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Coronavirus Disease 2019: A Gastroenterologist’s Perspective in May 2020

We are in the middle of coronavirus disease 2019 (COVID-19) pandemic which has affected every aspect of human life all over the world. Although COVID-19 primarily affects the lungs, it is in fact a multisystem disorder causing high mortality and panicking the whole world. Gastrointestinal (GI) manifestations of this disorder usually accompany respiratory manifestations and this combination is indicative of the severity of the disease. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, which causes COVID-19, enters the body by attaching to angiotensin converting enzyme-2 receptors which are not only present in the respiratory tract but also in the GI tract. Person-to-person droplet transmission is the main mode of spread although there is potential for fecal-oral transmission. Patients with inflammatory bowel disease (IBD) are not at increased risk of developing COVID-19 and they should continue to take their current medications. If they become positive for SARS-CoV-2 RNA or COVID-19, their biologic therapy should be either delayed or on hold temporarily. GI endoscopy units are high-risk areas and GI procedures are high-risk procedures for the transmission of SARS-CoV-2 infection. Only emergency and semi-emergency procedures should be done, and elective procedures should be temporarily on hold until adequate resources are available. Endoscopists should use appropriate personal protective equipment. Mildly abnormal liver function tests (LFTs) are common in COVID-19 patients and are mostly due to systemic inflammatory response, hepatic ischemia or hepatotoxic medications. Close monitoring of liver function and supportive care of COVID-19 patients are recommended.

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Which type of cancer patients are more susceptible to the SARS-COX-2: evidence from a meta-analysis and bioinformatics analysis

OBJECTIVE: Numerous studies have reported that patients with cancer seem to be more likely to be diagnosed with COVID-19. However, it is still unknown the prevalence of different types of cancer in patients with COVID-19. Therefore, this study will explore which type of cancer patients are more susceptible to the SARS-COX-2. METHODS: Eligible studies were identified by searching several electronic databases for relevant studies published before April 28, 2020. The language was restricted to English or Chinese. The meta-analysis was performed using Stata 12.0. The GEPIA database evaluated the expression of SARS-COX-2 infection key genes in different types of normal and tumor samples. RESULTS: A total of 6 studies, including 205 patients, were identified to be eligible for this meta-analysis. Among the cancer patients infected by SARS-COX-2, the proportion of patients with the lung, colorectal,breast,esophagus,bladder,pancreatic and cervical cancer were 24.7%, 20.5%, 13.0%, 7.6%,7.3%,6.1%,and 6.0%, respectively. These findings were also corroborated by the results of the GEPIA database. CONCLUSION: Compared with other types of cancer, lung cancer and colorectal cancer are more susceptible to SARS-COX-2 infection.

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Immunopathogenesis of coronavirus infections: implications for SARS

At the end of 2002, the first cases of severe acute respiratory syndrome (SARS) were reported, and in the following year, SARS resulted in considerable mortality and morbidity worldwide. SARS is caused by a novel species of coronavirus (SARS-CoV) and is the most severe coronavirus-mediated human disease that has been described so far. On the basis of similarities with other coronavirus infections, SARS might, in part, be immune mediated. As discussed in this Review, studies of animals that are infected with other coronaviruses indicate that excessive and sometimes dysregulated responses by macrophages and other pro-inflammatory cells might be particularly important in the pathogenesis of disease that is caused by infection with these viruses. It is hoped that lessons from such studies will help us to understand more about the pathogenesis of SARS in humans and to prevent or control outbreaks of SARS in the future.

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Profile–profile comparisons by COMPASS predict intricate homologies between protein families

Recently we proposed a novel method of alignment–alignment comparison, COMPASS (the tool for COmparison of Multiple Protein Alignments with Assessment of Statistical Significance). Here we present several examples of the relations between PFAM protein families that were detected by COMPASS and that lead to the predictions of presently unresolved protein structures. We discuss relatively straightforward COMPASS predictions that are new and interesting to us, and that would require a substantial time and effort to justify even for a skilled PSI-BLAST user. All of the presented COMPASS hits are independently confirmed by other methods, including the ab initio structure-prediction method ROSETTA. The tertiary structure predictions made by ROSETTA proved to be useful for improving sequence-derived alignments, because they are based on a reasonable folding of the polypeptide chain rather than on the information from sequence databases. The ability of COMPASS to predict new relations within the PFAM database indicates the high sensitivity of COMPASS searches and substantiates its potential value for the discovery of previously unknown similarities between protein families.

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Partial Purification of IBV and Subsequent Isolation of Viral RNA for Next-Generation Sequencing

RNA viruses are known for a high mutation rate and rapid genomic evolution. As such an RNA virus population does not consist of a single genotype but is rather a collection of individual viruses with closely related genotypes—a quasispecies, which can be analyzed by next-generation sequencing (NGS). This diversity of genotypes provides a mechanism in which a virus population can evolve and adapt to a changing environment. Sample preparation is vital for successful sequencing. The following protocol describes the process of generating a high-quality RNA preparation from IBV grown in embryonated eggs and then partially purified and concentrated through a 30 % sucrose cushion for NGS.

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Control of the PI3K/Akt pathway by porcine reproductive and respiratory syndrome virus

Phosphatidylinositol-3-kinase (PI3K)/Akt is an important cellular pathway that has been shown to participate in various replication steps of multiple viruses. In the present study, we compared the phosphorylation status of Akt during infection of MARC-145 cells and porcine alveolar macrophages (PAMs) with highly pathogenic PRRSV (HP-PRRSV) strain HuN4. We observed that biphasic activation of Akt was induced in at both the early stage (5, 15 and 30 min postinfection) and the late stage (12 and 24 h postinfection) of HP-PRRSV infection of MARC-145 cells, while an early-phase activation of Akt was found exclusively in virus-infected PAMs in vitro. Analysis with the PI3K-specific inhibitor LY294002 confirmed that PI3K acted as the upstream activator for the virus-induced activation of Akt. UV-irradiation-inactivated virus still induced the early event in PAMs but not in MARC-145 cells, suggesting that different mechanisms are employed for the early-stage induction of phosphorylated Akt within different cell cultures. We further demonstrated that FoxO1 and Bad, which serve as downstream targets of Akt, were phosphorylated in virus-infected MARC-145 cells. Moreover, the suppression of phosphorylated Akt with LY294002 significantly inhibited the virus-induced cytopathic effect (CPE) on MARC-145 cells, but it had a negligible effect on virus propagation. Collectively, our data provide new evidence of a novel role for the PI3K/Akt pathway in PRRSV infection of MARC-145 cells.

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Pandemic preparedness of community pharmacies for COVID-19: A cross-sectional survey

BACKGROUND: Community pharmacies provide an important healthcare service, which is broadly established, and constitutes the preferred and initial contact for members of the community. The significant value of community pharmacies was further highlighted during the COVID-19 pandemic crisis. OBJECTIVE: The assessment of community pharmacies preparedness for the COVID-19 pandemic. METHODS: A cross‐sectional interview survey of 1018 community pharmacies working in four regions of Egypt (South, East, Centre, and North). Data collection was conducted from 8–19 April 2020. RESULTS: Availability of personal protective equipment (PPE) and medication was better than alcohol (70% conc.). Home delivery services were available in 49.1% of pharmacies. Infection control measures covering interactions between staff were in place in up to 99.5% of pharmacies. Conversely, there was less frequent availability of contactless payment (29.1%), hand sanitizers (62.1%) or masks (86.5%) for customer use, or a separate area for patients with suspected COVID-19 (64%). Verbal customer education (90.4%) was used preferably to written (81.3%). Despite high clinical knowledge and awareness (97.6%–99.2%), only 8.8% of pharmacists had reported suspected COVID-19 cases, however this varied significantly with pharmacist demographics (geographic region P < 0.001; pandemic training p < 0.001; position p = 0.019; age p = 0.046). CONCLUSIONS: Government and policymakers strive to mitigate the shortage of PPE and medication. More attention should be given to infection control measures around interactions between staff and customers to ensure community pharmacists are fit and able to provide continuity in their important role. Educating customers using regularly-updated posters, banners or signs will contribute to decreasing contact with patients, and reducing the number and duration of visits to the pharmacy. Pandemic preparedness of community pharmacists must also extend to reporting procedures. By avoiding under-reporting or over-reporting, community pharmacists will contribute to accurate monitoring of the national spread of infection.

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Right Ventricular Function and Pulmonary Pressures as Independent Predictors of Survival in Patients With COVID-10 Pneumonia

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Delivery technologies for human vaccines

There is currently intense research activity aimed at the development of new delivery systems for vaccines. The goal is to identify optimal methods for presenting target antigens to the immune system in a manner that will elicit immune responses appropriate for protection against, or treatment of, a specific disease. Several different approaches to this general goal have been developed, some are empirical and remain poorly understood, others are more rational, being based, for example, on mimicking natural infections in vivo or on targeting particular features of the immune system. This article will review three categories of delivery systems: (i) adjuvants and formulations; (ii) antigen vectors, including live attenuated micro-organisms and synthetic vectors; and (iii) novel devices for vaccine administration. The review will be restricted to late stage developments in the field of human vaccination.

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Negative pressure of the environmental air in the cleaning area of the materials and sterilization center: a systematic review

OBJECTIVE: to analyze the scientific evidence on aerosols generated during cleaning activities of health products in the Central Service Department (CSD) and the impact of the negative pressure of the ambient air in the cleaning area to control the dispersion of aerosols to adjacent areas. METHOD: for this literature systematic review the following searches were done: search guidelines, manuals or national and international technical standards given by experts; search in the portal and databases PubMed, Scopus, CINAHL and Web of Science; and a manual search of scientific articles. RESULTS: the five technical documents reviewed recommend that the CSD cleaning area should have a negative differential ambient air pressure, but scientific articles on the impact of this intervention were not found. The four articles included talked about aerosols formed after the use of a ultrasonic cleaner (an increased in the contamination especially during use) and pressurized water jet (formation of smaller aerosols 5μm). In a study, the aerosols formed from contaminated the hot tap water with Legionella pneumophila were evaluated. CONCLUSIONS: there is evidence of aerosol formation during cleanup activities in CSD. Studies on occupational diseases of respiratory origin of workers who work in CSD should be performed.

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A call to action for public health nurses during the COVID‐19 pandemic

Public health nurses (PHNs) are on the frontline of the public health crisis the world now knows as the COVID-19 pandemic. They serve on mobile strike teams investigating case-contacts, deliver education on self-isolation and quarantine through hotlines and home visits, and interpret the rapidly shifting guidance from the Centers for Disease Control and Prevention (CDC). They are reliable and proven responders during infectious disease emergencies, providing safe, effective, and nondiscriminatory care to the communities in which they serve.

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Viral Infection in the Development and Progression of Pediatric Acute Respiratory Distress Syndrome

Viral infections are an important cause of pediatric acute respiratory distress syndrome (ARDS). Numerous viruses, including respiratory syncytial virus (RSV) and influenza A (H1N1) virus, have been implicated in the progression of pneumonia to ARDS; yet the incidence of progression is unknown. Despite acute and chronic morbidity associated with respiratory viral infections, particularly in “at risk” populations, treatment options are limited. Thus, with few exceptions, care is symptomatic. In addition, mortality rates for viral-related ARDS have yet to be determined. This review outlines what is known about ARDS secondary to viral infections including the epidemiology, the pathophysiology, and diagnosis. In addition, emerging treatment options to prevent infection, and to decrease disease burden will be outlined. We focused on RSV and influenza A (H1N1) viral-induced ARDS, as these are the most common viruses leading to pediatric ARDS, and have specific prophylactic and definitive treatment options.

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Agents and Robots for Collaborating and Supporting Physicians in Healthcare Scenarios

Monitoring patients through robotics telehealth systems is an interesting scenario where patients’ conditions, and their environment, are dynamic and unknown variables. We propose to improve telehealth systems’ features to include the ability to serve patients with their needs, operating as human caregivers. The objective is to support the independent living of patients at home without losing the opportunity to monitor their health status. Application scenarios are several, and they spread from simple clinical assisting scenarios to an emergency one. For instance, in the case of a nursing home, the system would support in continuously monitoring the elderly patients. In contrast, in the case of an epidemic diffusion, such as COVID-19 pandemic, the system may help in all the early triage phases, significantly reducing the risk of contagion. However, the system has to let medical assistants perform actions remotely such as changing therapies or interacting with patients that need support. The paper proposes and describes a multi-agent architecture for intelligent medical care. We propose to use the beliefs-desires-intentions agent architecture, part of it is devised to be deployed in a robot. The result is an intelligent system that may allow robots the ability to select the most useful plan for unhandled situations and to communicate the choice to the physician for his validation and permission.

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Longitudinal study of interventional radiology activity in a large metropolitan Italian tertiary care hospital: how the COVID-19 pandemic emergency has changed our activity

OBJECTIVES: To retrospectively analyze interventional radiology (IR) activity changes in the COVID-19 era and to describe how to safely and effectively reorganize IR activity. METHODS: All IR procedures performed between January 30 and April 8, 2020 (COVID-era group) and the same 2019 period (non-COVID-era group) were retrospectively included and compared. A sub-analysis for the lockdown period (LDP: 11 March–8 April) was also conducted. Demographic, hospitalization, clinical, and procedural data were obtained for both groups and statistically compared with univariable analysis. RESULTS: A total of 1496 procedures (non-COVID era, 825; COVID era, 671) performed in 1226 patients (64.9 ± 15.1 years, 618 women) were included. The number of procedures decreased by 18.6% between 2019 and 2020 (825 vs 671, p < .001), with a reduction by 48.2% in LDP (188 vs 363, p < .0001). In the LDP COVID era, bedside procedures were preferred (p = .013), with an increase in procedures from the intensive care unit compared with the emergency department and outpatients (p = .048), and an increased activity for oncological patients (p = .003). No incidents of cross-infection of non-infected from infected patients and no evidence of COVID-19 infection of healthcare workers in the IR service was registered. CONCLUSIONS: Coronavirus disease outbreak changed the interventional radiology activity with an overall reduction in the number of procedures. However, this study confirms that interventional radiology continuum of care can be safely performed also during the pandemic, following defined measures and protocols, taking care of all patients. KEY POINTS: • Coronavirus disease pandemic determined a reduction of interventional radiology activity as compared to the same period of the previous year. • Interventional radiology procedures for life-threatening conditions and non-deferrable oncologic treatments were prioritized as opposed to elective procedures. • Strict adoption of safe procedures allowed us to have until now no incidents of cross-infection of non-infected from infected patients and no evidence of COVID-19 infection of HCWs in the IR service.

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Is Higher Viral Load in the Upper Respiratory Tract Associated With Severe Pneumonia? Findings From the PERCH Study

BACKGROUND. The etiologic inference of identifying a pathogen in the upper respiratory tract (URT) of children with pneumonia is unclear. To determine if viral load could provide evidence of causality of pneumonia, we compared viral load in the URT of children with World Health Organization–defined severe and very severe pneumonia and age-matched community controls. METHODS. In the 9 developing country sites, nasopharyngeal/oropharyngeal swabs from children with and without pneumonia were tested using quantitative real-time polymerase chain reaction for 17 viruses. The association of viral load with case status was evaluated using logistic regression. Receiver operating characteristic (ROC) curves were constructed to determine optimal discriminatory viral load cutoffs. Viral load density distributions were plotted. RESULTS. The mean viral load was higher in cases than controls for 7 viruses. However, there was substantial overlap in viral load distribution of cases and controls for all viruses. ROC curves to determine the optimal viral load cutoff produced an area under the curve of <0.80 for all viruses, suggesting poor to fair discrimination between cases and controls. Fatal and very severe pneumonia cases did not have higher viral load than less severe cases for most viruses. CONCLUSIONS. Although we found higher viral loads among pneumonia cases than controls for some viruses, the utility in using viral load of URT specimens to define viral pneumonia was equivocal. Our analysis was limited by lack of a gold standard for viral pneumonia.

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Viral Etiology of Influenza-Like Illnesses in Cameroon, January–December 2009

Background. No information is available on the viral etiology of upper respiratory tract infections in Cameroon. Methods. We prospectively enrolled outpatients with influenza-like illness (ILI) presenting at 14 sentinel clinics located across the country from January through December 2009. The specimens were tested using real-time and multiplex reverse-transcription polymerase chain reaction methods for the detection of 15 RNA respiratory viruses. Results. We detected at least 1 respiratory virus in 365 of 561 specimens (65.1%). Overall, influenza virus was the most commonly detected virus (28.2% of specimens), followed by human rhinovirus (17.8%); parainfluenza virus (PIV) types 1–4 (7.5%); enterovirus (5.9%); respiratory syncytial virus (RSV; 5.7%); human coronavirus (HCoV) OC43, 229E, NL63, and HKU1 (5.3%); and human metapneumovirus (HMPV; 5.0%). RSV (26 of 31 specimens [83.9%]), PIV (30 of 39 [76.9%]), and HRV (64 of 99 [64.6%]) were most common among children <5 years of age. Coinfections were found in 53 of 365 positive specimens (14.5%), and most (71.7%) were in children <5 years of age. While influenza virus, enterovirus, RSV, and HMPV had a defined period of circulation, the other viruses were detected throughout the year. Conclusions. We found that respiratory viruses play an important role in the etiology of ILI in Cameroon, particularly in children <5 years of age.

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Interdependent Citizens: The Ethics of Care in Pandemic Recovery

The crisis of Covid‐19 has forced us to notice two things: our human interdependence and American society's tolerance for what Nancy Krieger has called “inequalities embodied in health inequities,” reflected in data on Covid‐19 mortality and geographies. Care is integral to our recovery from this catastrophe and to the development of sustainable public health policies and practices that promote societal resilience and reduce the vulnerabilities of our citizens. Drawing on the insights of Joan Tronto and Eva Feder Kittay, we argue that the ethics of care offers a critical alternative to utilitarian and deontological approaches and provides a street‐ready framework for integration into public health deliberations to anchor public policy and investments concerning the recovery and future well‐being of America's citizens and society.

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Complement Receptor C5aR1 Inhibition Reduces Pyroptosis in hDPP4-Transgenic Mice Infected with MERS-CoV

Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic virus with a crude mortality rate of ~35%. Previously, we established a human DPP4 transgenic (hDPP4-Tg) mouse model in which we studied complement overactivation-induced immunopathogenesis. Here, to better understand the pathogenesis of MERS-CoV, we studied the role of pyroptosis in THP-1 cells and hDPP4 Tg mice with MERS-CoV infection. We found that MERS-CoV infection induced pyroptosis and over-activation of complement in human macrophages. The hDPP4-Tg mice infected with MERS-CoV overexpressed caspase-1 in the spleen and showed high IL-1β levels in serum, suggesting that pyroptosis occurred after infection. However, when the C5a-C5aR1 axis was blocked by an anti-C5aR1 antibody (Ab), expression of caspase-1 and IL-1β fell. These data indicate that MERS-CoV infection induces overactivation of complement, which may contribute to pyroptosis and inflammation. Pyroptosis and inflammation were suppressed by inhibiting C5aR1. These results will further our understanding of the pathogenesis of MERS-CoV infection.

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EARLY REPORT ON THE IMPACT OF COVID-19 OUTBREAK IN NEUROSURGICAL PRACTICE AMONG MEMBERS OF THE LATIN AMERICAN FEDERATION OF NEUROSURGICAL SOCIETIES

Abstract Background The COVID-19 pandemic has caused severe economic consequences by local governmental measures to contain the outbreak1 We provide insight on the impact that healthcare restriction has made on neurosurgical activity in Latin Iberoamerica. METHODS: We performed an internet-based survey among Presidents and Members of the Societies of the Latin American Federation of Neurosurgical Societies (FLANC). We blindly analyzed information about local conditions and their impact on neurosurgical praxis using SPSS® software. Results Information came from 21 countries. Sixteen Society Presidents reported having suspended regular activities, and differing local scheduled congresses, fourteen reported mandatory isolation by government, and four instituted a telemedicine project. Four-hundred eighty-six colleagues, mean age 49 years, reported a mean 79% reduction in their neurosurgical praxis. Seventy-six percent of neurosurgeons had savings to self-support for 3-6 months, if restrictions are long lasting. Conclusions Stopping activities among Societies of the FLANC, together with a drop of 79% of neurosurgical praxis, adds to deficits in provider´s protection equipment and increasing demand for attention in the healthcare systems; representing a huge financial risk for their sustainability. Neurosurgeons should involve in local policies to protect health and economy. Telemedicine represents an excellent solution, avoiding another pandemic of severe diseases across all-specialties as non-essential care can turn essential if left untreated. Financial support and ethics code review is needed to battle this new disease, designated the occupational disease of the decade, that continues to struggle the healthcare systems. Times of crisis are times of great opportunities for humanity to evolve.

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Adding Colchicine to the Antiretroviral Medication - Lopinavir/Ritonavir (Kaletra) in Hospitalized Patients with Non-Severe Covid-19 Pneumonia: A Structured Summary of a Study Protocol for a Randomized Controlled Trial

OBJECTIVES: Colchicine is a well-known drug, which has been used for years to treat a wide range of rheumatic and inflammatory disorders. It helps break the cycle of inflammation through diverse mechanisms including reducing Intereukin-6, Interleukin-8, Tumour Necrosis Factor-alpha besides controlling oxidative stress pathways which all are important and pathologic components in the clinical course and outcome of patients infected with COVID-19. This study aims to assess the anti-inflammatory effects of colchicine in non-severe hospitalized COVID-19 patients. TRIAL DESIGN: Prospective, randomized (1:1 ratio), double blind study with parallel group design. PARTICIPANTS: Hospitalized patients with positive nasopharyngeal swab for COVID-19 infection (RT -PCR) and lung Computed tomography scan involvement compatible with COVID-19 pneumonia. The patients are not severely hypoxic, do not need intubation or invasive oxygenation. Exclusion criteria: known hypersensitivity to colchicine; known hepatic failure; estimated glomerular filtration rate (eGFR)<30 ml/min/1.73m(2) (by the CKD-EPI Creatinine Equation for Glomerular Filtration Rate (GFR) which estimates GFR based on serum creatinine. ; kidney transplant recipients, using Digoxin, QTc >450 msec. Participants will be recruited from inpatients at Labbafinejad Meidcal Center , Tehran, Iran. INTERVENTION AND COMPARATOR: Eligible enrolled patients will be randomized into two groups. Group A will receive the antiretroviral Lopinavir/Ritonavir (Kaletra) while group B will receive Lopinavir/Ritonavir (Kaletra) + Colchicine 1.5 mg loading then 0.5 mg twice daily orally. All patients in both groups will receive the same amounts of essential minerals, vitamins as antioxidants, and antibiotics. Patients of both groups will be treated under optimal treatment based on the CDC and WHO guidelines and national consensus proposed in Iran including the same dosages of Lopinavir/Ritonavir, antibiotics, trace elements and antioxidants while only in group-B patients Colchicine will be added on top of this protocol. MAIN OUTCOMES: Primary: Time for clinical improvement and lung CT score changes 14 days after treatment. Secondary: 14 days after treatment – C-Reactive Protein test x Neutrophil to Lymphocyte Ratio , Interleukin-6, malondialdehyde (MDA) levels reduction – Percentage of patients who require supplemental Oxygen – Mean hospital stay length RANDOMISATION: Patients will be allocated to each group (ratio 1:1) by using an online randomization tool: http://www.graphpad.com/quickcalcs/index.cfm BLINDING (MASKING): This will be a double-blind study in which participants and those assessing the final outcomes will be blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Regarding the pandemic crisis and our center capacity to hospitalize confirmed COVID-19 patients, a total of 80 patients was found to be logical to be randomized into two groups of 40- patients. TRIAL STATUS: Recruitment is ongoing. Recruitment began on 20/03/2020 and the date by which the recruitment is anticipated to be completed is 30/05/2020. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04360980, registered 24/04/2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in 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.

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Aspectos medicolegales derivados de la pandemia del COVID-19.

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Chapter 59 Respiratory Virus Vaccines

Abstract This chapter reviews the main viral pathogens of the respiratory tract, the immune responses they induce, currently available vaccines, and vaccines that are in development to control them. The main viruses responsible for acute respiratory infection in people include respiratory syncytial, influenza, human parainfluenza, human metapneumo-, human rhino-, corona-, and adenoviruses. Licensed vaccines are available only for influenza virus, with vaccines against the other pathogens either in clinical trials or in preclinical stages of development. The majority of studies evaluating respiratory virus vaccines measure serum antibody responses, because, although both cellular and humoral responses contribute to the clearance of a primary infection, neutralizing antibodies are known to protect against secondary infection. Humoral responses can be readily detected after vaccination with inactivated or subunit vaccines; however, fewer individuals seroconvert after vaccination with live vaccines. Alternative immune mechanisms such as mucosal antibody responses are probably responsible for protection by live attenuated vaccines, and immune correlates of protection are under investigation.

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Platelet‐to‐lymphocyte ratio is associated with prognosis in patients with coronavirus disease‐19

Since December 2019, novel coronavirus infected pneumonia emerged in Wuhan city and rapidly spread throughout China. In severe novel coronavirus pneumonia cases, the number of platelets, their dynamic changes during the treatment, platelet‐to‐lymphocyte ratio (PLR) were a concern. We sought to describe the platelet feature of these cases. Single‐center case series of the 30 hospitalized patients with confirmed coronavirus disease (COVID)‐19 in Huizhou municipal central hospital from January 2020 to February 2020 were retrospectively analyzed. Demographic, clinical, blood routine results, other laboratory results, and treatment data were collected and analyzed. Outcomes of severe patients and nonsevere patients were compared. Univariate analysis showed that: age, platelet peaks, and PLR at peak platelet were the influencing factors in severe patients, multivariate analysis showed that the PLR value at peak platelet during treatment was an independent influencing factor in severe patients. The average hospitalization day of patients with platelet peaks during treatment was longer than those without platelet peaks (P < .05). The average age of patients with platelet peaks during treatment was older than those without platelet peaks (P < .05). The patients with significantly elevated platelets during treatment had longer average hospitalization days. And the higher PLR of patients during treatment had longer average hospitalization days. Single‐center case series of the 30 hospitalized patients with confirmed COVID‐19 in Huizhou Municipal Central Hospital, presumed that the number of platelets and their dynamic changes during the treatment may have a suggestion on the severity and prognosis of the disease. The patient with markedly elevated platelets and longer average hospitalization days may be related to the cytokine storm. The PLR of patients means the degree of cytokine storm, which might provide a new indicator in the monitoring in patients with COVID‐19.

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Remdesivir — An Important First Step

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Principles of Virus Uncoating: Cues and the Snooker Ball

Viruses are spherical or complex shaped carriers of proteins, nucleic acids and sometimes lipids and sugars. They are metastable and poised for structural changes. These features allow viruses to communicate with host cells during entry, and to release the viral genome, a process known as uncoating. Studies have shown that hundreds of host factors directly or indirectly support this process. The cell provides molecules that promote stepwise virus uncoating, and direct the virus to the site of replication. It acts akin to a snooker player who delivers accurate and timely shots (cues) to the ball (virus) to score. The viruses, on the other hand, trick (snooker) the host, hijack its homeostasis systems, and dampen innate immune responses directed against danger signals. In this review, we discuss how cellular cues, facilitators, and built‐in viral mechanisms promote uncoating. Cues come from receptors, enzymes and chemicals that act directly on the virus particle to alter its structure, trafficking and infectivity. Facilitators are defined as host factors that are involved in processes which indirectly enhance entry or uncoating. Unraveling the mechanisms of virus uncoating will continue to enhance understanding of cell functions, and help counteracting infections with chemicals and vaccines. [Image: see text]

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Crystal structure of the receptor binding domain of the spike glycoprotein of human betacoronavirus HKU1

Human coronavirus (CoV) HKU1 is a pathogen causing acute respiratory illnesses and so far little is known about its biology. HKU1 virus uses its S1 subunit C-terminal domain (CTD) and not the N-terminal domain like other lineage A β-CoVs to bind to its yet unknown human receptor. Here we present the crystal structure of HKU1 CTD at 1.9 Å resolution. The structure consists of three subdomains: core, insertion and subdomain-1 (SD-1). While the structure of the core and SD-1 subdomains of HKU1 are highly similar to those of other β-CoVs, the insertion subdomain adopts a novel fold, which is largely invisible in the cryo-EM structure of the HKU1 S trimer. We identify five residues in the insertion subdomain that are critical for binding of neutralizing antibodies and two residues essential for receptor binding. Our study contributes to a better understanding of entry, immunity and evolution of CoV S proteins.

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Compassionate drug use: an imperative challenge for Bulgarian health system during COVID-19

• The health care system in Bulgaria faces unprecedented challenges trying to take control over the pandemic of COVID-19. • The existing national regulation in Bulgaria leads to delayed and difficult access to investigational drugs via compassionate use programs. • The COVID-19 pandemic will initiate a dialogue among health policy makers and BDA for the establishment of new health policy and clear national regulation due to higher demand for investigational drugs.

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Evaluation of a peptide‐based enzyme immunoassay for anti‐SARS coronavirus IgG antibody

High throughput assays for anti‐SARS‐CoV IgG antibody detection are need for large‐scale epidemiologic studies. The performance of a microplate enzyme immunoassay, DETECT‐SARS™, was evaluated for the detection of anti‐SARS‐CoV IgG antibody. This assay is based on synthetic peptides derived from the nucleocapsid and spike proteins. The results showed that the assay provided a high degree of sensitivity (95.9%) for convalescent serum samples. The level of specificity was close to 90%, and did not show significant variation among different control groups. The high degree of sensitivity together with the high‐throughput nature makes it advantageous as a screening assay for studies where handling of a large number of specimens is required. J. Med. Virol. 74:517–520, 2004. © 2004 Wiley‐Liss, Inc.

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Ribavirin and Interferon Therapy for Critically Ill Patients With Middle East Respiratory Syndrome: A Multicenter Observational Study

BACKGROUND: The objective of this study was to evaluate the effect of ribavirin and recombinant interferon (RBV/rIFN) therapy on the outcomes of critically ill patients with Middle East respiratory syndrome (MERS), accounting for time-varying confounders. METHODS: This is a retrospective cohort study of critically ill patients with laboratory-confirmed MERS from 14 hospitals in Saudi Arabia diagnosed between September 2012 and January 2018. We evaluated the association of RBV/rIFN with 90-day mortality and MERS coronavirus (MERS-CoV) RNA clearance using marginal structural modeling to account for baseline and time-varying confounders. RESULTS: Of 349 MERS patients, 144 (41.3%) patients received RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a; none received rIFN-β1b). RBV/rIFN was initiated at a median of 2 days (Q1, Q3: 1, 3 days) from intensive care unit admission. Crude 90-day mortality was higher in patients with RBV/rIFN compared to no RBV/rIFN (106/144 [73.6%] vs 126/205 [61.5%]; P = .02]. After adjusting for baseline and time-varying confounders using a marginal structural model, RBV/rIFN was not associated with changes in 90-day mortality (adjusted odds ratio, 1.03 [95% confidence interval {CI}, .73–1.44]; P = .87) or with more rapid MERS-CoV RNA clearance (adjusted hazard ratio, 0.65 [95% CI, .30–1.44]; P = .29). CONCLUSIONS: In this observational study, RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a) therapy was commonly used in critically ill MERS patients but was not associated with reduction in 90-day mortality or in faster MERS-CoV RNA clearance.

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DDX3 functions in antiviral innate immunity through translational control of PACT

It has emerged that DDX3 plays a role in antiviral innate immunity. However, the exact mechanism by which DDX3 functions in antiviral innate immunity remains to be determined. We found that the expression of the protein activator of the interferon‐induced protein kinase (PACT) was regulated by DDX3 in human cells. PACT acts as a cellular activator of retinoic acid‐inducible gene‐I‐like receptors in the sensing of viral RNAs. DDX3 facilitated the translation of PACT mRNA that may contain a structured 5′ UTR. Knockdown of DDX3 decreased the viral RNA detection sensitivity of the cells. PACT partially rescued defects of interferon‐β1 and chemokine (C‐C motif) ligand 5/RANTES (regulated on activation normal T cell expressed and secreted) induction in DDX3‐knockdown HEK293 cells. Therefore, DDX3 may participate in antiviral innate immunity, at least in part, by translational control of PACT. Moreover, we show that overexpression of the hepatitis C virus (HCV) core protein inhibited the translation of a reporter mRNA harboring the PACT 5′ UTR. The HCV core protein was associated and colocalized with DDX3 in cytoplasmic stress granules, suggesting that the HCV core may abrogate the function of DDX3 by sequestering DDX3 in stress granules. The perturbation of DDX3 by viral proteins delineates a critical role for DDX3 in antiviral host defense.

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Zika virus: mapping and reprogramming the entry

BACKGROUND: The flaviviridae family comprises single-stranded RNA viruses that enter cells via clathrin-mediated pH-dependent endocytosis. Although the initial events of the virus entry have been already identified, data regarding intracellular virus trafficking and delivery to the replication site are limited. The purpose of this study was to map the transport route of Zika virus and to identify the fusion site within the endosomal compartment. METHODS: Tracking of viral particles in the cell was carried out with confocal microscopy. Immunostaining of two structural proteins of Zika virus enabled precise mapping of the route of the ribonucleocapsid and the envelope and, consequently, mapping the fusion site in the endosomal compartment. The results were verified using RNAi silencing and chemical inhibitors. RESULTS: After endocytic internalization, Zika virus is trafficked through the endosomal compartment to fuse in late endosomes. Inhibition of endosome acidification using bafilomycin A1 hampers the infection, as the fusion is inhibited; instead, the virus is transported to late compartments where it undergoes proteolytic degradation. The degradation products are ejected from the cell via slow recycling vesicles. Surprisingly, NH(4)Cl, which is also believed to block endosome acidification, shows a very different mode of action. In the presence of this basic compound, the endocytic hub is reprogrammed. Zika virus-containing vesicles never reach the late stage, but are rapidly trafficked to the plasma membrane via a fast recycling pathway after the clathrin-mediated endocytosis. Further, we also noted that, similarly as other members of the flaviviridae family, Zika virus undergoes furin- or furin-like-dependent activation during late steps of infection, while serine or cysteine proteases are not required for Zika virus maturation or entry. CONCLUSIONS: Zika virus fusion occurs in late endosomes and is pH-dependent. These results broaden our understanding of Zika virus intracellular trafficking and may in future allow for development of novel treatment strategies. Further, we identified a novel mode of action for agents commonly used in studies of virus entry. Schematic representation of differences in ZIKV trafficking in the presence of Baf A1 and NH(4)Cl [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12964-019-0349-z) contains supplementary material, which is available to authorized users.

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Human cytomegalovirus and Herpes Simplex type I virus can engage RNA polymerase I for transcription of immediate early genes

Human cytomegalovirus (HCMV) utilizes RNA polymerase II to transcribe viral genes and produce viral mRNAs. It can specifically target the nucleolus to facilitate viral transcription and translation. As RNA polymerase I (Pol I)-mediated transcription is active in the nucleolus, we investigated the role of Pol I, along with relative contributions of the human Pol II and Pol III, to early phases of viral transcription in HCMV infected cells, compared with Herpes Simplex Virus-1 (HSV-1) and Murine cytomegalovirus (MCMV). Inhibition of Pol I with siRNA or the Pol I inhibitors CX-5461 or Actinomycin D (5nM) resulted in significantly decreased IE and pp65 mRNA and protein levels in human fibroblasts at early times post infection. This initially delayed replication was compensated for later during the replication process, at which stage it didn’t significantly affect virus production. Pol I inhibition also reduced HSV-1 ICP0 and gB transcripts, suggesting that some herpesviruses engage Pol I for their early transcription. In contrast, inhibition of Pol I failed to affect MCMV transcription. Collectively, our results contribute to better understanding of the functional interplay between RNA Pol I-mediated nucleolar events and the Herpes viruses, particularly HCMV whose pathogenic impact ranges from congenital malformations and potentially deadly infections among immunosuppressed patients, up to HCMV’s emerging oncomodulatory role in human tumors.

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Management of breast cancer during COVID‐19 pandemic in Morocco

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Elucidating biophysical basis of binding of inhibitors to SARS-CoV-2 main protease by using molecular dynamics simulations and free energy calculations

The recent outbreak of novel “coronavirus disease 2019” (COVID-19) has spread rapidly worldwide, causing a global pandemic. In the present work, we have elucidated the mechanism of binding of two inhibitors, namely α-ketoamide and Z31792168, to SARS-CoV-2 main protease (M(pro) or 3CL(pro)) by using all-atom molecular dynamics simulations and free energy calculations. We calculated the total binding free energy (ΔG(bind)) of both inhibitors and further decomposed ΔG(bind) into various forces governing the complex formation using the Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) method. Our calculations reveal that α-ketoamide is more potent (ΔG(bind)= − 9.05 kcal/mol) compared to Z31792168 (ΔG(bind)= − 3.25 kcal/mol) against COVID-19 3CL(pro). The increase in ΔG(bind) for α-ketoamide relative to Z31792168 arises due to an increase in the favorable electrostatic and van der Waals interactions between the inhibitor and 3CL(pro). Further, we have identified important residues controlling the 3CL(pro)-ligand binding from per-residue based decomposition of the binding free energy. Finally, we have compared ΔG(bind) of these two inhibitors with the anti-HIV retroviral drugs, such as lopinavir and darunavir. It is observed that α-ketoamide is more potent compared to lopinavir and darunavir. In the case of lopinavir, a decrease in van der Waals interactions is responsible for the lower binding affinity compared to α-ketoamide. On the other hand, in the case of darunavir, a decrease in the favorable intermolecular electrostatic and van der Waals interactions contributes to lower affinity compared to α-ketoamide. Our study might help in designing rational anti-coronaviral drugs targeting the SARS-CoV-2 main protease. Communicated by Ramaswamy H. Sarma

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Clinical features, genetics, and outcome of pediatric patients with hemophagocytic lymphohistiocytosis in Korea: report of a nationwide survey from Korea Histiocytosis Working Party

BACKGROUND: We analyzed a nationwide registry of pediatric patients with hemophagocytic lymphohistiocytosis (HLH) in Korea to assess the clinical and genetic features and treatment outcomes in pediatric HLH. METHODS: The Korea Histiocytosis Working Party retrospectively analyzed data on 251 pediatric patients diagnosed with HLH between 1996 and 2011. RESULTS: In the study cohort, 25 cases were categorized with familial HLH, 64 with presumed secondary HLH, and 162 with unspecified HLH. Of 217 evaluable patients, 91 (42%) had concomitant Epstein–Barr virus infection. Of 238 evaluable patients, central nervous system (CNS) involvement, which was more frequent in the familial group, was evident in 81 cases (34%). Genetic tests revealed a predominant UNC13D mutation with a high incidence of two recurrent splicing mutations (c.118‐308C>T and c.754‐1G>C). The 5‐yr overall survival rate was 68% (38% in the familial group and 81% in the presumed secondary group). The 5‐yr overall survival rate among 32 patients who underwent allogeneic hematopoietic stem cell transplantation was 64%. In multivariate analysis, a younger age at diagnosis, severe transaminasemia, and a coagulation abnormality were independent prognostic factors for survival. Responses during initial treatments were also significant indicators of outcome. CONCLUSION: Our study showed the unique predominance of a UNC13D mutation and vulnerability to Epstein–Barr virus infection in Korean children with HLH and emphasizes the prognostic significance of age, liver dysfunction, and treatment responses in this disease. A multicenter prospective trial that builds on the present results is warranted to identify subgroups of patients with a poor prognosis and identify optimal treatments.

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NLRP3 Inflammasome—A Key Player in Antiviral Responses

The NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome is an oligomeric complex comprised of the NOD-like receptor NLRP3, the adaptor ASC, and caspase-1. This complex is crucial to the host's defense against microbes as it promotes IL-1β and IL-18 secretion and induces pyroptosis. NLRP3 recognizes variety of pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) generated during viral replication that triggers the NLRP3 inflammasome-dependent antiviral immune responses and facilitates viral eradication. Meanwhile, several viruses have evolved elaborate strategies to evade the immune system by targeting the NLRP3 inflammasome. In this review, we will focus on the crosstalk between the NLRP3 inflammasome and viruses, provide an overview of viral infection-induced NLRP3 inflammasome activation, and the immune escape strategies of viruses through their modulation of the NLRP3 inflammasome activity.

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Buscas na internet sobre medidas de enfrentamento à COVID-19 no Brasil: descrição de pesquisas realizadas nos primeiros 100 dias de 2020/ Búsquedas en Internet sobre medidas para combatir el COVID-19 en Brasil: descripción de las investigaciones realizadas en los primeros 100 días de 2020/ Internet searches for measures to address COVID-19 in Brazil: a description of searches in the first 100 days of 2020

Resumo Objetivo descrever os perfis de interesse de busca de informações na internet sobre termos relacionados à epidemia da Covid-19 no Brasil. Métodos realizou-se uma pesquisa quantitativa exploratória usando o Google Health Trends; foram analisados dados diários de interesse, definido como probabilidade de consulta (Pr), sobre 23 termos nas buscas realizadas por usuários conectados no Brasil no período de 1º de janeiro a 9 de abril de 2020. Resultados o pico de interesse (Pr=0,0651) pelo tema coronavirus ocorreu em 21 de março; o interesse pelos temas uso de máscaras (Pr=0,0041), distanciamento social (Pr=0,0043) e higienização das mãos com álcool em gel (Pr=0,0037) foi superior ao interesse pelos temas etiqueta respiratória (Pr=0,0010) e higienização das mãos com água e sabão (Pr=0,0005). Conclusão a diferença de interesse pelos temas relacionados ao combate à Covid-19 foi expressiva e pode orientar novas estratégias de divulgação de informações em saúde.(AU)

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3 Loss of Biological Diversity and Emergence of Infectious Diseases

Abstract: Abiotic factors, climatic factors (such as temperature and rainfall) and biotic factors (such as population density and the structure of host communities and reservoirs) are essential variables in the transmission of infectious or parasitic agents.

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Human Coronavirus NL63 Is Not Detected in the Respiratory Tracts of Children with Acute Kawasaki Disease

Kawasaki disease (KD) is a self-limited, systemic vasculitis of children for which an infectious trigger is suspected. Recently, an association between KD and human coronavirus (HCoV)–New Haven (NH) was reported, on the basis of polymerase chain reaction (PCR) with primers that also amplified HCoV-NL63. We investigated the possible association between these HCoVs in the respiratory tract and KD by reverse-transcriptase (RT) PCR and viral culture in a geographically and ethnically diverse population. Only 1 (2%) of 48 patients with acute KD was positive by RT-PCR for HCoV-NL63/NH in a nasopharyngeal swab. These data do not support an association between these HCoVs and KD.

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Isolated olfactory cleft involvement in SARS-CoV-2 infection: prevalence and clinical correlates

PURPOSE: Smell alterations are a symptom of COVID-19 and have been associated with olfactory cleft mucosal thickening (OCMT). Although their pathogenesis is unclear, evidences link them to viral neuroinvasive potential. This study aims at estimating the prevalence of OCMT in CT scans of COVID-19 patients and investigating its clinical correlates. METHODS: In a single-institution retrospective cross-sectional study, we included all patients hospitalized for COVID-19 undergoing head CT scan for any reason. Exclusion criteria were history of recent head trauma or chronic rhinosinusitis; opacification > 2 mm in any sinonasal space other than the olfactory cleft; CT performed during/after invasive ventilation or feeding via nasogastric tube. We recorded the prevalence of OCMT and related it to age, sex, need for invasive ventilation during hospital stay, outcome, length of hospital stay, diffusion of lung SARS-CoV-19 lesions and outcome. RESULTS: 63 eligible patients were identified (39 male, 24 female; median age 77.82 ± 17.77 years). OCMT was identified in 16 patients (25.4%; 95% CI 15.3–37.9%). Patients with OCMT had longer hospital stays (median 16 ± 4 vs. 9 ± 14.5 days, p = .009, Mann–Whitney U test) and required invasive ventilation more frequently than patients without mucosal thickening (OR 4.89, 95% CI 0.96–24.89, p = .063, Fisher’s test). No other difference was observed. CONCLUSION: OCMT affects nearly one in four patients hospitalized for COVID-19. It is associated with a worse disease course irrespective of age, sex and diffusion of lung lesions, although with no direct effect on survival.

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Lung health in a changing world

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Landscape analysis of pharmacovigilance and related practices among 34 vaccine manufacturers’ from emerging countries

Developing Countries’ Vaccine Manufacturers Network was tasked with the strategic goal of seeking solutions, jointly with manufacturers, for enabling the stable, sustainable supply of quality vaccines to developing countries to increase global immunization. As vaccines are given to millions of healthy people, including children, to prevent life-threatening diseases, vaccines must meet high safety standards. Vaccine safety monitoring is of paramount importance to maintain trust in vaccination programs globally. Once a vaccine is licensed and recommended for use, its safety and effectiveness must be monitored during its whole lifecycle, as the safety profile and protective effectiveness may change over time. A well-established safety governance model across the organization with underlying processes for data collection, signal and risk management and communication is essential. A “fit for purpose” pharmacovigilance system may vary as it depends on several factors. However, all vaccine manufacturers strive to achieve a pharmacovigilance system satisfying Good Pharmacovigilance Practices, in compliance with national, international and supranational requirements, as applicable. A landscape analysis, using a questionnaire covering nine pharmacovigilance key areas related to an effective system, was conducted to understand the existing pharmacovigilance structures, practices and expertise of vaccine manufacturers from emerging countries, on an institutional level. 34 of the 43 contacted manufacturers participated voluntarily. The survey results show that all respondents have established vaccine safety capacity, mainly in collecting and handling adverse events following immunization and implementing standardized processes; the survey also shows differences in the maturity of the manufacturers’ pharmacovigilance system, Quality Management System, signal and risk management, and safety governance. The analysis provides a tool for manufacturers to gain a “bird's-eye” view of the structure of pharmacovigilance key areas and the operational dimensions covered by each area, to benchmarking against international expectations, serving as a basis to further strengthen pharmacovigilance systems, to support accelerated global vaccine supply.

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Cutaneous manifestations in SARS‐CoV‐2 infection (COVID‐19): a French experience and a systematic review of the literature

Skin manifestations have been increasingly reported in the setting of COVID‐19. However, their incidence and presentation are debated, and the role, direct or undirect, of SARS‐CoV‐2 in their pathogenesis has yet to be determined. In this work, we aimed to analyze our experience in a French referral center and to perform a systematic review of the literature to evaluate the incidence and prognosis of cutaneous lesions observed in COVID‐19 patients. Cutaneous manifestations were assessed in COVID‐19 patients admitted to Cochin Hospital (Paris, France) between March 16(th) and April 27(th) 2020. 759 confirmed moderate‐to‐severe COVID‐19 cases were diagnosed in our institution. Eight patients (1%, 6 males, 2 females, mean age 55.6) presented with skin lesions, mainly disseminated maculo‐papular exanthema, but also digitate papulo‐squamous rash (reported in(1)), herpes recurrence, papulo‐vesicular rash and Grover’s disease. The mean delay between respiratory/systemic and dermatological signs was 13 days.

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Recombination in Enteroviruses, a Multi-Step Modular Evolutionary Process

RNA recombination is a major driving force in the evolution and genetic architecture shaping of enteroviruses. In particular, intertypic recombination is implicated in the emergence of most pathogenic circulating vaccine-derived polioviruses, which have caused numerous outbreaks of paralytic poliomyelitis worldwide. Recent experimental studies that relied on recombination cellular systems mimicking natural genetic exchanges between enteroviruses provided new insights into the molecular mechanisms of enterovirus recombination and enabled to define a new model of genetic plasticity for enteroviruses. Homologous intertypic recombinant enteroviruses that were observed in nature would be the final products of a multi-step process, during which precursor nonhomologous recombinant genomes are generated through an initial inter-genomic RNA recombination event and can then evolve into a diversity of fitter homologous recombinant genomes over subsequent intra-genomic rearrangements. Moreover, these experimental studies demonstrated that the enterovirus genome could be defined as a combination of genomic modules that can be preferentially exchanged through recombination, and enabled defining the boundaries of these recombination modules. These results provided the first experimental evidence supporting the theoretical model of enterovirus modular evolution previously elaborated from phylogenetic studies of circulating enterovirus strains. This review summarizes our current knowledge regarding the mechanisms of recombination in enteroviruses and presents a new evolutionary process that may apply to other RNA viruses.

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Carrier proteins for fusion expression of antimicrobial peptides in Escherichia coli

Antimicrobial peptides are an essential component of innate immunity and play an important role in host defence against microbial pathogens. They have received increasing attention recently as potential novel pharmaceutical agents. To meet the requirement for necessary basic science studies and clinical trials, large quantities of these peptides are needed. In general, isolation from natural sources and chemical synthesis are not cost‐effective. The relatively low cost and easy scale‐up of the recombinant approach renders it the most attractive means for large‐scale production of antimicrobial peptides. Among the many systems available for protein expression, Escherichia coli remains the most widely used host. Antimicrobial peptides produced in E. coli are often expressed as fusion proteins, which effectively masks these peptides' potential lethal effect towards the bacterial host and protects the peptides from proteolytic degradation. Although some carriers confer peptide solubility, others promote the formation of inclusion bodies. The present minireview considers the most commonly used carrier proteins for fusion expression of antimicrobial peptides in E. coli. The favourable properties of SUMO (small ubiquitin‐related modifier) as a novel fusion partner are also discussed.

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Ethical framework for head and neck cancer care impacted by COVID‐19

The COVID‐19 pandemic has upended head and neck cancer care delivery in ways unforeseen and unprecedented. The impact of these changes parallels other fields in oncology, but is disproportionate due to protective measures and limitations on potentially aerosolizing procedures and related interventions specific to the upper aerodigestive tract. The moral and professional dimensions of providing ethically appropriate and consistent care for our patients in the COVID‐19 crisis are considered herein for head and neck oncology providers.

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Considerations for Obstetric Care during the COVID-19 Pandemic

The novel coronavirus disease 2019 (COVID-19) is a growing pandemic that is impacting daily life across the globe. Though disease is often mild, in high-risk populations, severe disease often leads to intubation, intensive care admission (ICU) admission, and in many cases death. The implications for pregnancy remain largely unknown. Early data suggest that COVID-19 may not pose increased risk in the pregnant population. Vertical transmission has not been confirmed. Because no treatment, no vaccine and no herd immunity exist, social distancing is the best mechanism available to protect patients and health care workers from infection. This review will discuss what is known about the virus as it relates to pregnancy and then consider management considerations based on these data. Key Points: COVID-19 severity in pregnancy is unclear. Social distancing is the best protective mechanism. No clear evidence of vertical transmission exists. Mother/baby separation avoids transmission.

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Formulation and efficacy evaluation of the safe and efficient moisturizing snow mushroom hand sanitizer

OBJECTIVES: Snow fungus or snow mushroom or white jelly mushroom (Tremella fuciformis), the edible mushroom, was formulated into hand sanitizer in form of moisturizing alcohol‐based hand rubs (ABHR) gel. METHODS: The stable base ABHRs were developed. The preferred bases were incorporated with various concentrations of snow mushroom extract. The stable and preferred snow mushroom ABHR was moisturizing and sanitizing efficacies evaluated in 20 human volunteers in a comparison with its placebo. RESULTS: The stable hand sanitizer gel bases containing 66.5% of ethanol and 0.3% triclosan were developed and incorporated with the extract of snow mushroom polysaccharide. Of which, the preparations containing 10% of snow mushroom and 0.3% of gelling agent gained the highest preferences as assessed in 20 Thai volunteers. The snow mushroom hand sanitizer was proved to be none irritated in the same group of the volunteers as was the placebo. The snow mushroom gel significantly (P < 0.05) moist the skin better than the placebo at all time of the interval assessment until the end of the study at 180 min. The hand sanitizers were confirmed on their anti‐septic, at which the efficacies of the active and placebo ABHR were comparable (P = 0.90). CONCLUSIONS: Snow mushroom ABHR gel with its confirmed moisturizing and sanitizing efficacies is presented. It is meetings with the recommendation on hand hygienic improvement to combat the infections of diseases spreading. The preparation can be frequency applied with its proved skin hydrating efficacy co‐contributes in a good condition of hand hygiene.

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The first evidence of a new genotype of nephropathogenic infectious bronchitis virus circulating in vaccinated and unvaccinated broiler flocks in Algeria

BACKGROUND AND AIM: Avian infectious bronchitis virus (IBV) frequently infects broilers and is responsible for severe economic losses to the poultry industry worldwide. It has also been associated with kidney damage in the broiler flocks. The aim of the present study is to determine the presence of IBV and its possible involvement in kidney damage of broiler chicks. MATERIALS AND METHODS: 14 clinically diseased broiler flocks from Western and Central Algeria were sampled and analyzed by hemagglutination inhibition (HI) test and reverse transcriptase-polymerase chain reaction (RT-PCR) followed by phylogenic analysis. RESULTS: The QX (100%) and 4/91 (60%) IBV serotypes were the most prevalent in the kidney damaged broilers regardless of vaccination status. The molecular detection of avian IBV by RT-PCR identified six samples as positive, of which only two isolates were typable by sequencing. We identified a novel IBDZ13a genotype which showed 93% sequence homology to the partial-S1 gene sequence of the IB 4/91 commercial vaccine strain. Sequencing analysis characterized this virus as a novel and divergent IB 4/91 field virus with eight amino acid substitutions that might have resulted in altered immunogenicity. CONCLUSION: The isolation of a new IBV strain (IBDZ13a) from vaccinated broiler flocks may explain the failure of the vaccination programs against IBV field strains. Combination of the HI test and RT-PCR indicated that the nephropathogenic IB outbreaks in broilers are related to this novel strain.

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Monitoring infectious diseases in the big data era

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Unsupervised cluster analysis of SARS-CoV-2 genomes reflects its geographic progression and identifies distinct genetic subgroups of SARS-CoV-2 virus

Over 10,000 viral genome sequences of the SARS-CoV-2 virus have been made readily available during the ongoing coronavirus pandemic since the initial genome sequence of the virus was released on the open access Virological website (http://virological.org/) early on January 11. We utilize the published data on the single stranded RNAs of 11, 132 SARS-CoV-2 patients in the GISAID (Elbe and Buckland-Merrett, 2017; Shu and McCauley, 2017) database, which contains fully or partially sequenced SARS-CoV-2 samples from laboratories around the world. Among many important research questions which are currently being investigated, one aspect pertains to the genetic characterization/classification of the virus. We analyze data on the nucleotide sequencing of the virus and geographic information of a subset of 7, 640 SARS-CoV-2 patients without missing entries that are available in the GISAID database. Instead of modelling the mutation rate, applying phylogenetic tree approaches, etc., we here utilize a model-free clustering approach that compares the viruses at a genome-wide level. We apply principal component analysis to a similarity matrix that compares all pairs of these SARS-CoV-2 nucleotide sequences at all loci simultaneously, using the Jaccard index (Jaccard, 1901; Tan et al., 2005; Prokopenko et al., 2016; Schlauch et al., 2017). Our analysis results of the SARS-CoV-2 genome data illustrates the geographic and chronological progression of the virus, starting from the first cases that were observed in China to the current wave of cases in Europe and North America. We also observe that, based on their sequence data, the SARS-CoV-2 viruses cluster in distinct genetic subgroups. It is the subject of ongoing research to examine whether the genetic subgroup could be related to diseases outcome and its potential implications for vaccine development.

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Cardiopulmonary Resuscitation in Intensive Care Unit patients with COVID-19

Cardiopulmonary resuscitation (CPR) in SARS-CoV-2-associated disease (COVID-19) patients poses a unique challenge to health care providers due to the risk of viral aerosolization and disease transmission. This has caused some centers to modify existing CPR procedures, limit the duration of CPR or consider avoiding CPR altogether. In this review, we propose a procedure for CPR in the ICU that minimizes the number of personnel in the immediate vicinity of the patient and conserves the use of scarce personal protection equipment (PPE). Highlighting the low likelihood of successful resuscitation in high risk patients may prompt them to decline CPR. We recommend the preemptive placement of central venous lines in high risk patients with intravenous tubing extensions that allow medication delivery from outside the patients’ rooms. During CPR, this practice can be used to deliver critical medications without delay. The use of a mechanical compression system for CPR further reduces the risk of infectious exposure to health care providers. ECMO should be reserved for patients with few comorbidities and a single failing organ system. Reliable teleconferencing tools are essential to facilitate communication between providers inside and outside of the patient's room. General principles regarding the ethics and peri-resuscitative management of COVID-19 patients are also discussed.

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A combination of mutations in the S1 part of the spike glycoprotein gene of coronavirus MHV-A59 abolishes demyelination

The A59 strain of coronavirus, mouse hepatitis virus (MHV), produces acute hepatitis, meningoencephalitis, and chronic demyelination. The authors have previously shown that the spike (S) glycoprotein gene of MHV contains determinants of virulence, hepatitis, and demyelination. They then identified viruses containing mutations in the S gene that exhibit alterations in viral pathogenesis. In the present study, the authors produced new recombinant viruses with each one of these S gene mutations by site-directed mutagenesis and targeted recombination and studied the effect of each individual mutation on the pathogenesis of the virus. They identified a combination of mutations in the S1 gene (I375M and L652I) that abolishes demyelination. Individual mutation and other combinations of mutations in the S gene only interfere with virulence and hepatitis and only reduce demyelination (I375M), but do not abolish demyelination completely. Thus, demyelination determinants exist within genomic regions on both sides of the hypervariable region, downstream from the receptor-binding domain in the S1 part of the MHV spike glycoprotein gene. The structure and precise function of these regions awaits further investigation.

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A novel methodology for large-scale phylogeny partition

Understanding the determinants of virus transmission is a fundamental step for effective design of screening and intervention strategies to control viral epidemics. Phylogenetic analysis can be a valid approach for the identification of transmission chains, and very-large data sets can be analysed through parallel computation. Here we propose and validate a new methodology for the partition of large-scale phylogenies and the inference of transmission clusters. This approach, on the basis of a depth-first search algorithm, conjugates the evaluation of node reliability, tree topology and patristic distance analysis. The method has been applied to identify transmission clusters of a phylogeny of 11,541 human immunodeficiency virus-1 subtype B pol gene sequences from a large Italian cohort. Molecular transmission chains were characterized by means of different clinical/demographic factors, such as the interaction between male homosexuals and male heterosexuals. Our method takes an advantage of a flexible notion of transmission cluster and can become a general framework to analyse other epidemics.

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Advocacy, promotion and e-learning: Supercourse for zoonosis

This paper discusses the history of emerging infectious diseases, risk communication and perception, and the Supercourse lectures as means to strengthen the concepts and definition of risk management and global governance of zoonosis. The paper begins by outlining some of the key themes and issues in infectious diseases, highlighting the way which historical analysis challenges ideas of the ‘newness’ of some of these developments. It then discusses the role of risk communication to public accountability. The bulk of the paper presents an overview of developments of the Internet-based learning system through the Supercourse lectures that may prove to be a strong arm for the promotion of the latest medical information particularly to developing countries.

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Pandemic Disease: A Past and Future Challenge to Governance in the United States

Throughout history, pandemics have posed significant challenges to governments. Examination of the ways that governments have responded to pandemics can contribute to the U.S. government's ability to react in the future. We utilize past cases of Severe Acute Respiratory Syndrome (SARS) and multiple forms of influenza to identify specific challenges governments have faced. Based on that knowledge, we discuss the major issues that the United States will have to address in the event of a future pandemic.

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Assessing Continuous Quality Improvement in Public Health: Adapting Lessons from Healthcare

CONTEXT: Evidence of the effect of continuous quality improvement (CQI) in public health and valid tools to judge that such effects are not fully formed. OBJECTIVE: The objective was to adapt and apply Shortell et al.'s (1998) four dimensions of CQI in an examination of a public health accountability and performance management initiative in Ontario, Canada. METHODS: In total, 24 semi-structured, in-depth interviews were conducted with informants from public health units and the Ministry of Health and Long-Term Care. A web survey of public health managers in the province was also carried out. RESULTS: A mix of facilitators and barriers was identified. Leadership and organizational cultures, conducive to CQI success were evident. However, limitations in performance measurement and managerial discretion were key barriers. CONCLUSION: The four dimensions of CQI provided insight into both facilitators and barriers of CQI adoption in public health. Future research should compare the outcomes of public health CQI initiatives to the framework's stated facilitators and barriers.

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Avian influenza aided readiness for swine flu

Despite gains from threat of bird flu, pandemic preparedness is patchy.

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Assessment of pathogenicity and tissue distribution of infectious bronchitis virus strains (Italy 02 genotype) isolated from moroccan broiler chickens

BACKGROUND: Avian infectious bronchitis (IB) is one of the most important viral diseases of poultry, affecting chickens of all ages and causing major economic losses in poultry flocks. Mass vaccination is conducted in Morocco using a vaccine against Massachusetts, which is the most dominant serotype; however no information about the pathogenesis and tissue distribution of the Moroccan Italy 02 genotype was reported. 40 one-day-old specific pathogen free chickens were divided randomly into four groups. Group1, 2 and 3 were inoculated intra oculo-nasally with 103.5 EID50 of Italy02 viruses, and group 4 was kept as control. Chickens in each group were monitored for 14 days post-infection (pi). RESULTS: Chickens in all infected groups showed severe respiratory signs, which most of them have been reproduced on 2dpi, with varying times of appearance and disappearance. The infected birds appeared lethargic, reluctant to move, with specific respiratory clinical signs and macroscopic lesions. However no nephritis lesions or mortality were recorded in all groups. The specific histological lesions finding in all infected birds, exhibited tracheal lesions with mucosal thickening, hyperplasia of the surface epithelium, mononuclear inflammatory cell infiltrate of lamina propria. Primary and secondary bronchi, epithelial hyperplasia and mononuclear inflammatory cell infiltrate of the lamina propria were also observed. Tracheal lesions developed in all infected birds, confirm the ability of the three tested strains to induce respiratory disease. The results at 14 dpi also revealed that all strains were able to induce serological response. Virus re-isolation from infected organs and amplification of the viral RNA by real-time PCR proved the presence of the virus in lung and trachea of infected chicks. Neither re-isolation nor significant viral RNA detection were detected in the kidney. CONCLUSION: The results demonstrated that the three strains Italy02 genotype emerging in Moroccan poultry farms have a wide distribution for respiratory system, without kidney damage and without causing mortality.

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Sharing public health data and information across borders: lessons from Southeast Asia

BACKGROUND: The importance of data and information sharing for the prevention and control of infectious diseases has long been recognised. In recent years, public health emergencies such as avian influenza, drug-resistant malaria, and Ebola have brought renewed attention to the need for effective communication channels between health authorities, particularly in regional contexts where neighbouring countries share common health threats. However, little empirical research has been conducted to date to explore the range of factors that may affect the transfer, exchange, and use of public health data and expertise across borders, especially in developing contexts. METHODS: To explore these issues, 60 interviews were conducted with domestic and international stakeholders in Cambodia and Vietnam, selected amongst those who were involved in regional public health programmes and networks. Data analysis was structured around three categories mapped across the dataset: (1) the nature of shared data and information; (2) the nature of communication channels; and (3) how information flow may be affected by the local, regional, and global system of rules and arrangements. RESULTS: There has been a great intensification in the circulation of data, information, and expertise across borders in Southeast Asia. However, findings from this study document ways in which the movement of data and information from production sites to other places can be challenging due to different standards and practices, language barriers, different national structures and rules that govern the circulation of health information inside and outside countries, imbalances in capacities and power, and sustainability of financing arrangements. CONCLUSIONS: Our study highlights the complex socio-technical nature of data and information sharing, suggesting that best practices require significant involvement of an independent third-party brokering organisation or office, which can redress imbalances between country partners at different levels in the data sharing process, create meaningful communication channels and make the most of shared information and data sets.

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Lectins from the Edible Mushroom Agaricus bisporus and Their Therapeutic Potentials

The mushroom Agaricus bisporus secretes biologically active compounds and proteins with benefits for human health. Most reported proteins from A. bisporus are tyrosinases and lectins. Lectins are of therapeutic or pharmaceutical interest. To date, only limited information is available on A. bisporus lectins and lectin-like proteins. No therapeutic products derived from A. bisporus lectin (ABL) are available on the market despite its extensive exploration. Recently, A. bisporus mannose-binding protein (Abmb) was discovered. Its discovery enriches the information and increases the interest in proteins with therapeutic potential from this mushroom. Furthermore, the A. bisporus genome reveals the possible occurrence of other lectins in this mushroom that may also have therapeutic potential. Most of these putative lectins belong to the same lectin groups as ABL and Abmb. Their relationship is discussed. Particular attention is addressed to ABL and Abmb, which have been explored for their potential in medicinal or pharmaceutical applications. ABL and Abmb have anti-proliferative activities toward cancer cells and a stimulatory effect on the immune system. Possible scenarios for their use in therapy and modification are also presented.

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Forensic mental telehealth assessment (FMTA) in the context of COVID-19

Due to the present COVID-19 pandemic, forensic mental telehealth assessment (FMTA) is an increasingly utilized means of conducting court-sanctioned psychiatric and psychological evaluations. FMTA is not a novel development, and studies have been published during the past two decades that opine on the positive and negative implications of conducting testing and interview procedures online, in forensic and traditionally clinical matters alike. The present article examines the prospects for eventual legal challenges to FMTA, describes considerations for conducting FMTA in both institutional and residential settings, and concludes that FMTA is now—due to predicted accommodations on the part of courts, attorneys, institutions, and professional guilds—a permanent part of the forensic evaluation landscape, even once the present COVID-19 pandemic has subsided.

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Situation der Deutschen Universitätspathologien unter den Einschränkungen der Corona-Pandemie – Auswertung einer ersten repräsentativen Umfrage

German University Pathologies are affected by the Corona Pandemics and respective measures. A survey among all 36 University Pathologies was conducted (return rate 83%) and evaluated; it allows to assess the current situation and shows significant restrictions in the diagnostic and research performance and high willingness to perform Coviid autopsies

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Chapter 15 Cord Blood Banking Operational and Regulatory Aspects

Abstract Umbilical cord blood (UCB) is an alternative source of hematopoietic stem cells for transplantation in patients with hematological malignancies, bone marrow failures, immunodeficiencies, and inherited metabolic disorders. In order to facilitate these transplants, large repositories of frozen UCB units collected from altruistic unrelated donations have been established and to date there are more than 600,000 units stored in cord blood banks all over the world. These products have been collected, stored, and released for transplantation under stringent quality conditions in order to ensure their safety and efficacy. The development and evolution of the policies and procedures currently in use in cord blood banking have been largely influenced by the clinical outcome of the transplants performed using these units. This review will describe some of the main steps and procedures involved in the clinical banking of unrelated UCB donations starting from the recruitment and selection of the potential donor (the mother) to the final distribution of the unit to the transplant program and its clinical outcome follow-up.

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A simple method for differentiating direct and indirect exposure to exhaled contaminants in mechanically ventilated rooms

Many airborne infectious diseases can be transmitted via exhaled contaminants transported in the air. Direct exposure occurs when the exhaled jet from the infected person directly enters the breathing zone of the target person. Indirect exposure occurs when the contaminants disperse in the room and are inhaled by the target person. This paper presents a simple method for differentiating the direct and indirect exposure to exhaled contaminants in mechanically ventilated rooms. Experimental data for 191 cases were collected from the literature. After analyzing the data, a simple method was developed to differentiate direct and indirect exposure in mixing and displacement ventilated rooms. The proposed method correctly differentiated direct and indirect exposure for 120 out of the 133 mixing ventilation cases and 47 out of the 58 displacement ventilation cases. Therefore, the proposed method is suitable for use at the early design stage to quickly assess whether there will be direct exposure to exhaled contaminants in a mechanically ventilated room.

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Pre-existing immunity to SARS-CoV-2: the knowns and unknowns

T cell reactivity against SARS-CoV-2 was observed in unexposed people; however, the source and clinical relevance of the reactivity remains unknown. It is speculated that this reflects T cell memory to circulating ‘common cold’ coronaviruses. It will be important to define specificities of these T cells and assess their association with COVID-19 disease severity and vaccine responses.

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Valor pronóstico de biomarcadores cardíacos en la enfermedad por COVID-19

Resumen Introducción: en la enfermedad por COVID-19 se ha establecido que los pacientes con enfermedad cardiometabólica de base, tienen mayor riesgo de presentar desenlaces adversos. Esto ha incrementado el interés en estudiar variables cardiovasculares relevantes, para plantear su correlación con los desenlaces clínicos en esta población. Objetivo: describir el valor pronóstico de los biomarcadores cardíacos en la enfermedad por COVID-19. Métodos: revisión no sistemática de la literatura en bases de datos como PubMed, Google Scholar, Clinical Key, SciELO, entre otras, utilizando palabras clave, términos planos y términos MeSh. Resultados: se eligieron 22 bibliografías, entre ellas artículos de revisión de tema, revisiones sistemáticas, metaanálisis, estudios observacionales y artículos originales publicados hasta la fecha (mayo 13 de 2020), que en la mayoría describen la alteración de biomarcadores cardiacos y su relación con la evolución clínica de los pacientes con COVID-19. Discusión: se encontró que la troponina y el péptido natriurético se comportan como factores de riesgo independientes para compromiso clínico severo, requerimiento de soporte ventilatorio o hemodinámico, estancia en la UCI, y aumento de la mortalidad. Conclusiones: es razonable plantear el uso de estos biomarcadores en la estratificación del riesgo en pacientes con COVID-19 y enfermedad cardiovascular establecida. Abstract Introduction: It has been established that patients with an underlying cardiometabolic disease and COVID-19 infections, have a higher risk of an adverse outcome. This has led to an increase in the interest of studying relevant cardiovascular variables, in order to establish their association with clinical outcomes in this population. Objective: To describe the prognostic value of cardiac biomarkers in disease caused by COVID-19. Methods: A non-systematic review of the literature was carried out in data bases that included PubMed, Google Scholar, Clinical Key, SciELO, using the keywords, plain terms, and MeSH terms. Results: A total of 22 articles were chosen. They consisted of review articles on the subject, systematic reviews, meta-analyses, observational studies, and original articles published up until 13 May 2020. The majority of them described the changes in cardiac biomarkers and their relationship with the clinical outcome of patients COVID-19. Discussion: It was found that Troponin and Natriuretic Peptide behaved as independent risk factors for severe clinical compromise, requiring ventilatory or haemodynamic support, admission to ICU, and an increase in mortality. Conclusions: It is reasonable to recommend the use of these biomarkers in the stratification of risk in patients with COVID-19 and an established cardiovascular disease.

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Prevention of EAE in non-human primates by a type IV phosphodiesterase inhibitor that suppresses tumor necrosis factor

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Impact of COVID-19 on pediatric asthma: practice adjustments and disease burden.

Abstract Background It is unclear whether asthma may affect susceptibility or severity of the Coronavirus Disease 2019 (COVID-19) in children and how pediatric asthma services worldwide have responded to the pandemic. Objective To describe the impact of the COVID-19 pandemic on pediatric asthma services and on disease burden in their patients. Methods An online survey was sent to members of the Pediatric Asthma in Real Life (PeARL) think-tank and the World Allergy Organization Pediatric Asthma Committee. It included questions on service provision, disease burden and on the clinical course of confirmed cases of COVID-19 infection among children with asthma. Results Ninety-one respondents, caring for an estimated population of >133,000 children with asthma, completed the survey. COVID-19 significantly impacted pediatric asthma services: 39% ceased physical appointments, 47% stopped accepting new patients, 75% limited patients visits. Consultations were almost halved to a median of 20 (IQR: 10-25) patients per week. Virtual clinics and helplines were launched in most centers. Better than expected disease control was reported in 20% (10-40%) of patients, while control was negatively affected in only 10% (7.5-12.5%). Adherence also appeared to increase. Only 15 confirmed cases of COVID-19 were reported among the population; the estimated incidence is not apparently different from the reports of general pediatric cohorts. Conclusion Children with asthma do not appear to be disproportionately affected by COVID-19. Outcomes may even have improved, possibly through increased adherence and/or reduced exposures. Clinical services have rapidly responded to the pandemic by limiting and replacing physical appointments with virtual encounters.

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The Ebola Virus Disease Outbreak in West Africa: A Wake-up Call to Revitalize Implementation of the International Health Regulations

The 2014/15 Ebola virus disease (EVD) outbreak in West Africa has highlighted the inherent weaknesses associated with the implementation of the International Health Regulations (IHR). In this perspective article, the lessons learnt from the outbreak are used to review the challenges impeding effective implementation of the IHR and to propose policy and strategic options for enhancing its application. While some progress has been achieved in implementing the IHR in several countries, numerous challenges continue to impede its effectiveness, especially in developing countries, such as those affected by the West Africa EVD outbreak. Political and economic sensitivities associated with reporting public health emergencies of international concern (PHEIC), inadequate resources (human and financial), and lack of technical know-how required for implementation of the IHR are weaknesses that continue to constrain the implementation of the regulations. In view of the complex sociopolitical, cultural, and public health dimensions of PHEICs, frameworks, such as the IHR, which have legal backing, seem to be the most effective and sustainable option for assuring timely detection, notification, and response to such events. Renewed efforts to strengthen national and global institutional frameworks for implementation of the IHR are therefore required. Improvements in transparency, commitment, and accountability of parties to the IHR, mainstreaming of the IHR into national public health governance structures, use of multidisciplinary approaches, and mobilization of the required resources for the implementation of the IHR are imperative.

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Core Minimal Datasets to Advance Clinical Research for Priority Epidemic Diseases

The Ebola virus disease outbreak in west Africa has prompted significant progress in responding to the clinical needs of patients affected by emerging infectious disease outbreaks. Among the noteworthy successes of vaccine trials, and the commendable efforts to implement clinical treatment trials during Ebola outbreaks, we should also focus on strengthening the collection and curation of epidemiological and observational data that can improve the conception and design of clinical research.

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Replication and immune response in HAE of HCoV-HKU1 isolate from a pediatric patient with severe acute respiratory infection

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Matrix metalloproteinase 3 as a valuable marker for patients with COVID‐19

The situation of the coronavirus disease 2019 (COVID‐19) continues to evolve, our study explored the significance of serum levels of matrix metalloproteinase 3 (MMP3) as a marker for patients with COVID‐19. Sixty‐two COVID‐19 patients in the First Hospital of Hunan University of Chinese Medicine and Loudi Center for Diseases Prevention and Control, from January to March 2020, were sampled as the novel coronavirus pneumonia infected group. One hundred and thirty‐one cases from the First Hospital of Hunan University of Chinese Medicine, including 67 healthy individuals and 64 non‐COVID‐19 inpatients, served as the noninfected group. Approximately every 5 days, sera from 20 cases were collected and analyzed three times, using an automatic biochemical analyzer, to detect serum MMP3 concentrations. Correlation was analyzed between MMP3 and other proinflammatory cytokines. Following normality tests, differences in serum MMP3 levels between the infected and noninfected group were analyzed via SPSS (version 25.0) software, using the Wilcoxon rank sum test. The MMP3 concentration was 44.44 (23.46 ~ 72.12) ng/mL in the infected group and 32.42 (28.16 ~ 41.21) ng/mL in the noninfected group. The difference between the two groups was statistically significant (Z = −2.799, P = .005 < .05). A positive correlation was found between MMP3 and interleukin 1β (IL‐1β; r = .681, P = .000 < .05), and IL‐6 (r = .529, P = .002 < .05). Serum MMP3 concentration, measured over three separate time points, were 55.98 (30.80 ~ 75.97) ng/mL, 34.84 (0.00 ~ 51.84) ng/mL, and 5.71 (0.00 ~ 40.46) ng/mL, respectively. Detection of serum MMP3 levels may play an important role in the development of therapeutic approaches for COVID‐19 and may indicate the severity of disease.

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Broad Spectrum Antiviral Agent Niclosamide and Its Therapeutic Potential

[Image: see text] The recent outbreak of coronavirus disease 2019 (COVID-19) highlights an urgent need for therapeutics. Through a series of drug repurposing screening campaigns, niclosamide, an FDA-approved anthelminthic drug, was found to be effective against various viral infections with nanomolar to micromolar potency such as SARS-CoV, MERS-CoV, ZIKV, HCV, and human adenovirus, indicating its potential as an antiviral agent. In this brief review, we summarize the broad antiviral activity of niclosamide and highlight its potential clinical use in the treatment of COVID-19.

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Discussies in crisistijd

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Immunofluorescence Assay for Serologic Diagnosis of SARS

We evaluated a virus-infected cell-based indirect immunofluorescence assay for detecting anti–severe acute respiratory syndrome-associated coronavirus (SARS-CoV) immunoglobulin (Ig) G antibody. All confirmed SARS cases demonstrated seroconversion or fourfold rise in IgG antibody titer; no control was positive. Sensitivity and specificity of this assay were both 100%. Immunofluorescence assay can ascertain the status of SARS-CoV infection.

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Repurposing old drugs as antiviral agents for coronaviruses

BACKGROUND: New therapeutic options to address the ongoing COVID-19 pandemic are urgently needed. One possible strategy is the repurposing of existing drugs approved for other indications as antiviral agents for SARS-CoV-2. Due to the commercial unavailability of SARS-CoV-2 drugs for treating COVID-19, we screened approximately 250 existing drugs or pharmacologically active compounds for their inhibitory activities against feline infectious peritonitis coronavirus (FIPV) and human coronavirus OC43 (HCoV-OC43), a human coronavirus in the same genus (Betacoronavirus) as SARS-CoV-2. METHODS: FIPV was proliferated in feline Fcwf-4 cells and HCoV-OC43 in human HCT-8 cells. Viral proliferation was assayed by visualization of cytopathic effects on the infected Fcwf-4 cells and immunofluorescent assay for detection of the nucleocapsid proteins of HCoV-OC43 in the HCT-8 cells. The concentrations (EC(50)) of each drug necessary to diminish viral activity to 50% of that for the untreated controls were determined. The viabilities of Fcwf-4 and HCT-8 cells were measured by crystal violet staining and MTS/PMS assay, respectively. RESULTS: Fifteen out of the 252 drugs or pharmacologically active compounds screened were found to be active against both FIPV and HCoV-OC43, with EC(50) values ranging from 11 nM to 75 μM. They are all old drugs as follows, anisomycin, antimycin A, atovaquone, chloroquine, conivaptan, emetine, gemcitabine, homoharringtonine, niclosamide, nitazoxanide, oligomycin, salinomycin, tilorone, valinomycin, vismodegib. CONCLUSION: All of the old drugs identified as having activity against FIPV and HCoV-OC43 have seen clinical use in their respective indications and are associated with known dosing schedules and adverse effect or toxicity profiles in humans. Those, when later confirmed to have an anti-viral effect on SARS-CoV-2, should be considered for immediate uses in COVID-19 patients.

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COVID‐19 mortality in patients on anticoagulants and antiplatelet agents

Coagulopathy (Tang, et al 2020) and a prothrombotic diathesis with high D‐dimer and fibrinogen levels (Al‐Samkari, et al 2020) are associated with coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Extensive thrombosis in small vessels and the microvasculature in lungs and extrapulmonary organs has been confirmed histologically (Zhang et al 2020). Early studies showed that the venous thromboembolism (VTE) incidence in hospitalised COVID‐19 patients can be as high as 25% (Songping, et al 2020), and more recent studies have indicated this can be expanded to other macrovascular thrombotic complications, such as a higher than expected prevalence of pulmonary emboli in patients with COVID‐19 (Klok, et al 2020, Stoneham, et al).

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Pain: A Potential New Label of COVID-19

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Promoting attachment between parents and neonates despite the COVID‐19 pandemic

Social distancing is the only option available during the COVID‐19 pandemic until a vaccine is developed. However, this is having a major impact on human relationships and bonding between parents and neonates is a major concern. Separation during this health emergency could have lifelong consequences for offspring and there are even greater concerns if newborn infants are sick or vulnerable and need intensive care. We look at how bonding can be safely supported and maintained without risking infecting neonates, by comparing the international guidelines and proposing safe actions within those frameworks.

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Cyclophilin A Associates with Enterovirus-71 Virus Capsid and Plays an Essential Role in Viral Infection as an Uncoating Regulator

Viruses utilize host factors for their efficient proliferation. By evaluating the inhibitory effects of compounds in our library, we identified inhibitors of cyclophilin A (CypA), a known immunosuppressor with peptidyl-prolyl cis-trans isomerase activity, can significantly attenuate EV71 proliferation. We demonstrated that CypA played an essential role in EV71 entry and that the RNA interference-mediated reduction of endogenous CypA expression led to decreased EV71 multiplication. We further revealed that CypA directly interacted with and modified the conformation of H-I loop of the VP1 protein in EV71 capsid, and thus regulated the uncoating process of EV71 entry step in a pH-dependent manner. Our results aid in the understanding of how host factors influence EV71 life cycle and provide new potential targets for developing antiviral agents against EV71 infection.

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There are no best practices in a pandemic: Organ donation within the COVID‐19 epicenter

LiveOnNY, the organ procurement organization (OPO) for the greater New York metropolitan area, suspended several best practices to manage the rising referrals of deaths from hospitals during the SARS‐CoV‐2 pandemic. On April 2, 2020 hospitals in the donor service area were notified that COVID‐19 referrals should be deferred. Still, only 2% of referred patients to the OPO in April, 2020 were on ventilators and considered possible organ donors, versus a baseline of 11% in 2019. Few of these deaths were unrelated to COVID‐19. Accordingly, organ donors declined to 10 in April (from 26 in March). Despite the exclusion of marginal donors and organs, the implementation of COVID‐19 donor testing and the availability of local procurement surgeons, only 1 organ (a liver) was accepted by a transplant center outside of New York State and 8 organs (5 livers, 4 kidneys) were transplanted in state. 11 organs (1 liver, 10 kidneys) were discarded. Allocation was unsuccessful for 11 additional organs (1 liver, 4 kidneys, 4 hearts, 2 lungs). Despite the obstacles, organ donation remained an important model of collaboration and satisfaction for the healthcare community in the pandemic’s U.S. epicenter. Declining COVID‐19 deaths led to the resumption of the comprehensive referral policy on May 6, 2020, with improvement to 18 donors in May.

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Cutaneous manifestations in COVID‐19: Family cluster of Urticarial Rash

Coronavirus disease (COVID‐19) is rapidly spread across the world. Many clinical manifestations of the virus are described, and new symptoms are emerging, only few cases of patients with skin manifestation were described since the pandemic was announced by the WHO on March. Common clinical features of COVID‐19 reported include fever, cough, myalgia, fatigue, headache, shortness of breath and diarrhea.

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The role of airway macrophages in apoptotic cell clearance following acute and chronic lung inflammation

Acute and chronic inflammatory responses in the lung are associated with the accumulation of large quantities of immune and structural cells undergoing apoptosis, which need to be engulfed by phagocytes in a process called ‘efferocytosis’. Apoptotic cell recognition and removal from the lung is mediated predominantly by airway macrophages, though immature dendritic cells and non-professional phagocytes, such as epithelial cells and mesenchymal cells, can also display this function. Efficient clearance of apoptotic cells from the airways is essential for successful resolution of inflammation and the return to lung homeostasis. Disruption of this process leads to secondary necrosis of accumulating apoptotic cells, release of necrotic cell debris and subsequent uncontrolled inflammatory activation of the innate immune system by the released ‘damage associated molecular patterns’ (DAMPS). To control the duration of the immune response and prevent autoimmune reactions, anti-inflammatory signalling cascades are initiated in the phagocyte upon apoptotic cell uptake, mediated by a range of receptors that recognise specific phospholipids or proteins externalised on, or secreted by, the apoptotic cell. However, prolonged activation of apoptotic cell recognition receptors, such as the family of receptor tyrosine kinases Tyro3, Axl and MerTK (TAM), may delay or prevent inflammatory responses to subsequent infections. In this review, we will discuss recent advances in our understanding of the mechanism controlling apoptotic cell recognition and removal from the lung in homeostasis and during inflammation, the contribution of defective efferocytosis to chronic inflammatory lung diseases, such as chronic obstructive pulmonary disease, asthma and cystic fibrosis, and implications of the signals triggered by apoptotic cells in the susceptibility to pulmonary microbial infections.

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A dynamic vaccination strategy to suppress the recurrent epidemic outbreaks

Abstract Efficient vaccination strategy is crucial for controlling recurrent epidemic spreading on networks. In this paper, based on the analysis of real epidemic data and simulations, it’s found that the risk indicator of recurrent epidemic outbreaks could be determined by the ratio of the epidemic infection rate of the year to the average infected density of the former year. According to the risk indicator, the dynamic vaccination probability of each year can be designed to suppress the epidemic outbreaks. Our simulation results show that the dynamic vaccination strategy could effectively decrease the maximal and average infected density, and meanwhile increase the time intervals of epidemic outbreaks and individuals attacked by epidemic. In addition, our results indicate that to depress the influenza outbreaks, it is not necessary to keep the vaccination probability high every year; and adjusting the vaccination probability at right time could decrease the outbreak risks with lower costs. Our findings may present a theoretical guidance for the government and the public to control the recurrent epidemic outbreaks.

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CSANZ Position Statement on the Evaluation of Patients Presenting With Suspected Acute Coronary Syndromes During the COVID-19 Pandemic #

Abstract A pandemic of Coronavirus-19 disease was declared by the World Health Organization on March 11, 2020. The pandemic is expected to place unprecedented demand on health service delivery. This position statement has been developed by the Cardiac Society of Australia and New Zealand to assist clinicians to continue to deliver rapid and safe evaluation of patients presenting with suspected acute cardiac syndrome at this time. The position statement complements, and should be read in conjunction with, the National Heart Foundation of Australia & Cardiac Society of Australia and New Zealand: Australian Clinical Guidelines for the Management of Acute Coronary Syndromes 2016: Section 2 ‘Assessment of Possible Cardiac Chest Pain’.

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The philosophy of paediatric teaching: An interview with Dr Nikolaos Myriokefalitakis, former Clinical Director of the ‘Penteli’ Children's Hospital in Athens (Greece)

Dr Nikolaos Myriokefalitakis, one of the most experienced paediatricians in the city of Athens, Greece, has worked as a consultant paediatrician at the ‘P. & A. Kyriakou’ Children's Hospital for more than 25 years, while during the 2004–2011 period, he was the clinical director of the 1st Paediatric Department of the ‘Penteli’ Children's Hospital. Under his leadership, in 2008, his department was renovated by ‘Stavros Niarchos Foundation’ and was organised as one of the most modern and exemplary national paediatric departments in Greece. Having the title of the ‘teacher in paediatrics’ by his junior Greek colleagues, he supports that clinical experience obtained through ward-based bedside teaching is the fundamental principle of paediatric teaching. He notes that paediatric diagnosis is performed thorough medical history and detailed physical examination of the patient and it is rarely established with the help of laboratory, common or specialised, investigations. According to Dr Myriokefalitakis, a modern paediatric department cannot function ‘in a vacuum’, but requires technological support, adequate medical and nursing personnel and team-working between paediatricians and experts on paediatric subspecialties and other basic specialties. He accepts that the current financial crisis in Greece has clearly affected negatively the clinical practice of primary as well as hospital-based paediatric care, while he regrets to note that as the years go by, physicians become more obsessed with defense medicine and technology. He suggests that it is necessary to distinguish paediatric virology from virology and he ends up encouraging the improvement of paediatric training in Greece highlighting the basic need to ‘train the trainers’ in medical education.

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Clinical and CT features in pediatric patients with COVID‐19 infection: Different points from adults

PURPOSE: To discuss the different characteristics of clinical, laboratory, and chest computed tomography (CT) in pediatric patients from adults with 2019 novel coronavirus (COVID‐19) infection. METHODS: The clinical, laboratory, and chest CT features of 20 pediatric inpatients with COVID‐19 infection confirmed by pharyngeal swab COVID‐19 nucleic acid test were retrospectively analyzed during 23 January and 8 February 2020. The clinical and laboratory information was obtained from inpatient records. All the patients were undergone chest CT in our hospital. RESULTS: Thirteen pediatric patients (13/20, 65%) had an identified history of close contact with COVID‐19 diagnosed family members. Fever (12/20, 60%) and cough (13/20, 65%) were the most common symptoms. For laboratory findings, procalcitonin elevation (16/20, 80%) should be pay attention to, which is not common in adults. Coinfection (8/20, 40%) is common in pediatric patients. A total of 6 patients presented with unilateral pulmonary lesions (6/20, 30%), 10 with bilateral pulmonary lesions (10/20, 50%), and 4 cases showed no abnormality on chest CT (4/20, 20%). Consolidation with surrounding halo sign was observed in 10 patients (10/20, 50%), ground‐glass opacities were observed in 12 patients (12/20, 60%), fine mesh shadow was observed in 4 patients (4/20, 20%), and tiny nodules were observed in 3 patients (3/20, 15%). CONCLUSION: Procalcitonin elevation and consolidation with surrounding halo signs were common in pediatric patients which were different from adults. It is suggested that underlying coinfection may be more common in pediatrics, and the consolidation with surrounding halo sign which is considered as a typical sign in pediatric patients.

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La Obesidad y el coronavirus 2019-nCoV. Una relación de riesgo

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Response to the commentary by Pisoni E. and Van Dingenen R. on ‘Assessing nitrogen dioxide (NO(2)) levels as a contributing factor to coronavirus (COVID-19) fatality’

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Response to the COVID-19 Epidemic: The Chinese Experience and Implications for Other Countries

The ongoing outbreak of the novel coronavirus disease (COVID-19) that occurred in China is rapidly spreading globally. China’s bond and strict containment measures have been proved (in practice) to significantly reduce the spread of the epidemic. This was obtained through the use of emergency control measures in the epidemic areas and the integration of resources from multiple systems, including business, community, technology, education, and transportation, across the country. In order to better understand how China has managed to reduce the public health and economic impacts of the COVID-19 epidemic, this editorial systematically reviews the specific measures for infection prevention and control of the disease. The best practices for COVID-19 eradication in China provide evidence-based strategies that could be replicated in other countries.

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The outbreak of coronavirus disease in China: Risk perceptions, knowledge, and information sources among prenatal and postnatal women

BACKGROUND: The COVID-19 pandemic has created anxiety among members of the public, including all women over the childbirth continuum, who are considered to be at a greater risk of contracting most infectious diseases. Understanding the perspectives of health care consumers on COVID-19 will play a crucial role in the development of effective risk communication strategies. This study aimed to examine COVID-19-related risk perceptions, knowledge, and information sources among prenatal and postnatal Chinese women during the initial phase of the COVID-19 pandemic. METHODS: A cross-sectional survey design was adopted, and a four-section online questionnaire was used to collect data. Using a social media platform, the online survey was administered to 161 participants during the outbreak of COVID-19 in Nanjing, China, in February 2020. RESULTS: The participants perceived their risk of contracting and dying from COVID-19 to be lower than their risk of contracting influenza, however many of them were worried that they might contract COVID-19. The participants demonstrated adequate knowledge about COVID-19. The three major sources from which they obtained information about COVID-19 were doctors, nurses/midwives, and the television, and they placed a high level of confidence in these sources. There was no significant relationship between the perceived risk of contracting COVID-19 and knowledge about this disease. CONCLUSION: The present findings offer valuable insights to healthcare professionals, including midwives, who serve on the frontline and provide care to pregnant women. Although the participants were adequately knowledgeable about COVID-19, they had misunderstood some of the recommendations of the World Health Organization.

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Prevalence of Reovirus-Specific Antibodies in Young Children in Nashville, Tennessee

Although reovirus infections are thought to be common in adults, there have been few assessments of the seroprevalence of reovirus in young children. We developed an indirect enzyme-linked immunosorbent assay to measure levels of total antireovirus immunoglobulin A, G, and M in serum specimens collected from otherwise healthy infants and children (1 month to 5 years of age) in Nashville, Tennessee. Of the 272 serum specimens evaluated, 64 (23.5%) tested positive for reovirus-specific antibodies. We observed an age-dependent increase in reovirus-specific antibodies in children 1 year of age and older, peaking at 50.0% in children 5–6 years of age. These findings suggest that reovirus infections are common during early childhood

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Oxygen: under or over a surgical facemask for COVID‐19 patients?

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Prevalence and Outcomes of Acute Ischemic Stroke Among Patients ≤ 50 Years of Age with Laboratory Confirmed COVID-19 Infection

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Haemophagocytosis in bone marrow aspirates in patients with COVID‐19

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40 Infection in Renal Transplant Recipients

Abstract Infections are a major cause of morbidity and mortality in renal transplant recipients. This chapter reviews major risk factors for infection as well as important preventive measures. More common infections, including cytomegalovirus and urinary tract infection, are reviewed in detail.

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N-Acetylcysteine: a potential therapeutic agent for SARS-CoV-2

COVID-19, a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to spread across the globe. Predisposing factors such as age, diabetes, cardiovascular disease, and lowered immune function increase the risk of disease severity. T cell exhaustion, high viral load, and high levels of TNF-ɑ, IL1β, IL6, IL10 have been associated with severe SARS-CoV-2. Cytokine and antigen overstimulation are potentially responsible for poor humoral response to the virus. Lower cellular redox status, which leads to pro-inflammatory states mediated by TNF-ɑ is also potentially implicated. In vivo, in vitro, and human clinical trials have demonstrated N-acetylcysteine (NAC) as an effective method of improving redox status, especially when under oxidative stress. In human clinical trials, NAC can be used to replenish glutathione stores and increase the proliferative response of T cells. NAC has also been shown to inhibit the NLRP3 inflammasome pathway (IL1β and IL18) in vitro, and decrease plasma TNF-ɑ in human clinical trials. Mediation of the viral load could occur through NAC’s ability to increase cellular redox status via maximizing the rate limiting step of glutathione synthesis, and thereby potentially decreasing the effects of virally induced oxidative stress and cell death. We hypothesize that NAC could act as a potential therapeutic agent in the treatment of COVID-19 through a variety of potential mechanisms, including increasing glutathione, improving T cell response, and modulating inflammation. In this article, we present evidence to support the use of NAC as a potential therapeutic agent in the treatment of COVID-19.

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Drug treatment of coronavirus disease 2019 (COVID-19) in China.

Since December 2019, the coronavirus disease 2019 (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread throughout China as well as other countries. More than 8,700,000 confirmed COVID-19 cases have been recorded worldwide so far, with much more cases popping up overseas than those inside. As the initial epicenter in the world, China has been combating the epidemic for a relatively longer period and accumulated valuable experience in prevention and control of COVID-19. This article reviewed the clinical use, mechanism and efficacy of the clinically approved drugs recommended in the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (DTPNCP) released by National Health Commission of P.R.China, and the novel therapeutic agents now undergoing clinical trials approved by China National Medical Products Administration (NMPA) to evaluate experimental treatment for COVID-19. Reviewing the progress in drug development for the treatment against COVID-19 in China may provide insight into the epidemic control in other countries.

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ROLE OF MOUSE HEPATITIS CORONAVIRUS ENVELOPE PROTEIN TRANSMEMBRANE DOMAIN