title: Presence of Subgenomic mRNAs in Virions of Coronavirus IBV

text: Abstract The presence of subgenomic mRNAs in virions of IBV was examined by probing Northern blots of RNA extracted from virions using as a probe a cDNA of the 3′-terminal nucleocapsid protein (N) gene. This detects all five mRNAs because of the 3′-coterminal, nested-set arrangement of coronavirus mRNAs. The mRNAs were readily detected even after extensive purification of virions and after RNase A treatment of virions. In sucrose gradients the peaks of virus particles, genomic RNA (gRNA), and mRNAs were coincident. Cellular mRNA was not detected in virions. The molar ratio of gRNA to each mRNA ranged from about 10 to 30 for IBV-Beaudette and 25 to 800 for IBV-M41. The molar ratio of genomic to intracellular viral mRNAs was also determined. From this it was estimated that the efficiency of incorporation of gRNA into virions was at least 20- to 100-fold greater, depending on the mRNA species, for IBV-Beaudette and 100- to 500-fold for IBV-M41. It is concluded that most virions contain only gRNA or contain only one species of mRNA on average in addition to gRNA.


title: Immunogenicity of the spike glycoprotein of Bat SARS-like coronavirus

text: A group of SARS-like coronaviruses (SL-CoV) have been identified in horseshoe bats. Despite SL-CoVs and SARS-CoV share identical genome structure and high-level sequence similarity, SL-CoV does not bind to the same cellular receptor as for SARS-CoV and the N-terminus of the S proteins only share 64% amino acid identity, suggesting there are fundamental differences between these two groups of coronaviruses. To gain insight into the basis of this difference, we established a recombinant adenovirus system expressing the S protein from SL-CoV (rAd-Rp3-S) to investigate its immune characterization. Our results showed that immunized mice generated strong humoral immune responses against the SL-CoV S protein. Moreover, a strong cellular immune response demonstrated by elevated IFN-γ and IL-6 levels was also observed in these mice. However, the induced antibody from these mice had weaker cross-reaction with the SARS-CoV S protein, and did not neutralize HIV pseudotyped with SARS-CoV S protein. These results demonstrated that the immunogenicity of the SL-CoV S protein is distinct from that of SARS-CoV, which may cause the immunological differences between human SARS-CoV and bat SL-CoV. Furthermore, the recombinant virus could serve as a potential vaccine candidate against bat SL-CoV infection.


title: Computation screening of narcissoside a glycosyloxyflavone for potential novel coronavirus 2019 (COVID-19) inhibitor

text: OBJECTIVE: The present study demonstrates the potential of flavanoid narcissoside against the novel corona virus (COVID-19) complications using molecular docking studies. METHOD: The computation molecular docking screening was performed using Molegro Virtual Docker software (MVD) with grid resolution of 30 Å. Protein of COVID 19 virus was taken from protein data bank. RESULT: The standard inhibitor X77 (N-(4-tert-butylphenyl)-N-[(1R)-2-(cyclohexylamino)-2-oxo-1-(pyridin-3-yl)ethyl]-1H-imidazole-4-carboxamide) identified from the protein inhibitor complex 6W63 from protein data bank was docked with COVID 19 protein 6W63 which showed MolDock score of −156.913, rerank Sore −121.296 and H Bond −5.7369, while the flavanoid narcissoside had showed MolDock score −180.739, Rerank Sore −137.092 and H Bond −18.6771. The narcissoside showed potent inhibitory effect which is greater than standard X77. The result showed that narcissoside have high affinity towards 6W63 as it showed thirteen hydrogen bonds with nine amino acids (Arg 188, Glu 166, His 164, Cys 145 (2 bonds), Asn 14 (2 bonds), Cys 44 (2 bonds), His 41 (2 bonds), Gln 192, Thr 190) while X777 showed four hydrogen bonds with amino acids (Gly 143, Cys 145, Glu 166, Ser 144). CONCLUSION: From computation approach it was concluded that narcissoside is a potent inhibitor of viral COVID 19 protein 6W63. The narcissoside have high affinity and inhibition potential than standard inhibitor X77 (N-(4-tert-butylphenyl)-N-[(1R)-2-(cyclohexylamino)-2-oxo-1-(pyridin-3-yl)ethyl]-1H-imidazole-4-carboxamide). The narcissoside predicted as more potent inhibitor which can be further optimize, pharmacologically and clinically evaluated for the treatment of novel coronavirus COVID-19.


What’s new in the renin-angiotensin system?: What’s new in the renin-angiotensin system?


title: Anti-SARS-CoV-2 hyperimmune plasma workflow

text: Coronavirus disease 2019 (COVID-19) caused by the novel coronavirus has become a Public Health Emergency of International Concern. Among the various treatment proposals for COVID-19 infection, passive immunotherapy using plasma from recovering patients - "convalescent plasma" (CP )- could be a promising option in the treatment of SARS-CoV-2 infections. Immune (i.e. "convalescent") plasma refers to plasma that is collected from individuals, following resolution of infection and development of antibodies. Passive antibody administration through transfusion of convalescent plasma may offer the only short-term strategy to confer immediate immunity to susceptible individuals. According to the World Health Organization (WHO), the use of plasma therapy is permitted when faced with «serious diseases for which there are no effective pharmacological treatments». Several clinical trials are underway to test the effectiveness of hyperimmune plasma at various stages of SARS-CoV2.The Food and Drug Administration (FDA), the U.S. regulatory authority, has approved the use of CP for compassionate use in the treatment of patients with a critical COVID-19 infection. Below are the general indications for drawing up clinical protocols for the integral management of "COVID-19-convalescent plasma" for which the validation and approval of the Ethics Committees is still necessary.


title: Truth Distancing? Whistleblowing as Remedy to Censorship during COVID-19

text: In the COVID-19 pandemic, whistleblowers have become the essential watchdogs disrupting suppression and control of information. Many governments have intentionally not disclosed information or failed to do so in a timely manner, misled the public or even promoted false beliefs. Fierce public interest defenders are pushing back against this censorship. Dr Fen and Dr Wenliang were the first whistleblowers in China to report that a new pandemic was possibly underway, and ever since, numerous other whistleblowers around the world have been reporting on the spread of the virus, the lack of medical equipment and other information of public interest. This paper maps the relevant whistleblowing cases in China, the USA and Europe and shows that many whistleblowers are initially censored and face disciplinary measures or even dismissals. At the same time, whistleblowing during the COVID-19 pandemic has drawn public attention to the shortcomings of institutional reporting systems and a wider appreciation of whistleblowers as uniquely placed to expose risk at early stages. Ultimately, whistleblowing as a means of transparency is not only becoming ever less controversial, but during COVID-19 it has become the “remedy” to censorship.


title: American Association of Hip and Knee Surgeons Advocacy Efforts in Response to the SARS-CoV-2 Pandemic

text: Abstract: As soon as it became clear that our economy was going to be paralyzed by the SARS-CoV-2 pandemic, AAHKS leadership acted swiftly to ensure that our members were going to be eligible for the anticipated federal economic stimulus. The cessation of elective surgery, enacted in mid-March and necessary to stop the spread of the SARS-CoV-2 virus, would surely challenge the solvency of many of our members’ practices. While our advocacy efforts discussed below have helped, clearly more relief is needed. Fortunately, our mitigation efforts have led to a “flattening of the curve” and discussions have begun on when, where, and how to safely start elective surgery again.


title: C-reactive protein in outpatients with acute exacerbation of COPD: its relationship with microbial etiology and severity

text: BACKGROUND: C-reactive protein (CRP) measurement has proven valuable for detecting exacerbations, but its usefulness in predicting etiology remains controversial. Likewise, its potential value as a marker of severity, which is well established in patients with pneumonia, remains unproven in chronic obstructive pulmonary disease (COPD) exacerbations. METHODS: A cohort study of 118 patients with severe COPD and acute infectious exacerbations were included and followed up over 1 year. Episodes of exacerbations meeting Anthonisen’s criteria type I–II were evaluated, analyzing the etiology and inflammatory response as measured by CRP in blood. RESULTS: A total of 380 episodes were recorded. Full microbiological analysis was available in 265 samples. Haemophilus influenzae was the most commonly isolated bacteria and rhinovirus the most common virus. Median CRP levels from the 265 episodes were higher in the cases with positive cultures for bacteria (58.30 mg/L, interquartile range [IQR] 21.0–28.2) than in episodes only positive for viruses (37.3 mg/L, IQR 18.6–79.1) and cases negative for any microorganism (36.4 mg/L, IQR 10.8–93.7) (P<0.014). H. influenzae and Streptococcus pneumoniae reached the highest CRP levels of 74.5 mg/L (IQR 23.9–167.9) and 74.1 mg/L (IQR 42.0–220.7), respectively. In the 380 exacerbations studied, 227 (~60%) were community-managed, while 153 (~40%) required hospital admission. In the multivariate analysis to assess the influence of inflammatory response on exacerbation severity, baseline hypercapnia (odds ratio [OR]: 2.70, 95% confidence interval [CI]: 1.46–4.9) and CRP levels >100 mg/L (OR: 4.23, 95% CI: 2.12–8.44) were independent predictors after adjustment for baseline characteristics. CONCLUSION: CRP level was higher in bacterial infections, especially when H. influenzae and S. pneumoniae were isolated. CRP values >100 mg/L were associated with a fourfold increased risk of hospital admission. Therefore, CRP blood levels may be a useful biomarker in the management of exacerbations appearing in patients with severe disease.


title: Recent highlights in the development of new antiviral drugs

text: Twenty antiviral drugs, that is about half of those that are currently approved, are formally licensed for clinical use in the treatment of human immunodeficiency virus infections (acquired immune deficiency syndrome). The others are used in the treatment of herpesvirus (e.g. herpes simplex virus, varicella zoster virus and cytomegalo virus), hepatitis B virus, hepatitis C virus or influenza virus infections. Recent endeavours have focussed on the development of improved antiviral therapies for virus infections that have already proved amenable to antiviral drug treatment, as well as for virus infections for which, at present, no antiviral drugs have been formally approved (i.e. human papilloma viruses, adenoviruses, human herpesvirus type 6, poxviruses, severe acute respiratory syndrome coronavirus and hemorrhagic fever viruses).


title: SARS-CoV-2 does not replicate in embryonated hen’s eggs or in MDCK cell lines

text: The advent of COVID-19, has posed a risk that human respiratory samples containing human influenza viruses may also contain SARS-CoV-2. This potential risk may lead to SARS-CoV-2 contaminating conventional influenza vaccine production platforms as respiratory samples are used to directly inoculate embryonated hen’s eggs and continuous cell lines that are used to isolate and produce influenza vaccines. We investigated the ability of these substrates to propagate SARS-CoV-2 and found that neither could support SARS-CoV-2 replication.


title: Epidemiological analysis of bovine torovirus in Japan

text: Abstract Bovine torovirus (BToV), a member of the Coronaviridae family, is an established gastrointestinal infectious agent in cattle. No epidemiological research on BToV has been reported from Japan. In this study, we performed a survey to detect BToV in Japan in 2004 and 2005 using 231 fecal samples (167 from diarrheic cattle and 64 from asymptomatic cattle) that were analyzed by nested reverse transcription (RT) PCR using primers located in the consensus sequences of the reported BToV nucleocapsid (N), membrane (M), and spike (S) genes. BToV N, M, and S genes were detected in 6.5% (15/231), 6.1% (14/231), and 5.6% (13/231) of samples by nested-RT-PCR, respectively. In conclusion, detectability was improved compared to the results of the first round of RT-PCR. BToV was detected at a significantly higher rate in diarrheic samples than in asymptomatic samples (14/167 diarrheic samples [8.4%] and 1/64 asymptomatic samples [1.6%]), suggesting that BToV may act as a risk factor for diarrhea in Japanese cattle. The nucleotide sequence of M fragments from the BToV isolates including the newly identified Japanese isolates showed more than 97% identity. A similar degree of homology was observed in the N gene fragment among BToV isolates with the exception of BRV-1 and BRV-2. Domestic samples were classified into three clusters by phylogenetic analysis of the S gene fragment, which were considerably correlated with the geographic origin of the samples. BToV positive areas did not adjoin each other but were spread across a wide range, suggesting that BToV exists conventionally in Japan and is geographically differentiated. We also developed an RFLP method to distinguish these clusters using two restriction enzymes, HaeIII and AccI. This method should be useful for comparing newly acquired BToV-positive samples with the reported BToVs.


title: The interaction of HIV with dendritic cells: outcomes and pathways

text: Dendritic cells (DCs), including Langerhans Cells (LCs), are probably among the earliest targets of HIV infection. Their localization in mucosal epithelia and in the T cell areas of lymphoid organs, as well as their crucial role in capturing antigens and initiating T cell responses, highlight their potential importance. Studies with cells in culture have addressed different outcomes of the HIV-–DC interaction, which include: direct productive infection of DC; carriage of virus by DC to CD4+ T cells; transfer of virus between DC and T cells at an infectious synapse; and immune evasion strategies of infected DC. Here we review the literature covering these areas, including current knowledge of underlying mechanisms or pathways.


COVID-19 treatments, QT interval and arrhythmic risk: the need for an international Registry on Arrhythmias


Will environmental impacts of social distancing due to the SARS-CoV-2 pandemic decrease allergic disease?


Potential yellow fever epidemics in unexposed populations


title: Management of chronic rhinosinusitis with steroid nasal irrigations: a viable non‐surgical alternative in the COVID‐19 Era

text: BACKGROUND: High‐dose, high‐volume steroid nasal irrigations (NSI) have been incorporated into the medical management of recalcitrant CRS, primarily following surgical intervention. The objective of this study was to evaluate the role of NSI as a preoperative management and to identify the percentage of patients who ultimately underwent ESS for recalcitrant CRS despite being on NSI. METHODS: Retrospective chart review of patients presenting with CRS who underwent a trial of NSI for at least six weeks. Pre‐irrigation and post‐irrigation outcomes measured included Lund‐Mackay scores (LMS), SNOT‐22 scores, and whether or not the patient underwent ESS. RESULTS: Of the 90 patients who underwent NSI, 32 patients underwent ESS, while 58 patients had a significant enough improvement in symptoms to avoid ESS. The likelihood of decision for surgery did not differ between the mometasone and budesonide groups (p=0.3094), comorbid asthma status (p=0.3585), smoking status (p=0.2256), polyp status (p=0.7288), or history of prior ESS (p=0.5803). SNOT scores significantly improvement following NSI in the group of patients that did not go on to ESS (p<0.0001) and in the group that did (p<0.0001). LMS also improved following NSI, but this was only statistically significant in the patients that ultimately went on to ESS (p=0.0102). CONCLUSIONS: After a trial of NSI, 64.4% of patients with CRS no longer met candidacy for ESS and had a significant improvement in SNOT‐22 scores. This supports the use of nasal steroid irrigations in the medical management of CRS with and without surgical intervention and with and without nasal polyposis. This article is protected by copyright. All rights reserved


title: Multicenter point-prevalence evaluation of the utilization and safety of drug therapies for COVID-19

text: Background: There are currently no FDA-approved medications for the treatment of COVID-19. At the onset of the pandemic, off-label medication use was supported by limited or no clinical data. We sought to characterize experimental COVID-19 therapies and identify safety signals during this period. Methods: We conducted a non-interventional, multicenter, point prevalence study of patients hospitalized with suspected/confirmed COVID-19. Clinical and treatment characteristics within a 24-hour window were evaluated in a random sample of up to 30 patients per site. The primary objective was to describe COVID-19 targeted therapies. The secondary objective was to describe adverse drug reactions (ADRs). Results: A total of 352 patients from 15 US hospitals were included. Most patients were treated at academic medical centers (53.4%) or community hospitals (42.6%). Sixty-seven patients (19%) were receiving drug therapy in addition to supportive care. Drug therapies included hydroxychloroquine (69%), remdesivir (10%), and interleukin-6 inhibitors (9%). Five patients (7.5%) were receiving combination therapy. Patients with a history of asthma (14.9% vs. 7%, p=0.037) and those enrolled in clinical trials (26.9% vs. 3.2%, p<0.001) were more likely to receive therapy. Among those receiving COVID-19 therapy, eight patients (12%) experienced an ADR, and ADRs were more commonly recognized in patients enrolled in clinical trials (62.5% vs 22%, OR=5.9, p=0.028). Conclusions: While we observed high rates of supportive care for patients with COVID-19, we also found that ADRs were common among patients receiving drug therapy including in clinical trials. Comprehensive systems are needed to identify and mitigate ADRs associated with experimental COVID-19 therapies.


title: Design, synthesis, and molecular hybrids of caudatin and cinnamic acids as novel anti-hepatitis B virus agents

text: Forty-six conjugated derivatives of caudatin with substituted cinnamic acids were synthesized, and their anti-hepatitis B virus (HBV) activity was evaluated in HepG 2.2.15 cells. Most of the derivatives exhibited potent anti-HBV activity, especially inhibiting the HBV DNA replication with the IC(50) values from 2.44 to 22.89 μΜ. Compound 18 showed significant activity against the secretion of HBsAg, HBeAg, and HBV DNA replication with IC(50) values of 5.52, 5.52, 2.44 μΜ, respectively, and had good safety (LD(50) > 1250 mg/kg) according to the acute toxicity study. Preliminary mechanism investigation suggested that compound 18 exerted antivirus effects via interfering HBV X promoter and enhancer I to influence HBV transcriptions.


title: EBNA3C interacts with Gadd34 and counteracts the unfolded protein response

text: EBNA3C is an EBV-encoded nuclear protein, essential for proliferation of EBV infected B-lymphocytes. Using EBNA3C amino acids 365-545 in a yeast two hybrid screen, we found an interaction with the Growth Arrest and DNA-damage protein, Gadd34. When both proteins are overexpressed, Gadd34 can interact with EBNA3C in both nuclear and cytoplasmic compartments. Amino acids 483-610 of Gadd34, including the two PP1a interaction, and the HSV-1 ICPγ34.5 homology domains, are required for the interaction. Furthermore, interaction is lost with a mutant of EBNA3C ((509 )DVIEVID (515)→AVIAVIA), that abolishes EBNA3C coactivation ability as well as SUMO interaction[1]. In B-cells, Gadd34, and EBNA3C are present in a complex with PP1a using microcystin sepharose affinity purification, Using a lymphoblastoid cell line in which EBNA3C protein levels are conditional on hydroxytamoxifen, surprisingly, we found that (i) EBNA3C maintains phosphorylation of eIF2α at serine 51, and (ii) protects against ER stress induced activation of the unfolded protein response as measured by XBP1 (u) versus XBP1(s) protein expression and N-terminal ATF6 cleavage. In reporter assays, overexpression of Gadd34 enhances EBNA3C's ability to co-activate EBNA2 activation of the LMP1 promoter. Collectively the data suggest that EBNA3C interacts with Gadd34, activating the upstream component of the UPR (eIF2α phosphorylation) while preventing downstream UPR events (XBP1 activation and ATF6 cleavage).


title: The Greek study in the effects of colchicine in COvid-19 complications prevention (GRECCO-19 study): Rationale and study design

text: Abstract Objective Colchicine has been utilized safely in a variety of cardiovascular clinical conditions. Among its potential mechanisms of action is the non-selective inhibition of NLRP3 inflammasome which is thought to be a major pathophysiologic component in the clinical course of patients with COVID-19. GRECCO-19 will be a prospective, randomized, open-labeled, controlled study to assess the effects of colchicine in COVID-19 complications prevention. Methods Patients with laboratory confirmed SARS-CoV-2 infection (under RT PCR) and clinical picture that involves temperature >37.5 oC and at least two out of the: i. sustained coughing, ii. sustained throat pain, iii. Anosmia and/or ageusia, iv. fatigue/tiredness, v. PaO2<95 mmHg will be included. Patients will be randomised (1:1) in colchicine or control group. Results Trial results will be disseminated through peer-reviewed publications and conference presentations. Conclusion GRECCO-19 trial aims to identify whether colchicine may positively intervene in the clinical course of COVID-19. (ClinicalTrials.gov Identifier: NCT04326790).


title: Mass Spectrometric Identification of SARS-CoV-2 Proteins from Gargle Solution Samples of COVID-19 Patients

text: [Image: see text] Mass spectrometry (MS) can deliver valuable diagnostic data that complement genomic information and allow us to increase our current knowledge of the COVID-19 disease caused by the SARS-CoV-2 virus. We developed a simple, MS-based method to specifically detect SARS-CoV-2 proteins from gargle solution samples of COVID-19 patients. The protocol consists of an acetone precipitation and tryptic digestion of proteins contained within the gargle solution, followed by a targeted MS analysis. Our methodology identifies unique peptides originating from SARS-CoV-2 nucleoprotein. Building on these promising initial results, faster MS protocols can now be developed as routine diagnostic tools for COVID-19 patients. Data are available via ProteomeXchange with identifier PXD019423.


title: HRCT imaging features in representative imported cases of 2019 novel coronavirus pneumonia

text: With the spread of novel coronavirus (2019-nCoV) pneumonia, chest high-resolution computed tomography (HRCT) has been one of the key diagnostic tools. To achieve early and accurate diagnostics, determining the radiological characteristics of the disease is of great importance. In this small scale research we retrospectively reviewed and selected six cases confirmed with 2019-nCoV infection in West China Hospital and investigated their initial and follow-up HRCT features, along with the clinical characteristics. The 2019-nCoV pneumonia basically showed a multifocal or unifocal involvement of ground-glass opacity (GGO), sometimes with consolidation and fibrosis. No pleural effusion or lymphadenopathy was identified in our presented cases. The follow-up CT generally demonstrated mild to moderate progression of the lesion, with only one case showing remission by the reducing extent and density of the airspace opacification.


title: Ligand‐centered assessment of SARS‐CoV‐2 drug target models in the Protein Data Bank

text: A bright spot in the SARS‐CoV‐2 (CoV‐2) coronavirus pandemic has been the immediate mobilization of the biomedical community, working to develop treatments and vaccines for COVID‐19. Rational drug design against emerging threats depends on well‐established methodology, mainly utilizing X‐ray crystallography, to provide accurate structure models of the macromolecular drug targets and of their complexes with candidates for drug development. In the current crisis the structural biological community has responded by presenting structure models of CoV‐2 proteins and depositing them in the Protein Data Bank (PDB), usually without time embargo and before publication. Since the structures from the first‐line research are produced in an accelerated mode, there is an elevated chance of mistakes and errors, with the ultimate risk of hindering, rather than speeding‐up, drug development. In the present work, we have used model‐validation metrics and examined the electron density maps for the deposited models of CoV‐2 proteins and a sample of related proteins available in the PDB as of 1 April 2020. We present these results with the aim of helping the biomedical community establish a better‐validated pool of data. The proteins are divided into groups according to their structure and function. In most cases, no major corrections were necessary. However, in several cases significant revisions in the functionally sensitive area of protein‐inhibitor complexes or for bound ions justified correction, re‐refinement, and eventually re‐versioning in the PDB. The re‐refined coordinate files and a tool for facilitating model comparisons are available at https://covid-19.bioreproducibility.org.


title: Clinical Application of Rapid Diagnostic Test Kit for SARS-CoV-2 Antibodies into the Field of Patient Care

text: Abstract Clinical applicability of rapid diagnostic test kit for SARS-CoV-2 antibodies was evaluated. The kit detected antibodies from day 9 to 56 of illness. IgG bands were observed up to 1: 1,000 dilutions. The kit could detect 90.5% of IgG and 61.9% of IgM antibodies of mild febrile patients without pneumonia.


title: Monitoring the Spread of Swine Enteric Coronavirus Diseases in the United States in the Absence of a Regulatory Framework

text: The reporting and monitoring of swine enteric coronavirus diseases (SECD), including porcine epidemic diarrhea virus and porcine delta coronavirus, in the United States have been challenging because of the initial absence of a regulatory framework and the emerging nature of these diseases. The National Animal Health Laboratory Network, the Emergency Management and Response System, and the Swine Health Monitoring Project were used to monitor the disease situation between May 2013 and March 2015. Important differences existed between and among them in terms of nature and extent of reporting. Here, we assess the implementation of these systems from different perspectives, including a description and comparison of collected data, disease metrics, usefulness, simplicity, flexibility, acceptability, representativeness, timeliness, and stability. This assessment demonstrates the limitations that the absence of premises identification imposes on certain animal health surveillance and response databases, and the importance of federally regulated frameworks in collecting accurate information in a timely manner. This study also demonstrates the value that the voluntary and producer-organized systems may have in monitoring emerging diseases. The results from all three data sources help to establish the baseline information on SECD epidemiological dynamics after almost 3 years of disease occurrence in the country.


title: SARS‐CoV‐2 as an extrahepatic precipitator of acute‐on‐chronic liver failure

text: We read with great interest the report by Qiu and colleages reporting the first case of acute-on-chronic liver failure (ACLF) following SARS-CoV-2 infection. Based on elevated transaminases, jaundice, and coagulopathy, the authors discuss hepatic virus entry and systemic inflammation as possible underlying mechanisms. As ACLF following hepatic versus extrahepatic insults may differ in presentation, course, and prognosis, we herein report the case of a patient with ACLF precipitated by extrahepatic complications of SARS-CoV-2.


title: Molecular Detection and Genetic Characterization of Novel RNA Viruses in Wild and Synanthropic Rodents and Shrews in Kenya

text: The majority of emerging and reemerging zoonotic viral pathogens are RNA viruses. Pathogen discovery programs of emerging infectious diseases (EIDs) in wildlife have implicated rodents and shrews as hosts of diverse human pathogens, such as hantaviruses, arenaviruses, paramyxoviruses, etc. Despite these threats, little is known about the diversity of viruses circulating among rodents and shrews in Kenya, meaning the risk of infectious disease outbreak from these small mammals could be oblivious. This study reports the first surveillance toward understanding the diversity of RNA viruses carried by rodents and shrews in areas of high-potential contact with humans in Kenya through molecular detection. A total of 617 samples comprising fecal, urine, and tissues from 138 rodents and 5 shrews were screened for eight different families of viruses using RT-PCR assays. The results highlight the presence of diverse astroviruses, paramyxoviruses, hepeviruses, and arenavirus, circulating in both wild and synanthropic Kenyan rodents and shrews. Most of the viruses detected in this study are novel strains and some belong to the families that contain important human viral pathogens. Notably, a novel arenavirus was detected in Grammomys macmillani, a rodent species newly identified to harbor arenavirus, and it potentially represent a novel arenavirus species. Our findings demonstrate the need for continued pathogen surveillance among these small mammals as well as among the vulnerable and exposed livestock and humans. This would help in development and implementation of effective preventive and control strategies on EIDs in countries with rich wildlife biodiversity like Kenya.


title: Proteomic analysis of Pteropus alecto kidney cells in response to the viral mimic, Poly I:C

text: BACKGROUND: Bats are recognised as an important reservoir for a number of highly pathogenic zoonotic viruses. While many of these viruses cause severe and often fatal disease in humans, bats are able to coexist with these viruses without clinical signs of disease. The mechanism conferring this antiviral response is not fully understood. Here, we investigated the differential protein expression of immortalised Pteropus alecto kidney cells (PaKiT03) following transfection with the viral mimic, Poly I:C. Two complementary proteomic approaches, difference gel electrophoresis (DIGE) and isobaric tagging for relative and absolute quantitation (iTRAQ) were used to quantify changes in protein expression following Poly I:C stimulation at 4, 8 and 20 hr post treatment (hpt). RESULTS: The expression of ISG54 gene, a known responder to virus infection and Poly I:C treatment, was significantly induced in transfected cells compared with mock-transfected cells. Through iTRAQ analysis we show that Poly I:C up-regulates key glycolytic enzymes at 4 hpt within PaKiT03 cells. In contrast, at 20 hpt PaKiT03 cells down-regulated ribosomal subunit proteins. The analysis with DIGE of Poly I:C transfected PaKiT03 cells showed over 215 individual spots differentially regulated, however only 25 spots could be unambiguously identified by LC-MS/MS. Immunoblotting confirmed the up-regulation of Eno1 and Tpi1 in PaKiT03 cells following Poly I:C transfection. A comparison with human cells (HEK293T and HeLa) and one additional bat cell line (PaLuT02), demonstrated that glycolytic pathways are also induced in these cell types, but at different intensities. CONCLUSION: The two techniques, DIGE and iTRAQ identified largely overlapping sets of differentially expressed proteins, however DIGE unambiguously identified significantly less proteins than iTRAQ. Poly I:C induced a rapid metabolic shift towards glycolysis within the PaKiT03 cells at 4 hpt, presumably as a consequence of increased energy requirements. On the other hand ribosomal subunit proteins were seen as down-regulated by iTRAQ, these proteins may be the limiting factors in the translational machinery available for virus replication. This study provides new insight into the antiviral response of bat cells, highlighting the importance of energy metabolism. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12953-015-0081-6) contains supplementary material, which is available to authorized users.


Microsurgical reconstruction in the time of COVID‐19


title: Inhibition of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infectivity by peptides analogous to the viral spike protein

text: Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is the cause of an atypical pneumonia that affected Asia, North America and Europe in 2002–2003. The viral spike (S) glycoprotein is responsible for mediating receptor binding and membrane fusion. Recent studies have proposed that the carboxyl terminal portion (S2 subunit) of the S protein is a class I viral fusion protein. The Wimley and White interfacial hydrophobicity scale was used to identify regions within the CoV S2 subunit that may preferentially associate with lipid membranes with the premise that peptides analogous to these regions may function as inhibitors of viral infectivity. Five regions of high interfacial hydrophobicity spanning the length of the S2 subunit of SARS-CoV and murine hepatitis virus (MHV) were identified. Peptides analogous to regions of the N-terminus or the pre-transmembrane domain of the S2 subunit inhibited SARS-CoV plaque formation by 40–70% at concentrations of 15–30 μM. Interestingly, peptides analogous to the SARS-CoV or MHV loop region inhibited viral plaque formation by >80% at similar concentrations. The observed effects were dose-dependent (IC50 values of 2–4 μM) and not a result of peptide-mediated cell cytotoxicity. The antiviral activity of the CoV peptides tested provides an attractive basis for the development of new fusion peptide inhibitors corresponding to regions outside the fusion protein heptad repeat regions.


title: Perioperative planning for cardiovascular operations in the COVID-19 pandemic

text: Coronavirus disease-2019 (COVID-19) is a serious health concern which alert all healthcare professionals worldwide. There are two main issues caused by this pandemic regarding for the healthcare system. First, it is a necessity to postpone many elective procedures/surgeries to reduce the burden of the healthcare system which may be confronted with strain by the increased speed of transmission. Therefore, we aimed to develop an algorithm called as Level of Priority to identify the priority and deferrability of cardiovascular diseases requiring surgery. Second, it is essential to perform surgery and intensive care unit follow-up in a setting where the infection prevention measures are followed for primary patients requiring emergency cardiovascular surgery. In this article, we present necessary precautions to be exercised to provide the patient safety and the highest level of protection for the surgical team.


title: Where are the airlines headed? Implications of airline industry structure and change for consumers

text: The airline industry is undergoing unprecedented change. This paper explores the consumer impacts of recent airline industry change, in the context of its oligopoly market structure and current industry environment. Economic and noneconomic events, increasing competition from low‐fare carriers, technological developments, and changes in industry practices are transforming consumer travel and interaction with airlines. Consumers can anticipate more direct flights, increased price transparency, and increased fees and time cost of security.


title: Dynamics of COVID-19 under social distancing measures are driven by transmission network structure

text: In the absence of pharmaceutical interventions, social distancing is being used worldwide to curb the spread of COVID-19. The impact of these measures has been inconsistent, with some regions rapidly nearing disease elimination and others seeing delayed peaks or nearly flat epidemic curves. Here we build a stochastic epidemic model to examine the effects of COVID-19 clinical progression and transmission network structure on the outcomes of social distancing interventions. We find that the strength of within-household transmission is a critical determinant of success, governing the timing and size of the epidemic peak, the rate of decline, individual risks of infection, and the success of partial relaxation measures. The structure of residual external connections, driven by workforce participation and essential businesses, interacts to determine outcomes. These findings can improve future predictions of the timescale and efficacy of interventions needed to control similar outbreaks, and highlight the need for better quantification and control of household transmission.


title: Anatomical features of anti-viral immunity in the respiratory tract

text: Abstract The mucosal surfaces of the lungs are a major portal of entry for virus infections and there are urgent needs for new vaccines that promote effective pulmonary immunity. However, we have only a rudimentary understanding of the requirements for effective cellular immunity in the respiratory tract. Recent studies have revealed that specialized cellular immune responses and lymphoid tissues are involved in the protection of distinct anatomical microenvironments of the respiratory tract, such as the large airways of the nose and the alveolar airspaces. This review discusses some of the anatomical features of anti-viral immunity in the respiratory tract including the role of local lymphoid tissues and the relationship between effector and memory T cells in the airways, the lung parenchyma, and lymphoid organs.


title: Experimental demyelination induced by coronavirus JHM (MHV-4): molecular identification of a viral determinant of paralytic disease

text: Abstract The molecular basis for demyelination induced by the neurotropic murine coronavirus JHM (JHMV or MHV4) is unknown. We have attempted to explore this issue by using neutralizing monoclonal antibodies specific for the major JHMV glycoprotein (E2) to select sets of neutralization resistant (NR) antigenic variant viruses. Monoclonal antibodies J.7.2 and J.2.2 bind to topographically distinct sites on E2. NR variants selected with J.7.2, like parental JHMV, predominantly cause a fatal encephalitis when given intracerebrally to mice, while J.2.2-selected NR variants cause a subacute disease characterized by paralysis and severe demyelination. We report here that consecutive selection with both J.2.2 and J.7.2 monoclonal antibodies results in NR variants which are markedly attenuated in both encephalitic potential and ability to induce demyelination. Analysis of the different variants suggests that the subregion of E2 bound by monoclonal antibody J.7.2 may be a critical viral determinant of paralysis and demyelination in this model system.


title: Development of a novel DNA microarray to detect bacterial pathogens in patients with chronic obstructive pulmonary disease (COPD)

text: Abstract A novel microarray was constructed with DNA PCR product probes targeting species specific functional genes of nine clinically significant respiratory pathogens, including the Gram-positive organisms (Streptococcus pneumoniae, Streptococcus pyogenes), the Gram-negative organisms (Chlamydia pneumoniae, Coxiella burnetii Haemophilus spp., Legionella pneumophila, Moraxella catarrhalis, and Pseudomonas aeruginosa), as well as the atypical bacterium, Mycoplasma pneumoniae. In a “proof-of-concept” evaluation of the developed microarray, the microarray was compared with real-time PCR from 14 sputum specimens from COPD patients. All of the samples positive for bacterial species in real-time PCR were also positive for the same bacterial species using the microarray. This study shows that a microarray using PCR probes is a potentially useful method to monitor the populations of bacteria in respiratory specimens and can be tailored to specific clinical needs such as respiratory infections of particular patient populations, including patients with cystic fibrosis and bronchiectasis.


Mayo Clinic Strategies for COVID-19: Revamping Outpatient Care for Patients Without COVID-19


title: Application of proteomics methods for pathogen discovery

text: Abstract Proteomics have been used widely to study proteins in complex materials such as cells, body fluids, tissues, and organisms. Application of advance proteomic techniques for the characterization of disease-specific proteins may provide information for the detection of potential infectious agents. In this report, two proteomics techniques, a two-dimensional differential gel electrophoresis (2D-DIGE) and a one-dimensional gel electrophoresis and one-dimensional liquid chromatography coupled with mass spectrometry (GeLC-MS/MS), were applied for investigating viral proteins from cultured cells inoculated with a clinical sample. The 2D-DIGE method identified five viral proteins of vaccinia virus that are only present in infected cells, these results are in agreement with findings determined by genome based methods. The GeLC-MS/MS method identified eight vaccinia virus proteins out of 428 proteins detected in the sample. These results demonstrate that proteomic techniques can be used effectively for the detection of infectious agents. Given that the methods are capable of applying to proteins without a prior knowledge of the pathogen present, proteomics has a potential of being developed as a molecular tool for pathogen discovery, and disease diagnosis of emerging infectious diseases and for bioterrorism defense.


title: Rapid reviews for rapid decision-making during the coronavirus disease (COVID-19) pandemic, Norway, 2020

text: In response to urgent needs for updated evidence for decision-making on various aspects related to coronavirus disease (COVID-19), the Norwegian Institute of Public Health established a rapid review team. Using simplified processes and shortcuts, this team produces summary reviews on request within 1–3 days that inform advice provided by the institute. All reviews are published with explicit messages about the risk of overlooking key evidence or making misguided judgements by using such rapid processes.


title: Nucleolar Protein Trafficking in Response to HIV-1 Tat: Rewiring the Nucleolus

text: The trans-activator Tat protein is a viral regulatory protein essential for HIV-1 replication. Tat trafficks to the nucleoplasm and the nucleolus. The nucleolus, a highly dynamic and structured membrane-less sub-nuclear compartment, is the site of rRNA and ribosome biogenesis and is involved in numerous cellular functions including transcriptional regulation, cell cycle control and viral infection. Importantly, transient nucleolar trafficking of both Tat and HIV-1 viral transcripts are critical in HIV-1 replication, however, the role(s) of the nucleolus in HIV-1 replication remains unclear. To better understand how the interaction of Tat with the nucleolar machinery contributes to HIV-1 pathogenesis, we investigated the quantitative changes in the composition of the nucleolar proteome of Jurkat T-cells stably expressing HIV-1 Tat fused to a TAP tag. Using an organellar proteomic approach based on mass spectrometry, coupled with Stable Isotope Labelling in Cell culture (SILAC), we quantified 520 proteins, including 49 proteins showing significant changes in abundance in Jurkat T-cell nucleolus upon Tat expression. Numerous proteins exhibiting a fold change were well characterised Tat interactors and/or known to be critical for HIV-1 replication. This suggests that the spatial control and subcellular compartimentaliation of these cellular cofactors by Tat provide an additional layer of control for regulating cellular machinery involved in HIV-1 pathogenesis. Pathway analysis and network reconstruction revealed that Tat expression specifically resulted in the nucleolar enrichment of proteins collectively participating in ribosomal biogenesis, protein homeostasis, metabolic pathways including glycolytic, pentose phosphate, nucleotides and amino acids biosynthetic pathways, stress response, T-cell signaling pathways and genome integrity. We present here the first differential profiling of the nucleolar proteome of T-cells expressing HIV-1 Tat. We discuss how these proteins collectively participate in interconnected networks converging to adapt the nucleolus dynamic activities, which favor host biosynthetic activities and may contribute to create a cellular environment supporting robust HIV-1 production.


title: Using telehealth for hospice reauthorization visits: results of a quality improvement analysis

text: BACKGROUND: Increasing hospice need, a growing shortage of hospice providers, and concerns about in-person services due to COVID-19 require hospices to innovate care delivery. MEASURES: This project compared outcomes between hospice reauthorization visits conducted via telehealth and in-person. After each visit, providers, patients and caregivers completed telehealth acceptance surveys, and providers recorded reauthorization recommendations. INTERVENTION: Providers conducted 88 concurrent in-person and telehealth visits between June and November, 2019. OUTCOMES: No statistically significant differences in reauthorization recommendations were found between telehealth and in-person visits. Satisfaction with telehealth was high; 88% of patients/caregivers and 78% of providers found telehealth services as effective as in-person visits. CONCLUSIONS/LESSONS LEARNED: Results indicate that telehealth can successfully support clinical decision making for hospice reauthorization. These findings show telehealth to be reliable and acceptable for certain types of hospice care even prior to COVID-19, which emphasizes its importance both during and after the current public health emergency.


title: Social determinants of health inequalities: towards a theoretical perspective using systems science

text: A systems approach offers a novel conceptualization to natural and social systems. In recent years, this has led to perceiving population health outcomes as an emergent property of a dynamic and open, complex adaptive system. The current paper explores these themes further and applies the principles of systems approach and complexity science (i.e. systems science) to conceptualize social determinants of health inequalities. The conceptualization can be done in two steps: viewing health inequalities from a systems approach and extending it to include complexity science. Systems approach views health inequalities as patterns within the larger rubric of other facets of the human condition, such as educational outcomes and economic development. This anlysis requires more sophisticated models such as systems dynamic models. An extension of the approach is to view systems as complex adaptive systems, i.e. systems that are 'open' and adapt to the environment. They consist of dynamic adapting subsystems that exhibit non-linear interactions, while being 'open' to a similarly dynamic environment of interconnected systems. They exhibit emergent properties that cannot be estimated with precision by using the known interactions among its components (such as economic development, political freedom, health system, culture etc.). Different combinations of the same bundle of factors or determinants give rise to similar patterns or outcomes (i.e. property of convergence), and minor variations in the initial condition could give rise to widely divergent outcomes. Novel approaches using computer simulation models (e.g. agent-based models) would shed light on possible mechanisms as to how factors or determinants interact and lead to emergent patterns of health inequalities of populations.


title: Molecular and phylogenetic analysis of bovine coronavirus based on the spike glycoprotein gene

text: Abstract Bovine coronavirus has been associated with diarrhoea in newborn calves, winter dysentery in adult cattle and respiratory tract infections in calves and feedlot cattle. In Cuba, the presence of BCoV was first reported in 2006. Since then, sporadic outbreaks have continued to occur. This study was aimed at deepening the knowledge of the evolution, molecular markers of virulence and epidemiology of BCoV in Cuba. A total of 30 samples collected between 2009 and 2011 were used for PCR amplification and direct sequencing of partial or full S gene. Sequence comparison and phylogenetic studies were conducted using partial or complete S gene sequences as phylogenetic markers. All Cuban bovine coronavirus sequences were located in a single cluster supported by 100% bootstrap and 1.00 posterior probability values. The Cuban bovine coronavirus sequences were also clustered with the USA BCoV strains corresponding to the GenBank accession numbers EF424621 and EF424623, suggesting a common origin for these viruses. This phylogenetic cluster was also the only group of sequences in which no recombination events were detected. Of the 45 amino acid changes found in the Cuban strains, four were unique.


title: No involvement of alveolar macrophages in the initiation of carbon nanoparticle induced acute lung inflammation in mice

text: BACKGROUND: Carbonaceous nanoparticles (CNP) represent a major constituent of urban particulate air pollution, and inhalation of high CNP levels has been described to trigger a pro-inflammatory response of the lung. While several studies identified specific particle characteristics driving respiratory toxicity of low-solubility and low-toxicity particles such as CNP, the major lung cell type, which initiates and drives that response, remains still uncertain. Since alveolar macrophages (AM) are known to effectively phagocytose inhaled particles and play a crucial role for the initiation of pulmonary inflammation caused by invading microbes, we aimed to determine their role for sterile stimuli such as CNP by profiling the primary alveolar cell compartments of the lung. We exposed C57BL/6 mice to 20 μg CNP by intratracheal instillation and comprehensively investigated the expression of the underlying mediators during a time span of 3 to 72 h in three different lung cell populations: CD45- (negative) structural cells, CD45+ (positive) leukocytes, and by BAL recovered cells. RESULTS: Bronchoalveolar lavage (BAL) analysis revealed an acute inflammatory response characterized by the most prominent culmination of neutrophil granulocytes from 12 to 24 h after instillation, which declined to basal levels by day 7. As early as 3 h after CNP exposure 50 % of the AM revealed particle laden. BAL concentrations and lung gene expression profiles of TNFα, and the neutrophil chemoattractants CXCL1,-2 and-5 preceded the neutrophil recruitment and showed highest levels after 12 h of CNP exposure, pointing to a significant activation of the inflammation-evoking lung cells at this point of time. AM, isolated from lungs 3 to 12 h after CNP instillation, however, did not show a pro-inflammatory signature. On the contrary, gene expression analysis of different lung cell populations isolated 12 h after CNP instillation revealed CD45-, mainly representing alveolar epithelial type II (ATII) cells as major producer of inflammatory CXCL cytokines. Particularly by CD45- cells expressed Cxcl5 proved to be the most abundant chemokine, being 12 h after CNP exposure 24 (±11) fold induced. CONCLUSION: Our data suggests that AM are noninvolved in the initiation of the inflammatory response. ATII cells, which induced highest CXCL levels early on, might in contrast be the driver of acute neutrophilic inflammation upon pulmonary CNP exposure. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12989-016-0144-6) contains supplementary material, which is available to authorized users.


title: Identification of WU polyomavirus from pediatric patients with acute respiratory infections in Beijing, China

text: A novel polyomavirus (WU virus) has been identified in pediatric patients with acute respiratory tract infections (ARI), but its role as a respiratory pathogen has not yet been demonstrated. To investigate if WU virus is related to acute respiratory infections in infants and children in Beijing, specimens collected from 674 pediatric patients with ARI from April 2007 to May 2008 and from 202 children without ARI were used for this investigation. Common respiratory viruses were tested by virus isolation and/or antigen detection by indirect immunofluorescent assay followed by RT-PCR or PCR for other viruses associated with respiratory infections in specimens collected from patients with ARI before WU virus DNA was detected. WU virus DNA was detected by initial screening and secondary confirmation PCR for all specimens. The region encoding the VP2 gene of the virus was amplified from 17 WU-virus-positive clinical specimens, and sequence analysis was performed. Thirty-eight of 674 (5.6%) specimens from patients with ARI and 3 of 202 (1.5%) specimens from children without ARI yielded PCR products with the predicted molecular weight, using either screening or confirmation primer sets, indicating that these specimens were WU virus positive. However, more than 60% of the 38 WU-virus-positive specimens from patients with ARI were also positive for one or more respiratory viruses. The nucleotide and deduced amino acid sequences of the region encoding the VP2 gene from 17 Beijing WU viruses shared high homology (>98.5%) with sequences from GenBank and among themselves. The data indicated that WU virus in Beijing occurred 3.7 times more frequently in pediatric patients with ARI than in those without ARI (p < 0.05).


title: Statistical Issues and Lessons Learned From COVID-19 Clinical Trials With Lopinavir-Ritonavir and Remdesivir

text: BACKGROUND: Recently, three randomized clinical trials on coronavirus disease (COVID-19) treatments were completed: one for lopinavir-ritonavir and two for remdesivir. One trial reported that remdesivir was superior to placebo in shortening the time to recovery, while the other two showed no benefit of the treatment under investigation. OBJECTIVE: The aim of this paper is to, from a statistical perspective, identify several key issues in the design and analysis of three COVID-19 trials and reanalyze the data from the cumulative incidence curves in the three trials using more appropriate statistical methods. METHODS: The lopinavir-ritonavir trial enrolled 39 additional patients due to insignificant results after the sample size reached the planned number, which led to inflation of the type I error rate. The remdesivir trial of Wang et al failed to reach the planned sample size due to a lack of eligible patients, and the bootstrap method was used to predict the quantity of clinical interest conditionally and unconditionally if the trial had continued to reach the originally planned sample size. Moreover, we used a terminal (or cure) rate model and a model-free metric known as the restricted mean survival time or the restricted mean time to improvement (RMTI) to analyze the reconstructed data. The remdesivir trial of Beigel et al reported the median recovery time of the remdesivir and placebo groups, and the rate ratio for recovery, while both quantities depend on a particular time point representing local information. We use the restricted mean time to recovery (RMTR) as a global and robust measure for efficacy. RESULTS: For the lopinavir-ritonavir trial, with the increase of sample size from 160 to 199, the type I error rate was inflated from 0.05 to 0.071. The difference of RMTIs between the two groups evaluated at day 28 was –1.67 days (95% CI –3.62 to 0.28; P=.09) in favor of lopinavir-ritonavir but not statistically significant. For the remdesivir trial of Wang et al, the difference of RMTIs at day 28 was –0.89 days (95% CI –2.84 to 1.06; P=.37). The planned sample size was 453, yet only 236 patients were enrolled. The conditional prediction shows that the hazard ratio estimates would reach statistical significance if the target sample size had been maintained. For the remdesivir trial of Beigel et al, the difference of RMTRs between the remdesivir and placebo groups at day 30 was –2.7 days (95% CI –4.0 to –1.2; P<.001), confirming the superiority of remdesivir. The difference in the recovery time at the 25th percentile (95% CI –3 to 0; P=.65) was insignificant, while the differences became more statistically significant at larger percentiles. CONCLUSIONS: Based on the statistical issues and lessons learned from the recent three clinical trials on COVID-19 treatments, we suggest more appropriate approaches for the design and analysis of ongoing and future COVID-19 trials.


title: A glycan cluster on the SARS-CoV-2 spike ectodomain is recognized by Fab-dimerized glycan-reactive antibodies

text: The COVID-19 pandemic caused by SARS-CoV-2 has escalated into a global crisis. The spike (S) protein that mediates cell entry and membrane fusion is the current focus of vaccine and therapeutic antibody development efforts. The S protein, like many other viral fusion proteins such as HIV-1 envelope (Env) and influenza hemagglutinin, is glycosylated with both complex and high mannose glycans. Here we demonstrate binding to the SARS-CoV-2 S protein by a category of Fab-dimerized glycan-reactive (FDG) HIV-1-induced broadly neutralizing antibodies (bnAbs). A 3.1 Å resolution cryo-EM structure of the S protein ectodomain bound to glycan-dependent HIV-1 bnAb 2G12 revealed a quaternary glycan epitope on the spike S2 domain involving multiple protomers. These data reveal a new epitope on the SARS-CoV-2 spike that can be targeted for vaccine design. Highlights Fab-dimerized, glycan-reactive (FDG) HIV-1 bnAbs cross-react with SARS-CoV-2 spike. 3.1 Å resolution cryo-EM structure reveals quaternary S2 epitope for HIV-1 bnAb 2G12. 2G12 targets glycans, at positions 709, 717 and 801, in the SARS-CoV-2 spike. Our studies suggest a common epitope for FDG antibodies centered around glycan 709.


Detection of 20 respiratory viruses and bacteria by influenza-like illness surveillance in Beijing, China, 2016–2018


title: Managing Oncology Services During a Major Coronavirus Outbreak: Lessons From the Saudi Arabia Experience

text: Outbreaks of infectious etiology, particularly those caused by a novel virus that has no known treatment or vaccine, may result in the interruption of medical care provided to patients with cancer and put them at risk for undertreatment in addition to the risk of being exposed to infection, a life-threatening event among patients with cancer. This article describes the approach used to manage patients with cancer during a large-scale Middle East respiratory syndrome–coronavirus hospital outbreak in Saudi Arabia to ensure continuity of care and minimize harm from treatment interruption or acquiring infection. The approach taken toward managing this high-risk situation (COVID-19) could be easily adopted by health care organizations and would be helpful to ensure readiness for the occurrence of future outbreaks of different infectious etiologies like those recent episodes of new coronavirus.


title: Characterization of the guanine-N7 methyltransferase activity of coronavirus nsp14 on nucleotide GTP

text: Abstract Most eukaryotic viruses that replicate in the cytoplasm, including coronaviruses, have evolved strategies to cap their RNAs. In our previous work, the nonstructural protein (nsp) 14 of severe acute respiratory syndrome coronavirus (SARS-CoV) was identified as a cap (guanine-N7)-methyltransferase (N7-MTase). In this study, we found that GTP, dGTP as well as cap analogs GpppG, GpppA and m7GpppG could be methylated by SARS-CoV nsp14. In contrast, the nsp14 could not modify ATP, CTP, UTP, dATP, dCTP, dUTP or cap analog m7GpppA. Critical residues of nsp14 essential for the methyltransferase activity on GTP were identified, which include F73, R84, W86, R310, D331, G333, P335, Y368, C414, and C416. We further showed that the methyltransferase activity of GTP was universal for nsp14 of other coronaviruses. Moreover, the accumulation of m7GTP or presence of protein nsp14 could interfere with protein translation of cellular mRNAs. Altogether, the results revealed a new enzymatic activity of coronavirus nsp14.


title: Molecular mechanisms of sex bias differences in COVID-19 mortality

text: More men than women have died from COVID-19. Genes encoded on X chromosomes, and sex hormones may explain the decreased fatality of COVID-19 in women. The angiotensin-converting enzyme 2 gene is located on X chromosomes. Men, with a single X chromosome, may lack the alternative mechanism for cellular protection after exposure to SARS-CoV-2. Some Toll-like receptors encoded on the X chromosomes can sense SARS-CoV-2 nucleic acids, leading to a stronger innate immunity response in women. Both estrogen and estrogen receptor-α contribute to T cell activation. Interventional approaches including estrogen-related compounds and androgen receptor antagonists may be considered in patients with COVID-19.


title: Study of transmission dynamics of novel COVID-19 by using mathematical model

text: In this research work, we present a mathematical model for novel coronavirus-19 infectious disease which consists of three different compartments: susceptible, infected, and recovered under convex incident rate involving immigration rate. We first derive the formulation of the model. Also, we give some qualitative aspects for the model including existence of equilibriums and its stability results by using various tools of nonlinear analysis. Then, by means of the nonstandard finite difference scheme (NSFD), we simulate the results for the data of Wuhan city against two different sets of values of immigration parameter. By means of simulation, we show how protection, exposure, death, and cure rates affect the susceptible, infected, and recovered population with the passage of time involving immigration. On the basis of simulation, we observe the dynamical behavior due to immigration of susceptible and infected classes or one of these two.


title: “I will never go to Hong Kong again!” How the secondary crisis communication of “Occupy Central” on Weibo shifted to a tourism boycott

text: Social media, an open space for the public's opinion and expression, has become an increasingly essential issue in crisis events, leading to secondary crisis communication. Realizing the potential risk of that, this study took the “Occupy Central” spreading on Weibo as a case, and applied topic clustering and sentiment analysis to examine the sequential characteristics of secondary crisis communication on social media in topics and emotions. Results show that the topics Weibo users discussed shifted from a political event to tourism boycott, with emotions turning increasingly negative. The turning point of such a transfer was aroused group conflicts and negative emotions elicited between people from mainland China and Hong Kong. The results indicate the necessity of emphasizing secondary crisis communication during a crisis due to the dynamic and sequential change of topics and public's emotions, which may result in new crises impacting the tourism destination where the initial crisis occurs.


title: COVID-19 herd immunity strategies: walking an elusive and dangerous tightrope

text: The rapid growth in cases of COVID-19 has threatened to overwhelm healthcare systems in multiple countries. In response, severely affected countries have had to consider a range of public health strategies achieved by implementing non-pharmaceutical interventions. Broadly, these strategies have fallen into two categories: i) “mitigation”, which aims to achieve herd immunity by allowing the SARS-CoV-2 virus to spread through the population while mitigating disease burden, and ii) “suppression”, aiming to drastically reduce SARS-CoV-2 transmission rates and halt endogenous transmission in the target population. Using an age-structured transmission model, parameterised to simulate SARS-CoV-2 transmission in the UK, we assessed the prospects of success using both of these approaches. We simulated a range of different non-pharmaceutical intervention scenarios incorporating social distancing applied to differing age groups. We found that it is possible to suppress SARS-CoV-2 transmission if social distancing measures are sustained at a sufficient level for a period of months. Our modelling did not support achieving herd immunity as a practical objective, requiring an unlikely balancing of multiple poorly-defined forces. Specifically, we found that: i) social distancing must initially reduce the transmission rate to within a narrow range, ii) to compensate for susceptible depletion, the extent of social distancing must be vary over time in a precise but unfeasible way, and iii) social distancing must be maintained for a long duration (over 6 months).


Options thérapeutiques en cancérologie génito-urinaire en période épidémique du COVID-19


title: Emerging and re‐emerging infections at the turn of the millennium

text: Summary. After World War II, mankind believed that infectious diseases were on the way to being defeated. Unfortunately, they still are the second worldwide cause of death. Globalization changes promote the emergence of new infections and pandemics; international deliveries and travelling facilitate the dissemination of infectious agents; man‐induced environmental changes create new opportunities for contacts between species, leading to infections in aberrant hosts, including man; global warming enables insects, a major vector of pathogens, to thrive in more countries. The main pandemics have been caused by viruses, such as HIV and novel subtypes of influenza viruses. In addition, prion proteins are a threat. The transmission of the Creutzfeld Jakob disease variant through blood transfusion and the recent discovery of prion protein in the spleen of a haemophilia patient are a matter of further concern. The end of the war against infectious diseases is not in sight. Mankind’s battle with pathogens has lasted millennia and is destined to continue.


title: Dogs immunized with LBSap vaccine displayed high levels of IL-12 and IL-10 cytokines and CCL4, CCL5 and CXCL8 chemokines in the dermis

text: Abstract The complex interplay between cytokines and chemokines regulates innate and adaptive immune responses against pathogens; specifically, cytokine and chemokine expression drives activation of immune effector cells and their recruitment to tissue infection sites. Herein, we inoculated dogs with Leishmania braziliensis antigens plus saponin (the LBSap vaccine), as well as with the vaccine components, and then used real-time PCR to evaluate the kinetics of dermal expression of mRNAs of cytokines (IL-12, IFN-γ, TNF-α, IL-4, IL-13, TGF-β and IL-10) and chemokines (CCL2, CCL4, CCL5, CCL21 and CXCL8) 1, 12, 24 and 48h after inoculation. We also evaluated the correlation between cytokine and chemokine expression and dermal cellularity. The LBSap vaccine induced high levels of IL-12 and IL-10 expression at 12 and 24h, respectively. Furthermore, we observed positive correlations between IL-12 and IL-13 expression, IFN-γ and IL-13 expression, and IL-13 and TGF-β expression, suggesting that a mixed cytokine microenvironment developed after immunization with the vaccine. Inoculation with the saponin adjuvant alone induced a chemokine and cytokine expression profile similar to that observed in the LBSap group. CCL4 and CXCL8 chemokine expression was up regulated by the LBSap vaccine. CCL5 expression was initially highest in the LBSap group, but at 48h, expression was highest in the LB group. Information about the kinetics of the immune response to this vaccine gained using this dog model will help to elucidate the mechanisms of and factors involved in a protective response against Leishmania infection and will aid in establishing rational approaches for the development of vaccines against canine visceral leishmaniasis.


title: Advances in Meningeal Immunity

text: The central nervous system (CNS) is an immunologically specialized tissue protected by a blood–brain barrier. The CNS parenchyma is enveloped by a series of overlapping membranes that are collectively referred to as the meninges. The meninges provide an additional CNS barrier, harbor a diverse array of resident immune cells, and serve as a crucial interface with the periphery. Recent studies have significantly advanced our understanding of meningeal immunity, demonstrating how a complex immune landscape influences CNS functions under steady-state and inflammatory conditions. The location and activation state of meningeal immune cells can profoundly influence CNS homeostasis and contribute to neurological disorders, but these cells are also well equipped to protect the CNS from pathogens. In this review, we discuss advances in our understanding of the meningeal immune repertoire and provide insights into how this CNS barrier operates immunologically under conditions ranging from neurocognition to inflammatory diseases.


title: ACUTE KIDNEY INJURY IN PATIENTS HOSPITALIZED WITH COVID-19

text: The rate of acute kidney injury (AKI) associated with patients hospitalized with Covid-19, and associated outcomes are not well understood. This study describes the presentation, risk factors and outcomes of AKI in patients hospitalized with Covid-19. We reviewed the health records for all patients hospitalized with Covid-19 between March 1, and April 5, 2020, at 13 academic and community hospitals in metropolitan New York. Patients younger than 18 years of age, with end stage kidney disease or with a kidney transplant were excluded. AKI was defined according to KDIGO criteria. Of 5,449 patients admitted with Covid-19, AKI developed in 1,993 (36.6%). The peak stages of AKI were stage 1 in 46.5%, stage 2 in 22.4% and stage 3 in 31.1%. Of these, 14.3% required renal replacement therapy (RRT). AKI was primarily seen in Covid-19 patients with respiratory failure, with 89.7% of patients on mechanical ventilation developing AKI compared to 21.7% of non-ventilated patients. 276/285 (96.8%) of patients requiring RRT were on ventilators. Of patients who required ventilation and developed AKI, 52.2% had the onset of AKI within 24 hours of intubation. Risk factors for AKI included older age, diabetes mellitus, cardiovascular disease, black race, hypertension and need for ventilation and vasopressor medications. Among patients with AKI, 694 died (35%), 519 (26%) were discharged and 780 (39%) were still hospitalized. AKI occurs frequently among patients with Covid-19 disease. It occurs early and in temporal association with respiratory failure and is associated with a poor prognosis.


title: Complete Genome Sequence of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) from the First Imported MERS-CoV Case in China

text: On 26 May 2015, an imported Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in Guangdong Province, China, and found to be closely related to the MERS-CoV strain prevalent in South Korea. The full genome of the ChinaGD01 strain was sequenced and analyzed to investigate the epidemiology and evolution of MERS-CoV circulating in South Korea and China.


title: Analysis of the mechanism by which BALB/c mice having prior immunization with nucleocapsid protein of SARS-CoV develop severe pneumonia after SARS-CoV infection

text: Abstract The precise mechanism of severe acute respiratory syndrome (SARS), which is caused by SARS-associated coronavirus (SARS-CoV), is still unclear. We generated recombinant vaccinia virus (rVV) LC16m8 strain which simultaneously expresses four structural proteins of SARS-CoV, including nucleocapsid (N), membrane (M), envelop (E), spike (S) proteins (rVV-NMES) and reported that old BALB/c mice having prior immunization with rVV-NMES develop severe pneumonia similar to those of control mice though rVV-NMES-immunized mice showed lower pulmonary viral titer than in the control mice. Furthermore, we determined which SARS-CoV structural protein for the prior rVV-immunization is responsible for the severe pneumonia after the SARS-CoV infection as observed in the rVV-NMES-immunized mice. Old BALB/c mice were inoculated intradermally with rVV that expressed each structural proteins of SARS-CoV (rVV-N, -M, -E, or -S) with or without rVV-S and then infected intranasally with SARS-CoV more than 4 weeks later. At 9 days after SARS-CoV infection, the rVV-N-immunized mice show more severe pneumonia than in other groups. Furthermore, significant up-regulation of Th1 (IL-2)- and Th2 (IL-4 and IL-5)-bias cytokines and down-regulation of anti-inflammatory cytokine (IL-10 and TGF-β) were observed in rVV-N-immunized mice, resulting in the intensive infiltration of immunocompetent cells into the lung. In contrast, rVV-S-immunized mice showed only low pulmonary viral tier and slight pneumonia. However, the mice having co-immunization with both rVV-N and rVV-S showed severe pneumonia though their pulmonary viral titer was low. These results suggest that an excessive host immune response against the N protein of SARS-CoV is involved in severe pneumonia caused by SARS-CoV infection. These findings increase our understanding of the pathogenesis of SARS.


title: Should Institutions Disclose the Names of Employees with Covid‐19?

text: Prestigious University is a large, private educational institution with a medical school, a university hospital, a law school, and graduate and undergraduate colleges all on a single campus. In the face of the Covid‐19 pandemic, students were told during spring break to return to campus only briefly to retrieve their belongings. Classes then went online. On March 23, 2020, the faculty, students, and staff were emailed the following by the university's director of infection control and public health: We have become aware that a Prestigious University staff member has tested positive for the virus that causes Covid‐19. The individual, who was last on campus on March 16, is now in isolation at their permanent residence and is doing well clinically. The university has already identified those members of our community who may have been in close contact with this individual, and we are working to notify them. Further, this individual's local health department has a protocol for identifying people who have been in direct contact with anyone testing positive for Covid‐19 (such as this Prestigious University staff member) so that they can self‐quarantine and watch for COVID‐19 symptoms for a period of 14 days from their last contact with the infected individual. A professor in the Philosophy Department has asked the ethicists at the medical school whether such contact tracing suffices. “Don't the members of the community deserve to know who this is? Isn't there a mandate to identify this person in order to maximize public health benefits and slow the spread of this deadly virus?”


title: Role of MAPK/MNK1 signaling in virus replication

text: Abstract Viruses are obligate intracellular parasites; they heavily depend on the host cell machinery to effectively replicate and produce new progeny virus particles. Following viral infection, diverse cell signaling pathways are initiated by the cells, with the major goal of establishing an antiviral state. However, viruses have been shown to exploit cellular signaling pathways for their own effective replication. Genome-wide siRNA screens have also identified numerous host factors that either support (proviral) or inhibit (antiviral) virus replication. Some of the host factors might be dispensable for the host but may be critical for virus replication; therefore such cellular factors may serve as targets for development of antiviral therapeutics. Mitogen activated protein kinase (MAPK) is a major cell signaling pathway that is known to be activated by diverse group of viruses. MAPK interacting kinase 1 (MNK1) has been shown to regulate both cap-dependent and internal ribosomal entry sites (IRES)-mediated mRNA translation. In this review we have discuss the role of MAPK in virus replication, particularly the role of MNK1 in replication and translation of viral genome.


title: Viral pneumonia

text: Summary About 200 million cases of viral community-acquired pneumonia occur every year—100 million in children and 100 million in adults. Molecular diagnostic tests have greatly increased our understanding of the role of viruses in pneumonia, and findings indicate that the incidence of viral pneumonia has been underestimated. In children, respiratory syncytial virus, rhinovirus, human metapneumovirus, human bocavirus, and parainfluenza viruses are the agents identified most frequently in both developed and developing countries. Dual viral infections are common, and a third of children have evidence of viral-bacterial co-infection. In adults, viruses are the putative causative agents in a third of cases of community-acquired pneumonia, in particular influenza viruses, rhinoviruses, and coronaviruses. Bacteria continue to have a predominant role in adults with pneumonia. Presence of viral epidemics in the community, patient's age, speed of onset of illness, symptoms, biomarkers, radiographic changes, and response to treatment can help differentiate viral from bacterial pneumonia. However, no clinical algorithm exists that will distinguish clearly the cause of pneumonia. No clear consensus has been reached about whether patients with obvious viral community-acquired pneumonia need to be treated with antibiotics. Apart from neuraminidase inhibitors for pneumonia caused by influenza viruses, there is no clear role for use of specific antivirals to treat viral community-acquired pneumonia. Influenza vaccines are the only available specific preventive measures. Further studies are needed to better understand the cause and pathogenesis of community-acquired pneumonia. Furthermore, regional differences in cause of pneumonia should be investigated, in particular to obtain more data from developing countries.


title: COVID-19 in patients with rheumatic disease in Hubei province, China: a multicentre retrospective observational study

text: BACKGROUND: In the ongoing COVID-19 pandemic, the susceptibility of patients with rheumatic diseases to COVID-19 remains unclear. We aimed to investigate susceptibility to COVID-19 in patients with autoimmune rheumatic diseases during the ongoing COVID-19 pandemic. METHODS: We did a multicentre retrospective study of patients with autoimmune rheumatic diseases in Hubei province, the epicentre of the COVID-19 outbreak in China. Patients with rheumatic diseases were contacted through an automated telephone-based survey to investigate their susceptibility to COVID-19. Data about COVID-19 exposure or diagnosis were collected. Families with a documented history of COVID-19 exposure, as defined by having at least one family member diagnosed with COVID-19, were followed up by medical professionals to obtain detailed information, including sex, age, smoking history, past medical history, use of medications, and information related to COVID-19. FINDINGS: Between March 20 and March 30, 2020, 6228 patients with autoimmune rheumatic diseases were included in the study. The overall rate of COVID-19 in patients with an autoimmune rheumatic disease in our study population was 0·43% (27 of 6228 patients). We identified 42 families in which COVID-19 was diagnosed between Dec 20, 2019, and March 20, 2020, in either patients with a rheumatic disease or in a family member residing at the same physical address during the outbreak. Within these 42 families, COVID-19 was diagnosed in 27 (63%) of 43 patients with a rheumatic disease and in 28 (34%) of 83 of their family members with no rheumatic disease (adjusted odds ratio [OR] 2·68 [95% CI 1·14–6·27]; p=0·023). Patients with rheumatic disease who were taking hydroxychloroquine had a lower risk of COVID-19 infection than patients taking other disease-modifying anti-rheumatic drugs (OR 0·09 [95% CI 0·01–0·94]; p=0·044). Additionally, the risk of COVID-19 was increased with age (adjusted OR 1·04 [95%CI 1·01–1·06]; p=0·0081). INTERPRETATION: Patients with autoimmune rheumatic disease might be more susceptible to COVID-19 infection than the general population. FUNDING: National Natural Science Foundation of China and the Tongji Hospital Clinical Research Flagship Program.


Le ‘’COVID-Sleep’’ des chirurgiens…. Jusqu’à quand?


title: Recommendations on vaccination for Latin American small animal practitioners: a report of the WSAVA Vaccination Guidelines Group

text: The World Small Animal Veterinary Association Vaccination Guidelines Group has produced global guidelines for small companion animal practitioners on best practice in canine and feline vaccination. Recognising that there are unique aspects of veterinary practice in certain geographical regions of the world, the Vaccination Guidelines Group undertook a regional project in Latin America between 2016 and 2019, culminating in the present document. The Vaccination Guidelines Group gathered scientific and demographic data during visits to Argentina, Brazil and Mexico, by discussion with national key opinion leaders, visiting veterinary practices and review of the scientific literature. A questionnaire survey was completed by 1390 veterinarians in five Latin American countries and the Vaccination Guidelines Group delivered continuing education at seven events attended by over 3500 veterinarians. The Vaccination Guidelines Group recognised numerous challenges in Latin America, for example: (1) lack of national oversight of the veterinary profession, (2) extraordinary growth in private veterinary schools of undetermined quality, (3) socioeconomic constraints on client engagement with preventive health care, (4) high regional prevalence of some key infectious diseases (e.g. feline leukaemia virus infection, canine visceral leishmaniosis), (5) almost complete lack of minimal antigen vaccine products as available in other markets, (6) relative lack of vaccine products with extended duration of immunity as available in other markets, (7) availability of vaccine products withdrawn from other markets (e.g. Giardia vaccine) or unique to Latin America (e.g. some Leishmania vaccines), (8) accessibility of vaccines directly by pet owners or breeders such that vaccination is not delivered under veterinary supervision, (9) limited availability of continuing education in veterinary vaccinology and lack of compulsion for continuing professional development and (10) limited peer‐reviewed published scientific data on small companion animal infectious diseases (with the exception of leishmaniosis) and lack of support for such academic research. In this document, the Vaccination Guidelines Group summarises the findings of this project and assesses in evidence‐based fashion the scientific literature pertaining to companion animal vaccine‐preventable diseases in Latin America. The Vaccination Guidelines Group makes some recommendations on undergraduate and postgraduate education and academic research. Recognising that current product availability in Latin America does not permit veterinarians in these countries to vaccinate according to the global World Small Animal Veterinary Association guidelines, the Vaccination Guidelines Group makes a series of “pragmatic” recommendations as to what might be currently achievable, and a series of “aspirational” recommendations as to what might be desirable for the future. The concept of “vaccine husbandry” is addressed via some simple guidelines for the management of vaccine products in the practice. Finally, the Vaccination Guidelines Group emphasises the global trend towards delivery of vaccination as one part of an “annual health check” or “health care plan” that reviews holistically the preventive health care needs of the individual pet animal. Latin American practitioners should transition towards these important new practices that are now well embedded in more developed veterinary markets. The document also includes 70 frequently asked questions and their answers; these were posed to the Vaccination Guidelines Group during our continuing education events and small group discussions and should address many of the issues surrounding delivery of vaccination in the Latin American countries. Spanish and Portuguese translations of this document will be made freely available from the on‐line resource pages of the Vaccination Guidelines Group.


title: Antiviral Agents Against Ebola Virus Infection: Repositioning Old Drugs and Finding Novel Small Molecules

text: Ebola virus (EBOV) causes a deadly hemorrhagic syndrome in humans with mortality rate up to 90%. First reported in Zaire in 1976, EBOV outbreaks showed a fluctuating trend during time and fora long period it was considered a tragic disease confined to the isolated regions of the African continent where the EBOV fear was perpetuated among the poor communities. The extreme severity of the recent 2014–16 EBOV outbreak in terms of fatality rate and rapid spread out of Africa led to the understanding that EBOV is a global health risk and highlights the necessity to find countermeasures against it. In the recent years, several small molecules have been shown to display in vitro and in vivo efficacy against EBOV and some of them have advanced into clinical trials. In addition, also existing drugs have been tested for their anti-EBOV activity and were shown to be promising candidates. However, despite the constant effort addressed to identify anti-EBOV therapeutics, no approved drugs are available against EBOV yet. In this chapter, we describe the main EBOV life cycle steps, providing a detailed picture of the druggable viral and host targets that have been explored so far by different technologies. We then summarize the small molecules, nucleic acid oligomers, and antibody-based therapies reported to have an effect either in in silico, or in biochemical and cell-based assays or in animal models and clinical trials, listing them according to their demonstrated or putative mechanism of action.


title: Balancing revenue generation with capacity generation: Case distribution, financial impact and hospital capacity changes from cancelling or resuming elective surgeries in the US during COVID-19

text: BACKGROUND: To increase bed capacity and resources, hospitals have postponed elective surgeries, although the financial impact of this decision is unknown. We sought to report elective surgical case distribution, associated gross hospital earnings and regional hospital and intensive care unit (ICU) bed capacity as elective surgical cases are cancelled and then resumed under simulated trends of COVID-19 incidence. METHODS: A retrospective, cohort analysis was performed using insurance claims from 161 million enrollees from the MarketScan database from January 1, 2008 to December 31,2017. COVID-19 cases were calculated using a generalized Richards model. Centers for Disease Control (CDC) reports on the number of hospitalized and intensive care patients by age were used to estimate the number of cases seen in the ICU, the reduction in elective surgeries and the financial impact of this from historic claims data, using a denominator of all inpatient revenue and outpatient surgeries. RESULTS: Assuming 5% infection prevalence, cancelling all elective procedures decreases ICU overcapacity from 340% to 270%, but these elective surgical cases contribute 78% (IQR 74, 80) (1.1 trillion (T) US dollars) to inpatient hospital plus outpatient surgical gross earnings per year. Musculoskeletal, circulatory and digestive category elective surgical cases compose 33% ($447B) of total revenue. CONCLUSIONS: Procedures involving the musculoskeletal, cardiovascular and digestive system account for the largest loss of hospital gross earnings when elective surgery is postponed. As hospital bed capacity increases following the COVID-19 pandemic, restoring volume of these elective cases will help maintain revenue.


title: Decoding of persistent multiscale structures in complex biological networks

text: Networks of genes, proteins, and cells exhibit significant multiscale organization, with distinct communities appearing at different spatial resolutions. Here, we apply the concept of ‘persistent homology’ to identify network communities that persist within defined scale ranges, yielding a hierarchy of robust structures in data. Application to mouse single-cell transcriptomes significantly expands the catalog of cell types identified by current tools, while analysis of SARS-COV-2 networks suggests pro-viral hijacking of WNT.


title: A Comprehensive Review of Common Bacterial, Parasitic and Viral Zoonoses at the Human-Animal Interface in Egypt

text: Egypt has a unique geographical location connecting the three old-world continents Africa, Asia and Europe. It is the country with the highest population density in the Middle East, Northern Africa and the Mediterranean basin. This review summarizes the prevalence, reservoirs, sources of human infection and control regimes of common bacterial, parasitic and viral zoonoses in animals and humans in Egypt. There is a gap of knowledge conerning the epidemiology of zoonotic diseases at the human-animal interface in different localities in Egypt. Some zoonotic agents are “exotic” for Egypt (e.g., MERS-CoV and Crimean-Congo hemorrhagic fever virus), others are endemic (e.g., Brucellosis, Schistosomiasis and Avian influenza). Transboundary transmission of emerging pathogens from and to Egypt occurred via different routes, mainly importation/exportation of apparently healthy animals or migratory birds. Control of the infectious agents and multidrug resistant bacteria in the veterinary sector is on the frontline for infection control in humans. The implementation of control programs significantly decreased the prevalence of some zoonoses, such as schistosomiasis and fascioliasis, in some localities within the country. Sustainable awareness, education and training targeting groups at high risk (veterinarians, farmers, abattoir workers, nurses, etc.) are important to lessen the burden of zoonotic diseases among Egyptians. There is an urgent need for collaborative surveillance and intervention plans for the control of these diseases in Egypt.


title: COVID‐19 encephalopathy masquerading as substance withdrawal

text: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), first identified in December 2019 in Wuhan, China, is the virus responsible for the current pandemic known as COVID-19. We report the case of a patient with past medical history of substance abuse who presented with suspected drug overdose. He was agitated and altered in the emergency room and he was treated with benzodiazepines for his agitation. He was admitted for substance withdrawal, however his encephalopathy did not improve and he developed choreiform movements. Metabolic, infectious, and rheumatologic workup was negative until he subsequently tested positive for COVID-19. An MRI was performed which showed multiple focal enhancing lesions primarily affecting the bilateral medial putamen and left cerebellum along with subcortical lesions suggesting COVID-19 encephalopathy. He was given glucocorticoids and his mentation and choreiform movements improved. While neurologic presentations are increasingly becoming more common, encephalopathy with choreiform movements appears to be a rare manifestation of SARS-CoV-2, and may be due to direct viral invasion or, more likely, autoimmune mediated toxicity precipitated by the initial viral infection This article is protected by copyright. All rights reserved.


title: Cell Host Response to Infection with Novel Human Coronavirus EMC Predicts Potential Antivirals and Important Differences with SARS Coronavirus

text: A novel human coronavirus (HCoV-EMC) was recently identified in the Middle East as the causative agent of a severe acute respiratory syndrome (SARS) resembling the illness caused by SARS coronavirus (SARS-CoV). Although derived from the CoV family, the two viruses are genetically distinct and do not use the same receptor. Here, we investigated whether HCoV-EMC and SARS-CoV induce similar or distinct host responses after infection of a human lung epithelial cell line. HCoV-EMC was able to replicate as efficiently as SARS-CoV in Calu-3 cells and similarly induced minimal transcriptomic changes before 12 h postinfection. Later in infection, HCoV-EMC induced a massive dysregulation of the host transcriptome, to a much greater extent than SARS-CoV. Both viruses induced a similar activation of pattern recognition receptors and the interleukin 17 (IL-17) pathway, but HCoV-EMC specifically down-regulated the expression of several genes within the antigen presentation pathway, including both type I and II major histocompatibility complex (MHC) genes. This could have an important impact on the ability of the host to mount an adaptive host response. A unique set of 207 genes was dysregulated early and permanently throughout infection with HCoV-EMC, and was used in a computational screen to predict potential antiviral compounds, including kinase inhibitors and glucocorticoids. Overall, HCoV-EMC and SARS-CoV elicit distinct host gene expression responses, which might impact in vivo pathogenesis and could orient therapeutic strategies against that emergent virus.


title: Bovine Eimeria species in Austria

text: Bovine eimeriosis is considered to be of considerable importance for the productivity and health of cattle worldwide. Despite the importance of cattle farming in Austria, little is known in this country about the abundance and distribution of bovine Eimeria spp. The objective of this study was to obtain detailed information about the occurrence of different Eimeria spp. on Austrian dairy farms. Fecal samples from individual calves (n = 868) from 296 farms all over Austria (82 districts) were collected. Additionally, each farmer was questioned about the occurrence of calf diarrhea, and about the knowledge on coccidiosis and possible control measures. On 97.97% of the investigated farms, calves excreted Eimeria oocysts, and 83.67% of the individual samples were positive. After sporulation of positive samples pooled from each farm, 11 Eimeria species were found, with E. bovis (in 65.54% of the samples and 27.74% of the farms), E.zuernii (63.85%/13.86%), E. auburnensis (56.76%/13.41%) and E. ellipsoidalis (54.05%/14.38%) being the most prevalent, followed by E. alabamensis (45.61%/11.56%), E. subspherica (35.14%/5.5.05%), E. cylindrica (33.11%/7.00%), and E. canadensis (31.08%/7.74%). E. wyomingensis, E. pellita and E. bukidnonensis were only found sporadically (3.04–4.73% of the samples and 0.16–0.59% of the farms). Mixed infections were present on all farms (2–9 Eimeria species/farm). Prevalences by state provinces were high throughout with 77.1–87.9% of the samples and 93.8–100% of the farms. Lower Austria had the highest percentage of positive farms, and Vorarlberg the lowest. Individual OPG (oocysts per gram of feces) values were generally low; 75% of the samples had an OPG of 1,000 or less. The highest detected OPG was 72,400. The mean OPG was 2,525 with above average numbers in Tirol, Carinthia, and Lower Austria. The mean OPG values were significantly positively correlated with the cattle density in the different districts. The majority of the samples were from female Simmenthal calves. Clinical coccidiosis (diarrhea) was observed in 74 cases, and (semi-)liquid diarrhea (56 animals) was significantly correlated with OPG (p < 0.05). Linear regression on the OPG data showed that OPG values significantly decreased with increasing age of the calves, while the percentage of positive samples increased with age (p < 0.05 for both). The term “coccidia” was familiar to 45% of the farmers, and anticoccidial treatment was performed by 13.51% of them, most commonly with toltrazuril. Considering the ubiquitous occurrence and the possible clinical and economic relevance of calf eimeriosis, infections should receive increased attention by both farmers and veterinarians.


title: Lung progenitors from lambs can differentiate into specialized alveolar or bronchiolar epithelial cells

text: BACKGROUND: Airways progenitors may be involved in embryogenesis and lung repair. The characterization of these important populations may enable development of new therapeutics to treat acute or chronic lung disease. In this study, we aimed to establish the presence of bronchioloalveolar progenitors in ovine lungs and to characterize their potential to differentiate into specialized cells. RESULTS: Lung cells were studied using immunohistochemistry on frozen sections of the lung. Immunocytochemistry and flow cytometry were conducted on ex-vivo derived pulmonary cells. The bronchioloalveolar progenitors were identified by their co-expression of CCSP, SP-C and CD34. A minor population of CD34(pos)/SP-C(pos)/CCSP(pos) cells (0.33% ± 0.31) was present ex vivo in cell suspensions from dissociated lungs. Using CD34 magnetic positive-cell sorting, undifferentiated SP-C(pos)/CCSP(pos) cells were purified (>80%) and maintained in culture. Using synthetic media and various extracellular matrices, SP-C(pos)/CCSP(pos) cells differentiated into either club cells (formerly named Clara cells) or alveolar epithelial type-II cells. Furthermore, these ex vivo and in vitro derived bronchioloalveolar progenitors expressed NANOG, OCT4 and BMI1, specifically described in progenitors or stem cells, and during lung development. CONCLUSIONS: We report for the first time in a large animal the existence of bronchioloalveolar progenitors with dual differentiation potential and the expression of specialized genes. These newly described cell population in sheep could be implicated in regeneration of the lung following lesions or in development of diseases such as cancers.