title: Differential recognition of peptides within feline coronavirus polyprotein 1 ab by sera from healthy cats and cats with feline infectious peritonitis

text: Abstract The aim of the study was to identify peptides within the polyprotein (Pp) 1 ab that are differentially recognised by cats with either enteric or systemic disease following infection with feline coronavirus. Overlapping 12-mer peptides (n = 28,426) across the entire Pp1ab were arrayed on peptide chips and reacted with pooled sera from coronavirus seropositive cats and from one seronegative cat. Eleven peptides were further tested in ELISA with individual serum samples, and three were selected for further screening. Two peptides (16433 and 4934) in the nsp3 region encoding the papain 1 and 2 proteases were identified for final testing. Peptide 4934 reacted equally with positive sera from healthy cats and cats with feline infectious peritonitis (FIP), while peptide 16433 was recognized predominantly by FIP-affected cats. The value of antibody tests based on these peptides in differentiating between the enteric and FIP forms of feline coronavirus infection remains to be determined.


title: Frequency of detection of respiratory viruses in the lower respiratory tract of hospitalized adults

text: Abstract Background Respiratory infections are the most common infections in humans. The prevalence of respiratory viruses in adults is largely underestimated, and relevant data mostly concern infants and children. Objectives To evaluate the prevalence of respiratory viruses in adults hospitalized in Italy. Study design During April 2004–May 2005, 510 consecutive lower respiratory tract samples were prospectively collected. These were evaluated with a molecular panel that detected 12 respiratory viruses. Results Two hundred and fifteen samples were positive for at least one viral pathogen, with an overall sample prevalence of 42.2%. Human rhinoviruses (HRVs) were the most commonly detected viruses (32.9%), followed by influenza virus (FLU)-A (9.0%); the other viruses were 2% or less. Multiple agents were detected in 30 samples from 29 patients, resulting in a co-infection rate of 6.7%. Conclusions This study shows a high prevalence of viruses in the lower respiratory tract samples of hospitalized adults, mostly HRV and FLU-A. It is not possible to establish the role of viruses detected at low frequency, but our findings suggest the necessity to consider them as potential causes or precursors of lower respiratory tract infections (LRTIs).


Psychological Impact of COVID-19 in pregnant women


COVID-19 Impact in Community Care – A Perspective on Older Persons with Dementia in Singapore.


Documenting the SARS epidemic in mainland China


title: Severe COVID-19 infection in pregnancy requiring intubation without preterm delivery: A case report

text: Abstract Background Coronavirus-2019 (COVID-19) is a global health crisis, but there is limited guidance for the critical care management of pregnant patients experiencing respiratory collapse. We describe our management of a peri-viable pregnant patient requiring intubation; discussion includes pharmacologic interventions, mechanical ventilation adjustments, and consideration of fetal interventions, including delivery timing. Case A 36-year-old, gravida 2, para 1 woman positive for COVID-19 at 23 weeks of gestation with severe disease required admission to the intensive care unit and intubation. She completed 5 days of hydroxychloroquine and 7 days of prednisone. She was successfully intubated after 8 days and discharged home in a stable condition without preterm delivery on hospital day 11. Conclusion Fortunately, the patient responded to aggressive respiratory support with intubation and mechanical ventilation early upon presentation. It is unclear whether our institution's empiric use of hydroxychloroquine and prednisone facilitated her recovery. We hope that our report helps other institutions navigate the complex care surrounding pregnant patients with severe COVID-19 pneumonia requiring intensive care.


No Evidence of Rapid Antiviral Clearance or Clinical Benefit with the Combination of Hydroxychloroquine and Azithromycin in Patients with Severe COVID-19 Infection


title: The global dynamics for a stochastic SIS epidemic model with isolation

text: Abstract In this paper, we investigate the dynamical behavior for a stochastic SIS epidemic model with isolation which is as an important strategy for the elimination of infectious diseases. It is assumed that the stochastic effects manifest themselves mainly as fluctuation in the transmission coefficient, the death rate and the proportional coefficient of the isolation of infective. It is shown that the extinction and persistence in the mean of the model are determined by a threshold value R 0 S . That is, if R 0 S < 1 , then disease dies out with probability one, and if R 0 S > 1 , then the disease is stochastic persistent in the means with probability one. Furthermore, the existence of a unique stationary distribution is discussed, and the sufficient conditions are established by using the Lyapunov function method. Finally, some numerical examples are carried out to confirm the analytical results.


title: Diagnostic evaluation of assays for detection of antibodies against porcine epidemic diarrhea virus (PEDV) in pigs exposed to different PEDV strains

text: Abstract Porcine epidemic diarrhea virus (PEDV) has caused economic losses in the Americas, Asia and Europe in recent years. Reliable serological assays are essential for epidemiological studies and vaccine evaluation. The objective of this study was to compare the ability of five enzyme-linked immunosorbent assays (ELISAs) to detect antibodies against different PEDV strains in pig serum. A total of 732 serum samples from North American or European pigs were tested. Samples included experimental samples from pigs infected with classical (G1a PEDV) or variant genogroup 1 PEDV (G1b PEDV), pandemic genogroup 2 PEDV (G2b PEDV) or non-infected controls. Field samples from herds with confirmed or unknown PEDV exposure were also used. Three indirect ELISAs based on G2b antigens (ELISAs 1, 2 and 3), a competitive ELISA based on the G2b antigen (ELISA 4) and a competitive ELISA based on the G1a antigen (ELISA 5) were compared. Overall, the tests had a moderate agreement (κ=0.61). G1a PEDV infected pigs were earliest detected by ELISA 3, G1b PEDV infected pigs were earliest detected by ELISAs 4 and 5 and the performance of all tests was similar for the G2b PEDV group. ELISA 1 showed the overall lowest detection on experimentally and field derived samples. Diagnostic sensitivity and specificity with a 95% probability interval were estimated to be 68.2% (62.1–74.4%) and 97.5% (95.2–99.0%) for ELISA 1, 73.7% (71.5–79.6%) and 98.4% (96.6–99.5%) for ELISA 2, 86.2% (81.1–90.6%) and 91.6% (87.7–94.8%) for ELISA 3, 78.3% (72.8–83.5%) and 99.7% (98.2–100%) for ELISA 4, and 93.5% (90.3–96.0%) and 91.2% (83.8–97.9%) for ELISA 5. Differences in detection among assays seem to be more related to intrinsic factors of an assay than to the PEDV antigen used.


title: Antioxidant, Anti-Inflammatory, and Microbial-Modulating Activities of Essential Oils: Implications in Colonic Pathophysiology

text: Essential oils (EOs) are a complex mixture of hydrophobic and volatile compounds synthesized from aromatic plants, most of them commonly used in the human diet. In recent years, many studies have analyzed their antimicrobial, antioxidant, anti-inflammatory, immunomodulatory and anticancer properties in vitro and on experimentally induced animal models of colitis and colorectal cancer. However, there are still few clinical studies aimed to understand their role in the modulation of the intestinal pathophysiology. Many EOs and some of their molecules have demonstrated their efficacy in inhibiting bacterial, fungi and virus replication and in modulating the inflammatory and oxidative processes that take place in experimental colitis. In addition to this, their antitumor activity against colorectal cancer models makes them extremely interesting compounds for the modulation of the pathophysiology of the large bowel. The characterization of these EOs is made difficult by their complexity and by the different compositions present in the same oil having different geographical origins. This review tries to shift the focus from the EOs to their individual compounds, to expand their possible applications in modulating colon pathophysiology.


title: Occupational Risks of Health Professionals in Turkey as an Emerging Economy

text: Abstract Background Health services are one of the work areas that contain important risks in terms of the occupational health and safety of the laborer. Professionals in various areas of health services encounter biological, chemical, physical, ergonomic, and psychosocial risks, particularly in hospitals. Objectives This study has been performed to evaluate the impacts of the occupational risks on health of health professionals in Turkey. Findings In Turkey, as an emerging economy, the history of studies on health professionals is not longstanding. There have been various regulations intended for the occupational health and safety of health professionals in line with the Regulation of the Provision on Patient and Staff Safety prepared in 2012. However, applications can differ from region to region, institution to institution, and person to person. Conclusions We believe that this review will lead health professionals to be aware of occupational risks and contribute to planning health services for health professionals.


Call for Papers: Special Issue on Coronaviruses


title: Readiness of hospital nurses for disaster responses in Taiwan: A cross-sectional study

text: BACKGROUND: Because patients in disaster areas require the most critical care, mobilising hospital nurses has become a pivotal strategy. Given the importance of disaster nursing training programmes, understanding how well prepared hospital nurses are to provide disaster care is vital. OBJECTIVES: This paper analyses the perceived readiness of hospital nurses for a disaster response and the factors influencing their report for work outside the hospital environment. DESIGN: A cross-sectional research design was used. SETTINGS: This study was conducted at a military hospital in Taiwan. PARTICIPANTS: A sample of 311 registered nurses participated in this study. METHODS: Data were collected on readiness for disaster responses using a 40-item researcher-designed, self-administered questionnaire found to have satisfactory reliability and validity. The questionnaire has four domains: personal preparation (16 items), self-protection (11 items), emergency response (6 items), and clinical management (7 items). Data were analysed using descriptive statistics, independent t-tests and generalised linear models. RESULTS: The majority of hospital nurses demonstrated poor readiness for disaster responses. Scores on the four domains were most associated with nurses' disaster-related training, experience in disaster response and emergency/intensive care experience. CONCLUSIONS: Our results indicate that disaster-related training should be included in undergraduate programmes and continuing education courses to help hospital nurses recognise and improve their own readiness for disaster responses outside the hospital environment. Future research is needed to improve hospital nurses' disaster-response readiness in Taiwan and other countries.


title: An Evaluation of Florida’s Zika Response Using the WHO Health Systems Framework: Can We Apply These Lessons to COVID-19?

text: OBJECTIVES: From 2016 to 2018 Florida documented 1471 cases of Zika virus, 299 of which were pregnant women (Florida Department of Health, https://www.floridahealth.gov/diseases-and-conditions/mosquito-bornediseases/surveillance.html, 2019a). Florida’s response required unprecedented rapid and continuous cross-sector communication, adaptation, and coordination. Zika tested public health systems in new ways, particularly for maternal child health populations. The systems are now being challenged again, as the Coronavirus COVID-19 pandemic spreads throughout Florida. This qualitative journey mapping evaluation of Florida’s response focused on care for pregnant women and families with infants exposed to Zika virus. METHODS: Fifteen focus groups and interviews were conducted with 33 public health and healthcare workers who managed outbreak response, case investigations, and patient care in south Florida. Data were thematically analyzed, and the results were framed by the World Health Organization’s (WHO) Healthcare Systems Framework of six building blocks: health service delivery, health workforce, health information systems, access to essential medicines, financing, and leadership and governance (World Health Organization, https://www.who.int/healthsystems/strategy/everybodys_business.pdf, 2007, https://www.who.int/healthinfo/systems/monitoring/en/, 2010). RESULTS: Results highlighted coordination of resources, essential services and treatment, data collection, communication among public health and healthcare systems, and dissemination of information. Community education, testing accuracy and turnaround time, financing, and continuity of health services were areas of need, and there was room for improvement in all indicator areas. CONCLUSIONS: The WHO Framework encapsulated important infrastructure and process factors relevant to the Florida Zika response as well as future epidemics. In this context, similarities, differences, and implications for the Coronavirus COVID-19 pandemic response are discussed.


title: Chauves-souris et virus : quelles relations ? Quelles conséquences ?

text: On connaît plus de 1 240 espèces de chauves-souris ; beaucoup sont insectivores, d’autres frugivores et quelques espèces américaines sont hématophages. Ces mammifères peuvent héberger plus de 100 virus différents, en particulier des Rhabdoviridae (des Lyssavirus, dont le virus rabique), des Paramyxoviridae (comme les virus Nipah et Hendra), des Filoviridae (virus Ebola et Marburg) et des Coronaviridae (agents du SRAS et du MERS). Ces infections sont généralement asymptomatiques chez les chauves-souris mais le mécanisme de cette tolérance n’est pas encore bien compris. Quoi qu’il en soit, les chauves-souris apparaissent pour ces virus comme des réservoirs et des disséminateurs efficaces ; elles représentent donc un risque important en santé publique humaine et vétérinaire, justifiant la mise en place d’une surveillance spécifique et de programmes de recherche portant notamment sur les mécanismes de l’immunité propres à ces animaux. SUMMARY: More than 1 240 species of bats are known ; many of them are insectivorous, others are frugivorous and some american species are haematophagous. More than 100 different viruses are associated with these mammals, particularly Rhabdoviridae (Lyssavirus like rabies virus), Paramyxoviridae (like Nipah and Hendra viruses), Filoviridae (Ebola and Marburg viruses) and Coronaviridae (viruses causing SARS and MERS). These infections are usually asymptomatic in bats but the mechanism of this tolerance is not yet understood. For those viruses, bats are efficient reservoirs and disseminators. So, they represent a significative risk for human and animal public health, that justifies to set up surveillance of batassociated viruses and research programs about the particular immunity mechanisms of bats.


title: The Singapore Field Epidemiology Service: Insights Into Outbreak Management

text: Field epidemiology involves the implementation of quick and targeted public health interventions with the aid of epidemiological methods. In this article, we share our practical experiences in outbreak management and in safeguarding the population against novel diseases. Given that cities represent the financial nexuses of the global economy, global health security necessitates the safeguard of cities against epidemic diseases. Singapore's public health landscape has undergone a systemic and irreversible shift with global connectivity, rapid urbanization, ecological change, increased affluence, as well as shifting demographic patterns over the past two decades. Concomitantly, the threat of epidemics, ranging from severe acute respiratory syndrome and influenza A (H1N1) to the resurgence of vector-borne diseases as well as the rise of modern lifestyle-related outbreaks, have worsened difficulties in safeguarding public health amidst much elusiveness and unpredictability. One critical factor that has helped the country overcome these innate and man-made public health vulnerabilities is the development of a resilient field epidemiology service, which includes our enhancement of surveillance and response capacities for outbreak management, and investment in public health leadership. We offer herein the Singapore story as a case study in meeting the challenges of disease control in our modern built environment.


title: A Yeast Suppressor Screen Used To Identify Mammalian SIRT1 as a Proviral Factor for Middle East Respiratory Syndrome Coronavirus Replication

text: Viral proteins must intimately interact with the host cell machinery during virus replication. Here, we used the yeast Saccharomyces cerevisiae as a system to identify novel functional interactions between viral proteins and eukaryotic cells. Our work demonstrates that when the Middle East respiratory syndrome coronavirus (MERS-CoV) ORF4a accessory gene is expressed in yeast it causes a slow-growth phenotype. ORF4a has been characterized as an interferon antagonist in mammalian cells, and yet yeast lack an interferon system, suggesting further interactions between ORF4a and eukaryotic cells. Using the slow-growth phenotype as a reporter of ORF4a function, we utilized the yeast knockout library collection to perform a suppressor screen where we identified the YDL042C/SIR2 yeast gene as a suppressor of ORF4a function. The mammalian homologue of SIR2 is SIRT1, an NAD-dependent histone deacetylase. We found that when SIRT1 was inhibited by either chemical or genetic manipulation, there was reduced MERS-CoV replication, suggesting that SIRT1 is a proviral factor for MERS-CoV. Moreover, ORF4a inhibited SIRT1-mediated modulation of NF-κB signaling, demonstrating a functional link between ORF4a and SIRT1 in mammalian cells. Overall, the data presented here demonstrate the utility of yeast studies for identifying genetic interactions between viral proteins and eukaryotic cells. We also demonstrate for the first time that SIRT1 is a proviral factor for MERS-CoV replication and that ORF4a has a role in modulating its activity in cells. IMPORTANCE Middle East respiratory syndrome coronavirus (MERS-CoV) initially emerged in 2012 and has since been responsible for over 2,300 infections, with a case fatality ratio of approximately 35%. We have used the highly characterized model system of Saccharomyces cerevisiae to investigate novel functional interactions between viral proteins and eukaryotic cells that may provide new avenues for antiviral intervention. We identify a functional link between the MERS-CoV ORF4a proteins and the YDL042C/SIR2 yeast gene. The mammalian homologue of SIR2 is SIRT1, an NAD-dependent histone deacetylase. We demonstrate for the first time that SIRT1 is a proviral factor for MERS-CoV replication and that ORF4a has a role in modulating its activity in mammalian cells.


title: Correlation between the presence of neutralizing antibodies against porcine circovirus 2 (PCV2) and protection against replication of the virus and development of PCV2-associated disease

text: BACKGROUND: In a previous study, it was demonstrated that high replication of Porcine circovirus 2 (PCV2) in a gnotobiotic pig was correlated with the absence of PCV2-neutralizing antibodies. The aim of the present study was to investigate if this correlation could also be found in SPF pigs in which PMWS was experimentally reproduced and in naturally PMWS-affected pigs. RESULTS: When looking at the total anti-PCV2 antibody titres, PMWS-affected and healthy animals seroconverted at the same time point, and titres in PMWS-affected animals were only slightly lower compared to those in healthy animals. In healthy animals, the evolution of PCV2-neutralizing antibodies coincided with that of total antibodies. In PMWS-affected animals, neutralizing antibodies could either not be found (sera from field studies) or were detected in low titres between 7 and 14 DPI only (sera from experimentally inoculated SPF pigs). Differences were also found in the evolution of specific antibody isotypes titres against PCV2. In healthy pigs, IgM antibodies persisted until the end of the study, whereas in PMWS-affected pigs they quickly decreased or remained present at low titres. The mean titres of other antibody isotypes (IgG1, IgG2 and IgA), were slightly lower in PMWS-affected pigs compared to their healthy group mates at the end of each study. CONCLUSION: This study describes important differences in the development of the humoral immune response between pigs that get subclinically infected with PCV2 and pigs that experience a high level of PCV2-replication which in 3 of 4 experiments led to the development of PMWS. These observations may contribute to a better understanding of the pathogenesis of a PCV2-infection.


title: Gain-of-function experiments: time for a real debate

text: According to the WHO, dual use research of concern (DURC) is “life sciences research that is intended for benefit, but which might easily be misapplied to do harm”. Recent studies, particularly those on influenza viruses, have led to renewed attention on DURC, as there is an ongoing debate over whether the benefits of gain-of-function (GOF) experiments that result in an increase in the transmission and/or pathogenicity of potential pandemic pathogens (PPPs) are outweighed by concerns over biosecurity and biosafety. In this Viewpoint article, proponents and opponents of GOF experiments discuss the benefits and risks associated with these studies, as well as the implications of the current debate for the scientific community and the general public, and suggest how the current discussion should move forward.


title: Interactions of Respiratory Viruses and the Nasal Microbiota during the First Year of Life in Healthy Infants

text: Traditional culture techniques have shown that increased bacterial colonization is associated with viral colonization; however, the influence of viral colonization on the whole microbiota composition is less clear. We thus aimed to understand the interaction of viral infections and the nasal microbiota in early life to appraise their roles in disease development. Thirty-two healthy, unselected infants were included in this prospective longitudinal cohort study within the first year of life. Biweekly nasal swabs (n = 559) were taken, and the microbiota was analyzed by 16S rRNA pyrosequencing, and 10 different viruses and 2 atypical bacteria were characterized by real-time PCR (combination of seven duplex samples). In contrast to asymptomatic human rhinovirus (HRV) colonization, symptomatic HRV infections were associated with lower alpha diversity (Shannon diversity index [SDI]), higher bacterial density (PCR concentration), and a difference in beta diversities (Jaccard and Bray-Curtis index) of the microbiota. In addition, infants with more frequent HRV infections had a lower SDI at the end of the study period. Overall, changes in the microbiota associated with symptomatic HRV infections were characterized by a loss of microbial diversity. The interaction between HRV infections and the nasal microbiota in early life might be of importance for later disease development and indicate a potential approach for future interventions. IMPORTANCE Respiratory viral infections are very frequent in infancy and of importance in acute and chronic disease development. Infections with human rhinovirus (HRV) are, e.g., associated with the later development of asthma. We found that only symptomatic HRV infections were associated with acute changes in the nasal microbiota, mainly characterized by a loss of microbial diversity. Infants with more frequent symptomatic HRV infections had a lower bacterial diversity at the end of the first year of life. Whether the interaction between viruses and the microbiota is one pathway contributing to asthma development will be assessed in the follow-ups of these children. Independent of that, measurements of microbial diversity might represent a potential marker for risk of later lung disease or monitoring of early life interventions.


title: Generation of monoclonal antibodies specific of the postfusion conformation of the Pneumovirinae fusion (F) protein

text: Abstract Paramyxovirus entry into cells requires fusion of the viral and cell membranes mediated by one of the major virus glycoproteins, the fusion (F) glycoprotein which transits from a metastable pre-fusion conformation to a highly stable post-fusion structure during the membrane fusion process. F protein refolding involves large conformational changes of the protein trimer. One of these changes results in assembly of two heptad repeat sequences (HRA and HRB) from each protomer into a six-helix bundle (6HB) motif. To assist in distinguishing pre- and post-fusion conformations of the Pneumovirinae F proteins, and as extension of previous work (Palomo et al., 2014), a general strategy was designed to obtain polyclonal and particularly monoclonal antibodies specific of the 6HB motif of the Pneumovirinae fusion protein. The antibodies reported here should assist in the characterization of the structural changes that the F protein of human metapneumovirus or respiratory syncytial virus experiences during the process of membrane fusion.


title: Fever in the Returning Traveler

text: Millions of children travel annually, whether they are refugees, international adoptees, visitors, or vacationers. Although most young travelers do well, many develop a febrile illness during or shortly after their trips. Approaching a fever in the returning traveler requires an appropriate index of suspicion to diagnose and treat in a timely manner. As many as 34% of patients with recent travel history are diagnosed with routine infections, but serious infections such as malaria, enteric fever, and dengue fever should be on the differential diagnosis due the high morbidity and mortality in children.


title: Early diagnosis of SARS Coronavirus infection by real time RT-PCR

text: Abstract Background: A novel coronavirus was recently identified as the aetiological agent of Severe Acute Respiratory Syndrome (SARS). Molecular assays currently available for detection of SARS-coronavirus (SARS-Cov) have low sensitivity during the early stage of the illness. Objective: To develop and evaluate a sensitive diagnostic test for SARS by optimizing the viral RNA extraction methods and by applying real-time quantitative RT-PCR technology. Study design: 50 nasopharyngeal aspirate (NPA) samples collected from days 1–3 of disease onset from SARS patients in whom SARS CoV infections was subsequently serologically confirmed and 30 negative control samples were studied. Samples were tested by: (1) our first generation conventional RT-PCR assay with a routine RNA extraction method (Lancet 361 (2003) 1319), (2) our first generation conventional RT-PCR assay with a modified RNA extraction method, (3) a real-time quantitative RT-PCR assay with a modified RNA extraction method. Results: Of 50 NPA specimens collected during the first 3 days of illness, 11 (22%) were positive in our first generation RT-PCR assay. With a modification in the RNA extraction protocol, 22 (44%) samples were positive in the conventional RT-PCR assay. By combining the modified RNA extraction method and real-time quantitative PCR technology, 40 (80%) of these samples were positive in the real-time RT-PCR assay. No positive signal was observed in the negative controls. Conclusion: By optimizing RNA extraction methods and applying quantitative real time RT-PCR technologies, the sensitivity of tests for early diagnosis of SARS can be greatly enhanced.


title: Pandethics

text: Summary This paper explains the ethical importance of infectious diseases, and reviews four major ethical issues associated with pandemic influenza: the obligation of individuals to avoid infecting others, healthcare workers' ‘duty to treat’, allocation of scarce resources, and coercive social distancing measures. In each case, ways in which the ethical issues turn on both philosophical and empirical questions are highlighted. The paper concludes that ethicists should play a greater role in identifying ethically important empirical questions, and that scientists should take the ethical as well as the scientific importance of such questions into consideration when choosing research projects.


title: Natural killer cells as an initial defense against pathogens

text: Natural killer (NK) cells serve as a crucial first line of defense against tumors and a diverse range of pathogens. Recognition of infection by NK cells is accomplished by the activation of receptors on the NK cell surface, which initiate NK cell effector functions. Many of the receptors and ligands involved in NK cell antimicrobial activity have been identified, and we are beginning to appreciate how they function during infection. In addition, NK cells are activated by cytokines (e.g. interleukin 12 and type I interferons), which are products of activated macrophages and dendritic cells. In response to these activating stimuli, NK cells secrete cytokines and chemokines and lyse target cells. Recent studies have focused on the mechanisms by which NK cells recognize and respond to viruses, parasites and bacteria, and on the unique role of NK cells in innate immunity to infection.


title: Etiology of Community-Acquired Pneumonia

text: Community-acquired pneumonia (CAP) is a serious lower respiratory tract infection associated with significant morbidity and mortality that is characterized by disputes over diagnostic evaluations and therapeutic decisions. With the widespread use of broad-spectrum antimicrobial agents and the increasing number of immunocompromised hosts, the etiology and the drug resistance patterns of pathogens responsible for CAP have changed. Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis remain the leading causes of CAP in immunocompetent patients. Opportunistic infections with organisms such as Pneumocystis jiroveci and Mycobacterium tuberculosis and other opportunistic fungal pneumonias should also be considered in the differential diagnosis of CAP in immunocompromised patients. This article examines the current peer-reviewed literature on etiology, risk factors, and outcomes of patients with CAP.


Protection effectiveness of a building-integrated COVID-19 sampling station that uses a sealed acrylic window as a physical barrier


title: Emociones, preocupaciones y reflexiones frente a la pandemia del COVID-19 en Argentina/ Emotions, concerns and reflections regarding the COVID-19 pandemic in Argentina

text: Resumen El objetivo de este trabajo es explorar los sentimientos y expectativas que genera el COVID-19 en Argentina durante la primera etapa de la pandemia. Se aplicó una encuesta de la Organización Mundial de la Salud adaptada al contexto local. Se incluyeron preguntas abiertas para indagar sentimientos de las personas frente al COVID-19, y se realizó un análisis de contenido. Como resultados se advierte que la población encuestada siente incertidumbre, miedo y angustia, pero también emerge un sentimiento de responsabilidad y cuidado frente al COVID-19. Así mismo se destacan sentimientos positivos para la sociedad como una valoración de la interdependencia social. Los resultados arribados señalan que el impacto en la salud mental es desigual según el género, el nivel educativo alcanzado y el confort percibido en el hogar. El estudio permite concluir que las dimensiones emocionales y vinculares de las personas resultan aspectos centrales ante la pandemia del COVID-19 en Argentina. Es recomendable que estas dimensiones, así como y su impacto subjetivo y social diferencial entre los diversos grupos poblacionales, sean consideradas en la planificación de políticas para afrontar el COVID-19.


title: Medical waste production at hospitals and associated factors

text: Abstract This study was conducted to evaluate the quantities of medical waste generated and the factors associated with the generation rate at medical establishments in Taiwan. Data on medical waste generation at 150 health care establishments were collected for analysis in 2003. General medical waste and infectious waste production at these establishments were examined statistically with the potential associated factors. These factors included the types of hospital and clinic, reimbursement payment by National Health Insurance, total number of beds, bed occupancy, number of infectious disease beds and outpatients per day. The average waste generation rates ranged from 2.41 to 3.26kg/bed/day for general medical wastes, and 0.19–0.88kg/bed/day for infectious wastes. The total average quantity of infectious wastes generated was the highest from medical centers, or 3.8 times higher than that from regional hospitals (267.8 vs. 70.3Tons/yr). The multivariate regression analysis was able to explain 92% of infectious wastes and 64% of general medical wastes, with the amount of insurance reimbursement and number of beds as significant prediction factors. This study suggests that large hospitals are the major source of medical waste in Taiwan. The fractions of medical waste treated as infectious at all levels of healthcare establishments are much greater than that recommended by the USCDC guidelines.


title: GOING TO WAR ON COVID19: MOBILIZING AN ACADEMIC NEPHROLOGY GROUP PRACTICE

text: AIMS: The COVID‐19 pandemic poses unprecedented operational challenges to nephrology divisions in every country as they cope with COVID‐19‐related kidney disease in addition to regular patient care. Although general approaches have been proposed, there is a lack of practical guidance for nephrology division response in a hospital facing a surge of cases. Here, we describe the specific measures that our division has taken in the hope that our experience in Singapore may be helpful to others METHODS: Descriptive narrative RESULTS: A compilation of operational responses to the COVID‐19 pandemic taken by a nephrology division at a Singapore university hospital CONCLUSION: Nephrology operational readiness for COVID‐19 requires a clinical mindset shift from usual standard of care to a crisis exigency model that targets best outcomes for available resources. Rapid multi‐disciplinary efforts that evolve flexibly with the local dynamics of the outbreak are required. This article is protected by copyright. All rights reserved.


title: Perspectives on the development of neutralizing antibodies against SARS-CoV-2

text: SARS-CoV-2 gains entry to human cells through its spike (S) protein binding to angiotensin-converting enzyme 2 (ACE2). Therefore, the receptor binding domain (RBD) of the S protein is the primary target for neutralizing antibodies. Selection of broad-neutralizing antibodies against SARS-CoV-2 and SARS-CoV is attractive and might be useful for treating not only COVID-19 but also future SARS-related CoV infections. Broad-neutralizing antibodies, such as 47D11, S309, and VHH-72, have been reported to target a conserved region in the RBD of the S1 subunit. The S2 subunit required for viral membrane fusion might be another target. Due to their small size and high stability, single-domain antibodies might have the ability to be administered by an inhaler making them potentially attractive therapeutics for respiratory infections. A cocktail strategy combining two (or more) antibodies that recognize different parts of the viral surface that interact with human cells might be the most effective.


title: Complete genome sequence of a novel infectious bronchitis virus strain circulating in China with a distinct S gene

text: An avian infectious bronchitis virus (IBV) was isolated and identified from a commercial layer flock vaccinated with live attenuated H120 vaccine in China, designed as ck/CH/IBTZ/2012. To determine the origination and evolution of this isolated strain, we have carried out a complete genome sequencing of this strain. The genome of the ck/CH/IBTZ/2012 strain is 27,691 nucleotides in length and includes more than 10 open reading frames. Sequence comparison and phylogenetic analysis based on the full-length genomic sequences showed that ck/CH/IBTZ/2012 is mostly related to the LX4-like strains. However, sequence analysis based on the spike protein (S) gene sequences revealed that ck/CH/IBTZ/2012 possesses a distinct S gene setting it apart from the Massachusetts-type strains and LX4-type strains. The cleavage site within the spike protein (S) of ck/CH/IBTZ/2012 is HRRKR, which is different from the majority of the IBVs in China for their cleavage sits are HRRRR. Recombination analysis showed that ck/CH/IBTZ/2012 is a chimeric virus with a LX4-like backbone except S gene which might be from an unknown strain. Based on the data presented in this paper, it can be concluded that genetic changes due to adaptive evolution and recombination both contributed to the origin of strain ck/CH/IBTZ/2012, which belongs to a new genotype. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11262-014-1063-y) contains supplementary material, which is available to authorized users.


title: Chapter 17 Meat Safety—I Foodborne Pathogens and Other Biological Issues

text: Abstract This chapter presents information pertinent to foodborne pathogens (bacteria and bacterial toxins, viruses, parasites) and other biological issues (prions) with importance to the safety of meat and meat products. Aspects covered refer mainly to the characteristics of the most important pathogenic organisms, their distribution in the environment, their transmission routes to humans, as well as their epidemiology and association with sporadic or epidemic foodborne illness. Current and emerging challenges to meat safety management also are discussed.


title: Effectiveness of national cervical cancer screening programme in Taiwan: 12-year experiences

text: BACKGROUND: We examined cervical cancer incidence before and after nationwide cervical cancer screening was initiated in Taiwan in mid-1995. RESULTS: The invasive cancer incidence decreased by 47.8% during 1995–2006. The carcinoma in situ incidence increased 1.7-fold during 1995–2000, and decreased by 19.6% during 2000–2006. CONCLUSION: The Taiwan national programme has significantly decreased invasive cervical cancer.


title: Respiratory disease associated with migrating Ascaris larvae in a beef calf

text: Abstract A group of 4-month-old beef calves were examined for clinical respiratory disease with labored breathing, coughing, and fevers of over 104°F. Necropsy of one of the calves revealed lungs that were not collapsed but had red mottled appearance on cut surface. Assessment of lung tissue by bacterial culture and PCR did not reveal bovine bacterial or viral respiratory pathogens. Histopathology of affected tissues and lymph nodes revealed larval ascarid nematodes. In combination with phylogenetic analysis, amplification and sequencing of ITS1 was used to identify the larvae as Ascaris.


title: Prevalence of human metapneumovirus among hospitalized children younger than 1 year in Catalonia, Spain

text: Human metapneumovirus was discovered recently respiratory virus implicated in both upper and lower respiratory tract infection. In children, the clinical symptoms of human metapneumovirus are similar to those produced by respiratory syncytial virus, ranging from mild to severe diseases such as bronchiolitis and pneumonia. The aim of the present study was to describe the prevalence of human metapneumovirus and other common respiratory viruses among admitted to hospital infants. From January 2006 to June 2006, 99 nasopharyngeal aspirates were collected from hospitalized children younger than 12 months in order to study respiratory viruses. Human metapneumovirus detection was performed by cell culture and two RT‐PCR targeting on polymerase and fusion genes. The latter gene was used for phylogenetic analysis. In 67/99 children (67%) at least one viral pathogen was identified, the viruses detected most frequently were respiratory syncytial virus (35%), human metapneumovirus (25%) and rhinovirus (19%). The results obtained in this study, show that: (1) human metapneumovirus is one of the most important viruses among children less than 12 months; (2) children infected with human metapneumovirus were significantly older than those infected by respiratory syncytial virus; (3) human metapneumovirus was associated more frequently with pneumonia whereas respiratory syncytial virus was only detected in patients with bronchiolitis; (4) there was a clear epidemiological succession pattern with only a small overlap among the viruses detected most frequently; (5) all human metapneumovirus samples were clustered within sublineage A2. J. Med. Virol. 80:1452–1460, 2008. © 2008 Wiley‐Liss, Inc.


title: Care of immunocompromised patients with head and neck cancer during the COVID‐19 pandemic: Two challenging and informative clinical cases

text: BACKGROUND AND METHODS: There is an added level of complexity in the management of head and neck cancer patients with underlying immunosuppressive disorders during the COVID‐19 pandemic. Head and neck oncologists are tasked with balancing the dual risks of cancer progression in the setting of impaired tumor immunity and increased susceptibility to life‐threatening complications from exposure to viral infection for patients and providers. Through two cases of immunocompromised patients with newly diagnosed head and neck malignancies, we aim to provide guidance to clinicians struggling with how to best counsel and manage this unique subset of patients under these difficult circumstances. RESULTS: After careful consideration of the options, we took different approaches in the care of these two patients. CONCLUSIONS: Ultimately, there is no uniform set of rules to apply to this heterogeneous group of immunocompromised patients. We provide some general principles to help guide patient management during the current pandemic.


title: PCR–Electrospray Ionization Mass Spectrometry The Potential to Change Infectious Disease Diagnostics in Clinical and Public Health Laboratories

text: During the past 20 years, microbial detection methods that are genetically based, such as real-time PCR and peptide nucleic acid fluorescent hybridization, coexisted with traditional microbiological methods and were typically based on the identification of individual genetic targets. For these methods to be successful, a potential cause of infection must be suspected. More recently, multiplex PCR and multiplex RT-PCR were used to enable more broad-range testing based on panels of suspected pathogens. PCR–electrospray ionization mass spectrometry (PCR-ESI/MS) has emerged as a technology that is capable of identifying nearly all known human pathogens either from microbial isolates or directly from clinical specimens. Assay primers are strategically designed to target one or more of the broad pathogen categories: bacterial, mycobacterial, fungal, or viral. With broad-range amplification followed by detection of mixed amplicons, the method can identify genetic evidence of known and unknown pathogens. This unique approach supports a higher form of inquiry, asking the following question: What is the genetic evidence of known or unknown pathogens in the patient sample? This approach has advantages over traditional assays that commonly target the presence or absence of one or more pathogens with known genetic composition. This review considers the breadth of the published literature and explores the possibilities, advantages, and limitations for implementation of PCR-ESI/MS in diagnostic laboratories.


title: Viral Infection in Adults with Severe Acute Respiratory Infection in Colombia

text: OBJECTIVES: To identify the viral aetiology in adult patients with severe acute respiratory infection (SARI) admitted to sentinel surveillance institutions in Bogotá in 2012. DESIGN: A cross-sectional study was conducted in which microarray molecular techniques for viral identification were used on nasopharyngeal samples of adult patients submitted to the surveillance system, and further descriptions of clinical features and relevant clinical outcomes, such as mortality, need for critical care, use of mechanical ventilation and hospital stay, were obtained. SETTING: Respiratory infections requiring hospital admission in surveillance centres in Bogotá, Colombia. PARTICIPANTS: Ninety-one adult patients with acute respiratory infection (55% were female). MEASUREMENTS: Viral identification, intensive care unit admission, hospital stay, and mortality. RESULTS: Viral identification was achieved for 63 patients (69.2%). Comorbidity was frequently identified and mainly involved chronic pulmonary disease or pregnancy. Influenza, Bocavirus and Adenovirus were identified in 30.8%, 28.6% and 18.7% of the cases, respectively. Admission to the intensive care unit occurred in 42.9% of the cases, while mechanical ventilation was required for 36.3%. The average hospital stay was 9.9 days, and mortality was 15.4%. Antibiotics were empirically used in 90.1% of patients. CONCLUSIONS: The prevalence of viral aetiology of SARI in this study was high, with adverse clinical outcomes, intensive care requirements and high mortality.


title: Echinacea purpurea for Prevention of Experimental Rhinovirus Colds

text: A randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the ability of Echinacea purpurea to prevent infection with rhinovirus type 39 (RV-39). Forty-eight previously healthy adults received echinacea or placebo, 2.5 mL 3 times per day, for 7 days before and 7 days after intranasal inoculation with RV-39. Symptoms were assessed to evaluate clinical illness. Viral culture and serologic studies were performed to evaluate the presence of rhinovirus infection. A total of 92% of echinacea recipients and 95% of placebo recipients were infected. Colds developed in 58% of echinacea recipients and 82% of placebo recipients (P = .114, by Fisher's exact test). Administration of echinacea before and after exposure to rhinovirus did not decrease the rate of infection; however, because of the small sample size, statistical hypothesis testing had relatively poor power to detect statistically significant differences in the frequency and severity of illness.


title: Frequency of Acute Respiratory Illnesses and Circulation of Respiratory Viruses in Households With Children Over 3 Surveillance Seasons

text: Background. The household has traditionally been the site for studying acute respiratory illnesses (ARIs). Most studies were conducted many years ago, and more broadly sensitive laboratory methods to determine ARI etiology are now available. Methods. We recruited and followed households with children over 3 annual surveillance periods and collected respiratory tract specimens from subjects with reported ARI. Virus etiology was determined by real-time reverse-transcription polymerase chain reaction (RT-PCR) analysis. Results. Individuals in larger households (defined as households with >4 members) and those in households with children aged <5 years had significantly higher ARI frequencies than others. ARI frequency generally declined with increasing age. Virus etiology was most likely to be determined in young children, who were also most likely to have virus coinfection. Overall, 16% of ARIs with 1 virus identified had ≥1 coinfecting virus. Rhinoviruses and coronaviruses were the most frequently identified agents of ARI in all age categories. Influenza virus and adenovirus were less frequently identified but were most likely to cause ARI that required medical attention. Conclusions. Longitudinal studies in families remain a valuable way to study respiratory infections. RT-PCR has increased the sensitivity of virus detection, including coinfecting viruses, and expanded our ability to detect viruses now known to cause ARI.


title: Structure of the sirtuin‐linked macrodomain SAV0325 from Staphylococcus aureus

text: Cells use the post‐translational modification ADP‐ribosylation to control a host of biological activities. In some pathogenic bacteria, an operon‐encoded mono‐ADP‐ribosylation cycle mediates response to host‐induced oxidative stress. In this system, reversible mono ADP‐ribosylation of a lipoylated target protein represses oxidative stress response. An NAD(+)‐dependent sirtuin catalyzes the single ADP‐ribose (ADPr) addition, while a linked macrodomain‐containing protein removes the ADPr. Here we report the crystal structure of the sitruin‐linked macrodomain protein from Staphylococcus aureus, SauMacro (also known as SAV0325) to 1.75‐Å resolution. The monomeric SauMacro bears a previously unidentified Zn(2+)‐binding site that putatively aids in substrate recognition and catalysis. An amino‐terminal three‐helix bundle motif unique to this class of macrodomain proteins provides a structural scaffold for the Zn(2+) site. Structural features of the enzyme further indicate a cleft proximal to the Zn(2+) binding site appears well suited for ADPr binding, while a deep hydrophobic channel in the protein core is suitable for binding the lipoate of the lipoylated protein target.


title: An Italian sacrifice to COVID-19 epidemic

text: The report of Italian doctors dead during the COVID-19 outbreak should inform us not to forget


title: Emerging Infections and Pregnancy: West Nile Virus, Monkeypox, Severe Acute Respiratory Syndrome, and Bioterrorism

text: As new infectious diseases, such as West Nile virus, monkeypox, and severe acute respiratory syndrome (SARS) are recognized in the United States, there are critical questions about how these infectious diseases will affect pregnant women and their infants. In addition, the implications of bioterrorist attacks for exposed pregnant women need to be considered. In this article, the authors address the following questions for a number of infectious disease threats: (1) does pregnancy affect the clinical course of these novel infectious diseases?, (2) what are the implications for prophylaxis and treatment of exposed or infected pregnant women?, and (3) are these novel infectious diseases transmitted during pregnancy, labor and delivery, or breastfeeding?


Interpretations of “Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7)”


The Precautions Required for the Safe Return of Elective Surgery - A Letter to the Editor in Response to “Impact of the coronavirus (COVID-19) pandemic on surgical practice - Part 2 (surgical prioritisation)”


title: Exploring the new horizons of drug repurposing: A vital tool for turning hard work into smart work

text: Abstract Drug discovery and development are long and financially taxing processes. On an average it takes 12–15 years and costs 1.2 billion USD for successful drug discovery and approval for clinical use. Many lead molecules are not developed further and their potential is not tapped to the fullest due to lack of resources or time constraints. In order for a drug to be approved by FDA for clinical use, it must have excellent therapeutic potential in the desired area of target with minimal toxicities as supported by both pre-clinical and clinical studies. The targeted clinical evaluations fail to explore other potential therapeutic applications of the candidate drug. Drug repurposing or repositioning is a fast and relatively cheap alternative to the lengthy and expensive de novo drug discovery and development. Drug repositioning utilizes the already available clinical trials data for toxicity and adverse effects, at the same time explores the drug's therapeutic potential for a different disease. This review addresses recent developments and future scope of drug repositioning strategy.


title: The cholinergic anti-inflammatory pathway alleviates acute lung injury

text: The ubiquiotous nuclear protein HMGB1 is extracellularly released by dying cells or activated innate immunity cells to promote inflammation. Extracellular HMGB1 plays a prominent role in the pathogenesis of acute lung injury of infectious as well as sterile origin including hyperoxia. Excessive amounts of systemic HMGB1 and HMGB1-partner molecule complexes can be retained in the pulmonary circulation indicated by a substantial reduction of HMGB1 plasma levels in arterial versus venous blood. The cholinergic antiinflammatory mechanism ameliorates pulmonary inflammation by inhibiting HMGB1 release and HMGB1 receptor expression. This comprehension was recently reinforced by results reported in Molecular Medicine by Sitapara and coworkers demonstrating that administration of an α7 nicotinic acetylcholine receptor agonist attenuated hyperoxia-induced acute inflammatory lung injury by alleviating the accumulation of HMGB1 in the airways and the circulation. Activating the cholinergic antiinflammatory path might be considered to alleviate severe COVID-19 with or without concurrent oxygen-induced lung injury.


Das neue dual-use-Dilemma der modernen Biomedizin


title: Newly emerged porcine enteric alphacoronavirus in southern China: Identification, origin and evolutionary history analysis

text: Abstract Coronaviruses have a wide host range and can cause a variety of diseases with varying severity in different animals. Several enteric coronaviruses have been identified that are associated with diarrhea in swine and that have caused substantial economic losses. In this study, a newly emerged porcine enteric alphacoronavirus (PEAV), PEAV-GD-CH/2017, was identified from suckling piglets with diarrhea in southern China, and a full-length genome sequence of PEAV was obtained for systematic analysis. The novel PEAV sequence was most identical to that of bat-HKU2, and the differences between them were comprehensively compared, especially the uniform features of the S protein, which was shown to have a close relationship with betacoronaviruses and to perhaps represent unrecognized betacoronaviruses. In addition, Bayesian analysis was conducted to address the origin of PEAV, and the divergence time between PEAV and bat-HKU2 was estimated at 1926, which indicates that PEAV is not newly emerged and may have circulated in swine herds for several decades since the interspecies transmission of this coronavirus from bat to swine. The evolutionary rate of coronaviruses was estimated to be 1.93 × 10−4 substitutions per site per year for the RdRp gene in our analysis. For the origin of PEAV, we suspect that it is the result of the interspecies transmission of bat-HKU2 from bat to swine. Our results provide valuable information about the uniform features, origin and evolution of the novel PEAV, which will facilitate further investigations of this newly emerged pathogen.


title: Recombinant Tula hantavirus shows reduced fitness but is able to survive in the presence of a parental virus: analysis of consecutive passages in a cell culture

text: Tula hantavirus carrying recombinant S RNA segment (recTULV) grew in a cell culture to the same titers as the original cell adapted variant but presented no real match to the parental virus. Our data showed that the lower competitiveness of recTULV could not be increased by pre-passaging in the cell culture. Nevertheless, the recombinant virus was able to survive in the presence of the parental virus during five consecutive passages. The observed survival time seems to be sufficient for transmission of newly formed recombinant hantaviruses in nature.


title: Optimized microbial DNA extraction from diarrheic stools

text: BACKGROUND: The detection of enteropathogens in stool specimens increasingly relies on the detection of specific nucleic acid sequences. We observed that such detection was hampered in diarrheic stool specimens and we set-up an improved protocol combining lyophilization of stools prior to a semi-automated DNA extraction. FINDINGS: A total of 41 human diarrheic stool specimens comprising of 35 specimens negative for enteropathogens and six specimens positive for Salmonella enterica in culture, were prospectively studied. One 1-mL aliquot of each specimen was lyophilised and total DNA was extracted from lyophilised and non-lyophilised aliquots by combining automatic and phenol-chloroform DNA extraction. DNA was incorporated into real-time PCRs targeting the 16S rRNA gene of Bacteria and the archaea Methanobrevibacter smithii and the chorismate synthase gene of S. enterica. Whereas negative controls consisting in DNA-free water remained negative, M. smithii was detected in 26/41 (63.4%) non-lyophilised (Ct value 28.78 ± 9.1) versus 39/41 (95.1%) lyophilised aliquots (Ct value 22.04 ± 5.5); bacterial 16S rRNA was detected in 33/41 (80.5%) non-lyophilised (Ct value 28.11 ± 5.9) versus 40/41 (97.6%) lyophilised aliquots (Ct value 24.94 ± 6.6); and S. enterica was detected in 6/6 (100%) non-lyophilized and lyophilized aliquots (Ct value 26.98 ± 4.55 and 26.16 ± 4.97, respectively). S. enterica was not detected in the 35 remaining diarrheal-stool specimens. The proportion of positive specimens was significantly higher after lyophilization for the detection of M. smithii (p = 0.00043) and Bacteria (p = 0.015). CONCLUSION: Lyophilization of diarrheic stool specimens significantly increases the PCR-based detection of microorganisms. The semi-automated protocol described here could be routinely used for the molecular diagnosis of infectious diarrhea.


title: Porcine reproductive and respiratory syndrome virus (PRRSV) suppresses interferon-β production by interfering with the RIG-I signaling pathway

text: Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) is the cause of an economically important swine disease that has been devastating the swine industry since the late 1980s. Accumulating evidences have revealed that PRRSV infection fails to induce type I interferon (IFN-α/β), which are normally induced rapidly during virus replication in virus-infected cells. However, the potential mechanisms remain largely unclear. In this study, we showed that PRRSV infection activated the signal transduction components of NF-κB and AP-1, but not of interferon regulatory factor 3 (IRF3), an essential IFN-β transcription factor. Furthermore, PRRSV infection significantly blocked synthetic dsRNA-induced IFN-β production and IRF3 nuclear translocation. To better understand the upstream signaling events that suppress IRF3 activation, we further investigated the roles of individual components of the retinoic acid-inducible gene I (RIG-I)- and Toll-like receptor 3 (TLR3)-mediated signaling pathway for IFN-β production during PRRSV infection. We observed that PRRSV infection significantly inhibited dsRNA-induced IRF3 activation and IFN-β generation by inactivating IFN-β promoter stimulator 1 (IPS-1), an adaptor molecule of RIG-I. In contrast, PRRSV infection only partially reduced the activation of TIR domain-containing adaptor inducing IFN-β (TRIF), an adaptor molecule of TLR3. Our results suggest that PRRSV infection suppresses production of IFN-β primarily by interfering with the IPS-1 activation in the RIG-I signaling pathway.


title: Viruses detected by systematic multiplex polymerase chain reaction in adults with suspected community-acquired pneumonia attending emergency departments in France

text: Abstract Infectious agents associated with community-acquired pneumonia (CAP) are under-studied. This study attempted to identify viruses from the upper respiratory tract in adults visiting emergency departments for clinically suspected CAP. Adults with suspected CAP enrolled in the ESCAPED study (impact of computed tomography on CAP diagnosis) had prospective nasopharyngeal (NP) samples studied by multiplex PCR (targeting 15 viruses and four intracellular bacteria). An adjudication committee composed of infectious disease specialists, pneumologists and radiologists blinded to PCR results reviewed patient records, including computed tomography and day 28 follow up, to categorize final diagnostic probability of CAP as definite, probable, possible, or excluded. Among the 254 patients enrolled, 78 (31%) had positive PCR, which detected viruses in 72/254 (28%) and intracellular bacteria in 8 (3%) patients. PCR was positive in 44/125 (35%) patients with definite CAP and 21/83 (25%) patients with excluded CAP. The most frequent organisms were influenza A/B virus in 27 (11%), rhinovirus in 20 (8%), coronavirus in seven (3%), respiratory syncytial virus in seven (3%) and Mycoplasma pneumoniae in eight (3%) of 254 patients. Proportion of rhinovirus was higher in patients with excluded CAP compared with other diagnostic categories (p = 0.01). No such difference was observed for influenza virus. Viruses seem common in adults attending emergency departments with suspected CAP. A concomitant clinical, radiological and biological analysis of the patient's chart can contribute to either confirm their role, or suggest upper respiratory tract infection or shedding. Their imputability and impact in early management of CAP deserve further studies. Clinical Trials Registration. NCT01574066.


title: Infection risks following accidental exposure to blood or body fluids in health care workers: A review of pathogens transmitted in published cases

text: Hospital staff and all other human or veterinary health care workers, including laboratory, research, emergency service, or cleaning personnel are exposed to the risk of occupational infection following accidental exposure to blood or body fluids (BBF) contaminated with a virus, a bacteria, a parasite, or a yeast. The human immunodeficiency virus (HIV) or those of hepatitis B (HBV) or C (HCV) account for most of this risk in France and worldwide. Many other pathogens, however, have been responsible for occupational infections in health care workers following exposure to BBF, some with unfavorable prognosis. In developed countries, a growing number of workers are referred to clinicians responsible for the evaluation of occupational infection risks following accidental exposure. Although their principal task remains the evaluation of the risks of HIV, HBV, or HCV transmission and the possible usefulness of postexposure prophylaxis, these experts are also responsible for evaluating risks of occupational infection with other emergent or more rare pathogens and their possible timely prevention. The determinants of the risks of infection and the characteristics of described cases are discussed in this article.


title: Genetic Diversity of Spike, 3a, 3b and E Genes of Infectious Bronchitis Viruses and Emergence of New Recombinants in Korea

text: The nucleotide sequences of a region including S1, S2, 3a, 3b and E genes of twenty-seven infectious bronchitis virus (IBV) isolates in Korea between 1990–2011 were determined and phylogenetic and computational recombination analyses were conducted. The sizes of coding regions of some genes varied among IBV isolates due to deletion or insertion of nucleotides; the nucleotide similarities of S1, S2, 3a, 3b and E genes among the 27 isolates were 75.9%–100.0%, 85%–100.0%, 64.0%–100.0%, 60.4%–100.0% and 83.1%–100.0%, respectively. According to phylogenetic analysis of S1 gene, the 27 isolates were divided into five genotypes, Mass, Korean-I (K-I), QX-like, KM91-like and New cluster 1. The phylogenetic trees based on the S2, 3a, 3b, E genes and S1-S2-3a-3b-E (S1-E) region nucleotide sequences did not closely follow the clustering based on the S1 sequence. The New cluster 1 prevalent during 2009 and 2010 was not found in 2011 but QX-like viruses became prevalent in 2011. The recombination analysis revealed two new S gene recombinants, 11036 and 11052 which might have been derived from recombinations between the New cluster 1 and QX-like viruses and between the K-I and H120 (vaccine) viruses, respectively. In conclusion, multiple IBV genotypes have co-circulated; QX-like viruses have recurred and new recombinants have emerged in Korea. This has enriched molecular epidemiology information of IBV and is useful for the control of IB in Korea.


title: Siglecs at the Host–Pathogen Interface

text: Siglecs are sialic acid (Sia) recognizing immunoglobulin-like receptors expressed on the surface of all the major leukocyte lineages in mammals. Siglecs recognize ubiquitous Sia epitopes on various glycoconjugates in the cell glycocalyx and transduce signals to regulate immunological and inflammatory activities of these cells. The subset known as CD33-related Siglecs is principally inhibitory receptors that suppress leukocyte activation, and recent research has shown that a number of bacterial pathogens use Sia mimicry to engage these Siglecs as an immune evasion strategy. Conversely, Siglec-1 is a macrophage phagocytic receptor that engages GBS and other sialylated bacteria to promote effective phagocytosis and antigen presentation for the adaptive immune response, whereas certain viruses and parasites use Siglec-1 to gain entry to immune cells as a proximal step in the infectious process. Siglecs are positioned in crosstalk with other host innate immune sensing pathways to modulate the immune response to infection in complex ways. This chapter summarizes the current understanding of Siglecs at the host–pathogen interface, a field of study expanding in breadth and medical importance, and which provides potential targets for immune-based anti-infective strategies.


title: Insights into pathogenesis of fatal COVID‐19 pneumonia from histopathology with immunohistochemical and viral RNA studies

text: INTRODUCTION: We describe postmortem pulmonary histopathologic findings of COVID‐19 pneumonia in patients with a spectrum of disease course, from rapid demise to prolonged hospitalization. METHODS: Histopathologic findings in postmortem lung tissue from eight patients who died from COVID‐19 pneumonia were reviewed. Immunohistochemistry (IHC) and next generation sequencing (NGS) were performed to detect virus. RESULTS: Diffuse alveolar damage (DAD) was seen in all cases with a spectrum of acute phase and/or organizing phase. IHC with monoclonal antibodies against SARS‐CoV‐2 viral nucleoprotein and spike protein detected virus in areas of acute but not organizing DAD, with intracellular viral antigen and RNA expression seen predominantly in patients with duration of illness less than 10 days. Major vascular findings included thrombi in medium and large caliber vessels, platelet microthrombi detected by CD61 IHC, and fibrin microthrombi. CONCLUSIONS: Presence of SARS‐CoV‐2 viral RNA by NGS early in the disease course and expression of viral antigen by IHC exclusively in the acute but not in the organizing phase of DAD, suggests that the virus may play a major role in initiating the acute lung injury of DAD, but when DAD progresses to the organizing phase, the virus may have been cleared from the lung by the patient’s immune response. These findings suggest the possibility of a major change during the disease course of COVID‐19 pneumonia that may have therapeutic implications. Frequent thrombi and microthrombi may also present potential targets for therapeutic intervention.


title: Differences in SARS-CoV-2 recommendations from major ophthalmology societies worldwide

text: OBJECTIVE: Since the WHO declared the COVID-19 outbreak as a public health emergency, medical societies around the world published COVID-19 recommendations to physicians to ensure patient care and physician safety. During this pandemic, ophthalmologists around the world adapted their clinical and surgical practice following such guidelines. This original research examines all publicly available COVID-19 recommendations from twelve major ophthalmology societies around the world. METHODS AND ANALYSIS: Twelve ophthalmology societies recognised by the International Council of Ophthalmology were included in this study. One society per each WHO region was included: the society selected was the one who had the highest number of national COVID-19 confirmed cases on 11 May 2020. In addition to these countries, the major ophthalmology society in each G7 country was included. RESULTS: Ten out of 12 major international ophthalmology societies from countries covering all six WHO regions have given recommendations regarding urgent patient care, social distancing, telemedicine and personal protective equipment when caring for ophthalmic patients during the COVID-19 pandemic. While all guidelines emphasise the importance of postponing non-urgent care and taking necessary safety measures, specific recommendations differ between countries. CONCLUSIONS: As there is no clear consensus on ophthalmology guidelines across countries, this paper highlights the differences in international ophthalmic care recommendations during the COVID-19 pandemic. Knowledge of the differences in ophthalmic management plans will allow ophthalmologists and all eye care providers to consider the variety of international approaches and apply best practices following evidence-based recommendations during pandemics.


title: Self-disinfecting surfaces and infection control

text: Abstract According to World Health Organization, every year in the European Union, 4 million patients acquire a healthcare associated infection. Even though some microorganisms represent no threat to healthy people, hospitals harbor different levels of immunocompetent individuals, namely patients receiving immunosuppressors, with previous infections, or those with extremes of age (young children and elderly), requiring the implementation of effective control measures. Public spaces have also been found an important source of infectious disease outbreaks due to poor or none infection control measures applied. In both places, surfaces play a major role on microorganisms’ propagation, yet they are very often neglected, with very few guidelines about efficient cleaning measures and microbiological assessment available. To overcome surface contamination problems, new strategies are being designed to limit the microorganisms’ ability to survive over surfaces and materials. Surface modification and/or functionalization to prevent contamination is a hot-topic of research and several different approaches have been developed lately. Surfaces with anti-adhesive properties, with incorporated antimicrobial substances or modified with biological active metals are some of the strategies recently proposed. This review intends to summarize the problems associated with contaminated surfaces and their importance on infection spreading, and to present some of the strategies developed to prevent this public health problem, namely some already being commercialized.


title: Experimental feline enteric coronavirus infection reveals an aberrant infection pattern and shedding of mutants with impaired infectivity in enterocyte cultures

text: Feline infectious peritonitis (FIP) results from mutations in the viral genome during a common feline enteric coronavirus (FECV) infection. Since many virological and immunological data on FECV infections are lacking, the present study investigated these missing links during experimental infection of three SPF cats with FECV strain UCD. Two cats showed mild clinical signs, faecal shedding of infectious virus from 4 dpi, a cell-associated viraemia at inconsistent time points from 5 dpi, a highly neutralising antibody response from 9 dpi, and no major abnormalities in leukocyte numbers. Faecal shedding lasted for 28–56 days, but virus shed during this stage was less infectious in enterocyte cultures and affected by mutations. Remarkably, in the other cat neither clinical signs nor acute shedding were seen, but virus was detected in blood cells from 3 dpi, and shedding of non-enterotropic, mutated viruses suddenly occurred from 14 dpi onwards. Neutralising antibodies arose from 21 dpi. Leukocyte numbers were not different compared to the other cats, except for the CD8(+) regulatory T cells. These data indicate that FECV can infect immune cells even in the absence of intestinal replication and raise the hypothesis that the gradual adaptation to these cells can allow non-enterotropic mutants to arise.


title: Guild-level responses of bats to habitat conversion in a lowland Amazonian rainforest: species composition and biodiversity

text: Landscape modification represents one of the most severe threats to biodiversity from local to global scales. Conversion of forest to agricultural production generally results in patches of habitat that subdivide or isolate populations, alter the behavior of species, modify interspecific interactions, reduce biodiversity, and compromise ecosystem processes. Moreover, conversion may increase exposure of humans to zoonoses to which they would otherwise rarely be exposed. We evaluated the effects of forest conversion to agriculture, and its subsequent successional dynamics, on bat communities in a region of the Amazon that was predominantly closed-canopy rainforest. Based on a nonmanipulative experiment, we quantified differences in species composition, community structure, and taxonomic biodiversity among closed-canopy forest (bosque), agricultural lands (chacra), and secondary forest (purma) for two phyllostomid guilds (frugivores and gleaning animalivores) during the wet and dry seasons. Responses were complex and guild-specific. For frugivores, species composition (species abundance distributions) differed between all possible pairs of habitats in both wet and dry seasons. For gleaning animalivores, species composition differed between all possible pairs of habitats in the dry season, but no differences characterized the wet season. Ecological structure (rank abundance distributions) differed among habitats in guild-specific and season-specific manners. For frugivores, mean diversity, evenness, and dominance were greater in bosque than in purma; mean dominance was greater in bosque than in chacra, but local rarity was greater in chacra than in bosque, and no differences were manifest between purma and chacra. For gleaning animalivores, mean diversity and evenness were greater in bosque than in purma, but no differences were manifest between chacra and bosque, or between purma and chacra. Such results have important implications for management, conservation, and the epidemiology of zoonotic diseases. La actual modificación del paisaje, a escalas que van de lo local a lo global, es una de las amenazas más severas a la biodiversidad. De manera general, la conversión de bosques a áreas agrícolas produce parches de hábitat que subdividen o aíslan poblaciones, alteran la conducta de las especies, modifican las interacciones interespecíficas, reducen la biodiversidad y comprometen las funciones de los ecosistemas. Más aún, la transformación de estos ambientes puede incrementar la probabilidad de que las poblaciones humanas interactúen con zoonosis con las que de otra manera raramente entrarían en contacto. Evaluamos los efectos de la conversión de hábitat en comunidades de murciélagos en una región de Amazonia en la que la vegetación dominante es un bosque lluvioso de copas cerradas, y en la cual los efectos de la conversión a usos agrícolas sobre la biodiversidad, y la subsecuente dinámica sucesional, son aún poco comprendidos. Por medio de un experimento no-manipulativo, cuantificamos las diferencias en composición de especies, estructura de la comunidad y diversidad taxonómica entre bosque cerrado (bosque), áreas agrícolas (chacra) y bosque secundario (purma) para dos gremios tróficos de murciélagos filostómidos (frugívoros y forrajeadores de sustrato) durante dos temporadas (secas y lluvias). Las respuestas fueron complejas y diferentes para cada gremio. Para los frugívoros, la composición de especies (distribución de las abundancias) fue diferente para todos los posibles pares de hábitats tanto para secas como para lluvias. Para los forrajeadores de sustrato, la composición de especies difirió entre todos los posibles pares de hábitats en la temporada seca, pero no en la de lluvias. La estructura ecológica (distribuciones rango-abundancia) fue también específica para gremios y temporadas. Para los frugívoros, la diversidad promedio, equidad y dominancia fueron mayores en bosque que en purma; la dominancia promedio fue mayor en bosque que en chacra, pero la rareza local fue mayor en chacra que en bosque, y no se encontraron diferencias entre purma y chacra. Para los forrajeadores de sustrato, la diversidad promedio y la dominancia fueron mayores en bosque que en purma, pero no se detectaron diferencias entre chacra y bosque, o entre purma y chacra. Estos resultados tienen importantes implicaciones para el manejo, conservación y epidemiología de zoonosis.


Out of the East – Emerging infections


title: Machine learning using intrinsic genomic signatures for rapid classification of novel pathogens: COVID-19 case study

text: As of February 20, 2020, the 2019 novel coronavirus (renamed to COVID-19) spread to 30 countries with 2130 deaths and more than 75500 confirmed cases. COVID-19 is being compared to the infamous SARS coronavirus, which resulted, between November 2002 and July 2003, in 8098 confirmed cases worldwide with a 9.6% death rate and 774 deaths. Though COVID-19 has a death rate of 2.8% as of 20 February, the 75752 confirmed cases in a few weeks (December 8, 2019 to February 20, 2020) are alarming, with cases likely being under-reported given the comparatively longer incubation period. Such outbreaks demand elucidation of taxonomic classification and origin of the virus genomic sequence, for strategic planning, containment, and treatment. This paper identifies an intrinsic COVID-19 genomic signature and uses it together with a machine learning-based alignment-free approach for an ultra-fast, scalable, and highly accurate classification of whole COVID-19 genomes. The proposed method combines supervised machine learning with digital signal processing for genome analyses, augmented by a decision tree approach to the machine learning component, and a Spearman’s rank correlation coefficient analysis for result validation. These tools are used to analyze a large dataset of over 5000 unique viral genomic sequences, totalling 61.8 million bp. Our results support a hypothesis of a bat origin and classify COVID-19 as Sarbecovirus, within Betacoronavirus. Our method achieves high levels of classification accuracy and discovers the most relevant relationships among over 5,000 viral genomes within a few minutes, ab initio, using raw DNA sequence data alone, and without any specialized biological knowledge, training, gene or genome annotations. This suggests that, for novel viral and pathogen genome sequences, this alignment-free whole-genome machine-learning approach can provide a reliable real-time option for taxonomic classification.


title: Aetiological Significance of Infectious Stimuli in Kawasaki Disease

text: Kawasaki disease (KD) is a pediatric vasculitis syndrome that is often involves coronary artery lesions (e. g., coronary artery aneurysms). Although its causal factors and entire pathogenesis remain elusive, the available evidence indicates that the pathogenesis of KD is closely associated with dysregulation of immune responses to various viruses or microbes. In this short review, we address several essential aspects of the etiology of KD with respect to the immune response to infectious stimuli: 1) the role of viral infections, 2) the role of bacterial infections and the superantigen hypothesis, 3) involvement of innate immune response including pathogens/microbe-associated molecular patterns and complement pathways, and 4) the influence of genetic background on the response to infectious stimuli. Based on the clinical and experimental evidence, we discuss the possibility that a wide range of microbes and viruses could cause KD through common and distinct immune processes.


Impact of Coronavirus Disease 2019 (COVID-19) Outbreak on ST-Segment–Elevation Myocardial Infarction Care in Hong Kong, China


title: Generation of a mouse scFv library specific for porcine aminopeptidase N using the T7 phage display system

text: Abstract Porcine aminopeptidase N (pAPN) is a common cellular receptor for swine transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PEDV). To investigate single-chain fragment variable (scFv) repertoire against pAPN, the genes encoding the immunoglobulin light chain variable region (VL) and heavy chain variable region (VH) were amplified by reverse transcript polymerase chain reaction (RT-PCR) using a series of degenerate primers from the spleen of BABL/c mice immunized with native pAPN. The VL and VH amplicons were combined randomly by a 12 amino acid flexible linker by splicing by overlap extension PCR (SOE-PCR), which produced the scFv gene repertoire. After ligation of the scFv gene repertoire into the T7Select10-3b vector, a mouse scFv phage library specific for pAPN was produced through in vitro packaging. The primary scFv library against pAPN contained 2.0×107 recombinant phage clones, and the titer of the amplified library was 3.6×109 pfu/mL. BstNI restriction analysis and DNA sequencing revealed that 28 phage clones from the primary pAPN scFv library showed excellent diversity. The effectiveness of the scFv library against pAPN was verified further by phage ELISA using the recombinant protein of the pAPN C subunit as coating antigen. The construction and evaluation of a murine scFv library against the common receptor pAPN of porcine coronaviruses TGEV and PEDV using the T7 phage display system are described.


title: The ethical challenges of the SARS‐CoV‐2 pandemic in the global south and the global north – same and different

text: The global COVID‐19 death toll stands at the time of writing at 163,500. By the time you read this, that number will have increased significantly, and it is likely that we won’t have seen the end of it by that time. Policy makers in both the global north as well as the global south rose to the challenge, with decidedly mixed responses as well as decidedly mixed results, as comparisons between reported case loads of, say the UK and Germany or between Brazil and the PR of China, show. Discipline specific responses translated into many global collaborative efforts aimed at developing treatments, modelling of the impact of varying policy options on the continuing pandemic, preventive vaccine trials, and so on and so forth.


Unprecedented Solutions for Extraordinary Times: Helping Long-Term Care Settings Deal with the COVID-19 Pandemic


Transient IgA, steady IgG?


title: A Chain Multinomial Model for Estimating the Real-Time Fatality Rate of a Disease, with an Application to Severe Acute Respiratory Syndrome

text: It is well known that statistics using cumulative data are insensitive to changes. World Health Organization (WHO) estimates of fatality rates are of the above type, which may not be able to reflect the latest changes in fatality due to treatment or government policy in a timely fashion. Here, the authors propose an estimate of a real-time fatality rate based on a chain multinomial model with a kernel function. It is more accurate than the WHO estimate in describing fatality, especially earlier in the course of an epidemic. The estimator provides useful information for public health policy makers for understanding the severity of the disease or evaluating the effects of treatments or policies within a shorter time period, which is critical in disease control during an outbreak. Simulation results showed that the performance of the proposed estimator is superior to that of the WHO estimator in terms of its sensitivity to changes and its timeliness in reflecting the severity of the disease.


title: The immunoreactivity of a chimeric multi-epitope DNA vaccine against IBV in chickens

text: Abstract Epitope-based vaccines designed to induce cellular immune response and antibody responses specific for infectious bronchitis virus (IBV) are being developed as a means for increasing vaccine potency. In this study, we selected seven epitopes from the spike (S1), spike (S2), and nucleocapsid (N) protein and constructed a multi-epitope DNA vaccine. The 7-day-old chickens were immunized intramuscularly with multi-epitope DNA vaccine encapsulated by liposome and boosted two weeks later, and were challenged by virulent IBV strain five weeks post booster. The results showed that multi-epitope DNA vaccine led to a dramatic augmentation of humoral and cellular responses, and provided up to 80.0% rate of immune protection. The novel immunogenic chimeric multi-epitope DNA vaccine revealed in this study provided a new candidate target for IBV vaccine development.


title: Dengue: what it is and why there is more

text: In 2014, China experienced the worst outbreak of dengue fever in the last decade with over 40,000 dengue cases including six deaths by the end of October. As one of the “neglected” tropical diseases, dengue is affecting substantially increasing number of people and proportion of global population due to factors including globalization, human settlement, and possibly climate change. Here, the authors summarized the most recent data about dengue outbreaks in China and reviewed the global trend of dengue epidemiology. Future directions for dengue surveillance, control and prevention are also introduced.


title: Serodiagnosis of sporotrichosis infection in cats by enzyme-linked immunosorbent assay using a specific antigen, SsCBF, and crude exoantigens

text: Abstract The main objective of this study is to standardize an ELISA for the diagnosis of feline sporotrichosis. Sporothrix schenckii is the etiological agent of human and animal sporotrichosis. Cats may act as reservoirs for S. schenckii and can transmit the infection to humans by a bite or scratch. There are few methods for the serological diagnosis of fungal diseases in animals. In this paper, an ELISA test for the diagnosis of cat sporotrichosis is proposed, which detects S. schenckii-specific antibodies in feline sera. Two different kinds of antigens were used: “SsCBF”, a specific molecule from S. schenckii that consists of a Con A-binding fraction derived from a peptido-rhamnomannan component of the cell wall, and a S. schenckii crude exoantigen preparation. The ELISA was developed, optimized, and evaluated using sera from 30 cats with proven sporotrichosis (by culture isolation); 22 sera from healthy feral cats from a zoonosis center were used as negative controls. SsCBF showed 90% sensitivity and 96% specificity in ELISA; while crude exoantigens demonstrated 96% sensitivity and 98% specificity. The ELISA assay described here would be a valuable screening tool for the detection of specific S. schenckii antibodies in cats with sporotrichosis. The assay is inexpensive, quick to perform, easy to interpret, and permits the diagnosis of feline sporotrichosis.


title: Lactate dehydrogenase levels predict coronavirus disease 2019 (COVID-19) severity and mortality: A pooled analysis

text: Coronavirus disease 2019 (COVID-19) infection has now reached a pandemic state, affecting more than a million patients worldwide. Predictors of disease outcomes in these patients need to be urgently assessed to decrease morbidity and societal burden. Lactate dehydrogenase (LDH) has been associated with worse outcomes in patients with viral infections. In this pooled analysis of 9 published studies (n = 1532 COVID-19 patients), we evaluated the association between elevated LDH levels measured at earliest time point in hospitalization and disease outcomes in patients with COVID-19. Elevated LDH levels were associated with a ~6-fold increase in odds of developing severe disease and a ~16-fold increase in odds of mortality in patients with COVID-19. Larger studies are needed to confirm these findings.


title: Risk Perceptions Related to SARS and Avian Influenza: Theoretical Foundations of Current Empirical Research

text: BACKGROUND: The outbreak of severe acute respiratory syndrome in 2003 and the subsequent emergence of the H5N1 virus have highlighted the threat of a global pandemic influenza outbreak. Planning effective public health control measures for such a case will be highly dependent on sound theory-based research on how people perceive the risks involved in such an event. PURPOSE: The present article aims to review theoretical models and concepts underlying current empirical research on pandemic influenza risk perception. METHOD: A review was conducted based on 28 empirical studies from 30 articles which were published between 2003 and 2007. RESULTS: Concepts of risk perception mostly seemed more pragmatic than theory-based and were highly heterogeneous, for instance, in terms of conceptualizing risk perception as an exclusively cognitive or as a cognitive and emotional phenomenon or whether the concept was dominated by expectancy or expectancy and value components. Similarly, the majority of studies investigating risk perceptions and protective behaviors were not model-based. CONCLUSIONS: The current body of knowledge can only provide preliminary insights. Unlike the reviewed studies, which were mostly launched as a rapid response to outbreak situations, future research will have to invest more strongly into theoretical work to provide sounder evidence.


title: Longitudinally Profiling Neutralizing Antibody Response to SARS Coronavirus with Pseudotypes

text: The severe acute respiratory syndrome–associated coronavirus (SARS-CoV) spike protein (S) is a major target for neutralizing antibodies. Retroviral SARS-CoV S pseudotypes have been constructed and used to develop an in vitro microneutralization assay that is both sensitive and specific for SARS-CoV neutralizing antibodies. Neutralization titers measured by this assay are highly correlated to those measured by an assay using replication-competent SARS-CoV. No cross-neutralization occurred with human sera known to contain antibodies to coronavirus strains OC43 and 229E. The pseudotype assay was used to profile neutralizing antibody responses against SARS-CoV S in sequential serum samples taken from 41 confirmed SARS patients during the 2003 outbreak in Hong Kong and shows long-lasting immunity in most recovered patients. The pseudotype assay does not require handling live SARS virus; it is a useful tool to determine neutralizing titers during natural infection and the preclinical evaluation of candidate vaccines.


Universal basic income and Covid‐19


title: Dynamics of airway microbiota identify a critical window for interplay of pathogenic bacteria and allergic sensitization in childhood respiratory disease

text: Repeated cycles of infection-associated lower airway inflammation drives the pathogenesis of persistent wheezing disease in children. Tracking these events across a birth cohort during their first five years, we demonstrate that >80% of infectious events indeed involve viral pathogens, but are accompanied by a shift in the nasopharyngeal microbiome (NPM) towards dominance by a small range of pathogenic bacterial genera. Unexpectedly, this change in NPM frequently precedes the appearance of viral pathogens and acute symptoms. In non-sensitized children these events are associated only with “transient wheeze” that resolves after age three. In contrast, in children developing early allergic sensitization, they are associated with ensuing development of persistent wheeze, which is the hallmark of the asthma phenotype. This suggests underlying pathogenic interactions between allergic sensitization and anti-bacterial mechanisms.


title: Characterization of novel monoclonal antibodies against the MERS-coronavirus spike protein and their application in species-independent antibody detection by competitive ELISA

text: Abstract Since discovering the Middle East respiratory syndrome coronavirus (MERS-CoV) as a causative agent of severe respiratory illness in the Middle East in 2012, serological testing has been conducted to assess antibody responses in patients and to investigate the zoonotic reservoir of the virus. Although the virus neutralization test is the gold standard assay for MERS diagnosis and for investigating the zoonotic reservoir, it uses live virus and so must be performed in high containment laboratories. Competitive ELISA (cELISA), in which a labeled monoclonal antibody (MAb) competes with test serum antibodies for target epitopes, may be a suitable alternative because it detects antibodies in a species-independent manner. In this study, novel MAbs against the spike protein of MERS-CoV were produced and characterized. One of these MAbs was used to develop a cELISA. The cELISA detected MERS-CoV-specific antibodies in sera from MERS-CoV-infected rats and rabbits immunized with the spike protein of MERS-CoV. The MAb-based cELISA was validated using sera from Ethiopian dromedary camels. Relative to the neutralization test, the cELISA detected MERS-CoV-specific antibodies in 66 Ethiopian dromedary camels with a sensitivity and specificity of 98% and 100%, respectively. The cELISA and neutralization test results correlated well (Pearson’s correlation coefficients=0.71–0.76, depending on the cELISA serum dilution). This cELISA may be useful for MERS epidemiological investigations on MERS-CoV infection.


Control of Middle East respiratory syndrome


title: Discovery of Synergistic and Antagonistic Drug Combinations against SARS-CoV-2 In Vitro

text: COVID-19 is undoubtedly the most impactful viral disease of the current century, afflicting millions worldwide. As yet, there is not an approved vaccine, as well as limited options from existing drugs for treating this disease. We hypothesized that combining drugs with independent mechanisms of action could result in synergy against SARS-CoV-2. Using in silico approaches, we prioritized 73 combinations of 32 drugs with potential activity against SARS-CoV-2 and then tested them in vitro. Overall, we identified 16 synergistic and 8 antagonistic combinations, 4 of which were both synergistic and antagonistic in a dose-dependent manner. Among the 16 synergistic cases, combinations of nitazoxanide with three other compounds (remdesivir, amodiaquine and umifenovir) were the most notable, all exhibiting significant synergy against SARS-CoV-2. The combination of nitazoxanide, an FDA-approved drug, and remdesivir, FDA emergency use authorization for the treatment of COVID-19, demonstrate a strong synergistic interaction. Notably, the combination of remdesivir and hydroxychloroquine demonstrated strong antagonism. Overall, our results emphasize the importance of both drug repurposing and preclinical testing of drug combinations for potential therapeutic use against SARS-CoV-2 infections.


title: Mutations in SARS-CoV-2 viral RNA identified in Eastern India: Possible implications for the ongoing outbreak in India and impact on viral structure and host susceptibility

text: Direct massively parallel sequencing of SARS-CoV-2 genome was undertaken from nasopharyngeal and oropharyngeal swab samples of infected individuals in Eastern India. Seven of the isolates belonged to the A2a clade, while one belonged to the B4 clade. Specific mutations, characteristic of the A2a clade, were also detected, which included the P323L in RNA-dependent RNA polymerase and D614G in the Spike glycoprotein. Further, our data revealed emergence of novel subclones harbouring nonsynonymous mutations, viz. G1124V in Spike (S) protein, R203K, and G204R in the nucleocapsid (N) protein. The N protein mutations reside in the SR-rich region involved in viral capsid formation and the S protein mutation is in the S(2) domain, which is involved in triggering viral fusion with the host cell membrane. Interesting correlation was observed between these mutations and travel or contact history of COVID-19 positive cases. Consequent alterations of miRNA binding and structure were also predicted for these mutations. More importantly, the possible implications of mutation D614G (in S(D) domain) and G1124V (in S(2) subunit) on the structural stability of S protein have also been discussed. Results report for the first time a bird’s eye view on the accumulation of mutations in SARS-CoV-2 genome in Eastern India. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12038-020-00046-1) contains supplementary material, which is available to authorized users.


title: Under the epidemic situation of COVID‐19, should special attention to pregnant women be given?

text: The sudden outbreak and spread of COVID-19 in this spring led to a serious challenge to the global public health system. So far, the number of cases in the mainland of China has exceeded 80,000. In addition to China's neighboring countries like Japan, South Korea, Thailand and India, severe outbreaks have occurred in Italy and many other countries around the world. As dated on 12th Mar., WHO statistics showed that the confirmed cases reported outside China rise to more than 30,000. No epidemiological data on the prevalence and proportion of severe cases in pregnant women has been reported till now. This commentary gives some opinions on the issues that may be faced by three groups of pregnant population, i.e. late pregnancy, early and middle pregnancy and pregnant medical staff. Hoping to provide ideas for the development of relevant research and policy making. This article is protected by copyright. All rights reserved.