docid: nyocnvvj

title: Current perspectives in transfusion-transmitted infectious diseases: emerging and re-emerging infections

text: BACKGROUND: In August 2009, a group from the AABB (Stramer et al., Transfusion 2009;99:1S–29S, Emerging Infectious Disease Agents and their Potential Threat to Transfusion Safety; http://www.aabb.org/resources/bct/eid/Pages/default.aspx) published a Supplement to Transfusion that reviewed emerging infectious disease (EID) agents that pose a real or theoretical threat to transfusion safety, but for which an existing effective intervention is lacking. The necessary attributes for transfusion transmission were outlined including: presence of the agent in blood during the donor's asymptomatic phase, the agent's survival/persistence in blood during processing/storage, and lastly that the agent must be recognized as responsible for a clinically apparent outcome in at least a proportion of recipients who become infected. Without these attributes, agents are not considered as a transfusion-transmission threat and were excluded. Sixty-eight such agents were identified with enough evidence/likelihood of transfusion transmission (e.g., blood phase) and potential for clinical disease to warrant further consideration. In the Supplement, Fact Sheets (FS) were published providing information on: agent classification; disease agent's importance; clinical syndromes/diseases caused; transmission modes (including vectors/reservoirs); likelihood of transfusion transmission, and if proven to be transfusion-transmitted, information on known cases; the feasibility/predicted success of interventions for donor screening (questioning) and tests available for diagnostics/ adapted for donor screening; and finally, the efficacy, if known, of inactivation methods for plasma-derived products. The Supplement included a separate section on pathogen reduction using published data. Agents were prioritized relative to their scientific/epidemiologic threat and their perceived threat to the community including concerns expressed by the regulators of blood. Agents given the highest priority due to a known transfusion-transmission threat and severe/fatal disease in recipients were the vCJD prion, dengue viruses and the obligate red-cell parasite that causes babesiosis (B. microti and related Babesia). Although the focus of the Supplement was towards the United States and Canada, many of the agents (and the process) are applicable worldwide. NEXT STEPS: Since the publication of the Supplement, six new FSs (yellow fever viruses-including vaccine breakthrough infections, miscellaneous arboviruses, XMRV, human parvoviruses/bocaviruses other than B19, and most recently the Middle East respiratory syndrome coronavirus, MERS-CoV) were added and 14 existing FSs updated (Anaplasma, Babesia, Bartonella, Erhlichia, chronic wasting disease-CWD, human prions other than vCJD, vCJD, Coxiella burnetii-the agent of Q fever, dengue viruses, HAV, HEV, Japanese encephalitis-JE complex, tick-borne encephalitis viruses-TBEV, and human parvovirus B19). Also, tables were released outlining pathogen reduction clinical trials/results (published) and availability/commercial routine use of such technologies by country. Of necessity, the list of EID agents is not, and can never be, complete due to the nature of emergence. We recognized that a system of assessing the risk/threat of EIDs for their potential impact on blood safety and availability must include processes for monitoring, identifying, evaluating, estimating severity, assessing risk and developing interventions. Thus, a ‘toolkit’ containing the necessary ‘tools’ from EID monitoring (horizon scanning) to validation/effectiveness evaluations of interventions is being developed. The goal is, to develop a systematic approach to risk assessment and intervention development for the impact of emerging infectious upon blood safety intended to educate and provide advise about risks/interventions in a timely/accurate fashion. CONCLUSIONS: The process and final product (toolkit) including methods to monitor EID agent emergence, identification/recognition of a transfusion-transmission threat, methods for quantitative risk assessments, and the appropriate management of such threats should be considered for implementation by all blood systems.


title: THE EMERGENCE OF ARTHROPOD-BORNE VIRAL DISEASES: A GLOBAL PROSPECTIVE ON DENGUE, CHIKUNGUNYA AND ZIKA FEVERS

text: Arthropod-borne viruses (arboviruses) present a substantial threat to human and animal health worldwide. Arboviruses can cause a variety of clinical presentations that range from mild to life threatening symptoms. Many arboviruses are present in nature through two distinct cycles, the urban and sylvatic cycle that are maintained in complex biological cycles. In this review we briefly discuss the factors driving the emergence of arboviruses, such as the anthropogenic aspects of unrestrained human population growth, economic expansion and globalization. Also the important aspects of viruses and vectors in the occurrence of arboviruses epidemics. The focus of this review will be on dengue, zika and chikungunya viruses, particularly because these viruses are currently causing a negative impact on public health and economic damage around the world.


title: A Novel High-Mannose Specific Lectin from the Green Alga Halimeda renschii Exhibits a Potent Anti-Influenza Virus Activity through High-Affinity Binding to the Viral Hemagglutinin

text: We have isolated a novel lectin, named HRL40 from the green alga Halimeda renschii. In hemagglutination-inhibition test and oligosaccharide-binding experiment with 29 pyridylaminated oligosaccharides, HRL40 exhibited a strict binding specificity for high-mannose N-glycans having an exposed (α1-3) mannose residue in the D2 arm of branched mannosides, and did not have an affinity for monosaccharides and other oligosaccharides examined, including complex N-glycans, an N-glycan core pentasaccharide, and oligosaccharides from glycolipids. The carbohydrate binding profile of HRL40 resembled those of Type I high-mannose specific antiviral algal lectins, or the Oscillatoria agardhii agglutinin (OAA) family, which were previously isolated from red algae and a blue-green alga (cyanobacterium). HRL40 potently inhibited the infection of influenza virus (A/H3N2/Udorn/72) into NCI-H292 cells with half-maximal effective dose (ED(50)) of 2.45 nM through high-affinity binding to a viral envelope hemagglutinin (K(D), 3.69 × 10(−11) M). HRL40 consisted of two isolectins (HRL40-1 and HRL40-2), which could be separated by reverse-phase HPLC. Both isolectins had the same molecular weight of 46,564 Da and were a disulfide -linked tetrameric protein of a 11,641 Da polypeptide containing at least 13 half-cystines. Thus, HRL40, which is the first Type I high-mannose specific antiviral lectin from the green alga, had the same carbohydrate binding specificity as the OAA family, but a molecular structure distinct from the family.


title: Characterisation of canine parvovirus strains isolated from cats with feline panleukopenia

text: Abstract Unlike the original canine parvovirus type 2 (CPV-2), CPV-2 variants have gained the ability to replicate in vivo in cats but there is limited information on the disease patterns induced by these variants in the feline host. During 2008, two distinct cases of parvoviral infection were diagnosed in our laboratories. A CPV-2a variant was identified in a 3-month-old Persian kitten displaying clinical sign of feline panleukopenia (FPL) (acute gastroenteritis and marked leukopenia) and oral ulcerations, that died eight days after the onset of the disease. Two pups living in the same pet shop as the cat were found to shed a CPV-2a strain genetically identical to the feline virus and were likely the source of infection. Also, non-fatal infection by a CPV-2c strain occurred in a 2.5-month-old European shorthair kitten displaying non-haemorrhagic diarrhoea and normal white blood cell counts. By sequence analysis of the major capsid protein (VP2) gene, the feline CPV-2c strain showed 100% identity to a recent canine type-2c isolate. Both kittens had been administered multivalent vaccines against common feline pathogens including FPL virus. Whether and to which extent the FPL vaccines can protect cats adequately from the antigenic variants of CPV-2 should be assessed.


Abstracts for the 29th Annual Meeting of the Japan Neuroscience Society (Neuroscience2006)


title: Liposome-Coupled Peptides Induce Long-Lived Memory CD8(+) T Cells Without CD4(+) T Cells

text: CD8(+) T cells provide broad immunity to viruses, because they are able to recognize all types of viral proteins. Therefore, the development of vaccines capable of inducing long-lived memory CD8(+) T cells is desired to prevent diseases, especially those for which no vaccines currently exist. However, in designing CD8(+) T cell vaccines, the role of CD4(+) T cells in the induction and maintenance of memory CD8(+) T cells remains uncertain. In the present study, the necessity or not of CD4(+) T cells in the induction and maintenance of memory CD8(+) T cells was investigated in mice immunized with liposome-coupled CTL epitope peptides. When OVA-derived CTL epitope peptides were chemically coupled to the surfaces of liposomes and inoculated into mice, both primary and secondary CTL responses were successfully induced. The results were further confirmed in CD4(+) T cell-eliminated mice, suggesting that CD4(+) T cells were not required for the generation of memory CD8(+) T cells in the case of immunization with liposome-coupled peptides. Thus, surface-linked liposomal antigens, capable of inducing long-lived memory CD8(+) T cells without the contribution of CD4(+) T cells, might be applicable for the development of vaccines to prevent viral infection, especially for those viruses that evade humoral immunity by varying their surface proteins, such as influenza viruses, HIV, HCV, SARS coronaviruses, and Ebola viruses.


title: Zooming Towards a Telehealth Solution for Vulnerable Children with Obesity During COVID‐19

text: Health inequities exist throughout the life course, resulting in racial/ethnic and socioeconomic disparities in obesity and obesity‐related health complications. Obesity and its co‐morbidities appear linked to COVID‐19 mortality. Approaches to reduce obesity in the time of COVID‐19 closures are urgently needed and should start early in life. In New York City, we developed a telehealth pediatric weight management collaborative spanning NewYork‐Presbyterian, Columbia University Vagelos College of Physicians and Surgeons, and Weill Cornell Medicine during COVID‐19 with show rates 76‐89%. To stave off the impending exacerbation of health disparities related to obesity risk factors in the aftermath of the COVID‐19 pandemic, effective interventions that can be delivered remotely are urgently needed among vulnerable children with obesity. Challenges in digital technology access, social and linguistic differences, privacy security, and reimbursement must be overcome to realize the full potential of telehealth for pediatric weight management among low‐income and racial/ethnic minority children.


title: Inactivation of Middle East respiratory syndrome coronavirus (MERS‐CoV) in plasma products using a riboflavin‐based and ultraviolet light‐based photochemical treatment

text: BACKGROUND: Middle East respiratory syndrome coronavirus (MERS‐CoV) has been identified as a potential threat to the safety of blood products. The Mirasol Pathogen Reduction Technology System uses riboflavin and ultraviolet (UV) light to render blood‐borne pathogens noninfectious while maintaining blood product quality. Here, we report on the efficacy of riboflavin and UV light against MERS‐CoV when tested in human plasma. STUDY DESIGN AND METHODS: MERS‐CoV (EMC strain) was used to inoculate plasma units that then underwent treatment with riboflavin and UV light. The infectious titers of MERS‐CoV in the samples before and after treatment were determined by plaque assay on Vero cells. The treatments were initially performed in triplicate using pooled plasma (n = 3) and then repeated using individual plasma units (n = 6). RESULTS: In both studies, riboflavin and UV light reduced the infectious titer of MERS‐CoV below the limit of detection. The mean log reductions in the viral titers were ≥4.07 and ≥4.42 for the pooled and individual donor plasma, respectively. CONCLUSION: Riboflavin and UV light effectively reduced the titer of MERS‐CoV in human plasma products to below the limit of detection, suggesting that the treatment process may reduce the risk of transfusion transmission of MERS‐CoV.


title: Prevalence of a novel bovine coronavirus strain with a recombinant hemagglutinin/esterase gene in dairy calves in China

text: Bovine coronavirus (BCoV) is the causative agent of diarrhoea in newborn calves, winter dysentery in adult cattle and respiratory tract illnesses in cattle across the world. In this study, a total of 190 faecal samples from dairy calves with diarrhoea were collected from 14 farms in six Chinese provinces, and BCoV was detected in 18.95% (36/190) of the samples by reverse transcriptase polymerase chain reaction. Full‐length spike, hemagglutinin/esterase (HE), nucleocapsid and transmembrane genes were simultaneously cloned from 13 clinical samples (eight farms in four provinces), and most of the BCoV strains showed a unique evolutionary pattern based on the phylogenetic analysis of these genes. Interesting, 10 of the 13 strains were identified as HE recombinant strains, and these strains had experienced the same recombination event and carried the same recombination sites located between the esterase and lectin domain. They also shared an identical aa variant (F181V) in the R2‐loop. Moreover, 9/10 strains displayed another identical aa variant (P, S158A) in the adjacent R1‐loop of the HE gene, which differs from the other available BCoV HE sequences in the GenBank database. Our results showed that BCoV is widely circulating in dairy cattle in China, contributing to the diagnosis and control of dairy calves diarrhoea. Furthermore, a BCoV strain that carries a recombinant HE gene has spread in dairy calves in China. To the best of our knowledge, this is the first description of an HE recombination event occurring in BCoV; this is also the first description of the molecular prevalence of BCoV in China. Our findings will enhance current understanding about the genetic evolution of BCoV.


title: Full-Length Genome Sequence of Porcine Deltacoronavirus Strain USA/IA/2014/8734

text: Porcine deltacoronavirus (PDCoV) was detected in feces from diarrheic sows during an epidemic of acute and transmissible diarrhea. No transmissible gastroenteritis virus or porcine epidemic diarrhea virus was detected. The PDCoV USA/IA/2014/8734 from the herd was sequenced for full-length genomic RNA to further characterize PDCoV in U.S. swine.


The Imperative of Early Treatment for Children With COVID-19 Infection


title: Exploring the potential of endophytes from medicinal plants as sources of antimycobacterial compounds

text: Abstract Natural product drug discovery has regained interest due to low production costs, structural diversity, and multiple uses of active compounds to treat various diseases. Attention has been directed towards medicinal plants as these plants have been traditionally used for generations to treat symptoms of numerous diseases. It is established that plants harbour microorganisms, collectively known as endophytes. Exploring the as-yet untapped natural products from the endophytes increases the chances of finding novel compounds. The concept of natural products targeting microbial pathogens has been applied to isolate novel antimycobacterial compounds, and the rapid development of drug-resistant Mycobacterium tuberculosis has significantly increased the need for new treatments against this pathogen. It remains important to continuously screen for novel compounds from natural sources, particularly from rarely encountered microorganisms, such as the endophytes. This review focuses on bioprospecting for polyketides and small peptides exhibiting antituberculosis activity, although current treatments against tuberculosis are described. It is established that natural products from these structure classes are often biosynthesised by microorganisms. Therefore it is hypothesised that some bioactive polyketides and peptides originally isolated from plants are in fact produced by their endophytes. This is of interest for further endophyte natural product investigations.


title: Evasion by Stealth: Inefficient Immune Activation Underlies Poor T Cell Response and Severe Disease in SARS-CoV-Infected Mice

text: Severe Acute Respiratory Syndrome caused substantial morbidity and mortality during the 2002–2003 epidemic. Many of the features of the human disease are duplicated in BALB/c mice infected with a mouse-adapted version of the virus (MA15), which develop respiratory disease with high morbidity and mortality. Here, we show that severe disease is correlated with slow kinetics of virus clearance and delayed activation and transit of respiratory dendritic cells (rDC) to the draining lymph nodes (DLN) with a consequent deficient virus-specific T cell response. All of these defects are corrected when mice are treated with liposomes containing clodronate, which deplete alveolar macrophages (AM). Inhibitory AMs are believed to prevent the development of immune responses to environmental antigens and allergic responses by interacting with lung dendritic cells and T cells. The inhibitory effects of AM can also be nullified if mice or AMs are pretreated with poly I:C, which directly activate AMs and rDCs through toll-like receptors 3 (TLR3). Further, adoptive transfer of activated but not resting bone marrow–derived dendritic cells (BMDC) protect mice from lethal MA15 infection. These results may be relevant for SARS in humans, which is also characterized by prolonged virus persistence and delayed development of a SARS-CoV-specific immune response in individuals with severe disease.


title: Inactivation of 12 viruses by heating steps applied during manufacture of a hepatitis B vaccine

text: The efficacy of two heating cycles (90 sec at 103°C and 10 hr at 65°C) used during manufacture of a plasma‐derived hepatitis‐B vaccine was validated for the inactivation of 12 virus families. A period of 15 min warming up to 65°C had already completely inactivated representatives of nine virus families, ie, poxvirus (vaccinia), picornavirus (encephalomyocarditis virus), togavirus (sind bis virus), coronavirus (mouse hepatitis virus), orthomyxovirus (influenza virus), rhabdovirus (vesicular stomatitis virus), herpes virus (cytomegalovirus), lentivirus (human immunodeficiency virus), and retrovirus (murine leukemia virus). After prolonged heating at 65°C or heating for 90 sec at 103°C, parvovirus (canine parvovirus) and the phage phiX174 were also completely inactivated. Papovavirus represented by simian virus 40 (SV‐40) was the most heat‐resistant virus evaluated. The infectivity of SV‐40 was reduced by 10(4) Tissue Culture Infectious Doses (TCID(50)) per ml after 90 sec at 103°C, but a marginal residual activity (<5 TCID(50) per ml) was observed. Subsequent pasteurization for 10 h at 65°C did not further reduce the infectivity of SV‐40. This study shows that the two heat‐inactivation steps used during the production of this vaccine kill a wide variety of viruses that might be present in human blood.


title: Macaque Models of Human Infectious Disease

text: Macaques have served as models for more than 70 human infectious diseases of diverse etiologies, including a multitude of agents—bacteria, viruses, fungi, parasites, prions. The remarkable diversity of human infectious diseases that have been modeled in the macaque includes global, childhood, and tropical diseases as well as newly emergent, sexually transmitted, oncogenic, degenerative neurologic, potential bioterrorism, and miscellaneous other diseases. Historically, macaques played a major role in establishing the etiology of yellow fever, polio, and prion diseases. With rare exceptions (Chagas disease, bartonellosis), all of the infectious diseases in this review are of Old World origin. Perhaps most surprising is the large number of tropical (16), newly emergent (7), and bioterrorism diseases (9) that have been modeled in macaques. Many of these human diseases (e.g., AIDS, hepatitis E, bartonellosis) are a consequence of zoonotic infection. However, infectious agents of certain diseases, including measles and tuberculosis, can sometimes go both ways, and thus several human pathogens are threats to nonhuman primates including macaques. Through experimental studies in macaques, researchers have gained insight into pathogenic mechanisms and novel treatment and vaccine approaches for many human infectious diseases, most notably acquired immunodeficiency syndrome (AIDS), which is caused by infection with human immunodeficiency virus (HIV). Other infectious agents for which macaques have been a uniquely valuable resource for biomedical research, and particularly vaccinology, include influenza virus, paramyxoviruses, flaviviruses, arenaviruses, hepatitis E virus, papillomavirus, smallpox virus, Mycobacteria, Bacillus anthracis, Helicobacter pylori, Yersinia pestis, and Plasmodium species. This review summarizes the extensive past and present research on macaque models of human infectious disease.


title: Infectious entry of equine herpesvirus-1 into host cells through different endocytic pathways

text: Abstract We investigated the mechanism by which equine herpesvirus-1 (EHV-1) enters primary cultured equine brain microvascular endothelial cells (EBMECs) and equine dermis (E. Derm) cells. EHV-1 colocalized with caveolin in EBMECs and the infection was greatly reduced by the expression of a dominant negative form of equine caveolin-1 (ecavY14F), suggesting that EHV-1 enters EBMECs via caveolar endocytosis. EHV-1 entry into E. Derm cells was significantly reduced by ATP depletion and treatments with lysosomotropic agents. Enveloped virions were detected from E. Derm cells by infectious virus recovery assay after viral internalization, suggesting that EHV-1 enters E. Derm cells via energy- and pH-dependent endocytosis. These results suggest that EHV-1 utilizes multiple endocytic pathways in different cell types to establish productive infection.


Coronaviridae: Second Report1


title: Molecular typing of a novel canine parvovirus type 2a mutant circulating in Italy

text: Abstract Canine parvovirus (CPV) is the etiological agent of a severe viral disease of dogs. After its emergence in late 1970s, the CPV original type (CPV-2) was rapidly and totally replaced by three antigenic variants named CPV-2a, CPV-2b and CPV-2c. CPV has an evolutionary rate nearest to those of RNA viruses, with consequences on disease diagnosis and epidemiology. This paper reports the molecular characterization of eight CPV-2a strains collected from dogs in Italy in 2016–2017. Genetic analysis was conducted on a CPV genomic region encompassing both open reading frames (ORFs) encoding for nonstructural (NS1-NS2) and structural proteins (VP1-VP2). Sequence analysis indicates new and unreported sequence changes, mainly affecting the VP2 gene, which included the mutation Tyr324Leu. This study represents the first evidence of a new CPV-2a mutant (VP2 324Leu) and illustrates the importance of a continuous molecular survey in order to obtain more information on effective spread of new CPV mutants.


title: Bacteriological and clinical efficacy of various antibiotics used in the treatment of streptococcal pharyngitis in Italy. An epidemiological study

text: Abstract A total of 123 community paediatricians and 23 microbiology laboratories studied the clinical and bacteriological efficacy of treatment of group A streptococcal pharyngitis in Italy. Of 1065 patients, from whom Streptococcus pyogenes was isolated, 723 returned to follow up and of these 138 (19%) still had a positive throat culture. The erythromycin resistance (ER) rate was 23.7% with resistance phenotype distribution of: 31.7% constitutive (CR), 26.6% inducible (IR) and 41.7% efflux pump (M) resistance phenotype. All strains were susceptible to the β-lactam agents tested. CR strains were highly resistant to all 14, 15 and 16 membered macrolides with the exception of rokitamycin which showed activity against 37.8% of isolates. All phenotype M and some IR isolates were susceptible to clindamycin, rokitamycin, josamycin and spiramycin; clarithromycin was active against a small percentage of strains belonging to the IR and M phenotype. Bacterial eradication was found in 85.5, 78.7 and 75.8% of the penicillin, macrolide and cephalosporin treated groups. Genotyping of strains showed that 8.7% of the 19% of cases classified as ‘failed bacterial eradication’ were due to recolonization with a different isolate, observed exclusively among β-lactams treated patients. Clinical cure was achieved in a high percentage of cases, irrespective of the antibiotic prescribed, with the best clinical efficacy being found following therapy with amoxycillin and clarithromycin (90.9%).


Reply to Letter to the Editor: “Don’t judge too RAShly: the multifaceted role of the renin-angiotensin system and its therapeutic potential in COVID-19”


title: Respiratory viruses are continuously detected in children with chronic tonsillitis throughout the year

text: Abstract Objective To evaluate the oscillations on the viral detection in adenotonsillar tissues from patients with chronic adenotonsillar diseases as an indicia of the presence of persistent viral infections or acute subclinical infections. Study design Cross-sectional prospective study. Setting Tertiary hospital. Methods The fluctuations of respiratory virus detection were compared to the major climatic variables during a two-year period using adenoids and palatine tonsils from 172 children with adenotonsillar hypertrophy and clinical evidence of obstructive sleep apnoea syndrome or recurrent adenotonsillitis, without symptoms of acute respiratory infection (ARI), by TaqMan real-time PCR. Results The rate of detection of at least one respiratory virus in adenotonsillar tissue was 87%. The most frequently detected viruses were human adenovirus in 52.8%, human enterovirus in 47.2%, human rhinovirus in 33.8%, human bocavirus in 31.1%, human metapneumovirus in 18.3% and human respiratory syncytial virus in 17.2%. Although increased detection of human enterovirus occurred in summer/autumn months, and there were summer nadirs of human respiratory syncytial virus in both years of the study, there was no obvious viral seasonality in contrast to reports with ARI patients in many regions of the world. Conclusion Respiratory viruses are continuously highly detected during whole year, and without any clinical symptomatology, indicating that viral genome of some virus can persist in lymphoepithelial tissues of the upper respiratory tract.


title: Palmitoylation of SARS-CoV S protein is necessary for partitioning into detergent-resistant membranes and cell–cell fusion but not interaction with M protein

text: Abstract Coronaviruses are enveloped RNA viruses that generally cause mild disease in humans. However, the recently emerged coronavirus that caused severe acute respiratory syndrome (SARS-CoV) is the most pathogenic human coronavirus discovered to date. The SARS-CoV spike (S) protein mediates virus entry by binding cellular receptors and inducing fusion between the viral envelope and the host cell membrane. Coronavirus S proteins are palmitoylated, which may affect function. Here, we created a non-palmitoylated SARS-CoV S protein by mutating all nine cytoplasmic cysteine residues. Palmitoylation of SARS-CoV S was required for partitioning into detergent-resistant membranes and for cell–cell fusion. Surprisingly, however, palmitoylation of S was not required for interaction with SARS-CoV M protein. This contrasts with the requirement for palmitoylation of mouse hepatitis virus S protein for interaction with M protein and may point to important differences in assembly and infectivity of these two coronaviruses.


title: Safety and efficacy of different anesthetic regimens for parturients with COVID-19 undergoing Cesarean delivery: a case series of 17 patients

text: PURPOSE: To assess the management and safety of epidural or general anesthesia for Cesarean delivery in parturients with coronavirus disease (COVID-19) and their newborns, and to evaluate the standardized procedures for protecting medical staff. METHODS: We retrospectively reviewed the cases of parturients diagnosed with severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection disease (COVID-19). Their epidemiologic history, chest computed tomography scans, laboratory measurements, and SARS-CoV-2 nucleic acid positivity were evaluated. We also recorded the patients’ demographic and clinical characteristics, anesthesia and surgery-related data, maternal and neonatal complications, as well as the health status of the involved medical staff. RESULTS: The clinical characteristics of 17 pregnant women infected with SARS-CoV-2 were similar to those previously reported in non-pregnant adult patients. All of the 17 patients underwent Cesarean delivery with anesthesia performed according to standardized anesthesia/surgery procedures. Fourteen of the patients underwent continuous epidural anesthesia with 12 experiencing significant intraoperative hypotension. Three patients received general anesthesia with tracheal intubation because emergency surgery was needed. Three of the parturients are still recovering from their Cesarean delivery and are receiving in-hospital treatment for COVID-19. Three neonates were born prematurely. There were no deaths or serious neonatal asphyxia events. All neonatal SARS-CoV-2 nucleic acid tests were negative. No medical staff were infected throughout the patient care period. CONCLUSIONS: Both epidural and general anesthesia were safely used for Cesarean delivery in the parturients with COVID-19. Nevertheless, the incidence of hypotension during epidural anesthesia appeared excessive. Proper patient transfer, medical staff access procedures, and effective biosafety precautions are important to protect medical staff from COVID-19.


title: Stockpile of personal protective equipment in hospital settings: Preparedness for influenza pandemics

text: BACKGROUND: Personal protective equipment (PPE) is known to be a crucial means of preventing influenza pandemics; however, the amount of PPE that should be stored in hospital settings has been unclear. OBJECTIVES: The purpose of this paper is to propose a PPE calculation system to help hospitals to decide their PPE stockpile. METHODS: We searched influenza guidelines from a number of countries and research papers on protective devices and infectious diseases. The PPE calculation system included factors such as the influenza pandemic period, risk classification by health care workers (HCW) type, and the type and number of PPE for a HCW per day. RESULTS: We concluded that 4 sets of PPE (N95 respirators, double gloves, gowns, and goggles) per day should be prepared for HCWs in a high-risk group. Similarly, 2 sets of appropriate PPE, depending on the risk level, are required for medium- and low-risk groups. In addition, 2 surgical masks are required for every worker and inpatient and 1 for each outpatient. The PPE stockpile should be prepared to cover at least an 8-week pandemic. CONCLUSION: Purchasing a PPE stockpile requires a sizable budget. The PPE calculation system in this paper will hopefully support hospitals in deciding their PPE stockpile.


title: Electrophoresis on a microfluidic chip for analysis of fluorescence‐labeled human rhinovirus

text: We report the analysis of human rhinovirus serotype 2 (HRV2) on a commercially available lab‐on‐a‐chip instrument. Due to lack of sufficient native fluorescence, the proteinaceous capsid of HRV2 was labeled with Cy5 for detection by the red laser (λ (ex) 630 nm) implemented in the instrument. On the microdevice, electrophoresis of the labeled virus was possible in a BGE without stabilizing detergents, which is in contrast to conventional CE; moreover, analysis times were drastically shortened to the few 10 s range. Resolution of the sample constituents (virions, a contaminant present in all virus preparations, and excess dye) was improved upon adaptation of the separation conditions, mainly by adjusting the SDS concentration of the BGE. Purity of fractions from size‐exclusion chromatography after labeling of virus was assessed, and affinity complex formation of the labeled virus with various recombinant very‐low‐density lipoprotein receptor derivatives differing in the number of concatenated V3 ligand binding repeats was monitored. Virus analysis on microchip devices is of particular interest for experiments with infectious material because of easy containment and disposal of samples. Thus, the employment of microchip devices in routine analysis of viruses appears to be exceptionally attractive.


Viral respiratory tract infections increase platelet reactivity and activation: an explanation for the higher rates of myocardial infarction and stroke during viral illness


docid: yhmuvort

title: Does the pathogenesis of SAR-CoV-2 virus decrease at high-altitude?

text: Abstract In the present study we analyze the epidemiologic data of COVID-19 of Tibet and high-altitude regions of Bolivia and Ecuador, and compare to lowland data, to test the hypothesis that high-altitude inhabitants (+2500 m above sea-level) are less susceptible to develop severe adverse effect in acute SARS-CoV-2 virus infection. Analysis of available epidemiological data suggest that physiological adaptations that counterbalance the hypoxic environment altitude may protect from severe impact of acute SARS-CoV-2 virus infection. Potential underlying mechanisms such as: (i) a compromised half-live of the virus caused by the high-altitude environment, and (ii) a hypoxia mediated down regulation of angiotensin-converting enzyme 2 (ACE2), which is the main binding target of SARS-CoV-2 virus in the pulmonary epithelia are discussed.


docid: uuwvmltw

title: Rapid isolation of potent SARS-CoV-2 neutralizing antibodies and protection in a small animal model

text: The development of countermeasures to prevent and treat COVID-19 is a global health priority. In under 7 weeks, we enrolled a cohort of SARS-CoV-2-recovered participants, developed neutralization assays to interrogate serum and monoclonal antibody responses, adapted our high throughput antibody isolation, production and characterization pipeline to rapidly screen over 1000 antigen-specific antibodies, and established an animal model to test protection. We report multiple highly potent neutralizing antibodies (nAbs) and show that passive transfer of a nAb provides protection against high-dose SARS-CoV-2 challenge in Syrian hamsters. The study suggests a role for nAbs in prophylaxis, and potentially therapy, of COVID-19. The nAbs define protective epitopes to guide vaccine design.


docid: wnpiptly

title: Anticoagulation with Argatroban in patients with acute antithrombin deficiency in severe COVID ‐19

text: COVID‐19 is a highly prothrombotic disease, frequently requiring anticoagulation for prevention or treatment of thrombosis and to enable organ support (Bikdeli, Madhavan et al. 2020). The reported incidence of thrombosis in patients with COVID‐19 varies considerably depending on anticoagulant regimen, severity of disease and additional risk factors such as central lines. The most commonly used in‐hospital anticoagulants, unfractionated heparin (UFH) and low molecular weight heparin (LMWH), require antithrombin (AT) to exert their anticoagulant effect (Bussey and Francis 2004). Therefore, AT deficiency can result in failure achieve adequate anticoagulation with UFH or LMWH at usual doses.


title: Communicating infectious disease prevalence through graphics: results from an international survey

text: BACKGROUND: Graphics are increasingly used to represent the spread of infectious diseases (e.g., influenza, Zika, Ebola); however, the impact of using graphics to adequately inform the general population is unknown. OBJECTIVE: To examine whether three ways of visually presenting data (heat map, dot map, or picto-trendline)—all depicting the same information regarding the spread of a hypothetical outbreak of influenza—influence intent to vaccinate, risk perception, and knowledge. DESIGN: Survey with participants randomized to receive a simulated news article accompanied by one of the three graphics that communicated prevalence of influenza and number of influenza-related deaths. SETTING: International online survey PARTICIPANTS: 16,510 adults living in 11 countries selected using stratified random sampling based on age and gender MEASUREMENTS: After reading the article and viewing the presented graphic, participants completed a survey that measured interest in vaccination, perceived risk of contracting disease, knowledge gained, interest in additional information about the disease, and perception of the graphic. RESULTS: Heat maps and picto-trendlines were evaluated more positively than dot maps. Heat maps were more effective than picto-trendlines and no different from dot maps at increasing interest in vaccination, perceived risk of contracting disease, and interest in additional information about the disease. Heat maps and picto-trendlines were more successful at conveying knowledge than dot maps. Overall, heat maps were the only graphic to be superior in every outcome. LIMITATIONS: Results are based on a hypothetical scenario CONCLUSION: Heat maps are a viable option to promote interest in and concern about infectious diseases.


title: How virus size and attachment parameters affect the temperature sensitivity of virus binding to host cells: Predictions of a thermodynamic model for arboviruses and HIV

text: Abstract Virus binding to host cells involves specific interactions between viral (glyco)proteins (GP) and host cell surface receptors (Cr) (protein or sialic acid (SA)). The magnitude of the enthalpy of association changes with temperature according to the change in heat capacity (ΔCp) on GP/Cr binding, being little affected for avian influenza virus (AIV) haemagglutinin (HA) binding to SA (ΔCp = 0 kJ/mol/K) but greatly affected for HIV gp120 binding to CD4 receptor (ΔCp = −5.0 kJ/mol/K). A thermodynamic model developed here predicts that values of ΔCp from 0 to ~−2.0 kJ/mol/K have relatively little impact on the temperature sensitivity of the number of mosquito midgut cells with bound arbovirus, while intermediate values of ΔCp of ~−3.0 kJ/mol/K give a peak binding at a temperature of ~20 °C as observed experimentally for Western equine encephalitis virus. More negative values of ΔCp greatly decrease arbovirus binding at temperatures below ~20 °C. Thus to promote transmission at low temperatures, arboviruses may benefit from ΔCp ~ 0 kJ/mol/K as for HA/SA and it is interesting that bluetongue virus binds to SA in midge midguts. Large negative values of ΔCp as for HIV gp120:CD4 diminish binding at 37 °C. Of greater importance, however, is the decrease in entropy of the whole virus (ΔSa_immob) on its immobilisation on the host cell surface. ΔSa_immob presents a repulsive force which the enthalpy-driven GP/Cr interactions weakened at higher temperatures struggle to overcome. ΔSa_immob is more negative (less favourable) for larger diameter viruses which therefore show diminished binding at higher temperatures than smaller viruses. It is proposed that small size phenotype through a less negative ΔSa_immob is selected for viruses infecting warmer hosts thus explaining the observation that virion volume decreases with increasing host temperature from 0 °C to 40 °C in the case of dsDNA viruses. Compared to arboviruses which also infect warm-blooded vertebrates, HIV is large at 134 nm diameter and thus would have a large negative ΔSa_immob which would diminish its binding at human body temperature. It is proposed that prior non-specific binding of HIV through attachment factors takes much of the entropy loss for ΔSa_immob so enhancing subsequent specific gp120:CD4 binding at 37 °C. This is consistent with the observation that HIV attachment factors are not essential but augment infection. Antiviral therapies should focus on increasing virion size, for example through binding of zinc oxide nanoparticles to herpes simplex virus, hence making ΔSa_immob more negative, and thus reducing binding affinity at 37 °C.


title: Maintaining dental education and specialist dental care during an outbreak of a new coronavirus infection. Part 1: A deadly viral epidemic begins

text: During the three months from March 2003 the economically vibrant city of Hong Kong was seriously dislocated after becoming 'second port of call' of the new and potentially fatal disease, Severe Acute Respiratory Syndrome (SARS). The uncertainties during that period had a significant impact on the provision of dental care. However the city's only dental hospital continued to function and to support the Faculty of Dentistry of the University of Hong Kong in educating dental students and other members of the dental team. At the time of writing no transmissions of the disease have been attributed to procedures associated with dental healthcare. This article chronicles the sequence of events during the outbreak from a dental perspective. It highlights information that may be useful to dental colleagues who might someday be confronted with similar outbreaks of newly emerged potentially lethal infections.


title: The Discovery of the 27-nm Norwalk Virus: An Historic Perspective

text: In 1972, a 27-nm virus-like particle was discovered by use of immune electron microscopy (IEM) in an infectious stool filtrate derived from an outbreak of gastroenteritis in an elementary school in Norwalk, Ohio. IEM enabled the direct visualization of antigen-antibody interaction, as the particles were aggregated and coated by specific antibodies. This allowed the recognition and identification of a 27-nm virus-like particle that did not have a distinctive morphology, was low-titered, and was among the smallest viruses known. Serum antibody responses to the 27-nm particle were demonstrated in key individuals infected under natural or experimental conditions; this and other evidence suggested that this virus-like particle was the etiologic agent of the Norwalk gastroenteritis outbreak. The fastidious 27-nm Norwalk virus is now considered to be the prototype strain of a group of noncultivatable viruses that are important etiologic agents of epidemic gastroenteritis in adults and older children.


title: DIRECT RT-qPCR DETECTION OF SARS-CoV-2 RNA FROM PATIENT NASOPHARYNGEAL SWABS WITHOUT AN RNA EXTRACTION STEP

text: The ongoing COVID-19 pandemic has caused an unprecedented need for rapid diagnostic testing. The Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) recommend a standard assay that includes an RNA extraction step from a nasopharyngeal (NP) swab followed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to detect the purified SARS-CoV-2 RNA. The current global shortage of RNA extraction kits has caused a severe bottleneck to COVID-19 testing. We hypothesized that SARS-CoV-2 RNA could be detected from NP samples via a direct RT-qPCR assay that omits the RNA extraction step altogether, and tested this hypothesis on a series of blinded clinical samples. The direct RT-qPCR approach correctly identified 92% of NP samples (n = 155) demonstrated to be positive for SARS-CoV-2 RNA by traditional clinical diagnostic RT-qPCR that included an RNA extraction. Thus, direct RT-qPCR could be a front-line approach to identify the substantial majority of COVID-19 patients, reserving a repeat test with RNA extraction for those individuals with high suspicion of infection but an initial negative result. This strategy would drastically ease supply chokepoints of COVID-19 testing and should be applicable throughout the world.


title: Prevalence, clinical outcomes and rainfall association of acute respiratory infection by human metapneumovirus in children in Bogotá, Colombia

text: BACKGROUND: Acute respiratory infections (ARIs) are one of the main causes of morbidity and mortality in children. Viruses are the main etiological agents, and their behavior tends to be seasonal and vary by geographical location. Human metapneumovirus (HMPV) has recently been described as a cause of severe acute respiratory infection and its prevalence and clinical behavior in children at moderate altitudes is unknown. METHODS: A cross-sectional study was carried out on patients seen at a university hospital in Bogotá, Colombia between October 2015 and December 2017 in a city at a moderate altitude above sea level. Children with acute respiratory infections who had had a multiplex RT-PCR assay were selected. The prevalence of HMPV infection, its clinical outcomes and its relationship to rainfall were evaluated. RESULTS: Out of a total of 14,760 discharged patients, multiplex RT-PCR was performed on 502 and a virus was detected in 420 children with acute respiratory infection (ARI). The study group had a median age of 21 months (IQR 7–60), with similar proportion of males and females (56.4 and 43.6% respectively) and 5.2% (CI 95 3.3–7.8%) prevalence of HMPV infection. The group with HMPV infection showed a greater frequency of viral coinfection (22.7% vs 14% P = 0.03) compared with ARI caused by other viruses. The rate of bacterial coinfection (P = 0.31), presence of comorbidities (p = 0.75), length of hospital stay (P = 0.42), need for mechanical ventilation (P = 0.75) and mortality (P = 0.22) were similar for HMPV and other viral infections. A moderate correlation was established between HMPV infection and rainfall peaks (Spearman’s Rho 0.44 p = 0.02). CONCLUSIONS: Human metapneumovirus was the fifth most frequently isolated virus in children with ARI, had similar clinical behavior and severity to other viruses but a higher rate of viral coinfection. Its peaks seem to correlate to rainy seasons.


title: Nursing Home-Associated Pneumonia, Part II: Etiology and Treatment

text: Abstract This is the second of 2 parts of a narrative review of nursing home-associated pneumonia (NHAP) that deals with etiology and treatment in the nursing home. In the 1980s and 1990s, the etiology of NHAP was considered to be similar to community-acquired pneumonia (CAP). This belief was reflected in CAP guidelines until 2005 when the designation healthcare-associated pneumonia or HCAP was introduced and nursing home residents were included in the HCAP category. Patients in the HCAP group were thought to be at high risk for pneumonia because of multidrug resistant organisms and required empiric broad-spectrum antibiotic therapy much like people with hospital-acquired infection. Subsequent studies of the etiology of NHAP using sophisticated diagnostic testing found limited evidence of resistant organisms such as methicillin-resistant Staphylococcus aureus or resistant gram-negative organisms or atypical organisms. In terms of management of NHAP in the nursing home there are several considerations that are discussed: hospitalization decision, initial oral or parenteral therapy, timing of switch to an oral regimen if parenteral therapy is initially prescribed, duration of therapy with an emphasis on shorter courses, and follow-up during therapy including the use of the “antibiotic time out” protocol. The oral and parenteral antibiotic regimens recommended for treatment of NHAP in this report are based on limited information because there are no randomized controlled trials to define the optimum regimen. In conclusion, most residents with pneumonia can be treated successfully in the nursing home. However, there is an urgent need for a specific NHAP diagnosis and treatment guideline that will give providers guidance in the management of this infection in the nursing home.


Feline infectious peritonitis-like coronavirus in ferrets


title: Reposition of Montelukast either alone or in combination with Levocetirizine against SARS-CoV-2

text: It has been hypothesised that antiallergic medications (AAMs) like montelukast and levocetirizine both the two bitter chloro compounds could be repurposed either alone or combinedly as an antiviral against SARS-CoV-2, like chloroquine/hydroxychloroquine (CQ/HCQ), anorher two bitter chloro compounds. Both AAMs and CQ/HCQ are bitter tasted chloro compounds. Depending on their these two similar physical properties and the safety and efficacy of AAMs by controlling over post viral episodes as comparing with viral inhibitory activities including SARS-CoV-2 by CQ/HCQ, a reposition of AAMs either alone/combinedly could be rationalised as an antiviral approach to nCoV.


title: Microbes and Infection turns 20

text: Abstract The journal Microbes and Infection is celebrating its vigintennial anniversary and has reunited for this occasion two dozen reviews illustrating achievements of the past as well as future challenges in the field of infectious diseases. From top-notch vaccine development strategies, to high-throughput powered analysis of complex host-pathogen interactions, to innovative therapeutic designs, this issue covers the entire spectrum of pathogens and areas of their confrontation with the host.


title: Neonatal Sepsis

text: PURPOSE OF REVIEW: Neonatal sepsis is a diagnosis made in infants less than 28 days of life and consists of a clinical syndrome that may include systemic signs of infection, circulatory shock, and multisystem organ failure. RECENT FINDINGS: Commonly involved bacteria include Staphylococcus aureus and Escherichia coli. Risk factors include central venous catheter use and prolonged hospitalization. Neonates are at significant risk of delayed recognition of sepsis until more ominous clinical findings and vital sign abnormalities develop. Blood culture remains the gold standard for diagnosis. SUMMARY: Neonatal sepsis remains an important diagnosis requiring a high index of suspicion. Immediate treatment with antibiotics is imperative.


docid: rshpyyfj

title: Delivery of subunit vaccines in maize seed

text: Abstract The use of recombinant gene technologies by the vaccine industry has revolutionized the way antigens are generated, and has provided safer, more effective means of protecting animals and humans against bacterial and viral pathogens. Viral and bacterial antigens for recombinant subunit vaccines have been produced in a variety of organisms. Transgenic plants are now recognized as legitimate sources for these proteins, especially in the developing area of oral vaccines, because antigens have been shown to be correctly processed in plants into forms that elicit immune responses when fed to animals or humans. Antigens expressed in maize (Zea mays) are particularly attractive since they can be deposited in the natural storage vessel, the corn seed, and can be conveniently delivered to any organism that consumes grain. We have previously demonstrated high level expression of the B-subunit of Escherichia coli heat-labile enterotoxin and the spike protein of swine transmissible gastroenteritis in corn, and have demonstrated that these antigens delivered in the seed elicit protective immune responses. Here we provide additional data to support the potency, efficacy, and stability of recombinant subunit vaccines delivered in maize seed.


docid: cffozgju

title: Role of epithelial nitric oxide in airway viral infection

text: Abstract The airway mucosal epithelium is the first site of virus contact with the host, and the main site of infection and inflammation. Nitric oxide (NO) produced by the airway epithelium is vital to antiviral inflammatory and immune defense in the lung. Multiple mechanisms function coordinately to support high-level basal NO synthesis in healthy airway epithelium and further induction of NO synthesis in the infected airway of normal hosts. Hosts deficient in NO synthesis, such as those patients with cystic fibrosis, have impaired antiviral defense and may benefit from therapies to augment NO levels in the airways.


title: The virion N protein of infectious bronchitis virus is more phosphorylated than the N protein from infected cell lysates

text: Abstract Because phosphorylation of the infectious bronchitis virus (IBV) nucleocapsid protein (N) may regulate its multiple roles in viral replication, the dynamics of N phosphorylation were examined. 32P-orthophosphate labeling and Western blot analyses confirmed that N was the only viral protein that was phosphorylated. Pulse labeling with 32P-orthophosphate indicated that the IBV N protein was phosphorylated in the virion, as well as at all times during infection in either chicken embryo kidney cells or Vero cells. Pulse-chase analyses followed by immunoprecipitation of IBV N proteins using rabbit anti-IBV N polyclonal antibody demonstrated that the phosphate on the N protein was stable for at least 1 h. Simultaneous labeling with 32P-orthophosphate and 3H-leucine identified a 3.5-fold increase in the 32P:3H counts per minute (cpm) ratio of N in the virion as compared to the 32P:3H cpm ratio of N in the cell lysates from chicken embryo kidney cells, whereas in Vero cells the 32P:3H cpm ratio of N from the virion was 10.5-fold greater than the 32P:3H cpm ratio of N from the cell lysates. These studies are consistent with the phosphorylation of the IBV N playing a role in assembly or maturation of the viral particle.


title: Relationship between hepcidin and oxidant/antioxidant status in calves with suspected neonatal septicemia

text: AIM: This study has been conducted for the purpose of determining serum hepcidin, total antioxidant status (TAS), total oxidant status (TOS), and Fe levels in calves with suspected neonatal septicemia before and after treatment and the clinical significance of hepcidin in calves with suspected neonatal septicemia. MATERIALS AND METHODS: The study material consisted of 15 calves of different ages and sexes brought to the Training, Research and Application Center at the Kafkas University Faculty of Veterinary Medicine with suspected neonatal septicemia. 8.5 mL of blood was drawn from the jugular vein of each animal into coagulant tubes before and after treatment for one-off biochemical analyses and centrifuged. After this, the serum was separated. Hepcidin, TAS, TOS, and Fe levels in the serum were measured. RESULTS: While pre-treatment hepcidin levels were 58.42±3.46 ng/mL, post-treatment levels were 46.87±2.98 ng/mL (p<0.05). Pre-treatment Fe levels were 60.13±7.27 µg/dl, while post-treatment levels were 83.1±8.09 µg/dl (p<0.05). The changes in the TAS and TOS levels were also found to be statistically significant. CONCLUSION: In light of the fact that hepcidin plays a role function in the regulation of Fe as well as the fact that Fe is a significant nutritional source for many microorganisms, it was concluded that hepcidin may play a significant role in nutritional immunity and the pathogenesis of diseases.


title: Diagnosis of Ventilator-Associated Respiratory Infections (VARI): Microbiologic Clues for Tracheobronchitis (VAT) and Pneumonia (VAP)

text: Intubated patients are at risk of bacterial colonization and ventilator-associated respiratory infection (VARI). VARI includes tracheobronchitis (VAT) or pneumonia (VAP). VAT and VAP caused by multidrug-resistant (MDR) pathogens are increasing in the United States and Europe. In patients with risk factors for MDR pathogens, empiric antibiotics are often initiated for 48 to 72 hours pending the availability of pathogen identification and antibiotic sensitivity data. Extensive data indicate that early, appropriate antibiotic therapy improves outcomes for patients with VAP. Recognizing and treating VARI may allow earlier appropriate therapy and improved patient outcomes.


title: Towards universal health coverage: lessons from 10 years of healthcare reform in China

text: Universal health coverage (UHC) is driving the global health agenda. Many countries have embarked on national policy reforms towards this goal, including China. In 2009, the Chinese government launched a new round of healthcare reform towards UHC, aiming to provide universal coverage of basic healthcare by the end of 2020. The year of 2019 marks the 10th anniversary of China’s most recent healthcare reform. Sharing China’s experience is especially timely for other countries pursuing reforms to achieve UHC. This study describes the social, economic and health context in China, and then reviews the overall progress of healthcare reform (1949 to present), with a focus on the most recent (2009) round of healthcare reform. The study comprehensively analyses key reform initiatives and major achievements according to four aspects: health insurance system, drug supply and security system, medical service system and public health service system. Lessons learnt from China may have important implications for other nations, including continued political support, increased health financing and a strong primary healthcare system as basis.


title: Prevention of nosocomial COVID-19 infections in Otorhinolaryngology-Head and Neck Surgery

text: Coronavirus disease 2019 (COVID-19) has rapidly evolved into a pandemic, causing a global public health crisis. Many frontline healthcare workers providing ear, nose and throat services have been reported to contract COVID-19 at work. Early during the COVID-19 outbreak, several medical professionals in Otolaryngology-Head and Neck Surgery were infected in Wuhan, China. A series of measures were then taken immediately, which successfully halted the spread of the disease. Here we would like to share the lessons we have learned, and our experience to protect our health care workers during the COVID-19 pandemic.


title: RNA and polypeptide homology among murine coronaviruses

text: Abstract Using a 32P complementary DNA (cDNA) prepared against the A59 nucleocapsid protein messenger RNA, we have investigated the extent of homology between A59 and four other strains of murine hepatitis virus (MHV). Analysis by hybridization kinetics of the annealing between A59 [32P]cDNA and infected cell RNA from the other four MHV strains demonstrated 70–80% homology. By gel transfer analysis, the A59 [32P]cDNA was able to detect subgenomic-size virus-specific RNAs in cells infected with all of the five MHV strains. A similar pattern of seven viral RNAs was detected in cells infected with A59, MHV-1, MHV-3, and JHM. In contrast, cells infected with MHV-S contained seven virus-specific RNAs, of which only the two smallest species comigrated with RNAs from the other four strains. The results suggest that as previously shown with A59 (S. Cheley, R. Anderson, M. J. Cupples, E. C. M. Lee Chan, and V. L. Morris (1981) Virology, 112, 596–604), all MHV strains tested encode a nested set of subgenomic RNAs. Analysis of [35S]methionine-labeled viral proteins by SDS-polyacrylamide gel electrophoresis revealed that each strain of MHV specified four major viral polypeptides with apparent molecular weights very similar to those previously reported for the E2, N, El, and PEI polypeptides of A59. The strong degree of interstrain homology among the five MHV strains investigated was confirmed by comparative chymotryptic peptide mapping of the viral N proteins. A majority of the chymotryptic peptides from each of the [35Sknethionine-labeled N proteins was found to coelute by high-performance liquid chromotography. Moreover, this technique of peptide mapping indicated a particularly strong relatedness between MHV-1 and MHV-S and among MHV-3, JHM, and A59.


title: A RAPID SYSTEMATIC REVIEW OF THE EFFICACY OF FACE MASKS AND RESPIRATORS AGAINST CORONAVIRUSES AND OTHER RESPIRATORY TRANSMISSIBLE VIRUSES FOR THE COMMUNITY, HEALTHCARE WORKERS AND SICK PATIENTS

text: ABSTRACT Background The pandemic of COVID-19 is growing, and a shortage of masks and respirators has been reported globally. Policies of health organizations for healthcare workers are inconsistent, with a change in policy in the US for universal face mask use. The aim of this study was to review the evidence around the efficacy of masks and respirators for healthcare workers, sick patients and the general public. Methods A systematic review of randomized controlled clinical trials on use of respiratory protection by healthcare workers, sick patients and community members was conducted. Articles were searched on Medline and Embase using key search terms. Results A total of 19 randomised controlled trials were included in this study – 8 in community settings, 6 in healthcare settings and 5 as source control. Most of these randomised controlled trials used different interventions and outcome measures. In the community, masks appeared to be more effective than hand hygiene alone, and both together are more protective. Randomised controlled trials in health care workers showed that respirators, if worn continually during a shift, were effective but not if worn intermittently. Medical masks were not effective, and cloth masks even less effective. When used by sick patients randomised controlled trials suggested protection of well contacts. Conclusion The study suggests that community mask use by well people could be beneficial, particularly for COVID-19, where transmission may be pre-symptomatic. The studies of masks as source control also suggest a benefit, and may be important during the COVID-19 pandemic in universal community face mask use as well as in health care settings. Trials in healthcare workers support the use of respirators continuously during a shift. This may prevent health worker infections and deaths from COVID-19, as aerosolisation in the hospital setting has been documented.


title: Production of Recombinant EAV with Tagged Structural Protein Gp3 to Study Artervirus Minor Protein Localization in Infected Cells

text: Equine arteritis virus (EAV) is a prototype member of the Arterivirus family, comprising important pathogens of domestic animals. Minor glycoproteins of Arteriviruses are responsible for virus entry and cellular tropism. The experimental methods for studying minor Arterivirus proteins are limited because of the lack of antibodies and nested open reading frames (ORFs). In this study, we generated recombinant EAV with separated ORFs 3 and 4, and Gp3 carrying HA-tag (Gp3-HA). The recombinant viruses were stable on passaging and replicated in titers similar to the wild-type EAV. Gp3-HA was incorporated into the virion particles as monomers and as a Gp2/Gp3-HA/Gp4 trimer. Gp3-HA localized in ER and, to a lesser extent, in the Golgi, it also co-localized with the E protein but not with the N protein. The co-localization of Gp3-HA and the E protein with ERGIC was reduced. Moreover, EAV with Gp3-HA could become a valuable research tool for identifying host cell factors during infection and the role of Gp3 in virus attachment and entry.


Students Supporting Critical Care – A contention plan to prevent the decompensation of ICUs in the COVID-19 pandemic:Translating Bjorn Ibsens’ polio-lessons to modern times


title: Intoxication With Endogenous Angiotensin II: A COVID-19 Hypothesis

text: Severe acute respiratory syndrome coronavirus 2 has spread rapidly around the globe. However, despite its high pathogenicity and transmissibility, the severity of the associated disease, COVID-19, varies widely. While the prognosis is favorable in most patients, critical illness, manifested by respiratory distress, thromboembolism, shock, and multi-organ failure, has been reported in about 5% of cases. Several studies have associated poor COVID-19 outcomes with the exhaustion of natural killer cells and cytotoxic T cells, lymphopenia, and elevated serum levels of D-dimer. In this article, we propose a common pathophysiological denominator for these negative prognostic markers, endogenous, angiotensin II toxicity. We hypothesize that, like in avian influenza, the outlook of COVID-19 is negatively correlated with the intracellular accumulation of angiotensin II promoted by the viral blockade of its degrading enzyme receptors. In this model, upregulated angiotensin II causes premature vascular senescence, leading to dysfunctional coagulation, and immunity. We further hypothesize that angiotensin II blockers and immune checkpoint inhibitors may be salutary for COVID-19 patients with critical illness by reversing both the clotting and immune defects (Graphical Abstract).


title: Mitochondrial dynamics and viral infections: A close nexus

text: Abstract Viruses manipulate cellular machinery and functions to subvert intracellular environment conducive for viral proliferation. They strategically alter functions of the multitasking mitochondria to influence energy production, metabolism, survival, and immune signaling. Mitochondria either occur as heterogeneous population of individual organelles or large interconnected tubular network. The mitochondrial network is highly susceptible to physiological and environmental insults, including viral infections, and is dynamically maintained by mitochondrial fission and fusion. Mitochondrial dynamics in tandem with mitochondria-selective autophagy ‘mitophagy’ coordinates mitochondrial quality control and homeostasis. Mitochondrial dynamics impacts cellular homeostasis, metabolism, and innate-immune signaling, and thus can be major determinant of the outcome of viral infections. Herein, we review how mitochondrial dynamics is affected during viral infections and how this complex interplay benefits the viral infectious process and associated diseases. This article is part of a Special Issue entitled: Mitophagy.


title: La sécurité virale des médicaments d’origine biologique

text: Résumé Les crises sanitaires survenues dans les années 1980 ont dramatiquement contribué à la prise de conscience des risques iatrogènes liés aux médicaments d’origine biologique et, ainsi, au développement du concept de sécurité virale de ces médicaments, qu’ils soient d’origine humaine, avec notamment les médicaments dérivés du sang (MDS), animale ou issus des biotechnologies (produits par des cellules eucaryotes). La sécurité virale des médicaments repose sur trois éléments : la qualité de la matière première, le procédé de fabrication qui inclue des étapes aptes à éliminer ou à inactiver les virus et, éventuellement, les contrôles des produits intermédiaires ou finis. La qualité de la matière première est désormais aisément garantie, pour les MDS, par le screening des dons de sang ou de plasma (screening individuel ou en pool) pour les marqueurs directs (antigènes, génomes) et indirects (anticorps) de virus majeurs. La succession d’étapes de purification des principes actifs (étapes de partition), d’étapes d’inactivation des virus (traitement solvant–détergent, chauffage) et d’étapes dédiées spécifiquement à l’élimination des virus (nanofiltration) au cours du procédé de fabrication permet de réduire considérablement le risque viral. Cette réduction peut être estimée quantitativement lors des études de validation par épreuves de surcharge à échelle réduite. Les contrôles virologiques sur produits intermédiaires ou sur produits finis permettent de conforter la sécurité virale d’un médicament lorsque les contributions des deux premiers éléments, qualité de la matière première et procédé de fabrication, paraissent insuffisants. Le développement des principes et des techniques de sécurisation des médicaments d’origine biologique permet désormais de garantir au mieux l’absence d’infectiosité liée à des virus connus mais également, par anticipation, de garantir l’absence d’infectiosité liée à des virus inconnus. Summary The viral safety of biologicals, either human blood derivatives or animal products or recombinant proteins issued from biotechnology, relies on the quality of the starting material, the manufacturing process and, if necessary, the control of the final product. The quality of the starting material is highly guaranteed for blood derivatives due to the individual screening for specific markers (antigens, genome, antibodies) for major blood borne viruses such as hepatitis B and C viruses (HBV, HCV) and human immunodeficiency virus (HIV). It can be reinforced by the detection through amplification procedures (polymerase chain reaction) in the plasma pool of genomes from viruses that have been implicated in contaminations of blood derivatives in the past (parvovirus B19, hepatitis A virus). The association in the manufacturing process of different steps dedicated to purification of plasma proteins (partitioning), virus inactivation (solvent/detergent treatment, heat inactivation) or specific procedures allowing virus removal (nanofiltration) allows to reduce the viral risk very efficiently. The validation studies using scaled down systems and model viruses allow to evaluate the virus safety of any product quantitatively. The aim of these procedures is to guarantee the lack of infectivity due to any virus, either known or unknown.


title: Canine Adenoviruses and Herpesvirus

text: Canine adenoviruses (CAVs) and canine herpesvirus (CHV) are pathogens of dogs that have been known for several decades. The two distinct types of CAVs, type 1 and type 2, are responsible for infectious canine hepatitis and infectious tracheobronchitis, respectively. In the present article, the currently available literature on CAVs and CHV is reviewed, providing a meaningful update on the epidemiologic, pathogenetic, clinical, diagnostic, and prophylactic aspects of the infections caused by these important pathogens.


docid: gdveadvv

title: Enhancement of feline infectious peritonitis virus Type I infection in cell cultures using low-speed centrifugation

text: Abstract The effects of centrifugation on the ability of feline infectious peritonitis virus (FIPV) to infect cells in culture was investigated. The infectivity titer was the highest when the plates were centrifuged at 400 × g (1500 rpm) for 2 h. All five strains classified as FIPV Type I showed infectivity titers enhanced 10–100-fold by centrifugation at 400 × g for 2 h. The centrifugal enhancement of infection was obtained only by centrifugation immediately after inoculation of the virus, suggesting that the enhancement occurs during attachment or adsorption of viruses to the cells. This method may be useful for the culture of FIPV Type I strains.


title: Transplant patient’s isolation and social distancing due to covid-19: analysis of the resilient capacities of the transplant in the management of the coronavirus’ emergency.

text: Introduction One of the peculiar aspects of the transplant patient’s life is that in the post-surgery phase he lives in an “isolation” condition, having to pay particular attention to the living environment and preferring a limited social life given that the immunosuppressive treatment entails immunodepression in the patient. In covid 19, likewise in a post surgery situation, social isolation is being implemented. Material and Methods The study started on March 17th 2020 and ended on April 24rd 2020. Interviews consulting/phone were made. The phone questionnaire, submitted to 71 patients, consisted of a set of 15 questions that investigated the structure and the psychological resistance. 8 patients have been monitored exclusively for the psychological aspect through a more articulate supporting path. Results In essence, from the overall analysis of the data deriving from the study of the positioning of patients based on the stage of renal function and the bands related to the development of psychopathological aspects and the use of positive peronal resources, it emerges that patients in stage V "Kidney failure "are in the first bracket as regards the development of psychopathological aspects (absence of these experiences) and in the third bracket as regards the good use of positive resources to deal with isolation. Therefore, it can be deduced that, although with a data that can be expanded, a serious or medium-serious situation from an organic point of view in this socio-health emergency situation is well addressed by the transplanted patient Conclusions Transplant patients have faced the measure of social distancing adequately and in adherence to the treatment, thanks to the phone assistance of all the medical-surgical and psychological team.


title: The Evolution and Genetics of Virus Host Shifts

text: Emerging viral diseases are often the product of a host shift, where a pathogen jumps from its original host into a novel species. Phylogenetic studies show that host shifts are a frequent event in the evolution of most pathogens, but why pathogens successfully jump between some host species but not others is only just becoming clear. The susceptibility of potential new hosts can vary enormously, with close relatives of the natural host typically being the most susceptible. Often, pathogens must adapt to successfully infect a novel host, for example by evolving to use different cell surface receptors, to escape the immune response, or to ensure they are transmitted by the new host. In viruses there are often limited molecular solutions to achieve this, and the same sequence changes are often seen each time a virus infects a particular host. These changes may come at a cost to other aspects of the pathogen's fitness, and this may sometimes prevent host shifts from occurring. Here we examine how these evolutionary factors affect patterns of host shifts and disease emergence.


docid: cfnoxhtd

title: Immune responses in influenza A virus and human coronavirus infections: an ongoing battle between the virus and host

text: Respiratory viruses, especially influenza A viruses and coronaviruses such as MERS-CoV, represent continuing global threats to human health. Despite significant advances, much needs to be learned. Recent studies in virology and immunology have improved our understanding of the role of the immune system in protection and in the pathogenesis of these infections and of co-evolution of viruses and their hosts. These findings, together with sophisticated molecular structure analyses, omics tools and computer-based models, have helped delineate the interaction between respiratory viruses and the host immune system, which will facilitate the development of novel treatment strategies and vaccines with enhanced efficacy.


docid: czwgwnmn

title: Investigating time, strength, and duration of measures in controlling the spread of COVID-19 using a networked meta-population model

text: Policy makers around the world are facing unprecedented challenges in making decisions on when and what degrees of measures should be implemented to tackle the COVID-19 pandemic. Here, using a nationwide mobile phone dataset, we developed a networked meta-population model to simulate the impact of intervention in controlling the spread of the virus in China by varying the effectiveness of transmission reduction and the timing of intervention start and relaxation. We estimated basic reproduction number and transition probabilities between health states based on reported cases. Our model demonstrates that both the time of initiating an intervention and its effectiveness had a very large impact on controlling the epidemic, and the current Chinese intense social distancing intervention has reduced the impact substantially but would have been even more effective had it started earlier. The optimal duration of the control measures to avoid resurgence was estimated to be 2 months, although would need to be longer under less effective controls. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11071-020-05769-2) contains supplementary material, which is available to authorized users.


title: Adverse skin reactions to personal protective equipment against severe acute respiratory syndrome – a descriptive study in Singapore

text: Severe acute respiratory syndrome (SARS) was first recognized in February 2003. It is the first severe and readily transmissible new disease to emerge in the 21st century. Healthcare workers in affected countries were exposed to the regular use of personal protective equipment (PPE) such as the N95 mask, gloves, and gowns. Our aim was to study the prevalence of adverse skin reactions to PPE among healthcare workers in Singapore during the SARS outbreak. Healthcare staff in the National Skin Centre and Tan Tock Seng Hospital were surveyed using questionnaires. Of those asked to participate, 322 (94.7%) agreed. 14.3% of the respondents were doctors, 73.0% nurses, and 12.7% other ancillary staff. Mean age of respondents was 32.4 years, with the majority being women (85.7%) and Chinese (53.7%). 109 (35.5%) of the 307 staff who used masks regularly reported acne (59.6%), facial itch (51.4%), and rash (35.8%) from N95 mask use. 64 (21.4%) of the 299 who used gloves regularly reported dry skin (73.4%), itch (56.3%), and rash (37.5%). The use of PPE is associated with high rates of adverse skin reactions. There is a need to find suitable alternatives for affected staff and to encourage awareness among staff of the role of dermatologists in their care.


In Reply to Fiala LTE, Published Online 4-8-20: Lung Ultrasound for COVID-19 Evaluation in the Emergency Department: Is It Feasible?


title: Computed Tomography Imaging of an HIV‐infected Patient with Coronavirus Disease 2019 (COVID‐19)

text: In December 2019, an outbreak of Coronavirus disease 2019 (COVID‐19) occurred in Wuhan, China. Since then, this disease has infected more than 900,000 individuals worldwide. Here we report a case of non‐severe COVID‐19 pneumonia who was living with HIV. Chest computed tomography (CT) showed different abnormalities from those of conventional COVID‐19, and the faster absorption of pulmonary lesions also highlights the importance of antiretroviral therapy in this patient. This report provides reference for the diagnosis and treatment of HIV‐infected patients with COVID‐19. This article is protected by copyright. All rights reserved.


title: Adapting Management of Sarcomas in COVID-19: An Evidence-Based Review

text: With the novel coronavirus disease (COVID-19) being declared a global pandemic by the World Health Organization, the Indian healthcare sector is at the forefront to deliver optimal care. Patients with cancer especially are at serious risk for increased chances of morbidity and mortality due to their immunocompromised state. Currently there is a paucity of definitive guidelines for the management of sarcomas during the pandemic in a resource-constrained and diverse population setting like India. Health care professionals from various specialties involved in the management of sarcomas have collaborated to discuss various aspects of evidence-based sarcoma management during the COVID-19 pandemic. This article provides structured recommendations for HCP to adapt to the situation, optimize treatment protocols with judicious use of all resources while providing evidence-based treatment for sarcoma patients.


title: Blood type and outcomes in patients with COVID-19

text: This study aimed to determine if there is an association between ABO blood type and severity of COVID-19 defined by intubation or death as well as ascertain if there is variability in testing positive for COVID-19 between blood types. In a multi-institutional study, all adult patients who tested positive for COVID-19 across five hospitals were identified and included from March 6th to April 16th, 2020. Hospitalization, intubation, and death were evaluated for association with blood type. Univariate analysis was conducted using standard techniques and logistic regression was used to determine the independent effect of blood type on intubation and/or death and positive testing. During the study period, there were 7648 patients who received COVID-19 testing throughout the institutions. Of these, 1289 tested positive with a known blood type. A total of 484 (37.5%) were admitted to hospital, 123 (9.5%) were admitted to the ICU, 108 (8.4%) were intubated, 3 (0.2%) required ECMO, and 89 (6.9%) died. Of the 1289 patients who tested positive, 440 (34.2%) were blood type A, 201 (15.6%) were blood type B, 61 (4.7%) were blood type AB, and 587 (45.5%) were blood type O. On univariate analysis, there was no association between blood type and any of the peak inflammatory markers (peak WBC, p = 0.25; peak LDH, p = 0.40; peak ESR, p = 0.16; peak CRP, p = 0.14) nor between blood type and any of the clinical outcomes of severity (admission p = 0.20, ICU admission p = 0.94, intubation p = 0.93, proning while intubated p = 0.58, ECMO p = 0.09, and death p = 0.49). After multivariable analysis, blood type was not independently associated with risk of intubation or death (referent blood type A; blood type B: AOR: 0.72, 95% CI: 0.42–1.26, blood type AB: AOR: 0.78, CI: 0.33–1.87, blood type O: AOR: 0.77, CI: 0.51–1.16), rhesus factor positive (Rh+): AOR: 1.03, CI: 0.93–1.86. Blood type A had no correlation with positive testing (AOR: 1.00, CI: 0.88–1.13), blood type B was associated with higher odds of testing positive for disease (AOR: 1.28, CI: 1.08–1.52), AB was also associated with higher odds of testing positive (AOR: 1.37, CI: 1.02–1.83), and O was associated with a lower risk of testing positive (AOR: 0.84, CI: 0.75–0.95). Rh+ status was associated with higher odds of testing positive (AOR: 1.23, CI: 1.003–1.50). Blood type was not associated with risk of intubation or death in patients with COVID-19. Patients with blood types B and AB who received a test were more likely to test positive and blood type O was less likely to test positive. Rh+ patients were more likely to test positive.


docid: nqprluto

title: Rational Use of Tocilizumab in the Treatment of Novel Coronavirus Pneumonia

text: Since December 2019, a novel coronavirus pneumonia (COVID-19) has broken out in Wuhan, China and spread rapidly. Recent studies have found that ⁓ 15.7% of patients develop severe pneumonia, and cytokine storm is an important factor leading to rapid disease progression. Currently, there are no specific drugs for COVID-19 and the cytokine storm it causes. IL-6 is one of the key cytokines involved in infection-induced cytokine storm. Tocilizumab, which is the IL-6 receptor antagonist, has been approved by the US FDA for the treatment of cytokine release syndrome (CRS), is expected to treat cytokine storm caused by COVID-19 and is now in clinical trials. In this paper, we will elaborate the role of cytokine storm in COVID-19, the mechanism of tocilizumab on cytokine storm and the key points of pharmaceutical care based on the actual clinical application for COVID-19 in our hospital, the latest research reports, clinical trial progress of tocilizumab, drug instruction from the US FDA, and “Diagnosis and Treatment Plan of Novel Coronavirus Pneumonia (seventh trial edition)” in China, so as to provide reference for the treatment of COVID-19.


title: CXCL13 promotes isotype-switched B cell accumulation to the central nervous system during viral encephalomyelitis

text: Elevated CXCL13 within the central nervous system (CNS) correlates with humoral responses in several neuroinflammatory diseases, yet its role is controversial. During coronavirus encephalomyelitis CXCL13 deficiency impaired CNS accumulation of memory B cells and antibody-secreting cells (ASC) but not naïve/early-activated B cells. However, despite diminished germinal center B cells and follicular helper T cells in draining lymph nodes, ASC in bone marrow and antiviral serum antibody were intact in the absence of CXCL13. The data demonstrate that CXCL13 is not essential in mounting effective peripheral humoral responses, but specifically promotes CNS accumulation of differentiated B cells.


title: DDX5 RNA Helicases: Emerging Roles in Viral Infection

text: Asp-Glu-Ala-Asp (DEAD)-box polypeptide 5 (DDX5), also called p68, is a prototypical member of the large ATP-dependent RNA helicases family and is known to participate in all aspects of RNA metabolism ranging from transcription to translation, RNA decay, and miRNA processing. The roles of DDX5 in cell cycle regulation, tumorigenesis, apoptosis, cancer development, adipogenesis, Wnt-β-catenin signaling, and viral infection have been established. Several RNA viruses have been reported to hijack DDX5 to facilitate various steps of their replication cycles. Furthermore, DDX5 can be bounded by the viral proteins of some viruses with unknown functions. Interestingly, an antiviral function of DDX5 has been reported during hepatitis B virus and myxoma virus infection. Thus, the precise roles of this apparently multifaceted protein remain largely obscure. Here, we provide a rapid and critical overview of the structure and functions of DDX5 with a particular emphasis on its role during virus infection.


title: The first clusters of Middle East respiratory syndrome coronavirus in Oman: Time to act

text: Abstract Introduction Middle East respiratory syndrome coronavirus (MERS-CoV), is an emerging infectious disease of growing global importance. This review describes the latest MERS-CoV clusters and the first cases of nosocomial transmission within health care facilities in Oman. We have highlighted lessons learned and proposed steps to prevent healthcare-associated infections. Methods A descriptive analysis of MERS-CoV cases was conducted between January 23 and February 16, 2019. The data from officials and other published sources used. Results Thirteen laboratory-confirmed cases of MERS-CoV were reported from three simultaneous clusters from two governorates without an epidemiological link between the clusters. Two clusters were reported from North Al Batinah Governorate, with nine cases (69%) and 1 cluster from South Ash Sharqiyah Governorate with four cases (31%). In total, four deaths were reported (case fatality rate 31%). Four cases (31%) reported were household contacts from the first cluster, 3 (23%) were nosocomial transmission in health care facilities (two for first and one from the second cluster) and 7 (54%) were community-acquired cases. Conclusions The first local clusters of MERS-CoV reported with evidence suggestive of healthcare and household-associated transmission. Early diagnosis and strict implementation of infection control measures remain fundamental in preventing and managing MERS-CoV infection.


title: Expecting the unexpected: nucleic acid-based diagnosis and discovery of emerging viruses

text: Extrapolation from recent disease history suggests that changes in the global environment, including virus, vector and human behavior, will continue to influence the spectrum of viruses to which humans are exposed. In this article, these environmental changes will be enumerated, and their potential impact on target-focused, nucleic acid-based diagnostic tests will be considered, followed by a presentation of some emerging technological responses.


title: The methyltransferase domain of dengue virus protein NS5 ensures efficient RNA synthesis initiation and elongation by the polymerase domain

text: Viral RNA-dependent RNA polymerases (RdRps) responsible for the replication of single-strand RNA virus genomes exert their function in the context of complex replication machineries. Within these replication complexes the polymerase activity is often highly regulated by RNA elements, proteins or other domains of multi-domain polymerases. Here, we present data of the influence of the methyltransferase domain (NS5-MTase) of dengue virus (DENV) protein NS5 on the RdRp activity of the polymerase domain (NS5-Pol). The steady-state polymerase activities of DENV-2 recombinant NS5 and NS5-Pol are compared using different biochemical assays allowing the dissection of the de novo initiation, transition and elongation steps of RNA synthesis. We show that NS5-MTase ensures efficient RdRp activity by stimulating the de novo initiation and the elongation phase. This stimulation is related to a higher affinity of NS5 toward the single-strand RNA template indicating NS5-MTase either completes a high-affinity RNA binding site and/or promotes the correct formation of the template tunnel. Furthermore, the NS5-MTase increases the affinity of the priming nucleotide ATP upon de novo initiation and causes a higher catalytic efficiency of the polymerase upon elongation. The complex stimulation pattern is discussed under the perspective that NS5 adopts several conformations during RNA synthesis.


title: Coronavirus disease pandemic (Covid-19): Challenges and a global perspective

text: The technology-driven world of the 21stcentury is currently confronted with a major threat to humankind, represented by the coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome, coronavirus-2 (SARS-CoV-2). As of now, COVID-19 has affected more than 6 million confirmed cases and took 0.39 million human lives. SARS-CoV-2 spreads much faster than its two ancestors, SARS-CoV and Middle East respiratory syndrome-CoV (MERS-CoV), but has low fatality rates. Our analyses speculate that the efficient replication and transmission of SARS-CoV-2 might be due to the high-density basic amino acid residues, preferably positioned in close proximity at both the furin-like cleavage sites (S1/S2 and S2’) within the spike protein. Given the high genomic similarities of SARS-CoV-2 to bat SARS-like CoVs, it is likely that bats serve as a reservoir host for its progenitor. Women and children are less susceptible to SARS-CoV-2 infection, while the elderly and people with comorbidities are more prone to serious clinical outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. The cohesive approach amongst researchers across the globe has delivered high-end viral diagnostics. However, home-based point-of-care diagnostics are still under development, which may prove transformative in current COVID-19 pandemic containment. Similarly, vaccines and therapeutics against COVID-19 are currently in the pipeline for clinical trials. In this review, we discuss the noteworthy advancements, focusing on the etiological viral agent, comparative genomic analysis, population susceptibility, disease epidemiology and diagnosis, animal reservoirs, laboratory animal models, disease transmission, therapeutics, vaccine challenges, and disease mitigation measures.


docid: hlthvadj

title: A single chain Fv antibody displayed on phage surface recognises conformational group-specific epitope of bluetongue virus

text: Abstract A single chain fragment variable (scFv) antibody gene was isolated from hybridoma cell line secreting monoclonal antibody (MAb) 20E9 that recognises bluetongue virus (BTV) VP7. DNA fragments encoding variable regions of heavy and light chains were amplified by RT-PCR and library of scFv was constructed in phage vector. Two scFv clones that were selected showed specific reactivity with conformational epitope VP7. The N-terminal 22 amino acid residues of 20E9 light chain were identical to that deduced from scFv DNA sequence. An in-frame TAG stop codon was found in the coding sequence and its potential role in regulating the expression and stability of scFv in phage is discussed.


title: The mutual effects of COVID-19 and obesity

text: • The rate of obesity was increased during this era of the COVID-19 epidemic. • Obesity is dangerous in COVID-19 patients.


title: SARS Coronavirus 3b Accessory Protein Modulates Transcriptional Activity of RUNX1b

text: BACKGROUND: The causative agent of severe acute respiratory syndrome, SARS coronavirus (SARS-CoV) genome encodes several unique group specific accessory proteins with unknown functions. Among them, accessory protein 3b (also known as ORF4) was lately identified as one of the viral interferon antagonist. Recently our lab uncovered a new role for 3b in upregulation of AP-1 transcriptional activity and its downstream genes. Thus, we believe that 3b might play an important role in SARS-CoV pathogenesis and therefore is of considerable interest. The current study aims at identifying novel host cellular interactors of the 3b protein. METHODOLOGY/PRINCIPAL FINDINGS: In this study, using yeast two-hybrid and co-immunoprecipitation techniques, we have identified a host transcription factor RUNX1b (Runt related transcription factor, isoform b) as a novel interacting partner for SARS-CoV 3b protein. Chromatin immunoprecipitaion (ChIP) and reporter gene assays in 3b expressing jurkat cells showed recruitment of 3b on the RUNX1 binding element that led to an increase in RUNX1b transactivation potential on the IL2 promoter. Kinase assay and pharmacological inhibitor treatment implied that 3b also affect RUNX1b transcriptional activity by regulating its ERK dependent phosphorylation levels. Additionally, mRNA levels of MIP-1α, a RUNX1b target gene upregulated in SARS-CoV infected monocyte-derived dendritic cells, were found to be elevated in 3b expressing U937 monocyte cells. CONCLUSIONS/SIGNIFICANCE: These results unveil a novel interaction of SARS-CoV 3b with the host factor, RUNX1b, and speculate its physiological relevance in upregulating cytokines and chemokine levels in state of SARS virus infection.


title: Avian influenza A/H5N1 neuraminidase expressed in yeast with a functional head domain

text: Abstract The study reports heterologous expression in Pichia pastoris of active neuraminidase derived from avian influenza virus A/Viet Nam/DT-036/2005(H5N1). A gene encoding the neuraminidase N1 head domain (residues 63–449) was fused directly in-frame with the Saccharomyces cerevisiae α-factor secretion signal in pPICZ(A vector. Recombinant N1 neuraminidase was expressed in P. pastoris as a 72kDa secreted, soluble protein. Glycopeptidase F treatment generated a 45kDa product, indicating that the secreted recombinant N1 neuraminidase is an N-linked glycoprotein. Kinetic studies and inhibition tests with oseltamivir carboxylate demonstrated that the recombinant N1 neuraminidase has similar K m and K i values to those of the viral N1 neuraminidase. This yeast-based heterologous expression system provided functionally active recombinant N1 neuraminidase that should be useful in anti-influenza drug screening, and also as a potential protein-based vaccine.


docid: opgfgehy

title: What did we learn from preparing for cross-border transmission of Ebola virus disease into a complex humanitarian setting – The Republic of South Sudan?

text: BACKGROUND: Following the West Africa Ebola virus disease (EVD) outbreak (2013–2016), WHO developed a preparedness checklist for its member states. This checklist is currently being applied for the first time on a large and systematic scale to prepare for the cross border importation of the ongoing EVD outbreak in the Democratic Republic of Congo hence the need to document the lessons learnt from this experience. This is more pertinent considering the complex humanitarian context and weak health system under which some of the countries such as the Republic of South Sudan are implementing their EVD preparedness interventions. MAIN TEXT: We identified four main lessons from the ongoing EVD preparedness efforts in the Republic South Sudan. First, EVD preparedness is possible in complex humanitarian settings such as the Republic of South Sudan by using a longer-term health system strengthening approach. Second, the Republic of South Sudan is at risk of both domestic and cross border transmission of EVD and several other infectious disease outbreaks hence the need for an integrated and sustainable approach to outbreak preparedness in the country. Third, a phased and well-prioritized approach is required for EVD preparedness in complex humanitarian settings given the costs associated with preparedness and the difficulties in the accurate prediction of outbreaks in such settings. Fourth, EVD preparedness in complex humanitarian settings is a massive undertaking that requires effective and decentralized coordination. CONCLUSION: Despite a very challenging context, the Republic of South Sudan made significant progress in its EVD preparedness drive demonstrating that it is possible to rapidly scale up preparedness efforts in complex humanitarian contexts if appropriate and context-specific approaches are used. Further research, systematic reviews and evaluation of the ongoing preparedness efforts are required to ensure comprehensive documentation and application of the lessons learnt for future EVD outbreak preparedness and response efforts.


title: No slack in diseases threat

text: Summary A new WHO report argues that there should be no let up in efforts to increase global cooperation in the face of still unprecedented threats from new diseases. Nigel Williams reports.


docid: jbrdrxxx

title: A Python based Support Vector Regression Model for prediction of Covid19 cases in India

text: The proposed work utilizes Support Vector Regression model to predict the number of total number of deaths, recovered cases, cumulative number of confirmed cases and number of daily cases. The data is collected for the time period of 1(st) March,2020 to 30(th) April,2020 (61 Days). The total number of cases as on 30(th) April is found to be 35043 confirmed cases with 1147 total deaths and 8889 recovered patients. The model has been developed in Python 3.6.3 to obtain the predicted values of aforementioned cases till 30(th) June,2020. The proposed methodology is based on prediction of values using support vector regression model with Radial Basis Function as the kernel and 10% confidence interval for the curve fitting. The data has been split into train and test set with test size 40% and training 60%. The model performance parameters are calculated as mean square error, root mean square error, regression score and percentage accuracy. The model has above 97% accuracy in predicting deaths, recovered, cumulative number of confirmed cases and 87% accuracy in predicting daily new cases. The results suggest a gaussian decrease of the number of cases and could take another 3 to 4 months to come down the minimum level with no new cases being reported. The method is very efficient and has higher accuracy than linear or polynomial regression.