title: Counter-regulatory renin–angiotensin system in cardiovascular disease

text: The renin–angiotensin system is an important component of the cardiovascular system. Mounting evidence suggests that the metabolic products of angiotensin I and II — initially thought to be biologically inactive — have key roles in cardiovascular physiology and pathophysiology. This non-canonical axis of the renin–angiotensin system consists of angiotensin 1–7, angiotensin 1–9, angiotensin-converting enzyme 2, the type 2 angiotensin II receptor (AT(2)R), the proto-oncogene Mas receptor and the Mas-related G protein-coupled receptor member D. Each of these components has been shown to counteract the effects of the classical renin–angiotensin system. This counter-regulatory renin–angiotensin system has a central role in the pathogenesis and development of various cardiovascular diseases and, therefore, represents a potential therapeutic target. In this Review, we provide the latest insights into the complexity and interplay of the components of the non-canonical renin–angiotensin system, and discuss the function and therapeutic potential of targeting this system to treat cardiovascular disease.


title: Healthcare-associated infections: the hallmark of Middle East respiratory syndrome coronavirus with review of the literature

text: Summary Middle East respiratory syndrome coronavirus (MERS-CoV) is capable of causing acute respiratory illness. Laboratory-confirmed MERS-CoV cases may be asymptomatic, have mild disease, or have a life-threatening infection with a high case fatality rate. There are three patterns of transmission: sporadic community cases from presumed non-human exposure, family clusters arising from contact with an infected family index case, and healthcare-acquired infections among patients and from patients to healthcare workers. Healthcare-acquired MERS infection has become a well-known characteristic of the disease and a leading means of spread. The main factors contributing to healthcare-associated outbreaks include delayed recognition, inadequate infection control measures, inadequate triaging and isolation of suspected MERS or other respiratory illness patients, crowding, and patients remaining in the emergency department for many days. A review of the literature suggests that effective control of hospital outbreaks was accomplished in most instances by the application of proper infection control procedures. Prompt recognition, isolation and management of suspected cases are key factors for prevention of the spread of MERS. Repeated assessments of infection control and monitoring of corrective measures contribute to changing the course of an outbreak. Limiting the number of contacts and hospital visits are also important factors to decrease the spread of infection.


Zika virus and neurological disease—approaches to the unknown


title: Flu in wild birds sparks fears of mutating virus

text: Experts pressure China for samples that can be analysed.


title: Homologous recombination shapes the genetic diversity of African swine fever viruses

text: Abstract The African swine fever virus (ASFV) has severely influenced the swine industry of the world. Currently, there is no effective vaccine or drugs against the ASFV. How to effectively control the virus is challenging. In this study, we have analyzed all the publicly available ASFV genomes and demonstrated that there was a large genetic diversity of ASFV genomes. Interestingly, the genetic diversity was mainly caused by extensive genomic insertions and/or deletions (indels) instead of the point mutations. Further analyses showed that the indels may be attributed much to the homologous recombination, as supported by significant associations between the occurrence of extensive recombination events and the indels in the ASFV genomes. Besides, the homologous recombination also led to changes of gene content of ASFVs. Finally, repeated elements of dozens of nucleotides in length were observed to widely distribute and cluster in the adjacent positions of ASFV genomes, which may facilitate the occurrence of homologous recombination. This work highlighted the importance of homologous recombination in shaping the genetic diversity of the ASFVs, and could help understand the evolution of the virus.


title: Saliva sample as a non-invasive specimen for the diagnosis of coronavirus disease-2019 (COVID-19): a cross-sectional study

text: OBJECTIVES: Amid the increasing number of pandemic coronavirus disease 2019 (COVID-19) cases, there is a need for a quick and easy method to obtain a non-invasive sample for the detection of this novel coronavirus 2019 (SARS-CoV-2). We aimed to investigate the potential use of saliva samples as a non-invasive tool for the diagnosis of COVID-19. METHODS: From 27 March to 4 April, 2020, we prospectively collected saliva samples and a standard nasopharyngeal and throat swab in persons seeking care at an acute respiratory infection clinic in a university hospital during the outbreak of COVID-19. Real-time polymerase chain reaction (RT-PCR) was performed, and the results of the two specimens were compared. RESULTS: Two-hundred pairs of the samples were collected. Sixty-nine (34.5%) patients were male, and the median (interquartile) age was 36 (28-48) years. Using nasopharyngeal and throat swab RT-PCR as the reference standard, the prevalence of COVID-19 diagnosed by nasopharyngeal and throat swab RT-PCR was 9.5%. The sensitivity and specificity of the saliva sample RT-PCR were 84.2% [95% confidence interval (CI) 60.4%-96.6%], and 98.9% (95% CI 96.1%-99.9%), respectively. An analysis of the agreement between the two specimens demonstrated 97.5% observed agreement (kappa coefficient 0.851, 95% CI 0.723-0.979; p <0.001). CONCLUSIONS: Saliva might be an alternative specimen for the diagnosis of COVID-19. The collection is non-invasive, and non-aerosol generating. This method could facilitate the diagnosis of the disease, given the simplicity of specimen collection and good diagnostic performance.


title: Characteristic CT findings distinguishing 2019 novel coronavirus disease (COVID-19) from influenza pneumonia

text: OBJECTIVES: To investigate the different CT characteristics which may distinguish influenza from 2019 coronavirus disease (COVID-19). METHODS: A total of 13 confirmed patients with COVID-19 were enrolled from January 16, 2020, to February 25, 2020. Furthermore, 92 CT scans of confirmed patients with influenza pneumonia, including 76 with influenza A and 16 with influenza B, scanned between January 1, 2019, to February 25, 2020, were retrospectively reviewed. Pulmonary lesion distributions, number, attenuation, lobe predomination, margin, contour, ground-glass opacity involvement pattern, bronchial wall thickening, air bronchogram, tree-in-bud sign, interlobular septal thickening, intralobular septal thickening, and pleural effusion were evaluated in COVID-19 and influenza pneumonia cohorts. RESULTS: Peripheral and non-specific distributions in COVID-19 showed a markedly higher frequency compared with the influenza group (p < 0.05). Most lesions in COVID-19 showed balanced lobe localization, while in influenza pneumonia they were predominantly located in the inferior lobe (p < 0.05). COVID-19 presented a clear lesion margin and a shrinking contour compared with influenza pneumonia (p < 0.05). COVID-19 had a patchy or combination of GGO and consolidation opacities, while a cluster-like pattern and bronchial wall thickening were more frequently seen in influenza pneumonia (p < 0.05). The lesion number and attenuation, air bronchogram, tree-in-bud sign, interlobular septal thickening, and intralobular septal thickening were not significantly different between the two groups (all p > 0.05). CONCLUSIONS: Though viral pneumonias generally show similar imaging features, there are some characteristic CT findings which may help differentiating COVID-19 from influenza pneumonia. KEY POINTS: • CT can play an early warning role in the diagnosis of COVID-19 in the case of no epidemic exposure. • CT could be used for the differential diagnosis of influenza and COVID-19 with satisfactory accuracy. • COVID-19 had a patchy or combination of GGO and consolidation opacities with peripheral distribution and balanced lobe predomination.


The Crucible of Crisis Fellows’-in-Training and Early Career Cardiologists’ Responses to the COVID-19 Pandemic


title: Small Non-coding RNAs Associated with Viral Infectious Diseases of Veterinary Importance: Potential Clinical Applications

text: MicroRNAs (miRNAs) represent a class of small non-coding RNA (sncRNA) molecules that can regulate mRNAs by inducing their degradation or by blocking translation. Considering that miRNAs are ubiquitous, stable, and conserved across animal species, it seems feasible to exploit them for clinical applications. Unlike in human viral diseases, where some miRNA-based molecules have progressed to clinical application, in veterinary medicine, this concept is just starting to come into view. Clinically, miRNAs could represent powerful diagnostic tools to pinpoint animal viral diseases and/or prognostic tools to follow up disease progression or remission. Additionally, the possible consequences of miRNA dysregulation make them potential therapeutic targets and open the possibilities to use them as tools to generate viral disease-resistant livestock. This review presents an update of preclinical studies on using sncRNAs to combat viral diseases that affect pet and farm animals. Moreover, we discuss the possibilities and challenges of bringing these bench-based discoveries to the veterinary clinic.


title: A register-based study of the antimicrobial usage in Danish veal calves and young bulls

text: Abstract High antimicrobial usage and multidrug resistance have been reported in veal calves in Europe. This may be attributed to a high risk of disease as veal calves are often purchased from numerous dairy herds, exposed to stress related to the transport and commingling of new animals, and fed a new ration. In this study, we used national register data to characterize the use of antimicrobials registered for large Danish veal calf and young bull producing herds in 2014. A total of 325 herds with veal calf and potentially young bull production were identified from the Danish Cattle database. According to the national Danish database on drugs for veterinary use (VetStat), a total of 537,399 Animal Daily Doses (ADD200) were registered for these 325 herds during 2014. The amount of antimicrobials registered in 2014 varied throughout the year, with the highest amounts registered in autumn and winter. Antimicrobials were registered for respiratory disorders (79%), joints/limbs/CNS disorders (17%), gastrointestinal disorders (3.7%) and other disorders (0.3%). Of the registered antimicrobials, 15% were for oral and 85% for parenteral administration. Long-acting formulations with a therapeutic effect of more than 48h covered 58% of the drugs for parenteral use. Standardized at the herd-level, as ADD200/100 calves/day, antimicrobial use distributed as median [CI95%] for starter herds (n=22): 2.14 [0.19;7.58], finisher herds (n=24): 0.48 [0.00;1.48], full-line herds (n=183): 0.78 [0.05;2.20] and herds with an inconsistent pattern of movements (n=96): 0.62 [0.00;2.24]. Full-line herds are herds, which purchase calves directly from a dairy herd and raise them to slaughter. Furthermore, we performed a risk factor analysis on the 183 herds with a full-line production. Here, we investigated, whether the number of suppliers, the number of calves purchased, the frequency of purchase, the average age at introduction, the average time in the herd and vaccination influenced the amount of antimicrobials used in the herds. The final multivariable regression analysis revealed that the number of calves introduced was positively associated with the antimicrobial use in the herd.


Safer Through Surgery ASMBS statement regarding Metabolic and Bariatric Surgery during the COVID-19 pandemic.


title: Identification and characterization of a neutralizing-epitope-containing spike protein fragment in turkey coronavirus

text: Little is known about the neutralizing epitopes in turkey coronavirus (TCoV). The spike (S) protein gene of TCoV was divided into 10 fragments to identify the antigenic region containing neutralizing epitopes. The expression and antigenicity of S fragments was confirmed by immunofluorescence antibody (IFA) assay using an anti-histidine monoclonal antibody or anti-TCoV serum. Polyclonal antibodies raised against expressed S1 (amino acid position 1 to 573 from start codon of S protein), 4F/4R (482-678), 6F/6R (830-1071), or Mod4F/Epi4R (476-520) S fragment recognized native S1 protein and TCoV in the intestines of TCoV-infected turkey embryos. Anti-TCoV serum reacted with recombinant 4F/4R, 6F/6R, and Mod4F/Epi4R in a western blot. The results of a virus neutralization assay indicated that the carboxyl terminal region of the S1 protein (Mod4F/Epi4R) or the combined carboxyl terminal S1 and amino terminal S2 protein (4F/4R) possesses the neutralizing epitopes, while the S2 fragment (6F/6R) contains antigenic epitopes but not neutralizing epitopes.


title: No impact of early real-time PCR screening for respiratory viruses on length of stay and use of antibiotics in elderly patients hospitalized with symptoms of a respiratory tract infection in a single center in Norway

text: We tested the hypothesis that the results of real-time polymerase chain reaction (PCR) analyses for respiratory viruses would reduce antibiotic treatment and length of stay in elderly patients hospitalized with respiratory infections. Within 24 h of hospital admission, a total of 922 patients aged ≥60 years were interviewed for symptoms of ongoing respiratory tract infection. Symptomatic patients were swabbed for oropharyngeal/nasopharyngeal presence of viral pathogens immediately by members of the study group. During a 2-month period, non-symptomatic volunteers among interviewed patients were swabbed as well (controls). Oropharyngeal/nasopharyngeal swabs were analyzed with real-time PCR for nine common respiratory viruses. A total of 147 out of 173 symptomatic patients and 56 non-symptomatic patients (controls) agreed to participate in the study. The patients were allocated to three cohorts: (1) symptomatic and PCR-positive (S/PCR+), (2) symptomatic and PCR-negative (S/PCR−), or (3) non-symptomatic and PCR-negative (control). There were no non-symptomatic patients with a positive PCR result. A non-significant difference in the frequency of empiric antibiotic administration was found when comparing the S/PCR+ to the S/PCR− cohort; 16/19 (84 %) vs. 99/128 (77 %) (χ(2) = 0.49). Antibiotic treatment was withdrawn in only two patients in the S/PCR+ cohort after receiving a positive viral diagnosis. The length of stay did not significantly differ between the S/PCR+ and the S/PCR− groups. We conclude that, at least in our general hospital setting, access to early viral diagnosis by real-time PCR had little impact on the antimicrobial treatment or length of hospitalization of elderly patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10096-013-1963-0) contains supplementary material, which is available to authorized users.


title: A comparative study on the clinical features of COVID-19 pneumonia to other pneumonias

text: BACKGROUND: A novel coronavirus (2019-nCoV) has raised world concern since it emerged in Wuhan Hubei China in December, 2019. The infection may result into severe pneumonia with clusters illness onsets. Its impacts on public health make it paramount to clarify the clinical features with other pneumonias. METHODS: Nineteen 2019-nCoV pneumonia (NCOVID-19) and fifteen other pneumonia patients (NON-NCOVID-19) in out of Hubei places were involved in this study. Both NCOVID-19 and NON-NCOVID-19 patients were confirmed to be infected in throat swabs or/and sputa with or without 2019-nCoV by real-time RT-PCR. We analyzed the demographic, epidemiological, clinical, and radiological features from those patients, and compared the difference between NCOVID-19 and NON-NCOVID-19. RESULTS: All patients had a history of exposure to confirmed case of 2019-nCoV or travel to Hubei before illness. The median duration, respectively, was 8 (IQR:6~11) and 5 (IQR:4~11) days from exposure to onset in NCOVID-19 and NON-NCOVID-19. The clinical symptoms were similar between NCOVID-19 and NON-NCOVID-19. The most common symptoms were fever and cough. Fifteen (78.95%) NCOVID-19 but 4 (26.67%) NON-NCOVID-19 patients had bilateral involvement while 17 (89.47%) NCOVID-19 but 1 (6.67%) NON-NCOVID-19 patients had multiple mottling and ground-glass opacity of chest CT images. Compared to NON-NCOVID-19, NCOVID-19 present remarkably more abnormal laboratory tests including AST, ALT, γ-GT, LDH and α-HBDH. CONCLUSION: The 2019-nCoV infection caused similar onsets to other pneumonias. CT scan may be a reliable test for screening NCOVID-19 cases. Liver function damage is more frequent in NCOVID-19 than NON-NCOVID-19 patients. LDH and α-HBDH may be considerable markers for evaluation of NCOVID-19.


title: Modeling behavioral change and COVID-19 containment in Mexico: A trade-off between lockdown and compliance

text: Abstract Sanitary Emergency Measures (SEM) were implemented in Mexico on March 30th, 2020 requiring the suspension of non-essential activities. This action followed a Healthy Distance Sanitary action on March 23rd, 2020. The aim of both measures was to reduce community transmission of COVID-19 in Mexico by lowering the effective contact rate. Using a modification of the Kermack-McKendrick SEIR model we explore the effect of behavioral changes required to lower community transmission by introducing a time-varying contact rate, and the consequences of disease spread in a population subject to suspension of non-essential activities. Our study shows that there exists a trade-off between the proportion of the population under SEM and the average time an individual is committed to all the behavioral changes needed to achieve an effective social distancing. This trade-off generates an optimum value for the proportion of the population under strict mitigation measures, significantly below 1 in some cases, that minimizes maximum COVID-19 incidence. We study the population-level impact of three key factors: the implementation of behavior change control measures, the time horizon necessary to reduce the effective contact rate and the proportion of people under SEM in combating COVID-19. Our model is fitted to the available data. The initial phase of the epidemic, from February 17th to March 23rd, 2020, is used to estimate the contact rates, infectious periods and mortality rate using both confirmed cases (by date of symptoms initiation), and daily mortality. Data on deaths after march 23rd, 2020 is used to estimate the mortality rate after the mitigation measures are implemented. Our simulations indicate that the most likely dates for maximum incidence are between late May and early June, 2020 under a scenario of high SEM compliance and low SEM abandonment rate.


title: Chapter 16 Biology and Diseases of Swine

text: Swine are used in biomedical research as models for biomedical research and for teaching. This chapter covers normative biology and behavior along with common and emerging swine diseases. Xenotransplantation is discussed along with similarities and differences of swine immunology.


title: How Should the Rehabilitation Community Prepare for 2019-nCoV?

text: Abstract With the 2019-nCoV pandemic spreading quickly in USA and the world, it is urgent that the rehabilitation community quickly understands the epidemiology of the virus and what we can and must do to face this microbial adversary at the early stages of this likely long global pandemic. The 2019-nCoV is a novel virus so the majority of world’s population does not have prior immunity to it. It is more infectious and fatal than seasonal influenza, and definitive treatment and a vaccine are months away. Our arsenal against it are currently mainly social distancing and infection control measures.


title: Le bocavirus humain (HboV) un nouveau pathogene respiratoire?

text: Summary A new virus has been recently identified by molecular biology technics in respiratory samples collected from young children with respiratory disease. This virus is a new member of the Parvoviridae family and has been classified in the Bocavirus genus. This virus named human bocavirus (HboV) is genetically related to the bovine parvovirus and the canine minus virus that belong to the Bocavirus genus. Recent studies conducted in different countries showed that this virus is found in 3 to 10 % of children with respiratory disease worldwide with no real seasonal distribution and that it is frequently associated with other respiratory pathogens. Genetic analysis indicated that this virus probably includes only one type. The clinical signs are not different from those caused by other respiratory viruses. The exact role played by this virus in human diseases needs to be further investigated.


title: Correction: Impact of COVID-19 on ophthalmic specialist training in the United Kingdom—the trainees’ perspective

text: An amendment to this paper has been published and can be accessed via a link at the top of the paper.


title: In silico studies on the comparative characterization of the interactions of SARS‐CoV‐2 spike glycoprotein with ACE‐2 receptor homologs and human TLRs

text: Coronavirus disease‐2019 (COVID‐19) outbreak due to novel coronavirus or severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has come out as a major threat for mankind in recent times. It is continually taking an enormous toll on mankind by means of increasing number of deaths, associated comorbidities, and socioeconomic loss around the globe. Unavailability of chemotherapeutics/vaccine has posed tremendous challenges to scientists and doctors for developing an urgent therapeutic strategy. In this connection, the present in silico study aims to understand the sequence divergence of spike protein (the major infective protein of SARS‐CoV‐2), its mode of interaction with the angiotensin‐converting enzyme‐2 receptor (ACE2) receptor of human and related animal hosts/reservoir. Moreover, the involvement of the human Toll‐like receptors (TLRs) against the spike protein has also been demonstrated. Our data indicated that the spike glycoprotein of SARS‐CoV‐2 is phylogenetically close to bat coronavirus and strongly binds with ACE2 receptor protein from both human and bat origin. We have also found that cell surface TLRs, especially TLR4 is most likely to be involved in recognizing molecular patterns from SARS‐CoV‐2 to induce inflammatory responses. The present study supported the zoonotic origin of SARS‐CoV‐2 from a bat and also revealed that TLR4 may have a crucial role in the virus‐induced inflammatory consequences associated with COVID‐19. Therefore, selective targeting of TLR4‐spike protein interaction by designing competitive TLR4‐antagonists could pave a new way to treat COVID‐19. Finally, this study is expected to improve our understanding on the immunobiology of SARS‐CoV‐2 and could be useful in adopting spike protein, ACE2, or TLR‐guided intervention strategy against COVID‐19 shortly.


COVID-19 et Greffe de Cellules Souches Hématopoïétiques: Recommandations


title: Molecular characterization of low pathogenic avian influenza viruses, isolated from food products imported into Singapore

text: Abstract We have completed the genetic characterization of all eight gene segments for four low pathogenic avian influenza (LPAI) viruses. The objective of this study was to detect the presence of novel signatures that may serve as early warning indicators of the conversion of LPAI viruses to high pathogenic avian influenza (HPAI) viruses. This study included three H5N2 and one H5N3 viruses that were isolated from live poultry imported into Singapore as part of the national avian influenza virus (AIV) surveillance program. Based on the molecular criterion of the World Organisation for Animal Health (OIE), sequence analysis with the translated amino acid (aa) sequence of the hemagglutinin (HA) gene revealed the absence of multibasic aa at the HA cleavage site, identifying all four virus isolates as LPAI. Detailed phylogenetic tree analyses using the HA and neuraminidase (NA) genes clustered these isolates in the Eurasian H5 lineage, but away from the HPAI H5 subtypes. This analysis further revealed that the internal genes clustered to different avian and swine subtypes, suggesting that the four isolates may possibly share their ancestry with these different influenza subtypes. Our results suggest that the four LPAI isolates in this study contained mainly avian signatures, and the phylogenetic tree for the internal genes further suggests the potential for reassortment with other different circulating avian subtypes. This is the first comprehensive report on the genetic characterization of LPAI H5N2/3 viruses isolated in South-East Asia.


title: Reduced expression of COVID-19 host receptor, ACE2 is associated with small bowel inflammation, more severe disease, and response to anti-TNF therapy in Crohn’s disease

text: Angiotensin-Converting Enzyme 2 (ACE2) has been identified as the host receptor for SARS-coronavirus 2 (SARS-CoV-2) which has infected millions world-wide and likely caused hundreds of thousands of deaths. Utilizing transcriptomic data from four cohorts taken from Crohn’s disease (CD) and non-inflammatory bowel disease (IBD) subjects, we observed evidence of increased ACE2 mRNA in ileum with demographic features that have been associated with poor outcomes in COVID-19 including age and raised BMI. ACE2 was downregulated in CD compared to controls in independent cohorts. Within CD, ACE2 expression was reduced in inflamed ileal tissue and also remarkably, from un-involved tissue in patients with a worse prognosis in both adult and pediatric cohorts. In active CD, small bowel ACE2 expression was restored by anti-TNF therapy particularly in anti-TNF responders. Collectively our data suggest that ACE2 downregulation is associated with inflammation and worse outcomes in CD.


title: Usefulness of national respiratory virus surveillance data for clinicians who manage adult patients

text: The Korean Centers for Disease Control and Prevention (KCDC) provides weekly respiratory virus (RV) surveillance reports on its website (the KCDC data). Clinicians in clinical settings wherein the use of PCR for RVs is not a routine laboratory test for adult patients with acute respiratory illness (ARI) may question the clinical utility of such a national RV surveillance dataset in predicting RV outbreaks among their adult patients. We compared the KCDC data to the RV PCR data of adult patients who visited a tertiary care center. During a period of 108 weeks, a total of 6955 (5598 pediatric and 1257 adult) patients underwent RV PCR tests for ARI; most of these tests were administered while the patients were admitted (n = 6,920; 99.5%). From the KCDC website, we collected the RV PCR test results of 22 540 patients. Three graphs of weekly positivity rates were made for adults, children, and the KCDC data per each RV, and these graphs were then compared with one another. Whereas RV outbreaks were coincident between the KCDC and the adult graph with respect to influenza virus, respiratory syncytial virus, human metapneumovirus, and human coronavirus, the same was not true for human bocavirus, parainfluenza virus, rhinovirus, and adenovirus. However, a negative predictive value of the KCDC data in the prediction of the occurrence of an outbreak in the adult graph was high for the respective eight RVs (85‐100%). A national RV surveillance dataset may be useful in identifying RV outbreaks in adult patients with severe ARI.


title: Recomendaciones de la Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello para la realización de traqueotomías en relación con pacientes infectados por coronavirus COVID-19

text: Resumen La reciente pandemia por coronavirus COVID-19 está incrementando el número de pacientes que, debido a su situación ventilatoria pulmonar, pueden requerir de intubación orotraqueal. La infección por coronavirus COVID-19 ha demostrado una alta tasa de transmisibilidad, sobre todo por vía respiratoria y por dispersión de microgotas. La Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello, basándose en el artículo de Wei et al. de 2003 en relación con las traqueotomías realizadas por el síndrome respiratorio agudo grave (SARS), realiza una serie de recomendaciones para la realización segura de las traqueotomías. Abstract The recent COVID-19 (coronavirus) pandemic is causing an increase in the number of patients who, due to their pulmonary ventilatory status, may require orotracheal intubation. COVID-19 infection has demonstrated a high rate of transmissibility, especially via the respiratory tract and by droplet spread. The Spanish Society of Otolaryngology and Head and Neck Surgery, based on the article by Wei et al. of 2003 regarding tracheotomies performed due to severe acute respiratory syndrome (SARS), has made a series of recommendations for the safe performance of tracheotomies.


title: Efficacy and safety of lopinavir/ritonavir or arbidol in adult patients with mild/moderate COVID-19: an exploratory randomized controlled trial

text: Abstract Background Antiviral therapies against the novel coronavirus SARS-CoV-2, which has caused a global pandemic of respiratory illness called COVID-19, are still lacking. Methods Our study (NCT04252885, named ELACOI), was an exploratory randomized (2:2:1) controlled trial assessing the efficacy and safety of lopinavir/ritonavir (LPV/r) or arbidol monotherapy for treating patients with mild/moderate COVID-19. Findings This study successfully enrolled 86 patients with mild/moderate COVID-19 with 34 randomly assigned to receive LPV/r, 35 to arbidol and 17 with no antiviral medication as control. Baseline characteristics of the three groups were comparable. The primary endpoint, the rate of positive-to-negative conversion of SARS-CoV-2 nucleic acid, was similar between groups (all P>0.05). There were no differences between groups in the secondary endpoints, the rates of antipyresis, cough alleviation, or improvement of chest CT at days 7 or 14 (all P>0.05). At day 7, eight (23.5%) patients in the LPV/r group, 3 (8.6%) in the arbidol group and 2(11.8%) in the control group showed a deterioration in clinical status from moderate to severe/critical (P =0.206). Overall, 12 (35.3%) patients in the LPV/r group and 5 (14.3%) in the arbidol group experienced adverse events during the follow-up period. No apparent adverse event occurred in the control group. Conclusions LPV/r or arbidol monotherapy present little benefit for improving the clinical outcome of patients hospitalized with mild/moderate COVID-19 over supportive care. Funding This study was supported by project 2018ZX10302103-002, 2017ZX10202102-003-004 and Infectious Disease Specialty of Guangzhou High-level Clinical Key Specialty (2019-2021).


title: Structural analysis of inhibition mechanisms of Aurintricarboxylic Acid on SARS-CoV polymerase and other proteins

text: Abstract We recently published experimental results that indicated Aurintricarboxylic Acid (ATA) could selectively inhibit SARS-CoV replication inside host cells by greater than 1000 times. This inhibition suggested that ATA could be developed as potent anti-viral drug. Here, to extend our experimental observation, we have incorporated protein structural studies (with positive/negative controls) to investigate the potential binding modes/sites of ATA onto RNA-dependent RNA polymerase (RdRp) from SARS-CoV and other pathogenic positive-strand RNA-viruses, as well as other proteins in SARS-CoV based on the fact that ATA binds to Ca2+-activated neutral protease (m-calpain), the protein tyrosine phosphatase (PTP) and HIV integrase which have existing crystal structures. Eight regions with homologous 3D-conformation were derived for 10 proteins of interest. One of the region, R binding (754–766 in SARS-CoV's RdRp), located in the palm sub-domain mainly constituted of anti-parallel β-strand-turn-β-strand hairpin structures that covers two of the three RdRp catalytic sites (Asp 760, Asp761), was also predicted by molecular docking method (based on free energy of binding ΔG) to be important binding motif recognized by ATA. The existence of this strictly conserved region that incorporated catalytic residues, coupled with the homologous ATA binding pockets and their consistent ΔG values, suggested strongly ATA may be involved in an analogous inhibition mechanism of SARS-COV's RdRp in concomitant to the case in m-calpain, PTP and HIV integrase.


title: Production of adeno-associated virus (AAV) serotypes by transient transfection of HEK293 cell suspension cultures for gene delivery

text: Abstract Adeno-associated virus (AAV) is being used successfully in gene therapy. Different serotypes of AAV target specific organs and tissues with high efficiency. There exists an increasing demand to manufacture various AAV serotypes in large quantities for pre-clinical and clinical trials. A generic and scalable method has been described in this study to efficiently produce AAV serotypes (AAV1-9) by transfection of a fully characterized cGMP HEK293SF cell line grown in suspension and serum-free medium. First, the production parameters were evaluated using AAV2 as a model serotype. Second, all nine AAV serotypes were produced successfully with yields of 1013 Vg/L cell culture. Subsequently, AAV2 and AAV6 serotypes were produced in 3-L controlled bioreactors where productions yielded up to 1013 Vg/L similar to the yields obtained in shake-flasks. For example, for AAV2 1013 Vg/L cell culture (6.8×1011 IVP/L) were measured between 48 and 64h post transfection (hpt). During this period, the average cell specific AAV2 yields of 6800Vg per cell and 460IVP per cell were obtained with a Vg to IVP ratio of less than 20. Successful operations in bioreactors demonstrated the potential for scale-up and industrialization of this generic process for manufacturing AAV serotypes efficiently.


title: Chronic Cough Due to Acute Bronchitis ACCP Evidence-Based Clinical Practice Guidelines

text: Background: The purpose of this review is to present the evidence for the diagnosis and treatment of cough due to acute bronchitis and make recommendations that will be useful for clinical practice. Acute bronchitis is one of the most common diagnoses made by primary care clinicians and emergency department physicians. It is an acute respiratory infection with a normal chest radiograph that is manifested by cough with or without phlegm production that lasts for up to 3 weeks. Respiratory viruses appear to be the most common cause of acute bronchitis; however, the organism responsible is rarely identified in clinical practice because viral cultures and serologic assays are not routinely performed. Fewer than 10% of patients will have a bacterial infection diagnosed as the cause of bronchitis. The diagnosis of acute bronchitis should be made only when there is no clinical or radiographic evidence of pneumonia, and the common cold, acute asthma, or an exacerbation of COPD have been ruled out as the cause of cough. Acute bronchitis is a self-limited respiratory disorder, and when the cough persists for > 3 weeks, other diagnoses must be considered. Methods: Recommendations for this review were obtained from data using a National Library of Medicine (PubMed) search dating back to 1950, which was performed in August 2004. The search was limited to literature published in the English language and human studies, using search terms such as “cough,” “acute bronchitis,” and “acute viral respiratory infection.” Results: Unfortunately, most previous controlled trials guiding the treatment of acute bronchitis have not vigorously differentiated acute bronchitis and the common cold, and also have not distinguished between an acute exacerbation of chronic bronchitis and acute asthma as a cause of acute cough. For patients with the putative diagnosis of acute bronchitis, routine treatment with antibiotics is not justified and should not be offered. Antitussive agents are occasionally useful and can be offered as therapy for short-term symptomatic relief of coughing, but there is no role for inhaled bronchodilator or expectorant therapy. Children and adult patients with confirmed and probable whooping cough should receive a macrolide antibiotic and should be isolated for 5 days from the start of treatment; early treatment within the first few weeks will diminish the coughing paroxysms and prevent spread of the disease; the patient is unlikely to respond to treatment beyond this period. Conclusion: Acute bronchitis is an acute respiratory infection that is manifested by cough and, at times, sputum production that lasts for no more than 3 weeks. This syndrome should be distinguished from the common cold, an acute exacerbation of chronic bronchitis, and acute asthma as the cause of acute cough. The widespread use of antibiotics for the treatment of acute bronchitis is not justified, and vigorous efforts to curtail their use should be encouraged.


title: The Emerging Adults Gambling Survey: study protocol

text: The Emerging Adults Gambling Survey is a longitudinal survey of young adults aged 16-24 living in Great Britain. It aims to explore a range of gambling behaviours and harms among young adults and examine how this changes over time. It is part of a broader project funded by Wellcome into the gambling behaviours of young people and its relationship with technological change. Funding is currently available for two waves of data collection: the first collected in June/August 2019 (n=3549) and the second to be collected in June/August 2020. The second wave of data collection will also obtain information about the immediate impact of coronavirus on gambling behaviours. With a sample size of 3549 for Wave 1, this is one of the largest study of gambling behaviours among young adults to be conducted in Great Britain and is a resource for other researchers to draw on. Data will be deposited in the UK Data Archive upon completion of Wave 2 data collection and analysis. This protocol is intended to support other researchers to use this resource by setting out the study design and methods.


title: Chapter 2 Advanced Manufacturing Processes and Technologies

text: Abstract A general framework of the emerging risks linked with advanced manufacturing processes and technologies is showed. For this, the systemic and occupational nature of said risks is considered. To achieve this general objective, the chapter is organized in two parts. In the first part, a theoretical basis is developed. This theoretical basis is configured by an explanation of the emerging risk concept, as well as by the development of an overview of advanced manufacturing processes and technologies. In the second part, contents and tools of practical application are exposed. To do this, the main emerging risks are shown first. Among the fields of application of these risks, some of the most important cross-cutting manufacturing technologies have been selected. One of the main risk governance frameworks is shown. Subsequently, this framework is deployed with two of its main applications on emerging risks: the management and characterization of the risk.


title: Defining the true impact of coronavirus disease 2019 in the at-risk population of patients with cancer

text: BACKGROUND: In light of the coronavirus disease 2019 (COVID-19) pandemic, cancer centres in the United Kingdom and Europe re-organised their services at an unprecedented pace, and many patients with cancer have had their treatments severely disrupted. Patients with cancer were considered at high risk on sparse evidence, and despite a small number of emerging observational studies, the true incidence and impact of COVID-19 in the ‘at-risk’ population of patients with cancer is yet to be defined. METHODS: Epidemiological and clinical data were collected prospectively for patients attending the Royal Marsden Hospital and three network hospitals between March 1st and April 30th 2020 that were confirmed to have SARS-CoV2 infection. Significance of clinical and pathological characteristics was assessed using the Fisher's exact test and Wilcoxon rank sum test, whilst univariate and multivariate logistic regression models were used to further assess risk. The number of patients attending in March/April 2020 for face-to-face attendances was also extracted. FINDINGS: During the 2-month study period, 867 of 13,489 (6.4%) patients met the criteria leading to swab testing. Of the total at-risk population, only 113 of 13,489 (0.84%) were swab positive, 101 of 13,489 (0.75%) required hospital admission and 29 of 13,489 (0.21%) died of COVID-19. Of the patients that attended the hospital to receive cytotoxic chemotherapy alone or in combination with other therapy, 59 of 2001 (2.9%) were admitted to the hospital for COVID-19–related issues and 20 of 2001 (1%) died. Of the patients that collected targeted treatments, 16 of 1126 (1.4%) were admitted and 1 of 1126 (0.1%) died. Of the 11 patients that had received radiotherapy, 6 of 1042 (0.6%) required inpatient admission and 2 of 1042 (0.2%) died. INTERPRETATIONS: Administration of systemic anticancer therapy appears to be associated with a modest risk of severe COVID-19 infection. Based on this snapshot taken as the first wave of COVID-19 hit our practice, we conclude that continuation of active cancer treatment, even in the palliative setting, is appropriate.


title: Roles of LncRNAs in Viral Infections

text: Many proteins and signaling pathways participate in anti-viral host responses. Long non-coding RNAs (lncRNAs), a subset of non-coding RNAs greater than 200 nucleotides in length, have been recently described as critical regulators in viral infections. Accumulating research indicates that lncRNAs are important in the development and progression of infectious diseases. LncRNAs are not only involved in anti-viral responses, but in many different virus-host interactions, some of which may be beneficial to the virus. Here we review the current knowledge regarding host and viral lncRNAs and their roles in viral infections. In addition, the potential of using lncRNAs as diagnostic biomarkers is discussed.


title: Binding of DC-SIGN to the Hemagglutinin of Influenza A Viruses Supports Virus Replication in DC-SIGN Expressing Cells

text: Dendritic cells express lectins receptors, like DC-SIGN, which allow these cells to sense glycans that are present on various bacterial and viral pathogens. Interaction of DC-SIGN with carbohydrate moieties induces maturation of dendritic cells and promotes endocytosis of pathogens which is an important property of these professional antigen presenting cells. Uptake of pathogens by dendritic cells may lead to cross-presentation of antigens or infection of these cells, which ultimately results in activation of virus-specific T cells in draining lymph nodes. Little is known about the interaction of DC-SIGN with influenza A viruses. Here we show that a virus with a non-functional receptor binding site in its hemagglutinin, can replicate in cells expressing DC-SIGN. Also in the absence of sialic acids, which is the receptor for influenza A viruses, these viruses replicate in DC-SIGN expressing cells including human dendritic cells. Furthermore, the efficiency of DC-SIGN mediated infection is dependent on the extent of glycosylation of the viral hemagglutinin.


Free-floating right heart thrombus with pulmonary embolism in SARS-CoV-2 patient


Offline: 2019-nCoV—“A desperate plea”


title: The US Military Commitment to Vaccine Development: A Century of Successes and Challenges

text: The US military has been a leading proponent of vaccine development since its founding. General George Washington ordered the entire American army to be variolated against smallpox after recognizing the serious threat that it posed to military operations. He did this on the recommendation from Dr. John Morgan, the physician-in-chief of the American army, who wrote a treatise on variolation in 1776. Although cases of smallpox still occurred, they were far fewer than expected, and it is believed that the vaccination program contributed to victory in the War of Independence. Effective military force requires personnel who are healthy and combat ready for worldwide deployment. Given the geography of US military operations, military personnel should also be protected against diseases that are endemic in potential areas of conflict. For this reason, and unknown to many, the US military has strongly supported vaccine research and development. Four categories of communicable infectious diseases threaten military personnel: (1) diseases that spread easily in densely populated areas (respiratory and dysenteric diseases); (2) vector-borne diseases (disease carried by mosquitoes and other insects); (3) sexually transmitted diseases (hepatitis, HIV, and gonorrhea); and (4) diseases associated with biological warfare. For each category, the US military has supported research that has provided the basis for many of the vaccines available today. Although preventive measures and the development of drugs have provided some relief from the burden of malaria, dengue, and HIV, the US military continues to fund research and development of prophylactic vaccines that will contribute to force health protection and global health. In the past few years, newly recognized infections with Zika, severe acute respiratory syndrome, Middle East respiratory syndrome viruses have pushed the US military to fund research and fast track clinical trials to quickly and effectively develop vaccines for emerging diseases. With US military personnel present in every region of the globe, one of the most cost-effective ways to maintain military effectiveness is to develop vaccines against prioritized threats to military members’ health.


title: “Go no Go” in plasma fractionation in the world's emerging economies: Still a question asked 70 years after the COHN process was developed!

text: Abstract In the late 1980s, following the human immunodeficiency virus (HIV) epidemic and transfusion-transmitted infections from plasma-derived coagulation factor concentrates to hemophiliacs, many “advanced thinkers” claimed that plasma-derived products would be completely replaced by the year 2000 by safe recombinant products in most developed countries. However, things have not turned out that way, due to both the continual progress witnessed in plasma fractionation and viral-reduction technologies and technical difficulties still being encountered in developing more cost-effective non-immunogenic, fully active recombinant therapeutic proteins. Accordingly, plasma fractionation remains a reasonably healthy industry worldwide, with an ever-increasing volume of plasma fractionated each year to meet the demands for safe and effective plasma-derived medicines at the global level. While high-income countries currently have generally good access to a panel of plasma-derived and recombinant products, desperate shortages of fractionated plasma products remain in developing economies, and patients still have to be treated inadequately. The steady development of the collection of whole blood in developing economies, to gradually cover the recognized needs for red blood cell concentrates, generates an increasing volume of recovered plasma that is currently wasted. Incentives are therefore high for those countries to consider fractionating such plasma as a means of enhancing their supply of products to treat patients, thereby also decreasing the level of dependence on imported products. Challenges of local plasma fractionation in developing economies are high, in a context where the technological and regulatory sophistication of the plasma fractionation industry is often underestimated, and the blood supply may be exposed to emerging infectious agents. In parallel, plasma product quality requirements and drivers are evolving in developed economies as is the awareness of clinicians to newer uses of products such as intravenous immunoglobulins, somewhat deviating from what currently remain the basic needs of developing countries in terms of affordable safe plasma products. Global market trends for plasma-derived products, through plasma fractionation, are still increasing, despite increasing use of recombinant products, and attention is being focused on the five Ws of the fractionation field: which products; where; when; what and how much; and who will be the main suppliers?


title: Chemical properties of heavy metals in typical hospital waste incinerator ashes in China

text: Abstract Incineration has become the main mechanism for hospital waste (HW) disposal in China after the outbreak of Severe Acute Respiratory Syndrome (SARS) in 2003. However, little information is available on the chemical properties of the resulting ashes. In the present study, 22HW ash samples, including 14 samples of bottom ash and eight samples of fly ash, were collected from four typical HW incineration plants located across China. Chemical analysis indicated that the HW ashes contained large amounts of metal salts of Al, Ca, Fe, K, Mg, Na with a concentration range of 1.8–315gkg−1. Furthermore, the ashes contained high concentrations of heavy metals such as Ag, As, Ba, Bi, Cd, Cr, Cu, Mn, Ni, Pb, Ti, Sb, Sn, Sr, Zn with a vast range of 1.1–121,411mgkg−1, with higher concentrations found in the fly ash samples. Sequential extraction results showed that Ba, Cr, Ni and Sn are present in the residual fraction, while Cd existed in the exchangeable and carbonate fractions. As, Mn, Zn existed in the Fe–Mn oxide fraction, Pb was present in the Fe–Mn oxide and residual fractions, and Cu was present in the organic matter fraction. Furthermore, toxicity characteristic leaching procedure (TCLP) results indicated that leached amounts of Cd, Cu and Pb from almost all fly ash samples exceeded the USEPA regulated levels. A comparison between the HW ashes and municipal solid waste (MSW) ash showed that both HW bottom ash and fly ash contained higher concentrations of Ag, As, Bi, Cd, Cr, Cu, Pb, Ti, and Zn. This research provides critical information for appropriate HW incineration ash management plans.


title: Mentorship strategies to foster inclusivity in surgery during a virtual era

text: • Underrepresented and first-generation students are more at risk of becoming socially isolated during the pandemic, which will have detrimental effects on their academic and career achievements. • Intentional outreach from surgical leadership is necessary to promote inclusivity in surgery during a virtual age. • The establishment of structured virtual communities in each subspecialty will foster equitable access to mentors for those who need it most.


title: Bioinformatics Resources and Tools for Phage Display

text: Databases and computational tools for mimotopes have been an important part of phage display study. Five special databases and eighteen algorithms, programs and web servers and their applications are reviewed in this paper. Although these bioinformatics resources have been widely used to exclude target-unrelated peptides, characterize small molecules-protein interactions and map protein-protein interactions, a lot of problems are still waiting to be solved. With the improvement of these tools, they are expected to serve the phage display community better.


title: Quantifying spatiotemporal heterogeneity of MERS-CoV transmission in the Middle East region: A combined modelling approach

text: Abstract MERS coronavirus cases notified in the Middle East region since the identification of the virus in 2012 have displayed variations in time and across geography. Through a combined modelling approach, we estimate the rates of generation of cases along the zoonotic and human-to-human transmission routes and assess their spatiotemporal heterogeneity. We consider all cases notified to WHO from March 2012 to mid-September 2014. We use a stochastic modelling of the time series of case incidence in the Middle East region to estimate time- and space-dependent zoonotic and human-to-human transmission parameters. The model also accounts for possible lack of identification of secondary transmissions among notified cases. This approach is combined with the analysis of imported cases out of the region to assess the rate of underreporting of cases. Out of a total of 32 possible models, based on different parameterisation and scenario considered, the best-fit model is characterised by a large heterogeneity in time and across space for both zoonotic and human-to-human transmission. The variation in time that occurred during Spring 2014 led to a 17-fold and 3-fold increase in the two transmissions, respectively, bringing the reproductive rate to values above 1 during that period for all regions under study. The model suggests that 75% of MERS-CoV cases are secondary cases (human-to-human transmission), which is substantially higher than the 34% of reported cases with an epidemiological link to another case. Overall, estimated reporting rate is 0.26. Our findings show a higher level of spatial heterogeneity in zoonotic transmission compared to human-to-human, highlighting the strong environmental component of the epidemic. Since sporadic introductions are predicted to be a small proportion of notified cases and are responsible for triggering secondary transmissions, a more comprehensive understanding of zoonotic source and path of transmission could be critical to limit the epidemic spread.


title: The Exponential Phase of the Covid-19 Pandemic in Central Italy: An Integrated Care Pathway

text: The Coronavirus Disease (Covid-19) pandemic is rapidly spreading across the world, representing an unparalleled challenge for health care systems. There are differences in the estimated fatality rates, which cannot be explained easily. In Italy, the estimated case fatality rate was 12.7% in mid-April, while Germany remained at 1.8%. Moreover, it is to be noted that different areas of Italy have very different lethality rates. Due to the complexity of Covid-19 patient management, it is of paramount importance to develop a well-defined clinical workflow in order to avoid the inconsistent management of patients. The Integrated Care Pathway (ICP) represents a multidisciplinary outline of anticipated care to support patient management in the Sant’Andrea Hospital, Rome. The main objective of this pilot study was to develop a new ICP evaluated by care indicators, in order to improve the COVID-19 patient management. The suggested ICP was developed by a multi-professional team composed of different specialists and administrators already involved in clinical and management processes. After a review of current internal practices and published evidences, we identified (1) the activities performed during care delivery, (2) the responsibilities for these activities, (3) hospital structural adaptation needs and potential improvements, and (4) ICP indicators. The process map formed the basis of the final ICP document; 160 COVID-19 inpatients were considered, and the effect of the ICP implementation was evaluated over time during the exponential phase of the COVID-19 pandemic. In conclusion, a rapid adoption of ICP and regular audits of quality indicators for the management of COVID-19 patients might be important tools to improve the quality of care and outcomes.


title: In vitro antiviral effect of germacrone on feline calicivirus

text: Feline calicivirus (FCV) often causes respiratory tract and oral disease in cats and is a highly contagious virus. Widespread vaccination does not prevent the spread of FCV. Furthermore, the low fidelity of the RNA-dependent RNA polymerase of FCV leads to the emergence of new variants, some of which show increased virulence. Currently, few effective anti-FCV drugs are available. Here, we found that germacrone, one of the main constituents of volatile oil from rhizoma curcuma, was able to effectively reduce the growth of FCV strain F9 in vitro. This compound exhibited a strong anti-FCV effect mainly in the early phase of the viral life cycle. The antiviral effect depended on the concentration of the drug. In addition, germacrone treatment had a significant inhibitory effect against two other reference strains, 2280 and Bolin, and resulted in a significant reduction in the replication of strains WZ-1 and HRB-SS, which were recently isolated in China. This is the first report of antiviral effects of germacrone against a calicivirus, and extensive in vivo research is needed to evaluate this drug as an antiviral therapeutic agent for FCV.


title: A novel cohort analysis approach to determining the case fatality rate of COVID-19 and other infectious diseases

text: As the Coronavirus contagion develops, it is increasingly important to understand the dynamics of the disease. Its severity is best described by two parameters: its ability to spread and its lethality. Here, we combine a mathematical model with a cohort analysis approach to determine the range of case fatality rates (CFR). We use a logistical function to describe the exponential growth and subsequent flattening of COVID-19 CFR that depends on three parameters: the final CFR (L), the CFR growth rate (k), and the onset-to-death interval (t(0)). Using the logistic model with specific parameters (L, k and t(0)), we calculate the number of deaths each day for each cohort. We build an objective function that minimizes the root mean square error between the actual and predicted values of cumulative deaths and run multiple simulations by altering the three parameters. Using all of these values, we find out which set of parameters returns the lowest error when compared to the number of actual deaths. We were able to predict the CFR much closer to reality at all stages of the viral outbreak compared to traditional methods. This model can be used far more effectively than current models to estimate the CFR during an outbreak, allowing for better planning. The model can also help us better understand the impact of individual interventions on the CFR. With much better data collection and labeling, we should be able to improve our predictive power even further.


title: A comprehensive review of the Kumbh Mela: identifying risks for spread of infectious diseases

text: Abstract The Kumbh Mela in India is the largest mass gathering in the world which witnessed close to 100 million visitors in 2013. An event of this magnitude presents challenges. Increased population density, reduced hygienic conditions and exposure to environmental pollutants pave the way for easy transmission of pathogens. Due to the possibility of epidemics, the primary focus should be on identifying the potential risk factors and implementing appropriate preventive measures. The context of religion and psychology of the pilgrims is also closely associated with the evolution of the risk factors and so forms an important part of the discussion. We provide a brief background to the Kumbh Mela with a description of the existing and potential risk factors that require our attention.


title: DNA markers and nano-biosensing approaches for tuberculosis diagnosis

text: According to WHO 2018 report, 10 million people developed tuberculosis and 1.3 million died from it making it 1 of 10 deadliest diseases worldwide. Tuberculosis is caused by infection with the bacillus Mycobacterium tuberculosis (Mtb). WHO recommends using a specific diagnostic kit Xpert MTB/RIF developed by Cepheid (California, United States). An alarming number of new cases (ca. 558,000) of rifampicin-resistant tuberculosis was diagnosticated in 2017. In recent years, new diagnosis tools targeting the Mtb DNA biomarkers have emerged using a plethora of nanomaterials capable of delivering new technological approaches for the rapid diagnostics of TB and rifampicin-resistant TB (RR-TB). In this chapter, we summarized the state-of-the-art of the current available DNA biomarkers and the potential applications for the development of new diagnosis nanotechnology-based devices. The latter use carbonaceous nanomaterials (graphene and carbon nanotubes), noble metals (silver and gold), semi-conducting (metal oxides, magnetic beads, and quantum dots) in order to reveal and/or to amplify the signal after the recognition of target DNA biomarker. The readout techniques such as colorimetry, fluorescence, surface plasmon resonance, and electrochemical methods were also reviewed. Future is bright for point-of-care diagnostics with a sample-in answer-out approach that hampers user-error through miniaturization of biochip technology to the nanoscale range, which will enable their use by nonspecialized personnel.


title: Infections with Viruses and Mycoplasma pneumoniae during Exacerbations of Chronic Bronchitis

text: The association of viral and Mycoplasma pneumoniae infections with acute exacerbations of chronic bronchitis was studied by serologic or isolation techniques in 46 adult men during the five years from 1964 through 1968. Serologic evidence of viral or M. pneumoniae infection was detected in 25% of 166 episodes of exacerbation and 14% of 138 remission periods (P = 0.02). Influenza A virus, parainfluenza virus type 3, and coronavirus OC43 predominated; infections with other viruses were infrequent. Infection with M. pneumoniae was detected serologically in four patients, but this organism was never isolated from sputum specimens. Rhinoviruses were isolated from frozen-stored sputum specimens in 2.7% of the episodes of exacerbation and from 0.55% of the remission intervals (P not significant). These data suggest that although exacerbations of chronic bronchitis may be accompanied by viral and M. pneumoniae infections, patients with chronic bronchitis also acquire such infections without a worsening of their respiratory status.


Changes of the patient management in dentistry during the pandemic caused by the SARS-Coronavirus 2—initial perspectives of a clinic of operative dentistry in Europe


title: Antimicrobial drug use and reason for treatment in 203 western Canadian cow–calf herds during calving season

text: Abstract Investigators examined antimicrobial drug use practices and reason for treatment as part of a large on-farm observational study of cow–calf herds from western Canada. Reason for treatment and antimicrobial drug use (AMU) were described using data collected during the calving season (January 1 to June 30, 2002). The study included 28,573 calves and 36,634 cows and heifers from 203 beef herds. All herds had more than 50 cows. Individual animal treatment records and a herd-level standardized questionnaire were collected from every herd. During the period of January 1 to June 30, 2002 at least one treatment was reported in 14% (95% CI, 11–17) of calves and 2.7% (95% CI, 2.2–3.4) of cows and heifers from these herds. The median percent of calves reported as treated per farm was 6.5% (range 0–100%) while the median percent of cows and heifers reported as treated was 0.9% (range 0–15%). Antimicrobial drugs used during the calving season were primarily for disease treatment rather than prevention or growth promotion. Diarrhea was the primary reason for treating calves and metritis was the primary reason for treating cows. Parenteral antimicrobial drugs were the most common formulation used in both calves and cows. The most commonly used antimicrobial drugs in these herds were tetracyclines, sulphonamides, and florfenicol. This study provides baseline estimates of the frequency of antimicrobial drug exposure, the types of drugs used, and diseases treated in these cow–calf herds. The challenges identified in collecting these data can be used to improve the design of future on-farm studies.


MERS in South Korea and China: a potential outbreak threat?


title: Quantitative Genetics in the Study of Virus-Induced Disease

text: While the role of viral variants has long been known to play a key role in causing variation in disease severity, it is also clear that host genetic variation plays a critical role in determining virus-induced disease responses. However, a variety of factors, including confounding environmental variables, rare genetic variants requiring extremely large cohorts, the temporal dynamics of infections, and ethical limitation on human studies, have made the identification and dissection of variant host genes and pathways difficult within human populations. This difficulty has led to the development of a variety of experimental approaches used to identify host genetic contributions to disease responses. In this chapter, we describe the history of genetic associations within the human population, the development of experimentally tractable systems, and the insights these specific approaches provide. We conclude with a discussion of recent advances that allow for the investigation of the role of complex genetic networks that underlie host responses to infection, with the goal of drawing connections to human infections. In particular, we highlight the need for robust animal models with which to directly control and assess the role of host genetics on viral infection outcomes.


title: Bordetella bronchiseptica Colonization Limits Efficacy, but Not Immunogenicity, of Live-Attenuated Influenza Virus Vaccine and Enhances Pathogenesis After Influenza Challenge

text: Intranasally administered live-attenuated influenza virus (LAIV) vaccines provide significant protection against heterologous influenza A virus (IAV) challenge. However, LAIV administration can modify the bacterial microbiota in the upper respiratory tract, including alterations in species that cause pneumonia. We sought to evaluate the effect of Bordetella bronchiseptica colonization on LAIV immunogenicity and efficacy in swine, and the impact of LAIV and IAV challenge on B. bronchiseptica colonization and disease. LAIV immunogenicity was not significantly impacted by B. bronchiseptica colonization, but protective efficacy against heterologous IAV challenge in the upper respiratory tract was impaired. Titers of IAV in the nose and trachea of pigs that received LAIV were significantly reduced when compared to non-vaccinated, challenged controls, regardless of B. bronchiseptica infection. Pneumonia scores were higher in pigs colonized with B. bronchiseptica and challenged with IAV, but this was regardless of LAIV vaccination status. While LAIV vaccination provided significant protection against heterologous IAV challenge, the protection was not sterilizing and IAV replicated in the respiratory tract of all LAIV vaccinated pig. The interaction between IAV, B. bronchiseptica, and host led to development of acute-type B. bronchiseptica lesions in the lung. Thus, the data presented do not negate the efficacy of LAIV vaccination, but instead indicate that controlling B. bronchiseptica colonization in swine could limit the negative interaction between IAV and Bordetella on swine health.


title: Characterization of a coronavirus isolated from rats with sialoadenitis

text: A causative agent, provisionally designated as CARS, was isolated from the enlarged submaxillary gland of rat which was characterized as a sialoadenitis, using mouse-derived Balb/c3T3 clone A31 (3T3) cell culture. The virus could be propagated in 3T3 cell culture where it produced multinucleated giant cells and formed clear plaques. It was identified as a member of the coronavirus group from the following results: RNA content was suggested by the lack of the effect of cytosine arabinoside, the infectivity was sensitive to lipid solvents and inactivated at 56° C for 5 minutes, the viral particle showed typical coronavirus morphology which was approximately 100 nm in diameter. Serologically, although CARS and sialodacryoadenitis virus (SDAV) actually belonged to the rat-coronavirus group, some antigenic variations existed between these two agents in the results of both neutralization and complement-fixation tests using monovalent antisera. When inoculated intranasally into susceptible rats, CARS caused clinically and histologically overt sialoadenitis as observed in the natural outbreak, and retained its virulence for rats in several passages of mouse brain and even when cell culture was used, while rats which were inoculated with SDAV were asymptomatic.


title: Characterization of cellular furin content as a potential factor determining the susceptibility of cultured human and animal cells to coronavirus infectious bronchitis virus infection

text: Abstract In previous studies, the Beaudette strain of coronavirus infectious bronchitis virus (IBV) was adapted from chicken embryo to Vero, a monkey kidney cell line, by serial propagation for 65 passages. To characterize the susceptibility of other human and animal cells to IBV, 15 human and animal cell lines were infected with the Vero-adapted IBV and productive infection was observed in four human cell lines: H1299, HepG2, Hep3B and Huh7. In other cell lines, the virus cannot be propagated beyond passage 5. Interestingly, cellular furin abundance in five human cell lines was shown to be strongly correlated with productive IBV infection. Cleavage of IBV spike protein by furin may contribute to the productive IBV infection in these cells. The findings that IBV could productively infect multiple human and animal cells of diverse tissue and organ origins would provide a useful system for studying the pathogenesis of coronavirus.


The “helmet bundle” in COVID-19 patients undergoing non invasive ventilation


title: Steroid‐responsive encephalitis in Covid‐19 disease

text: Covid‐19 infection has the potential for targeting the central nervous system and several neurological symptoms have been described in patients with severe respiratory distress. Here we described the case of a 60‐year old subject with SARS‐CoV‐2 infection but only mild respiratory abnormalities who developed an akinetic mutism due to encephalitis. MRI was negative whereas EEG showed generalized theta slowing. CSF analyses during the acute stage were negative for SARS‐CoV‐2, positive for pleocytosis and hyperproteinorrachia, and showed increased IL‐8 and TNF‐α concentrations while other infectious or autoimmune disorders were excluded. A progressive clinical improvement along with a reduction of CSF parameters was observed after high‐dose steroid treatment, thus arguing for an inflammatory‐mediated brain involvement related to Covid‐19. This article is protected by copyright. All rights reserved.


title: Multi-System Inflammatory Syndrome in Children (MIS-C) Following SARS-CoV-2 Infection: Review of Clinical Presentation, Hypothetical Pathogenesis, and Proposed Management

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may result in the multisystem inflammatory syndrome in children (MIS-C) The clinical presentation of MIS-C includes fever, severe illness, and the involvement of two or more organ systems, in combination with laboratory evidence of inflammation and laboratory or epidemiologic evidence of SARS-CoV-2 infection Some features of MIS-C resemble Kawasaki Disease, toxic shock syndrome, and secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome The relationship of MIS-C to SARS-CoV-2 infection suggests that the pathogenesis involves post-infectious immune dysregulation Patients with MIS-C should ideally be managed in a pediatric intensive care environment since rapid clinical deterioration may occur Specific immunomodulatory therapy depends on the clinical presentation The relationship between the immune response to SARS-CoV-2 vaccines in development and MIS-C requires further study


title: COVID19 pandemic and people with opioid use disorder: innovation to reduce risk

text: Abstract The Covid-19 pandemic is creating a vast and growing number of challenges for all. People with a history of opioid use disorder (OUD) also may be exposed to additional risks. Piedmont one of the areas most severely affected by the Covid-19 pandemic, with large numbers of people infected and related mortality. In the region, specialists responsible for OUD care identified the risk that the existing care system exposed patients to. Teams designed and implemented innovation approaches to enable continuation of care and reduce the inherent system risk to patients with OUD.


title: Pathology of natural rotavirus infection in clinically normal calves

text: During a longitudinal study of the epidemiology of rotavirus infection in a calf rearing unit, excretion of virus in faeces was detected by enzyme-linked immunosorbent assay in 40 of 48 (83 per cent) unweaned calves aged between three days and five weeks. Fifty per cent of the infected calves had no clinical signs of disease. Enterocytes containing rotavirus antigen and intestinal lesions were found in all of 12 clinically normal calves selected for necropsy between days 1 and 4 of virus excretion. Stunting and fusion of villi, exfoliation, disarrangement and vacuolation of enterocytes and the presence of cuboidal enterocytes were observed in infected calves but not in rotavirus-free control calves. Lesions predominated in the upper small intestine, where rotavirus was most abundant, especially on the first two days of virus excretion. The numbers of enterocytes infected with rotavirus diminished before the lesions resolved.


title: Viral outbreaks in neonatal intensive care units: What we do not know

text: BACKGROUND: Nosocomial infection is among the most important causes of morbidity, prolonged hospital stay, increased hospital costs, and mortality in neonates, particularly those born preterm. The vast majority of scientific articles dealing with nosocomial infections address bacterial or fungal infections, and viral agents are often disregarded. This analysis reviews the medical literature in an effort to establish the incidence, types of pathogens, and clinical features of noncongenital neonatal viral infections. METHODS: This analysis was performed using the worldwide database of health care–associated outbreaks (http://www.outbreak-database.com). Items analyzed included causative pathogens, types of infection, source of outbreaks, and measures taken to stop outbreaks. RESULTS: The outbreak database contained a total of 590 neonatal outbreaks, of which 64 were originated by viruses, 44 of which (68.75%) were reported from neonatal intensive care units (NICUs). The 5 most frequent viral agents were rotavirus (23.44%), respiratory syncytial virus (17.19%), enterovirus (15.63%), hepatitis A virus (10.94%), and adenovirus (9.38%). CONCLUSION: Our analysis of the viral origins of nosocomial infections in NICUs can be a valuable tool in the investigation of neonatal infections. The mortality rates reported in this analysis demonstrate the significance of noncongenital viral infections in NICUs and the need for more effective outbreak prevention strategies.


title: Detection and genetic characterization of kobuvirus in cats: The first molecular evidence from Northeast China

text: Abstract Feline kobuvirus (FeKoV), a novel picornavirus of the genus kobuvirus, was initially identified in the feces of cats with diarrhea in South Korea in 2013. To date, there is only one report of the circulation of kobuvirus in cats in southern China. To investigate the presence and genetic variability of FeKoV in northeast China, 197 fecal samples were collected from 105 cats with obvious diarrhea and 92 asymptomatic cats in Shenyang, Jinzhou, Changchun, Jilin and Harbin regions, Northeast China, and viruses were detected by RT-PCR with universal primers targeting all kobuviruses. Kobuvirus was identified in 28 fecal samples with an overall prevalence of 14.2% (28/197) of which 20 samples were co-infected with feline parvovirus (FPV) and/or feline bocavirus (FBoV). Diarrhoeic cats had a higher kobuvirus prevalence (19.1%, 20/105) than asymptomatic cats (8.7%, 8/92). By genetic analysis based on partial 3D gene, all kobuvirus-positive samples were more closely related to previous FeKoV strains with high identities of 90.5%–97.8% and 96.6%–100% at the nucleotide and amino acid levels. Additionally, phylogenetic analysis based on the complete VP1 gene indicated that all FeKoV strains identified in this study were placed into a cluster, which separated from other reference strains previously reported, and three identical amino acid substitutions were present at the C-terminal of the VP1 protein for these FeKoV strains. Furthermore, two complete FeKoV polyprotein genomes were successfully obtained from two positive samples and designated 16JZ0605 and 17CC0811, respectively. The two strains shared 92.9%–94.9% nucleotide identities and 96.8%–98.4% amino acid identities to FeKoV prototype strains. Phylogenetic analysis indicated that FeKoVs were clustered according to their geographical regions, albeit with limited sequences support. This study provides the first molecular evidence that FeKoV circulates in cats in northeast China, and these FeKoVs exhibit genetic diversity and unique evolutionary trend.


Tainted hand sanitizer leads to outbreak of methanol toxicity during SARS-CoV-2 pandemic


title: Transcriptional profiling of feline infectious peritonitis virus infection in CRFK cells and in PBMCs from FIP diagnosed cats

text: BACKGROUND: Feline Infectious Peritonitis (FIP) is a lethal systemic disease, caused by the FIP Virus (FIPV); a virulent mutant of Feline Enteric Coronavirus (FECV). Currently, the viruses virulence determinants and host gene expressions during FIPV infection are not fully understood. METHODS: RNA sequencing of Crandell Rees Feline Kidney (CRFK) cells, infected with FIPV strain 79–1146 at 3 hours post infection (h.p.i), were sequenced using the Illumina next generation sequencing approach. Bioinformatic’s analysis, based on Felis catus 2X annotated shotgun reference genome, using CLC bio Genome Workbench mapped both control and infected cell reads to 18899 genes out of 19046 annotated genes. Kal’s Z test statistical analysis was used to analyse the differentially expressed genes from the infected CRFK cells. Real time RT-qPCR was developed for further transcriptional profiling of three genes (PD-1, PD-L1 and A3H) in infected CRFK cells and Peripheral Blood Mononuclear Cells (PBMCs) from healthy and FIP-diseased cats. RESULTS: Based on Kal’s Z-test, with False Discovery Rate (FDR) <0.05 and >1.99 fold change on gene expressions, a total of 61 genes were differentially expressed by both samples, where 44 genes were up-regulated and the remainder were down-regulated. Most genes were closely clustered together, suggesting a homogeneous expression. The majority of the genes that were significantly regulated, were those associated with monocytes-macrophage and Th1 cell functions, and the regulation of apoptosis. Real time RT-qPCR developed focusing on 2 up-regulated genes (PD-L1 and A3H) together with an apoptosis associated gene PD-1 expressions in FIPV infected CRFK cells and in PBMCs from healthy and FIP diagnosed cats produced concordant results with transcriptome data. CONCLUSION: The possible roles of these genes, and their importance in feline coronaviruses infection, are discussed.


title: A Brief Review of Computer-Assisted Approaches to Rational Design of Peptide Vaccines

text: The growing incidences of new viral diseases and increasingly frequent viral epidemics have strained therapeutic and preventive measures; the high mutability of viral genes puts additional strains on developmental efforts. Given the high cost and time requirements for new drugs development, vaccines remain as a viable alternative, but there too traditional techniques of live-attenuated or inactivated vaccines have the danger of allergenic reactions and others. Peptide vaccines have, over the last several years, begun to be looked on as more appropriate alternatives, which are economically affordable, require less time for development and hold the promise of multi-valent dosages. The developments in bioinformatics, proteomics, immunogenomics, structural biology and other sciences have spurred the growth of vaccinomics where computer assisted approaches serve to identify suitable peptide targets for eventual development of vaccines. In this mini-review we give a brief overview of some of the recent trends in computer assisted vaccine development with emphasis on the primary selection procedures of probable peptide candidates for vaccine development.


title: Abundance, survival, recruitment and effectiveness of sterilization of free-roaming dogs: A capture and recapture study in Brazil

text: The existence of free-roaming dogs raises important issues in animal welfare and in public health. A proper understanding of these animals’ ecology is useful as a necessary input to plan strategies to control these populations. The present study addresses the population dynamics and the effectiveness of the sterilization of unrestricted dogs using capture and recapture procedures suitable for open animal populations. Every two months, over a period of 14 months, we captured, tagged, released and recaptured dogs in two regions in a city in the southeast region of Brazil. In one of these regions the animals were also sterilized. Both regions had similar social, environmental and demographic features. We estimated the presence of 148 females and 227 males during the period of study. The average dog:man ratio was 1 dog for each 42 and 51 human beings, in the areas without and with sterilization, respectively. The animal population size increased in both regions, due mainly to the abandonment of domestic dogs. Mortality rate decreased throughout the study period. Survival probabilities did not differ between genders, but males entered the population in higher numbers. There were no differences in abundance, survival and recruitment between the regions, indicating that sterilization did not affect the population dynamics. Our findings indicate that the observed animal dynamics were influenced by density-independent factors, and that sterilization might not be a viable and effective strategy in regions where availability of resources is low and animal abandonment rates are high. Furthermore, the high demographic turnover rates observed render the canine free-roaming population younger, thus more susceptible to diseases, especially to rabies and leishmaniasis. We conclude by stressing the importance of implementing educational programs to promote responsible animal ownership and effective strategies against abandonment practices.


title: Bovine-like coronaviruses in domestic and wild ruminants

text: Coronaviruses (CoVs) produce a wide spectrum of disease syndromes in different mammalian and avian host species. These viruses are well-recognized for their ability to change tissue tropism, to hurdle the interspecies barriers and to adapt ecological variations. It is predicted that the inherent genetic diversity of CoVs caused by accumulation of point mutations and high frequency of homologous recombination is the principal determinant of these competences. Several CoVs (e.g. Severe acute respiratory syndrome-CoV, Middle East respiratory syndrome-CoV) have been recorded to cross the interspecies barrier, inducing different disease conditions in variable animal hosts. Bovine CoV (BCoV) is a primary cause of gastroenteritis and respiratory disease in cattle calves, winter dysentery in lactating cows and shipping fever pneumonia in feedlot cattle. Although it has long been known as a restrictive cattle pathogen, CoVs that are closely related to BCoV have been recognized in dogs, humans and in other ruminant species. Biologic, antigenic and genetic analyses of the so-called ‘bovine-like CoVs’ proposed classification of these viruses as host-range variants rather than distinct virus species. In this review, the different bovine-like CoVs that have been identified in domesticated ruminants (water buffalo, sheep, goat, dromedary camel, llama and alpaca) and wild ruminants (deer, wild cattle, antelopes, giraffes and wild goats) are discussed in terms of epidemiology, transmission and virus characteristics. The presented data denote the importance of these viruses in the persistence of BCoV in nature, spread to new geographical zones, and continuous emergence of disease epidemics in cattle farms.


title: Design, synthesis, and biological evaluation of novel iso-d-2′,3′-dideoxy-3′-fluorothianucleoside derivatives

text: Abstract Novel iso-d-2′,3′-dideoxythianucleoside derivatives 1–4 were designed and asymmetrically synthesized as a bioisostere of lamivudine to search for new anti-HIV agents. The information about using sulfur participation occurred on DAST fluorination and Mitsunobu reaction will be of great help in synthesizing sulfur-containing compounds. Final compounds 1–4 were evaluated against HIV-1 and 2, HSV-1 and 2, EMCV, Cox. B3, VSV, FluA (Taiwan), FluA (Johan.), FCV, and FIP. Only cytosine analogue 3 showed a potent anti-VSV activity (EC50 =9.43μg/mL). This result implies that iso-2′,3′-dideoxy sugar templates might play a role of a sugar surrogate of nucleosides for the development of anti-RNA virus agent.


title: Virtual Screening of Natural Products against Type II Transmembrane Serine Protease (TMPRSS2), the Priming Agent of Coronavirus 2 (SARS-CoV-2)

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused about 2 million infections and is responsible for more than 100,000 deaths worldwide. To date, there is no specific drug registered to combat the disease it causes, named coronavirus disease 2019 (COVID-19). In the current study, we used an in silico approach to screen natural compounds to find potent inhibitors of the host enzyme transmembrane protease serine 2 (TMPRSS2). This enzyme facilitates viral particle entry into host cells, and its inhibition blocks virus fusion with angiotensin-converting enzyme 2 (ACE2). This, in turn, restricts SARS-CoV-2 pathogenesis. A three-dimensional structure of TMPRSS2 was built using SWISS-MODEL and validated by RAMPAGE. The natural compounds library Natural Product Activity and Species Source (NPASS), containing 30,927 compounds, was screened against the target protein. Two techniques were used in the Molecular Operating Environment (MOE) for this purpose, i.e., a ligand-based pharmacophore approach and a molecular docking-based screening. In total, 2140 compounds with pharmacophoric features were retained using the first approach. Using the second approach, 85 compounds with molecular docking comparable to or greater than that of the standard inhibitor (camostat mesylate) were identified. The top 12 compounds with the most favorable structural features were studied for physicochemical and ADMET (absorption, distribution, metabolism, excretion, toxicity) properties. The low-molecular-weight compound NPC306344 showed significant interaction with the active site residues of TMPRSS2, with a binding energy score of −14.69. Further in vitro and in vivo validation is needed to study and develop an anti-COVID-19 drug based on the structures of the most promising compounds identified in this study.


title: Determination of suitable housekeeping genes for normalisation of quantitative real time PCR analysis of cells infected with human immunodeficiency virus and herpes viruses

text: The choice of an appropriate housekeeping gene for normalisation purposes has now become an essential requirement when designing QPCR experiments. This is of particular importance when using QPCR to measure viral and cellular gene transcription levels in the context of viral infections as viruses can significantly interfere with host cell pathways, the components of which traditional housekeeping genes often encode. In this study we have determined the reliability of 10 housekeeping genes in context of four heavily studied viral infections; human immunodeficiency virus type 1, herpes simplex virus type 1, cytomegalovirus and varicella zoster virus infections using a variety of cell types and virus strains. This provides researchers of these viruses with a shortlist of potential housekeeping genes to use as normalisers for QPCR experiments.


title: Community-Acquired Pneumonia: An Unfinished Battle

text: Community-acquired pneumonia remains a common illness with substantial morbidity and mortality. Current management challenges focus on identifying the likely etiologic pathogens based on an assessment of host risk factors, while attempting to make a specific etiologic diagnosis, which is often not possible. Therapy is necessarily empiric and focuses on pneumococcus and atypical pathogens for all patients, with consideration of other pathogens based on specific patient risk factors. It is important to understand the expected response to effective therapy, and to identify and manage clinical failure at the earliest possible time point. Prevention is focused on smoking cessation and vaccination against pneumococcus and influenza.


title: The Use of Antimalarial Drugs against Viral Infection

text: In recent decades, drugs used to treat malaria infection have been shown to be beneficial for many other diseases, including viral infections. In particular, they have received special attention due to the lack of effective antiviral drugs against new emerging viruses (i.e., HIV, dengue virus, chikungunya virus, Ebola virus, etc.) or against classic infections due to drug-resistant viral strains (i.e., human cytomegalovirus). Here, we reviewed the in vitro/in vivo and clinical studies conducted to evaluate the antiviral activities of four classes of antimalarial drugs: Artemisinin derivatives, aryl-aminoalcohols, aminoquinolines, and antimicrobial drugs.


title: Executive summary of imported infectious diseases after returning from foreign travel: Consensus document of the Spanish Society for Infectious Diseases and Clinical Microbiology (SEIMC)

text: Abstract In a global world, knowledge of imported infectious diseases is essential in daily practice, both for the microbiologist•parasitologist and the clinician who diagnoses and treats infectious diseases in returned travelers. Tropical and subtropical countries where there is a greater risk of contracting an infectious disease are among the most frequently visited tourist destinations. The SEIMC considers it appropriate to produce a consensus document that will be useful to primary care physicians as well as specialists in internal medicine, infectious diseases and tropical medicine who help treat travelers returning from tropical and sub-tropical areas with infections. Preventive aspects of infectious diseases and infections imported by immigrants are explicitly excluded here, since they have been dealt with in other SEIMC documents. Various types of professionals (clinicians, microbiologists, and parasitologists) have helped produce this consensus document by evaluating the available evidence-based data in order to propose a series of key facts about individual aspects of the topic. The first section of the document is a summary of some of the general aspects concerning the general assessment of travelers who return home with potential infections. The main second section contains the key facts (causative agents, diagnostic procedures and therapeutic measures) associated with the major infectious syndromes affecting returned travelers [gastrointestinal syndrome (acute or persistent diarrhea); febrile syndrome with no obvious source of infection; localized cutaneous lesions; and respiratory infections]. Finally, the characteristics of special traveler subtypes, such as pregnant women and immunocompromised travelers, are described.


title: Viral glycoproteins: biological role and application in diagnosis

text: The viruses that infect humans cause a huge global disease burden and produce immense challenge towards healthcare system. Glycoproteins are one of the major components of human pathogenic viruses. They have been demonstrated to have important role(s) in infection and immunity. Concomitantly high titres of antibodies against these antigenic viral glycoproteins have paved the way for development of novel diagnostics. Availability of appropriate biomarkers is necessary for advance diagnosis of infectious diseases especially in case of outbreaks. As human mobilization has increased manifold nowadays, dissemination of infectious agents became quicker that paves the need of rapid diagnostic system. In case of viral infection it is an emergency as virus spreads and mutates very fast. This review encircles the vast arena of viral glycoproteins, their importance in health and disease and their diagnostic applications.


title: Development of real-time fluorescent reverse transcription loop-mediated isothermal amplification assay with quenching primer for influenza virus and respiratory syncytial virus

text: Abstract Influenza virus and respiratory syncytial virus cause acute upper and lower respiratory tract infections, especially in children and the elderly. Early treatment for these infections is thought to be important, so simple and sensitive detection methods are needed for use at clinical sites. Therefore, in this study, real-time reverse transcription loop-mediated isothermal amplification assays with quenching primer for influenza virus and respiratory syncytial virus were developed. Evaluation of a total of 113 clinical specimens compared to real-time RT-PCR assays showed that the novel assays could distinguish between the types and subtypes of influenza virus and respiratory syncytial virus and had 100% diagnostic specificity. The diagnostic sensitivity of each assay exceeded 85.0% and the assays showed sufficient clinical accuracy. Furthermore, positive results could be obtained in around 15 min using the novel assays in cases with high concentrations of virus. The developed assays should be useful for identifying influenza virus and respiratory syncytial virus cases not only in experimental laboratories but also in hospital and quarantine laboratories.


title: Conserved amino acids W423 and N424 in receptor-binding domain of SARS-CoV are potential targets for therapeutic monoclonal antibody

text: Abstract The receptor-binding domain (RBD) on spike protein of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is the main region interacting with the viral receptor-ACE2 and is a useful target for induction of neutralizing antibodies against SARS-CoV infection. Here we generated two monoclonal antibodies (mAbs), targeting RBD, with marked virus neutralizing activity. The mAbs recognize a new conformational epitope which consists of several discontinuous peptides (aa. 343–367, 373–390 and 411–428) and is spatially located neighboring the receptor-binding motif (RPM) region of the RBD. Importantly, W423 and N424 residues are essential for mAb recognition and are highly conserved among 107 different strains of SARS, indicating that the residues are the most critical in the epitope which is a novel potential target for therapeutic mAbs. A human–mouse chimeric antibody, based upon the original murine mAb, was also constructed and shown to possess good neutralizing activity and high affinity.


title: SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract

text: Summary The mode of acquisition and causes for the variable clinical spectrum of COVID-19 remain unknown. We utilized a reverse genetics system to generate a GFP reporter virus to explore SARS-CoV-2 pathogenesis and a luciferase reporter virus to demonstrate sera collected from SARS and COVID-19 patients exhibited limited cross-CoV neutralization. High-sensitivity RNA in situ mapping revealed the highest ACE2 expression in the nose with decreasing expression throughout the lower respiratory tract, paralleled by a striking gradient of SARS-CoV-2 infection in proximal (high) vs distal (low) pulmonary epithelial cultures. COVID-19 autopsied lung studies identified focal disease and, congruent with culture data, SARS-CoV-2-infected ciliated and type 2 pneumocyte cells in airway and alveolar regions, respectively. These findings highlight the nasal susceptibility to SARS-CoV-2 with likely subsequent aspiration-mediated virus seeding to the lung in SARS-CoV-2 pathogenesis. These reagents provide a foundation for investigations into virus-host interactions in protective immunity, host susceptibility, and virus pathogenesis.


CEPI: preparing for the worst


title: Biological warfare, bioterrorism, and biocrime

text: Biological weapons achieve their intended target effects through the infectivity of disease-causing infectious agents. The ability to use biological agents in warfare is prohibited by the Biological and Toxin Weapon Convention. Bioterrorism is defined as the deliberate release of viruses, bacteria or other agents used to cause illness or death in people, but also in animals or plants. It is aimed at creating casualties, terror, societal disruption, or economic loss, inspired by ideological, religious or political beliefs. The success of bioterroristic attempts is defined by the measure of societal disruption and panic, and not necessarily by the sheer number of casualties. Thus, making only a few individuals ill by the use of crude methods may be sufficient, as long as it creates the impact that is aimed for. The assessment of bioterrorism threats and motives have been described before. Biocrime implies the use of a biological agent to kill or make ill a single individual or small group of individuals, motivated by revenge or the desire for monetary gain by extortion, rather than by political, ideological, religious or other beliefs. The likelihood of a successful bioterrorist attack is not very large, given the technical difficulties and constraints. However, even if the number of casualties is likely to be limited, the impact of a bioterrorist attack can still be high. Measures aimed at enhancing diagnostic and therapeutic capabilities and capacities alongside training and education will improve the ability of society to combat ‘regular’ infectious diseases outbreaks, as well as mitigating the effects of bioterrorist attacks.