title: Factors associated with post-traumatic stress disorder of nurses exposed to corona virus disease 2019 in China

text: Quantitative studies using validated questionnaires on post-traumatic stress disorder (PTSD) of Nurses exposed to corona virus disease 2019 (COVID-19) in China are rare and the baseline PTSD must first be evaluated before prevention. This study aimed to investigate the factors potentially involved in the level of PTSD of Nurses exposed to COVID-19 in China. In this cross-sectional study, male and female Nurses (n = 202) exposed to COVID-19 from HuBei China were included in the final sample. The PTSD Checklist-Civilian (PCL-C) questionnaire and Simplified Coping Style Questionnaire (SCSQ) were used for evaluation. Multivariate stepwise linear regression analysis and spearman correlation test were performed to assess the association between various factors associated with PTSD. The incidence of PTSD in Nurses exposed to COVID-19 was 16.83%, the PCL-C score was 27.00 (21.00–34.00), and the highest score in the three dimensions was avoidance dimension 9.50 (7.00–13.25); multivariable stepwise linear regression analysis showed that job satisfaction and gender were independently associated with lower PCL-C scores (both P < .001); PCL-C scores were correlated with positive coping (r = −0.151, P = .032), negative coping (r = 0.154, P = .029). Nurses exposed to COVID-19 from HuBei China with job satisfaction, male and positive coping had low PCL-C scores which necessitate reducing the PTSD level by ways of improving job satisfaction, positive response, and strengthening the psychological counseling of female nurses in order to reduce the risk of psychological impairment.


title: Chapter 2 Nanostructuring Biopolymers for Improved Food Quality and Safety

text: Abstract Food-grade biopolymers, apart from their inherent nutritional properties, can be tailored designed for improving food quality and safety, either serving as delivery vehicles for bioactive molecules, or as novel packaging components, not only improving the transport properties of biobased packaging structures, but also imparting active antibacterial and antiviral properties. In this chapter, the potential of different food-grade biopolymers (mainly proteins and carbohydrates but also some biopolyesters) to serve as encapsulating matrices for the protection of sensitive bioactives or as nanostructured packaging layers to improve transport properties and control the growth of pathogenic bacteria and viruses are described based on some developments carried out by the authors, as well as the most prominent works found in literature in this area.


title: Contents, Followers, and Retweets of the Centers for Disease Control and Prevention’s Office of Advanced Molecular Detection (@CDC_AMD) Twitter Profile: Cross-Sectional Study

text: BACKGROUND: The Office of Advanced Molecular Detection (OAMD), Centers for Disease Control and Prevention (CDC), manages a Twitter profile (@CDC_AMD). To our knowledge, no prior study has analyzed a CDC Twitter handle’s entire contents and all followers. OBJECTIVE: This study aimed to describe the contents and followers of the Twitter profile @CDC_AMD and to assess if attaching photos or videos to tweets posted by @CDC_AMD would increase retweet frequency. METHODS: Data of @CDC_AMD were retrieved on November 21, 2016. All followers (N=809) were manually categorized. All tweets (N=768) were manually coded for contents and whether photos or videos were attached. Retweet count for each tweet was recorded. Negative binomial regression models were applied to both the original and the retweet corpora. RESULTS: Among the 809 followers, 26.0% (210/809) were individual health professionals, 11.6% (94/809) nongovernmental organizations, 3.3% (27/809) government agencies’ accounts, 3.3% (27/809) accounts of media organizations and journalists, and 0.9% (7/809) academic journals, with 54.9% (444/809) categorized as miscellaneous. A total of 46.9% (360/768) of @CDC_AMD’s tweets referred to the Office’s website and their current research; 17.6% (135/768) referred to their scientists’ publications. Moreover, 80% (69/86) of tweets retweeted by @CDC_AMD fell into the miscellaneous category. In addition, 43.4% (333/768) of the tweets contained photos or videos, whereas the remaining 56.6% (435/768) did not. Attaching photos or videos to original @CDC_AMD tweets increases the number of retweets by 37% (probability ratio=1.37, 95% CI 1.13-1.67, P=.002). Content topics did not explain or modify this association. CONCLUSIONS: This study confirms CDC health communicators’ experience that original tweets created by @CDC_AMD Twitter profile sharing images or videos (or their links) received more retweets. The current policy of attaching images to tweets should be encouraged.


title: Role of Lopinavir/Ritonavir in the Treatment of Covid-19: A Review of Current Evidence, Guideline Recommendations, and Perspectives

text: A life-threatening respiratory illness (COVID-19) due to severe acute respiratory syndrome (SARS)-CoV-2 coronavirus was first described in December 2019 in Wuhan (China), rapidly evolving into a pandemic In the first phase, when the viral replication plays a pivotal pathogenetic role, antiviral drugs could be crucial in limiting viral-induced organ damage Unfortunately, there are no specific antivirals of proven efficacy for COVID-19, and several drugs have been repurposed to face this dramatic pandemic In this paper we review the studies evaluating lopinavir/ritonavir association (LPV/r) use in COVID-19, and previously in SARS and Middle East respiratory syndrome (MERS) We searched PubMed to identify all relevant clinical and laboratory studies published up to 15 May 2020;the guidelines on the use of LPV/r in COVID-19 were further directly searched on the website of the main international scientific societies and agencies Available evidence is currently scarce and of low quality The recommendations issued for COVID-19 vary from positions clearly against the use of LPV/r to other positions that are more favorable In our opinion, despite the controversial results of an important randomized clinical trial, and some recommendations, clinicians should not abandon the use of LPV/r for the treatment of COVID-19, possibly using this drug inside a prospective randomized trial, waiting for the results of the numerous ongoing trials evaluating its efficacy


title: Case Study: Control of bovine respiratory disease in dairy calves with tulathromycin and effect on calf health and performance from 0 to 4 months of age

text: ABSTRACT In phase 1, 96 male Holstein calves at risk for bovine respiratory disease initially 2 to 4 d of age from a single dairy farm were transported 3.5 h to southwest Ohio. Calves were randomly assigned to receive a s.c. injection of Draxxin (2.5 mg of tulathromycin/kg of BW; Zoetis, Florham Park, NJ; TUL) at arrival (d −1) and again at weaning (d 42) or receive no injections (CON). Milk replacer was fed at 0.66 kg of DM daily for 39 d and then 0.33 kg of DM daily for 3 d. A high-grain, textured starter and water were fed free choice for the first 56-d phase. In phase 2, the same calves from phase 1 were grouped by CON and TUL and moved to group pens (4 pens per treatment; 4 calves per pen) for the next 56 d. The same starter from phase 1 was blended with 5% chopped grass hay and fed free choice. In phase 1, postweaning starter intake and BW gain, overall BW gain, and final BW were greater for TUL than CON. Medical treatments did not differ. During phase 2, DMI (% of BW) was greater for CON than TUL. Calf BW gain, final BW, feed efficiency, and hip width change were greater for TUL than CON. Over the 112 d of both phases, TUL calves gained 9.0 kg (9%) more BW (106.4 vs. 97.4 kg) and 0.8 cm (8%) more hip width (10 vs. 9.2 cm) than CON calves, but TUL did not improve calf health.


title: Frequency of routine testing for SARS-CoV-2 to reduce transmission among workers

text: Shelter-in-place policies have been considered effective in mitigating the transmission of the virus SARS-CoV-2. To end such policies, routine testing and self-quarantine of those testing positive for active infection have been proposed, yet it remains unclear how often routine testing would need to be performed among workers returning to workplaces, and how effective this strategy would be to meaningfully prevent continued transmission of the virus. We simulated SARS-CoV-2 polymerase chain reaction testing to estimate the frequency of testing needed to avert continued epidemic propagation as shelter-in-place orders are relaxed. We find that testing strategies less frequent than twice weekly (e.g. weekly testing or testing once prior to returning to work) are unlikely to prevent workforce outbreaks. Even given unlimited testing capacity, the impact of frequent testing may not be sufficient to reliably relax shelter-in-place policies without risking continued epidemic propagation, unless other measures are instituted to complement testing and self-isolation.


title: Isfahan COvid-19 REgistry (I-CORE): Design and methodology

text: Health authorities usually exploit after-action reports to collect data on their experience in responding to public health emergencies. To develop an effective approach to manage and learning from health emergencies, we have launched Isfahan COvid-19 REgistry for data collection during routine clinical care as a first “critical incident registry” in Iran. Registries can be employed to explain the natural history of the disease, learn about a particular disease in terms of patient outcomes, the cost-effectiveness of clinical management, monitoring the quality of health-care service, and developing research hypotheses.


title: New technologies in computer-aided drug design: Toward target identification and new chemical entity discovery

text: In the postgenomic era, computer-aided drug design (CADD) has considerably extended its range of applications, spanning almost all stages in the drug discovery pipeline, from target identification to lead discovery, from lead optimization to preclinical or clinical trials. Two new technologies of CADD associated with target identification and new chemical entity discovery will be the focus of this review. Section editors: Li-he Zhang – School of Pharmaceutical Science, Peking University, Beijing, China Kaixian Chen – Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China


title: SARS-CoV-2 receptor networks in diabetic kidney disease, BK-Virus nephropathy and COVID-19 associated acute kidney injury

text: COVID-19 morbidity and mortality is significantly increased in patients with diabetes and kidney disease via unknown mechanisms. SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) for entry into human host cells, and ACE2 levels in target cells may influence SARS-CoV-2 susceptibility. We investigated how pre-existing conditions and drug treatments alter receptor expression in kidney tissue. Using single cell RNA profiling (scRNAseq) to assess ACE2 and associated SARS-CoV-2 proteases in healthy living donors (LD) kidneys, diabetic kidney disease (DKD), and in kidney injury during viral infection, ACE2 expression was primarily associated with proximal tubular epithelial cells (PTEC). ACE2 mRNA expression levels were significantly upregulated in DKD versus LD, however, ACE2 levels were not altered by exposures to renin angiotensin aldosterone system (RAAS) inhibitors. ACE2+ expression signatures were defined by differential expression analysis and characterized by Bayesian integrative analysis of a large compendium of public -omics datasets, resulting in the identification of network modules induced in ACE2 positive PTEC in DKD and BK virus nephropathy. These ACE2 upregulated cell programs were linked to viral entry, immune activation, endomembrane reorganization, and RNA processing and overlapped significantly with the cellular responses induced by SARS-CoV-2 infection. Similar cellular programs were activated in ACE2-positive PTEC isolated in a urine sample from a COVID19 patient with acute kidney injury, suggesting a consistent ACE2-coregulated expression program that may interact with SARS-Cov-2 infection processes. The SARS-CoV-2 receptor associated gene signatures could seed further research into therapeutic strategies for COVID-19. Functional networks of gene expression signatures are available for further exploration to researchers at HumanBase (hb.flatironinstitute.org/covid-kidney).


title: Fighting COVID-19: Enabling Graduating Students to Start Internship Early at Their Own Medical School

text: This perspective proposes one way to ensure enough doctors, nurses, and pharmacists during the COVID-19 pandemic: Enable graduating students to start internship early at their own medical school.


title: Evaluation of Diarrhea in HIV-Infected Patients

text: Diarrhea is a major problem for patients infected with HIV: initial studies indicated that 50% of HIV-seropositive patients developed diarrhea, but this may be an underestimate. Diarrhea has an appreciable adverse affect on the quality of life of these patients; also, they use more health care facilities and health care dollars than HIV-positive patients without diarrhea. Individuals who have homosexuality or bisexuality as their HIV risk factor are more likely to have diarrhea and to have an enteric pathogen identified as the cause of diarrhea than are patients who have heterosexuality or intravenous drug use as their risk factor.


title: STING modulators: Predictive significance in drug discovery

text: Cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS) — stimulator of interferon genes (STING) signaling pathway plays the critical role in the immune response to DNA. Pharmacological modulation of the STING pathway has been well characterized both from structural and functional perspectives, which paves the way for the drug design of small modulators by medicinal chemists. Here, we outline recent progress in studies on the STING pathway, the structure and biological function of STING, the STING related disease, as well as the rationale and progress in the development of STING modulators. Our review demonstrates that STING is a promising drug target, and providing clues for the discovery of novel STING agonists and antagonists for the potential treatment of various disease including microbial infectious diseases, cancer, and autoimmune disease.


title: Drug Repurposing for Viral Infectious Diseases: How Far Are We?

text: Despite the recent advances in controlling some viral pathogens, most viral infections still lack specific treatment. Indeed, the need for effective therapeutic strategies to combat ‘old’, emergent, and re-emergent viruses is not paralleled by the approval of new antivirals. In the past years, drug repurposing combined with innovative approaches for drug validation, and with appropriate animal models, significantly contributed to the identification of new antiviral molecules and targets for therapeutic intervention. In this review, we describe the main strategies of drug repurposing in antiviral discovery, discuss the most promising candidates that could be repurposed to treat viral infections, and analyze the possible caveats of this trendy strategy of drug discovery.


title: Rotavirus infection in calves in Bangladesh

text: Faecal samples from 434 calves under 1 year of age (307 diarrhoeal and 127 normal) were collected from three dairy farms and one village in selected areas of Bangladesh. The samples were tested by an enzyme-linked immunosorbent assay (ELISA) to detect the presence of rotavirus antigen. Of 402 dairy calves tested, 28 (7.0%) were positive, of which 21 (7.2%) were from diarrhoeic calves and 7 (6.3%) from non-diarrhoeic calves. Rotavirus infection varied from farm to farm (2.7–9.2%) and there was no positive response from any of the 32 village calves. Rotavirus was most commonly found in calves of 1 week of age or less (up to 22.2% in one group) but was not found in any calves later than 6 months of age. More than 80% of rotavirus-positive samples from diarrhoeic calves exhibited a titre of 128 or more (geometric mean 345±4.5), whereas non-diarrhoeal calves had titres less than or equal to 128 (geometric mean=29±1.9), suggesting that rotavirus infection in calves in Bangladesh was mostly associated with diarrhoea.


title: Bats and zoonotic viruses: can we confidently link bats with emerging deadly viruses?

text: An increasingly asked question is 'can we confidently link bats with emerging viruses?'. No, or not yet, is the qualified answer based on the evidence available. Although more than 200 viruses - some of them deadly zoonotic viruses - have been isolated from or otherwise detected in bats, the supposed connections between bats, bat viruses and human diseases have been raised more on speculation than on evidence supporting their direct or indirect roles in the epidemiology of diseases (except for rabies). However, we are convinced that the evidence points in that direction and that at some point it will be proved that bats are competent hosts for at least a few zoonotic viruses. In this review, we cover aspects of bat biology, ecology and evolution that might be relevant in medical investigations and we provide a historical synthesis of some disease outbreaks causally linked to bats. We provide evolutionary-based hypotheses to tentatively explain the viral transmission route through mammalian intermediate hosts and to explain the geographic concentration of most outbreaks, but both are no more than speculations that still require formal assessment.


title: Superior immune responses induced by intranasal immunization with recombinant adenovirus-based vaccine expressing full-length Spike protein of Middle East respiratory syndrome coronavirus

text: Middle East respiratory syndrome coronavirus (MERS-CoV) causes an acute and severe lower respiratory illness as well as vomiting, diarrhea, and renal failure. Because no licensed MERS-CoV vaccines are currently available, preventive and therapeutic measures are urgently needed. The surface spike (S) glycoprotein of MERS-CoV, which binds to the cellular receptor dipeptidyl peptidase 4 (DPP4), is considered as a major target for MERS-CoV vaccine development. Here, we designed recombinant replication-deficient adenovirus-based vaccines expressing the N-terminal domain (rAd/NTD) and receptor-binding domain (rAd/RBD) of the MERS-CoV S1 subunit and full-length Spike protein (rAd/Spike). We found that immunization with candidate vaccines via intranasal route induced S1-specific IgG antibodies and neutralizing antibodies against MERS spike pseudotyped virus. Especially, rAd/Spike induced the highest neutralizing antibody titer and the strongest cytokine-induced T cell responses among the three candidate vaccines. To compare the immune responses induced by different administration routes, rAd/Spike was administered via intranasal, sublingual, or intramuscular route. All these administration routes exhibited neutralizing effects in the serum. MERS-CoV-specific neutralizing IgA antibodies in the bronchoalveolar lavage fluid were only induced by intranasal and sublingual administration but not by intramuscular administration. Intranasal administration with rAd/Spike also created resident memory CD8 T cells in the airway and lung parenchyma. Taken together, our results showed that both the humoral and cellular immune responses are highly induced by rAd/Spike administration, suggesting that rAd/Spike may confer protection against MERS-CoV infection.


title: Molecular-based diagnostics, including future trends

text: Abstract Microbiology laboratories have traditionally relied upon phenotypic methods involving culture and biochemical testing to identify and characterize clinically important pathogens. These techniques have several disadvantages including poor sensitivity and long turn-around time. Molecular and mass spectroscopy techniques are rapidly changing infection diagnosis and management. Compared with conventional culture-based techniques, these modern approaches provide substantially more rapid and specific information on organism identification and on the presence of resistance mechanisms. These methods are expected to contribute substantially to enhancing antibiotic stewardship and to improving ‘time to appropriate antibiotics’, one of the most important factors in improving the prognosis of patients with life-threatening infections. This article gives an overview of some of the practical applications of these newer technologies.


title: The TARGET cohort study protocol: a prospective primary care cohort study to derive and validate a clinical prediction rule to improve the targeting of antibiotics in children with respiratory tract illnesses

text: BACKGROUND: Children with respiratory tract infections are the single most frequent patient group to make use of primary care health care resources. The use of antibiotics remains highly prevalent in young children, but can lead to antimicrobial resistance as well as reinforcing the idea that parents should re-consult for similar symptoms. One of the main drivers of indiscriminate antimicrobial use is the lack of evidence for, and therefore uncertainty regarding, which children are at risk of poor outcome. This paper describes the protocol for the TARGET cohort study, which aims to derive and validate a clinical prediction rule to identify children presenting to primary care with respiratory tract infections who are at risk of hospitalisation. METHODS/DESIGN: The TARGET cohort study is a large, multicentre prospective observational study aiming to recruit 8,300 children aged ≥3 months and <16 years presenting to primary care with a cough and respiratory tract infection symptoms from 4 study centres (Bristol, London, Oxford and Southampton). Following informed consent, symptoms, signs and demographics will be measured. In around a quarter of children from the Bristol centre, a single sweep, dual bacterial-viral throat swab will be taken and parents asked to complete a symptom diary until the child is completely well or for 28 days, whichever is sooner. A review of medical notes including clinical history, re-consultation and hospitalisations will be undertaken. Multivariable logistic regression will be used to identify the independent clinical predictors of hospitalisation as well as the prognostic significance of upper respiratory tract microbes. The clinical prediction rule will be internally validated using various methods including bootstrapping. DISCUSSION: The clinical prediction rule for hospitalisation has the potential to help identify a small group of children for hospitalisation and a much larger group where hospitalisation is very unlikely and antibiotic prescribing would be less warranted. This study will also be the largest natural history study to date of children presenting to primary care with acute cough and respiratory tract infections, and will provide important information on symptom duration, re-consultations and the microbiology of the upper respiratory tract.


title: Traditional Chinese Medicine as a Potential Source for HSV-1 Therapy by Acting on Virus or the Susceptibility of Host

text: Herpes simplex virus type 1 (HSV-1) is the most common virus, with an estimated infection rate of 60–95% among the adult population. Once infected, HSV-1 can remain latent in the host for a lifetime and be reactivated in patients with a compromised immune system. Reactivation of latent HSV-1 can also be achieved by other stimuli. Though acyclovir (ACV) is a classic drug for HSV-1 infection, ACV-resistant strains have been found in immune-compromised patients and drug toxicity has also been commonly reported. Therefore, there is an urge to search for new anti-HSV-1 agents. Natural products with potential anti-HSV-1 activity have the advantages of minimal side effects, reduced toxicity, and they exert their effect by various mechanisms. This paper will not only provide a reference for the safe dose of these agents if they are to be used in humans, referring to the interrelated data obtained from in vitro experiments, but also introduce the main pharmacodynamic mechanisms of traditional Chinese medicine (TCM) against HSV-1. Taken together, TCM functions as a potential source for HSV-1 therapy by direct (blocking viral attachment/absorption/penetration/replication) or indirect (reducing the susceptibility to HSV-1 or regulating autophagy) antiviral activities. The potential of these active components in the development of anti-HSV-1 drugs will also be described.


title: Sequence analysis of the S1 glycoprotein gene of infectious bronchitis viruses: identification of a novel phylogenetic group in Korea

text: Twelve Korean infectious bronchitis viruses (IBVs) were isolated in the field from chickens suspected of being carriers of infectious bronchitis between 2001 and 2003. The S1 glycoprotein genes of these IBV isolates were amplified by reverse transcriptase-polymerase chain reaction (RT-PCR) and analyzed by restriction fragment length polymorphism (RFLP) analysis. These Korean IBV isolates were classified into three groups according to their RFLP patterns obtained using the restriction enzyme HaeIII. Half of the twelve isolates were similar to the KM91 RFLP pattern, which is a common pattern in Korea. Three more isolates were related to the Arkansas strain pattern, but with some unique variations. The other three viruses showed variant RFLP patterns. For a comparison with the published sequences for non-Korean IBV strains, amplified PCR products from the twelve isolates were cloned and sequenced. The Korean IBV field isolates had 71.2-99.7% nucleotide sequence homology with each other and 45.9-80.7% nucleotide sequence homology with non-Korean IBV strains. With respect to the deduced amino acid sequence, the Korean IBV isolates had 71.5-99.3% similarity with each other and 44.9-80.3% similarity with non-Korean IBV strains. Phylogenetic tree analysis revealed that some of the IBV isolates appear to belong to a new group, different from the non-Korean IBV strains or from previously isolated Korean IBV strains. Specifically, the new Korean IBV isolates K10217-03, K3-3 and K1255-03 represented a separate group. These findings suggest that the Korean IBVs appear to be continuously evolving.


title: Modification of cellulose microfibers by polyglutamic acid and mesoporous silica nanoparticles for Enterovirus 71 adsorption

text: In this study, we synthesized a novel kind of cellulose-based microfibers for efficient adsorption of Enterovirus 71 (EV71), the leading causative agent of life-threatening hand, foot and mouth disease. The initial cellulose microfibers (CEL) were activated by (3-aminopropyl) triethoxysilane (APTES), and then covalently modified by polyglutamic acid (PGA) and mesoporous silica nanoparticles (MSN), obtaining the microfibers CEL-PGA-MSN. Owing to the electrostatic interaction between the negatively charged components (i.e., PGA and MSN) and positively charged amino acids of the epitope of EV71 capsid protein VP2 (VP2-ep), the obtained microfibers strongly adsorbed the epitope, and exhibited high EV71-adsorption capacity. This study sheds a novel light on development of cellulose-based materials for application in virus-capturing equipment.


title: A novel multiplex PCR for virus detection by melting curve analysis

text: Abstract Background Rapid and accurate laboratory diagnoses of viral infections are crucial for the management and treatment of patients with viral infections. Conventional methods for virus detection are labourious, time consuming, and only a single virus can be analysed in one assay. Objectives The objective of this study was to develop a novel real-time PCR method for multiple virus detection by melting curve analysis using Taqman probes in a single reaction. Study design As a model, six respiratory viruses were detected in one tube using three fluorophores. The specificity was assessed by cross-reaction tests with other common respiratory pathogens. The analytical sensitivity was assessed by testing the limit of detection of the assay using artificial plasmids as the positive template. The clinical evaluation of the established assay was evaluated for the detection of respiratory viruses in clinical samples, and the results were compared with direct fluorescent antibody testing (DFA). Results The six respiratory viruses were clearly distinguished by their respective melting temperature values in the corresponding fluorescence detection channels. No cross reactions were observed by cross reaction tests. The detection limits of this assay were 2 to 2 × 103 copies per reaction for each virus. The clinical evaluation of this assay was demonstrated by analysing 352 clinical samples, and 67(19.0%) samples were positive for at least one virus. The accordance rate between the established PCR and DFA testing was high, and ranged from 94.57% to 100%. Conclusions Taqman probe-based melting curve analysis is well suited for detection of multiple viruses in clinical and research laboratories because of its high throughput, reliability, and cost savings.


title: Detection of human Coronavirus 229E in nasal specimens in large scale studies using an RT-PCR hybridization assay

text: Abstract A novel human Coronavirus (HCoV) was this year recognized as the etiological agent of the Severe Acute Respiratory Syndrome. Two other HCoV (HCoV-229E and HCoV-OC43) have been known for 30 years. HCoV-229E has been recently involved in nosocomial respiratory viral infections in high-risk children. However, their diagnosis is not routinely performed. Currently, reliable immunofluorescence and cell culture methodologies are not available. As part of a four-year epidemiological study in a Pediatric and Neonatal Intensive care unit, we have performed and demonstrated the reliability of a reverse transcription-PCR-hybridization assay to detect HCoV of the 229E antigenic group in 2028 clinical respiratory specimens. In hospitalized children (children and newborns) and staff members we found a high incidence of HcoV-229E infection. This reverse transcription-PCR-hybridization assay gave a high specificity and a sensitivity of 0.5 50% Tissue Culture Infective Dose per ml. This technique is reliable and its application for screening large number of clinical samples would improve the diagnosis of HCoVs respiratory infection and our knowledge of these viruses epidemiology.


title: Coronavirus Disease 2019 (COVID-19) in Neonates and Children From China: A Review

text: At the end of 2019, a novel coronavirus began to spread in Wuhan, Hubei Province, China. The confirmed cases increased nationwide rapidly, in part due to the increased population mobility during the Chinese Lunar New Year festival. The World Health Organization (WHO) subsequently named the novel coronavirus pneumonia Coronavirus Disease 2019 (COVID-19) and named the virus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Soon, transmission from person to person was confirmed and the virus spread to many other countries. To date, many cases have been reported in the pediatric age group, most of which were from China. The management and treatment strategies have also been improved, which we believe would be helpful to pediatric series in other countries as well. However, the characteristics of neonatal and childhood infection still have not been evaluated in detail. This review summarizes the current understanding of SARS-CoV-2 infection in neonates and children from January 24 to May 1, as an experience from China.


title: The serotype of adenoviruses detected in faeces by electron microscopy

text: Abstract The specific identification of 100 adenoviruses detected in faeces by electron microscopy was attempted using a combination of group-specific and sub-genus F (type 40 41 ) specific enzyme assays, and isolation in cell culture followed by specific neutralization. Sixty-three were considered to be AdF strains i.e. types 40 or 41 and 37, of which 33 were isolated in cell culture, were deemed to be non-AdF serotypes. The relevance of these results in relation to the diagnosis of viral gastroenteritis is discussed.


title: Plasma from recovered COVID19 subjects inhibits spike protein binding to ACE2 in a microsphere-based inhibition assay

text: High throughput serological tests that can establish the presence and functional activity of anti-SARS-COV2 antibodies are urgently needed. Here we present microsphere-based Flow Cytometry assays that quantify both anti-spike IgGs in plasma, and the ability of plasma to inhibit the binding of spike protein to angiotensin converting enzyme 2 (ACE2). First, we detected anti-trimer IgGs in 22/24 and anti-RBD IgGs in 21/24 COVID+ subjects at a median of 36 (range 14-73) days following documented SARS-CoV-2 RNA (+) secretions. Next, we find that plasma from all 22/24 subjects with anti-trimer IgGs inhibited ACE2-trimer binding to a greater degree than controls, and that the degree of inhibition correlated with anti-trimer IgG levels. Depletion of trimer-reactive Igs from plasma reduced ACE2-trimer inhibitory capacity to a greater degree than depletion of RBD-reactive Igs, suggesting that inhibitory antibodies act by binding both within and outside of the RBD. Amongst the 24 subjects, presence of fever was associated with higher levels of anti-trimer IgG and inhibition of binding to human ACE2. This inhibition assay may be broadly useful to quantify the functional antibody response of recovered COVID19 patients or vaccine recipients in a cell-free assay system.


title: Buried treasure: evolutionary perspectives on microbial iron piracy

text: Host-pathogen interactions provide valuable systems for the study of evolutionary genetics and natural selection. The sequestration of essential iron has emerged as a critical innate defense system termed nutritional immunity, leading pathogens to evolve mechanisms of `iron piracy' to scavenge this metal from host proteins. This battle for iron carries numerous consequences not only for host-pathogen evolution, but also microbial community interactions. Here we highlight recent and potential future areas of investigation on the evolutionary implications of microbial iron piracy in relation to molecular arms races, host range, competition, and virulence. Applying evolutionary genetic approaches to the study of microbial iron acquisition could also provide new inroads for understanding and combating infectious disease.


Surgery in the COVID‐19 pandemic: clinical characteristics and outcomes


Coronavirus, Climate Change, and a Bit of Hope


title: Nexus between COVID-19, temperature and exchange rate in Wuhan City: New findings from Partial and Multiple Wavelet Coherence

text: Abstract This study attempts to document the nexus between weather, covid-19 outbreak in Wuhan and the Chinese economy. We employ 24-h daily average temperature, daily new confirmed cases of a covid-19 in Wuhan, and RMB exchange rate to represent the weather, covid-19 outbreak, and Chinese economy, respectively. The methodology of Wavelet Transform Coherence (WTC), Partial Wavelet Coherence (PWC), and Multiple Wavelet Coherence (MWC) is used to analyze the daily data collected from 21st January 2020 to 31st March 2020. Results reveal significant coherence between series at different time-frequency combinations. Overall results show the insignificance of an increase in temperature to contain new covid-19 infections. The Renminbi exchange rate showed a negative coherence at specific time-frequency spots suggesting a negative but limited impact of the covid-19 outbreak in Wuhan on the Chinese export economy. Our results are contrary to many earlier studies, which show a significant impact of increased temperature in slowing down covid-19 spread. These results can have important implications for economic and containment policy making regarding the covid-19 outbreak.


title: Statistical learning techniques applied to epidemiology: a simulated case-control comparison study with logistic regression

text: BACKGROUND: When investigating covariate interactions and group associations with standard regression analyses, the relationship between the response variable and exposure may be difficult to characterize. When the relationship is nonlinear, linear modeling techniques do not capture the nonlinear information content. Statistical learning (SL) techniques with kernels are capable of addressing nonlinear problems without making parametric assumptions. However, these techniques do not produce findings relevant for epidemiologic interpretations. A simulated case-control study was used to contrast the information embedding characteristics and separation boundaries produced by a specific SL technique with logistic regression (LR) modeling representing a parametric approach. The SL technique was comprised of a kernel mapping in combination with a perceptron neural network. Because the LR model has an important epidemiologic interpretation, the SL method was modified to produce the analogous interpretation and generate odds ratios for comparison. RESULTS: The SL approach is capable of generating odds ratios for main effects and risk factor interactions that better capture nonlinear relationships between exposure variables and outcome in comparison with LR. CONCLUSIONS: The integration of SL methods in epidemiology may improve both the understanding and interpretation of complex exposure/disease relationships.


title: Human parainfluenza virus type 2 V protein inhibits interferon production and signaling and is required for replication in non-human primates

text: In wild-type human parainfluenza virus type 2 (WT HPIV2), one gene (the P/V gene) encodes both the polymerase-associated phosphoprotein (P) and the accessory V protein. We generated a HPIV2 virus (rHPIV2-V(ko)) in which the P/V gene encodes only the P protein to examine the role of V in replication in vivo and as a potential live attenuated virus vaccine. Preventing expression of V protein severely impaired virus recovery from cDNA and growth in vitro, particularly in IFN-competent cells. rHPIV2-V(ko), unlike WT HPIV2, strongly induced IFN-β and permitted IFN signaling, leading to establishment of a robust antiviral state. rHPIV2-V(ko) infection induced extensive syncytia and cytopathicity that was due to both apoptosis and necrosis. Replication of rHPIV2-V(ko) was highly restricted in the respiratory tract of African green monkeys and in differentiated primary human airway epithelial (HAE) cultures, suggesting that V protein is essential for efficient replication of HPIV2 in organized epithelial cells and that rHPIV2-V(ko) is over-attenuated for use as a live attenuated vaccine.


title: Complete genome sequence of canine astrovirus with molecular and epidemiological characterisation of UK strains

text: Astroviruses are a common cause of gastroenteritis in children worldwide. These viruses can also cause infection in a range of domestic and wild animal species. Canine astrovirus (CaAstV) was first identified in the USA, and has since been reported in dogs from Europe, the Far East and South America. We sought to determine whether CaAstV is circulating in the UK dog population, and to characterise any identified strains. Stool samples were collected from pet dogs in the UK with and without gastroenteritis, and samples were screened for CaAstV by qPCR. Four CaAstV positive samples were identified from dogs with gastroenteritis (4/67, 6.0%), whereas no samples from healthy dogs were positive (p < 0.001). Sequencing of the capsid sequences from the four CaAstV strains found significant genetic heterogeneity, with only 80% amino acid identity between strains. The full genome sequence of two UK CaAstV strains was then determined, confirming that CaAstV conforms to the classic genome organisation of other astroviruses with ORF1a and ORF1b separated by a frameshift and ORF2 encoding the capsid protein. This is the first report describing the circulation of CaAstV in UK dogs with clinical signs of gastroenteritis, and the first description of the full-length genomes of two CaAstV strains.


title: The SARS-CoV-2 main protease as drug target

text: The unprecedented pandemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is threatening global health. The virus emerged in late 2019 and can cause a severe disease associated with significant mortality. Several vaccine development and drug discovery campaigns are underway. The SARS-CoV-2 main protease is considered a promising drug target, as it is dissimilar to human proteases. Sequence and structure of the main protease are closely related to those from other betacoronaviruses, facilitating drug discovery attempts based on previous lead compounds. Covalently binding peptidomimetics and small molecules are investigated. Various compounds show antiviral activity in infected human cells.


title: Meteorological impact on the COVID-19 pandemic: A study across eight severely affected regions in South America

text: The role of meteorological factors in the transmission of the COVID-19 still needs to be determined. In this study, the daily new cases of the eight severely affected regions in four countries of South America and their corresponding meteorological data (average temperature, maximum temperature, minimum temperature, average wind speed, visibility, absolute humidity) were collected. Daily number of confirmed and incubative cases, as well as time-dependent reproductive number (R(t)) was calculated to indicate the transmission of the diseases in the population. Spearman's correlation coefficients were assessed to show the correlation between meteorological factors and daily confirmed cases, daily incubative cases, as well as Rt. In particular, the results showed that there was a highly significant correlation between daily incubative cases and absolute humidity throughout the selected regions. Multiple linear regression model further confirmed the negative correlation between absolute humidity and incubative cases. The absolute humidity is predicted to show a decreasing trend in the coming months from the meteorological data of recent three years. Our results suggest the necessity of continuous controlling policy in these areas and some other complementary strategies to mitigate the contagious rate of the COVID-19.


title: Various Jobs of Proteolytic Enzymes in Skeletal Muscle during Unloading: Facts and Speculations

text: Skeletal muscles, namely, postural muscles, as soleus, suffer from atrophy under disuse. Muscle atrophy development caused by unloading differs from that induced by denervation or other stimuli. Disuse atrophy is supposed to be the result of shift of protein synthesis/proteolysis balance towards protein degradation increase. Maintaining of the balance involves many systems of synthesis and proteolysis, whose activation leads to muscle adaptation to disuse rather than muscle degeneration. Here, we review recent data on activity of signaling systems involved in muscle atrophy development under unloading and muscle adaptation to the lack of support.


title: Estimates of the severity of coronavirus disease 2019: a model-based analysis

text: BACKGROUND: In the face of rapidly changing data, a range of case fatality ratio estimates for coronavirus disease 2019 (COVID-19) have been produced that differ substantially in magnitude. We aimed to provide robust estimates, accounting for censoring and ascertainment biases. METHODS: We collected individual-case data for patients who died from COVID-19 in Hubei, mainland China (reported by national and provincial health commissions to Feb 8, 2020), and for cases outside of mainland China (from government or ministry of health websites and media reports for 37 countries, as well as Hong Kong and Macau, until Feb 25, 2020). These individual-case data were used to estimate the time between onset of symptoms and outcome (death or discharge from hospital). We next obtained age-stratified estimates of the case fatality ratio by relating the aggregate distribution of cases to the observed cumulative deaths in China, assuming a constant attack rate by age and adjusting for demography and age-based and location-based under-ascertainment. We also estimated the case fatality ratio from individual line-list data on 1334 cases identified outside of mainland China. Using data on the prevalence of PCR-confirmed cases in international residents repatriated from China, we obtained age-stratified estimates of the infection fatality ratio. Furthermore, data on age-stratified severity in a subset of 3665 cases from China were used to estimate the proportion of infected individuals who are likely to require hospitalisation. FINDINGS: Using data on 24 deaths that occurred in mainland China and 165 recoveries outside of China, we estimated the mean duration from onset of symptoms to death to be 17·8 days (95% credible interval [CrI] 16·9–19·2) and to hospital discharge to be 24·7 days (22·9–28·1). In all laboratory confirmed and clinically diagnosed cases from mainland China (n=70 117), we estimated a crude case fatality ratio (adjusted for censoring) of 3·67% (95% CrI 3·56–3·80). However, after further adjusting for demography and under-ascertainment, we obtained a best estimate of the case fatality ratio in China of 1·38% (1·23–1·53), with substantially higher ratios in older age groups (0·32% [0·27–0·38] in those aged <60 years vs 6·4% [5·7–7·2] in those aged ≥60 years), up to 13·4% (11·2–15·9) in those aged 80 years or older. Estimates of case fatality ratio from international cases stratified by age were consistent with those from China (parametric estimate 1·4% [0·4–3·5] in those aged <60 years [n=360] and 4·5% [1·8–11·1] in those aged ≥60 years [n=151]). Our estimated overall infection fatality ratio for China was 0·66% (0·39–1·33), with an increasing profile with age. Similarly, estimates of the proportion of infected individuals likely to be hospitalised increased with age up to a maximum of 18·4% (11·0–7·6) in those aged 80 years or older. INTERPRETATION: These early estimates give an indication of the fatality ratio across the spectrum of COVID-19 disease and show a strong age gradient in risk of death. FUNDING: UK Medical Research Council.


title: Protective efficacy of a broadly cross-reactive swine influenza DNA vaccine encoding M2e, cytotoxic T lymphocyte epitope and consensus H3 hemagglutinin

text: BACKGROUND: Pigs have been implicated as mixing reservoir for the generation of new pandemic influenza strains, control of swine influenza has both veterinary and public health significance. Unlike human influenza vaccines, strains used for commercially available swine influenza vaccines are not regularly replaced, making the vaccines provide limited protection against antigenically diverse viruses. It is therefore necessary to develop broadly protective swine influenza vaccines that are efficacious to both homologous and heterologous virus infections. In this study, two forms of DNA vaccines were constructed, one was made by fusing M2e to consensus H3HA (MHa), which represents the majority of the HA sequences of H3N2 swine influenza viruses. Another was made by fusing M2e and a conserved CTL epitope (NP147-155) to consensus H3HA (MNHa). Their protective efficacies against homologous and heterologous challenges were tested. RESULTS: BALB/c mice were immunized twice by particle-mediated epidermal delivery (gene gun) with the two DNA vaccines. It was shown that the two vaccines elicited substantial antibody responses, and MNHa induced more significant T cell-mediated immune response than MHa did. Then two H3N2 strains representative of different evolutional and antigenic clusters were used to challenge the vaccine-immunized mice (homosubtypic challenge). Results indicated that both of the DNA vaccines prevented homosubtypic virus infections completely. The vaccines’ heterologous protective efficacies were further tested by challenging with a H1N1 swine influenza virus and a reassortant 2009 pandemic strain. It was found that MNHa reduced the lung viral titers significantly in both challenge groups, histopathological observation showed obvious reduction of lung pathogenesis as compared to MHa and control groups. CONCLUSIONS: The combined utility of the consensus HA and the conserved M2e and CTL epitope can confer complete and partial protection against homologous and heterologous challenges, respectively, in mouse model. This may provide a basis for the development of universal swine influenza vaccines.


title: Antibodies against trimeric S glycoprotein protect hamsters against SARS-CoV challenge despite their capacity to mediate FcγRII-dependent entry into B cells in vitro

text: Vaccine-induced antibodies can prevent or, in the case of feline infectious peritonitis virus, aggravate infections by coronaviruses. We investigated whether a recombinant native full-length S-protein trimer (triSpike) of severe acute respiratory syndrome coronavirus (SARS-CoV) was able to elicit a neutralizing and protective immune response in animals and analyzed the capacity of anti-S antibodies to mediate antibody-dependent enhancement (ADE) of virus entry in vitro and enhancement of replication in vivo. SARS-CoV-specific serum and mucosal immunoglobulins were readily detected in immunized animals. Serum IgG blocked binding of the S-protein to the ACE2 receptor and neutralized SARS-CoV infection in vitro. Entry into human B cell lines occurred in a FcγRII-dependent and ACE2-independent fashion indicating that ADE of virus entry is a novel cell entry mechanism of SARS-CoV. Vaccinated animals showed no signs of enhanced lung pathology or hepatitis and viral load was undetectable or greatly reduced in lungs following challenge with SARS-CoV. Altogether our results indicate that a recombinant trimeric S protein was able to elicit an efficacious protective immune response in vivo and warrant concern in the safety evaluation of a human vaccine against SARS-CoV.


title: Trypsin treatment unlocks barrier for zoonotic coronaviruses infection

text: Traditionally, the emergence of coronaviruses (CoVs) has been attributed to a gain in receptor binding in a new host. Our previous work with SARS-like viruses argued that bats already harbor CoVs with the ability to infect humans without adaptation. These results suggested that additional barriers limit the emergence of zoonotic CoV. In this work, we describe overcoming host restriction of two MERS-like bat CoVs using exogenous protease treatment. We found that the spike protein of PDF2180-CoV, a MERS-like virus found in a Ugandan bat, could mediate infection of Vero and human cells in the presence of exogenous trypsin. We subsequently show that the bat virus spike can mediate infection of human gut cells, but is unable to infect human lung cells. Using receptor-blocking antibodies, we show that infection with the PDF2180 spike does not require MERS-CoV receptor DPP4 and antibodies developed against the MERS spike receptor-binding domain and S2 portion are ineffective in neutralizing the PDF2180 chimera. Finally, we found that addition of exogenous trypsin also rescues replication of HKU5-CoV, a second MERS-like group 2c CoV. Together, these results indicate that proteolytic cleavage of the spike, not receptor binding, is the primary infection barrier for these two group 2c CoVs. Coupled with receptor binding, proteolytic activation offers a new parameter to evaluate emergence potential of CoVs and offer a means to recover previously unrecoverable zoonotic CoV strains. Importance Overall, our studies demonstrate that proteolytic cleavage is the primary barrier to infection for a subset of zoonotic coronaviruses. Moving forward, the results argue that both receptor binding and proteolytic cleavage of the spike are critical factors that must be considered for evaluating the emergence potential and risk posed by zoonotic coronaviruses. In addition, the findings also offer a novel means to recover previously uncultivable zoonotic coronavirus strains and argue that other tissues, including the digestive tract, could be a site for future coronavirus emergence events in humans.


title: Regulation of ROS in transmissible gastroenteritis virus-activated apoptotic signaling

text: Abstract Transmissible gastroenteritis virus (TGEV), an enteropathogenic coronavirus, causes severe lethal watery diarrhea and dehydration in piglets. Previous studies indicate that TGEV infection induces cell apoptosis in host cells. In this study, we investigated the roles and regulation of reactive oxygen species (ROS) in TGEV-activated apoptotic signaling. The results showed that TGEV infection induced ROS accumulation, whereas UV-irradiated TGEV did not promote ROS accumulation. In addition, TGEV infection lowered mitochondrial transmembrane potential in PK-15 cell line, which could be inhibited by ROS scavengers, pyrrolidinedithiocarbamic (PDTC) and N-acetyl-l-cysteine (NAC). Furthermore, the two scavengers significantly inhibited the activation of p38 MAPK and p53 and further blocked apoptosis occurrence through suppressing the TGEV-induced Bcl-2 reduction, Bax redistribution, cytochrome c release and caspase-3 activation. These results suggest that oxidative stress pathway might be a key element in TGEV-induced apoptosis and TGEV pathogenesis.


Are erythema multiforme and urticaria related to a better outcome of COVID‐19?


title: Src siRNA prevents corticosteroid-associated osteoporosis in a rabbit model

text: Abstract In an established steroid-associated osteonecrosis (SAON) rabbit model we found recently that blockage Src by siRNA could improve reconstructive repair of osteonecrosis via enhancing osteogenesis and inhibiting bone resorption. The current study investigated if blocking Src was able to prevent steroid-associated osteoporosis (SAOP) in the same SAON animal model. Rabbits were treated with pulsed lipopolysaccharide (LPS) and corticosteroid methylprednisolone (MPS). At 2, 4, and 6weeks after induction, Src siRNA, control siRNA and saline were intramedullary injected into proximal femur, respectively. Two fluorescent dyes xylenol orange and calcein green were injected before sacrificing the animals for in vivo labeling of the newly formed bone. At week 6 after induction, proximal femora of rabbits were dissected for micro-CT and histological analysis. Results showed significant bone loss in the metaphysis of femoral head in the control rabbits after SAON induction. Src siRNA treatment was able to prevent steroid-associate bone loss in trabecular bone and increase cortical bone thickness at femoral neck. Histomorphometry showed that Src siRNA increased the osteoblastic bone formation and decreased the eroded bone surfaces suggesting decreased osteoclastic bone resorption. This was the first study to report bone loss after SAON induction in rabbit model that could be prevented by knocking down Src by siRNA.


title: Circular RNA CircEZH2 Suppresses Transmissible Gastroenteritis Coronavirus-induced Opening of Mitochondrial Permeability Transition Pore via Targeting MiR-22 in IPEC-J2

text: Transmissible gastroenteritis (TGE) is a contagious and infectious disease that is characterized by severe vomiting and diarrhea of swine , especially piglet, and caused by transmissible gastroenteritis coronavirus (TGEV) . TGEV infection provokes mitochondrial damage of porcine intestinal epthelial cell (IPEC), which is responsible for inflammation and cell death. In our previous study, we have demonstrated that circular RNA circEZH2 was down-regulated during TGEV infection and promoted the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) via targeting miR-22 in porcine intestinal epithelial cell line (IPEC-J2). Activation of NF-κB is an important factor for mitochondrial damage. Mitochondrial permeability transition pore (mPTP) opening is a key reason for mitochondrial damage. So, we speculate that circEZH2 may regulate TGEV-induced mPTP opening via NF-kB pathway. In the present study, we found that mPTP opening of IPEC-J2 was occured during TGEV infection and suppressed by circEZH2 via attaching miR-22. Hexokinase 2 (HK2) and interleukin 6 (IL-6) were identified as the targets of miR-22. Silencing HK2 enhanced TGEV-induced mPTP opening, while no effect on NF-κB pathway. Silencing IL-6 promoted TGEV-induced mPTP opening and inhibited NF-κB pathway. Inhibitor of NF-κB increased TGEV-induced mPTP opening. The data revealed that TGEV-induced mPTP opening was regulated via two pathways: circEZH2/miR-22/HK2 axis and circEZH2/miR-22/IL-6/NF-κB axis.


title: Case Report: Diagnosis of Novel Coronavirus Disease (COVID-19) versus Tropical Diseases in Pakistan

text: A 25-year-old medical student presented in Multan, Pakistan with a high fever, cough, myalgia, and diarrhea consistent with the typical signs and symptoms of novel coronavirus disease (COVID-19). The patient had traveled to high COVID-19–risk areas within Pakistan and had no significant medical and surgical history. Based on nasopharyngeal and oropharyngeal swab testing, the patient was found to be negative for COVID-19. He subsequently developed a diffuse rash and had serology consistent with dengue and measles. The patient was treated symptomatically, and his condition gradually improved over 7 days. This case highlights the high prevalence of many tropical diseases in low-income countries and the need for clinicians to consider alternate diagnoses in addition to testing for COVID-19 during the pandemic.


title: Nutrition Management for Critically and Acutely Unwell Hospitalised Patients with COVID-19 in Australia and New Zealand

text: Coronavirus disease 2019 (COVID-19) results from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical features and subsequent medical treatment, combined with the impact of a global pandemic, require specific nutritional therapy in hospitalised adults. This document aims to provide Australian and New Zealand clinicians with guidance on managing critically and acutely unwell adult patients hospitalised with COVID-19. These recommendations were developed using expert consensus, incorporating the documented clinical signs and metabolic processes associated with COVID-19, the literature from other respiratory illnesses, in particular Acute Respiratory Distress Syndrome, and published guidelines for medical management of COVID-19 and general nutrition and intensive care. Patients hospitalised with COVID-19 are likely to have pre-existing comorbidities, and the ensuing inflammatory response may result in increased metabolic demands, protein catabolism, and poor glycaemic control. Common medical interventions, including deep sedation, early mechanical ventilation, fluid restriction, and management in the prone position, may exacerbate gastrointestinal dysfunction and effect nutritional intake. Nutrition care should be tailored to pandemic capacity, with early gastric feeding commenced using an algorithm to provide nutrition for the first 5-7 days in lower nutritional risk patients, and individualised care for high nutritional risk patients where capacity allows. Indirect calorimetry should be avoided due to potential aerosole exposure and therefore infection risk to health care providers. Use of a volume-controlled, higher-protein enteral formula and gastric residual volume monitoring should be initiated. Careful monitoring, particularly post-ICU, is required to ensure appropriate nutrition delivery to prevent muscle deconditioning and aid recovery. The infectious nature of SARS-CoV-2 and the expected high volume of patient admissions will require contingency planning to optimise staffing resources including up-skilling, ensure adequate nutrition supplies, facilitate remote consultations and optimise foodservice management. These guidelines provide recommendations on how to manage the above aspects when providing nutrition support to patients during the SARS-CoV-2 pandemic.


The bright future of coronavirology


title: COVID-19 Super-spreaders: Definitional Quandaries and Implications

text: Uncertainty around the role ‘super-spreaders’ play in the transmission and escalation of infectious disease is compounded by its broad and vague definition. It is a term that has been much used in relation to COVID-19, particularly in social media. On its widest definition, it refers to a propensity to infect a larger than average number of people. Given the biological, behavioural and environmental variables relevant to infectivity, this might be pertinent to almost any infected individual who is not physically isolated from others. Nor is the term confined to individuals with a propensity to spread infectious disease: it can potentially be used to describe events, policies or settings. This article explores the use of the term and considers circumstances in which the wide definition can be problematic. One problem is that it can lead to undeserved apportionment of moral blame to alleged super-spreaders. Another is that it can detract from scientific investigation of the heterogeneity of COVID-19 transmission. The author calls for a clearer epidemiological definition.


title: Determination of total organic carbon and soluble solids contents in Tanreqing injection intermediates with NIR spectroscopy and chemometrics

text: Abstract Near infrared spectroscopy combined with chemometrics was investigated for the fast determination of total organic carbon (TOC) and soluble solids contents (SSC) of Tanreqing injection intermediates. The NIR spectra were collected in transflective mode, and the TOC and SSC reference values were determined with Multi N/C UV HS analyzer and loss on drying method. The samples were divided into calibration sets and validation sets using the Kennard–Stone (KS) algorithm. The Dixon test, leverage and studentized residual test were studied for the sample outlier analysis. The selection of wavebands, spectra pretreated method and the number of latent variables were optimized to obtain better results. The quantitative calibration models were established with 3 different PLS regression algorithms, named linear PLS, non-linear PLS and concentration weighted PLS, and the net result was defined as the average of the predicted values of the different calibration models. The overall results indicated that the presented method is more powerful than single multivariable regression method, characterized by higher mean recovery rate (MRR) of the validation set, and can be used for the rapid determination of TOC and SSC values of Tanreqing injection intermediates, which are two important quality indicators for the process monitoring.


title: Middle East respiratory syndrome coronavirus (MERS-CoV): A cluster analysis with implications for global management of suspected cases

text: Summary Since the initial description of the Middle East respiratory syndrome (MERS) in September 2012, a total of 1038 cases of MERS-CoV including 460 deaths have been reported from Saudi Arabia. From August 24, 2013 to September 3, 2013, a total of 397 patients and contacts were tested for MERS-CoV. Of those tested, there were 18 (4.5%) MERS-CoV cases reported in Al-Madinah al-Munawwarah with one large cluster. In this report, we describe the outcome, epidemiology and clinical characteristics of this cluster of which 4 cases involved healthcare workers. Fourteen cases appeared to be linked to one cluster involving healthcare workers (HCWs), family and patient contacts. Of the 18 cases, five (including 2 HCWs) were community acquired, two were household contacts, and 11 were healthcare associated (including 4 HCWs). All except 4 cases were symptomatic and the case fatality rate was 39% (7 of 18). The outbreak resulted in human to human transmission of an estimated 6 cases. Contact screening showed positive test in 1 of 56 (1.8%) household contacts, and 3 of 250 (1.2%) HCWs.


title: Reducing risks to health and wellbeing at mass gatherings: the role of the Sendai Framework for Disaster Risk Reduction

text: Summary Mass gatherings of people at religious pilgrimages and sporting events are linked to numerous health hazards, including the transmission of infectious diseases, physical injuries, and an impact on local and global health systems and services. As with other forms of disaster, mass gathering-related disasters are the product of the management of different hazards, levels of exposure, and vulnerability of the population and environment, and require comprehensive risk management that looks beyond single hazards and response. Incorporating an all-hazard, prevention-driven, evidence-based approach that is multisectoral and multidisciplinary is strongly advocated by the Sendai Framework for Disaster Risk Reduction 2015–2030. This paper reviews some of the broader impacts of mass gatherings, the opportunity for concerted action across policy sectors and scientific disciplines offered by the year 2015 (including through the Sendai Framework), and the elements of a 21st century approach to mass gatherings.


title: A scoping review of the impact of COVID-19 pandemic on surgical practice

text: BACKGROUND: The current COVID-19 pandemic has challenged the infrastructure of the healthcare systems. To cope with the pandemic, substantial changes were introduced to surgical practice and education all over the world. METHODS: A scoping search in PubMed and Google scholar was done using the search terms: “Coronavirus,” “COVID-19”, “SARS-CoV-2”, “nCoV-2019”, and “surgery.” They were either searched individually or in combination. All relevant articles of any study design (published within December 15, 2019, till the mid of June 2020), was included and narratively discussed in this review. RESULTS: Sixty-six articles were reviewed in this article. Through these articles, we provide guidance and recommendations on the preoperative preparation and safety precautions, intraoperative precautions, postoperative precautions, postoperative complications (related to COVID-19), surgical scheduling, emergency surgeries, elective surgeries, cancer surgery, psychological impact on surgical teams, and surgical training during the COVID-19 pandemic. CONCLUSION: COVID-19 pandemic has affected nearly all aspects of surgical procedures, scheduling, and staffing. Special precautions were taken before, during, or after surgeries. New treatment and teaching modalities emerged in response to the pandemic. Psychological support and training platforms are necessary for the surgical team.


title: COVID, Existentialism and Crisis Philosophy

text: This is the editorial for Vol 19 Issue 2 of Philosophy of Management. A reflection is made on COVID-19 measures and a call for papers is made to explore the crisis through philosophical inquiry on 1) disaster management and 2) existentialist views of work. Guidance is given based on papers published previously in the journal, and on Camus’ La Peste / The Plague.


Opinion: An Increase in Severe Late-Dental Complications May Result from Reliance on Home Dental Remedies During the COVID-19 Pandemic


Vaginal delivery in a woman infected with SARS-CoV-2 – the first case reported in Portugal


title: Receptor-binding loops in alphacoronavirus adaptation and evolution

text: RNA viruses are characterized by a high mutation rate, a buffer against environmental change. Nevertheless, the means by which random mutation improves viral fitness is not well characterized. Here we report the X-ray crystal structure of the receptor-binding domain (RBD) of the human coronavirus, HCoV-229E, in complex with the ectodomain of its receptor, aminopeptidase N (APN). Three extended loops are solely responsible for receptor binding and the evolution of HCoV-229E and its close relatives is accompanied by changing loop–receptor interactions. Phylogenetic analysis shows that the natural HCoV-229E receptor-binding loop variation observed defines six RBD classes whose viruses have successively replaced each other in the human population over the past 50 years. These RBD classes differ in their affinity for APN and their ability to bind an HCoV-229E neutralizing antibody. Together, our results provide a model for alphacoronavirus adaptation and evolution based on the use of extended loops for receptor binding.


title: Outcomes of novel coronavirus disease 2019 (COVID‐19) infection in 107 patients with cancer from Wuhan, China

text: BACKGROUND: Patients with cancer have a higher risk of coronavirus disease 2019 (COVID‐19) than noncancer patients. The authors conducted a multicenter retrospective study to investigate the clinical manifestations and outcomes of patients with cancer who are diagnosed with COVID‐19. METHODS: The authors reviewed the medical records of hospitalized patients who were treated at 5 hospitals in Wuhan City, China, between January 5 and March 18, 2020. Clinical parameters relating to cancer history (type and treatment) and COVID‐19 were collected. The primary outcome was overall survival (OS). Secondary analyses were the association between clinical factors and severe COVID‐19 and OS. RESULTS: A total of 107 patients with cancer were diagnosed with COVID‐19, with a median age of 66 years (range, 37‐98 years). Lung (21 patients; 19.6%), gastrointestinal (20 patients; 18.7%), and genitourinary (20 patients; 18.7%) cancers were the most common cancer diagnoses. A total of 37 patients (34.6%) were receiving active anticancer treatment when diagnosed with COVID‐19, whereas 70 patients (65.4%) were on follow‐up. Overall, 52.3% of patients (56 patients) developed severe COVID‐19; this rate was found to be higher among patients receiving anticancer treatment than those on follow‐up (64.9% vs 45.7%), which corresponded to an inferior OS in the former subgroup of patients (hazard ratio, 3.365; 95% CI, 1.455‐7.782 [P = .005]). The detrimental effect of anticancer treatment on OS was found to be independent of exposure to systemic therapy (case fatality rate of 33.3% [systemic therapy] vs 43.8% [nonsystemic therapy]). CONCLUSIONS: The results of the current study demonstrated that >50.0% of infected patients with cancer are susceptible to severe COVID‐19. This risk is aggravated by simultaneous anticancer treatment and portends for a worse survival, despite treatment for COVID‐19.


title: Identification of a Novel Human Rhinovirus C Type by Antibody Capture VIDISCA-454

text: Causative agents for more than 30 percent of respiratory infections remain unidentified, suggesting that unknown respiratory pathogens might be involved. In this study, antibody capture VIDISCA-454 (virus discovery cDNA-AFLP combined with Roche 454 high-throughput sequencing) resulted in the discovery of a novel type of rhinovirus C (RV-C). The virus has an RNA genome of at least 7054 nt and carries the characteristics of rhinovirus C species. The gene encoding viral protein 1, which is used for typing, has only 81% nucleotide sequence identity with the closest known RV-C type, and, therefore, the virus represents the first member of a novel type, named RV-C54.


title: Mass Air Medical Repatriation of Coronavirus Disease 2019 Patients

text: Abstract Recent coronavirus disease 2019 (COVID-19) events have presented challenges to health care systems worldwide. Air medical movement of individuals with potential infectious disease poses unique challenges and threats to crews and receiving personnel. The US Department of Health and Human Services air medical evacuation teams of the National Disaster Medical System directly supported 39 flights, moving over 2,000 individuals. Infection control precautions focused on source and engineering controls, personal protective equipment, safe work practices to limit contamination, and containment of the area of potential contamination. Source control to limit transmission distance was used by requiring all passengers to wear masks (surgical masks for persons under investigation and N95 for known positives). Engineering controls used plastic sheeting to segregate and treat patients who developed symptoms while airborne. Crews used Tyvek (Dupont Richmond, VA) suits with booties and a hood, a double layer of gloves, and either a powered air-purifying respirator or an N95 mask with a face shield. For those outside the 6-ft range, an N95 mask and gloves were worn. Safe work practices were used, which included mandatory aircraft surface decontamination, airflow exchanges, and designated lavatories. Although most patients transported were stable, to the best of our knowledge, this represents the largest repatriation of potentially contagious patients in history without infection of any transporting US Department of Health and Human Services air medical evacuation crews.


title: Improved inference of time-varying reproduction numbers during infectious disease outbreaks

text: Abstract Accurate estimation of the parameters characterising infectious disease transmission is vital for optimising control interventions during epidemics. A valuable metric for assessing the current threat posed by an outbreak is the time-dependent reproduction number, i.e. the expected number of secondary cases caused by each infected individual. This quantity can be estimated using data on the numbers of observed new cases at successive times during an epidemic and the distribution of the serial interval (the time between symptomatic cases in a transmission chain). Some methods for estimating the reproduction number rely on pre-existing estimates of the serial interval distribution and assume that the entire outbreak is driven by local transmission. Here we show that accurate inference of current transmissibility, and the uncertainty associated with this estimate, requires: (i) up-to-date observations of the serial interval to be included, and; (ii) cases arising from local transmission to be distinguished from those imported from elsewhere. We demonstrate how pathogen transmissibility can be inferred appropriately using datasets from outbreaks of H1N1 influenza, Ebola virus disease and Middle-East Respiratory Syndrome. We present a tool for estimating the reproduction number in real-time during infectious disease outbreaks accurately, which is available as an R software package (EpiEstim 2.2). It is also accessible as an interactive, user-friendly online interface (EpiEstim App), permitting its use by non-specialists. Our tool is easy to apply for assessing the transmission potential, and hence informing control, during future outbreaks of a wide range of invading pathogens.


title: What is the experience from previous mass gathering events? Lessons for Zika virus and the Olympics 2016

text: Summary All previous experiences from different mass gathering show that vaccine preventable diseases is the most important infections like influenza, hepatitis A, polio and meningitis. Three mass gathering held in Africa during the Ebola outbreak accepted participants from West Africa and was able to handle the theoretical risk without any incident. Therefore we believe that the Olympic games in Rio de Janeiro should not be cancelled. The number of visitors to the games is a tiny fraction (1%) of other visitors to Zika endemic countries and it will have no measurable effect on the risk of spreading Zika virus, if the games was cancelled.


title: Phylogenetic and antigenic characterization of newly isolated porcine epidemic diarrhea viruses in Japan

text: Abstract To evaluate the mechanism by which a large outbreak of porcine epidemic diarrhea (PED) occurred in Japan, where the majority of sows are vaccinated, we isolated two new strains of PED virus (PEDV) from the intestines of piglets and found that they showed greater similarity to US isolates (group II PEDV) than to the Japanese vaccine strain (group I PEDV). We compared the antigenicity of the vaccine type strain and newly isolated strains by means of a neutralization test using sera from a number of pigs from various farms; the results revealed that they are antigenically similar. This is the first report of the similarity of group I and II viruses using sera from individual pigs vaccinated with group I virus. These data suggest that the large outbreak of PED in Japan cannot be attributed to inefficient vaccination but may be due to the extremely high virulence of the newly appearing viruses.


title: Norwalk virus binds to histo-blood group antigens present on gastroduodenal epithelial cells of secretor individuals

text: Abstract Background & Aims: Norwalk Virus (NV) is a member of the Caliciviridae family, which causes acute epidemic gastroenteritis in humans of all ages and its cellular receptors have not yet been characterized. Another calicivirus, Rabbit Hemorrhagic Disease Virus, attaches to H type 2 histo-blood group oligosaccharide present on rabbit epithelial cells. Our aim was to test if, by analogy, recombinant NV-like particles (rNV VLPs) use carbohydrates present on human gastroduodenal epithelial cells as ligands. Methods: Attachment of rNV VLPs was tested on tissue sections of the gastroduodenal junction and on saliva from individuals of known ABO, Lewis, and secretor phenotypes. It was also tested on human Caco-2 cells and on animal cell lines transfected with glycosyltransferases complementary DNA (cDNA). Competition experiments were performed with synthetic oligosaccharides and anticarbohydrate antibodies. Internalization was monitored by confocal microscopy. Results: Attachment of rNV VLPs to surface epithelial cells of the gastroduodenal junction as well as to saliva was detected, yet only from secretor donors. It was abolished by α1,2fucosidase treatment, and by competition with the H types 1 and 3 trisaccharides or with anti-H type 1 and anti-H types¾ antibodies. Transfection of CHO and TS/A cells with an α1,2fucosyltransferase cDNA allowed attachment of VLPs. These transfectants as well as differentiated Caco-2 cells expressing H type 1 structures internalized the bound particles. Conclusions: rNV VLPs use H type 1 and/or H types¾ as ligands on gastroduodenal epithelial cells of secretor individuals. GASTROENTEROLOGY 2002;122:1967-1977


title: Spike protein binding prediction with neutralizing antibodies of SARS-CoV-2

text: Coronavirus disease 2019 (COVID-19) is a new emerging human infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, also previously known as 2019-nCoV), originated in Wuhan seafood and animal market, China. Since December 2019, more than 69,000 cases of COVID-19 have been confirmed in China and quickly spreads to other counties. Currently, researchers put their best efforts to identify effective drugs for COVID-19. The neutralizing antibody, which binds to viral capsid in a manner that inhibits cellular entry of virus and uncoating of the genome, is the specific defense against viral invaders. In this study, we investigate to identify neutralizing antibodies that can bind to SARS-CoV-2 Sipke (S) protein and interfere with the interaction between viral S protein and a host receptor by bioinformatic methods. The sequence analysis of S protein showed two major differences in the RBD region of the SARS-CoV-2 S protein compared to SARS-CoV and SARS-CoV related bat viruses (btSARS-CoV). The insertion regions were close to interacting residues with the human ACE2 receptor. Epitope analysis of neutralizing antibodies revealed that SARS-CoV neutralizing antibodies used conformational epitopes, whereas MERS-CoV neutralizing antibodies used a common linear epitope region, which contributes to form the β-sheet structure in MERS-CoV S protein and deleted in SARS-CoV-2 S protein. To identify effective neutralizing antibodies for SARS-CoV-2, the binding affinities of neutralizing antibodies with SARS-CoV-2 S protein were predicted and compared by antibody-antigen docking simulation. The result showed that CR3022 neutralizing antibody from human may have higher binding affinity with SARS-CoV-2 S protein than SARS-CoV S protein. We also found that F26G19 and D12 mouse antibodies could bind to SARS-CoV S protein with high affinity. Our findings provide crucial clues towards the development of antigen diagnosis, therapeutic antibody, and the vaccine against SARS-CoV-2.


title: Human Metapneumovirus

text: Respiratory tract infections (RTI) are the leading cause of death in low-income countries and the second leading cause of death worldwide in children less than 5 years old. Most RTI are viral. Human metapneumovirus (hMPV) was discovered in 2001 in routine viral cultures of respiratory specimens from children with RTI and has been implicated as a common cause of RTI in children and adults and a cause of severe disease in immunocompromised hosts. This article describes the microbiology, epidemiology, clinical presentation, pathogenesis, diagnosis, treatment, prognosis, long-term outcome, immunity and reinfection of hMPV.


Delayed pulmonary abscess following COVID-19 pneumonia: a case report


title: The Role of Viral Population Diversity in Adaptation of Bovine Coronavirus to New Host Environments

text: The high mutation rate of RNA viruses enables a diverse genetic population of viral genotypes to exist within a single infected host. In-host genetic diversity could better position the virus population to respond and adapt to a diverse array of selective pressures such as host-switching events. Multiple new coronaviruses, including SARS, have been identified in human samples just within the last ten years, demonstrating the potential of coronaviruses as emergent human pathogens. Deep sequencing was used to characterize genomic changes in coronavirus quasispecies during simulated host-switching. Three bovine nasal samples infected with bovine coronavirus were used to infect human and bovine macrophage and lung cell lines. The virus reproduced relatively well in macrophages, but the lung cell lines were not infected efficiently enough to allow passage of non lab-adapted samples. Approximately 12 kb of the genome was amplified before and after passage and sequenced at average coverages of nearly 950×(454 sequencing) and 38,000×(Illumina). The consensus sequence of many of the passaged samples had a 12 nucleotide insert in the consensus sequence of the spike gene, and multiple point mutations were associated with the presence of the insert. Deep sequencing revealed that the insert was present but very rare in the unpassaged samples and could quickly shift to dominate the population when placed in a different environment. The insert coded for three arginine residues, occurred in a region associated with fusion entry into host cells, and may allow infection of new cell types via heparin sulfate binding. Analysis of the deep sequencing data indicated that two distinct genotypes circulated at different frequency levels in each sample, and support the hypothesis that the mutations present in passaged strains were “selected” from a pre-existing pool rather than through de novo mutation and subsequent population fixation.


title: Inhibition of alcohol dehydrogenase by bismuth

text: Abstract Bismuth compounds have been widely used for the treatment of ulcers and Helicobacter pylori infection, and enzyme inhibition was thought to be crucial for bismuth anti-microbial activity. We have investigated the interaction of colloidal bismuth subcitrate (CBS) with alcohol dehydrogenase and our results demonstrate that bismuth can effectively inhibit the enzyme. Kinetic analysis revealed that CBS acted as a non-competitive inhibitor of yeast alcohol dehydrogenase. Both UV–vis and fluorescence data show that interaction of CBS with the enzyme exhibits biphasic processes. Bismuth can replace only half of Zn(II) from the enzyme (i.e., about one Zn(II) per monomer). Surprisingly, binding of CBS also induces the enzyme dissociation from its native form, tetramer into dimers. The inhibition of Bi(III) on the enzyme is probably due to its direct interference with the zinc sites. This study is likely to provide an insight into the mechanism of action of bismuth drugs.


Response by Zhang et al to Letter Regarding Article, “Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19”


Special care dentistry in the world of COVID‐19


title: A proposal for the return to routine endoscopy during the COVID-19 pandemic

text: Abstract In response to the COVID-19 pandemic, many jurisdictions and gastroenterological societies around the world have suspended nonurgent endoscopy. Subject to country-specific variability, it is projected that with current mitigation measures in place, the peak incidence of active COVID-19 infections may be delayed by over 6 months. Although this aims to prevent the overburdening of healthcare systems, prolonged deferral of elective endoscopy will become unsustainable. Herein, we propose that by incorporating readily available point-of-care tests and conducting accurate clinical risk assessments, a safe and timely return to elective endoscopy is feasible. Our algorithm not only focuses on the safety of patients and healthcare workers, but also assists in rationalizing the use of invaluable resources such as personal protective equipment.


title: The health and management of poultry production

text: Abstract The poultry industry in the USA is a fully integrated system of animal agriculture. Each company has control over the bird husbandry and health management aspects of production, including the use of antimicrobial agents. The three segments of the industry—broiler chickens, turkeys, and layer chickens—have few antibiotics available for the therapeutic treatment of bacterial diseases. Prior to approval of the fluoroquinolones, tetracyclines were the major antibiotics approved for the treatment of the most economically important disease in broiler chickens and turkeys, Escherichia coli airsacculitis. This resulted in levels of resistance to the tetracyclines in clinical E. coli isolates in excess of 90%.The integrated nature of the poultry industry lends itself well to preventive medicine utilizing the tools of biosecurity and vaccination. Therefore, very few flocks of birds require antibiotic therapy. When a flock must be treated, the poultry veterinarian will usually base the recommendation of the drug to use on culture and antibiogram results.


title: Adult ICU Triage During the Coronavirus Disease 2019 Pandemic: Who Will Live and Who Will Die? Recommendations to Improve Survival

text: OBJECTIVES: Coronavirus disease 2019 patients are currently overwhelming the world’s healthcare systems. This article provides practical guidance to front-line physicians forced to make critical rationing decisions. DATA SOURCES: PubMed and Medline search for scientific literature, reviews, and guidance documents related to epidemic ICU triage including from professional bodies. STUDY SELECTION: Clinical studies, reviews, and guidelines were selected and reviewed by all authors and discussed by internet conference and email. DATA EXTRACTION: References and data were based on relevance and author consensus. DATA SYNTHESIS: We review key challenges of resource-driven triage and data from affected ICUs. We recommend that once available resources are maximally extended, triage is justified utilizing a strategy that provides the greatest good for the greatest number of patients. A triage algorithm based on clinical estimations of the incremental survival benefit (saving the most life-years) provided by ICU care is proposed. “First come, first served” is used to choose between individuals with equal priorities and benefits. The algorithm provides practical guidance, is easy to follow, rapidly implementable and flexible. It has four prioritization categories: performance score, ASA score, number of organ failures, and predicted survival. Individual units can readily adapt the algorithm to meet local requirements for the evolving pandemic. Although the algorithm improves consistency and provides practical and psychologic support to those performing triage, the final decision remains a clinical one. Depending on country and operational circumstances, triage decisions may be made by a triage team or individual doctors. However, an experienced critical care specialist physician should be ultimately responsible for the triage decision. Cautious discharge criteria are proposed acknowledging the difficulties to facilitate the admission of queuing patients. CONCLUSIONS: Individual institutions may use this guidance to develop prospective protocols that assist the implementation of triage decisions to ensure fairness, enhance consistency, and decrease provider moral distress.


title: Tracing the transmission of bovine coronavirus infections in cattle herds based on S gene diversity

text: Abstract Bovine coronavirus (BCoV) is found worldwide and causes respiratory infections and diarrhoea in calves and adult cattle. In order to investigate the molecular epidemiology of BCoV, 27 reverse transcription polymerase chain reaction (RT-PCR) positive samples from 25 cattle herds in different parts of Sweden were analysed. A 1038-nucleotide fragment was PCR amplified and directly sequenced. The analysed BCoV strains showed a high sequence identity, regardless of whether they were obtained from outbreaks of respiratory disease or diarrhoea or from calves or adult cattle. Circulation of an identical BCoV strain during a 4-month period was demonstrated in calves in one dairy herd. In a regional epizootic of winter dysentery in Northern Sweden, highly similar BCoV strains were detected. In the Southern and Central regions, several genotypes of BCoV circulated contemporaneously, indicating that in these regions, which had a higher density of cattle than the Northern regions, more extensive transmission of the virus was occurring. Identical BCoV sequences supported the epidemiological data that inter-herd contact through purchased calves was important. Swedish BCoV strains unexpectedly showed a high homology with recently detected Italian strains. This study shows that molecular analysis of the spike (S) glycoprotein gene of BCoV can be a useful tool to support or rule out suspected transmission routes.


title: Temporal Dynamics of COVID-19 Outbreak and Future Projections: A Data-Driven Approach

text: Long-term predictions for an ongoing epidemic are typically performed using epidemiological models that predict the timing of the peak in infections followed by its decay using non-linear fits from the available data. The curves predicted by these methods typically follow a Gaussian distribution with a decay rate of infections similar to the climbing rate before the peak. However, as seen from the recent COVID-19 data from the US and European countries, the decay in the number of infections is much slower than their increase before the peak. Therefore, the estimates of the final epidemic size from these models are often underpredicted. In this work, we propose two data-driven models to improve the forecasts of the epidemic during its decay. These two models use Gaussian and piecewise-linear fits of the infection rate respectively during the deceleration phase, if available, to project the future course of the pandemic. For countries, which are not yet in the decline phase, these models use the peak predicted by epidemiological models but correct the infection rate to incorporate a realistic slow decline based on the trends from the recent data. Finally, a comparative study of predictions using both epidemiological and data-driven models is presented for a few most affected countries.


Response by Cohen et al to Letter Regarding Article, “Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19”


The COVID‐19 pandemic: What can bioengineers, computer scientists and big data specialists bring to the table


title: Pilgrimage and COVID-19: the risk among returnees from Muslim countries

text: Abstract Epidemic of COVID-19 has spread over the world. We confirmed 6 Muslim pilgrims with COVID-19 among the passages of a flight from Pakistan after border inspection in Guangzhou, China. We alerted the home countries to early prepare for the risk among the returning pilgrims. And the strategies of inspection and quarantine should cover those from all the Muslim countries, but not limited to Saudi Arabia.


title: Reasoning with rough description logics: An approximate concepts approach

text: Abstract The current research progress and the existing problems of uncertain or imprecise knowledge representation and reasoning in description logics are analyzed in this paper. Approximate concepts are introduced to description logics based on rough set theory, and a kind of new rough description logic RDL AC (rough description logic based on approximate concepts) is proposed based on approximate concepts. The syntax, semantics and properties of the RDL AC are given. It is proved that the approximate concept satisfiability (definitely satisfiability and possibly satisfiability) reasoning problem and approximate concepts rough subsumption reasoning problem w.r.t. rough TBox in RDL AC may be reduced to the concept satisfiability reasoning problem in (almost) standard ALC (the description logic that provides the Boolean concept constructors plus the existential and universal restriction constructors). The works of this paper provide logic foundations for approximate ontologies and theoretical foundations for reasoning algorithms of more expressive rough description logics including approximate concepts, number restrictions, nominals, inverse roles and role hierarchies.


title: Viral agents causing lower respiratory tract infections in hospitalized children: evaluation of the Speed-Oligo® RSV assay for the detection of respiratory syncytial virus

text: Respiratory syncytial virus (RSV) is the viral agent which is more frequently involved in lower respiratory tract infections (LRTIs) in infants under 1 year of age in developed countries. A new oligochromatographic assay, Speed-Oligo® RSV, was designed and optimized for the specific detection and identification of RSV subtypes A and B. The test was evaluated in 289 clinical samples from 169 hospitalized children using an immunochromatography (IC) test, virus isolation by culture, and an in-house real-time polymerase chain reaction (RT-PCR). Other viruses causing LRTIs were investigated by cell culture or PCR-based tests. Sixty-two patients were infected by RSV (36.7%). In addition, adenovirus, influenza B, parainfluenza 2, and human metapneumovirus were detected in rates ranging from 5 to 8%. A proportion of 10.1% of the patients had mixed infections. The sensitivity, specificity, and positive and negative predictive values were, respectively, 94.9, 99.4, 98.9, and 97.4% for Speed-Oligo® RSV, 92.9, 96.3, 92.9, and 96.3% for RT-PCR/RSV, and 58.4, 98.1, 93.3, and 82.6% for IC. Our rates of viral detection and co-infection were similar to those of previously reported series. Finally, we find that Speed-Oligo® RSV is a rapid and easy-to-perform technique for the detection of RSV and the identification of subtypes A and B.


COVID‐19 puts the spotlight on food insecurity in rural and remote Australia


title: Immune Responses to Middle East Respiratory Syndrome Coronavirus During the Acute and Convalescent Phases of Human Infection

text: BACKGROUND: An understanding of immune responses against the Middle East respiratory syndrome (MERS) is important for the development of treatments and preventive measures. Here, we investigated the spectrum of immune responses occurring in patients with MERS during the early period of infection. METHODS: We obtained peripheral blood samples from 27 hospitalized patients recruited during the epidemic that occurred in 2015 in South Korea. Plasma cytokines/chemokines and antibodies were quantified. Virus-specific T cells were examined by intracellular cytokine staining after stimulation of peripheral blood mononuclear cells with overlapping peptides spanning whole virus structural proteins. RESULTS: At the acute phase of infection, elevated levels of plasma proinflammatory cytokines/chemokines were detected in proportion to the severity of the disease. Distinctively high frequencies of MERS coronavirus–reactive CD8(+) T cells were also observed in patients with severe/moderate illness, whereas antibody and CD4(+) T-cell responses were minimally detected at this stage. At the convalescent phase, disease severity–dependent antibody responses emerged and antigen-reactive cells were identified in both T-cell subsets. These T cells belonged to the T-helper 1 or type 1 cytotoxic T cell subtypes. While CD8(+) T cells responded preferentially to the viral S protein compared with E/M/N proteins, especially at the acute stage, slightly more CD4(+) T cells recognized E/M/N proteins compared with S protein at the convalescent phase. CONCLUSIONS: Our findings show an association between the early CD8(+) T-cell response and the severity of the infection, and also provide basic information that may help to prepare effective control strategies for MERS in humans.