title: A pilot study of therapeutic plasma exchange for serious SARS CoV-2 disease (COVID-19): A structured summary of a randomized controlled trial study protocol

text: OBJECTIVES: To evaluate the safety of therapeutic plasma exchange (TPE) in adult patients with serious/life-threatening COVID-19 requiring intensive care unit (ICU) admission, and associated 28-day mortality. Serious and life threatening COVID-19 are defined as per published literature (please, refer to the full protocol, Additional file 1). The rationale is that TPE can remove interleukins-3, 6, 8, 10, interferon-gamma and tumor necrosis factor-alpha. Thus, it may reduce the cytokine release syndrome associated with fulminant COVID-19 disease. TRIAL DESIGN: Pilot, interventional, open-label, randomized controlled multicenter trial. PARTICIPANTS: Inclusion criteria are: 1) age ≥ 18 years old; 2) intubation and intensive care unit (ICU) admission; 3) serious and/or life-threatening COVID-19 (please, refer to the full protocol, Additional file 1). SARS-CoV-2 infection is confirmed by Real-Time-Polymerase-Chain-Reaction (RT-PCR) assays using QuantiNova Probe RT-PCR kit (Qiagen) in a Light-Cycler 480 real-time PCR system (Roche, Basel, Switzerland). Exclusion criteria are: 1) previous allergic reaction to plasma exchange or its ingredients (i.e., sodium citrate), 2) two consecutive negative RT-PCR tests for SARS-CoV-2 at least 24 hours apart, 3) mild COVID-19 not requiring ICU admission and 4) terminally ill patients receiving palliative care. The primary site will be King Saud Medical City (KSMC), Riyadh, Kingdom of Saudi Arabia (KSA). Also, the study will run in ICUs (Ministry of Health Cluster 1; Riyadh) and other centers in KSA pending their institutional review board (IRB) approval. INTERVENTIONS AND COMPARATOR: The intervention group will receive TPE, plus empiric treatment for COVID-19. TPE is administered using the Spectra Optia TM Apheresis System equipped with the Depuro D2000 Adsorption Cartridge (Terumo BCT Inc., USA). The first dose is 1.5 plasma volumes, followed by one plasma volume on alternate days or daily for five to seven total treatments. Spectra Optia TM Apheresis System operates with acid-citrate dextrose anticoagulant (ACDA) as per Kidney Disease Improving Global Outcomes (KDIGO) 2019 guidelines. Plasma is replaced with albumin 5% or fresh frozen plasma in patients with coagulopathy (prothrombin time >37 seconds; international normalized ratio >3; activated partial thromboplastin time >100 or fibrinogen level <100 mg/d). TPE sessions are performed daily over four hours and laboratory markers measured daily. The comparators are controls not receiving TPE but usual empiric treatment for COVID-19 as per institutional, national and international recommendations. Both groups will receive standard ICU supportive care. MAIN OUTCOMES: Primary study end-point is 28-day mortality and safety of TPE in serious and/or life-threatening COVID-19. Safety will be evaluated by the documentation of any pertinent adverse and/or serious adverse effects related to TPE as per institutional, national and international (Food and Drug Administration) guidelines. Secondary outcomes are: i) improvement in Sequential Organ Function Assessment (SOFA) score ; ii) changes in inflammatory markers: serum C-reactive protein, lactate dehydrogenase, ferritin, d-dimers and interleukin-6; iii) days on mechanical ventilation and ICU length of stay. RANDOMIZATION: Eligible consented patients are randomized (1:1 allocation) after stratification by ICU center and two PaO2/FIO2 ratio categories (> 150 and ≤ 150). Randomization occurs in variable block sizes of four to eight patients. A web-based randomization service, randomize.net, is used to allocate patients to their respective strata prior to the intervention or control therapy. BLINDING (MASKING): Given the visibility of TPE machinery, the intervention will be unblinded; hence, no enrollment concealment will be expedited. The lack of allocation concealment will be mitigated by several measures (please, refer to the full protocol, Additional file 1). NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): This pilot randomized trial aims to recruit a convenience sample of patients with serious and/or life-threatening COVID-19. Therefore, at least 20 patients are to be randomized to each group per participating center. We are hoping to consent and randomize approximately 60 patients in each group over a 3 to 6 months period giving a total of 120 participants. TRIAL STATUS: The protocol version 1 was approved 29/04/2020. Recruitment is ongoing, and began on 01/05/2020. We estimate completion by 29/10/2020. TRIAL REGISTRATION: Registered at ISRCTN on 18/05/2020 (ISRCTN21363594; doi.10.1186/ ISRCTN21363594). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.


title: Low‐Contact & High‐Interconnectivity Pathology (LC&HI Path): Post‐COVID19‐Pandemic Practice of Pathology

text: The COVID‐19 pandemic situation may be viewed as an opportunity to accelerate some of the ongoing transformations in modern Pathology. This refers primarily to the digitalization of the practice of tissue and cellular pathology diagnostics. However, it is also an opportunity to analyse the modus operandi of a discipline that has practiced in a similar manner for over 100 years. The challenge is to define the next generation of interconnectivity tools that would be necessary to achieve a new operational model that, while ensuring low face‐to‐face interaction between the main players of the diagnostic pipeline, allows maximum interconnectivity to serve our patients and the immediate teaching and research needs associated with clinical tissue/cellular samples. This viewpoint aims to describe what this new paradigm, a low‐contact & high‐interconnectivity pathology (LC&HC Path) operation, may require in the near future.


title: First genome sequences of buffalo coronavirus from water buffaloes in Bangladesh

text: We report the complete genome sequences of a buffalo coronavirus (BufCoV HKU26) detected from the faecal samples of two domestic water buffaloes (Bubalus bubalis) in Bangladesh. They possessed 98–99% nucleotide identities to bovine coronavirus (BCoV) genomes, supporting BufCoV HKU26 as a member of Betacoronavirus 1. Nevertheless, BufCoV HKU26 possessed distinct accessory proteins between spike and envelope compared to BCoV. Sugar-binding residues in the N-terminal domain of S protein in BCoV are conserved in BufCoV HKU26.


title: The impact analysis of a multiplex PCR respiratory panel for hospitalized pediatric respiratory infections in Japan

text: Abstract Background Rapid molecular diagnosis of infections has contributed to timely treatments and antimicrobial stewardship. However, the benefit and cost-effectiveness vary in each country or community because they have different standard practices and health care systems. In Japan, rapid antigen tests (RATs) have been frequently used for pediatric respiratory infections. We investigated the impact and cost-effectiveness of a multiplex PCR (mPCR) respiratory panel for pediatric respiratory infections in a Japanese community hospital. Methods We replaced RATs with an mPCR respiratory panel (FilmArray®) for admitted pediatric respiratory infections on March 26, 2018. We compared the days of antimicrobial therapy (DOT) and length of stay (LOS) during the mPCR period (March 2018 to April 2019) with those of the RAT period (March 2012 to March 2018). Results During the RAT and mPCR periods, 1132 and 149 patients were analyzed. The DOT/case was 12.82 vs 8.56 (p < 0.001), and the LOS was 8.18 vs 6.83 days (p = 0.032) in the RAT and mPCR groups, respectively. The total costs during admissions were ∖258,824 ($2331.7) and ∖243,841 ($2196.8)/case, respectively. Pathogen detection rates were 30.2% vs 87.2% (p < 0.001). Conclusion Compared to conventional RATs, the mPCR test contributed to a reduction in the DOT and LOS in a Japanese community hospital for admission-requiring pediatric respiratory infections. However, a proper stewardship program is essential to further reduce the unnecessary usage of antimicrobials.


title: Impact of Host Genetics and Biological Response Modifiers on Respiratory Tract Infections

text: Host susceptibility to respiratory tract infections (RTI) is dependent on both genetic and acquired risk factors. Repeated bacterial and viral RTI, such as pneumonia from encapsulated microorganisms, respiratory tract infections related to respiratory syncytial virus or influenza, and even the development of bronchiectasis and asthma, are often reported as the first symptom of primary immunodeficiencies. In the same way, neutropenia is a well-known risk factor for invasive aspergillosis, as well as lymphopenia for Pneumocystis, and mycobacterial infections. However, in the last decades a better knowledge of immune signaling networks and the introduction of next generation sequencing have increased the number and diversity of known inborn errors of immunity. On the other hand, the use of monoclonal antibodies targeting cytokines, such as tumor necrosis factor alpha has revealed new risk groups for infections, such as tuberculosis. The use of biological response modifiers has spread to almost all medical specialties, including inflammatory diseases and neoplasia, and are being used to target different signaling networks that may mirror some of the known immune deficiencies. From a clinical perspective, the individual contribution of genetics, and/or targeted treatments, to immune dysregulation is difficult to assess. The aim of this article is to review the known and newly described mechanisms of impaired immune signaling that predispose to RTI, including new insights into host genetics and the impact of biological response modifiers, and to summarize clinical recommendations regarding vaccines and prophylactic treatments in order to prevent infections.


title: Cystic Fibrosis Gene Therapy: Looking Back, Looking Forward

text: Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that encodes a cAMP-regulated anion channel. Although CF is a multi-organ system disease, most people with CF die of progressive lung disease that begins early in childhood and is characterized by chronic bacterial infection and inflammation. Nearly 90% of people with CF have at least one copy of the ΔF508 mutation, but there are hundreds of CFTR mutations that result in a range of disease severities. A CFTR gene replacement approach would be efficacious regardless of the disease-causing mutation. After the discovery of the CFTR gene in 1989, the in vitro proof-of-concept for gene therapy for CF was quickly established in 1990. In 1993, the first of many gene therapy clinical trials attempted to rescue the CF defect in airway epithelia. Despite the initial enthusiasm, there is still no FDA-approved gene therapy for CF. Here we discuss the history of CF gene therapy, from the discovery of the CFTR gene to current state-of-the-art gene delivery vector designs. While implementation of CF gene therapy has proven more challenging than initially envisioned; thanks to continued innovation, it may yet become a reality.


title: Regulation of Programmed Ribosomal Frameshifting by Co-Translational Refolding RNA Hairpins

text: RNA structures are unwound for decoding. In the process, they can pause the elongating ribosome for regulation. An example is the stimulation of -1 programmed ribosomal frameshifting, leading to 3′ direction slippage of the reading-frame during elongation, by specific pseudoknot stimulators downstream of the frameshifting site. By investigating a recently identified regulatory element upstream of the SARS coronavirus (SARS-CoV) −1 frameshifting site, it is shown that a minimal functional element with hairpin forming potential is sufficient to down-regulate−1 frameshifting activity. Mutagenesis to disrupt or restore base pairs in the potential hairpin stem reveals that base-pair formation is required for−1 frameshifting attenuation in vitro and in 293T cells. The attenuation efficiency of a hairpin is determined by its stability and proximity to the frameshifting site; however, it is insensitive to E site sequence variation. Additionally, using a dual luciferase assay, it can be shown that a hairpin stimulated +1 frameshifting when placed upstream of a +1 shifty site in yeast. The investigations indicate that the hairpin is indeed a cis-acting programmed reading-frame switch modulator. This result provides insight into mechanisms governing−1 frameshifting stimulation and attenuation. Since the upstream hairpin is unwound (by a marching ribosome) before the downstream stimulator, this study’s findings suggest a new mode of translational regulation that is mediated by the reformed stem of a ribosomal unwound RNA hairpin during elongation.


title: Loss aversion and market crashes

text: This study proposes a rational expectation equilibrium model of stock market crashes with information asymmetry and loss averse speculators. We obtain a state-dependent linear optimal trading strategy, which makes the equilibrium price tractable. The model predicts nonlinear market depth and the result that small shocks to fundamentals (e.g., supply or informational shocks) can cause abrupt price movements. We demonstrate that short-sale constraints intensify asset price collapses relative to upward movements. The model also generates contagion between uncorrelated assets. These results are consistent with the main puzzling features observed during market crashes, namely abrupt and asymmetric price movements that are not driven by major news events but coupled with a spillover effect between unrelated markets.


Letter to the Editor: (1)H, (13)C, and (15)N resonance assignments of the N-terminal domain of the SARS CoV nucleocapsid protein


title: Treating the Host Response to Ebola Virus Disease with Generic Statins and Angiotensin Receptor Blockers

text: Treatments targeting the Ebola virus may eventually be shown to work, but they will not have an impact on overall Ebola mortality in West Africa. Endothelial dysfunction is responsible for the fluid and electrolyte imbalances seen in Ebola patients. Because inexpensive generic statins and angiotensin receptor blockers restore endothelial barrier integrity, they can be used to treat the host response in these patients. In Sierra Leone, approximately 100 Ebola patients were treated with this combination, and reports indicate that survival was greatly improved.


title: Middle East Respiratory Syndrome Coronavirus Outbreak in the Republic of Korea, 2015

text: OBJECTIVES: The outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in the Republic of Korea started from the index case who developed fever after returning from the Middle East. He infected 26 cases in Hospital C, and consecutive nosocomial transmission proceeded throughout the nation. We provide an epidemiologic description of the outbreak, as of July 2015. METHODS: Epidemiological research was performed by direct interview of the confirmed patients and reviewing medical records. We also analyzed the incubation period, serial interval, the characteristics of superspreaders, and factors associated with mortality. Full genome sequence was obtained from sputum specimens of the index patient. RESULTS: A total of 186 confirmed patients with MERS-CoV infection across 16 hospitals were identified in the Republic of Korea. Some 44.1% of the cases were patients exposed in hospitals, 32.8% were caregivers, and 13.4% were healthcare personnel. The most common presenting symptom was fever and chills. The estimated incubation period was 6.83 days and the serial interval was 12.5 days. A total of 83.2% of the transmission events were epidemiologically linked to five superspreaders, all of whom had pneumonia at presentation and contacted hundreds of people. Older age [odds ratio (OR) = 4.86, 95% confidence interval (CI) 1.90–12.45] and underlying respiratory disease (OR = 4.90, 95% CI 1.64–14.65) were significantly associated with mortality. Phylogenetic analysis showed that the MERS-CoV of the index case clustered closest with a recent virus from Riyadh, Saudi Arabia. CONCLUSION: A single imported MERS-CoV infection case imposed a huge threat to public health and safety. This highlights the importance of robust preparedness and optimal infection prevention control. The lessons learned from the current outbreak will contribute to more up-to-date guidelines and global health security.


title: Genomic analysis of respiratory syncytial virus infections in households and utility in inferring who infects the infant

text: Infants (under 1-year-old) are at most risk of life threatening respiratory syncytial virus (RSV) disease. RSV epidemiological data alone has been insufficient in defining who acquires infection from whom (WAIFW) within households. We investigated RSV genomic variation within and between infected individuals and assessed its potential utility in tracking transmission in households. Over an entire single RSV season in coastal Kenya, nasal swabs were collected from members of 20 households every 3–4 days regardless of symptom status and screened for RSV nucleic acid. Next generation sequencing was used to generate >90% RSV full-length genomes for 51.1% of positive samples (191/374). Single nucleotide polymorphisms (SNPs) observed during household infection outbreaks ranged from 0–21 (median: 3) while SNPs observed during single-host infection episodes ranged from 0–17 (median: 1). Using the viral genomic data alone there was insufficient resolution to fully reconstruct within-household transmission chains. For households with clear index cases, the most likely source of infant infection was via a toddler (aged 1 to <3 years-old) or school-aged (aged 6 to <12 years-old) co-occupant. However, for best resolution of WAIFW within households, we suggest an integrated analysis of RSV genomic and epidemiological data.


title: A role for the Clostridium perfringens β2 toxin in bovine enterotoxaemia?

text: Abstract Non-enterotoxigenic type A Clostridium perfringens are associated with bovine enterotoxaemia, but the α toxin is not regarded as responsible for the production of typical lesions of necrotic and haemorrhagic enteritis. The purpose of this study was to investigate the putative role of the more recently described β2 toxin. Seven hundred and fourteen non-enterotoxigenic type A C. perfringens isolated from 133 calves with lesions of enterotoxaemia and high clostridial cell counts (study population) and 386 isolated from a control population of 87 calves were tested by a colony hybridisation assay for the β2 toxin. Two hundred and eighteen (31%) C. perfringens isolated from 83 calves (62%) of the study population and 113 (29%) C. perfringens isolated from 51 calves (59%) of the control population tested positive with the β2 probe. Pure and mixed cultures of four C. perfringens (one α+β2+, one α+enterotoxin+ and two α+) were tested in the ligated loop assay in one calf. Macroscopic haemorrhages of the intestinal wall, necrosis and haemorrhages of the intestinal content, and microscopic lesions of necrosis and polymorphonuclear and mononuclear cell infiltration of the intestinal villi were more pronounced in loops inoculated with the α and β2-toxigenic C. perfringens isolate. These results suggest in vivo synergistic role of the α and β2 toxins in the production of necrotic and haemorrhagic lesions of the small intestine in cases of bovine enterotoxaemia. However, isolation of β2-toxigenic C. perfringens does not confirm the clinical diagnosis of bovine enterotoxaemia and a clostridial cell counts must still be performed.


title: Significance of the Myxovirus Resistance A (MxA) Gene — 123C>A Single-Nucleotide Polymorphism in Suppressed Interferon β Induction of Severe Acute Respiratory Syndrome Coronavirus Infection

text: Myxovirus resistance A (MxA) is an antiviral protein induced by interferon α and β (IFN-α, IFN-β) that can inhibit viral replication. The minor alleles of the -88G>T and -123C>A MxA promoter single-nucleotide polymorphisms (SNPs) are associated with increased promoter activity and altered response to IFN-α and IFN-β treatment. Here, we demonstrate that the 123A minor allele provided stronger binding affinity to nuclear proteins extracted from IFN-β-untreated cells than did the wild-type allele, whereas the -88T allele showed preferential binding after IFN-β stimulation. Endogenous IFN-α and IFN-β induction can be suppressed in severe acute respiratory syndrome (SARS) coronavirus infection. In support of our in vitro findings, a large case-control genetic-association study for SARS coronavirus infection confirmed that the -123A minor-allele carriers were significantly associated with lower risk of SARS coronavirus infection, whereas the -88T minorallele carriers were insignificant after adjustment for confounding effects. This suggests that -123C>A plays a more important role in modulating basal MxA expression, thus contributing more significantly to innate immune response against viral infections that suppress endogenous IFN-α and IFN-β induction such as SARS coronavirus.


Controversies in CO(2) Insufflation and COVID-19


title: US Centers for Disease Control and Prevention and Its Partners’ Contributions to Global Health Security

text: To achieve compliance with the revised World Health Organization International Health Regulations (IHR 2005), countries must be able to rapidly prevent, detect, and respond to public health threats. Most nations, however, remain unprepared to manage and control complex health emergencies, whether due to natural disasters, emerging infectious disease outbreaks, or the inadvertent or intentional release of highly pathogenic organisms. The US Centers for Disease Control and Prevention (CDC) works with countries and partners to build and strengthen global health security preparedness so they can quickly respond to public health crises. This report highlights selected CDC global health protection platform accomplishments that help mitigate global health threats and build core, cross-cutting capacity to identify and contain disease outbreaks at their source. CDC contributions support country efforts to achieve IHR 2005 compliance, contribute to the international framework for countering infectious disease crises, and enhance health security for Americans and populations around the world.


title: How recent advances in molecular tests could impact the diagnosis of pneumonia

text: Molecular diagnostic tests have been the single major development in pneumonia diagnostics over recent years. Nucleic acid detection tests (NATs) have greatly improved the ability to detect respiratory viruses and bacterial pathogens that do not normally colonize the respiratory tract. In contrast, NATs do not yet have an established role for diagnosing pneumonia caused by bacteria that commonly colonize the nasopharynx due to difficulties discriminating between pathogens and coincidental carriage strains. New approaches are needed to distinguish infection from colonization, such as through use of quantitative methods and identification of discriminating cut-off levels. The recent realization that the lung microbiome exists has provided new insights into the pathogenesis of pneumonia involving the interaction between multiple microorganisms. New developments in molecular diagnostics must account for this new paradigm.


title: BCG vaccination policy and preventive chloroquine usage: do they have an impact on COVID-19 pandemic?

text: Coronavirus disease 2019 (COVID-19) is a severe acute respiratory syndrome caused by Coronavirus 2 (SARS-CoV-2). In the light of its rapid global spreading, on 11 March 2020, the World Health Organization has declared it a pandemic. Interestingly, the global spreading of the disease is not uniform, but has so far left some countries relatively less affected. The reason(s) for this anomalous behavior are not fully understood, but distinct hypotheses have been proposed. Here we discuss the plausibility of two of them: the universal vaccination with Bacillus Calmette–Guerin (BCG) and the widespread use of the antimalarial drug chloroquine (CQ). Both have been amply discussed in the recent literature with positive and negative conclusions: we felt that a comprehensive presentation of the data available on them would be useful. The analysis of data for countries with over 1000 reported COVID-19 cases has shown that the incidence and mortality were higher in countries in which BCG vaccination is either absent or has been discontinued, as compared with the countries with universal vaccination. We have performed a similar analysis of the data available for CQ, a widely used drug in the African continent and in other countries in which malaria is endemic; we discuss it here because CQ has been used as the drug to treat COVID-19 patients. Several African countries no longer recommend it officially for the fight against malaria, due to the development of resistance to Plasmodium, but its use across the continent is still diffuse. Taken together, the data in the literature have led to the suggestion of a possible inverse correlation between BCG immunization and COVID-19 disease incidence and severity.


title: (Un)intended Consequences? The Impact of the 2017 Tax Cuts and Jobs Act on Shareholder Wealth

text: We study the stock market reactions to the Tax Cuts and Jobs Act (TCJA), the most significant structural U.S. tax reform in over 30 years. In line with the stated intent of TCJA proponents, we find that the Act benefited highly taxed firms. However, the Act hindered firms with international operations as well as firms with high interest expense and tax losses. Counter to claims that the TCJA would quickly spur economic growth, we find that financially constrained and high growth opportunity firms did not benefit. Rather, market participants anticipate that most of the TCJA's benefits will be passed on to shareholders via higher corporate payouts. We confirm these market expectations by documenting that firms did increase payouts via repurchases after the TCJA, but did not increase their corporate investments.


Coronavirus HKU1 in an Italian pre-term infant with bronchiolitis


title: Encephalopathy in patients with COVID‐19: ‘Causality or coincidence?’

text: The main tropism of the novel coronavirus disease 2019 (COVID‐19) is respiratory. Increasing evidences show that SARS‐CoV‐2 is not always confined to the respiratory tract but can also invade the central nervous system (CNS) and induce neurological diseases. We report two cases illustrating this phenomenon. This article is protected by copyright. All rights reserved.


title: Computer-based fluorescence quantification: a novel approach to study nucleolar biology

text: BACKGROUND: Nucleoli are composed of possibly several thousand different proteins and represent the most conspicuous compartments in the nucleus; they play a crucial role in the proper execution of many cellular processes. As such, nucleoli carry out ribosome biogenesis and sequester or associate with key molecules that regulate cell cycle progression, tumorigenesis, apoptosis and the stress response. Nucleoli are dynamic compartments that are characterized by a constant flux of macromolecules. Given the complex and dynamic composition of the nucleolar proteome, it is challenging to link modifications in nucleolar composition to downstream effects. RESULTS: In this contribution, we present quantitative immunofluorescence methods that rely on computer-based image analysis. We demonstrate the effectiveness of these techniques by monitoring the dynamic association of proteins and RNA with nucleoli under different physiological conditions. Thus, the protocols described by us were employed to study stress-dependent changes in the nucleolar concentration of endogenous and GFP-tagged proteins. Furthermore, our methods were applied to measure de novo RNA synthesis that is associated with nucleoli. We show that the techniques described here can be easily combined with automated high throughput screening (HTS) platforms, making it possible to obtain large data sets and analyze many of the biological processes that are located in nucleoli. CONCLUSIONS: Our protocols set the stage to analyze in a quantitative fashion the kinetics of shuttling nucleolar proteins, both at the single cell level as well as for a large number of cells. Moreover, the procedures described here are compatible with high throughput image acquisition and analysis using HTS automated platforms, thereby providing the basis to quantify nucleolar components and activities for numerous samples and experimental conditions. Together with the growing amount of information obtained for the nucleolar proteome, improvements in quantitative microscopy as they are described here can be expected to produce new insights into the complex biological functions that are orchestrated by the nucleolus.


title: Coronavirus disease 2019 in an orthotopic liver transplant recipient living with human immunodeficiency virus

text: Coronavirus disease 2019 (COVID‐19), mediated by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), can manifest with flu‐like illness and severe pneumonia with acute respiratory distress syndrome (ARDS). Immunocompromised patients merit particular attention as altered host immunity may influence both disease severity and duration of viral shedding as is described with several other ribonucleic acid respiratory viruses. Yet immunocompromised status alone, in the absence of other comorbidities, may not necessarily predict severe illness presentations and poorer clinical outcomes as indicated by recent reports of COVID‐19‐infected solid organ transplant recipients and people living with human immunodeficiency virus (HIV). Such patients may even be spared the robust inflammatory response that precipitates ARDS associated with COVID‐19, complicating the management of iatrogenic immunosuppression in this setting. We present a case of an orthotopic liver transplant recipient with well‐controlled HIV who successfully recovered from a mild, flu‐like illness attributed to SARS‐CoV‐2.


title: Ethical Framework for Nutrition Support Resource Allocation During Shortages: Lessons From COVID‐19

text: The coronavirus disease (COVID‐19) pandemic has impacted all aspects of our population. The “Troubling Trichotomy” of what can be done technologically, what should be done ethically, and what must be done legally is a reality during these unusual circumstances. Recent ethical considerations regarding allocation of scarce resources, such as mechanical ventilators, have been proposed. These can apply to other disciplines such as nutrition support, although decisions regarding nutrition support have a diminished potential for devastating outcomes. The principal values and goals leading to an ethical framework for a uniform, fair, and objective approach are reviewed in this article, with a focus on nutrition support. Some historical aspects of shortages in nutrition supplies and products during normal circumstances, as well as others during national crises, are outlined. The development and implementation of protocols using a scoring system seems best addressed by multidisciplinary ethics and triage committees with synergistic but disparate functions. Triage committees should alleviate the burdens of unilateral decisions by the healthcare team caring for patients. The treating team should make every attempt to have patients and the public at large update or execute/develop advance directives. Legal considerations, as the third component of the Troubling Trichotomy, are of some concern when rationing care. The likelihood that criminal or civil charges could be brought against individual healthcare professionals or institutions can be minimized, if fair protocols are uniformly applied and deliberations well documented.


title: Incorporating one health into medical education

text: One Health is an emerging concept that stresses the linkages between human, animal, and environmental health, as well as the need for interdisciplinary communication and collaboration to address health issues including emerging zoonotic diseases, climate change impacts, and the human-animal bond. It promotes complex problem solving using a systems framework that considers interactions between humans, animals, and their shared environment. While many medical educators may not yet be familiar with the concept, the One Health approach has been endorsed by a number of major medical and public health organizations and is beginning to be implemented in a number of medical schools. In the research setting, One Health opens up new avenues to understand, detect, and prevent emerging infectious diseases, and also to conduct translational studies across species. In the clinical setting, One Health provides practical ways to incorporate environmental and animal contact considerations into patient care. This paper reviews clinical and research aspects of the One Health approach through an illustrative case updating the biopsychosocial model and proposes a basic set of One Health competencies for training and education of human health care providers.


title: Comprehensive Analysis of Severe Viral Infections of Respiratory Tract admitted to PICUs during the Winter Season in Turkey

text: OBJECTIVES: To analyze the course of seasonal viral infections of respiratory tract in patients hospitalized in pediatric intensive care units (PICU) of 16 centers in Turkey. MATERIALS AND METHODS: It is a retrospective, observational, and multicenter study conducted in 16 tertiary PICUs in Turkey includes a total of 302 children with viral cause in the nasal swab which required PICU admission with no interventions. RESULTS: Median age of patients was 12 months. Respiratory syncytial virus (RSV) was more common in patients over one year of age whereas influenza, human Bocavirus in patients above a year of age was more common (p <0.05). Clinical presentations influencing mortality were neurologic symptoms, tachycardia, hypoxia, hypotension, elevated lactate, and acidosis. The critical pH value related with mortality was ≤7.10, and critical PCO(2) ≥60 mm Hg. CONCLUSION: Our findings demonstrate that patients with neurological symptoms, tachycardia, hypoxia, hypotension, acidosis, impaired liver, and renal function at the time of admission exhibit more severe mortal progressions. Presence of acidosis and multiorgan failure was found to be predictor for mortality. Knowledge of clinical presentation and age-related variations among seasonal viruses may give a clue about severe course and prognosis. By presenting the analyzed data of 302 PICU admissions, current study reveals severity of viral respiratory tract infections and release tips for handling them. HOW TO CITE THIS ARTICLE: Kockuzu E, Bayrakcı B, Kesici S, Cıtak A, Karapınar K, Emeksiz S, et al. Comprehensive Analysis of Severe Viral Infections of Respiratory Tract admitted to PICUs During the Winter Season in Turkey. Indian J Crit Care Med 2019;23(6):263–269.


title: A Novel Video Tracking Method to Evaluate the Effect of Influenza Infection and Antiviral Treatment on Ferret Activity

text: Ferrets are the preferred animal model to assess influenza virus infection, virulence and transmission as they display similar clinical symptoms and pathogenesis to those of humans. Measures of disease severity in the ferret include weight loss, temperature rise, sneezing, viral shedding and reduced activity. To date, the only available method for activity measurement has been the assignment of an arbitrary score by a ‘blind’ observer based on pre-defined responsiveness scale. This manual scoring method is subjective and can be prone to bias. In this study, we described a novel video-tracking methodology for determining activity changes in a ferret model of influenza infection. This method eliminates the various limitations of manual scoring, which include the need for a sole ‘blind’ observer and the requirement to recognise the ‘normal’ activity of ferrets in order to assign relative activity scores. In ferrets infected with an A(H1N1)pdm09 virus, video-tracking was more sensitive than manual scoring in detecting ferret activity changes. Using this video-tracking method, oseltamivir treatment was found to ameliorate the effect of influenza infection on activity in ferret. Oseltamivir treatment of animals was associated with an improvement in clinical symptoms, including reduced inflammatory responses in the upper respiratory tract, lower body weight loss and a smaller rise in body temperature, despite there being no significant reduction in viral shedding. In summary, this novel video-tracking is an easy-to-use, objective and sensitive methodology for measuring ferret activity.


title: COVID‐19 in Parkinson's Disease Patients Living in Lombardy, Italy

text: BACKGROUND: It is unknown whether patients with Parkinson's disease (PD) are at greater risk of COVID‐19, what their risk factors are and whether their clinical manifestations differ from the general population. METHODS: In a case‐controlled survey, we interviewed 1486 PD patients attending a single tertiary centre in Lombardy, Italy and 1207 family members (controls). RESULTS: 105 (7.1%) and 92 controls (7.6%) were identified as COVID‐19 cases. COVID‐19 patients were younger, more likely to suffer from chronic obstructive pulmonary disease, to be obese and vitamin D non‐supplemented than unaffected patients. Six patients (5.7%) and seven family members (7.6%) died from COVID‐19. Patients were less likely to report shortness of breath and require hospitalization. CONCLUSIONS: In an unselected large cohort of non‐advanced PD patients, COVID‐19 risk and mortality did not differ from the general population but symptoms appeared to be milder. The possible protective role of vitamin D supplementation warrants future studies. This article is protected by copyright. All rights reserved.


title: Investigation of Plasmonic Detection of Human Respiratory Virus

text: The COVID‐19 virus has been recently identified as a new species of virus that can cause severe infections such as pneumonia. The sudden outbreak of this disease is being considered a pandemic. Given all this, it is essential to develop smart biosensors that can detect pathogens with minimum time delay. Surface plasmon resonance (SPR) biosensors make use of refractive index (RI) changes as the sensing parameter. In this work, based on actual data taken from previous experimental works done on plasmonic detection of viruses, a detailed simulation of the SPR scheme that can be used to detect the COVID‐19 virus is performed and the results are extrapolated from earlier schemes to predict some outcomes of this SPR model. The results indicate that the conventional Kretschmann configuration can have a limit of detection (LOD) of 2E‐05 in terms of RI change and an average sensitivity of 122.4 degRIU(−1) at a wavelength of 780 nm.


title: The Virus-Host Interplay: Biogenesis of +RNA Replication Complexes

text: Positive-strand RNA (+RNA) viruses are an important group of human and animal pathogens that have significant global health and economic impacts. Notable members include West Nile virus, Dengue virus, Chikungunya, Severe acute respiratory syndrome (SARS) Coronavirus and enteroviruses of the Picornaviridae family.Unfortunately, prophylactic and therapeutic treatments against these pathogens are limited. +RNA viruses have limited coding capacity and thus rely extensively on host factors for successful infection and propagation. A common feature among these viruses is their ability to dramatically modify cellular membranes to serve as platforms for genome replication and assembly of new virions. These viral replication complexes (VRCs) serve two main functions: To increase replication efficiency by concentrating critical factors and to protect the viral genome from host anti-viral systems. This review summarizes current knowledge of critical host factors recruited to or demonstrated to be involved in the biogenesis and stabilization of +RNA virus VRCs.


title: Use of GFP to Investigate Expression of Plant-Derived Vaccines

text: Plants are low-cost bioreactors for the production of various biopharmaceuticals including oral vaccines. Plant-derived oral vaccines are potentially useful in combating viral infections involving mucosal immunity. Transgenic plants have been generated to successfully produce mucosal vaccines against cholera, hepatitis B, foot-and-mouth disease, and Norwalk virus. As a first step toward the generation of oral vaccines against the severe acute respiratory syndrome coronavirus (SARS-CoV), we have expressed a recombinant S1 protein of the SARS-CoV in transformed tobacco. Since plant transformation and regeneration of stable transformants require considerable time, we initially used a green fluorescent protein (GFP) to tag the antigen in transient expression. GFP was fused to the carboxy-terminus of S1 for expression of S1-GFP to show expression of recombinant S1 by agroinfiltration of tobacco leaves. The GFP tag enables a relatively quick confirmation of antigen expression in plant cells by fluorescent microscopy. Such analysis using GFP that precedes stable plant transformation will enable the rapid screening of multiple constructs to attain optimal recombinant protein expression. Furthermore, this approach determines the subcellular localization of the recombinant protein in plant cells, providing information on optimal subcellular targeting for production in plant bioreactors.


title: Monitoring Novel Corona Virus (COVID-19) Infections in India by Cluster Analysis

text: It is a great challenge of identification as well as formation of groups of infectious disease data set. Data mining, a process of uncovering silent characteristics of big data is one of such techniques which have nowadays become more popular for treating massive volume of infectious disease data set. In the current study, we apply cluster analysis, one of the data mining techniques to classify real groups of infectious disease “novel corona virus disease (COVID-19)” data set of different states and union territories (UTs) in India according to their high similarity to each other. The results obtained permit us to have a sense of clusters of affected Indian states and UTs. The main objective of clustering in this study is to optimize monitoring techniques in affected states and UTs in India which will be very valuable to the government, doctors, the police and others involved in understanding seriousness of the spread of novel coronavirus (COVID-19) to improve government policies, decisions, medical facilities (ventilators, testing kits, masks etc.), treatment etc. to reduce number of infected and deceased persons.


title: Viral survival

text: How long do viruses like cold, flu and coronavirus survive outside the body? What factors affect this?


COVID‐19 – Looking beyond the immediate concerns


title: Detection of transmissible gastroenteritis virus neutralising antibody in cats

text: High titres of neutralising activity to transmissible gastroenteritis virus (TGEV), a porcine coronavirus, were found in sera and peritoneal fluids from cats infected with feline infectious peritonitis (FIP). A small proportion of cats, from a hospital population unaffected by FIP, also had neutralising activity. Procedures to remove non-specific viral inhibitors, including treatment by heat inactivation, trypsin, sulphydryl reagent and kaolin absorption were unsuccessful. The active component was unable to neutralise another porcine coronavirus, haemagglutinating encephalomyelitis virus or the porcine enterovirus, Talfan. Gel filtration of feline sera and peritoneal fluid demonstrated high levels of the neutralising activity in the area corresponding to 7S IgG, which could be removed by absorption with specific anti-IgG serum and these properties are suggested to be consistent with those of antibody. These findings imply that there is a coronavirus in cats which is antigenically related to TGEV and its possible nature is discussed.


Functional Dipeptidyl Peptidase 4 (DPP4) in mink supports entry and replication of Middle Eastern respiratory syndrome coronavirus: American Mink (Neovision vision), a novel in vivo model of MERS-CoV infection


title: Angiotensin‐converting enzyme 2 in severe acute respiratory syndrome coronavirus and SARS‐CoV‐2: A double‐edged sword?

text: Human angiotensin‐converting enzyme 2 (ACE2) facilitates cellular entry of severe acute respiratory syndrome coronavirus (SARS‐CoV) and SARS‐CoV‐2 as their common receptor. During infection, ACE2‐expressing tissues become direct targets, resulting in serious pathological changes and progressive multiple organ failure or even death in severe cases. However, as an essential component of renin‐angiotensin system (RAS), ACE2 confers protective effects in physiological circumstance, including maintaining cardiovascular homeostasis, fluid, and electrolyte balance. The absence of protective role of ACE2 leads to dysregulated RAS and thus acute changes under multiple pathological scenarios including SARS. This potentially shared mechanism may also be the molecular explanation for pathogenesis driven by SARS‐CoV‐2. We reasonably speculate several potential directions of clinical management including host‐directed therapies aiming to restore dysregulated RAS caused by ACE2 deficiency. Enriched knowledge of ACE2 learned from SARS and COVID‐19 outbreaks can provide, despite their inherent tragedy, informative clues for emerging pandemic preparedness.


title: Epitopes on the spike protein of a nephropathogenic strain of infectious bronchitis virus

text: Infectious bronchitis virus (IBV), the first coronavirus described, was initially associated with severe respiratory disease. However, outbreaks have more recently also been associated with nephropathogenesis. Topographically interrelated antigenic determinants of the nephropathogenic Gray strain of IBV were characterized using eleven monoclonal antibodies (MAbs). Four MAbs (IgG 2aκ) defined epitopes that were both conformation-independent and group specific, reacting with Gray, Arkansas (Ark), and Massachusetts 41 (Mass 41) strains. Seven MAbs (IgG 1κ) defined conformation-dependent epitopes that could differentiate the Gray from the Ark and Mass strains. The spike protein specificity of the MAbs was determined with the conformation-independent MAbs and one MAb that reacted only in “non-denaturing” western blot assays. Competitive binding studies using these MAbs suggested a high degree of functional dependency among the associated epitopes as might be expected with a protein of complex secondary and tertiary structure. At least two regions associated with complete protection of infected embryos were identified that consisted of both conformation-dependent and independent epitopes. However, a “non-neutralizing” MAb, which did not protect the embryo from gross lesions, did inhibit virus-induced lesions and replication in the kidneys. These MAbs should be valuable tools in studying IBV pathogenesis.


title: Influenza and Pneumonia in Pregnancy

text: Influenza is a significant cause of morbidity and mortality from febrile respiratory illness worldwide. Influenza in pregnant women has historically been associated with a higher rate of morbidity and mortality. Pneumonia is the sixth leading cause of death in the United States, and it is the number one cause of death from an infectious disease. Although pregnant women do not get pneumonia more often than nonpregnant women, it can result in greater morbidity and mortality because of the physiologic adaptations of pregnancy. Pregnant patients who have either of these conditions require a higher level of surveillance and intervention.


title: The effect of Allium sativum (Garlic) extract on infectious bronchitis virus in specific pathogen free embryonic egg

text: OBJECTIVE: Garlic is a plant has been used as a flavor, and anti-microbial and anti-diarrheal agent. Infectious bronchitis virus (IBV) is a coronavirus. The available vaccines against IBV cannot cover new variants. This study evaluated the inhibitory effects of garlic extract on IBV. MATERIALS AND METHODS: The constituents of garlic extract were detected by gas chromatography. This study was done in four groups of embryonic SPF eggs; first group was used for virus titration; second group received the mixture of different virus titration and constant amount of garlic extract; third group received 10(-3) titration of virus and after 8 hr received garlic extract and the last group received different dilutions of garlic extract. RESULTS: Based on our results, in the second group, IBV vaccine strain (4/91) at all titration and M41 in 10(-2) and 10(-3) titration and in the third group both variants of virus the embryonic Index (EI) was significantly increased. CONCLUSION: The garlic extract had inhibitory effects on IBV in the chickens embryo.


COVID-19 and healthcare systems: what should we do next?


Abstract We aimed to assess the Chinese mental health burden during the COVID-19 pandemic. Data were collected from 7,236 participants assessed with anxiety disorders, depressive symptoms, and poor sleep . The overall prevalence of anxiety disorders, depressive symptoms, sleep quality were 35.1%, 20.1%, 18.2%, respectively. Younger people reported a higher prevalence of anxiety disorders and depressive symptoms than older people (P < 0.001). Compared with other occupation, healthcare workers have the highest rate of poor sleep quality (P < 0.001). We identified a major mental health burden of the public during the COVID-19 pandemic outbreak in China. Younger people and healthcare workers were at high risk for mental illness.


Editorial: EAERE, ERE and the Research Challenges of the Coronavirus Pandemic


title: Alignment using genetic programming with causal trees for identification of protein functions

text: Abstract A hybrid evolutionary model is used to propose a hierarchical homology of protein sequences to identify protein functions systematically. The proposed model offers considerable potentials, considering the inconsistency of existing methods for predicting novel proteins. Because some novel proteins might align without meaningful conserved domains, maximizing the score of sequence alignment is not the best criterion for predicting protein functions. This work presents a decision model that can minimize the cost of making a decision for predicting protein functions using the hierarchical homologies. Particularly, the model has three characteristics: (i) it is a hybrid evolutionary model with multiple fitness functions that uses genetic programming to predict protein functions on a distantly related protein family, (ii) it incorporates modified robust point matching to accurately compare all feature points using the moment invariant and thin-plate spline theorems, and (iii) the hierarchical homologies holding up a novel protein sequence in the form of a causal tree can effectively demonstrate the relationship between proteins. This work describes the comparisons of nucleocapsid proteins from the putative polyprotein SARS virus and other coronaviruses in other hosts using the model.


title: Management strategies for children with COVID-19: ESPR practical recommendations

text: During the outbreak of the COVID-19 pandemic, guidelines have been issued by international, national and local authorities to address management and the need for preparedness. Children with COVID-19 differ from adults in that they are less often and less severely affected. Additional precautions required in the management of children address their increased radiosensitivity, need for accompanying carers, and methods for dealing with children in a mixed adult-paediatric institution. In this guidance document, our aim is to define a pragmatic strategy for imaging children with an emphasis on proven or suspected COVID-19 cases. Children suspected of COVID-19 should not be imaged routinely. Imaging should be performed only when expected to alter patient management, depending on symptoms, preexisting conditions and clinical evolution. In order to prevent disease transmission, it is important to manage the inpatient caseload effectively by triaging children and carers outside the hospital, re-scheduling nonurgent elective procedures and managing symptomatic children and carers as COVID-19 positive until proven otherwise. Within the imaging department one should consider conducting portable examinations with COVID-19 machines or arranging dedicated COVID-19 paediatric imaging sessions and performing routine nasopharyngeal swab testing before imaging under general anaesthesia. Finally, regular personal hygiene, appropriate usage of personal protective equipment, awareness of which procedures are considered aerosol generating and information on how to best disinfect imaging machinery after examinations should be highlighted to all staff members. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00247-020-04749-3) contains supplementary material, which is available to authorized users.


title: Treatment of Community-Acquired Lower Respiratory Tract Infections during Pregnancy

text: The incidence of lower respiratory tract infection (LRTI) in women of child-bearing age is approximately 64 per 1000 population. The spectrum of illness ranges from acute bronchitis, which is very common, through influenza virus infection and exacerbations of underlying lung disease, to pneumonia, which, fortunately is uncommon (<1.5% LRTI), but can be severe. Acute bronchitis is generally mild, self-limiting and usually does not require antibacterial therapy. Influenza virus infection in pregnant women has been recently related to increased hospitalization for acute cardiorespiratory conditions. At present, the safety of the newer neuraminidase inhibitors for the treatment of influenza virus infection has not been established in pregnancy and they are not routinely recommended. In influenza virus infection complicated by pneumonia, antibacterial agents active against Staphylococcus aureus and Streptococcus pneumoniae superinfection should be used. There are few data on infective complications of asthma or COPD in pregnancy. The latter is rare, as patients with COPD are usually male and aged over 45 years. Management is the same as for nonpregnant patients. The incidence and mortality of pneumonia in pregnancy is similar to that in nonpregnant patients. Infants born to pregnant patients with pneumonia have been found to be born earlier and weigh less than controls. Risk factors for the development of pneumonia include anemia, asthma and use of antepartum corticosteroids and tocolytic agents. Based on the few available studies, the main pathogens causing pneumonia are S. pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae and viruses. β-Lactam and macrolide antibiotics therefore remain the antibiotics of choice in terms of both pathogen coverage and safety in pregnancy. In HIV-infected pregnant patients, recurrent bacterial pneumonia, but not Pneumocystis carinii pneumonia (PCP), is more common than in nonpregnant patients. Trimethoprim/sulfamethoxazole (cotrimoxazole) has not definitely been associated with adverse clinical outcomes despite theoretical risks. Currently it is still the treatment of choice in PCP, where mortality remains high. In conclusion, there are few data specifically related to pregnant women with different types of LRTI. Where data are available, no significant differences compared with nonpregnant patients have been identified. In considering the use of any therapeutic agent or investigation in pregnant patients with LRTI, safety aspects must be carefully weighed against potential benefit. Otherwise, management strategies should not differ from those for nonpregnant patients. Further research in this area is warranted.


Recommandations COVID-19 pour les ophtalmologistes


title: MERS-CoV: Middle East respiratory syndrome corona virus: Can radiology be of help? Initial single center experience

text: Abstract Human infection with a novel coronavirus named Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia and the Middle East in September, 2012. The aim of this study was to establish the most pathognomonic radiological sign(s) to diagnose MERS CoV. Patients and methods This is a retrospective descriptive study. All patients were subjected to serial X-ray. High resolution non-contrast CT chest was also obtained for 10 patients. The scans were reviewed for findings including consolidation, ground-glass opacities, nodules, reticular opacities and hilar and mediastinal adenopathy. Results A total of 12 patients were included in our study with prevalence of males (2:1) with ages ranging between 18 and 76years having an average age of 36±2years. The outcome of these patients was as follows: 6 were treated with average hospital stay ranging between 21 and 35days, one case died after 14days, and 5 cases were transferred to Central Governmental hospital according the local authority rules. Conclusions MERS CoV virus may have a specific pattern in chest X-ray and CT developing a single or multiple opacities progressing into a widespread multifocal bilateral patches of ground glass opacities or confluent consolidation resembling organizing pneumonia.


Glia Expression of MHC During CNS Infection by Neurotropic Coronavirus


title: Respiratory Pathogens in Children 1 Month to 5 Years of Age Presenting With Undifferentiated Acute Respiratory Distress in 2 District-Level Hospitals in Ghana

text: Ghanaian children (2176) aged <5 years who presented with undifferentiated acute respiratory distress were tested for respiratory pathogens using a BioFire FilmArray polymerase chain reaction assay. Rhinovirus and/or enterovirus was detected in 36% of the assays, respiratory syncytial virus in 11%, and parainfluenza in 7%. Respiratory syncytial virus and metapneumovirus were detected more frequently in the rainy season than in the dry season.


title: Respiratory infections unique to Asia

text: Asia is a highly heterogeneous region with vastly different cultures, social constitutions and populations affected by a wide spectrum of respiratory diseases caused by tropical pathogens. Asian patients with community‐acquired pneumonia differ from their Western counterparts in microbiological aetiology, in particular the prominence of Gram‐negative organisms, Mycobacterium tuberculosis, Burkholderia pseudomallei and Staphylococcus aureus. In addition, the differences in socioeconomic and health‐care infrastructures limit the usefulness of Western management guidelines for pneumonia in Asia. The importance of emerging infectious diseases such as severe acute respiratory syndrome and avian influenza infection remain as close concerns for practising respirologists in Asia. Specific infections such as melioidosis, dengue haemorrhagic fever, scrub typhus, leptospirosis, salmonellosis, penicilliosis marneffei, malaria, amoebiasis, paragonimiasis, strongyloidiasis, gnathostomiasis, trinchinellosis, schistosomiasis and echinococcosis occur commonly in Asia and manifest with a prominent respiratory component. Pulmonary eosinophilia, endemic in parts of Asia, could occur with a wide range of tropical infections. Tropical eosinophilia is believed to be a hyper‐sensitivity reaction to degenerating microfilariae trapped in the lungs. This article attempts to address the key respiratory issues in these respiratory infections unique to Asia and highlight the important diagnostic and management issues faced by practising respirologists.


title: Involvement of the complement system in the protection of mice from challenge with respiratory syncytial virus Long strain following passive immunization with monoclonal antibody 18A2B2

text: Abstract Passive immunization of mice with 131 μg of the non-neutralizing monoclonal antibody (mAb) 18A2B2, directed against the A subgroup epitope of the G glycoprotein of respiratory syncytial virus Long strain (RSV), confers protection against viral i.n. challenge. The role of the Fc fragment of this antibody as well as the involvement of antibody-dependent cellular cytotoxicity (ADCC) and complement-mediated cytolysis towards protection was evaluated in vivo. Passive immunization with the Fab fragment alone (618–907 μg mouse−1) was unable to confer protection in mice. Furthermore, we passively immunized with the mAb 18A2B2 SCID beige mice, which are deficient in natural killer (NK) cell activity, to ascertain the role of NK cells in the protective mechanism. These mice were free of virus 5 days following viral challenge, indicating that NK cells do not contribute significantly towards the protective action of this antibody. Moreover, passively immunized BALB c mice decomplemented with 8–10 U of cobra venom factor (CoVF) and DBA 2J mice (C5 deficient) were only partially protected. These findings suggest that in mice the alternative and classical pathways of the complement system are involved in the passive protection mechanism conferred by the non-neutralizing mAb 18A2B2. To our knowledge, it is the first description of a protective mechanism in mice that involves a non-neutralizing antibody and the complement system.


title: Telehealth for musculoskeletal physiotherapy

text: INTRODUCTION: Musculoskeletal conditions are a leading cause of global morbidity. Access to traditional in-person healthcare can be difficult for some under usual conditions and has become a ubiquitous barrier throughout the COVID-19 pandemic. Telehealth, defined as the ‘delivery of healthcare at a distance using information and communication technology’ is a solution to many access barriers and has been rapidly adopted by many healthcare professions throughout the crisis. While significant advancements in technology has made the widespread adoption of telehealth feasible, there are many factors to be considered when implementing a telehealth service. PURPOSE: The aims of this masterclass are to (i) introduce telehealth and outline the current research within the context of musculoskeletal physiotherapy; (ii) provide insights into some of the broader challenges in the wide-scale adoption of telehealth; and (iii) to describe a systematic approach to implementing telehealth into existing healthcare settings, along with some practical considerations. IMPLICATIONS: Telehealth is a broad concept and should be implemented to meet the specific needs of a healthcare service. This masterclass offers a structured approach to the implementation of a musculoskeletal physiotherapy telehealth service, and highlights practical considerations required by both clinicians and healthcare organisations throughout all stages of the implementation process.


title: A review of immunologic diseases of the dog

text: Abstract The following review is based on notes used in the teaching of clinical immunology to veterinary students. Immune diseases of the dog are placed into six different categories: (1) type I or allergic conditions; (2) type II or auto- and allo-antibody diseases; (3) type III or immune complex disorders; (4) type IV or cell-mediated immune diseases; (5) type V conditions or gammopathies; and (6) type VI or immunodeficiency disorders. Separate discussions of transplantation immunology and the use of drugs to regulate unwanted immune responses are also included.


title: Quantum dots as a promising agent to combat COVID‐19

text: Approximately every 100 years, as witnessed in the last two centuries, we are facing an influenza pandemic, necessitating the need to combat a novel virus strain. As a result of the new coronavirus (severe acute respiratory syndrome coronavirus type 2 [SARS‐CoV‐2] outbreak in January 2020, many clinical studies are being carried out with the aim of combating or eradicating the disease altogether. However, so far, developing coronavirus disease 2019 (COVID‐19) detection kits or vaccines has remained elusive. In this regard, the development of antiviral nanomaterials by surface engineering with enhanced specificity might prove valuable to combat this novel virus. Quantum dots (QDs) are multifaceted agents with the ability to fight against/inhibit the activity of COVID‐19 virus. This article exclusively discusses the potential role of QDs as biosensors and antiviral agents for attenuation of viral infection.


title: 22 Microbiological Diagnosis of Respiratory Illness Recent Advances

text: Abstract A wide variety of microorganisms are potential respiratory pathogens, and the spectrum of known pathogens for each respiratory infection syndrome has not changed markers over recent years. Detection of likely etiologic agents of respiratory infections can help direct management and can also play an important role in disease surveillance. For this purpose, we are still reliant on many traditional diagnostic tools that have been used for decades in order to determine the microbial etiology of respiratory infections. However, these tools have been increasingly supplemented by newer methods, particular molecular diagnostic techniques, which have enabled the more rapid detection of many pathogens that were previously difficult to detect. These advances have particularly lead to improvements in the ability to detect respiratory viruses and also other microorganisms that do not normally colonize the respiratory tract. Recognition of the existence of the lung microbiome has challenged the traditional views of pneumonia pathogenesis and may provide the opportunity for new diagnostic tools that are focused on more than just detection of specific known pathogens. Continued liaison between clinicians and laboratory staff is vital in order to facilitate the most cost-effective use of laboratory diagnostics.


Cytosine drives evolution of SARS‐CoV‐2


title: Porcine reproductive and respiratory syndrome (PRRS): an immune dysregulatory pandemic

text: Porcine reproductive and respiratory disease syndrome (PRRS) is a viral pandemic that especially affects neonates within the “critical window” of immunological development. PRRS was recognized in 1987 and within a few years became pandemic causing an estimated yearly $600,000 economic loss in the USA with comparative losses in most other countries. The causative agent is a single-stranded, positive-sense enveloped arterivirus (PRRSV) that infects macrophages and plasmacytoid dendritic cells. Despite the discovery of PRRSV in 1991 and the publication of >2,000 articles, the control of PRRS is problematic. Despite the large volume of literature on this disease, the cellular and molecular mechanisms describing how PRRSV dysregulates the host immune system are poorly understood. We know that PRRSV suppresses innate immunity and causes abnormal B cell proliferation and repertoire development, often lymphopenia and thymic atrophy. The PRRSV genome is highly diverse, rapidly evolving but amenable to the generation of many mutants and chimeric viruses for experimental studies. PRRSV only replicates in swine which adds to the experimental difficulty since no inbred well-defined animal models are available. In this article, we summarize current knowledge and apply it toward developing a series of provocative and testable hypotheses to explain how PRRSV immunomodulates the porcine immune system with the goal of adding new perspectives on this disease.


title: Viral etiology of life‐threatening pediatric pneumonia: A matched case‐control study

text: BACKGROUND: Pediatric pneumonia remains a significant health challenge, while the viral risk factors for adverse outcomes in pediatric pneumonia are not yet fully clear. METHODS: A matched case‐control study of pediatric patients with pneumonia was carried out in Beijing, China, between 2007 and 2015. The study enrolled 334 intensive care unit patients who developed life‐threatening diseases and 522 controls matched to the sex, age, ethnicity, admission dates, and residing district of the cases suffered from pneumonia. Nasopharyngeal aspirates were taken from all participants and tested by PCR for 18 common respiratory viruses. RESULTS: At least, one virus was detected in 257 (77%) of the cases and 409 (78%) of the controls. We observed no difference in the prevalence of 17 respiratory viruses between cases and controls but found a higher frequency of influenza A virus (IFV‐A) in the cases than in the controls (7% vs 4%, P = .036). After adjusting for comorbid conditions and a history of reactive airway diseases, IFV‐A was associated with an increase in life‐threatening pneumonia (adjusted odds ratio = 2.55, 95% CI = 1.24‐5.24). Young age and congenital heart disease (aOR = 10.16‐10.27, P < .001) were also independent risk factors. CONCLUSIONS: The prevention of IFV infection is critical in decreasing the risk of life‐threatening pneumonia in children.


title: The antiparasitic drug niclosamide inhibits dengue virus infection by interfering with endosomal acidification independent of mTOR

text: BACKGROUND: The antiparasitic agent niclosamide has been demonstrated to inhibit the arthropod-borne Zika virus. Here, we investigated the antiviral capacity of niclosamide against dengue virus (DENV) serotype 2 infection in vitro and in vivo. PRINCIPLE FINDING: Niclosamide effectively retarded DENV-induced infection in vitro in human adenocarcinoma cells (A549), mouse neuroblastoma cells (Neuro-2a), and baby hamster kidney fibroblasts (BHK-21). Treatment with niclosamide did not retard the endocytosis of DENV while niclosamide was unable to enhance the antiviral type I interferon response. Furthermore, niclosamide did not cause a direct effect on viral replicon-based expression. Niclosamide has been reported to competitively inhibit the mTOR (mammalian target of rapamycin), STAT3 (signal transducer and activator of transcription 3), and NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling pathways; however, selective inhibitors of those pathways did not reduce DENV infection. Similar to the vacuolar-type H(+)-ATPase inhibitor bafilomycin A1, both niclosamide and other protonophores, such as CCCP (carbonyl cyanide m-chlorophenyl hydrazone), and FCCP (carbonyl cyanide-p-trifluoromethoxyphenylhydrazone), effectively reduced endosomal acidification and viral dsRNA replication. Co-administration of a single dose of niclosamide partially decreased viral replication, viral encephalitis, and mortality in DENV-infected ICR suckling mice. SIGNIFICANCE: These results demonstrate that niclosamide diminishes viral infection by hindering endosomal acidification.


title: Drinking, Smoking, and Morality: Do ‘Drinkers and Smokers’ Constitute a Stigmatised Stereotype or a Real TB Risk Factor in the Time of HIV/AIDS?

text: This paper follows up an unexpected finding from a community survey that identified drinking and smoking as the most important tuberculosis (TB) risk factor, far ahead of ones commonly associated with TB such as poverty, overcrowded living conditions, and HIV-positive status. It reports perceptions of drinking and smoking from a three-phased study of the stigma associated with TB, consisting of a qualitative pilot study using focus-group discussions (2006), a larger-scale community survey (2007), and follow-up group discussions (2009). The community attitude survey was conducted with a sample of 1,020 adults living in a low-income township in the Eastern Cape Province, South Africa. The study found that the moral and the biomedical understanding of TB risk are intertwined. In the community survey, perceptions of drinking and smoking as TB risk were predicted by fear of contracting TB and being a self-reported born-again Christian. In the follow-up study, heavy drinking and smoking in shebeens (unlicensed township liquor outlets) was associated with a risky lifestyle that can spread both TB and HIV. The paper discusses the similarities and differences in the roles of church and shebeen in providing social support to township dwellers to cope with problems of daily life. It is tentatively concluded that the stereotypical shebeen ‘drinkers and smokers’, alternatively pitied and maligned by moral society, might serve as the scapegoat that deflects pollution from the ‘new’ TB linked to the AIDS epidemic.


CT imaging of coronavirus disease 2019 (COVID-19): from the qualitative to quantitative.


The Perfect Storm: COVID-19, mass incarceration and the opioid epidemic


title: Nipah virus: epidemiology, pathology, immunobiology and advances in diagnosis, vaccine designing and control strategies – a comprehensive review

text: Nipah (Nee-pa) viral disease is a zoonotic infection caused by Nipah virus (NiV), a paramyxovirus belonging to the genus Henipavirus of the family Paramyxoviridae. It is a biosafety level-4 pathogen, which is transmitted by specific types of fruit bats, mainly Pteropus spp. which are natural reservoir host. The disease was reported for the first time from the Kampung Sungai Nipah village of Malaysia in 1998. Human-to-human transmission also occurs. Outbreaks have been reported also from other countries in South and Southeast Asia. Phylogenetic analysis affirmed the circulation of two major clades of NiV as based on currently available complete N and G gene sequences. NiV isolates from Malaysia and Cambodia clustered together in NiV-MY clade, whereas isolates from Bangladesh and India clusterered within NiV-BD clade. NiV isolates from Thailand harboured mixed population of sequences. In humans, the virus is responsible for causing rapidly progressing severe illness which might be characterized by severe respiratory illness and/or deadly encephalitis. In pigs below six months of age, respiratory illness along with nervous symptoms may develop. Different types of enzyme-linked immunosorbent assays along with molecular methods based on polymerase chain reaction have been developed for diagnostic purposes. Due to the expensive nature of the antibody drugs, identification of broad-spectrum antivirals is essential along with focusing on small interfering RNAs (siRNAs). High pathogenicity of NiV in humans, and lack of vaccines or therapeutics to counter this disease have attracted attention of researchers worldwide for developing effective NiV vaccine and treatment regimens.


title: Failed antibody response in a renal transplant recipient with SARS‐CoV‐2 infected

text: In late December 2019, severe acute respiratory syndrome corona virus 2 (SARS‐CoV‐2) has been identified as a novel pathogen causing Coronavirus Disease 2019 (COVID‐19) in Wuhan, China, subsequently spread to the rest of China and has been demonstrating a rapid global spread. Nucleic acid testing (NAT, tested by real‐time polymerase chain reaction) of SARS‐CoV‐2 virus in oropharyngeal/nasal swab samples has been described to be extremely sensitive for the diagnose of SARS‐CoV‐2 infection, but false‐negative results have been reported. Recent months, researches demonstrated the importance of IgM/IgG antibody detecting due to the unsatisfied positive rate of NAT, and the increasement IgM/IgG antibody was considered as a confirmed criteria of diagnosis in the official guides of the diagnosis and treatment of COVID‐19 in China (7(th) Edition) .


title: Regulation of nucleocytoplasmic trafficking of viral proteins: An integral role in pathogenesis?

text: Abstract Signal-dependent targeting of proteins into and out of the nucleus is mediated by members of the importin (IMP) family of transport receptors, which recognise targeting signals within a cargo protein and mediate passage through the nuclear envelope-embedded nuclear pore complexes. Regulation of this process is paramount to processes such as cell division and differentiation, but is also critically important for viral replication and pathogenesis; phosphorylation appears to play a major role in regulating viral protein nucleocytoplasmic trafficking, along with other posttranslational modifications. This review focuses on viral proteins that utilise the host cell IMP machinery in order to traffic into/out of the nucleus, and in particular those where trafficking is critical to viral replication and/or pathogenesis, such as simian virus SV40 large tumour antigen (T-ag), human papilloma virus E1 protein, human cytomegalovirus processivity factor ppUL44, and various gene products from RNA viruses such as Rabies. Understanding of the mechanisms regulating viral protein nucleocytoplasmic trafficking is paramount to the future development of urgently needed specific and effective anti-viral therapeutics. This article was originally intended for the special issue “Regulation of Signaling and Cellular Fate through Modulation of Nuclear Protein Import”. The Publisher apologizes for any inconvenience caused.


title: Dentist manpower development and geographical distribution of dentists in Taiwan

text: Abstract Background/purpose The development of dentists in Taiwan has been over a century. This study tried to explore the dentist manpower development and the current status of geographical distribution of dentists in Taiwan. Materials and methods This study used the secondary data analysis to survey the changes of total dentist number from 1986 to 2018 and the geographic distribution of dentists in different levels of dental institutions in 2019. Results The total number of dentists increased from 3739 in 1986 to 14,717 in 2018. The total number of hospital dentists increased from 809 in 1986 to 2121 in 2018. However, the proportion of hospital dentists in the total number of dentists decreased from 21.64% in 1986 to 14.41% in 2018. On the contrary, the total number of dental clinic dentists increased from 2930 in 1986 to 12,596 in 2018. The proportion of dental clinic dentists in the total number of dentists increased from 78.36% in 1986 to 85.59% in 2018. The northern region of Taiwan and Taipei City had 52.81% (7829/14,825) and 22.29% (3304/14,825) of the total number of dentists in 2019, respectively. Hospital dentists showed a significantly greater imbalance in geographic distribution than overall dentists. Conclusion Our results indicate that Taiwan has the problems of oversupply of dentists and imbalance in geographical distribution of dentists. Because continuation of the current dentist manpower development may accelerate the oversupply and geographical imbalance of dentists, a mechanism for controlling the total dentist manpower should be implemented to prevent the deterioration of the problems.


title: Relevance of Viroporin Ion Channel Activity on Viral Replication and Pathogenesis

text: Modification of host-cell ionic content is a significant issue for viruses, as several viral proteins displaying ion channel activity, named viroporins, have been identified. Viroporins interact with different cellular membranes and self-assemble forming ion conductive pores. In general, these channels display mild ion selectivity, and, eventually, membrane lipids play key structural and functional roles in the pore. Viroporins stimulate virus production through different mechanisms, and ion channel conductivity has been proved particularly relevant in several cases. Key stages of the viral cycle such as virus uncoating, transport and maturation are ion-influenced processes in many viral species. Besides boosting virus propagation, viroporins have also been associated with pathogenesis. Linking pathogenesis either to the ion conductivity or to other functions of viroporins has been elusive for a long time. This article summarizes novel pathways leading to disease stimulated by viroporin ion conduction, such as inflammasome driven immunopathology.


title: Building a picture: Prioritisation of exotic diseases for the pig industry in Australia using multi-criteria decision analysis

text: Abstract Diseases that are exotic to the pig industry in Australia were prioritised using a multi-criteria decision analysis framework that incorporated weights of importance for a range of criteria important to industry stakeholders. Measurements were collected for each disease for nine criteria that described potential disease impacts. A total score was calculated for each disease using a weighted sum value function that aggregated the nine disease criterion measurements and weights of importance for the criteria that were previously elicited from two groups of industry stakeholders. One stakeholder group placed most value on the impacts of disease on livestock, and one group placed more value on the zoonotic impacts of diseases. Prioritisation lists ordered by disease score were produced for both of these groups. Vesicular diseases were found to have the highest priority for the group valuing disease impacts on livestock, followed by acute forms of African and classical swine fever, then highly pathogenic porcine reproductive and respiratory syndrome. The group who valued zoonotic disease impacts prioritised rabies, followed by Japanese encephalitis, Eastern equine encephalitis and Nipah virus, interspersed with vesicular diseases. The multi-criteria framework used in this study systematically prioritised diseases using a multi-attribute theory based technique that provided transparency and repeatability in the process. Flexibility of the framework was demonstrated by aggregating the criterion weights from more than one stakeholder group with the disease measurements for the criteria. This technique allowed industry stakeholders to be active in resource allocation for their industry without the need to be disease experts. We believe it is the first prioritisation of livestock diseases using values provided by industry stakeholders. The prioritisation lists will be used by industry stakeholders to identify diseases for further risk analysis and disease spread modelling to understand biosecurity risks to this industry.


title: Pros and Cons of Antigen-Presenting Cell Targeted Tumor Vaccines

text: In therapeutic antitumor vaccination, dendritic cells play the leading role since they decide if, how, when, and where a potent antitumor immune response will take place. Since the disentanglement of the complexity and merit of different antigen-presenting cell subtypes, antitumor immunotherapeutic research started to investigate the potential benefit of targeting these subtypes in situ. This review will discuss which antigen-presenting cell subtypes are at play and how they have been targeted and finally question the true meaning of targeting antitumor-based vaccines.


title: The gene encoding the nucleocapsid protein: sequence analysis in murine hepatitis virus type 3 and evolution inCoronaviridae

text: The nucleoprotein-encoding gene (N) of murine hepatitis virus type 3 (MHV 3), from the Mill Hill strain, was cloned and sequenced. It was compared to gene N from other murine coronaviruses and was found to share more similarities with N sequences from MHV 1 and MHV JHM strains than with the published MHV 3 N sequence which is almost identical to MHV A59. We suggest that the evolution of some MHV N sequences resulted from a double recombination phenomenon between two ancestors. Furthermore, comparison of protein N from avian and mammalian coronaviruses leads to the hypothesis that horizontal transfer events of the virus from one host species to another have occurred.


title: Accidental Introduction of Viruses into Companion Animals by Commercial Vaccines

text: The use of biologics in veterinary medicine has been of tremendous value in safeguarding our animal populations from debilitating and oftentimes fatal disease. This article reviews the principles of vaccination and the extensive quality control efforts that are incorporated into preparing the vaccines. Examples of adverse events that have occurred in the past and how enhanced vigilance at the level of the veterinarian and the veterinary diagnostic laboratory help to curtail these events are discussed. Emphasis on understanding the ecology of viral infections in dogs and cats is introduced, together with the concepts of the potential role of vaccines in interspecies spread of viruses.


title: A viral metagenomic survey identifies known and novel mammalian viruses in bats from Saudi Arabia

text: Bats are implicated as natural reservoirs for a wide range of zoonotic viruses including SARS and MERS coronaviruses, Ebola, Marburg, Nipah, Hendra, Rabies and other lyssaviruses. Accordingly, many One Health surveillance and viral discovery programs have focused on bats. In this report we present viral metagenomic data from bats collected in the Kingdom of Saudi Arabia [KSA]. Unbiased high throughput sequencing of fecal samples from 72 bat individuals comprising four species; lesser mouse-tailed bat (Rhinopoma hardwickii), Egyptian tomb bat (Taphozous perforatus), straw-colored fruit bat (Eidolon helvum), and Egyptian fruit bat (Rousettus aegyptiacus) revealed molecular evidence of a diverse set of viral families: Picornaviridae (hepatovirus, teschovirus, parechovirus), Reoviridae (rotavirus), Polyomaviridae (polyomavirus), Papillomaviridae (papillomavirus), Astroviridae (astrovirus), Caliciviridae (sapovirus), Coronaviridae (coronavirus), Adenoviridae (adenovirus), Paramyxoviridae (paramyxovirus), and unassigned mononegavirales (chuvirus). Additionally, we discovered a bastro-like virus (Middle East Hepe-Astrovirus), with a genomic organization similar to Hepeviridae. However, since it shared homology with Hepeviridae and Astroviridae at ORF1 and in ORF2, respectively, the newly discovered Hepe-Astrovirus may represent a phylogenetic bridge between Hepeviridae and Astroviridae.


title: Delay in OnabotulinumtoxinA Treatment During the COVID‐19 Pandemic‐Perspectives from a Virus Hotspot

text: The COVID‐19 pandemic has undoubtedly changed our practice of medicine. With our collective resources and attention focused on caring for those afflicted with the disease, other medical conditions have temporarily but understandably faced constraint. For migraine patients who often require in‐person visits for infusions and procedures, this has become particularly challenging. Here, we share our experience in navigating this exigency amidst a local surge of COVID‐19.


title: Community-acquired pathogens associated with prolonged coughing in children: a prospective cohort study

text: A 2-year prospective study was performed of children with prolonged coughing to investigate the frequency of different respiratory pathogens, the rate of mixed infections, and possible differences in severity of disease between single and mixed infections. Sera from 135 children (136 episodes of prolonged coughing lasting 1–6 weeks) were tested for antibodies to different viruses and bacteria. Swabs were taken for culture and PCR to detect different viral and bacterial pathogens. One or more pathogens were found in 91 (67%) patients. One infectious agent was found in 49 (36%) patients, two agents in 35 (26%) patients, and more than two agents in seven (5%) patients. The most frequent pathogens encountered were rhinovirus (n = 43; 32%), Bordetella pertussis (n = 23; 17%) and respiratory syncytial virus (n = 15; 11%). The most frequent mixed infection was B. pertussis and rhinovirus (n = 14; 10%). No significant differences in clinical symptoms were observed between patients with or without pathogens; however, patients with mixed infections were significantly older. There was a strong seasonal influence on the number of infections, but not on the number of mixed infections. In children with prolonged coughing, there was a high frequency of mixed infections regardless of the season. However, mixed infection was not associated with increased disease severity. No clinical symptoms were found that allowed discrimination between specific pathogens.


title: Calu-3 cells are largely resistant to entry driven by filovirus glycoproteins and the entry defect can be rescued by directed expression of DC-SIGN or cathepsin L

text: Abstract Priming of the viral glycoprotein (GP) by the cellular proteases cathepsin B and L (CatB, CatL) is believed to be essential for cell entry of filoviruses. However, pseudotyping systems that predominantly produce non-filamentous particles have frequently been used to prove this concept. Here, we report that GP-mediated entry of retroviral-, rhabdoviral and filoviral particles depends on CatB/CatL activity and that this effect is cell line-independent. Moreover, we show that the human cell line Calu-3, which expresses low amounts of CatL, is largely resistant to entry driven by diverse filovirus GPs. Finally, we demonstrate that Calu-3 cell entry mediated by certain filovirus GPs can be rescued upon directed expression of CatL or DC-SIGN. Our results identify Calu-3 cells as largely resistant to filovirus GP-driven entry and demonstrate that entry is limited at the stage of virion attachment and GP priming.


title: Fetal Thrombotic Vasculopathy Perinatal Stroke, Growth Restriction, and Other Sequelae

text: Abstract Clots in the fetal circulation of the placenta may occlude or narrow the lumens of fetal vessels sufficiently to diminish the placental oxygen and nutritional exchange, causing significant reduction in placental function. When extensive, growth restriction, neonatal encephalopathy, and stillbirth may occur. Propagation of clots in other organs, such as brain, kidney, and liver, may affect the function of these organs, resulting in infarcts and neonatal stroke. This article presents an account of the placental pathology and clinical sequelae of this condition, called fetal thrombotic vasculopathy.


title: Studying the effects of emerging infections on the fetus: Experience with West Nile and Zika viruses

text: Emerging infections have the potential to produce adverse effects on the pregnant woman or her fetus; however, studying these effects is often challenging. We review our experiences with investigating the prenatal effects of two mosquito‐borne infections that emerged in the past 2 decades, West Nile virus (WNV) and Zika virus. Concerns regarding teratogenicity were raised about both viruses; Zika virus has been confirmed to be teratogenic, while WNV appears not to increase the risk for adverse outcomes, although teratogenicity has not been excluded. Study designs used to examine the effects of both viruses include case reports and series, pregnancy registries, and cohort studies. Case–control studies and birth defects surveillance systems are being used to study the effects during pregnancy of Zika virus, but not the effects of WNV, because a specific phenotype was observed among infants with congenital Zika infection, but not among infants with congenital WNV infection. Experimental data that demonstrated that Zika virus was neurotropic have also been useful because they provided biologic plausibility for Zika virus's teratogenic effects: these findings were consistent with observations in congenitally infected infants. Challenges encountered with studies to evaluate the effects of these infections include the broad range of possible adverse outcomes, the inability to include all infected pregnant women in studies because many infections are asymptomatic, and the difficulty with interpretation of diagnostic testing of infants (WNV and Zika) and pregnant women (Zika). This review might be helpful to guide future studies of the effects of emerging infections during pregnancy. Birth Defects Research 109:363–371, 2017. © 2017 Wiley Periodicals, Inc.


title: Reutilización limitada y uso extendido de mascarillas de media-alta filtración

text: ABSTRACT Aim: Personal protective equipment (PPE), including respirators, is essential in a pandemic like Covid-19, which has required, on many occasions, the reuse of material due to its shortage. The aim of this review is to summarize available evidence on the reuse and extended use of filtering facepiece respirator. Method: scoping review. Search through natural language in PUBMED and Centers, Agencies and Organizations for Disease Control. Limited to articles published between 2010-2020 in English and Spanish. Results: 83 articles were located, 14 were selected, plus 5 recommendations. The topics included in this study are classified in 7 sections: expiration, extended use and reuse of masks, handling techniques, sealing, physical-psychological effects and compliance, contamination and decontamination of respirators. Conclusions: the reuse of masks is not recommended by official organizations or manufacturers, and is only accepted in extraordinary cases, such as pandemics. The studies are characterized by having small samples, using different models of respirators adjusting their recommendation to the model.


Validity of the UK Early Access to Medicines Scheme Criteria for Remdesivir use in patients with COVID-19 disease


title: Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study

text: Summary Background Middle East respiratory syndrome coronavirus (MERS-CoV) infection is associated with high mortality and has no approved antiviral therapy. We aimed to compare ribavirin and interferon alfa-2a treatment for patients with severe MERS-CoV infection with a supportive therapy only. Methods In this retrospective cohort study, we included adults (aged ≥16 years) with laboratory-confirmed MERS-CoV infection and pneumonia needing ventilation support, diagnosed between Oct 23, 2012, and May 1, 2014, at the Prince Sultan Military Medical City (Riyadh, Saudi Arabia). All patients received appropriate supportive care and regular clinical and laboratory monitoring, but patients diagnosed after Sept 16, 2013, were also given oral ribavirin (dose based on calculated creatinine clearance, for 8–10 days) and subcutaneous pegylated interferon alfa-2a (180 μg per week for 2 weeks). The primary endpoint was 14-day and 28-day survival from the date of MERS-CoV infection diagnosis. We used χ2 and Fischer's exact test to analyse categorical variables and the t test to analyse continuous variables. Findings We analysed 20 patients who received ribavirin and interferon (treatment group; initiated a median of 3 days [range 0–8] after diagnosis) and 24 who did not (comparator group). Baseline clinical and laboratory characteristics were similar between groups, apart from baseline absolute neutrophil count, which was significantly lower in the comparator group (5·88 × 109/L [SD 3·95] vs 9·88 × 109/L [6·63]; p=0·023). 14 (70%) of 20 patients in the treatment group had survived after 14 days, compared with seven (29%) of 24 in the comparator group (p=0·004). After 28 days, six (30%) of 20 and four (17%) of 24, respectively, had survived (p=0·054). Adverse effects were similar between groups, apart from reduction in haemoglobin, which was significantly greater in the treatment group than in the comparator group (4·32 g/L [SD 2·47] vs 2·14 g/L [1·90]; p=0·002). Interpretation In patients with severe MERS-CoV infection, ribavirin and interferon alfa-2a therapy is associated with significantly improved survival at 14 days, but not at 28 days. Further assessment in appropriately designed randomised trials is recommended. Funding None.


title: Respiratory Syncytial Virus and Other Viral Infections among Children under Two Years Old in Southern Vietnam 2009-2010: Clinical Characteristics and Disease Severity

text: BACKGROUND: Despite a high burden of respiratory syncytial virus (RSV) infections among children, data on demographic and clinical characteristics of RSV are scarce in low and middle income countries. This study aims to describe the viral etiologies, the demographic, epidemiological, and clinical characteristics of children under two years of age who were hospitalized with a lower respiratory tract infections (LRTI), focusing on RSV (prevalence, seasonality, subgroups, viral load) and its association with disease severity. METHODS: A prospective study among children under two years of age, hospitalized with LRTI was conducted in two referral pediatric hospitals in Ho Chi Minh City, Vietnam, from May 2009 to December 2010. Socio-demographic, clinical data and nasopharyngeal swabs were collected on enrolment and discharge. Multiplex real-time RT-PCR (13 viruses) and quantitative RSV RT-PCR were used to identify viral pathogens, RSV load and subgroups. RESULTS: Among 632 cases, 48% were RSV positive. RSV infections occurred at younger age than three other leading viral infections i.e rhinovirus (RV), metapneumovirus (MPV), parainfluenza virus (PIV-3) and were significantly more frequent in the first 6 months of life. Clinical severity score of RSV infection was significantly higher than PIV-3 but not for RV or MPV. In multivariate analysis, RV infection was significantly associated with severity while RSV infection was not. Among RSV infections, neither viral load nor viral co-infections were significantly associated with severity. Young age and having fever at admission were significantly associated with both RSV and LRTI severity. A shift in RSV subgroup predominance was observed during two consecutive rainy seasons but was not associated with severity. CONCLUSION: We report etiologies, the epidemiological and clinical characteristics of LRTI among hospitalized children under two years of age and risk factors of RSV and LRTI severity.