title: Psychosocial factors and hospitalisations for COVID-19: Prospective cohort study of the general population

text: OBJECTIVE: To examine the association of a range of psychosocial factors with hospitalisation for COVID-19. DESIGN: Prospective cohort study. SETTING: England. PARTICIPANTS: UK Biobank comprises around half a million people who were aged 40 to 69 years at study induction between 2006 and 2010 when information on psychosocial factors and covariates were captured. MAIN OUTCOME MEASURE: Hospitalisation for COVID-19 in England between 16(th) March and 26(th) April 2020 as provided by Public Health England. RESULTS: There were 908 hospitalisations for COVID-19 in an analytical sample of 431,051 people. In age- and sex-adjusted analyses, an elevated risk of COVID-19 was related to disadvantaged levels of education (odds ratio; 95% confidence interval: 2.05; 1.70, 2.47), income (2.00; 1.63, 2,47), area deprivation (2.20; 1.86, 2.59), occupation (1.39; 1.14, 1.69), psychological distress (1.58; 1.32, 1.89), mental health (1.50; 1.25, 1.79), neuroticism (1.19; 1.00, 1.42), and performance on two tests of cognitive function - verbal and numerical reasoning (2.66; 2.06, 3.34) and reaction speed (1.27; 1.08, 1.51). These associations were graded (p-value for trend ≤0.038) such that effects were apparent across the full psychosocial continua. After mutual adjustment for these characteristics plus ethnicity, comorbidity, and lifestyle factors, only the relationship between lower cognitive function as measured using the reasoning test and a doubling in the risk of the infection remained (1.98; 1.38, 2.85). CONCLUSION: A range of psychosocial factors revealed associations with hospitalisations for COVID-19 of which the relation with cognitive function was most robust to statistical adjustment.


title: RAS-Inhibition in Zeiten der COVID-19-Pandemie — aktuelle ESH-Empfehlungen: Seminar / Hypertonie

text: Die COVID-19 Task Force der European Society of Hypertension (ESH) hat sich in einem Review erneut zur Bedeutung von Bluthochdruck und therapeutischer RAS-Blockade bei COVID-19-Patienten geäußert. Dargestellt und kritisch diskutiert werden v. a. die molekularen Mechanismen der Infektion und der RAS-Hemmung sowie die potenziellen klinischen Implikationen.


Proceedings of the Food and Drug Administration public workshop on pathogen reduction technologies for blood safety 2018 (Commentary, p. 3026)


title: Innate and adaptive immunity: specificities and signaling hierarchies revisited

text: The conventional classification of known immune responses by specificity may need re-evaluation. The immune system can be classified into two subsystems: the innate and adaptive immune systems. In general, innate immunity is considered a nonspecific response, whereas the adaptive immune system is thought of as being very specific. In addition, the antigen receptors of the adaptive immune response are commonly viewed as 'master sensors' whose engagement dictates lymphocyte function. Here we propose that these ideas do not genuinely reflect the organization of immune responses and that they bias our view of immunity as well as our teaching of immunology. Indeed, the level of specificity and mode of signaling integration used by the main cellular participants in the adaptive and innate immune systems are more similar than previously appreciated.


Planning for COVID-19 Vaccines Safety surveillance


title: Comparative epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia and South Korea

text: MERS-CoV infection emerged in the Kingdom of Saudi Arabia (KSA) in 2012 and has spread to 26 countries. However, 80% of all cases have occurred in KSA. The largest outbreak outside KSA occurred in South Korea (SK) in 2015. In this report, we describe an epidemiological comparison of the two outbreaks. Data from 1299 cases in KSA (2012–2015) and 186 cases in SK (2015) were collected from publicly available resources, including FluTrackers, the World Health Organization (WHO) outbreak news and the Saudi MOH (MOH). Descriptive analysis, t-tests, Chi-square tests and binary logistic regression were conducted to compare demographic and other characteristics (comorbidity, contact history) of cases by nationality. Epidemic curves of the outbreaks were generated. The mean age of cases was 51 years in KSA and 54 years in SK. Older males (⩾70 years) were more likely to be infected or to die from MERS-CoV infection, and males exhibited increased rates of comorbidity in both countries. The epidemic pattern in KSA was more complex, with animal-to-human, human-to-human, nosocomial and unknown exposure, whereas the outbreak in SK was more clearly nosocomial. Of the 1186 MERS cases in KSA with reported risk factors, 158 (13.3%) cases were hospital associated compared with 175 (94.1%) in SK, and an increased proportion of cases with unknown exposure risk was found in KSA (710, 59.9%). In a globally connected world, travel is a risk factor for emerging infections, and health systems in all countries should implement better triage systems for potential imported cases of MERS-CoV to prevent large epidemics.


title: Clinical outcomes of 402 patients with COVID‐2019 from a single center in Wuhan, China

text: The outbreak of SARS‐CoV‐2 has become a pandemic with significant mortality. Published studies describing clinical characteristics of the disease contain small cohorts from individual centers or larger series consisting of mixed series from multiple different hospitals. We report here analyses of mortality and disease severity among 402 patients from a single hospital. The cohort includes 297 patients with confirmed and 105 with clinical diagnosis. The latter group consists of cases with inconclusive nucleic acid test but meeting the criteria for clinical diagnosis. Data are compared between genders and among different age groups. The overall case fatality is 5.2%. However, age at 70 years or older is associated with a significantly higher mortality (17.8%) and higher rate of severe and critical illness (57.5%). Case fatality is 8% in patients 50 years of age or older, and 1.2% in those younger than 50 years. In addition, case fatality is 7.6% in male patients, as opposed to 2.9% in females, demonstrating a clear gender difference. This article is protected by copyright. All rights reserved.


Exercise as medicine for COVID-19: an ACE in the hole?


title: Optical theranostics and treatment dosimetry for COVID-19 lung complications: towards increasing the survival rate of vulnerable populations

text: • Although social isolation measures and adaptation of the healthcare system slowed the progress of the COVID-19 pandemic, no effective treatments are available for severe lung complications. • Optical theranostics methods can identify COVID-19 pulmonary manifestations and provide automated and real-time control of the treatment dosimetry as well as flexibility for combination with existing medical devices and drug repurposing protocols. • Implementation of reliable and safe theranostics methods requires strong collaboration among researchers, industry and medical institutions.


title: Combination Therapy Using Chimeric Monoclonal Antibodies Protects Mice from Lethal H5N1 Infection and Prevents Formation of Escape Mutants

text: BACKGROUND: Given that there is a possibility of a human H5N1 pandemic and the fact that the recent H5N1 viruses are resistant to the anti-viral drugs, newer strategies for effective therapy are warranted. Previous studies show that single mAbs in immune prophylaxis can be protective against H5N1 infection. But a single mAb may not be effective in neutralization of a broad range of different strains of H5N1 and control of potential neutralization escape mutants. METHODS/PRINCIPAL FINDINGS: We selected two mAbs which recognized different epitopes on the hemagglutinin molecule. These two mAbs could each neutralize in vitro escape mutants to the other and in combination could effectively neutralize viruses from clades 0, 1, 2.1, 2.2, 2.3, 4, 7 and 8 of influenza A H5N1 viruses. This combination of chimeric mAbs when administered passively, pre or post challenge with 10 MLD50 (50% mouse lethal dose) HPAI H5N1 influenza A viruses could protect 100% of the mice from two different clades of viruses (clades 1 and 2.1). We also tested the efficacy of a single dose of the combination of mAbs versus two doses. Two doses of the combination therapy not only affected early clearance of the virus from the lung but could completely prevent lung pathology of the H5N1 infected mice. No escape variants were detected after therapy. CONCLUSIONS/SIGNIFICANCE: Our studies provide proof of concept that the synergistic action of two or more mAbs in combination is required for preventing the generation of escape mutants and also to enhance the therapeutic efficacy of passive therapy against H5N1 infection. Combination therapy may allow for a lower dose of antibody to be administered for passive therapy of influenza infection and hence can be made available at reduced economic costs during an outbreak.


title: Identification of viral agents associated with diarrhea in young children during a winter season in Beijing, China

text: Abstract Background Viral diarrhea remains a major cause of childhood morbidity and mortality worldwide. Although rotavirus was extensively studied in China, few comprehensive studies of all viral agents related to diarrhea in children have been conducted. Objectives Our study was performed to investigate the role of enteric viruses in acute diarrhea in our country and to evaluate methods that could be used in routine diagnostics. Study design One hundred stool samples were collected from children under 5 years of age seeking medical care for acute diarrhea during the winter season 2000/2001 in Beijing Children's Hospital. All specimens were initially screened microscopically for leucocytes/red blood cells. Samples with negative results were analyzed for virus presence using commercial EIAs and/or in-house RT-PCRs. Results At least one viral agent was found in 67% of the specimens. The frequency of rotavirus, astrovirus, norovirus and enteric adenovirus was 59%, 8%, 6% and 2%, respectively. Dual infections were found in 9.0% (6/67) of the positive samples. The results from rotavirus and astrovirus EIAs were concordant with those of rotavirus and astrovirus RT-PCRs. Conclusions Enteric viruses play an important role in pediatric diarrhea during the winter season in China. A combination of microscopic examination of stool samples with specific EIA assays to detect virus antigen in stool specimens may be suitable for routine diagnostics.


title: The Association Between Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and the Number of Covid-19 Confirmed Cases and Deaths in the United States: Geospatial Study

text: Background: The novel coronavirus SARS-Cov2 uses the angiotensin-converting enzyme 2 (ACE2) receptor as an entry point to the cell. Cardiovascular disease (CVD) is a risk factor for the novel coronavirus disease (Covid-19) with poor outcomes. We hypothesized that the rate of ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) use is associated with the rate of Covid-19 confirmed cases and deaths. Methods: We conducted a geospatial study using publicly available county-level data. The Medicare ACEIs and ARBs prescription rate was exposure. The Covid-19 confirmed case and death rates were outcomes. Spatial autoregression models were adjusted for the percentage of Black residents, children, residents with at least some college degree, median household income, air quality index, CVD hospitalization rate in Medicare beneficiaries, and CVD death rate in a total county population. Results: The ACEI use had no effect on Covid-19 confirmed case rate. An average ACEIs use (compared to no-use) was associated with a higher Covid-19 death rate by 1.1 (95%CI 0.4-1.8)%. If the use of ACEIs increases by 0.5% for all counties, the Covid-19 death rate will drop by 0.4% to 0.7(95%CI 0.3-1.1)%; P<0.0001. An average ARBs use (compared to no-use) was associated with a higher Covid-19 confirmed case rate (by 4.2; 95%CI 4.1-4.3 %) and death rate (by 1.1; 95%CI 0.7-1.5 %). Each percent increase in ARBs use was associated with an increase in confirmed case rate by 0.2(0.03-0.4)% and death rate by 0.14(0.08-0.21)%. Conclusions: ARBs, but not ACEIs use rate, is associated with Covid-19 confirmed case rate.


title: Can biowarfare agents be defeated with light?

text: Biological warfare and bioterrorism is an unpleasant fact of 21st century life. Highly infectious and profoundly virulent diseases may be caused in combat personnel or in civilian populations by the appropriate dissemination of viruses, bacteria, spores, fungi, or toxins. Dissemination may be airborne, waterborne, or by contamination of food or surfaces. Countermeasures may be directed toward destroying or neutralizing the agents outside the body before infection has taken place, by destroying the agents once they have entered the body before the disease has fully developed, or by immunizing susceptible populations against the effects. A range of light-based technologies may have a role to play in biodefense countermeasures. Germicidal UV (UVC) is exceptionally active in destroying a wide range of viruses and microbial cells, and recent data suggests that UVC has high selectivity over host mammalian cells and tissues. Two UVA mediated approaches may also have roles to play; one where UVA is combined with titanium dioxide nanoparticles in a process called photocatalysis, and a second where UVA is combined with psoralens (PUVA) to produce “killed but metabolically active” microbial cells that may be particularly suitable for vaccines. Many microbial cells are surprisingly sensitive to blue light alone, and blue light can effectively destroy bacteria, fungi, and Bacillus spores and can treat wound infections. The combination of photosensitizing dyes such as porphyrins or phenothiaziniums and red light is called photodynamic therapy (PDT) or photoinactivation, and this approach cannot only kill bacteria, spores, and fungi, but also inactivate viruses and toxins. Many reports have highlighted the ability of PDT to treat infections and stimulate the host immune system. Finally pulsed (femtosecond) high power lasers have been used to inactivate pathogens with some degree of selectivity. We have pointed to some of the ways light-based technology may be used to defeat biological warfare in the future.


title: Prediction of Pediatric Critical Care Resource Utilization for Disaster Triage

text: Pediatric protocols to guide allocation of limited resources during a disaster lack data to validate their use. The 2011 Pediatric Emergency Mass Critical Care Task Force recommended that expected duration of critical care be incorporated into resource allocation algorithms. We aimed to determine whether currently available pediatric illness severity scores can predict duration of critical care resource use. DESIGN: Retrospective cohort study. SETTING: Seattle Children’s Hospital. PATIENTS: PICU patients admitted 2016–2018 for greater than or equal to 12 hours (n = 3,206). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We developed logistic and linear regression models in two-thirds of the cohort to predict need for and duration of PICU resources based on Pediatric Risk of Mortality-III, Pediatric Index of Mortality-3, and serial Pediatric Logistic Organ Dysfunction-2 scores. We tested the predictive accuracy of the models with the highest area under the receiver operating characteristic curve (need for each resource) and R(2) (duration of use) in a validation cohort of the remaining one of three of the sample and among patients admitted during one-third of the sample and among patients admitted during surges of respiratory illness. Pediatric Logistic Organ Dysfunction score calculated 12 hours postadmission had higher predictive accuracy than either Pediatric Risk of Mortality or Pediatric Index of Mortality scores. Models incorporating 12-hour Pediatric Logistic Organ Dysfunction score, age, Pediatric Overall Performance Category, Pediatric Cerebral Performance Category, chronic mechanical ventilation, and postoperative status had an area under the receiver operating characteristic curve = 0.8831 for need for any PICU resource (positive predictive value 80.2%, negative predictive value 85.9%) and area under the receiver operating characteristic curve = 0.9157 for mechanical ventilation (positive predictive value 85.7%, negative predictive value 89.2%) within 7 days of admission. Models accurately predicted greater than or equal to 24 hours of any resource use for 78.9% of patients and greater than or equal to 24 hours of ventilation for 83.1%. Model fit and accuracy improved for prediction of resource use within 3 days of admission, and was lower for noninvasive positive pressure ventilation, vasoactive infusions, continuous renal replacement therapy, extracorporeal membrane oxygenation, and length of stay. CONCLUSIONS: A model incorporating 12-hour Pediatric Logistic Organ Dysfunction score performed well in estimating how long patients may require PICU resources, especially mechanical ventilation. A pediatric disaster triage algorithm that includes both likelihood for survival and for requiring critical care resources could minimize subjectivity in resource allocation decision-making.


title: Spatial organization and activity patterns of the masked palm civet (Paguma larvata) in central-south China

text: Movement and activity patterns are important components of life history, being central to resource acquisition and defense, mating behavior, and individual survival and fitness. Here, we present results from the 1st systematic radiotracking study of the masked palm civet (Paguma larvata), a widespread viverrid found in subtropical and tropical forests of Asia. From June 2004 to November 2007, we radiotracked 12 masked palm civets (5 males and 7 females) in central-south China. Mean individual home-range size based on 95% minimum convex polygons was 192.6 ha ± 42.6 SE (range = 64–451 ha). Although males had larger mean home-range sizes than females (276.8 and 136.5 ha, respectively), these differences were not statistically significant. Males also exhibited greater daily movement distances and extents than females, but we found no evidence of sexual dimorphism in body size. Masked palm civets were predominantly nocturnal, but were active intermittently during the day. No significant seasonal (monthly) differences in daily activity patterns were apparent. We did, however, observe reduced hours of activity—but not continuous inactivity—during winter; consequently, we concluded that our study animals did not hibernate or semihibernate. We speculate that our observations of home-range overlap among individuals may indicate group living in the masked palm civet.


title: Evaluation of Antiviral Therapies for Coronavirus Disease 2019 (COVID‐19) Pneumonia in Shanghai, China

text: The aim of our study was to evaluate the therapeutic effect of antiviral drugs on COVID‐19 pneumonia. Patients confirmed with COVID‐19 pneumonia were enrolled and divided into 7 groups according to the treatment option. Information including age, gender and duration from illness onset to admission, clinical manifestations and laboratory data at admission, and length of hospital stay were evaluated. The chest CT imaging obtained at admission and after a 5‐d treatment cycle were assessed. The clinical symptoms and laboratory tests at discharge were also assessed. At admission, no significant differences were found among the groups, including duration from illness onset to admission, clinical symptoms and main laboratory results. No significant differences were found among the groups in terms of the proportion of patients with pneumonia resolution (P=0.151) after treatment or the length of hospital stay (P=0.116). At discharge, 7/184 (4%) patients had a mild cough while their other symptoms had disappeared, and the proportion of patients with abnormal liver function and with increased leucocytes, neutrophils or erythrocyte sedimentation rate among the 184 patients were close to those at admission. According to the results, the inclusion of antiviral drugs in therapeutic regimens based on symptomatic treatment had no significant additional impact on the improvement in COVID‐19 patients. In addition, the results of chest CT imaging, clinical manifestations, and laboratory tests at discharge were not completely consistent. This article is protected by copyright. All rights reserved.


title: Will heat kill the coronavirus?

text: We don't know if changing seasons will help stem the outbreak, says Michael Le Page


title: Chapter 7 Pathogenesis

text: Publisher Summary Virus pathogenesis is a complex, variable, and relatively rare state. Like the course of a virus infection, pathogenesis is determined by the balance between host and virus factors. Not all the pathogenic symptoms seen in virus infections are caused directly by the virus but are side effects of the immune response. In the past few decades, molecular genetic analysis has contributed enormously in understanding the virus pathogenesis. In the chapter, three major aspects of virus pathogenesis are considered: direct cell damage resulting from virus replication, damage resulting from immune activation or suppression, and cell transformation caused by viruses. The chapter also discusses the mechanisms of cellular injury, virus-induced immunodeficiency, virus-related diseases, bacteriophages, and cell transformation by viruses, retroviruses, and DNA viruses. The chapter ends with a discussion of new pathogenic viruses that are being discovered all the time, and changes in human activities that have resulted in the emergence of new or previously unrecognized diseases.


title: The uses of disorder in negotiated information orders: information leveraging and changing norms in global public health governance

text: The SARS epidemic that broke out in late 2002 in China’s Guangdong Province highlighted the difficulties of reliance on state‐provided information when states have incentives to conceal discrediting information about public health threats. Using SARS and the International Health Regulations (IHR) as a starting point, this article examines negotiated information orders in global public health governance and the irregularities in the supply of data that underlie them. Negotiated information orders within and among the organizations in a field (here, e.g., the World Health Organization, member states, government agencies, and international non‐governmental organizations) spell out relationships among different categories of knowledge and non‐knowledge – what is known, acknowledged to be known, and available for use in decision making versus what might be known but cannot be acknowledged or officially used. Through information leveraging, technically sufficient information then becomes socially sufficient information. Thus it is especially information initially categorized as non‐knowledge – including suppressed data, rumour, unverified evidence, and unofficial information – that creates pressure for the renegotiation of information orders. The argument and evidence of the article also address broader issues about how international law and global norms are realigned, how global norms change, and how social groups manage risk.


title: The POP-DOC Loop: A continuous process for situational awareness and situational action

text: Abstract Among the most critical challenges crisis leaders face is evaluating “the situation”—what is happening and what to do about it. Extensive scholarship on Situational Awareness (SA) has identified a gap: a disciplined process for achieving accurate SA. Further, SA only addresses the first half of that situation equation; awareness is necessary, yet not sufficient, unless linked to and integrated with meaningful decisions and actions. The POP-DOC Loop is a six-step SA tool that combines analysis and action into a continuous process. The analytic side is Perceive, Orient, Predict. The Action side is Decide, Operationalize, Communicate. POP-DOC builds upon Boyd's Observe, Orient, Decide, Act, or OODA Loop. OODA evolves from and focuses upon military command-and-control contexts, though it is applied in other settings as well. The advance design of POP-DOC incorporates a wider range of human factors, including neuro- and decision science research, in order to equip leaders to build SA in high-stress, high-stakes, evolving, and unpredictable situations.


title: Don’t Uncover that Face! Covid-19 Masks and the Niqab: Ironic Transfigurations of the ECtHR’s Intercultural Blindness

text: This essay, between serious and facetious, addresses an apparently secondary implication of the planetary tragedy produced by Covid-19. It coincides with the ‘problem of the veil,’ a bone of contention in Islam/West relationships. More specifically, it will address the question of why the pandemic has changed the proxemics of public spaces and the grammar of ‘living together.’ For some time—and it is not possible to foresee how much—in many countries people cannot go out, or enter any public places, without wearing a sanitary mask. In short, almost all of us, by obligation or by urgent advice from the public authorities of the various countries, will not live the public sphere with our faces uncovered. The alteration of the social context affecting many Western countries will inevitably involve also the ‘local’ perception of the Islamic veil and—as a matter of equality—the consistency of the prohibition of wearing it. What will thus become of the ban on wearing it in public places established by some countries such as France and asseverated by the ECHR? If everyone can and will have to go around with their faces covered, why should only Islamic women be discriminated against? Will not the change in boundary conditions produced by Covid-19 also induce Western people to re-categorize the meaning of the veil? And will this re-categorization not directly affect the ‘fact’ of wearing the veil, that is, its empirical perception? And still, will this psycho-semantic change not show how empirical perceptions are cultural constructs rather than ‘objective facts,’ as such allegedly independent from the observer’s point of view? Consequentially, will the plurality of perceptions and cultural meanings related to the gesture of covering one’s own face not gain renewed relevance in determining the legitimacy of wearing the veil? The socio-semantic earthquake produced by Covid-19 compels us to rethink this and other issues orbiting around the translation of ‘facts’ into legal language; furthermore, it highlights the instrumentality of many ideological/partisan and ethnocentric assumptions passed off as objectivity regarding those alleged ‘facts.’ The essay will attempt to provide an answer to the above questions by proposing a semiotic-legal approach to intercultural conflicts and, indirectly, the pluralism in law.


title: Evaluation of Antiseptic Antiviral Activity of Chemical Agents

text: Antiviral antisepsis and disinfection are crucial for preventing the environmental spread of viral infections. Emerging viruses and associated diseases, as well as nosocomial viral infections, have become a real issue in medical fields, and there are very few efficient and specific treatments available to fight most of these infections. Another issue is the potential environmental resistance and spread of viral particles. Therefore, it is essential to properly evaluate the efficacy of antiseptics‐disinfectants (ATS‐D) on viruses. ATS‐D antiviral activity is evaluated by (1) combining viruses and test product for an appropriately defined and precise contact time, (2) neutralizing product activity, and (3) estimating the loss of viral infectivity. A germicide can be considered to have an efficient ATS‐D antiviral activity if it induces a >3 or >4 log(10) reduction (American and European regulatory agency requirements, respectively) in viral titers in a defined contact time. This unit describes a global methodology for evaluating chemical ATS‐D antiviral activity. Curr. Protoc. Cell Biol. 51:26.10.1‐26.10.22. © 2011 by John Wiley & Sons, Inc.


title: Elevated troponin in patients with Coronavirus Disease 2019 (COVID-19): possible mechanisms

text: Abstract Coronavirus disease 2019 (COVID-19) is a pandemic that has affected more than 1.8 million people worldwide, overwhelmed health care systems due to the high proportion of critical presentations, and resulted in over 100,000 deaths. Since the first data analyses in China, elevated cardiac troponin has been noted in a substantial proportion of patients, implicating myocardial injury as a possible pathogenic mechanism contributing to severe illness and mortality. Accordingly, high troponin levels are associated with increased mortality in patients with COVID-19. This brief review explores the available evidence regarding the association between COVID-19 and myocardial injury.


title: Nucleocapsid-independent assembly of coronavirus-like particles by co-expression of viral envelope protein genes.

text: Budding of enveloped viruses has been shown to be driven by interactions between a nucleocapsid and a proteolipid membrane. By contrast, we here describe the assembly of viral envelopes independent of a nucleocapsid. Membrane particles containing coronaviral envelope proteins were assembled in and released from animal cells co-expressing these proteins' genes from transfected plasmids. Of the three viral membrane proteins only two were required for particle formation, the membrane glycoprotein (M) and the small envelope protein (E). The spike (S) protein was dispensable but was incorporated when present. Importantly, the nucleocapsid protein (N) was neither required not taken into the particles when present. The E protein, recently recognized to be a structural protein, was shown to be an integral membrane protein. The envelope vesicles were found by immunogold labelling and electron microscopy to form a homogeneous population of spherical particles indistinguishable from authentic coronavirions in size (approximately 100 nm in diameter) and shape. They were less dense than virions and sedimented slightly slower than virions in sucrose velocity gradients. The nucleocapsid-independent formation of apparently bona fide viral envelopes represents a novel mode of virus assembly.


H7N9 avian influenza virus - search and re-search


title: SARS‐CoV‐2 infection in a psoriatic patient treated with IL‐17 inhibitor

text: we read with great interest the article entitled “SARS‐CoV‐2 infection in a psoriatic patient treated with IL‐23 inhibitor” published by Messina F. and Piaserico S. in the JEADV.(1) This is the first report of COronaVIrus DIsease 2019 (COVID‐19) in a psoriatic patient treated with a biologic. Whilst the authors reported an infection that occurred during therapy with an IL‐23 inhibitor, we would like to briefly report one that occurred during therapy with an IL‐17 inhibitor.


title: Dose-dependent effects of specific egg-yolk antibodies on diarrhea of newborn calves

text: Abstract In a field trial on a farm in Turkey, we tested whether specific egg-yolk antibodies had a prophylactic effect on neonatal diarrhea. Owing to its antibody spectrum, this egg powder was very suitable for this farm since mainly rotavirus was identified. Regardless of the dosage (2 g, 4 g, or 8 g egg powder), the calves (n = 164) which received specific egg-yolk antibodies via the whole egg during the first 14 days of life showed significant improvements in risk and duration of diarrhea and in body weight gain compared with calves of the control group (n = 80) which had not received any egg powder. These significant differences in body weight still persisted after 3 months of life. The mortality risk in the control group amounted to 8.8%, while in all egg powder groups (n = 164) only one calf died as a result of diarrhea. Breed-dependent differences in the parameters were not observed.


title: Impact of human mobility on the transmission dynamics of infectious diseases

text: Spatial heterogeneity is an important aspect to be studied in infectious disease models. It takes two forms: one is local, namely diffusion in space, and other is related to travel. With the advancement of transportation system, it is possible for diseases to move from one place to an entirely separate place very quickly. In a developing country like India, the mass movement of large numbers of individuals creates the possibility of spread of common infectious diseases. This has led to the study of infectious disease model to describe the infection during transport. An SIRS-type epidemic model is formulated to illustrate the dynamics of such infectious disease propagation between two cities due to population dispersal. The most important threshold parameter, namely the basic reproduction number, is derived, and the possibility of existence of backward bifurcation is examined, as the existence of backward bifurcation is very unsettling for disease control and it is vital to know from modeling analysis when it can occur. It is shown that dispersal of populations would make the disease control difficult in comparison with nondispersal case. Optimal vaccination and treatment controls are determined. Further to find the best cost-effective strategy, cost-effectiveness analysis is also performed. Though it is not a case study, simulation work suggests that the proposed model can also be used in studying the SARS epidemic in Hong Kong, 2003.


title: Pathogenesis of acute and chronic central nervous system infection with variants of mouse hepatitis virus, strain JHM

text: Infection of mice with variants of mouse hepatitis virus, strain JHM (MHV-JHM), provide models of acute and chronic viral infection of the central nervous system (CNS). Through targeted recombination and reverse genetic manipulation, studies of infection with MHV-JHM variants have identified phenotypic differences and examined the effects of these differences on viral pathogenesis and anti-viral host immune responses. Studies employing recombinant viruses with a modified spike (S) glycoprotein of MHV-JHM have identified the S gene as a major determinant of neurovirulence. However, the association of S gene variation and neurovirulence with host ability to generate anti-viral CD8 T cell responses is not completely clear. Partially protective anti-viral immune responses may result in persistent infection and chronic demyelinating disease characterized by myelin removal from axons of the CNS and associated with dense macrophage/microglial infiltration. Demyelinating disease during MHV-JHM infection is immune-mediated, as mice that lack T lymphocytes fail to develop disease despite succumbing to encephalitis with high levels of infectious virus in the CNS. However, the presence of T lymphocytes or anti-viral antibody can induce disease in infected immunodeficient mice. The mechanisms by which these immune effectors induce demyelination share an ability to activate and recruit macrophages and microglia, thus increasing the putative role of these cells in myelin destruction.


title: Potential Broad Spectrum Inhibitors of the Coronavirus 3CL(pro): A Virtual Screening and Structure-Based Drug Design Study

text: Human coronaviruses represent a significant disease burden; however, there is currently no antiviral strategy to combat infection. The outbreak of severe acute respiratory syndrome (SARS) in 2003 and Middle East respiratory syndrome (MERS) less than 10 years later demonstrates the potential of coronaviruses to cross species boundaries and further highlights the importance of identifying novel lead compounds with broad spectrum activity. The coronavirus 3CL(pro) provides a highly validated drug target and as there is a high degree of sequence homology and conservation in main chain architecture the design of broad spectrum inhibitors is viable. The ZINC drugs-now library was screened in a consensus high-throughput pharmacophore modeling and molecular docking approach by Vina, Glide, GOLD and MM-GBSA. Molecular dynamics further confirmed results obtained from structure-based techniques. A highly defined hit-list of 19 compounds was identified by the structure-based drug design methodologies. As these compounds were extensively validated by a consensus approach and by molecular dynamics, the likelihood that at least one of these compounds is bioactive is excellent. Additionally, the compounds segregate into 15 significantly dissimilar (p < 0.05) clusters based on shape and features, which represent valuable scaffolds that can be used as a basis for future anti-coronaviral inhibitor discovery experiments. Importantly though, the enriched subset of 19 compounds identified from the larger library has to be validated experimentally.


Comment on: “Controversies regarding mask usage in ophthalmic units in the United Kingdom during the COVID-19 pandemic”


title: Applications of Plant Viruses in Bionanotechnology

text: The capsids of most plant viruses are simple and robust structures consisting of multiple copies of one or a few types of protein subunit arranged with either icosahedral or helical symmetry. In many cases, capsids can be produced in large quantities either by the infection of plants or by the expression of the subunit(s) in a variety of heterologous systems. In view of their relative simplicity, stability and ease of production, plant virus particles or virus-like particles (VLPs) have attracted attention as potential reagents for applications in bionanotechnology. As a result, plant virus particles have been subjected to both genetic and chemical modification, have been used to encapsulate foreign material and have, themselves, been incorporated into supramolecular structures.


title: Aptamers that bind specifically to human KPNA2 (importin-α1) and efficiently interfere with nuclear transport

text: The importin-α family of proteins plays an important role in the eukaryotic importin/exportin nuclear transport system. These proteins recognize a nuclear localization signal (NLS) within cargo proteins and import them into the nucleus through nuclear pores, in a process mediated by importin-β. Recent studies have shown that importin-α proteins specifically recognize the NLS of several cellular factors and viral proteins, thus regulating their movement. Dysregulation of importin-α is a common hallmark of many pathologies including, multiple cancers. In this study, we isolated aptamers 76 and 72, which bind specifically and efficiently to KPNA2, a member of a subfamily of importin-α1. Both of these aptamers bind to KPNA2 with an equilibrium dissociation constant (K(d)) of 150 nM and discriminate between KPNA2 and other sub-family members of importin-α, such as KPNA1 and KPNA3. These aptamers specifically interfere with the nuclear transport of cargo proteins mediated by KPNA2 but neither with KPNA1 nor KPNA3, which belongs to other subfamily of importins. These results suggest that the selected aptamers (76 and 72) warrant further study to explore not only their application in cancer diagnosis but also their use as a specific reagent to potentially block KPNA2-dependent nuclear transport of macromolecules across the nuclear membrane.


title: Diverse gammacoronaviruses detected in wild birds from Madagascar

text: To date, infectious bronchitis virus (IBV) is potentially found in wild birds of different species. This work reports the survey of coronaviruses in wild birds from Madagascar based on the targeting of a conserved genome sequence among different groups of CoVs. Phylogenetic analyses revealed the presence of gammacoronaviruses in different species of Gruiformes, Passeriformes, Ciconiiformes, Anseriformes, and Charadriiformes. Furthermore, some sequences were related to various IBV strains. Aquatic and migratory birds may play an important role in the maintenance and spread of coronaviruses in nature, highlighting their possible contribution in the emergence of new coronavirus diseases in wild and domestic birds.


title: Medical and Surgical Emergencies in Ferrets

text: In the last few years, significant improvement in diagnosis and treatment of ferret emergencies has occurred. Scientific advances demonstrated the need of specific practices when dealing with emergencies in ferrets. The risk of overdiagnosis of hypoglycemia with human portable blood glucose meters is a clear example. The purpose of this article is to describe the current approach to common medical and surgical emergencies in ferrets.


title: CPAP Added to Oxygen Administration Avoid Intubation in Acute Respiratory Distress in COVID-19 Pneumonia. Case Report

text: It was recently described that COVID-19 pneumonia patients had an atypical form of the ARDS syndrome and required gentle ventilation. We report here on benefits of CPAP treatment in a patient with COVID-19 pneumonia. A 63-year-old patient of African origin presented to the emergency room with COVID-19 pneumonia. Fever had started 5 days before her admission. On day 4, rapid clinical deterioration associated to a high respiratory rate and increased oxygen requirements was noted. The patient was working in an intensive care unit and refused to be intubated. Oxygen was administered at a rate of 15 litres per minute via a Boussignac valve, which initially restored normal oxygen saturation, but this treatment was poorly tolerated and the patient withdrew it after 2 h. A CPAP set at a pressure of 8 cm of water (Goodknight®) was then introduced with better tolerance, allowing the patient to wear it almost continuously for more than 38 h. The patient also benefited from the administration of methypredinsolone 40 mg. Concerning tolerance, a substantial advantage was noted for CPAP machine compared to the Boussignac valve with in addition, a clear decrease in respiratory rate. We would like to encourage the use of CPAP, better tolerated for extended hours with lower oxygen flows, in patients with COVID-19 pneumonia, where acute respiratory distress all too often leads to patient intubation and the genesis of deleterious lung lesions.


title: COVID-19 projections for reopening Connecticut

text: Closure of schools and the statewide "Stay Safe, Stay Home" order have effectively reduced COVID-19 transmission in Connecticut, with model projections estimating incidence at about 1,300 new infections per day. If close interpersonal contact increases quickly in Connecticut following reopening on May 20, the state is at risk of a substantial increase of COVID-19 infections, hospitalizations, and deaths by late Summer 2020. Real-time metrics including case counts, hospitalizations, and deaths may fail to provide enough advance warning to avoid resurgence. Substantial uncertainty remains in our knowledge of cumulative COVID-19 incidence, the proportion of infected individuals who are asymptomatic, infectiousness of children, the effects of testing and contact tracing on isolation of infected individuals, and how contact patterns may change following reopening.


title: Insights into potential pathogenesis mechanisms associated with Campylobacter jejuni-induced abortion in ewes

text: BACKGROUND: Campylobacter jejuni is commonly found in the gastrointestinal tract of many food-animals including sheep without causing visible clinical symptoms of disease. However, C. jejuni has been implicated in ovine abortion cases worldwide. Specifically, in the USA, the C. jejuni sheep abortion (SA) clone has been increasingly associated with sheep abortion. In vivo studies in sheep (the natural host) are needed to better characterize the virulence potential and pathogenesis of this clone. RESULTS: Pregnant ewes intravenously (IV) or orally inoculated with ovine or bovine abortion-associated C. jejuni SA clones exhibited partial or complete uterine prolapse with retained placenta, and abortion or stillbirth, whereas delivery of healthy lambs occurred in pregnant ewes inoculated with C. jejuni 81–176 or in the uninfected group. In sheep inoculated with the SA clone, histopathological lesions including suppurative necrotizing placentitis and/or endometritis coincided with: 1) increased apoptotic death of trophoblasts, 2) increased expression of the host genes (e.g. genes encoding interleukin IL-6 and IL-15) related to cellular necrosis and pro-inflammatory responses in uterus, and 3) decreased expression of the genes encoding GATA binding protein 6, chordin, and insulin-like 3 (INSL3) that account for embryonic development in uterus. Immunohistochemistry revealed localization of bacterial antigens in trophoblasts lining the chorioallantoic membrane of ewes inoculated with the C. jejuni SA clone. CONCLUSIONS: The results showed that C. jejuni SA clones are capable of causing abortion or stillbirth in experimentally infected sheep. Furthermore, down- or up-regulation of specific genes in the uterus of infected pregnant ewes might implicate host genes in facilitating the disease progression. Since the C. jejuni SA strains share genotypic similarities with clones that have been isolated from human clinical cases of gastroenteritis, these strains might represent a potential public health risk. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-014-0274-8) contains supplementary material, which is available to authorized users.


title: Endogenous R&D spillover and location choice in a mixed oligopoly

text: We consider a three-stage game where a public firm and a private firm choose R&D, location, and price, under the assumption that R&D spillovers rely on their locations. We show that, in equilibrium, whether the public firm engages in innovation more aggressively than the private firm depends on the degree of spillovers. Moreover, firms’ equilibrium locations exhibit neither maximal nor minimal differentiation. Finally, privatization could reduce social welfare because it may generate inefficient location and insufficient R&D investment. This suggests that a mixed duopoly could be socially preferable to a private duopoly in the presence of endogenous R&D spillovers.


title: COVID-19 and Japanese shareholder activism: brief respite for Japan’s self-healing concrete

text: Extrapolating from modern international understanding of corporate Japan’s distinct form of managerial capitalism, we elaborate on the growing momentum of shareholder activism in Japan leading up to the COVID-19 health crisis, so as to inform the subsequent discussion on the relevant primary considerations that belie the future direction of shareholder activism in Japan post-COVID-19. On an initial logical extrapolation, it appears probable that COVID-19 could mark the peak of Japanese activism. However, it is crucial to acknowledge that the success of Japan’s managerial capitalism have also declined, which poses a question on to which direction Japanese corporate governance may be shifting. Finally, we point out how corporate Japan’s impeding market developments will provide a useful case-study for global financial discourse.


title: A child with a severe multi‐system inflammatory syndrome following an asymptomatic COVID‐19 infection: a novel management for a new disease?

text: Clinical presentation of COVID‐19 disease is only in part due to viral infection itself, with the host response playing an important role.(1‐3) Despite the mild clinical course during the acute phase of infection in children, latest ongoing researches are pointing the attention towards a hyperinflammatory shock or a Kawasaki‐like disease as a possible consequence to COVID‐19 exposure.(4,5) This article is protected by copyright. All rights reserved.


title: Determining Causality and Controlling Disease is Based on Collaborative Research involving Multidisciplinary Approaches

text: Understanding the causes of infectious disease to facilitate better control requires observational and experimental studies. Often these must be conducted at many scales such as at the molecular, cellular, organism, and population level. Studies need to consider both intrinsic and extrinsic factors affecting the pathogen/host interaction. They also require a combination of study methods covered by disciplines such as pathology, epidemiology, microbiology, and ecology. Therefore, it is important that disciplines work together when designing and conducting studies. Finally, we need to integrate and interpret data across levels and disciplines to better formulate control strategies. This requires another group of specialists with broad cross-disciplinary training in epidemiology and an ability to readily work with others.


title: A Multicenter Consortium to Define the Epidemiology and Outcomes of Pediatric Solid Organ Transplant Recipients With Inpatient Respiratory Virus Infection

text: BACKGROUND: Respiratory virus infection (RVI) in pediatric solid organ transplant (SOT) recipients poses a significant risk; however, the epidemiology and effects of an RVI after pediatric SOT in the era of current molecular diagnostic assays are unclear. METHODS: A retrospective observational cohort of pediatric SOT recipients (January 2010 to June 2013) was assembled from 9 US pediatric transplant centers. Charts were reviewed for RVI events associated with hospitalization within 1 year after the transplant. An RVI diagnosis required respiratory symptoms and detection of a virus (ie, human rhinovirus/enterovirus, human metapneumovirus, influenza virus, parainfluenza virus, coronavirus, and/or respiratory syncytial virus). The incidence of RVI was calculated, and the association of baseline SOT factors with subsequent pulmonary complications and death was assessed. RESULTS: Of 1096 pediatric SOT recipients (448 liver, 289 kidney, 251 heart, 66 lung, 42 intestine/multivisceral), 159 (14.5%) developed RVI associated with hospitalization within 12 months after their transplant. RVI occurred at the highest rates in intestine/abdominal multivisceral (38%), thoracic (heart/lung) (18.6%), and liver (15.6%) transplant recipients and a lower rate in kidney (5.5%) transplant recipients. RVI was associated with younger median age at transplant (1.72 vs 7.89 years; P < .001) and among liver or kidney transplant recipients with the receipt of a deceased-donor graft compared to a living donor (P = .01). The all-cause and attributable case-fatality rates within 3 months of RVI onset were 4% and 0%, respectively. Multivariable logistic regression models revealed that age was independently associated with increased risk for a pulmonary complication (odds ratio, 1.24 [95% confidence interval, 1.02–1.51]) and that receipt of an intestine/multivisceral transplant was associated with increased risk of all-cause death (odds ratio, 24.54 [95% confidence interval, 1.69–327.96]). CONCLUSIONS: In this study, hospital-associated RVI was common in the first year after pediatric SOT and associated with younger age at transplant. All-cause death after RVI was rare, and no definitive attributable death occurred.


title: Therapeutic management of Crimean-Congo haemorrhagic fever

text: Abstract Crimean-Congo haemorrhagic fever has been reported in more than 30 countries in Africa, Asia, the Middle East and Eastern Europe, with an increasing incidence in recent years, especially in Europe. Because no specific treatments have demonstrated efficacy, supportive treatment is essential, as well as the provision of a centre with the appropriate means to guarantee the safety of its healthcare professionals. Laboratory monitoring of thrombocytopenia, severe coagulopathy or liver failure is of critical importance. Patients with Crimean-Congo haemorrhagic fever should be admitted to High Level Isolation Units where appropriate biocontainment procedures can prevent nosocomial transmission through infected fluids or accidents with contaminated material. In case of high-risk exposures, early administration of ribavirin should be considered.


title: The potential impact of the next influenza pandemic on a national primary care medical workforce

text: BACKGROUND: Another influenza pandemic is all but inevitable. We estimated its potential impact on the primary care medical workforce in New Zealand, so that planning could mitigate the disruption from the pandemic and similar challenges. METHODS: The model in the "FluAid" software (Centers for Disease Control and Prevention, CDC, Atlanta) was applied to the New Zealand primary care medical workforce (i.e., general practitioners). RESULTS: At its peak (week 4) the pandemic would lead to 1.2% to 2.7% loss of medical work time, using conservative baseline assumptions. Most workdays (88%) would be lost due to illness, followed by hospitalisation (8%), and then premature death (4%). Inputs for a "more severe" scenario included greater health effects and time spent caring for sick relatives. For this scenario, 9% of medical workdays would be lost in the peak week, and 3% over a more compressed six-week period of the first pandemic wave. As with the base case, most (64%) of lost workdays would be due to illness, followed by caring for others (31%), hospitalisation (4%), and then premature death (1%). CONCLUSION: Preparedness planning for future influenza pandemics must consider the impact on this medical workforce and incorporate strategies to minimise this impact, including infection control measures, well-designed protocols, and improved health sector surge capacity.


title: Our education, our concerns: The impact on medical student education of COVID‐19

text: March 2020, it seemed as if my world was turned upside down. I opened an email from my medical school dean of student affairs stating: Match Day, cancelled. The day that would determine where we trained as postgraduate residents, the day my class had worked towards for 4 years, cancelled due to this new virus that we seemed to know so little about: COVID-19. However, as important as that day was to my fellow 4th year medical students and I, we quickly learned that the impact was much larger. What about our electives, our mandatory rotations, and even the Sub-Internship's students still had to complete? Not just that, but "what can we do to help," became a common statement echoed by all students. We don't want to see this as a detriment to our education but a learning experience. A learning experience for how to be best prepared to help now, and in the future. One way to help is to make changes in medical education to ensure all students are still getting the absolute best level of education possible. This starts with recognizing the options we have and utilizing all of the tools at our disposal, despite the boundaries created by COVID-19.


title: Kidney manifestations of mild, moderate and severe coronavirus disease 2019: a retrospective cohort study

text: BACKGROUND: Coronavirus disease 2019 (COVID-19) is a pandemic that has affected more than 3 million patients globally. Previous data from Wuhan city showed that acute kidney injury (AKI), proteinuria and hematuria occurred frequently in patients with severe COVID-19. However, the prevalence of kidney injury in milder cases remains unclear. METHODS: This retrospective study included two major consecutive cohorts of COVID-19 patients in Sichuan Province. Baseline characteristics, laboratory data including renal function, proteinuria and dipstick hematuria, and other laboratory parameters were collected. A subgroup of patients was followed up for 2–4 weeks to evaluate the short-term outcome of renal impairment. RESULTS: Overall, 168 COVID-19-positive patients were included in the study. The majority of patients (79.7%) were diagnosed with mild or moderate disease. Half of patients presented with fever; however, in The Tibetan cohort, fever only occurred in 13.4% of patients. On hospital admission, proteinuria and dipstick hematuria were noted in 18.4% and 17.4% of patients, respectively, while AKI only occurred in one patient. Further analysis showed that severe or critical COVID-19 was associated with higher risk of proteinuria [relative risk (RR) 7.37, 95% confidence interval (CI) 2.45–22.18, P = 3.8 × 10(−4)] and dipstick hematuria (RR 8.30, 95% CI 2.69–25.56, P = 2.3 × 10(−4)). Proteinuria, dipstick hematuria, or the combination of proteinuria and hematuria could significantly predict severe or critical severe COVID-19. CONCLUSIONS: Proteinuria and dipstick hematuria are not uncommon in patients with COVID-19 infection, especially in severe or critical cases.


title: Interfacial pre-transmembrane domains in viral proteins promoting membrane fusion and fission

text: Abstract Membrane fusion and fission underlie two limiting steps of enveloped virus replication cycle: access to the interior of the host-cell (entry) and dissemination of viral progeny after replication (budding), respectively. These dynamic processes proceed mediated by specialized proteins that disrupt and bend the lipid bilayer organization transiently and locally. We introduced Wimley–White membrane-water partitioning free energies of the amino acids as an algorithm for predicting functional domains that may transmit protein conformational energy into membranes. It was found that many viral products possess unusually extended, aromatic-rich pre-transmembrane stretches predicted to stably reside at the membrane interface. Here, we review structure–function studies, as well as data reported on the interaction of representative peptides with model membranes, all of which sustain a functional role for these domains in viral fusion and fission. Since pre-transmembrane sequences also constitute antigenic determinants in a membrane-bound state, we also describe some recent results on their recognition and blocking at membrane interface by neutralizing antibodies.


title: Glycyrrhizin prevents of lipopolysaccharide/D‐galactosamine‐induced liver injury through down‐regulation of matrix metalloproteinase‐9 in mice

text: Glycyrrhizin, a biological active compound isolated from the liquorice root, has been used as a treatment for chronic hepatitis. We have examined the involvement of matrix metalloproteinase (MMP)‐9 in the development of lipopolysaccharide (LPS) and D‐galactosamine (GalN)‐induced liver injury in mice. We also investigated the effect of glycyrrhizin on expression of MMP‐9 in this model. Levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increased after LPS/GalN treatment. Expression of MMP‐9 mRNA and protein was markedly up‐regulated in liver tissues 6–8 h after LPS/GalN treatment. Pretreatment with glycyrrhizin (50 mg kg(−1)) and the MMP inhibitor (5 mg kg(−1)) suppressed increases in serum levels of ALT and AST in mice treated with LPS/GalN. Furthermore, glycyrrhizin inhibited levels of both mRNA and protein for MMP‐9. Immunohistochemical reaction for MMP‐9 was observed in macrophages/monocytes infiltrated in the inflammatory area of liver injury. Glycyrrhizin reduced the infiltration of inflammatory cells and immunoreactive MMP‐9 in liver injury. The results indicated that MMP‐9 played a role in the development of LPS/GalN‐induced mouse liver injury, and suggested that an inhibition by glycyrrhizin of the acute liver injury may have been due to a down‐regulation of MMP‐9.


title: Neurological immunotherapy in the era of COVID-19 — looking for consensus in the literature

text: The coronavirus disease 2019 (COVID-19) pandemic is concerning for patients with neuroimmunological diseases who are receiving immunotherapy. Uncertainty remains about whether immunotherapies increase the risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or increase the risk of severe disease and death upon infection. National and international societies have developed guidelines and statements, but consensus does not exist in several areas. In this Review, we attempt to clarify where consensus exists and where uncertainty remains to inform management approaches based on the first principles of neuroimmunology. We identified key questions that have been addressed in the literature and collated the recommendations to generate a consensus calculation in a Delphi-like approach to summarize the information. We summarize the international recommendations, discuss them in light of the first available data from patients with COVID-19 receiving immunotherapy and provide an overview of management approaches in the COVID-19 era. We stress the principles of medicine in general and neuroimmunology in particular because, although the risk of viral infection has become more relevant, most of the considerations apply to the general management of neurological immunotherapy. We also give special consideration to immunosuppressive treatment and cell-depleting therapies that might increase susceptibility to SARS-CoV-2 infection but reduce the risk of severe COVID-19.


title: SARS CTL vaccine candidates; HLA supertype‐, genome‐wide scanning and biochemical validation

text: Abstract: An effective Severe Acute Respiratory Syndrome (SARS) vaccine is likely to include components that can induce specific cytotoxic T‐lymphocyte (CTL) responses. The specificities of such responses are governed by human leukocyte antigen (HLA)‐restricted presentation of SARS‐derived peptide epitopes. Exact knowledge of how the immune system handles protein antigens would allow for the identification of such linear sequences directly from genomic/proteomic sequence information (Lauemoller et al., Rev Immunogenet 2001: 2: 477–91). The latter was recently established when a causative coronavirus (SARS‐CoV) was isolated and full‐length sequenced (Marra et al., Science 2003: 300: 1399–404). Here, we have combined advanced bioinformatics and high‐throughput immunology to perform an HLA supertype‐, genome‐wide scan for SARS‐specific CTL epitopes. The scan includes all nine human HLA supertypes in total covering >99% of all individuals of all major human populations (Sette & Sidney, Immunogenetics 1999: 50: 201–12). For each HLA supertype, we have selected the 15 top candidates for test in biochemical binding assays. At this time (approximately 6 months after the genome was established), we have tested the majority of the HLA supertypes and identified almost 100 potential vaccine candidates. These should be further validated in SARS survivors and used for vaccine formulation. We suggest that immunobioinformatics may become a fast and valuable tool in rational vaccine design.


title: A review of treatment modalities for Middle East Respiratory Syndrome

text: The Middle East Respiratory Syndrome coronavirus (MERS-CoV) has been a focus of international attention since its identification in 2012. Epidemiologically it is characterized by sporadic community cases, which are amplified by hospital-based outbreaks. Healthcare facilities in 27 countries from most continents have experienced imported cases, with the most significant outbreak involving 186 cases in Korea. The mortality internationally is 36% and guidance for clinical management has yet to be developed. Most facilities and healthcare providers outside of the Middle East receiving patients have no or little experience in the clinical management of MERS. When a case does occur there is likely little time for a critical appraisal of the literature and putative pharmacological options. We identified published literature on the management of both MERS-CoV and the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) through searches of PubMed and WHO and the US CDC websites up to 30 April 2016. A total of 101 publications were retrieved for critical appraisal. Most published literature on therapeutics for MERS are in vitro experiments, animal studies and case reports. Current treatment options for MERS can be categorized as: immunotherapy with virus-specific antibodies in convalescent plasma; polyclonal and monoclonal antibodies produced in vitro or in genetically modified animals; and antiviral agents. The use of any therapeutics in MERS-CoV remains investigational. The therapeutic agents with potential benefits and warranting further investigation include convalescent plasma, interferon-β/ribavirin combination therapy and lopinavir. Corticosteroids, ribavirin monotherapy and mycophenolic acid likely have toxicities that exceed potential benefits.


title: To punish or to assist? Divergent reactions to ingroup and outgroup members disobeying social distancing

text: In response to the COVID‐19 pandemic, societies face the formidable challenge of developing sustainable forms of sociability‐cumsocial‐distancing – enduring social life while containing the virus and preventing new outbreaks. Accordant public policies often balance between retributive (punishment‐based) and assistance (solidarity‐based) measures to foster responsible behaviour. Yet, the uncontrolled spreading of the disease has divided public opinion about which measures are best suited, and it has made salient group disparities in behaviour, potentially straining intergroup relations, elevating heated emotions, and undercutting coordinated international responses. In a 2 × 2 between‐subjects experiment, British citizens (N = 377) read about national in‐group or outgroup members (categorical differentiation), who were either conforming to or deviating from the corona regulations (normative differentiation). Participants then reported moral emotions towards the target national group and indicated support for public policies. In general, support for assistance policies outweighed support for retributive measures. Second, however, norm deviation was associated with less positive and more negative moral emotions, the latter category further relating to more punitiveness and less assistance support. Finally, respondents who read about norm‐violating outgroup members especially reported support for retributive measures, indicating that people might use norm deviation to justify outgroup derogation. We discuss implications for policymakers and formulate future research avenues.


title: Comment les enfants et adolescents avec le trouble déficit d’attention/hyperactivité (TDAH) vivent-ils le confinement durant la pandémie COVID-19 ?

text: OBJECTIVES: During the COVID-19 pandemic, the French government has decided a general lockdown. This unprecedented situation has raised concerns about children's and adolescent's mental health. Children and adolescents diagnosed with attention deficit hyperactivity disorder (ADHD) may find this context of restrained activity particularly tricky. The objectives of our study are to gather information about the well-being and global life conditions of children and adolescents with ADHD during the COVID-19 outbreak in France. METHODS: We designed a survey including both open-ended questions and questionnaire items for parents of children and adolescents with ADHD. Parents responded to the following open-ended questions: 1) “How is your child doing since the lockdown?” 2) “How is life at home since the lockdown?” 3) “If you had a remote service provision with a mental health professional (e.g. by telephone or video technology), please share your thoughts and any suggestions with us” 4) “Please share any other items that you think are important about ADHD symptoms of your child and the lockdown situation”. This survey was posted on social media on the 6th of April and disseminated by French ADHD-parent and patient organizations. The present article reports the descriptive, qualitative and textometrical analyses of the survey. RESULTS: Between day 20 and 30 of lockdown, 538 parents responded to the survey, and we included 533 responses in the final analysis. The vast majority of responders were women 95 % (95 % CI 93,50; 97,18) with children whose mean age was 10,5 (95 % CI 7.58; 13.44). Since the lockdown, 34.71 % (95 % CI 30.70; 38.94) of children experienced a worsening in well-being, 34.33 % (95 % CI 30.34; 38.56) showed no significant changes and 30.96 % (95 % CI 27.09; 35.10) were doing better according to their parents. The thematic analysis showed that an improvement of their children's anxiety was one of the main topics addressed by parents. This improvement related to less school-related strain and flexible schedules that respected their children's rhythm. Improved self-esteem was another topic that parents linked with a lesser exposure of their children to negative feed-back. Parents repeatedly reported both inattention and hyperactivity/impulsivity. However, optimal lockdown life conditions seemed to compensate for the impact of ADHD symptoms (e.g. sufficient space at home, presence of a garden). Some parents reported worsening of general well-being in their children, and this manifested as oppositional/defiant attitudes and emotional outbursts. Parents also cited sleep problems and anxiety in this context. As regards everyday life during lock-down, at-home schooling was another major topic–parents described that their children struggled to complete school-related tasks and that teachers seemed to have forgotten about academic accommodations. The lockdown situation seems to have raised parents’ awareness of the role of inattention and ADHD symptoms in their children's learning difficulties. Due to potential selection biases, the results of our survey may not be generalizable to all children and adolescents with ADHD. The main strengths of this rapid survey-based study lies in the reactivity of the participants and the quality and diversity of their responses to the open-ended questions. CONCLUSIONS: According to their parents, most children and adolescents with ADHD experience stability or improvement of their well-being. An improvement in school-related anxiety and the flexible adjustment to the children's’ rhythms as well as parents’ increased awareness of the difficulties their children experience are among the key topics in parents’ descriptions.


title: Viral quantity and pathological changes in broilers experimentally infected by IRFIBV32 isolate of infectious bronchitis virus

text: An Iranian isolate of avian infectious bronchitis virus IRFIBV32 was quantified in experimentally infected broilers using real-time reverse transcriptase polymerase chain reaction and histopathological changes was investigated. Thirty-six 3-week-old commercial broilers were inoculated by 10(5) ELD50/0.1 ml of the virus. On the various days post inoculation (dpi) different tissues were collected. The virus strongly started the replication in trachea at 1 dpi and reached to the maximum titer at 3 dpi. The highest IBV RNA level was shown in this organ. In lung, the virus was replicated with the titer lower than that of the trachea, but it rose up more at 5 dpi. The kidneys were the tissues with the least viral genome copy number, although the duration of the virus presence was considerable. The virus replicated in testes sooner than ovaries also disappeared sooner but the maximum viral yield in the ovaries was more. The virus titer in the studied tissues had an interesting fluctuation especially in caecal tonsils. Testes and ovaries were the organs that the virus could reactivate without using any chemical. The most severe lesions were observed in tracheae but they appeared in the lungs later. Lymphocyte infiltration in the kidneys was noted from 5 dpi even sooner than the lungs. There were no lesions in the caecal tonsils, testes and ovaries in spite of the virus replication in a high titer.


Protection of CT suites from COVID‑19 infection in a tertiary emergency hospital


title: Responding to COVID-19: What’s the Problem?

text: This commentary argues that the coronavirus SARS-CoV-2 pandemic should be considered as a transdisciplinary societal challenge that requires coordinated systemic thinking and actions in the context of uncertainty. Responses to the propagation of the coronavirus SARS-CoV-2 and the health, economic and social impacts of Covid-19 are complex, emergent and unpredictable. We describe the virtuous relations between three prerequisite conditions—multilevel governance, knowledge and types of resources and individual and collective behaviours—that should be combined in transdisciplinary responses.


Global surgery in the time of COVID-19: A trainee perspective


title: Viral Etiology and Clinical Profiles of Children with Severe Acute Respiratory Infections in China

text: BACKGROUND: No comprehensive analysis is available on the viral etiology and clinical characterization among children with severe acute respiratory infection (SARI) in China during 2009 H1N1 pandemic and post-pandemic period. METHODS: Cohort of 370 hospitalized children (1 to 72 months) with SARI from May 2008 to March 2010 was enrolled in this study. Nasopharyngeal aspirate (NPA) specimens were tested by a commercial assay for 18 respiratory viral targets. The viral distribution and its association with clinical character were statistically analyzed. RESULTS: Viral pathogen was detected in 350 (94.29%) of children with SARI. Overall, the most popular viruses were: enterovirus/rhinovirus (EV/RV) (54.05%), respiratory syncytial virus (RSV) (51.08%), human bocavirus (BoCA) (33.78%), human parainfluenzaviruse type 3 (PIV3) (15.41%), and adenovirus (ADV) (12.97%). Pandemic H1N1 was the dominant influenza virus (IFV) but was only detected in 20 (5.41%) of children. Moreover, detection rate of RSV and human metapneumovirus (hMPV) among suburb participants were significantly higher than that of urban area (P<0.05). Incidence of VSARI among suburb participants was also significant higher, especially among those of 24 to 59 months group (P<0.05). CONCLUSION: Piconaviruses (EV/RV) and paramyxoviruses are the most popular viral pathogens among children with SARI in this study. RSV and hMPV significantly increase the risk of SARI, especially in children younger than 24 months. Higher incidence of VSARI and more susceptibilities to RSV and hMPV infections were found in suburban patients.


title: The identification and characterization of nucleic acid chaperone activity of human enterovirus 71 nonstructural protein 3AB

text: Abstract Human enterovirus 71 (EV71) belongs to the genus Enterovirus in the family Picornaviridae and has been recognized as one of the most important pathogens that cause emerging infectious disease. Despite of the importance of EV71, the nonstructural protein 3AB from this virus is little understood for its function during EV71 replication. Here we expressed EV71 3AB protein as recombinant protein in a eukaryotic expression system and uncovered that this protein possesses a nucleic acid helix-destabilizing and strand annealing acceleration activity in a dose-dependent manner, indicating that EV71 3AB is a nucleic acid chaperone protein. Moreover, we characterized the RNA chaperone activity of EV71 3AB, and revealed that divalent metal ions, such as Mg2+ and Zn2+, were able to inhibit the RNA helix-destabilizing activity of 3AB to different extents. Moreover, we determined that 3B plus the last 7 amino acids at the C-terminal of 3A (termed 3B+7) possess the RNA chaperone activity, and five amino acids, i.e. Lys-80, Phe-82, Phe-85, Tyr-89, and Arg-103, are critical and probably the active sites of 3AB for its RNA chaperone activity. This report reveals that EV71 3AB displays an RNA chaperone activity, adds a new member to the growing list of virus-encoded RNA chaperones, and provides novel knowledge about the virology of EV71.


title: 11 Contingency Planning Emergency Response and Safety

text: Abstract Although there is some recognition of the importance of contingency planning, far too few firms have anything beyond a contingency plan that sits on a shelf in the CEO’s office. Even in those companies with crisis management teams (CMTs), the members often do not meet to plan or even discuss how the team would function in an actual situation. The most progressive firms offer the team members, fire brigades, and employees an opportunity to preplan (contingency planning) through mock exercises that replicate industrial disasters, explosions, fires, or tornado alerts. The end result is a better-prepared team of employees ready to respond to any contingency. Unfortunately, many firms have not gone this far. Contingency planning may not have been a traditional security process, but in today’s global business environment the security organization is assuming a much greater role and responsibility for its implementation. Even prior to the events of September 11, 2001, many organizations were becoming more conscious of the need to have contingency plans. A complete contingency planning program has three major elements: 1. Emergency Response 2. Crisis Management 3. Business Continuity: Business Recovery and Business Resumption Emergency response activities involve responding to an incident, crisis or disaster and managing that incident at the scene. Should an incident escalate to the crisis or disaster stage, a CMT should take over managing the crisis to its conclusion. If the crisis or disaster does cause damage to a company building, facility or operation, the CMT should hand over to a business continuity team the responsibility of recovery and resumption. After a disaster, it is critical that the business recovers and resumes normal (pre-event) operations as soon as possible. Customers, shareholders and stakeholders expect nothing less. Executive management has the obligation to ensure contingency planning is properly considered and addressed within their company. The consequences of not planning for contingencies can be catastrophic with numerous liability issues.


title: “Diseases and Natural Kinds”

text: David Thomasma called for the development of a medical ethics based squarely on the philosophy of medicine. He recognized, however, that widespread anti-essentialism presented a significant barrier to such an approach. The aim of this article is to introduce a theory that challenges these anti-essentialist objections. The notion of natural kinds presents a modest form of essentialism that can serve as the basis for a foundationalist philosophy of medicine. The notion of a natural kind is neither static nor reductionistic. Disease can be understood as making necessary reference to living natural kinds without invoking the claim that diseases themselves are natural kinds. The idea that natural kinds have a natural disposition to flourish as the kinds of things that they are provides a telos to which to tether the notion of disease – an objective telos that is broader than mere survival and narrower than subjective choice. It is argued that while nosology is descriptive and may have therapeutic implications, disease classification is fundamentally explanatory. Sickness and illness, while referring to the same state of affairs, can be distinguished from disease phenomenologically. Scientific and diagnostic fallibility in making judgments about diseases do not diminish the objectivity of this notion of disease. Diseases are things, not kinds. Injury is a concept parallel to disease that also makes necessary reference to living natural kinds. These ideas provide a new possibility for the development of a philosophy of medicine with implications for medical ethics.


title: A Single Mass Gathering Resulted in Massive Transmission of COVID-19 Infections in Malaysia with Further International Spread

text: Malaysia has recorded the highest number of COVID-19 cases in Southeast Asia with more than 35% of new COVID-19 cases linked to the Sri Petaling gathering, a Moslem missionary movement attended by more than 19 000 people of different nationalities, in March 2020 in Kuala Lumpur. From this cluster, 1701 samples have been tested positive out of 21 920 tests carried out. Thus, mass gathering during COVID-19 pandemic period should be banned to curb disease transmission.


title: Impact of the COVID‐19 pandemic on urological practice in emergency departments in Italy

text: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the disease it causes, coronavirus disease 2019 (COVID-19), are causing a rapid and tragic health emergency worldwide [1,2]. Italy was the first European country to experience a virus outbreak, starting on Feb, 21st 2020. It resulted in national quarantine, and the official lockdown of the country's non-essential businesses and services began on Mar, 9th 2020. Although several reports are available in the literature on recommendations for reorganization of the clinical and surgical activities [3-7], to our knowledge, no data is available on the effective impact of COVID-19 pandemic on the outcomes of other medical conditions.


title: The control of necrotic enteritis in sucking piglets by means of a Clostridium perfringens toxoid vaccine

text: Abstract Necrotic enteritis in sucking piglets constitutes a serious problem in piglet rearing units because of the high morbidity and mortality associated with the disease. The primary causal agent is Clostridium perfringens type C. The β-toxin plays a decisive role in the pathogenesis of this disease. A toxoid vaccine for use in sows has been developed and studied in field trials. The European Pharmacopoeia Monograph on vaccines for use in animals lays down a method of the efficacy testing based on the immunization of rabbits, the collection of pooled sera and the subsequent assay of anti-toxin antibodies in mice using an appropriate test toxin. The vaccine is regarded as effective if it induces a minimum of 10 IU of β-anti-toxin per ml of rabbit serum. We have established a range of 17.14–98.23 IU β-anti-toxin per ml rabbit serum induced by a sample of C. perfringens toxoid vaccine. The vaccine has been used under field conditions in different rearing units at the same time, mostly in the form of emergency vaccinations following the outbreak of disease. The outcome of vaccination was evaluated by recording the total numbers of piglets born alive and the piglet losses. Use of the vaccine, coupled with other measures, resulted in an approximately 30% reduction in the number of losses.


title: Myocardial and Microvascular Injury Due to Coronavirus Disease 2019

text: Over the past few months, health systems worldwide have been put to the test with the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Even though the leading clinical manifestations of the SARS-CoV-2 infection involve the respiratory tract, there is a non-negligible risk of systemic involvement leading to the onset of multi-organ failure with fatal consequences. Since the onset of COVID-19, patients with underlying cardiovascular disease have been at increased risk of poor clinical outcomes with higher death rates. Moreover, the occurrence of new-onset cardiac complications is not uncommon among patients hospitalised for COVID-19. Of importance, a significant portion of COVID-19 patients present with myocardial injury. Herein, the authors discuss the mechanisms leading to myocardial and microvascular injury in SARS-CoV-2 infection and their clinical implications.


title: A systematic review of the smartphone applications available for coronavirus disease 2019 (COVID19) and their assessment using the mobile app rating scale (MARS)

text: The global impact of COVID-19 pandemic has increased the need to rapidly develop and improve utilization of mobile applications across the healthcare continuum to address rising barriers of access to care due to social distancing challenges and allow continuity in sharing of health information, assist with COVID-19 activities including contact tracing, and providing useful information as needed. Here we provide an overview of mobile applications being currently utilized for COVID-19 related activities. We performed a systematic review of the literature and mobile platforms to assess mobile applications been currently utilized for COVID-19, and quality assessment of these applications using the Mobile Application Rating Scale (MARS) for overall quality, Engagement, Functionality, Aesthetics, and Information. Finally, we provide an overview of the key salient features that should be included in mobile applications being developed for future use. Our search identified 63 apps that are currently being used for COVID-19. Of these, 25 were selected from the Google play store and Apple App store in India, and 19 each from the UK and US. 18 apps were developed for sharing up to date information on COVID-19, and 8 were used for contact tracing while 9 apps showed features of both. On MARS Scale, overall scores ranged from 2.4 to 4.8 with apps scoring high in areas of functionality and lower in Engagement. Future steps should involve developing and testing of mobile applications using assessment tools like the MARS scale and the study of their impact on health behaviors and outcomes.


title: Biotechnological Potential of Bacteria Isolated from the Sea Cucumber Holothuria leucospilota and Stichopus vastus from Lampung, Indonesia

text: In order to minimize re-discovery of already known anti-infective compounds, we focused our screening approach on understudied, almost untapped marine environments including marine invertebrates and their associated bacteria. Therefore, two sea cucumber species, Holothuria leucospilota and Stichopus vastus, were collected from Lampung (Indonesia), and 127 bacterial strains were identified by partial 16S rRNA-gene sequencing analysis and compared with the NCBI database. In addition, the overall bacterial diversity from tissue samples of the sea cucumbers H. leucospilota and S. vastus was analyzed using the cultivation-independent Illumina MiSEQ analysis. Selected bacterial isolates were grown to high densities and the extracted biomass was tested against a selection of bacteria and fungi as well as the hepatitis C virus (HCV). Identification of putative bioactive bacterial-derived compounds were performed by analyzing the accurate mass of the precursor/parent ions (MS(1)) as well as product/daughter ions (MS(2)) using high resolution mass spectrometry (HRMS) analysis of all active fractions. With this attempt we were able to identify 23 putatively known and two previously unidentified precursor ions. Moreover, through 16S rRNA-gene sequencing we were able to identify putatively novel bacterial species from the phyla Actinobacteria, Proteobacteria and also Firmicutes. Our findings suggest that sea cucumbers like H. leucospilota and S. vastus are promising sources for the isolation of novel bacterial species that produce compounds with potentially high biotechnological potential.


title: Global analysis of multi-host and multi-vector epidemic models

text: Abstract We formulate a multi-group and multi-vector epidemic model in which hosts' dynamics is captured by staged-progression S E I R framework and the dynamics of vectors is captured by an SI framework. The proposed model describes the evolution of a class of zoonotic infections where the pathogen is shared by m host species and transmitted by p arthropod vector species. In each host, the infectious period is structured into n stages with a corresponding infectiousness parameter to each vector species. We determine the basic reproduction number R 0 2 ( m , n , p ) and investigate the dynamics of the systems when this threshold is less or greater than one. We show that the dynamics of the multi-host, multi-stage, and multi-vector system is completely determined by the basic reproduction number and the structure of the host-vector network configuration. Particularly, we prove that the disease-free equilibrium is globally asymptotically stable (GAS) whenever R 0 2 ( m , n , p ) < 1 , and a unique strongly endemic equilibrium exists and is GAS if R 0 2 ( m , n , p ) > 1 and the host-vector configuration is irreducible. That is, either the disease dies out or persists in all hosts and all vector species.


title: VIP: an integrated pipeline for metagenomics of virus identification and discovery

text: Identification and discovery of viruses using next-generation sequencing technology is a fast-developing area with potential wide application in clinical diagnostics, public health monitoring and novel virus discovery. However, tremendous sequence data from NGS study has posed great challenge both in accuracy and velocity for application of NGS study. Here we describe VIP (“Virus Identification Pipeline”), a one-touch computational pipeline for virus identification and discovery from metagenomic NGS data. VIP performs the following steps to achieve its goal: (i) map and filter out background-related reads, (ii) extensive classification of reads on the basis of nucleotide and remote amino acid homology, (iii) multiple k-mer based de novo assembly and phylogenetic analysis to provide evolutionary insight. We validated the feasibility and veracity of this pipeline with sequencing results of various types of clinical samples and public datasets. VIP has also contributed to timely virus diagnosis (~10 min) in acutely ill patients, demonstrating its potential in the performance of unbiased NGS-based clinical studies with demand of short turnaround time. VIP is released under GPLv3 and is available for free download at: https://github.com/keylabivdc/VIP.


title: Call to Action: Preserving and Advocating for Essential Care for Women during the COVID-19 Pandemic

text: Abstract The COVID-19 pandemic has redefined ‘essential care’, and reproductive healthcare has become a frequently targeted and debated topic. As Obstetricians and Gynecologists (OBGYN), we stand with our patients and others as advocates for women’s reproductive health. With the medical and surgical training to provide all aspects of reproductive healthcare, OBGYNs are indispensable and uniquely positioned to advocate for the full spectrum of care that our patients need right now. All patients have a right to these services. Contraception and abortion care remain essential, and we need to work at the local, state and federal level on policies that preserve these critical services. We must also support policies that will promote expansion of care, including lengthening Medicaid pregnancy/postpartum coverage. While we continue to see patients, this is the time to engage outside clinical encounters by participating in lobbying and other advocacy efforts to preserve essential services, protecting the health, life, and welfare of our patients during COVID-19.


title: A vaccine effective against Zika virus is theoretically possible but may not be delivered anytime soon

text: Following the first report in May 2015 of the unexpected emergence of Zika in north east Brazil, there has been an explosive epidemic of this infection across Latin America. The outbreak has caused alarm among social and news media as to the virulence and transmission potential of the Aedes mosquito-borne virus. This debate is heightened by the proximity, both in time and distance, to the forthcoming Olympic Games to be held in Rio de Janeiro this August, provoking fears for the safety of athletes and spectators alike. The threat, real or perceived, is exacerbated by the movement between nations in the same or separate continents of persons who act unwittingly as asymptomatic carriers. Pregnant females are considered at greatest risk because microcephaly in newborn infants is linked to, if not yet proven as caused by, Zika infection. In February this year, the World Health Organization declared that further to the then unconfirmed association between the virus and the clinical manifestations of microcephaly and also Guillain-Barré syndrome, the Zika epidemic was a “public health emergency of international concern”. No anti-Zika therapy, vaccine or drug, is currently available and while the production of the former has now been prioritized by multiple funding agencies, the history of infectious disease vaccine development indicates that this may take several years to reach the market place. The fact that Zika is a close relative of yellow fever and Japanese encephalitis viruses, for both of which there are already effective vaccines, provides a rational basis for the fast-tracked laboratory-based preparation of a candidate vaccine. However, undertaking clinical trials on pregnant females provides ethical and practical hurdles to overcome before licensure is granted for public administration. Meanwhile, public health management strategies, including mosquito control programs to reduce breeding, are needed to limit the global spread of this re-emerging disease.


title: Immune responses and pathogenesis of SARS‐CoV‐2 during an outbreak in Iran: Comparison with SARS and MERS

text: The beginning of 2020 has seen the emergence of COVID‐19, an outbreak caused by a novel coronavirus, SARS‐CoV‐2, an important pathogen for humans. There is an urgent need to better understand this new virus and to develop ways to control its spread. In Iran, the first case of the COVID‐19 was reported after spread from China and other countries. Fever, cough, and fatigue were the most common symptoms of this virus. In worldwide, the incubation period of COVID‐19 was 3 to 7 days and approximately 80% of infections are mild or asymptomatic, 15% are severe, requiring oxygen, and 5% are critical infections, requiring ventilation. To mount an antiviral response, the innate immune system recognizes molecular structures that are produced by the invasion of the virus. COVID‐19 infection induces IgG antibodies against N protein that can be detected by serum as early as day 4 after the onset of disease and with most patients seroconverting by day 14. Laboratory evidence of clinical patients showed that a specific T‐cell response against SARS‐CoV‐2 is important for the recognition and killing of infected cells, particularly in the lungs of infected individuals. At present, there is no specific antiviral therapy for COVID‐19 and the main treatments are supportive. In this review, we investigated the innate and acquired immune responses in patients who recovered from COVID‐19, which could inform the design of prophylactic vaccines and immunotherapy for the future.


title: Life Interrupted – On the Front Lines with COVID-19

text: [Figure: see text]


title: Mesenchymal stem cell (MSc) secretome: A possible therapeutic strategy for intensive-care COVID-19 patients

text: As an emerging global health challenge, COVID-19 requires international knowledge to reach novel possible therapeutic strategies, especially for intensive-care patients. During the early stages of infection, pneumocytes II are the primary infected cells, harming the respiratory system. We have previous evidence in murine models that MSc’s secretome can be used to treat pulmonary injuries induced with bleomycin, due to its content: growth factors, extracellular vesicles, and exosomes. We hypothesize and strongly recommend MSc secretome testing and production, in xenofree conditions, to be used as an alternative approach in SARS-Cov-2 patients in critical conditions.


title: Understanding Covid and the associated post- infectious hyper-inflammatory inflammatory state (PIMS-TS) in children

text: Summary When SARS-CoV2 infection was first reported from China, very few children had severe lung or systemic disease. Approximately six weeks after the first adult cases were reported in the United Kingdom, a small subgroup of children of largely non-white backgrounds, presented with severe hyper-inflammatory disease, most likely associated with Covid. The possible reasons for this ethnic predilection are explored.


title: Oropharyngeal candidiasis in hospitalized COVID‐19 Patients from Iran: Species identification and antifungal susceptibility pattern

text: BACKGROUND: Emergence of coronavirus disease 2019 (COVID‐19) is a major healthcare threat. Apparently, the novel coronavirus (SARS‐CoV‐2) is armed by special abilities to spread and dysregulate the immune mechanisms. The likelihood of oropharyngeal candidiasis (OPC) development in COVID‐19 patients with a list of attributable risk factors for oral infections has not yet been investigated. OBJECTIVES: We here aim to investigate the prevalence, causative agents, and antifungal susceptibility pattern of OPC in Iranian COVID‐19 patients. PATIENTS AND METHODS: A total of 53 hospitalized COVID‐19 patients with OPC were studied. Relevant clinical data were mined. Strain identification was performed by 21‐plex PCR and sequencing of the internal transcribed spacer region (ITS1‐5.8S‐ITS2). Antifungal susceptibility testing to fluconazole, itraconazole, voriconazole, amphotericin B, caspofungin, micafungin and anidulafungin was performed according to the CLSI broth dilution method. RESULTS: In 53 COVID‐19 patients with OPC, cardiovascular diseases (52.83 %), and diabetes (37.7 %) were the principal underlying conditions. The most common risk factor was lymphopenia (71%). In total, 65 Candida isolates causing OPC were recovered. C. albicans (70.7%) was the most common, followed by C. glabrata (10.7%), C. dubliniensis (9.2%), C. parapsilosis sensu stricto (4.6%), C. tropicalis (3%), and Pichia kudriavzevii (=C. krusei, 1.5%). Majority of the Candida isolates were susceptible to all three classes of antifungal drugs. CONCLUSION: Our data clarified some concerns regarding the occurrence of OPC in Iranian COVID‐19 patients. Further studies should be conducted to design an appropriate prophylaxis program and improve management of OPC in critically ill COVID‐19 patients.


Erupción tipo pitiriasis rosada de Gibert en una paciente asintomática con positividad para COVID-19


Volunteering During the Coronavirus Pandemic


title: Design and construction of African swine fever virus chimeras incorporating foreign viral epitopes

text: In the present work we have studied the feasibility of introducing foreign epitopes into the African swine fever virus (ASFV) particle by genetic manipulation of the virus. For this purpose, we developed specific transfer vectors containing the gene encoding for the highly antigenic structural ASFV protein p54 in which foreign sequences were introduced. DNA sequences encoding continuous linear epitopes, the antigenic site A from foot-and-mouth disease virus (FMDV) VP1 protein and the DAff3 antigenic determinant from transmissible gastroenteritis coronavirus (TGEV) nucleoprotein N, were separately cloned into the p54 gene, in a region encoding a non-essential domain of the protein. Chimeric p54 genes were inserted by homologous recombination into the thymidine kinase (TK) locus of ASFV genome. The resulting recombinant viruses efficiently expressed both chimeric proteins under transcriptional control of the p54 promoter, and the chimeric gene products were recognized by antibodies to both p54 and foreign epitopes. The modified p54 proteins were also found in the viral particles and complemented the function of the wild-type p54, since deletion of the p54 gene from recombinant viruses did not affected virus replication in Vero cells. This work demonstrates for the first time the feasibility of incorporating foreign amino acid sequences (up to 18 residues) into a protein component of the ASFV particle without affecting virus viability.