as possible. Financial concerns were minimal in this cohort. Patients suffering from pain of hip and knee arthritis continue to struggle with their end-stage disease and despite anxiety about the COVID-19 pandemic, plan to undergo arthroplasty as soon as possible.


title: Inhibition of porcine circovirus type 1 and type 2 production in PK-15 cells by small interfering RNAs targeting the Rep gene

text: Abstract Porcine circovirus type 1 (PCV1) and type 2 (PCV2) are two genotypes of porcine circovirus. Both of them are presumed to be widespread in the swine population. Currently, there is no specific treatment for their infections. RNA interference (RNAi) is a sequence-specific RNA degradation mechanism mediated by small interfering RNA (siRNA), which represents a possible therapeutic application for the treatment of viral infections. In this study, three siRNA expression plasmids (pS-RepA, pS-RepB and pS-RepC) were generated to target three different coding regions of the Rep protein (Rep) of PCV. These siRNAs were used to inhibit PCV production in a porcine kidney cell line, PK-15 cells. Our results revealed that Rep gene expression was inhibited by pS-RepA, pS-RepB and pS-RepC to different degrees. Moreover, our study also showed that the production of PCV1 and PCV2 was reduced by these siRNAs. pS-RepC, which targets the middle region of Rep gene, proved to be the most efficient siRNA for inhibition of Rep expression and viral production. Taken together, our data suggest that RNAi could be investigated as a potential treatment for PCV infection.


title: Occurrence of enterotoxigenic and nonenterotoxigenic Bacteroides fragilis in calves and evaluation of their antimicrobial susceptibility

text: Bacteroides fragilis is considered an important clinical pathogen and the most common anaerobe isolated from human and animal clinical specimens; enterotoxigenic strains produce diarrhea. The presence of enterotoxigenic (ETBF) and nonenterotoxigenic B. fragilis in stool samples from calves with or without acute diarrhea and the antimicrobial susceptibility of the strains were evaluated. The stool samples were plated onto a selective B. fragilis–bile–esculin agar, and incubated anaerobically (10% CO(2)/90% N(2)), at 37°C, for 72 h. Species of the B. fragilis group were identified by using the API 32-A kit. Enterotoxigenic strains were detected by PCR and the cytotoxic assay. From 54 diarrhea and 54 nondiarrhea stools, 124 and 92 members of the B. fragilis group, respectively, were recovered. Only two ETBF strains were isolated from two different diarrhea samples and the bft gene was detected in both. Moreover, the bft gene was detected in DNA from four different diarrheal stools samples but no ETBF strain was recovered. All the bacteria were susceptible to chloramphenicol, imipenem, moxifloxacin, piperacillin/tazobactam, metronidazole and tigecycline. Most of the isolates from both calves with and without diarrhea were resistant to all metals. Our results are of concern, and suggest the need to increase the surveillance of antibiotic and metal resistance of this microbial group isolated from animal production such as calves.


title: The cloning and sequencing of the virion protein genes from a British isolate of porcine respiratory coronavirus: comparison with transmissible gastroenteritis virus genes

text: Abstract Previous analysis of porcine respiratory coronavirus (PRCV) mRNA species showed that mRNAs 2 and 3 were smaller than the corresponding transmissible gastroenteritis virus (TGEV) mRNA species (Page et al. (1991) J. Gen. Virol. 72, 579–587). Sequence analysis showed that mRNA 3 was smaller due to the presence of a new putative RNA-leader binding site upstream of the PRCV ORF-3 gene. However, this observation did not explain the deletion observed in PRCV mRNA 2. Polymerase chain reaction (PCR) was used to generate cDNA from the 3' coding region of the putative polymerase gene to the poly (A) tail of PRCV for comparison to the equivalent region from TGEV. The PRCV S protein was found to consist of 1225 amino acids, which had 98% similarity to the TGEV S protein. However, the PRCV S gene contained a 672 nucleotide deletion, corresponding to 224 amino acids (residues 21 to 245 in TGEV S protein), 59 nucleotides downstream of the S gene initiation codon. The PRCV genome from the ORF-3 gene to the poly (A) tail was sequenced for comparison to TGEV in order to identify other potential differences between the two viruses. Four ORFs were identified that showed 98% similarity to the TGEV ORF-4, M, N and ORF-7 genes. No other deletions or any PRCV specific sequences were identified.


title: GLIPR1L1 is an IZUMO-binding protein required for optimal fertilization in the mouse

text: BACKGROUND: The sperm protein IZUMO1 (Izumo sperm-egg fusion 1) and its recently identified binding partner on the oolemma, IZUMO1R, are among the first ligand-receptor pairs shown to be essential for gamete recognition and adhesion. However, the IZUMO1-IZUMO1R interaction does not appear to be directly responsible for promoting the fusion of the gamete membranes, suggesting that this critical phase of the fertilization cascade requires the concerted action of alternative fusogenic machinery. It has therefore been proposed that IZUMO1 may play a secondary role in the organization and/or stabilization of higher-order heteromeric complexes in spermatozoa that are required for membrane fusion. RESULTS: Here, we show that fertilization-competent (acrosome reacted) mouse spermatozoa harbor several high molecular weight protein complexes, a subset of which are readily able to adhere to solubilized oolemmal proteins. At least two of these complexes contain IZUMO1 in partnership with GLI pathogenesis-related 1 like 1 (GLIPR1L1). This interaction is associated with lipid rafts and is dynamically remodeled upon the induction of acrosomal exocytosis in preparation for sperm adhesion to the oolemma. Accordingly, the selective ablation of GLIPR1L1 leads to compromised sperm function characterized by a reduced ability to undergo the acrosome reaction and a failure of IZUMO1 redistribution. CONCLUSIONS: Collectively, this study characterizes multimeric protein complexes on the sperm surface and identifies GLIPRL1L1 as a physiologically relevant regulator of IZUMO1 function and the fertilization process.


title: Mathematical epidemiology is not an oxymoron

text: A brief description of the importance of communicable diseases in history and the development of mathematical modelling of disease transmission is given. This includes reasons for mathematical modelling, the history of mathematical modelling from the foundations laid in the late nineteenth century to the present, some of the accomplishments of mathematical modelling, and some challenges for the future. Our purpose is to demonstrate the importance of mathematical modelling for the understanding and management of infectious disease transmission.


title: Hemorrhagic Fever Viruses

text: This article reviews the epidemiology, pathophysiology, and clinical management of patients with suspected or confirmed viral hemorrhagic fever infection. The focus is on clinical management based on case series from naturally occuring outbreaks of viral hemorrhagic fever infection as well as imported cases of viral hemorrhagic fever encountered in industrialized nations. The potential risk of bioterrorism involving these agents is discussed as well as emergency department and critical care management of isolated cases or larger outbreaks. Important aspects of management, including recognition of infected patients, isolation and decontamination procedures, as well as available vaccines and therapies are emphasized.


Suicides related to the COVID-19 outbreak in India: a pilot study of media reports


title: Metallothionein (I+II) confers, via c-myc, immune plasticity in oldest mice: model of partial hepatectomy/liver regeneration

text: Abstract Because of its similarity to ageing in impaired immune efficiency 48 h after surgical procedures on young partially hepatectomised mice, partial hepatectomy/liver regeneration (pHx) provides a good model for the study of inflammation in ageing. In old age, high metallothionein (I+II) (MT) sequesters a substantial number of intracellular zinc ions consequently leading to low zinc ion bioavailability for an adequate immune response. Corticosterone and IL-6 affect MTmRNA induction in inflammation and after pHx against oxidative damage. The aim of this study was to investigate the role played by MT in conferring immune plasticity in ageing and in very old age using the pHx model. 48 h after their partial hepatectomy, the crude zinc balance was negative in young, old and very old mice coupled with increased MT, corticosterone, sIL-6R and IL-6. Concomitantly, Natural Killer (NK) cell activity and IL-2 production decreased. Complete restoration of the nutritional–endocrine–immune parameters occurred 15 days from the surgical procedures in young and very old mice, but not in old or transgenic mice overexpressing MT. A significant positive or inverse correlation among nutritional–endocrine–immune parameters exists in young and very old mice, but not in old mice during liver regeneration. Since MT also affects c-myc, the gene expression of c-myc declines from 48 h to days 7 and 15 after pHx in young and very old mice, but remains constantly high in old pHx mice for the same days. This circumstance leads to the appearance of tumours in the long run in old pHx mice and survival times that are shorter than old sham controls. Because complete remodelling also occurs in IL-6 and in sIL-6R in very old mice during liver regeneration, the pre-existing inflammation is not detrimental in very old age. As such, very old mice are still responsive to large inflammation, such as pHx, thanks to correct MT homeostasis. Correct MT homeostasis, via c-myc, is therefore pivotal in both suitable liver regeneration and in conferring immune plasticity with subsequent successful ageing. High MT plays an extremely harmful role in ageing: on one hand it lowers zinc ion bioavailability levels required for immune efficiency and on the other hand it increases c-myc expression. The combination of immune depression and enhanced c-myc, via high MT, may trigger the appearance of age-related degenerative diseases.


Sierra Leone – Pandemic Politics


title: The role of viruses in the induction and progression of asthma

text: Viral respiratory infections have been related to asthma in several ways. It is well established that viral common colds precipitate exacerbations of asthma. Severe bronchiolitis in early life is related to subsequent wheezing and therefore may represent a marker of susceptibility to asthma; alternatively, it could be involved in the initiation of the disease. Finally, it is possible that some infections may protect from the development of asthma and allergies by promoting a type-1 host response. However, whether respiratory or other viruses could mediate such a protective effect is debated. The design and implementation of novel anti- or proviral strategies targeting asthma depends on the resolution of these questions. This review presents current evidence on the epidemiologic correlations and proposed mechanisms for the involvement of viral infections in the development and progression of asthma.


At the epicenter of severe acute respiratory syndrome


title: The clinical feature of silent infections of novel coronavirus infection (COVID‐19) in Wenzhou

text: Here were reported clinical features of silent infected COVID‐19 patients. Our study showed that the prevalence of the silent infection of COVID‐19 is 5.8% (95% CI: 3.4‐9.9%), which is much higher than 1.2% which from the report in China CDC. The silent infection patients were more likely to be young adults, the patients without chronic disease. All of the cases in the presented study was found because they were traced as close contact of confirmed cases. Our study indicated that traced the close contract of confirmed case, long time self‐quarantine, and screening is necessary to prevent the secondary cases in community. This article is protected by copyright. All rights reserved.


Editorial: Challenges to Opioid Use Disorders During COVID‐19


title: The pivotal link between ACE2 deficiency and SARS-CoV-2 infection

text: Abstract Angiotensin converting enzyme-2 (ACE2) receptors mediate the entry into the cell of three strains of coronavirus: SARS-CoV, NL63 and SARS-CoV-2. ACE2 receptors are ubiquitous and widely expressed in the heart, vessels, gut, lung (particularly in type 2 pneumocytes and macrophages), kidney, testis and brain. ACE2 is mostly bound to cell membranes and only scarcely present in the circulation in a soluble form. An important salutary function of membrane-bound and soluble ACE2 is the degradation of angiotensin II to angiotensin1-7. Consequently, ACE2 receptors limit several detrimental effects resulting from binding of angiotensin II to AT1 receptors, which include vasoconstriction, enhanced inflammation and thrombosis. The increased generation of angiotensin1-7 also triggers counter-regulatory protective effects through binding to G-protein coupled Mas receptors. Unfortunately, the entry of SARS-CoV2 into the cells through membrane fusion markedly down-regulates ACE2 receptors, with loss of the catalytic effect of these receptors at the external site of the membrane. Increased pulmonary inflammation and coagulation have been reported as unwanted effects of enhanced and unopposed angiotensin II effects via the ACE→Angiotensin II→AT1 receptor axis. Clinical reports of patients infected with SARS-CoV-2 show that several features associated with infection and severity of the disease (i.e., older age, hypertension, diabetes, cardiovascular disease) share a variable degree of ACE2 deficiency. We suggest that ACE2 down-regulation induced by viral invasion may be especially detrimental in people with baseline ACE2 deficiency associated with the above conditions. The additional ACE2 deficiency after viral invasion might amplify the dysregulation between the ‘adverse’ ACE→Angiotensin II→AT1 receptor axis and the ‘protective’ ACE2→Angiotensin1-7→Mas receptor axis. In the lungs, such dysregulation would favor the progression of inflammatory and thrombotic processes triggered by local angiotensin II hyperactivity unopposed by angiotensin1-7. In this setting, recombinant ACE2, angiotensin1-7 and angiotensin II type 1 receptor blockers could be promising therapeutic approaches in patients with SARS-CoV-2 infection.


title: Development of potent dipeptide-type SARS-CoV 3CL protease inhibitors with novel P3 scaffolds: Design, synthesis, biological evaluation, and docking studies

text: We report the design and synthesis of a series of dipeptide-type inhibitors with novel P3 scaffolds that display potent inhibitory activity against SARS-CoV 3CL(pro). A docking study involving binding between the dipeptidic lead compound 4 and 3CL(pro) suggested the modification of a structurally flexible P3 N-(3-methoxyphenyl)glycine with various rigid P3 moieties in 4. The modifications led to the identification of several potent derivatives, including 5c–k and 5n with the inhibitory activities (K(i) or IC(50)) in the submicromolar to nanomolar range. Compound 5h, in particular, displayed the most potent inhibitory activity, with a K(i) value of 0.006 μM. This potency was 65-fold higher than the potency of the lead compound 4 (K(i) = 0.39 μM). In addition, the K(i) value of 5h was in very good agreement with the binding affinity (16 nM) observed in isothermal titration calorimetry (ITC). A SAR study around the P3 group in the lead 4 led to the identification of a rigid indole-2-carbonyl unit as one of the best P3 moieties (5c). Further optimization showed that a methoxy substitution at the 4-position on the indole unit was highly favorable for enhancing the inhibitory potency.


title: Point of care and intensive care lung ultrasound: A reference guide for practitioners during COVID-19

text: Abstract Objectives Current events with the recent COVID-19 outbreak are necessitating steep learning curves for the NHS workforce. Ultrasound, although not used in the diagnosis of COVID-19 may be utilised by practitioners at the point of care (POC) or on the intensive care units (ITUs) where rapid assessment of the lung condition may be required. The aim of this article was to review current literature surrounding the use of lung ultrasound in relation to COVID-19 and provide Sonographers with a quick and digestible reference guide for lung pathologies. Key findings Ultrasound is being used in Italy and China to help review lung condition during the COVID-19 outbreak however not strictly as a diagnostic tool as Computed Tomography (CT) of the chest and chest radiographs are currently gold standard. Ultrasound is highly sensitive in the detection of multiple lung pathologies which can be demonstrated in conjunction with COVID-19 however to date there are no specific, nor pathognomonic findings which relate to COVID-19 on ultrasound. Conclusion Lung ultrasound is highly sensitive and can quickly and accurately review lung condition creating potential to assess for changes or resolution over time, especially in the ITU and POC setting. However it should not be used as a diagnostic tool for COVID-19 due to low specificity in relation to the virus. Implications for practice The adoption of lung ultrasound to monitor lung condition during the COVID-19 outbreak may reduce the need for serial exposure to ionising radiation on the wards and in turn reduce the number of radiographers required to attend infected wards and bays, protecting both patients and the workforce.


title: Comparative Evaluation of Three Homogenization Methods for Isolating Middle East Respiratory Syndrome Coronavirus Nucleic Acids From Sputum Samples for Real-Time Reverse Transcription PCR

text: BACKGROUND: Real-time reverse transcription PCR (rRT-PCR) of sputum samples is commonly used to diagnose Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Owing to the difficulty of extracting RNA from sputum containing mucus, sputum homogenization is desirable prior to nucleic acid isolation. We determined optimal homogenization methods for isolating viral nucleic acids from sputum. METHODS: We evaluated the following three sputum-homogenization methods: proteinase K and DNase I (PK-DNase) treatment, phosphate-buffered saline (PBS) treatment, and N-acetyl-L-cysteine and sodium citrate (NALC) treatment. Sputum samples were spiked with inactivated MERS-CoV culture isolates. RNA was extracted from pretreated, spiked samples using the easyMAG system (bioMérieux, France). Extracted RNAs were then subjected to rRT-PCR for MERS-CoV diagnosis (DiaPlex Q MERS-coronavirus, SolGent, Korea). RESULTS: While analyzing 15 spiked sputum samples prepared in technical duplicate, false-negative results were obtained with five (16.7%) and four samples (13.3%), respectively, by using the PBS and NALC methods. The range of threshold cycle (Ct) values observed when detecting upE in sputum samples was 31.1–35.4 with the PK-DNase method, 34.7–39.0 with the PBS method, and 33.9–38.6 with the NALC method. Compared with the control, which were prepared by adding a one-tenth volume of 1:1,000 diluted viral culture to PBS solution, the ranges of Ct values obtained by the PBS and NALC methods differed significantly from the mean control Ct of 33.2 (both P<0.0001). CONCLUSIONS: The PK-DNase method is suitable for homogenizing sputum samples prior to RNA extraction.


title: Failure in initial stage containment of global COVID‐19 epicenters

text: With multiple virus epicenters, COVID‐19 has been declared a pandemic by the World Health Organization. Consequently, many countries have implemented different policies to manage this crisis including curfew and lockdown. However, the efficacy of individual policies remains unclear with respect to COVID‐19 case development. We analyzed available data on COVID‐19 cases of eight majorly affected countries, including China, Italy, Iran, Germany, France, Spain, South Korea, and Japan. Growth rates and doubling time of cases were calculated for the first 6 weeks after the initial cases were declared for each respective country and put into context with implemented policies. Although the growth rate of total confirmed COVID‐19 cases in China has decreased, those for Japan have remained constant. For European countries, the growth rate of COVID‐19 cases considerably increased during the second time interval. Interestingly, the rates for Germany, Spain, and France are the highest measured in the second interval and even surpass the numbers in Italy. Although the initial data in Asian countries are encouraging with respect to case development at the initial stage, the opposite is true for European countries. Based on our data, disease management in the 2 weeks following the first reported cases is of utmost importance.


COVID-19: a multifaceted threat to refugee camps


title: Fever and the Rational Use of Antimicrobials in the Emergency Department

text: Any patient presenting to the emergency department (ED) with fever triggers consideration of the administration of an antimicrobial. Empiric antimicrobial therapy has become a cornerstone of treatment. Frequently, the decision to initiate empiric treatment needs to be made before the definitive diagnosis is known. In such cases, an organized approach is helpful. This article aims to provide a systems-based approach to prescribing antimicrobials to patients presenting to the ED with fever, while understanding the risk associated with overutilization. An understanding of the key considerations is needed to ensure that decisions are made well and appropriate treatment begins promptly.


title: Evaluation of Four Commercial Multiplex Molecular Tests for the Diagnosis of Acute Respiratory Infections

text: Acute Respiratory Infections (ARIs) are responsible for considerable morbidity and mortality worldwide. Documentation of respiratory specimens can help for an appropriate clinical management with a significant effect on the disease progress in patient, the antimicrobial therapy used and the risk of secondary spread of infection. Here, we compared the performances of four commercial multiplex kits used in French University Hospital diagnostic microbiology laboratories for the detection of ARI pathogens (i.e., the xTAG Respiratory Viral Panel Fast, RespiFinder SMART 22, CLART PneumoVir and Fast Track Diagnostics Respiratory Pathogen 33 kits). We used a standardised nucleic acids extraction protocol and a comprehensive comparative approach that mixed reference to well established real-time PCR detection techniques and analysis of convergent positive results. We tested 166 respiratory clinical samples and identified a global high degree of correlation for at least three of the techniques (xTAG, RespiFinder and FTD33). For these techniques, the highest Youden’s index (YI), positive predictive (PPV) and specificity (Sp) values were observed for Core tests (e.g., influenza A [YI:0.86–1.00; PPV:78.95–100.00; Sp:97.32–100.00] & B [YI:0.44–1.00; PPV:100.00; Sp:100.00], hRSV [YI:0.50–0.99; PPV:85.71–100.00; Sp:99.38–100.00], hMPV [YI:0.71–1.00; PPV:83.33–100.00; Sp:99.37–100.00], EV/hRV [YI:0.62–0.82; PPV:93.33–100.00; Sp:94.48–100.00], AdV [YI:1.00; PPV:100.00; Sp:100.00] and hBoV [YI:0.20–0.80; PPV:57.14–100.00; Sp:98.14–100.00]). The present study completed an overview of the multiplex techniques available for the diagnosis of acute respiratory infections.


title: Digital Approaches to Remote Pediatric Health Care Delivery During the COVID-19 Pandemic: Existing Evidence and a Call for Further Research

text: The global spread of the coronavirus disease (COVID-19) outbreak poses a public health threat and has affected people worldwide in various unprecedented ways, both personally and professionally. There is no question that the current global COVID-19 crisis, now more than ever, is underscoring the importance of leveraging digital approaches to optimize pediatric health care delivery in the era of this pandemic. In this perspective piece, we highlight some of the available digital approaches that have been and can continue to be used to streamline remote pediatric patient care in the era of the COVID-19 pandemic, including but not limited to telemedicine. JMIR Pediatrics and Parenting is currently publishing a COVID-19 special theme issue in which investigators can share their interim and final research data related to digital approaches to remote pediatric health care delivery in different settings. The COVID-19 pandemic has rapidly transformed health care systems worldwide, with significant variations and innovations in adaptation. There has been rapid expansion of the leveraging and optimization of digital approaches to health care delivery, particularly integrated telemedicine and virtual health. Digital approaches have played and will play major roles as invaluable and reliable resources to overcome restrictions and challenges imposed during the COVID-19 pandemic and to increase access to effective, accessible, and consumer-friendly care for more patients and families. However, a number of challenges remain to be addressed, and further research is needed. Optimizing digital approaches to health care delivery and integrating them into the public health response will be an ongoing process during the current COVID-19 outbreak and during other possible future pandemics. Regulatory changes are essential to support the safe and wide adoption of these approaches. Involving all relevant stakeholders in addressing current and future challenges as well as logistical, technological, and financial barriers will be key for success. Future studies should consider evaluating the following research areas related to telemedicine and other digital approaches: cost-effectiveness and return on investment; impact on quality of care; balance in use and number of visits needed for the management of both acute illness and chronic health conditions; system readiness for further adoption in other settings, such as inpatient services, subspecialist consultations, and rural areas; ongoing user-centered evaluations, with feedback from patients, families, and health care providers; strategies to optimize health equity and address disparities in access to care related to race and ethnicity, socioeconomic status, immigration status, and rural communities; privacy and security concerns for protected health information with Health Insurance Portability and Accountability Act (HIPAA)–secured programs; confidentiality issues for some specific populations, especially adolescents and those in need of mental health services; early detection of exposure to violence and child neglect; and integration of training into undergraduate and graduate medical education and subspecialty fellowships. Addressing these research areas is essential to understanding the benefits, sustainability, safety, and optimization strategies of telemedicine and other digital approaches as key parts of modern health care delivery. These efforts will inform long-term adoption of these approaches with expanded dissemination and implementation efforts.


title: Diagnostic System for Rapid and Sensitive Differential Detection of Pathogens

text: Naturally emerging and deliberately released pathogens demand new detection strategies to allow early recognition and containment. We describe a diagnostic system for rapid, sensitive, multiplex discrimination of microbial gene sequences and report its application for detecting 22 respiratory pathogens in clinical samples.


title: Frequency of PRRS live vaccine virus (European and North American genotype) in vaccinated and non-vaccinated pigs submitted for respiratory tract diagnostics in North-Western Germany

text: Abstract The frequency of PRRSV corresponding to live vaccines and wild-type was determined in 902 pigs from North-Western Germany submitted for post-mortem examination. Overall, 18.5% of the samples were positive for the EU wild-type virus. EU genotype vaccine virus was detected in 1.3% and the NA genotype vaccine virus in 8.9% of all samples. The detection of the EU vaccine was significantly higher in pigs vaccinated with the corresponding vaccine (OR=9.4). Pigs vaccinated with NA genotype had significantly higher detection chances for the corresponding vaccine virus when compared to non-vaccinated animals (OR=3.34) animals, however, NA vaccine was also frequently detected in non-vaccinated pigs. Concluding, the dynamics of NA genotype vaccine and EU wild-type virus corresponds with studies on PRRSV spread in endemically infected herds. The potential of spontaneous spread of the NA genotype vaccine should be considered in the planning of eradication programs.


title: Intestinal lymphatic transport for drug delivery

text: Abstract Intestinal lymphatic transport has been shown to be an absorptive pathway following oral administration of lipids and an increasing number of lipophilic drugs, which once absorbed, diffuse across the intestinal enterocyte and while in transit associate with secretable enterocyte lipoproteins. The chylomicron-associated drug is then secreted from the enterocyte into the lymphatic circulation, rather than the portal circulation, thus avoiding the metabolically-active liver, but still ultimately returning to the systemic circulation. Because of this parallel and potentially alternative absorptive pathway, first-pass metabolism can be reduced while increasing lymphatic drug exposure, which opens the potential for novel therapeutic modalities and allows the implementation of lipid-based drug delivery systems. This review discusses the physiological features of the lymphatics, enterocyte uptake and metabolism, links between drug transport and lipid digestion/re-acylation, experimental model (in vivo, in vitro, and in silico) of lymphatic transport, and the design of lipid- or prodrug-based drug delivery systems for enhancing lymphatic drug transport.


title: Coronavirus infections in hospitalized pediatric patients with acute respiratory tract disease

text: BACKGROUND: Acute viral respiratory infections are an important cause of morbidity and mortality in humans worldwide. The etiological backgrounds of these infections remain unconfirmed in most clinical cases. The aim of this study was to estimate the prevalence of human coronavirus infections in a series of children hospitalized with symptoms of acute respiratory tract disease in a one-year period in Slovenia. METHODS: The 664 specimens from 592 children under six years of age hospitalized at the University Children’s Hospital in Ljubljana were sent for the routine laboratory detection of respiratory viruses. Respiratory viruses were detected with a direct immunofluorescence assay and human coronaviruses were detected with a modified real-time RT–PCR. RESULTS: HCoV RNA was detected in 40 (6%, 95% CI: 4.3%–8.1%) of 664 samples. Of these specimens, 21/40 (52.5%) were identified as species HKU1, 7/40 (17.5%) as OC43, 6/40 (15%) as 229E, and 6/40 (15%) as NL63. Infection with HCoV occurred as a coinfection with one or more other viruses in most samples (70%). Of the HCoV-positive children, 70.3% had lower respiratory tract infections. CONCLUSION: The results of our study show that HCoV are frequently detected human pathogens, often associated with other respiratory viruses and acute respiratory tract infections in hospitalized children. An association between age and the viral load was found. The highest viral load was detected in children approximately 10 months of age.


title: Palmitoylation of the feline immunodeficiency virus envelope glycoprotein and its effect on fusion activity and envelope incorporation into virions

text: Abstract The feline immunodeficiency virus (FIV) envelope glycoprotein (Env) possesses a short cytoplasmic domain of 53 amino acids containing four highly conserved cysteines at Env positions 804, 811, 815 and 848. Since palmitoylation of transmembrane proteins occurs at or near the membrane anchor, we investigated whether cysteines 804, 811 and 815 are acylated and analyzed the relevance of these residues for Env functions. Replacement of cysteines 804, 811 and 815 individually or in combination by serine residues resulted in Env glycoproteins that were efficiently expressed and processed. However, mutations C804S and C811S reduced Env fusogenicity by 93% and 84%, respectively, compared with wild-type Env. By contrast, mutant C815S exhibited a fusogenic capacity representing 50% of the wild-type value. Remarkably, the double mutation C804S/C811S abrogated both Env fusion activity and Env incorporation into virions. Finally, by means of Click chemistry assays we demonstrated that the four FIV Env cytoplasmic cysteines are palmitoylated.


title: Recommendations on the use of radiation therapy in managing patients with gastrointestinal malignancies in the era of COVID-19

text: Abstract As of April 6, 2020, there are over 1,200,000 reported cases and 70,000 deaths worldwide due to COVID-19, the disease caused by the SARS-CoV-2 virus, and these numbers rise exponentially by the day.[1] According to the Centers for Disease Control (CDC), the most effective means of minimizing the spread of the virus is through reducing interactions between individuals.[2] We performed a review of the literature, as well as national and international treatment guidelines, seeking data in support of the RADS principle (Remote visits, Avoid radiation, Defer radiation, Shorten radiation)[3] as it applies to gastrointestinal cancers. The purpose of the present work is to guide radiation oncologists managing patients with gastrointestinal cancers during the COVID-19 crisis in order to maintain the safety of our patients, while minimizing the impact of the pandemic on cancer outcomes.


title: Pharyngitis: Certain clinico-pictorial differentiators

text: Abstract Pharyngitis is an acute inflammatory infection of pharynx and/or tonsils, most cases are caused by viruses and occur as part of common cold syndromes. As there is marked overlap between clinical findings of viral and bacterial pharyngitis and it is difficult to distinguish GABHS from viral causes clinicians tend to prescribe antibiotics for any sore throat and therefore pharyngitis has become the raison d'être for antibiotic misuses. Although clinical findings may not specifically differentiate the various pharyngitis pathogens yet many of these pathogens have clinical markers which could give us some clues to clinical suspicion. A good picture is equal to thousand words, believing in this axiom article presents few simple clinico-pictorial clues which could help suspecting pharyngitis pathogens, this in turn may boost clinical confidence to avoid unnecessary antibiotic prescriptions.