docid: oovkoiyj

title: Chapter 7 Commonly Used Animal Models

text: Abstract This chapter provides an introduction to animals that are commonly used for research. It presents information on basic care topics such as biology, behavior, housing, feeding, sexing, and breeding of these animals. The chapter provides some insight into the reasons why these animals are used in research. It also gives an overview of techniques that can be utilized to collect blood or to administer drugs or medicine. Each section concludes with a brief description of how to recognize abnormal signs, in addition to lists of various diseases.


title: Qiangzhi Decoction (羌跖汤) protects mice from influenza A pneumonia through inhibition of inflammatory cytokine storm

text: OBJECTIVE: To investigate the preventive effects of Qiangzhi Decoction (羌跖汤, QZD) on influenza A pneumonia through inhibition of inflammatory cytokine storm in vivo and in vitro. METHODS: One hundred ICR mice were randomly divided into the virus control, the Tamiflu control and the QZD high-, medium-, and low-dose groups. Mice were infected intranasally with influenza virus (H1N1) at 10 median lethal dose (LD(50)). QZD and Tamiflu were administered intragastrically twice daily from day 0 to day 7 after infection. The virus control group was treated with distilled water alone under the same condition. The number of surviving mice was recorded daily for 14 days after viral infection. The histological damage and viral replication and the expression of inflammatory cytokines were monitored. Additionally, the suppression capacity on the secretion of regulated on activation normal T cells expressed and secreted (RANTES) and tumor necrosis factor-α (TNF-α) in epithelial and macrophage cell-lines were evaluated. RESULTS: Compared with the virus control group, the survival rate of the QZD groups signifificantly improved in a dose-dependent manner (P<0.05), the viral titers in lung tissue was inhibited (P<0.05), and the production of inflammatory cytokines interferon-γ (IFN-γ), interleukin-6 (IL-6), TNF-α, and intercellular adhesion molecule-1 (ICAM-1) were suppressed (P<0.05). Meanwhile, the secretion of RANTETS and TNF-α by epithelial and macrophage cell-lines was inhibited with the treatment of QZD respectively in vitro (p<0.05) CONCLUSIONS: The preventive effects of QZD on influenza virus infection might be due to its unique cytokine inhibition mechanism. QZD may have significant therapeutic potential in combination with antiviral drugs.


Drinking Bat Blood May Be Hazardous to Your Health


title: Guidance on Minimizing Risk of Drug-Induced Ventricular Arrhythmia During Treatment of COVID-19: A Statement from the Canadian Heart Rhythm Society

text: Abstract The COVID-19 pandemic has led to efforts at rapid investigation and application of drugs which may improve prognosis but for which safety and efficacy are not yet established. This document attempts to provide reasonable guidance for the use of antimicrobials which have uncertain benefit but may increase risk of QT interval prolongation and ventricular proarrhythmia, notably, chloroquine, hydroxychloroquine, azithromycin, and lopinavir/ritonavir. During the pandemic, efforts to reduce spread and minimize effects on health care resources mandate minimization of unnecessary medical procedures and testing. We recommend that the risk of drug proarrhythmia be minimized by 1) discontinuing unnecessary medications that may also increase the QT interval, 2) identifying outpatients who are likely to be at low risk and do not need further testing (no history of prolonged QT interval, unexplained syncope, or family history of premature sudden cardiac death, no medications that may prolong the QT interval, and/or a previous known normal corrected QT interval [QTc]), and 3) performing baseline testing in hospitalized patients or those who may be at higher risk. If baseline electrocardiographic testing reveals a moderately prolonged QTc, optimization of medications and electrolytes may permit therapy. If the QTc is markedly prolonged, drugs that further prolong it should be avoided, or expert consultation may permit administration with mitigating precautions. These recommendations are made while there are no known effective treatments for COVID-19 and should be revisited when further data on efficacy and safety become available.


title: Preventing COVID-19 from the perspective of industrial information integration: Evaluation and continuous improvement of information networks for sustainable epidemic prevention

text: COVID-19 is accelerating industrial information integration (III) for sustainable epidemic prevention and innovation design. It is important to emphasize that this interaction makes it reciprocal. To prevent COVID-19, the III of industrial sectors should be strengthened to encourage innovation for sustainable epidemic prevention. Accordingly, we studied the overall dynamic change trend of industrial sectors’ information integration networks (IIN), the characteristics of individual IIN, and their influence on IIN performance. In the study, the gravity model and social network analysis were used to determine the variables of industrial sectors’ information distance and quality, and to construct the IIN of industrial sectors. The results show that the overall relevance of the IIN of industrial sectors is low, and the network density fluctuates, with high network efficiency and poor stability. Two-way, strong correlation between industrial sectors is relatively low. The spillover effect of industrial sectors in the upstream of the industrial chain is poor, and it is difficult to have a strong information integration driving effect on the downstream industrial sectors. The interplate linkage of the IIN of industrial sectors is insufficient. Compared with point centrality and closeness, improvement of the betweenness centrality of industrial sectors can significantly improve IIN performance.


title: Shrinkage of Genome Size in a Plant RNA Virus upon Transfer of an Essential Viral Gene into the Host Genome

text: Nonretroviral integrated RNA viruses (NIRVs) are genes of nonretroviral RNA viruses found in the genomes of many eukaryotic organisms. NIRVs are thought to sometimes confer virus resistance, meaning that they could impact spread of the virus in the host population. However, a NIRV that is expressed may also impact the evolution of virus populations within host organisms. Here, we experimentally addressed the evolution of a virus in a host expressing a NIRV using Tobacco etch virus (TEV), a plant RNA virus, and transgenic tobacco plants expressing its replicase, NIb. We found that a virus missing the NIb gene, TEV-ΔNIb, which is incapable of autonomous replication in wild-type plants, had a higher fitness than the full-length TEV in the transgenic plants. Moreover, when the full-length TEV was evolved by serial passages in transgenic plants, we observed genomic deletions within NIb—and in some cases the adjacent cistrons—starting from the first passage. When we passaged TEV and TEV-ΔNIb in transgenic plants, we found mutations in proteolytic sites, but these only occurred in TEV-ΔNIb lineages, suggesting the adaptation of polyprotein processing to altered NIb expression. These results raise the possibility that NIRV expression can indeed induce the deletion of the corresponding genes in the viral genome, resulting in the formation of viruses that are replication defective in hosts that do not express the same NIRV. Moreover, virus genome evolution was contingent upon the deletion of the viral replicase, suggesting NIRV expression could also alter patterns of virus evolution.


title: Chapter 12 Next generation agents (synthetic agents): Emerging threats and challenges in detection, protection, and decontamination

text: Abstract Biological weapons are highly contagious in nature, designed for warfare scenarios, and cause mass destruction by hammering the economic, environmental, and societal attributes of a country. Rapid advances in genetic engineering and synthetic biology have revolutionized the development of highly lethal and reliable biological agents with enhanced virulence, survivability, and drug resistance. In the current scenario, construction and misuse of next generation synthetic agents is not mere science fiction, but has become a harsh reality. Next generation bioweapons are potential bio-threats to peace, security, and well-being of the targeted country. Thus, effective diagnostic and prophylactic measures need to be developed to mitigate adverse effects caused by the hazardous biological agents. This chapter provides a systematic overview of emergence and synthesis of next generation agents, methods, and challenges associated with detection, protection, and decontamination of the concerned biological agents.


title: Serological relation between calf diarrhea coronavirus and hemagglutinating encephalomyelitis virus

text: Neutralizing (NT) and hemagglutination-inhibiting (HI) antibodies to calf diarrhea coronavirus (CDCV) and hemagglutinating encephalomyelitis virus of swine (HEV) (strain 67 N) were detected in high proportions of normal adult cattle and pigs in Japan. Since comparison of NT and HI titers in the serum samples suggested an antigenic difference between the viruses, cross NT and HI tests of these viruses were carried out with antisera raised in rabbits. The homologous NT titers were markedly higher than the heterologous titers. In HI tests essentially the same results were obtained. These findings indicate the presence of a marked difference in antigenic make-up between CDCV and HEV. NT and HI tests can clearly differentiate the viruses, although there is some cross reaction.


title: Comparison of commercial lateral flow immunoassays and ELISA for SARS-CoV-2 antibody detection

text: BACKGROUND: COVID-19 pandemic has spread worldwide since December 2019. Serological tests for SARS-CoV-2 antibody testing are needed for detection of current or past infections. A wide range of commercial tests is available. However, most of them need to be validated. STUDY DESIGN: The aim was to compare a commercial IgG and IgA ELISA (Euroimmun) with three lateral flow immunoassays (LFI): Hangzhou Alltest Biotech, Wuhan UNscience Biotechnology and Guangzhou Wondfo Biotech. Specificity was calculated with 62 available serum samples from 2018/19. The study included 152 sera from patients of which 109 were RT-PCR positive. Sensitivities for ELISA anti SARS-CoV-2 IgG and IgA were 81,5% and 93,1% and specificities 100% and 80,6%, respectively. LFI showed variable performances, overall results being better for Guangzhou Wondfo Biotech. CONCLUSIONS: Commercial serological tests are useful for detection of antibodies in patients with COVID-19. ELISA presented better results than LFI. The results allowed to incorporate the most sensitive LFI to the daily workflow, combining with ELISA. Careful validation is encouraged before clinical laboratories start using these tests.


title: Evaluation of relationship between Rotavirus and Coronavirus infections with calf diarrhea by capture ELISA

text: Rotavirus and Coronavirus are two main causes of severe diarrhea in human infants and many animal species worldwide. Calves up to 3 months old can be affected by these viruses. The importance of these viruses in cattle industry is due to substantial economic loss, treatment costs, and reduced growth rates in beef and dairy calves. Mixed infections caused by Rotavirus and Coronavirus can lead to severe form of diarrhea. In present case-control study, 261 samples of healthy and diarrheic calves from farms around Mashhad were collected. These samples were tested by antigen-capture enzyme-linked immunosorbent assay (Bio-X diagnosis kit). The results showed that the prevalence of Rotavirus and Coronavirus infection in diarrheic calves is 26.98% and 3.17%, respectively. Also, there was no significant relationship between infection with Rotavirus, Coronavirus, and diarrhea in the studied population.


Evolving Healthcare Delivery in Neurology During the Coronavirus Disease 2019 (COVID-19) Pandemic


title: Prevalence and characterization of asthma in hospitalized and non-hospitalized patients with COVID-19

text: Abstract: Background The Centers for Disease Control and Prevention advises that patients with moderate-to-severe asthma belong to a high-risk group that is susceptible to severe COVID-19. However, the association between asthma and COVID-19 has not been well-established. Objective The primary objective was to determine the prevalence of asthma among COVID-19 patients in a major U.S. health system. We assessed the clinical characteristics and comorbidities in asthmatic and non-asthmatic COVID-19 patients. We also determined the risk of hospitalization associated with asthma and/or inhaled corticosteroid use. Methods Medical records of patients with COVID-19 were searched by a computer algorithm (March 1–April 15, 2020), and chart review was used to validate the diagnosis of asthma and medications prescribed for asthma. All patients were PCR-confirmed COVID-19. Demographics and clinical features were characterized. Regression models were used to assess the associations between asthma and corticosteroid use and the risk of COVID-19-related hospitalization. Results Of 1,526 patients identified with COVID-19, 220 (14%) were classified as having asthma. Asthma was not associated with an increased risk of hospitalization (RR of 0.96 [95%CI: 0.77-1.19]) after adjusting for age, sex, gender, and comorbidities. The ongoing use of ICS did not increase the risk of hospitalization in a similar adjusted model (RR of 1.39 [95%CI: 0.90-2.15]). Conclusions Despite a substantial prevalence of asthma in our COVID-19 cohort, asthma was not associated with an increased risk of hospitalization. Similarly, the use of ICS with or without systemic corticosteroids was not associated with COVID-19-related hospitalization.


title: Technologies and Standardization in Research on Extracellular Vesicles

text: Extracellular vesicles (EVs) are phospholipid bilayer membrane-enclosed structures containing RNAs, proteins, lipids, metabolites, and other molecules, secreted by various cells into physiological fluids. EV-mediated transfer of biomolecules is a critical component of a variety of physiological and pathological processes. Potential applications of EVs in novel diagnostic and therapeutic strategies have brought increasing attention. However, EV research remains highly challenging due to the inherently complex biogenesis of EVs and their vast heterogeneity in size, composition, and origin. There is a need for the establishment of standardized methods that address EV heterogeneity and sources of pre-analytical and analytical variability in EV studies. Here, we review technologies developed for EV isolation and characterization and discuss paths toward standardization in EV research.


COVID‐19 pandemic: University of Naples Federico II Dermatology's model of dermatology reorganization


Prevención del síndrome respiratorio agudo grave en la unidad de cuidados intensivos


title: Community Surveillance of Respiratory Viruses Among Families in the Utah Better Identification of Germs-Longitudinal Viral Epidemiology (BIG-LoVE) Study

text: Background. This study: (1) describes the viral etiology of respiratory illness by prospectively collecting weekly symptom diaries and nasal swabs from families for 1 year, (2) analyzed data by reported symptoms, virus, age, and family composition, and (3) evaluated the duration of virus detection. Methods. Twenty-six households (108 individuals) provided concurrent symptom and nasal swab data for 4166 person-weeks. The FilmArray polymerase chain reaction (PCR) platform (BioFire Diagnostics, LLC) was used to detect 16 respiratory viruses. Viral illnesses were defined as ≥1 consecutive weeks with the same virus detected with symptoms reported in ≥1 week. Results. Participants reported symptoms in 23% and a virus was detected in 26% of person-weeks. Children younger than 5 years reported symptoms more often and were more likely to have a virus detected than older participants (odds ratio [OR] 2.47, 95% confidence interval [CI], 2.08–2.94 and OR 3.96, 95% CI, 3.35–4.70, respectively). Compared with single person households, individuals living with children experienced 3 additional weeks of virus detection. There were 783 viral detection episodes; 440 (56%) associated with symptoms. Coronaviruses, human metapneumovirus, and influenza A detections were usually symptomatic; bocavirus and rhinovirus detections were often asymptomatic. The mean duration of PCR detection was ≤2 weeks for all viruses and detections of ≥3 weeks occurred in 16% of episodes. Younger children had longer durations of PCR detection. Conclusions. Viral detection is often asymptomatic and occasionally prolonged, especially for bocavirus and rhinovirus. In clinical settings, the interpretation of positive PCR tests, particularly in young children and those who live with them, may be confounded.


title: The role of extracellular vesicles in COVID-19 virus infection

text: Extracellular vesicles releasing from various types of cells contribute to intercellular communication via delivering bio-molecules like nucleic acids, proteins, and lipids to recipient cells. Exosomes are 30–120 nm extracellular vesicles that participate in several pathological conditions. Virus-infected cells release exosomes that are implicated in infection through transferring viral components such as viral-derived miRNAs and proteins. As well, exosomes contain receptors for viruses that make recipient cells susceptible to virus entry. Since December 2019, SARS-CoV-2 (COVID-19) infection has become a worldwide urgent public health concern. There is currently no vaccine or specific antiviral treatment existing for COVID-19 virus infection. Hence, it is critical to find a safe and effective therapeutic tool to patients with severe COVID-19 virus infection. Extracellular vesicles may contribute to spread this virus as they transfer such receptors as CD9 and ACE2, which make recipient cells susceptible to virus docking. Upon entry, COVID-19 virus may be directed into the exosomal pathway, and its component is packaged into exosomes for secretion. Exosome-based strategies for the treatment of COVID-19 virus infection may include following items: inhibition of exosome biogenesis and uptake, exosome-therapy, exosome-based drug delivery system, and exosome-based vaccine. Mesenchymal stem cells can suppress nonproductive inflammation and improve/repair lung cells including endothelial and alveolar cells, which damaged by COVID-19 virus infection. Understanding molecular mechanisms behind extracellular vesicles related COVID-19 virus infection may provide us with an avenue to identify its entry, replication, spreading, and infection to overcome its adverse effects.


title: Can thrombotic events be a major concern in hepatocellular carcinoma patients under systemic treatment during SARS‐Cov‐2?

text: We read with interest the editorial by Sharma and Pinato on the management of hepatocellular carcinoma (HCC) in the time of SARS-Cov-2 (1). The points raised by the authors will be of paramount importance to guide HCC groups worldwide.


title: Characterization of haemagglutinin-esterase protein (HE) of murine corona virus DVIM by monoclonal antibodies

text: We analyzed the characteristics of seven monoclonal antibodies (mAbs) raised against purified HE (hemagglutinin-esterase) glycoprotein of the murine coronavirus DVIM (diarrhea virus of infant mice). Immunocrossreaction of these mAbs with JHM and/or MHV-S suggest that antigenic epitopes of HE of DVIM are similar to those of JHM and/or MHV-S. Four mAbs (1b4, 3Aff28, 4c19, 10b7), designated as group A mAbs, strongly inhibited both HA and AE activities. On the other hand, three mAbs (5Aff3, 6Aff6, 13Aff4), referred to as group B, had a comparatively weak HA inhibition activity. These results indicate that the antigenic epitopes of this glycoprotein can be classified into at least two groups and that the functional sites of HA and AE activities are similar but not identical. Neutralizing activity was shown in group A mAbs exclusively, suggesting that the ratio of HA and/or AE activities may play important roles in the cell fusion activity of DVIM-infected cells.


title: Shedding Light on the Effect of Natural Anti-Herpesvirus Alkaloids on SARS-CoV-2: A Treatment Option for COVID-19

text: The whole world is currently facing an unseen enemy, called coronavirus disease 2019 (COVID-19), which is causing a global pandemic. This disease is caused by a novel single-stranded enveloped RNA virus, known as the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Although huge efforts are being made to produce effective therapies to combat this disease, it continues to be one of the greatest challenges in medicine. There is no doubt that herpesviruses are one of the most important viruses that infect humans and animals, and infections induced by these pathogens have developed into a great threat to public health. According to the currently available evidence, the correlation between herpesviruses and coronaviruses is limited to the induced complications following the infections. For instance, the inflammation that is induced at the sites of infection could tie these viruses to each other in a relationship. Another example, bovine herpesvirus 1, which is an important pathogen of cattle, can cause a severe respiratory infection; the same way in which SARS-CoV-2 affects humans. Considering the current circumstances related to the COVID-19 crisis, this editorial paper, which belongs to the Special Issue “Recent Advances in Herpesviruses Research: What’s in the Pipeline?” aims to draw attention to some natural anti-herpesvirus alkaloid compounds, which have recently been proven to have excellent inhibitory efficacy against SARS-CoV-2 replication. Thus, this special focus is an attempt to hunt down various treatment options to combat COVID-19 based on repurposing drugs that are known to have multiple antiviral properties, including against herpesvirus.


title: CRISPR-mediated activation of endogenous BST-2/tetherin expression inhibits wild-type HIV-1 production

text: The CRISPR technology not only can knock out target genes by using the RNA-guided Cas9 nuclease but also can activate their expression when a nuclease-deficient Cas9 (dCas9) is employed. Using the latter function, we here show the effect of the CRISPR-mediated pinpoint activation of endogenous expression of BST-2 (also known as tetherin), a virus restriction factor with a broad antiviral spectrum. Single-guide RNA (sgRNA) sequences targeting the BST-2 promoter were selected by promoter assays. Potential sgRNAs and dCas9 fused to the VP64 transactivation domain, along with an accessory transcriptional activator complex, were introduced into cells by lentiviral transduction. Increased expression of BST-2 mRNA in transduced cells was confirmed by real-time RT-PCR. Cells in which BST-2 expression was highly enhanced showed the effective inhibition of HIV-1 production and replication even in the presence of the viral antagonist Vpu against BST-2. These findings confirm that the physiological stoichiometry between host restriction factors and viral antagonists may determine the outcome of the battle with viruses.


title: COVID-19 and kidney transplantation: an Italian Survey and Consensus

text: Italy was the first Western country to face the COVID-19 pandemic. Here we report the results of a national survey on kidney transplantation activity in February and March 2020, and the results of a three-round Delphi consensus promoted by four scientific societies: the Italian Society of Organ Transplantation, the Italian Society of Nephrology, the Italian Society of Anesthesia and Intensive Care, and the Italian Group on Antimicrobial Stewardship. All 41 Italian transplant centers were invited to express their opinion in the Delphi rounds along with a group of seven experts. The survey revealed that, starting from March 2020, there was a decline in kidney transplantation activity in Italy, especially for living-related transplants. Overall, 60 recipients tested positive for SARS-CoV2 infection, 57 required hospitalization, 17 were admitted to the ICU, and 11 died. The online consensus had high response rates at each round (95.8%, 95.8%, and 89.5%, respectively). Eventually, 27 of 31 proposed statements were approved (87.1%), 12 at the first or second round (38.7%), and 3 at the third (9.7%). Based on the Italian experience, we discuss the reasons for the changes in kidney transplantation activity during the COVID-19 pandemic in Western countries. We also provide working recommendations for the organization and management of kidney transplantation under these conditions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40620-020-00755-8) contains supplementary material, which is available to authorized users.


title: Ebola Virus Disease: Experience and Decision Making for the First Patients outside of Africa

text: David Stephens and colleagues describe their experience of treating patients with Ebola virus disease at Emory University in the United States.


docid: gfkuffjq

title: Organ Donation during the Covid-19 pandemic

text: Abstract The Covid-19 pandemic is a rapidly changing circumstance with dramatic policy changes and universal efforts to deal with the initial crisis and minimize its consequences To identify changes to organ donation and transplantation during this time, an anonymous web-based survey was distributed to 19 select organ procurement organizations (OPOs) throughout the US comparing 90-day activity during March - May 2020 and March ? May 2019 17 OPOs responded to the survey (response rate of 89 5%) Organ authorization decreased by 11% during the current pandemic (n=1379 vs n=1552, p=0 0001) Organ recovery for transplantation fell by 17% (p=0 0001) with a further 18% decrease in the number of organs transplanted (p=0 0001) Donor cause of death demonstrated a 4 5% decline in trauma but a 35% increase in substance abuse cases during the Covid-19 period All OPOs reported significant modifications in response to the pandemic, limiting the onsite presence of staff and transitioning to telephonic approaches for donor family correspondence Organ donation during the current climate has seen significant changes and the long-term implications of such shifts remain unclear These trends during the Covid-19 era warrant further investigation to address unmet needs, plan for a proportionate response to the virus and mitigate the collateral impact


title: New Adenovirus Groups in Western Palaearctic Bats

text: In the context of long-term screening for viruses on Western Palaearctic bats, we tested for the presence of adenovirus 1392 oropharyngeal swabs and 325 stool samples taken from 27 bat species. Adenoviruses were detected in 12 species of the Vespertilionidae and the Rhinolophidae families. Fifty positive respiratory and 26 positive stool samples were studied. Phylogenetic analyses of partial hexon protein and partial DNA-dependent DNA polymerase genes indicate that all these bat adenoviruses belong to the genus Mastadenovirus but without constituting a monophyletic cluster. According to genetic identities, the new groups are distinct to the previously described Bat mastadenovirus A and B species and contribute with potentially new members. Our data support that diversity of bat mastadenovirus is host-dependent and increase the knowledge of potentially pathogenic virus from bats. Due to the active role of bats as viral reservoirs, the characterization of these viruses is relevant for Public Health.


Is asthma protective against COVID‐19?


title: Three Novel Prevention, Diagnostic and Treatment Options for COVID-19 Urgently Necessitating Controlled Randomized Trials

text: PURPOSE: Asymptomatic or minimally symptomatic infection with COVID-19 can result in silent transmission to large numbers of individuals, resulting in expansion of the pandemic with a global increase in morbidity and mortality. New ways of screening the general population for COVID-19 are urgently needed along with novel effective prevention and treatment strategies. HYPOTHESIS: A hypothetical three-part prevention, diagnostic, and treatment approach based on an up-to-date scientific literature review for COVID- 19 is proposed. Regarding diagnosis, a validated screening questionnaire and digital app for COVID-19 could help identify individuals who are at risk of transmitting the disease, as well as those at highest risk for poor clinical outcomes. Global implementation and online tracking of vital signs and scored questionnaires that are statistically validated would help health authorities properly allocate essential health care resources to test and isolate those at highest risk for transmission and poor outcomes. Second, regarding prevention, no validated protocols except for physical distancing, hand washing, and isolation exist, and recently ivermectin and the antimalarial drugs chloroquine and hydroxychloroquine has been published to have anti-viral properties against COVID-19. A randomized trial of ivermectin or hydroxychloroquine alone, and/or nutraceuticals that have been published to support immune function including Vitamin C, zinc, and immunomodulatory supplements (3,6 Beta glucan) could be beneficial in preventing transmission or lessening symptomatology but requires statistical validation. Third, concerning treatment, COVID-19 induced inflammation and “cytokine storm syndrome” with hemophagocytic lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS) have resulted in extreme morbidity and mortality in those with certain comorbidities, secondary to “acute respiratory distress syndrome” (ARDS) and multiorgan dysfunction with disseminated intravascular coagulation (DIC). Deficiency in red blood cell, serum and alveolar glutathione has been published in the medical literature for ARDS, as well as viral and bacterial pneumonias, resulting from increased levels of free radical/oxidative stress. A randomized controlled trial of blocking NFKappa B and cytokine formation using glutathione precursors (N-acetyl-cysteine [NAC] and alpha lipoic acid) and PO/IV glutathione should be performed, along with an evaluation of Nrf2 activators (curcumin, sulforaphane glucosinolate) which have been scientifically proven to lower inflammation. Since high mortality rates from sepsis induced DIC due to COVID 19 infection has also been associated with thrombotic events and elevated levels of D-dimer, randomized controlled trials of using anticoagulant therapy with heparin is urgently required. This is especially important in patients on ventilators who have met certain sepsis induced coagulopathy (SIC) criteria. The use of acetazolamide with or without sildenafil also needs to be explored with or without heparin, since increased oxygen delivery to vital organs through prevention of thrombosis/pulmonary emboli along with carbonic anhydrase inhibition may help increase oxygenation and prevent adverse clinical outcomes. CONCLUSION AND IMPLICATIONS: a three-part prevention, diagnostic, and treatment plan is proposed for addressing the severe complications of COVID-19. Digital monitoring of symptoms to clinically diagnose early exposure and response to treatment; prevention with hydroxychloroquine and/or ivermetin as well as nutritional therapies that support a healthy immune response; treatment with anti-inflammatory therapies that block NFKappaB and activate Nrf2 pathways, as well as novel therapies that address COVID-19 pneumonia and ARDS with DIC including anticoagulation and/ or novel respiratory therapies with or without acetazolamide and sildenafil. These three broad-based interventions urgently need to be subjected to randomized, controlled trials.


title: Insights into laser safety considerations during COVID 19 pandemic

text: The World Health Organization has recently defined the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infections as a pandemic. The infection, that may cause a potentially very severe respiratory disease, now called coronavirus disease 2019 (COVID‐19), has airborne transmission via droplets while less attention focused on aerosol transmission. Surgical smoke and plumes in laser clinics represent a source for aerosol particles. The aim of this article is to provide the authors opinion for the correct use of “laser devices” in the COVID‐19 emergency and to reduce potential risks of laser airborne contaminants. This article is protected by copyright. All rights reserved.


Whistleblowing and patient safety during COVID-19


title: Are positive pressure ventilation lobby rooms effective for protective and source isolation?

text: High efficiency particulate air supplied to a positive-pressure ventilation lobby (PPVL) in isolation rooms offers the dual advantage of protective and source isolation. We demonstrate the in-use validity of PPVL-rooms for protective isolation of patients. Of the 48 PPVL-air samples investigated, Aspergillus fumigatus was detected from only one (2%) sample. Local and remote-monitoring of the PPVL-rooms is essential for the safety of patients and healthcare workers. Remote and point-of-use engineering controls are essential for ongoing ventilation monitoring, but this should be complimented by visual inspection of the isolation suite. Periodic microbiological monitoring should also be considered with other control-measures.


title: Critical adjustments and trauma surgery trends in adaptation to COVID-19 pandemic in Malaysia

text: Malaysia has one of the highest numbers of COVID-19 infections within the Southeast Asian nations, which led to enforcements of drastic measures of Malaysian Movement Control Order” to curb disease transmission. The overwhelming increasing amount of infections has led to a major strain on healthcare services. This causes shortages in hospital beds, ventilators and various critical personnel protective equipment. This article focuses on the critical adaptations from a general surgery department in Malaysia which is part of a Malaysia tertiary centre that treats COVID-19 patients. The core highlights of these strategies during this pandemic are: (1) surgery ward and clinic decongestions; (2) deferment of elective surgeries; (3) restructuring of medical personnel; (4) utilization of online applications for tele-communication; (5) operating room adjustments and patient screening; and (6) continuing learning and updating practices in context to COVID-19. These adaptations are important for the continuation of emergency surgery services, preventing transmission of COVID-19 amongst healthcare workers and optimization of medical personnel work force in times of a global pandemic. In addition, an early analysis on the impact of COVID-19 pandemic and lockdown measures in Malaysia towards the reduction in total number of elective/emergent/trauma surgeries performed is described in this article.


Emergency Medicine’s COVID Future: facing the triple challenge after flattening the curve


title: Rapid relief of acute sore throat with AMC/DCBA throat lozenges: randomised controlled trial

text: Aim: As antibiotics are generally not recommended for the treatment of acute sore throat, the availability of clinically efficacious, over‐the‐counter (OTC) treatment alternatives is becoming increasingly important. This study was designed to determine the analgesic properties of amylmetacresol and 2,4‐dichlorobenzyl alcohol (AMC/DCBA) throat lozenges (Strepsils(®)) in the relief of acute sore throat caused by upper respiratory tract infections. Methods: Patients (n = 310) were randomly assigned to receive AMC/DCBA throat lozenges (n = 155) or non‐medicated placebo lozenges (n = 155). After baseline assessments, patients completed three rating assessments at 10 timepoints from 5 to 20 min after first dose. Subsequent lozenges were taken as required, and assessments were made at the end of Day 1, 24 h after first dose, and at the end of Days 2 and 3. Analgesic properties were assessed by comparing severity of throat soreness and sore throat relief ratings. Difficulty in swallowing and functional impairment scores were also assessed. Results: Amylmetacresol/DCBA throat lozenges reduced throat soreness at 5 min after first dose, which persisted for 2 h and was significantly different vs. non‐medicated lozenges at all assessment timepoints for the duration of the 3‐day study. Similar significant effects were observed with sore throat relief, easing of difficulty with swallowing and functional impairment scores. There were no differences in adverse events reported between treatment groups. Conclusion: Amylmetacresol/DCBA throat lozenges provide rapid analgesic effects that last for 2 h, providing ongoing relief long after the lozenge has dissolved. The superior analgesic effects and improvements in functional impairment scores observed with AMC/DCBA throat lozenges translate into pain relief benefits that are clinically meaningful and are thus a suitable OTC treatment option for patients in the self‐management of acute sore throat.


Reduced Fractionation in Lung Cancer Patients Treated with Curative-intent Radiotherapy during the COVID-19 Pandemic


title: SARS virus: The beginning of the unraveling of a new coronavirus

text: Severe acute respiratory syndrome (SARS) virus caused a severe outbreak in several regions of the world in 2003. The virus is a novel coronavirus, which may have an origin in wild animals such as civet cats in southern China. Its genome structure, gene expression pattern and protein profiles are similar to those of other coronaviruses. However, distinct patterns of several open reading frames in the SARS virus genome may contribute to its severe virulence. The potential mutability of the coronavirus genome may pose problems in the control of future SARS outbreaks. The mechanism of SARS pathogenesis may involve both direct viral cytocidal effects on the target cells and immune-mediated mechanisms. The life cycle of the SARS virus is largely unknown; however, based on the analogy with other coronaviruses, several potential targets for antiviral development are identified. Vaccines offer an important preventive measure for possible future recurrences of SARS, but the prospect for their development is still unknown because of the uncertainty regarding the role of immune responses in SARS virus pathogenesis. The comparative studies of other coronaviruses offer insights into the understanding of SARS virus.


title: Serum iron level as a potential predictor of COVID-19 severity and mortality: a retrospective study

text: BACKGROUND: Various types of pulmonary diseases are associated with iron deficiency. However, information on iron status in COVID-19 is scarce. METHODS: This study included 50 hospitalized patients with confirmed COVID-19. The role of serum iron in predicting severity and mortality of COVID-19 was evaluated. RESULTS: The most common symptoms of COVID-19 patients in this study were cough (82%), fever (64%), and chest distress (42%). Of the 50 patients, 45 (90%) patients had abnormally low serum iron levels (<7.8 μmol/L). The severity of COVID-19 was negatively correlated with serum iron levels before and after treatment and was positively correlated with C-reactive protein (CRP), serum amyloid A (SAA), D-dimer, lactate dehydrogenase (LDH), urea nitrogen, and myoglobin levels. Decreased serum iron level could predict the transition of COVID-19 from mild to severe and critical illness. 7 (53.8%) patients with lower serum iron level after treatment in the critical group had died. There was a significant difference in post-treatment serum iron levels between COVID-19 survivors and non-survivors . CONCLUSIONS: Serum iron deficiency was detected in the patients with COVID-19. The severity and mortality of the disease was closely correlated with serum iron levels. Low serum iron concentration was an independent risk factor for death in COVID-19 patients.


title: Health care-associated infections – an overview

text: Health care-associated infections (HCAIs) are infections that occur while receiving health care, developed in a hospital or other health care facility that first appear 48 hours or more after hospital admission, or within 30 days after having received health care. Multiple studies indicate that the common types of adverse events affecting hospitalized patients are adverse drug events, HCAIs, and surgical complications. The US Center for Disease Control and Prevention identifies that nearly 1.7 million hospitalized patients annually acquire HCAIs while being treated for other health issues and that more than 98,000 patients (one in 17) die due to these. Several studies suggest that simple infection-control procedures such as cleaning hands with an alcohol-based hand rub can help prevent HCAIs and save lives, reduce morbidity, and minimize health care costs. Routine educational interventions for health care professionals can help change their hand-washing practices to prevent the spread of infection. In support of this, the WHO has produced guidelines to promote hand-washing practices among member countries.


Universal SARS-CoV-2 testing on admission to Labor and Delivery: Low prevalence among asymptomatic obstetric patients


title: Extraction, Characterization, and Anticoagulant Activity of a Sulfated Polysaccharide from Bursatella leachii Viscera

text: [Image: see text] Bioactive compounds for drug discovery are increasingly extracted and purified from natural sources including marine organisms. Heparin is a therapeutic agent that has been used for several decades as an anticoagulant. However, heparin is known to cause many undesirable complications such as thrombocytopenia and risk of hemorrhage. Hence, there is a need to find alternatives to current widely used anticoagulant drugs. Here, we extract a sulfated polysaccharide from sea hare, that is, Bursatella leachii viscera, by enzymatic digestion. Several analytical approaches including elemental analysis, Fourier-transform infrared spectroscopy, nuclear magnetic resonance, and high-performance liquid chromatography–mass spectrometry analysis show that B. leachii polysaccharides have chemical structures similar to glycosaminoglycans. We explore the anticoagulant activity of the B. leachii extract using the activated partial thromboplastin time and the thrombin time. Our results demonstrate that the extracted sulfated polysaccharide has heparin-like anticoagulant activity, thus showing great promise as an alternative anticoagulant therapy.


title: Models for facilitating access to patents on genetic inventions

text: The genetics community is increasingly concerned that patents might lead to restricted access to research and health care. We explore various measures that are designed to render patented genetic inventions accessible to further use in research, and to diagnosis and/or treatment. They include the often-recited research or experimental-use exemption, conventional one-to-one licensing and compulsory licensing, as well as patent pools and clearing-house mechanisms. The last two alternatives deserve special attention in the area of human genetics.


title: The efficacy and tolerance of intranasal interferons: studies at the Common Cold Unit

text: Intranasal sprays of interferons (IFNs) given one day before and for three days after virus challenge can protect human volunteers from infection with rhinoviruses, corona virus, and influenza. Longer dosage of IFN gives rise to nasal symptoms and signs such as bloodstained nasal discharge. More effective IFNs and regimes are therefore needed. IFNβ is active but the degree to which it will irritate the nose is unknown. Combining IFNs with synthetic antiviral drugs can produce synergistic increases in antiviral activity. It is suggested that these increases may be exploited in future experiments.


title: Clinical value of the emergency department in screening and diagnosis of COVID-19 in China

text: 目 的: 通过对浙江大学医学院附属第一医院急诊科筛查出的 4 例新型冠状病毒肺炎 (新冠肺炎) 病例进行分析, 探讨急诊科在新冠肺炎精准筛查和诊断中的作用。 创新点: 分析新型冠状病毒肺炎的致病机制、 传播方式和临床特征; 总结急诊科医护人员的自身防护和诊断策略. 方 法: 回顾性分析我院急诊科筛查出的 4 例新型冠状病毒肺炎病例, 总结急诊科的临床价值. 结 论: 在新冠肺炎的筛查和诊断体系中, 中国急诊科发挥了不可替代的作用. 急诊科医护人员应充分做好自身防护, 对患者进行细致、 耐心、 谨慎地病史采集和全面的体格检查, 并关注患者的心理状态, 有效应用肺部计算机断层扫描 (CT)、 核酸检测等检测方法, 做好新冠肺炎筛查工作.


title: Studying human lung infection in mice

text: Mice implanted with human lung tissue model pathogen infection and immune responses.


title: Data-driven exploration of ‘spatial pattern-time process-driving forces’ associations of SARS epidemic in Beijing, China

text: BACKGROUND: Severe Acute Respiratory Syndrome (SARS) was first reported in November 2002 in China, and spreads to about 30 countries over the next few months. While the characteristics of epidemic transmission are individually assessed, there are also important implicit associations between them. METHODS: A novel methodological framework was developed to overcome barriers among separate epidemic statistics and identify distinctive SARS features. Individual statistics were pair-wise linked in terms of their common features, and an integrative epidemic network was formulated. RESULTS: The study of associations between important SARS characteristics considerably enhanced the mainstream epidemic analysis and improved the understanding of the relationships between the observed epidemic determinants. The response of SARS transmission to various epidemic control factors was simulated, target areas were detected, critical time and relevant factors were determined. CONCLUSION: It was shown that by properly accounting for links between different SARS statistics, a data-based analysis can efficiently reveal systematic associations between epidemic determinants. The analysis can predict the temporal trend of the epidemic given its spatial pattern, to estimate spatial exposure given temporal evolution, and to infer the driving forces of SARS transmission given the spatial exposure distribution.


title: Beliefs towards the COVID-19 pandemic among patients with emotional disorders in China

text: BACKGROUND: The novel coronavirus disease 2019 (COVID-19) pandemic has given rise to fear and panic in the public. Although hospitals in China reduced outpatient visits and restricted inpatient admission to lower the risk of transmission of COVID-19, this has significantly affected patients in need of medical attention, for example, patients with emotional disorders. AIMS: This study aimed to compare the beliefs towards COVID-19 among outpatients with emotional disorders (ie, anxiety or depression) with those of family caregivers and the general public and examine factors that shape the beliefs towards COVID-19 among outpatients with emotional disorders. METHODS: Survey data from 570 outpatients with anxiety or depression disorders, 449 family caregivers and 470 general public subjects were collected. Multiple stepwise regression analyses were used to describe participants’ level of concern, prevention attitude and positive expectations towards the COVID-19 outbreak. RESULTS: About 70.9% of outpatients had to postpone their mental health treatment; 43.2% of patients admitted that their mental health was adversely affected by the COVID-19 outbreak—these patients tended to be older, male and less educated. After controlling for age and education level, outpatients with emotional disorders had significantly lower levels of concerns but more negative expectations towards COVID-19, compared with family caregivers and the public. Multivariate linear stepwise regression analysis showed that age, education and the perception of the impact of COVID-19 on one’s existing mental illness were significantly associated with outpatients’ beliefs about the epidemic. CONCLUSION: Outpatients with anxiety or depression disorders were relatively less focused on the COVID-19 outbreak, but the impact of the infection was found to be independently associated with their beliefs towards COVID-19. In addition, outpatients who were older and of low educational levels particularly held more negative beliefs about the epidemic, which may place them at a higher risk for poor mental health.


title: Explanation for COVID‐19 infection neurological damage and reactivations

text: A new pathogenic virus, COVID-19, appeared in 2019, in Wuhan, China, typically causing fever, cough, diarrhea and fatigue and significant mortality (Mao, 2020). From mid-January to mid-February in 2020, 214 patients with both non-severe and severe COVID-19 infections confirmed by nucleic acid tests, were examined by a panel of neurologists. Seventy-eight patients (36.4%) displayed neurological symptoms, including central nervous system symptoms of dizziness, headache, impaired consciousness, acute cerebrovascular disease with either ischemic stroke or cerebral hemorrhage, ataxia, seizures; peripheral nervous system symptoms of taste impairment, smell impairment, vision impairment, and nerve pain; and skeletal muscle injury (Mao, 2020).


title: Legal and Ethical Implications of Wastewater SARS-CoV-2 Monitoring for COVID-19 Surveillance

text: Scientists have observed that molecular markers for COVID-19 can be detected in wastewater of infected communities both during an outbreak and, in some cases, before the first case is confirmed. The CDC and other government entities are considering whether to add community surveillance through wastewater monitoring to assist in tracking disease prevalence and guiding public health responses to the COVID-19 pandemic. This scientific breakthrough may lead to many useful potential applications for tracking disease, intensifying testing, initiating social distancing or quarantines, and even lifting restrictions once a cessation of infection is detected and confirmed. Yet, new technologies developed in response to a public health crisis may raise difficult legal and ethical questions about how such technologies may impact both the public health and civil liberties of the population. This Article describes recent scientific evidence regarding COVID-19 detection in wastewater, identifying public health benefits that may result from this breakthrough, as well as the limitations of existing data. The Article then assesses the legal and ethical implications of implementing policy based on positive sewage signals. It concludes that the first step to implementing legal and ethical wastewater monitoring is to develop scientific understanding. Even if reliability and efficacy are established, limits on sample and data collection, use, and sharing, must also be considered to prevent undermining privacy and autonomy in order to implement these public health strategies consistent with legal and ethical considerations.


title: Enzymatic activity characterization of SARS coronavirus 3C-like protease by fluorescence resonance energy transfer technique

text: AIM: To characterize enzymatic activity of severe acute respiratory syndrome (SARS) coronavirus (CoV) 3C-like protease (3CL(pro)) and its four site-directed mutants. METHODS: Based on the fluorescence resonance energy transfer (FRET) principle using 5-[(2′-aminoethyl)-amino] naphthelenesulfonic acid (EDANS) and 4-[[4-(dimethylamino) phenyl] azo] benzoic acid (Dabcyl) as the energy transfer pair, one fluorogenic substrate was designed for the evaluation of SARS-CoV 3CL(pro) proteolytic activity. RESULTS: The kinetic parameters of the fluorogenic substrate have been determined as K(m)=404 μmol·L(−1), k(cat)=1.08 min(−1), and k(cat)/K(m)=2.7 mmol(−1)·L·min(−1). SARS-CoV 3CL(pro) showed substantial pH and temperature-triggered activity switches, and site-directed mutagenesis analysis of SARS-CoV 3CL(pro) revealed that substitutions of His(41), Cys(145), and His(163) resulted in complete loss of enzymatic activity, while replacement of Met(162) with Ala caused strongly increased activity. CONCLUSION: This present work has provided valuable information for understanding the catalytic mechanism of SARS-CoV 3CL(pro). This FRET-based assay might supply an ideal approach for the exploration SARS-CoV 3CL(pro) putative inhibitors.


title: ‘Masking the evidence’: perspectives of the COVID‐19 pandemic

text: The COVID‐19 pandemic presents a severe and acute public health emergency around the world. The event of the pandemic has seen an upsurge in the general public wearing of disposable surgical masks (DSM) and other types of face masks. The World Health Organisation of mask wearing has been widely debated in the press a(WHO) have changed their advice, to now recommend the routine wearing of fabric masks by the general public as a means of preventing the spread of COVID‐19 (WHO 2020a).


title: Comparable mRNA expression of inflammatory markers but lower claudin-1 mRNA levels in foreskin tissue of HSV-2 seropositive versus seronegative asymptomatic Kenyan young men

text: OBJECTIVES: Skin biopsies from local sites of herpes simplex virus 2 (HSV-2)-induced ulcers can show infiltrates of inflammatory cells several months after macroscopic healing. We hypothesise that foreskin tissue samples of asymptomatic HSV-2 seropositive men had remaining signs of inflammation at the molecular level. Even in the absence of clinical lesions, genital inflammation may contribute to increased HIV susceptibility on sexual exposure to the virus. SETTING: Foreskin tissue samples were collected from men undergoing elective circumcision in Kisumu, Kenya. PARTICIPANTS: The foreskin tissue samples (n=86) were stratified into study groups based on HSV-2 serology and assessed for mRNA expression of inflammatory markers. Markers of interest were further assessed by immunohistochemical staining within the tissue samples. RESULTS: The two study groups had comparable levels of all molecular markers (CD3, CD4, CD8, CD69, CCR5, HLA-DR, Langerin, DC-SIGN, Mannose Receptor 1, IL-1, IL-6, TNF-α, β7, IgA, IFN-α, CCL5, E-cadherin, ZO-1 and occludin), except for lower mRNA levels of the epithelial junction protein claudin-1 in the HSV-2 seropositive group (p=0.008). Although mRNA levels of claudin-1 were lower in HSV-2 seropositive individuals, the corresponding protein could be visualised in the foreskin epithelium of all samples tested. CONCLUSIONS: Whereas no general inflammation was demonstrated in the foreskin of asymptomatic HSV-2 seropositive individuals, a decreased expression of claudin-1 indicates a less robust genital epithelial barrier. An intact epithelial barrier is essential for blocking mucosal entry of genital infections, including HIV.


title: Composition and divergence of coronavirus spike proteins and host ACE2 receptors predict potential intermediate hosts of SARS‐CoV‐2

text: From the beginning of 2002 and 2012, severe respiratory syndrome coronavirus (SARS‐CoV) and Middle East respiratory syndrome coronavirus (MERS‐CoV) crossed the species barriers to infect humans, causing thousands of infections and hundreds of deaths, respectively. Currently, a novel coronavirus (SARS‐CoV‐2), which has become the cause of the outbreak of Coronavirus Disease 2019 (COVID‐19), was discovered. Until 18 February 2020, there were 72 533 confirmed COVID‐19 cases (including 10 644 severe cases) and 1872 deaths in China. SARS‐CoV‐2 is spreading among the public and causing substantial burden due to its human‐to‐human transmission. However, the intermediate host of SARS‐CoV‐2 is still unclear. Finding the possible intermediate host of SARS‐CoV‐2 is imperative to prevent further spread of the epidemic. In this study, we used systematic comparison and analysis to predict the interaction between the receptor‐binding domain (RBD) of coronavirus spike protein and the host receptor, angiotensin‐converting enzyme 2 (ACE2). The interaction between the key amino acids of S protein RBD and ACE2 indicated that, other than pangolins and snakes, as previously suggested, turtles (Chrysemys picta bellii, Chelonia mydas, and Pelodiscus sinensis) may act as the potential intermediate hosts transmitting SARS‐CoV‐2 to humans.


title: Epidemiology of Sarcoidosis

text: Sarcoidosis is a multisystemic disease in which lung involvement is common. Its incidence and prevalence have been extensively studied, but with contradictory results because of the lack of standard diagnostic criteria, variations in the methods for detecting cases, and the low sensitivity and specificity of diagnostic tests. Prognosis is generally favorable. Many of those affected remain asymptomatic and remission often occurs spontaneously, although between 10% and 30% of the patients have chronic disease and permanent deterioration in lung function. Sarcoidosis is caused by an external agent that triggers a characteristic immune response in genetically susceptible individuals. Environmental, occupational, and genetic factors have all been implicated, but research is still in the early stages. Case-control studies, as well as advances in molecular biology, will help to identify genetic susceptibility factors and to understand the different phenotypes of sarcoidosis.


title: Comparative genomic analysis of two emergent human adenovirus type 14 respiratory pathogen isolates in China reveals similar yet divergent genomes

text: Human adenovirus type 14 (HAdV-B14p) was originally identified as an acute respiratory disease (ARD) pathogen in The Netherlands in 1955. For approximately fifty years, few sporadic infections were observed. In 2005, HAdV-B14p1, a genomic variant, re-emerged and was associated with several large ARD outbreaks across the U.S. and, subsequently, in Canada, the U.K., Ireland, and China. This strain was associated with an unusually higher fatality rate than previously reported for both this prototype and other HAdV types in general. In China, HAdV-B14 was first observed in 2010, when two unrelated HAdV-B14-associated ARD cases were reported in Southern China (GZ01) and Northern China (BJ430), followed by three subsequent outbreaks. While comparative genomic analysis, including indel analysis, shows that the three China isolates, with whole genome data available, are similar to the de Wit prototype, all are divergent from the U.S. strain (303600; 2007). Although the genomes of strains GZ01 and BJ430 are nearly identical, as per their genome type characterization and percent identities, they are subtly divergent in their genome mutation patterns. These genomes indicate possibly two lineages of HAdV-B14 and independent introductions into China from abroad, or subsequent divergence from one; CHN2012 likely represents a separate sub-lineage. Observations of these simultaneously reported emergent strains in China add to the understanding of the circulation, epidemiology, and evolution of these HAdV pathogens, as well as provide a foundation for developing effective vaccines and public health strategies, including nationwide surveillance in anticipation of larger outbreaks with potentially higher fatality rates associated with HAdV-B14p1.


title: GILT restricts the cellular entry mediated by the envelope glycoproteins of SARS-CoV, Ebola virus and Lassa fever virus

text: Interferons (IFNs) control viral infections by inducing expression of IFN-stimulated genes (ISGs) that restrict distinct steps of viral replication. We report herein that gamma-interferon-inducible lysosomal thiol reductase (GILT), a lysosome-associated ISG, restricts the infectious entry of selected enveloped RNA viruses. Specifically, we demonstrated that GILT was constitutively expressed in lung epithelial cells and fibroblasts and its expression could be further induced by type II interferon. While overexpression of GILT inhibited the entry mediated by envelope glycoproteins of SARS coronavirus (SARS-CoV), Ebola virus (EBOV) and Lassa fever virus (LASV), depletion of GILT enhanced the entry mediated by these viral envelope glycoproteins. Furthermore, mutations that impaired the thiol reductase activity or disrupted the N-linked glycosylation, a posttranslational modification essential for its lysosomal localization, largely compromised GILT restriction of viral entry. We also found that the induction of GILT expression reduced the level and activity of cathepsin L, which is required for the entry of these RNA viruses in lysosomes. Our data indicate that GILT is a novel antiviral ISG that specifically inhibits the entry of selected enveloped RNA viruses in lysosomes via disruption of cathepsin L metabolism and function and may play a role in immune control and pathogenesis of these viruses.


title: Oxidative tissue injury in multiple sclerosis is only partly reflected in experimental disease models

text: Recent data suggest that oxidative injury may play an important role in demyelination and neurodegeneration in multiple sclerosis (MS). We compared the extent of oxidative injury in MS lesions with that in experimental models driven by different inflammatory mechanisms. It was only in a model of coronavirus-induced demyelinating encephalomyelitis that we detected an accumulation of oxidised phospholipids, which was comparable in extent to that in MS. In both, MS and coronavirus-induced encephalomyelitis, this was associated with massive microglial and macrophage activation, accompanied by the expression of the NADPH oxidase subunit p22phox but only sparse expression of inducible nitric oxide synthase (iNOS). Acute and chronic CD4(+) T cell-mediated experimental autoimmune encephalomyelitis lesions showed transient expression of p22phox and iNOS associated with inflammation. Macrophages in chronic lesions of antibody-mediated demyelinating encephalomyelitis showed lysosomal activity but very little p22phox or iNOS expressions. Active inflammatory demyelinating lesions induced by CD8(+) T cells or by innate immunity showed macrophage and microglial activation together with the expression of p22phox, but low or absent iNOS reactivity. We corroborated the differences between acute CD4(+) T cell-mediated experimental autoimmune encephalomyelitis and acute MS lesions via gene expression studies. Furthermore, age-dependent iron accumulation and lesion-associated iron liberation, as occurring in the human brain, were only minor in rodent brains. Our study shows that oxidative injury and its triggering mechanisms diverge in different models of rodent central nervous system inflammation. The amplification of oxidative injury, which has been suggested in MS, is only reflected to a limited degree in the studied rodent models. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00401-014-1263-5) contains supplementary material, which is available to authorized users.


title: Epidemiology of HBoV1 infection and relationship with meteorological conditions in hospitalized pediatric patients with acute respiratory illness: a 7-year study in a subtropical region

text: BACKGROUND: Human bocavirus 1 (HBoV1) is an important cause of acute respiratory illness (ARI), yet the epidemiology and effect of meteorological conditions on infection is not fully understood. To investigate the distribution of HBoV1 and determine the effect of meteorological conditions, hospitalized pediatric patients were studied in a subtropical region of China. METHODS: Samples from 11,399 hospitalized pediatric patients (≤14 years old), with ARI were tested for HBoV1 and other common respiratory pathogens using real-time PCR, between July 2009 and June 2016. In addition, local meteorological data were collected. RESULTS: Of the 11,399 patients tested, 5606 (49.2%) were positive for at least one respiratory pathogen. Two hundred forty-eight of 11,399 (2.2%) were positive for HBoV1 infection. Co-infection was common in HBoV1-positive patients (45.2%, 112/248). A significant difference in the prevalence of HBoV1 was found in patients in different age groups (p < 0.001), and the peak prevalence was found in patients aged 7–12 months (4.7%, 56/1203). Two HBoV1 prevalence peaks were found in summer (between June and September) and winter (between November and December). The prevalence of HBoV1 was significantly positively correlated with mean temperature and negatively correlated with mean relative humidity, and the mean temperature in the preceding month had better explanatory power than the current monthly temperature. CONCLUSIONS: This study provides a better understanding of the characteristics of HBoV1 infection in children in subtropical regions. Data from this study provide useful information for the future control and prevention of HBoV1 infections.


title: Influence of Population Immunosuppression and Past Vaccination on Smallpox Reemergence

text: We built a SEIR (susceptible, exposed, infected, recovered) model of smallpox transmission for New York, New York, USA, and Sydney, New South Wales, Australia, that accounted for age-specific population immunosuppression and residual vaccine immunity and conducted sensitivity analyses to estimate the effect these parameters might have on smallpox reemergence. At least 19% of New York’s and 17% of Sydney’s population are immunosuppressed. The highest smallpox infection rates were in persons 0–19 years of age, but the highest death rates were in those >45 years of age. Because of the low level of residual vaccine immunity, immunosuppression was more influential than vaccination on death and infection rates in our model. Despite widespread smallpox vaccination until 1980 in New York, smallpox outbreak severity appeared worse in New York than in Sydney. Immunosuppression is highly prevalent and should be considered in future smallpox outbreak models because excluding this factor probably underestimates death and infection rates.


title: Differential cellular gene expression in duck trachea infected with a highly or low pathogenic H5N1 avian influenza virus

text: BACKGROUND: Avian influenza A (AI) viruses of subtypes H5 can cause serious disease outbreaks in poultry including panzootic due to H5N1 highly pathogenic (HP) viruses. These viruses are a threat not only for animal health but also public health due to their zoonotic potential. The domestic duck plays a major role in the epidemiological cycle of influenza virus subtypes H5 but little is known concerning host/pathogen interactions during influenza infection in duck species. In this study, a subtracted library from duck trachea (a primary site of influenza virus infection) was constructed to analyse and compare the host response after a highly or low pathogenic (LP) H5N1-infection. RESULTS: Here, we show that more than 200 different genes were differentially expressed in infected duck trachea to a significant degree. In addition, significant differentially expressed genes between LPAI- and HPAI-infected tracheas were observed. Gene ontology annotation was used and specific signalling pathways were identified. These pathways were different for LPAI and HPAI-infected tracheas, except for the CXCR4 signalling pathway which is implicated in immune response. A different modulation of genes in the CXCR4 signalling pathway and TRIM33 was induced in duck tracheas infected with a HPAI- or a LPAI-H5N1. CONCLUSION: First, this study indicates that Suppressive Subtractive Hybridization (SSH) is an alternative approach to gain insights into the pathogenesis of influenza infection in ducks. Secondly, the results indicate that cellular gene expression in the duck trachea was differently modulated after infection with a LPAI-H5N1 or after infection with a HPAI-H5N1 virus. Such difference found in infected trachea, a primary infection site, could precede continuation of infection and could explain appearance of respiratory symptoms or not.


title: Establishment, Immortalisation and Characterisation of Pteropid Bat Cell Lines

text: BACKGROUND: Bats are the suspected natural reservoir hosts for a number of new and emerging zoonotic viruses including Nipah virus, Hendra virus, severe acute respiratory syndrome coronavirus and Ebola virus. Since the discovery of SARS-like coronaviruses in Chinese horseshoe bats, attempts to isolate a SL-CoV from bats have failed and attempts to isolate other bat-borne viruses in various mammalian cell lines have been similarly unsuccessful. New stable bat cell lines are needed to help with these investigations and as tools to assist in the study of bat immunology and virus-host interactions. METHODOLOGY/FINDINGS: Black flying foxes (Pteropus alecto) were captured from the wild and transported live to the laboratory for primary cell culture preparation using a variety of different methods and culture media. Primary cells were successfully cultured from 20 different organs. Cell immortalisation can occur spontaneously, however we used a retroviral system to immortalise cells via the transfer and stable production of the Simian virus 40 Large T antigen and the human telomerase reverse transcriptase protein. Initial infection experiments with both cloned and uncloned cell lines using Hendra and Nipah viruses demonstrated varying degrees of infection efficiency between the different cell lines, although it was possible to infect cells in all tissue types. CONCLUSIONS/SIGNIFICANCE: The approaches developed and optimised in this study should be applicable to bats of other species. We are in the process of generating further cell lines from a number of different bat species using the methodology established in this study.


title: Effects of Timely Control Intervention on the Spread of Middle East Respiratory Syndrome Coronavirus Infection

text: OBJECTIVES: The 2015 Middle East Respiratory Syndrome Coronavirus (MERS-CoV) outbreak in Korea caused major economic and social problems. The control intervention was conducted during the MERS-CoV outbreak in Korea immediately after the confirmation of the index case. This study investigates whether the early risk communication with the general public and mass media is an effective preventive strategy. METHODS: The SEIR (Susceptible, Exposed, Infectious, Recovered) model with estimated parameters for the time series data of the daily MERS-CoV incidence in Korea was considered from May to December 2015. For 10,000 stochastic simulations, the SEIR model was computed using the Gillespie algorithm. Depending on the time of control intervention on the 20th, 40th, and 60th days after the identification of the index case, the box plots of MERS-CoV incidences in Korea were computed, and the results were analyzed via ANOVA. RESULTS: The box plots showed that there was a significant difference between the non-intervention and intervention groups (the 20th day, 40th day, and 60th day groups) and seemed to show no significant difference based on the time of intervention. However, the ANOVA revealed that early intervention was a good strategy to control the disease. CONCLUSION: Appropriate risk communication can secure the confidence of the general public in the public health authorities.


Fake news : et si moustiques et tiques transmettaient le Covid-19 ?


title: COVID-19 pandemic: an overview of epidemiology, parthenogenesis, diagnostics and potential vaccines and therapeutics

text: At the time of writing this review, severe acute respiratory coronavirus syndrome-2 (SARS-CoV-2) has infected more than 2,355,853 patients and resulted in more than 164,656 deaths worldwide (as of 20 April 2020). This review highlights the preventive measures, available clinical therapies and the potential of vaccine development against SARS-CoV-2 by taking into consideration the strong genetic similarities of the 2003 epidemic SARS-CoV. Recent studies are investigating the repurposing of US FDA-approved drugs as there is no available vaccine yet with many attempts under clinical evaluation. Several antivirals, antimalarials and immunomodulators that have shown activity against SARS-CoV and Middle East coronavirus respiratory syndromes are being evaluated. In particular, hydroxychloroquine, remdesivir, favipiravir, arbidol, tocilizumab and bevacizumab have shown promising results. The main aim of this review is to provide an overview of this pandemic and where we currently stand.


title: Evolving geographic diversity in SARS-CoV2 and in silico analysis of replicating enzyme 3CL(pro) targeting repurposed drug candidates

text: BACKGROUND: Severe acute respiratory syndrome (SARS) has been initiating pandemics since the beginning of the century. In December 2019, the world was hit again by a devastating SARS episode that has so far infected almost four million individuals worldwide, with over 200,000 fatalities having already occurred by mid-April 2020, and the infection rate continues to grow exponentially. SARS coronavirus 2 (SARS-CoV-2) is a single stranded RNA pathogen which is characterised by a high mutation rate. It is vital to explore the mutagenic capability of the viral genome that enables SARS-CoV-2 to rapidly jump from one host immunity to another and adapt to the genetic pool of local populations. METHODS: For this study, we analysed 2301 complete viral sequences reported from SARS-CoV-2 infected patients. SARS-CoV-2 host genomes were collected from The Global Initiative on Sharing All Influenza Data (GISAID) database containing 9 genomes from pangolin-CoV origin and 3 genomes from bat-CoV origin, Wuhan SARS-CoV2 reference genome was collected from GeneBank database. The Multiple sequence alignment tool, Clustal Omega was used for genomic sequence alignment. The viral replicating enzyme, 3-chymotrypsin-like cysteine protease (3CL(pro)) that plays a key role in its pathogenicity was used to assess its affinity with pharmacological inhibitors and repurposed drugs such as anti-viral flavones, biflavanoids, anti-malarial drugs and vitamin supplements. RESULTS: Our results demonstrate that bat-CoV shares > 96% similar identity, while pangolin-CoV shares 85.98% identity with Wuhan SARS-CoV-2 genome. This in-depth analysis has identified 12 novel recurrent mutations in South American and African viral genomes out of which 3 were unique in South America, 4 unique in Africa and 5 were present in-patient isolates from both populations. Using state of the art in silico approaches, this study further investigates the interaction of repurposed drugs with the SARS-CoV-2 3CL(pro) enzyme, which regulates viral replication machinery. CONCLUSIONS: Overall, this study provides insights into the evolving mutations, with implications to understand viral pathogenicity and possible new strategies for repurposing compounds to combat the nCovid-19 pandemic.


title: Rapid detection of reassortment of pandemic H1N1/2009 influenza virus

text: BACKGROUND: Influenza viruses can generate novel reassortants in co-infected cells. The global circulation and occasional introductions of pandemic H1N1/2009 virus in humans and in pigs, respectively, might provide opportunities for this virus to reassort with other influenza viruses. These possible reassortment events might alter virulence and/or transmissibility of the new reassortants. Investigations that can detect such possible reassortants should therefore be included as a part of pandemic influenza surveillance plans. METHODS: We established a real-time RT-PCR-based strategy for the detection of reassortment of pandemic H1N1/2009 virus. Singleplex SYBR green-based RT-PCR assays specific for each gene segment of pandemic H1N1/2009 were developed. These assays were evaluated by influenza viruses with different genetic backgrounds. RESULTS: All human pandemic H1N1 (N=27) and all seasonal human (N=58) isolates were positive and negative, respectively, for all 8 segments. Of 48 swine influenza viruses isolated from our on-going surveillance program of influenza viruses in swine, 10 were positive in all reactions. All 8 viral segments of these 10 samples were confirmed to be of pandemic H1N1 origin, indicating that these were caused by zoonotic transmissions from human to pigs. The 38 swine viruses that are non-pandemic H1N1/2009 had 1 to 6 gene segments positive in the tests. Further characterization of these non-pandemic H1N1/2009 swine viruses indicated that these PCR positive genes are the precursor genes of pandemic H1N1/2009 virus. CONCLUSIONS: Our results demonstrated that these assays can detect re-introductions of pandemic H1N1/2009 virus in pigs. These assays might be useful screening tools for identifying viral reassortants derived from pandemic H1N1/2009 or its precursors.


title: Severe acute respiratory syndrome-related coronavirus: The species and its viruses – a statement of the Coronavirus Study Group

text: The present outbreak of lower respiratory tract infections, including respiratory distress syndrome, is the third spillover, in only two decades, of an animal coronavirus to humans resulting in a major epidemic. Here, the Coronavirus Study Group (CSG) of the International Committee on Taxonomy of Viruses, which is responsible for developing the official classification of viruses and taxa naming (taxonomy) of the Coronaviridae family, assessed the novelty of the human pathogen tentatively named 2019-nCoV. Based on phylogeny, taxonomy and established practice, the CSG formally recognizes this virus as a sister to severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the species Severe acute respiratory syndrome-related coronavirus and designates it as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To facilitate communication, the CSG further proposes to use the following naming convention for individual isolates: SARS-CoV-2/Isolate/Host/Date/Location. The spectrum of clinical manifestations associated with SARS-CoV-2 infections in humans remains to be determined. The independent zoonotic transmission of SARS-CoV and SARS-CoV-2 highlights the need for studying the entire (virus) species to complement research focused on individual pathogenic viruses of immediate significance. This research will improve our understanding of virus-host interactions in an ever-changing environment and enhance our preparedness for future outbreaks.


title: Infecciones víricas

text: Resumen Los virus pueden causar enfermedad, tras superar las barreras protectoras naturales del organismo y evadir el control inmunológico, destruyendo células o desencadenando una respuesta inflamatoria e inmunitaria que puede causar daño al propio organismo. El desarrollo de la infección vírica está determinado por el tipo de relación virus/hospedador y la respuesta de este a la infección. Las infecciones víricas pueden ser líticas o persistentes (latencia, recurrencia y/o transformación de la célula). La respuesta inmunitaria es la mejor herramienta para controlar la diseminación del virus; sin embargo, en ocasiones, contribuye a la patogénesis de la infección. El laboratorio aporta información relevante mediante la descripción del efecto citopático inducido por el virus, la detección de las partículas víricas utilizando microscopía electrónica, el aislamiento y crecimiento del virus en medios celulares in vitro, la detección de componentes víricos (proteínas y ácidos nucleicos) y la evaluación de la respuesta inmunitaria del paciente frente al virus. Abstract Viruses cause disease after they break through the natural protective barriers of the body, evade immune control, and either kill cells of an important tissue or trigger a destructive immune and inflammatory response. The outcome of a viral infection is determined by the nature of the virushost interaction and the host's response to the infection. Viral infections can be lytic or persistent (latency, recurrence and / or transformation of the the cell). Immune response is the best treatment, but it often contributes to the pathogenesis of a viral infection. The laboratory methods accomplish the following results: description of virus-induced cytopathologic effects (CPEs) on cells, electron microscopic detection of viral particles, isolation and growth of the virus, detection of viral components (proteins and nucleic acids) and evaluation of the patient's immune response to the virus.


title: Treatment of Community-Acquired Pneumonia During the Coronavirus Disease 2019 (COVID-19) Pandemic

text: Although pneumonia caused by severe acute respiratory syndrome coronavirus 2 is a prominent feature of COVID-19, clinicians must consider whether treatment for additional potential causes of community-acquired pneumonia (CAP) is appropriate. The cochairs of the recently released American Thoracic Society and Infectious Diseases Society of America Guideline for Treatment of Adults with CAP offer their interpretation of this guideline's application to the evaluation and treatment of patients with COVID-19.


COVID-19: Let's not forget Africa!


title: A physicist's approach to COVID-19 transmission via expiratory droplets

text: In this paper, a physicist's approach is given to support the necessity to wear surgical masks during the COVID-19 pandemics; they have become compulsory in Eastern countries, while in Western countries they are still an optional. My thesis is supported and described on the basis of a physicist's model which studies the droplets behavior when emitted by the respiratory apparatus of an infected person, symptomatic or not. The intermediate dimensioned droplets are proved to be changed into aerosol, losing their water content and becoming seriously contagious, but in their initial phase they could be easily caught by a simple surgical mask. The actual efficiency of FFP3 masks has been examined and found to be lower than expected.


title: Publication of COVID‐19 case reports: are we hurrying?

text: The global situation that has been established is worrying due to the pandemic of COVID‐19. In this context, the great majority of government entities have turned their attention even more to the importance of scientific research in solving health issues since public policies must be strongly based on science to perform their function efficiently. We are on the right track when choosing to survive. And surviving means sparing no effort to find a cure. Such a process involves investments and acceleration of steps (Van Norman, 2016). One example is the creation of the CTAP (Coronavirus Treatment Acceleration Program) by the FDA (U.S Foods And Drugs Administration) to support clinical trials.


title: Effects of Micronutrients or Conditional Amino Acids on COVID-19 Related Outcomes: An Evidence Analysis Center Scoping Review

text: Abstract Recent narrative reviews have described the potential efficacy of providing individuals infected with COVID-19 with additional micronutrients to reduce disease severity. While there are compelling reasons why providing additional micronutrients or conditional amino acids may affect COVID-19-related outcomes, evidence is lacking. The objective of this scoping review is to explore and describe the literature examining the effect of providing additional micronutrients or conditional amino acids (glutamine, arginine) in adults with conditions or infections similar to COVID-19 infection on COVID-19 related health outcomes. A literature search of the MEDLINE database and hand-search of Cochrane Database of systematic reviews retrieved 1,423 unique studies, and eight studies were included in this scoping review. Four studies examined a target population with ventilator-related pneumonia and acute respiratory distress syndrome, while the other four studies included patients who were at risk for ventilator-associated pneumonia. Interventions included intravenous vitamin C, intramuscular vitamin D, enteral and intramuscular vitamin E, enteral zinc sulfate, and oral and parenteral glutamine. In six of the eight included studies, baseline status of the nutrient of interest was not reported and, thus, it is uncertain how outcomes may vary in the context of nutrient deficiency or insufficiency compared to sufficiency. In the absence of direct evidence examining efficacy of providing additional micronutrients or conditional amino acids to standard care, registered dietitian nutritionists (RDNs) must rely on clinical expertise, and indirect evidence to guide medical nutrition therapy (MNT) for patients infected with COVID-19.


title: The population genetics and evolutionary epidemiology of RNA viruses

text: RNA viruses are ubiquitous intracellular parasites that are responsible for many emerging diseases, including AIDS and SARS. Here, we discuss the principal mechanisms of RNA virus evolution and highlight areas where future research is required. The rapidity of sequence change in RNA viruses means that they are useful experimental models for the study of evolution in general and it enables us to watch them change in 'real time', and retrace the spread through populations with molecular phylogenies. An understanding of the mechanisms of RNA virus sequence change is also crucial to predicting important aspects of their emergence and long-term evolution.


title: Decreased Pattern Recognition Receptor Signaling, Interferon-Signature, and Bactericidal/Permeability-Increasing Protein Gene Expression in Cord Blood of Term Low Birth Weight Human Newborns

text: BACKGROUND: Morbidity and mortality rates of low birth weight (LBW) newborns at term are higher than rates in normal birth weight (NBW) newborns. LBW newborns are at greater risk to acquire recurrent bacterial and viral infections during their first few weeks of life possibly as an outcome of compromised innate immune functions. As adaptive immunity is in a naive state, increased risk of infection of LBW as compared to NBW newborns may reflect impairments in innate immunity. METHODOLOGY: To characterize the increased susceptibility to infections in LBW newborns we used microarray technology to identify differences in gene expression in LBW newborns (n = 8) compared to NBW newborns (n = 4) using cord blood. The results obtained from the microarray study were validated on a larger number of samples using real time RT-PCR (LBW = 22, NBW = 18) and western blotting (LBW = 12, NBW = 12). The Interferome database was used to identify interferon (IFN) signature genes and ingenuity pathway analysis identified canonical pathways and biological functions associated with the differentially expressed genes in LBW newborns. ELISAs for IFNs and bactericidal/permeability-increasing protein were performed in both LBW and NBW newborns and in adults (LBW = 18, NBW = 18, Adults = 8). PRINCIPAL FINDINGS: Upon microarray analysis, we identified 1,391 differentially expressed genes, of which, 1,065 genes were down-regulated and 326 genes were up-regulated in the LBW compared to NBW newborns. Of note, 70 IFN-signature genes were found to be significantly down-regulated in LBW compared to NBW newborns. Ingenuity pathway analysis revealed pattern recognition receptors signaling including Toll-Like Receptors (TLRs) -1, -5, and -8 genes and IFN signaling as the most significantly impacted pathways. Respiratory infectious diseases were the most significantly affected bio-functions in LBW newborns. CONCLUSION AND SIGNIFICANCE: Diminished PRRs, IFN-signature, and BPI gene expression raises the possibility that impairments in these pathways contribute to the susceptibility of LBW term infants to infection.


title: International COVID-19 palliative care guidance for nursing homes leaves key themes unaddressed

text: COVID-19 mortality disproportionally affects nursing homes, creating enormous pressures to deliver high-quality end-of-life care. Comprehensive palliative care should be an explicit part of both national and global COVID-19 response plans. Therefore, we aimed to identify, review and compare national and international COVID-19 guidance for nursing homes concerning palliative care, issued by government bodies and professional associations. We performed a directed documentary and content analysis of newly developed or adapted COVID-19 guidance documents from across the world. Documents were collected via expert consultation and independently screened against pre-specified eligibility criteria. We applied thematic analysis and narrative synthesis techniques. We identified 21 eligible documents covering both nursing homes and palliative care; from the World Health Organization (n=3), and eight individual countries: USA (n=7), the Netherlands (n=2), Ireland (n=1), United Kingdom (n=3), Switzerland (n=3), New Zealand (n=1), Belgium (n=1). International documents focused primarily on infection prevention and control, including only a few sentences on palliative care related topics. Palliative care themes most frequently mentioned across documents were end-of-life visits, advance care planning documentation, and clinical decision-making towards the end of life (focusing on hospital transfers). There is a dearth of comprehensive international COVID-19 guidance on palliative care for nursing homes. Most have a limited focus both regarding breadth of topics and recommendations made. Key aspects of palliative care, i.e. symptom management, staff education and support, referral to specialist services or hospice, and family support, need greater attention in future guidelines.


Collective action and “social distancing” in COVID-19 responses


Sars-COV-2 in Romania – analysis of the first confirmed case and evolution of the pandemic in Romania in the first three months


title: Respiratory Virus Infections in Hematopoietic Cell Transplant Recipients

text: Highly immunocompromised pediatric and adult hematopoietic cell transplant (HCT) recipients frequently experience respiratory infections caused by viruses that are less virulent in immunocompetent individuals. Most of these infections, with the exception of rhinovirus as well as adenovirus and parainfluenza virus in tropical areas, are seasonal variable and occur before and after HCT. Infectious disease management includes sampling of respiratory specimens from nasopharyngeal washes or swabs as well as sputum and tracheal or tracheobronchial lavages. These are subjected to improved diagnostic tools including multiplex PCR assays that are routinely used allowing for expedient detection of all respiratory viruses. Disease progression along with high mortality is frequently associated with respiratory syncytial virus, parainfluenza virus, influenza virus, and metapneumovirus infections. In this review, we discuss clinical findings and the appropriate use of diagnostic measures. Additionally, we also discuss treatment options and suggest new drug formulations that might prove useful in treating respiratory viral infections. Finally, we shed light on the role of the state of immune reconstitution and on the use of immunosuppressive drugs on the outcome of infection.


title: RNA-RNA and RNA-protein interactions in coronavirus replication and transcription

text: Coronavirus (CoV) RNA synthesis includes the replication of the viral genome, and the transcription of sgRNAs by a discontinuous mechanism. Both processes are regulated by RNA sequences such as the 5′ and 3′ untranslated regions (UTRs), and the transcription regulating sequences (TRSs) of the leader (TRS-L) and those preceding each gene (TRS-Bs). These distant RNA regulatory sequences interact with each other directly and probably through protein-RNA and protein-protein interactions involving viral and cellular proteins.1 By analogy to other plus-stranded RNA viruses, such as polioviruses, in which translation and replication switch involves a cellular factor (PCBP) and a viral protein (3CD),2 it is conceivable that in CoVs the switch between replication and transcription is also associated with the binding of proteins that are specifically recruited by the replication or transcription complexes. Complexes between RNA motifs such as TRS-L and the TRS-Bs located along the CoV genome are probably formed previously to the transcription start, and most likely promote template-switch of the nascent minus RNA to the TRS-L region.3 Many cellular proteins interacting with regulatory CoV RNA sequences4 are members of the heterogeneous nuclear ribonucleoprotein (hnRNP) family of RNA-binding proteins, involved in mRNA processing and transport, which shuttle between the nucleus and the cytoplasm. In the context of CoV RNA synthesis, these cellular ribonucleoproteins might also participate in RNA-protein complexes to bring into physical proximity TRS-L and distant TRS-B, as proposed for CoV discontinuous transcription.5–7 In this review, we summarize RNA-RNA and RNA-protein interactions that represent modest examples of complex quaternary RNA-protein structures required for the fine-tuning of virus replication. Design of chemically defined replication and transcription systems will help to clarify the nature and activity of these structures.


title: Guillain-Barré Syndrome associated with SARS-CoV-2 infection

text: Abstract We present a case of Guillain- Barré Syndrome (GBS) in a patient with confirmed COVID-19 infection. GBS in commonly encountered after an antecedent trigger, most commonly an infection. To date, only one case of GBS associated with this infection has been described. Clinicians should consider this entity since it may warrant appropriate isolation precautions especially in a patient who may not present primarily with typical constitutional and respiratory symptoms associated with COVID-19.


title: Why Are Lopinavir and Ritonavir Effective against the Newly Emerged Coronavirus 2019? Atomistic Insights into the Inhibitory Mechanisms

text: [Image: see text] Since the emergence of a novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported from Wuhan, China, neither a specific vaccine nor an antiviral drug against SARS-CoV-2 has become available. However, a combination of two HIV-1 protease inhibitors, lopinavir and ritonavir, has been found to be effective against SARS-CoV, and both drugs could bind well to the SARS-CoV 3C-like protease (SARS-CoV 3CL(pro)). In this work, molecular complexation between each inhibitor and SARS-CoV-2 3CL(pro) was studied using all-atom molecular dynamics simulations, free energy calculations, and pair interaction energy analyses based on MM/PB(GB)SA and FMO-MP2/PCM/6-31G* methods. Both anti-HIV drugs interacted well with the residues at the active site of SARS-CoV-2 3CL(pro). Ritonavir showed a somewhat higher number atomic contacts, a somewhat higher binding efficiency, and a somewhat higher number of key binding residues compared to lopinavir, which correspond with the slightly lower water accessibility at the 3CL(pro) active site. In addition, only ritonavir could interact with the oxyanion hole residues N142 and G143 via the formation of two hydrogen bonds. The interactions in terms of electrostatics, dispersion, and charge transfer played an important role in the drug binding. The obtained results demonstrated how repurposed anti-HIV drugs could be used to combat COVID-19.


title: Serological report of pandemic (H1N1) 2009 infection among cats in Northeastern China in 2012-02 and 2013-03

text: BACKGROUND: Influenza A virus has a wide range of hosts. It has not only infected human, but also been reported interspecies transmission from humans to other animals, such as pigs, poultry, dogs and cats. However, prevalence of A (H1N1) pdm09 influenza virus infections in cats in northeastern China is unknown. Therefore, the prevalence of A (H1N1) pdm09 influenza virus infections was performed among cats in northeastern China in this study. FINDINGS: Of all samples in this study, the overall seroprevalence of pandemic (H1N1) 2009 infection in cats was 21% (240/1140). It also showed a higher prevalence rate of pandemic(H1N1) 2009 infection in pet cats (30.6%) than roaming cats (11%) based on NT. In addition, the results also showed a trend of difference in term of species of cats and it was statistically significant. CONCLUSIONS: This is the first survey on the seroprevalence of pandemic (H1N1) 2009 infection among cats in northeastern China. This study has observed a relatively high seroprevalence of pandemic (H1N1) 2009 among different cat populations in northeastern China, similar seroprevalence studies should be conducted elsewhere.


Do antibodies enhance the infection of cells by HIV?


title: The impact of influenza and respiratory syncytial virus on hospitalizations for lower respiratory tract infections in young children: Slovenia, 2006–2011

text: BACKGROUND: Influenza and respiratory syncytial viruses (RSV) are important viral pathogens in childhood. OBJECTIVES: Our aim was to estimate the effect of influenza and RSV on excess hospitalizations for acute lower respiratory tract infections (ALRTI) in children aged ≤5. METHODS: Retrospective, population‐based study was performed for five seasons (2006–2011). Slovenian national hospital discharge data and surveillance data were used to estimate the effect of influenza and/or RSV on ALRTI hospitalizations (acute bronchiolitis, pneumonia, and acute bronchitis) using rate difference method. RESULTS: An excess was observed in average weekly ALRTI hospitalizations per 100 000 among children aged ≤5 in all five seasons during influenza and/or RSV active period. During three seasons, there was higher excess in ALRTI hospitalizations in the period when influenza/RSV cocirculated compared with the RSV period. In pandemic season (2009/2010), the only one without influenza/RSV overlap, excess hospitalization was higher in RSV period. The highest excess of hospitalizations was found among the youngest children (0‐5 months old). In all five seasons, acute bronchiolitis was the most common ALRTI recorded in hospitalized young children. CONCLUSIONS: Respiratory syncytial viruses was leading viral pathogen associated with ALRTI hospitalizations in children aged ≤5. The cocirculation of influenza virus increased the burden of ALRTI hospitalizations especially in seasons with A(H3) predominance.