title: Neurocovid: Pharmacological recommendations for delirium associated with COVID-19

text: BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as one of the biggest health threats of our generation. A significant portion of patients are presenting with delirium and neuropsychiatric sequelae of the disease. Unique exam findings and responses to treatment have been identified. We seek to provide pharmacologic and treatment recommendations specific to delirium in patients with COVID-19. METHODS: We performed a literature search reviewing the neuropsychiatric complications and treatments in prior coronavirus epidemics including middle eastern respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) coronaviruses as well as the emerging literature regarding COVID-19. We also convened a work group of consultation-liaison psychiatrists actively managing COVID-19 patients in our hospital. Finally, we synthesized these findings to provide preliminary pharmacologic recommendations for treating delirium in these patients. RESULTS: Delirium is frequently found in patients who test positive for COVID-19, even in the absence of respiratory symptoms. There appears to be a higher rate of agitation, myoclonus, abulia, and alogia. No data are currently available on the treatment of delirium in COVID-19 patients. Extrapolating from general delirium treatment, MERS/SARS case reports, and our experience, preliminary recommendations for pharmacologic management have been assembled. CONCLUSIONS: COVID-19 is associated with neuropsychiatric symptoms. Low potency neuroleptics and alpha-2 adrenergic agents may be especially useful in this setting. Further research into the pathophysiology of COVID-19 will be key in developing more targeted treatment guidelines.


title: The effects of past SARS experience and proximity on declines in numbers of travelers to the Republic of Korea during the 2015 MERS outbreak: A retrospective study

text: Abstract Background The experience of previous sizable outbreaks may affect travelers’ decisions to travel to an area with an ongoing outbreak. Methods We estimated changes in monthly numbers of visitors to the Republic of Korea (ROK) in 2015 compared to projected values by selected areas. We tested whether areas’ experience of a previous SARS outbreak of ≥100 cases or distance to the ROK had a significant effect on travel to the ROK during the MERS outbreak using t-tests and regression models. Results The percentage changes in visitors from areas with a previous SARS outbreak of ≥100 cases decreased more than the percentage changes in visitors from their counterparts in June (52.4% vs. 23.3%) and July (60.0% vs. 31.4%) during the 2015 MERS outbreak. The percentage changes in visitors from the close and intermediate categories decreased more than the far category. The results from regression models and sensitivity analyses demonstrated that areas with ≥100 SARS cases and closer proximity to the ROK had significantly larger percentage decreases in traveler volumes during the outbreak. Conclusions During the 2015 MERS outbreak, areas with a previous sizable SARS outbreak and areas near the ROK showed greater decreases in percentage changes in visitors to the ROK.


title: Sherlock Genomes — viral investigator

text: This month's Genome Watch highlights how deep sequencing technologies have vastly reduced the time and prior knowledge needed to generate viral genomes.


title: Clinical analysis of ten pregnant women with COVID-19 in Wuhan, China: A retrospective study

text: Abstract Background COVID-19 is spreading globally. This study aims to evaluate the clinical characteristics and outcomes of pregnant women confirmed with COVID-19 to provide reference for clinical work. Methods The clinical features and outcomes of 10 pregnant women confirmed with COVID-19 at Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, a tertiary- care teaching hospital in Hubei province, Wuhan, China from January 23 to February 23, 2020 were retrospectively analyzed. Results All the 10 observed pregnant women including 9 singletons and 1 twin were native people in Wuhan. All of them were diagnosed mild COVID-19, and none one of the patients developed severe COVID-19 or died. Among the 10 patients, two patients underwent vaginal delivery, two patients underwent intrapartum cesarean section, and the remaining six patients underwent elective cesarean section. All of 10 patients showed lung abnormalities by pulmonary CT images after delivery. Their eleven newborns were recorded and no neonatal asphyxia was observed. Conclusions Pulmonary CT screening on admission may be necessary to reduce the risk of nosocomial transmission of COVID-19 during the outbreak period. And COVID-19 is not an indication of cesarean section.


title: The importance of dog population contact network structures in rabies transmission

text: Canine rabies transmission was interrupted in N’Djaména, Chad, following two mass vaccination campaigns. However, after nine months cases resurged with re-establishment of endemic rabies transmission to pre-intervention levels. Previous analyses investigated district level spatial heterogeneity of vaccination coverage, and dog density; and importation, identifying the latter as the primary factor for rabies resurgence. Here we assess the impact of individual level heterogeneity on outbreak probability, effectiveness of vaccination campaigns and likely time to resurgence after a campaign. Geo-located contact sensors recorded the location and contacts of 237 domestic dogs in N’Djaména over a period of 3.5 days. The contact network data showed that urban dogs are socially related to larger communities and constrained by the urban architecture. We developed a network generation algorithm that extrapolates this empirical contact network to networks of large dog populations and applied it to simulate rabies transmission in N’Djaména. The model predictions aligned well with the rabies incidence data. Using the model we demonstrated, that major outbreaks are prevented when at least 70% of dogs are vaccinated. The probability of a minor outbreak also decreased with increasing vaccination coverage, but reached zero only when coverage was near total. Our results suggest that endemic rabies in N’Djaména may be explained by a series of importations with subsequent minor outbreaks. We show that highly connected dogs hold a critical role in transmission and that targeted vaccination of such dogs would lead to more efficient vaccination campaigns.


title: ACE2, TMPRSS2 AND FURIN GENE EXPRESSION IN THE AIRWAYS OF PEOPLE WITH ASTHMA – IMPLICATIONS FOR COVID-19

text: Abstract To-date, there has not been a clear signal suggesting that asthma or treatment with inhaled steroids are a risk factor for severe COVID-19 disease. We have therefore explored ACE2 receptor mRNA expression, and co-factors for Sars-CoV-2 infectivity (TMPRSS2 and furin) in bronchial brushes and biopsies from people with asthma and healthy controls, and looked for relationships between asthma severity, Th2- and IL-17 dependent gene signatures, and clinical demographics (age, sex). We have looked at a cohort of 356 research participants from previously described studies. The only significant association was a positive correlation between ACE2 and IL-17-dependent gene expression, and an inverse correlation between ACE2 and Th2-cytokine-dependent gene expression. These data suggest that differences in ACE2, TMPRSS2 and furin epithelial and airway gene expression are unlikely to confer enhanced COVID-19 pneumonia risk in patients with asthma across all treatment intensities and severity.


title: Which curve provides the best explanation of the growth in confirmed COVID-19 cases in Chile?

text: OBJECTIVE: to explore the best type of curve or trend model that could explain the epidemiological behavior of the infection by COVID-19 and derive the possible causes that contribute to explain the corresponding model and the health implications that can be inferred. METHOD: data were collected from the COVID-19 reports of the Department of Epidemiology, Ministry of Health, Chile. Curve adjustment studies were developed with the data in four different models: quadratic, exponential, simple exponential smoothing, and double exponential smoothing. The significance level used was α≤0.05. RESULTS: the curve that best fits the evolution of the accumulated confirmed cases of COVID-19 in Chile is the doubly-smoothed exponential curve. CONCLUSION: the number of infected patients will continue to increase. Chile needs to remain vigilant and adjust the strategies around the prevention and control measures. The behavior of the population plays a fundamental role. We suggest not relaxing restrictions and further improving epidemiological surveillance. Emergency preparations are needed and more resource elements need to be added to the current health support. This prediction is provisional and depends on keeping all intervening variables constant. Any alteration will modify the prediction.


title: Declines in Hospitalizations for Acute Cardiovascular Conditions During the COVID-19 Pandemic: A Multicenter Tertiary Care Experience

text: Abstract Background While patients with cardiovascular disease face excess risks of severe illness with coronavirus disease-2019 (COVID-19), there may be indirect consequences of the pandemic on this high-risk patient segment. Objectives To examine longitudinal trends in hospitalizations for acute cardiovascular conditions across a tertiary care healthcare system. Methods We tracked acute cardiovascular hospitalizations between January 1st, 2019 and March 31st, 2020. We estimated daily hospitalization rates using negative binomial models. Temporal trends in hospitalization rates were compared across the first 3 months of 2020, with the first 3 months of 2019 as a reference. Results From January 1, 2019 to March 31, 2020, 6,083 patients experienced 7,187 hospitalizations for primary acute cardiovascular reasons. There was 43.4% (27.4% to 56.0%) fewer estimated daily hospitalizations in March 2020 as compared with March 2019 (P<0.001). The daily rate of hospitalizations did not change throughout 2019 (-0.01% per day [-0.04% to +0.02%], P=0.50), January 2020 (-0.5% per day [-1.6% to +0.5%], P=0.31), or February 2020 (+0.7% per day [-0.6% to +2.0%], P=0.27). There was significant daily decline in hospitalizations in March 2020 (-5.9% per day [-7.6% to -4.3%], P<0.001). Length of stay was shorter (4.8 [2.4,8.3] days vs. 6.0 [3.1,9.6] days; P=0.003) and in-hospital mortality was not significantly different (6.2% vs. 4.4%; P=0.30) in March 2020 compared with March 2019. Conclusions During the first phase of the COVID-19 pandemic, there was a marked decline in acute cardiovascular hospitalizations and patients who were admitted had shorter lengths of stay. These data substantiate concerns that acute care of cardiovascular conditions may be delayed, deferred, or abbreviated during the COVID-19 pandemic.


title: Health as a “global public good”: creating a market for pandemic risk

text: In the final article of the series Felix Stein and Devi Sridhar examine how the World Bank is trying to provide finance to improve preparedness for global pandemics


title: RNA recombination at Chikungunya virus 3'UTR as an evolutionary mechanism that provides adaptability

text: The potential of RNA viruses to adapt to new environments relies on their ability to introduce changes in their genomes, which has resulted in the recent expansion of re-emergent viruses. Chikungunya virus is an important human pathogen transmitted by mosquitoes that, after 60 years of exclusive circulation in Asia and Africa, has rapidly spread in Europe and the Americas. Here, we examined the evolution of CHIKV in different hosts and uncovered host-specific requirements of the CHIKV 3’UTR. Sequence repeats are conserved at the CHIKV 3’UTR but vary in copy number among viral lineages. We found that these blocks of repeated sequences favor RNA recombination processes through copy-choice mechanism that acts concertedly with viral selection, determining the emergence of new viral variants. Functional analyses using a panel of mutant viruses indicated that opposite selective pressures in mosquito and mammalian cells impose a fitness cost during transmission that is alleviated by recombination guided by sequence repeats. Indeed, drastic changes in the frequency of viral variants with different numbers of repeats were detected during host switch. We propose that RNA recombination accelerates CHIKV adaptability, allowing the virus to overcome genetic bottlenecks within the mosquito host. These studies highlight the role of 3’UTR plasticity on CHIKV evolution, providing a new paradigm to explain the significance of sequence repetitions.


title: Outbreak of pneumonia of unknown etiology in Wuhan, China: The mystery and the miracle

text: Since December 2019, a total of 41 cases of pneumonia of unknown etiology have been confirmed in Wuhan city, Hubei Province, China. Wuhan city is a major transportation hub with a population of more than 11 million people. Most of the patients visited a local fish and wild animal market last month. At a national press conference held today, Dr. Jianguo Xu, an academician of the Chinese Academy of Engineering, who led a scientific team announced that a new-type coronavirus, tentatively named by World Health Organization as the 2019-new coronavirus (2019-nCoV), had caused this outbreak (1).


title: Coronavirus Endoribonuclease and Deubiquitinating Interferon Antagonists Differentially Modulate the Host Response during Replication in Macrophages

text: Coronaviruses (CoVs) encode multiple interferon (IFN) antagonists that modulate the host response to virus replication. Here, we evaluated the host transcriptional response to infection with murine coronaviruses encoding independent mutations in one of two different viral antagonists, the deubiquitinase (DUB) within nonstructural protein 3 or the endoribonuclease (EndoU) within nonstructural protein 15. We used transcriptomics approaches to compare the scope and kinetics of the host response to the wild-type (WT), DUBmut, and EndoUmut viruses in infected macrophages. We found that the EndoUmut virus activates a focused response that predominantly involves type I interferons and interferon-related genes, whereas the WT and DUBmut viruses more broadly stimulate upregulation of over 2,800 genes, including networks associated with activating the unfolded protein response (UPR) and the proinflammatory response associated with viral pathogenesis. This study highlights the role of viral interferon antagonists in shaping the kinetics and magnitude of the host response during virus infection and demonstrates that inactivating a dominant viral antagonist, the coronavirus endoribonuclease, dramatically alters the host response in macrophages. IMPORTANCE Macrophages are an important cell type during coronavirus infections because they “notice” the infection and respond by inducing type I interferons, which limits virus replication. In turn, coronaviruses encode proteins that mitigate the cell’s ability to signal an interferon response. Here, we evaluated the host macrophage response to two independent mutant coronaviruses, one with reduced deubiquitinating activity (DUBmut) and the other containing an inactivated endoribonuclease (EndoUmut). We observed a rapid, robust, and focused response to the EndoUmut virus, which was characterized by enhanced expression of interferon and interferon-related genes. In contrast, wild-type virus and the DUBmut virus elicited a more limited interferon response and ultimately activated over 2,800 genes, including players in the unfolded protein response and proinflammatory pathways associated with progression of significant disease. This study reveals that EndoU activity substantially contributes to the ability of coronaviruses to evade the host innate response and to replicate in macrophages.


title: Building and Optimizing a Virus-specific T Cell Receptor Library for Targeted Immunotherapy in Viral Infections

text: Restoration of antigen-specific T cell immunity has the potential to clear persistent viral infection. T cell receptor (TCR) gene therapy can reconstitute CD8 T cell immunity in chronic patients. We cloned 10 virus-specific TCRs targeting 5 different viruses, causing chronic and acute infection. All 10 TCR genetic constructs were optimized for expression using a P2A sequence, codon optimization and the addition of a non-native disulfide bond. However, maximum TCR expression was only achieved after establishing the optimal orientation of the alpha and beta chains in the expression cassette; 9/10 TCRs favored the beta-P2A-alpha orientation over alpha-P2A-beta. Optimal TCR expression was associated with a significant increase in the frequency of IFN-gamma+ T cells. In addition, activating cells for transduction in the presence of Toll-like receptor ligands further enhanced IFN-gamma production. Thus, we have built a virus-specific TCR library that has potential for therapeutic intervention in chronic viral infection or virus-related cancers.


title: Coagulopathy in COVID‐19

text: The COVID‐19 pandemic has become an urgent issue in every country. Based on recent reports, the most severely ill patients present with coagulopathy, and disseminated intravascular coagulation (DIC)‐like massive intravascular clot formation is frequently seen in this cohort. Therefore, coagulation tests may be considered useful to discriminate severe cases of COVID‐19. The clinical presentation of COVID‐19‐associated coagulopathy is organ dysfunction primarily, while hemorrhagic events are less frequent. Changes in hemostatic biomarkers represented by increase in D‐dimer and fibrin/fibrinogen degradation products indicate the essence of coagulopathy is massive fibrin formation. In comparison with bacterial‐sepsis‐associated coagulopathy/DIC, prolongation of prothrombin time, and activated partial thromboplastin time, and decrease in antithrombin activity is less frequent and thrombocytopenia is relatively uncommon in COVID‐19. The mechanisms of the coagulopathy are not fully elucidated, however. It is speculated that the dysregulated immune responses orchestrated by inflammatory cytokines, lymphocyte cell‐death, hypoxia, and endothelial damage are involved. Bleeding tendency is uncommon, but the incidence of thrombosis in COVID‐19 and the adequacy of current recommendations regarding standard venous thromboembolic dosing are uncertain.


title: Reply to McDonald, “Protections against the Risk of Airborne SARS-CoV-2 Infection”

text: We thank Dr McDonald ([1][1]) for his close reading of our paper ([2][2]) and acknowledge that he makes important arguments for exercising precautions in order to prevent built environment-mediated transmission of SARS-CoV-2 We would like to address two specific points that Dr McDonald brings up


title: A hypothesized role for dysregulated bradykinin signaling in COVID‐19 respiratory complications

text: As of April 20, 2020, over time, the COVID‐19 pandemic has resulted in 157 970 deaths out of 2 319 066 confirmed cases, at a Case Fatality Rate of ~6.8%. With the pandemic rapidly spreading, and health delivery systems being overwhelmed, it is imperative that safe and effective pharmacotherapeutic strategies are rapidly explored to improve survival. In this paper, we use established and emerging evidence to propose a testable hypothesis that, a vicious positive feedback loop of des‐Arg(9)‐bradykinin‐ and bradykinin‐mediated inflammation → injury → inflammation, likely precipitates life threatening respiratory complications in COVID‐19. Through our hypothesis, we make the prediction that the FDA‐approved molecule, icatibant, might be able to interrupt this feedback loop and, thereby, improve the clinical outcomes. This hypothesis could lead to basic, translational, and clinical studies aimed at reducing COVID‐19 morbidity and mortality.


title: Interferon gamma and interleukin 1, but not interferon alfa, inhibit rotavirus entry into human intestinal cell lines

text: Abstract BACKGROUND & AIMS: Rotavirus, an important agent of gastroenteritis in children, causes diarrhea by infecting differentiated villus enterocytes in the small intestine. The aim of this study was to determine whether cytokines that can be expressed by mucosal cells have an effect on the rotavirus susceptibility of cultured human enterocytes. METHODS: Caco-2 and HT-29 cells were pretreated with various cytokines before challenge with rotavirus. RESULTS: Interleukin (IL)-1, interferon (IFN)-alpha, and IFN-gamma pretreatment led to a dose-dependent resistance to rotavirus infection. Maximum effects occurred after 72 hours of pretreatment, whereas no detectable inhibition occurred with <12 hours of pretreatment. Liposomal transfection of single-shelled and double-shelled rotavirus particles bypassed the block to rotavirus replication in IFN-gamma- and IL-1- treated but not IFN-alpha-treated cells. Binding studies with purified, metabolically labeled rotavirus showed no significant difference among IFN-gamma- and IFN-alpha-treated and control Caco-2 cells. Viral entry into Caco-2 cells was significantly inhibited by IFN-gamma and IL-1 but not IFN-alpha. CONCLUSIONS: IFN-alpha and IFN-gamma induce rotavirus resistance by different mechanisms, suggesting that cytokines play a role in host defense against viral agents by changing the phenotype of intestinal epithelial cells. (Gastroenterology 1997 Jul;113(1):81-9)


title: Early non-invasive ventilation treatment for severe influenza pneumonia

text: Abstract The role of non-invasive ventilation (NIV) in acute respiratory failure caused by viral pneumonia remains controversial. Our objective was to evaluate the use of NIV in a cohort of (H1N1)v pneumonia. Usefulness and success of NIV were assessed in a prospective, observational registry of patients with influenza A (H1N1) virus pneumonia in 148 Spanish intensive care units (ICUs) in 2009–10. Significant variables for NIV success were included in a multivariate analysis. In all, 685 patients with confirmed influenza A (H1N1)v viral pneumonia were admitted to participating ICUs; 489 were ventilated, 177 with NIV. The NIV was successful in 72 patients (40.7%), the rest required intubation. Low Acute Physiology and Chronic Health Evaluation (APACHE) II, low Sequential Organ Failure Assessment (SOFA) and absence of renal failure were associated with NIV success. Success of NIV was independently associated with fewer than two chest X-ray quadrant opacities (OR 3.5) and no vasopressor requirement (OR 8.1). However, among patients with two or more quadrant opacities, a SOFA score ≤7 presented a higher success rate than those with SOFA score >7 (OR 10.7). Patients in whom NIV was successful required shorter ventilation time, shorter ICU stay and hospital stay than NIV failure. In patients in whom NIV failed, the delay in intubation did not increase mortality (26.5% versus 24.2%). Clinicians used NIV in 25.8% of influenza A (H1N1)v viral pneumonia admitted to ICU, and treatment was effective in 40.6% of them. NIV success was associated with shorter hospital stay and mortality similar to non-ventilated patients. NIV failure was associated with a mortality similar to those who were intubated from the start.


title: Clinical and Epidemiological Characteristics of COVID-19 Patients in Chongqing China

text: Objectives: To study in-depth the clinical and epidemiological characteristics of pneumonia resulting from COVID-19 and provide evidence for effective public health decisions. Methods: This was a retrospective, single-center research study. Participants were enrolled from patients presenting at the Chongqing Public Health Medical Treatment Center from Jan 24 to Feb 7, 2020, and were confirmed as having COVID-19. Results: A total of 114 COVID-19 patients (99 mild, 4 severe, 11 critical) of which 56 (56/114; 49.1%) were male, 58 (58/114; 50.9%) were female with a mean age of 46.05 years. Twenty nine (29/114; 25.44%) patients suffered from chronic diseases. Neutrophils counts in 23.68% (27/114) of patients were abnormally low and abnormally high in 21.05% (24/114). Erythrocyte sedimentation rate and the C-reactive protein levels were abnormally elevated in 76.5% (62/81) and 62.9% (66/105) of patients, respectively. Creatine kinase isoenzymes (CK-MB), pro-brain natriuretic peptide (pro-BNP) and troponin levels were above the normal range in 7.10% (8/112), 66.7% (10/15), and 100% of patients, respectively. The percentage of patients in which the partial pressure of oxygen (PaO(2))/fraction of inspired O(2)(FiO(2)) ratio exceeded 200 was 60%. A total of 91 (91/114; 79.82%) patients displayed severe bilateral pneumonia, 52 (52/114; 45.61%) exhibited ground-glass opacity, and pulmonary consolidation was observed in 4 (3.51%) patients. Differences in shortness of breath, insomnia, inappetence, the procalcitonin (PCT) levels, FiO(2) and PaO(2)/FiO(2) among the three groups were statistically significant (p < 0.05). Differences between the mild and severe groups was observed in neutrophil and lymphocyte counts, CD4 expression, and levels of C-reactive protein, alanine aminotransferase, aspartate aminotransferase and albumin (P < 0.05). Between the mild and critical groups, differences were observed in neutrophils, platelets, and CD4 expression (P < 0.05). A difference in C-reactive protein levels between severe and critical groups was also found (P < 0.05). Conclusions: In the majority of cases no gender differences were observed and mostly the symptoms were mild. Evidence of efficient human-to-human virus transmission was found. The elderly with comorbidities were more prone to develop into severe or critical illness. Age and comorbidity may be risk factors for poor outcome.


title: Macrophages and cytokines in the early defence against herpes simplex virus

text: Herpes simplex virus (HSV) type 1 and 2 are old viruses, with a history of evolution shared with humans. Thus, it is generally well-adapted viruses, infecting many of us without doing much harm, and with the capacity to hide in our neurons for life. In rare situations, however, the primary infection becomes generalized or involves the brain. Normally, the primary HSV infection is asymptomatic, and a crucial element in the early restriction of virus replication and thus avoidance of symptoms from the infection is the concerted action of different arms of the innate immune response. An early and light struggle inhibiting some HSV replication will spare the host from the real war against huge amounts of virus later in infection. As far as such a war will jeopardize the life of the host, it will be in both interests, including the virus, to settle the conflict amicably. Some important weapons of the unspecific defence and the early strikes and beginning battle during the first days of a HSV infection are discussed in this review. Generally, macrophages are orchestrating a multitude of anti-herpetic actions during the first hours of the attack. In a first wave of responses, cytokines, primarily type I interferons (IFN) and tumour necrosis factor are produced and exert a direct antiviral effect and activate the macrophages themselves. In the next wave, interleukin (IL)-12 together with the above and other cytokines induce production of IFN-γ in mainly NK cells. Many positive feed-back mechanisms and synergistic interactions intensify these systems and give rise to heavy antiviral weapons such as reactive oxygen species and nitric oxide. This results in the generation of an alliance against the viral enemy. However, these heavy weapons have to be controlled to avoid too much harm to the host. By IL-4 and others, these reactions are hampered, but they are still allowed in foci of HSV replication, thus focusing the activity to only relevant sites. So, no hero does it alone. Rather, an alliance of cytokines, macrophages and other cells seems to play a central role. Implications of this for future treatment modalities are shortly considered.


title: An Upstream Open Reading Frame Modulates Ebola Virus Polymerase Translation and Virus Replication

text: Ebolaviruses, highly lethal zoonotic pathogens, possess longer genomes than most other non-segmented negative-strand RNA viruses due in part to long 5′ and 3′ untranslated regions (UTRs) present in the seven viral transcriptional units. To date, specific functions have not been assigned to these UTRs. With reporter assays, we demonstrated that the Zaire ebolavirus (EBOV) 5′-UTRs lack internal ribosomal entry site function. However, the 5′-UTRs do differentially regulate cap-dependent translation when placed upstream of a GFP reporter gene. Most dramatically, the 5′-UTR derived from the viral polymerase (L) mRNA strongly suppressed translation of GFP compared to a β-actin 5′-UTR. The L 5′-UTR is one of four viral genes to possess upstream AUGs (uAUGs), and ablation of each uAUG enhanced translation of the primary ORF (pORF), most dramatically in the case of the L 5′-UTR. The L uAUG was sufficient to initiate translation, is surrounded by a “weak” Kozak sequence and suppressed pORF translation in a position-dependent manner. Under conditions where eIF2α was phosphorylated, the presence of the uORF maintained translation of the L pORF, indicating that the uORF modulates L translation in response to cellular stress. To directly address the role of the L uAUG in virus replication, a recombinant EBOV was generated in which the L uAUG was mutated to UCG. Strikingly, mutating two nucleotides outside of previously-defined protein coding and cis-acting regulatory sequences attenuated virus growth to titers 10–100-fold lower than a wild-type virus in Vero and A549 cells. The mutant virus also exhibited decreased viral RNA synthesis as early as 6 hours post-infection and enhanced sensitivity to the stress inducer thapsigargin. Cumulatively, these data identify novel mechanisms by which EBOV regulates its polymerase expression, demonstrate their relevance to virus replication and identify a potential therapeutic target.


title: Rapid screening of COVID‐19 patients by White blood cells scattergrams, a study on 381 patients

text: Complementary tools are warranted to increase the sensitivity of the initial testing for COVID‐19. We identified a specific “sandglass” aspect on the white blood cells scattergram of COVID‐19 patients reflecting the presence of circulating plasmacytoid lymphocytes. Patients were dichotomized as COVID‐19 positive or negative based on RT‐PCR and chest CT scan results. Sensitivity and specificity of the “sandglass” aspect were 85.9% and 83.5% respectively. The positive predictive value was 94.3%. Our findings provide a non‐invasive and simple tool to quickly categorize symptomatic patients as either COVID‐19 probable or improbable especially when RT‐PCR and/or chest CT are not rapidly available.


title: In Reply

text: This letter to the editor remarks on additional considerations for the management of febrile neutropenia during the COVID‐19 pandemic, in response to the letter by Boutayeb et al.


WUPyV in Children with Acute Respiratory Tract Infections, China


title: Prenatal Care Redesign: Creating Flexible Maternity Care Models Through Virtual Care

text: Abstract: Each year, over 98% of the almost 4 million pregnant patients in the United States receive prenatal care—a crucial preventive service to improve outcomes for moms and babies. National guidelines currently recommend 12-14 in-person prenatal visits, a schedule unchanged since 1930. In scrutinizing the standard prenatal visit schedule, it quickly becomes clear that prenatal care is overdue for a redesign. We have strong evidence of the benefit of many prenatal services, like screening for gestational diabetes and maternal vaccination. Yet how to deliver these services is much less clear. Studies of prenatal services consistently demonstrate such care can be delivered in fewer than 14 visits, and that we do not need to provide all maternity services in person. Telemedicine has emerged as a promising care delivery option for patients seeking greater flexibility, and early trials leveraging virtual care and remote monitoring have shown positive maternal and fetal outcomes with high patient satisfaction. Our institution has worked for the past year on a new prenatal care pathway. Our initial work assessed the literature, elicited patient perspectives, and captured the insights of experts in patient-centered care delivery. Two key principles emerged to inform prenatal care redesign: 1) design care delivery around essential services, using in-person care for services that cannot be delivered remotely and offering video visits for other essential services; and 2) create flexible services for anticipatory guidance and psychosocial support that allow patients to tailor support to meet their needs through opt-in programs. The rise of COVID-19 prompted us to extend this early work and rapidly implement a redesigned prenatal care pathway. In this paper, we outline our experience rapidly transitioning prenatal care to a new model with 4 in-person visits, 1 ultrasound visit, and 4 virtual visits (the 4-1-4 prenatal plan). We then explore how lessons from this implementation can inform patient-centered prenatal care redesign during and beyond the COVID-19 pandemic.


title: Biomarkers associated with COVID-19 disease progression

text: The coronavirus disease 2019 (COVID-19) pandemic is a scientific, medical, and social challenge. The complexity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is centered on the unpredictable clinical course of the disease that can rapidly develop, causing severe and deadly complications. The identification of effective laboratory biomarkers able to classify patients based on their risk is imperative in being able to guarantee prompt treatment. The analysis of recently published studies highlights the role of systemic vasculitis and cytokine mediated coagulation disorders as the principal actors of multi organ failure in patients with severe COVID-19 complications. The following biomarkers have been identified: hematological (lymphocyte count, neutrophil count, neutrophil–lymphocyte ratio (NLR)), inflammatory (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT)), immunological (interleukin (IL)-6 and biochemical (D-dimer, troponin, creatine kinase (CK), aspartate aminotransferase (AST)), especially those related to coagulation cascades in disseminated intravascular coagulation (DIC) and acute respiratory distress syndrome (ARDS). New laboratory biomarkers could be identified through the accurate analysis of multicentric case series; in particular, homocysteine and angiotensin II could play a significant role.


How to optimize the management of gestational trophoblastic disease during the COVID era?


The Response of Women’s Dermatologic Society and the International Journal of Women’s Dermatology to the COVID-19 Pandemic


title: Evidence for reassortment of highly divergent novel rotaviruses from bats in Cameroon, without evidence for human interspecies transmissions

text: Bats are an important reservoir for pathogenic human respiratory and hemorrhagic viruses but only little is known about bat viruses causing gastroenteritis in humans, including rotavirus A strains (RVA). Only three RVA strains have been reported in bats in Kenya (straw-colored fruit bat) and in China (lesser horseshoe and a stoliczka’s trident bat), being highly divergent from each other. To further elucidate the potential of bat RVAs to cause gastroenteritis in humans we started by investigating the genetic diversity of RVAs in fecal samples from 87 straw-colored fruit bats living in close contact with humans in Cameroon using metagenomics. Five samples contained significant numbers of RVA Illumina reads, sufficient to obtain their (near) complete genomes. A single RVA strain showed a close phylogenetic relationship with the Kenyan bat RVA strain in six gene segments, including VP7 (G25), whereas the other gene segments represented novel genotypes as ratified by the RCWG. The 4 other RVA strains were highly divergent from known strains (but very similar among each other) possessing all novel genotypes. Only the VP7 and VP4 genes showed a significant variability representing multiple novel G and P genotypes, indicating the frequent occurrence of reassortment events. Comparing these bat RVA strains with currently used human RVA screening primers indicated that several of the novel VP7 and VP4 segments would not be detected in routine epidemiological screening studies. Therefore, novel VP6 based screening primers matching both human and bat RVAs were developed and used to screen samples from 25 infants with gastroenteritis living in close proximity with the studied bat population. Although RVA infections were identified in 36% of the infants, Sanger sequencing did not indicate evidence of interspecies transmissions. This study identified multiple novel bat RVA strains, but further epidemiological studies in humans will have to assess if these viruses have the potential to cause gastroenteritis in humans.


title: Analysis of a Therapeutic Antibody Cocktail Reveals Determinants for Cooperative and Broad Ebolavirus Neutralization

text: Structural principles underlying the composition of protective antiviral monoclonal antibody (mAb) cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a therapeutic mAb cocktail against Ebola virus. We systematically analyzed the antibody repertoire in human survivors and identified a pair of potently neutralizing mAbs that cooperatively bound to the ebolavirus glycoprotein (GP). High-resolution structures revealed that in a two-antibody cocktail, molecular mimicry was a major feature of mAb-GP interactions. Broadly neutralizing mAb rEBOV-520 targeted a conserved epitope on the GP base region. mAb rEBOV-548 bound to a glycan cap epitope, possessed neutralizing and Fc-mediated effector function activities, and potentiated neutralization by rEBOV-520. Remodeling of the glycan cap structures by the cocktail enabled enhanced GP binding and virus neutralization. The cocktail demonstrated resistance to virus escape and protected non-human primates (NHPs) against Ebola virus disease. These data illuminate structural principles of antibody cooperativity with implications for development of antiviral immunotherapeutics.


title: Natural feline coronavirus infection: Differences in cytokine patterns in association with the outcome of infection

text: Abstract Natural and experimental feline coronavirus (FCoV) infection leads to systemic viral spread via monocyte-associated viraemia and induces systemic proliferation of monocytes/macrophages. In the majority of naturally infected animals, FCoV infection remains subclinical and is associated with generalised B and T cell hyperplasia, but no other pathological findings. A minority of cats, however, develop feline infectious peritonitis (FIP), a fatal systemic granulomatous disease. This is generally accompanied by B and T cell depletion. The obvious functional differences of lymphatic tissues in FCoV-infected cats with and without FIP suggest that they contribute to the outcome of FCoV infection. This study attempted to evaluate the functional changes in haemolymphatic tissues after natural FCoV infection, with special emphasis on the magnitude, phenotype and function of the monocyte/macrophage population. The spleen, mesenteric lymph nodes and bone marrow from naturally FCoV-infected cats with and without FIP and specific pathogen-free (SPF) control cats were examined for the quantity and activation state of monocytes/macrophages both by immunohistology and by quantitative real time PCR for the transcription of interleukin (IL)-1β, IL-6, IL-10, IL-12 p40, tumour necrosis factor (TNF), granulocyte colony stimulating factor (G-CSF), macrophage-CSF (M-CSF) and GM-CSF. Compared to cats with FIP, FCoV-infected cats without FIP exhibited significantly higher IL-10 levels in the spleen and significantly lower levels of IL-6, G- and M-CSF in mesenteric lymph nodes. In cats with FIP, however, IL-12 p40 levels were significantly lower in lymphatic tissues in comparison to both SPF cats and FCoV-infected cats without FIP. In comparison to SPF cats, FIP cats had significantly higher IL-1β levels and lower TNF levels in mesenteric lymph nodes and lower M-CSF levels in the spleen. Findings indicate that FCoV-infected cats which do not develop FIP are able to mount an effective FCoV-specific immune response and can avoid excessive macrophage activation and FIP, possibly by upregulation of IL-10 production. Development of FIP, however, might be due to a lack of IL-12 which inhibits an effective cellular immune response and allows for monocyte/macrophage activation and the development of FIP.


title: Noninvasive ventilation support during fiberoptic bronchoscopy-guided nasotracheal intubation effectively prevents severe hypoxemia

text: Abstract Purpose This study investigated the feasibility and efficacy of continuous noninvasive ventilation (NIV) support with 100% oxygen using a specially designed face mask, for reducing desaturation during fiberoptic bronchoscopy (FOB)-guided intubation in critically ill patients with respiratory failure. Materials and methods This was a single-center prospective randomized study. All patients undergoing FOB-guided nasal tracheal intubation were randomized to bag-valve-mask ventilation or NIV for preoxygenation followed by intubation. The NIV group were intubated through a sealed hole in a specially designed face mask during continuous NIV support with 100% oxygen. Control patients were intubated with removal of the mask and no ventilatory support. Results We enrolled 106 patients, including 53 in each group. Pulse oxygen saturation (SpO2) after preoxygenation (99% (96%–100%) vs. 96% (90%–99%), p = .001) and minimum SpO2 during intubation (95% (87%–100%) vs. 83% (74%–91%), p < .01) were both significantly higher in the NIV compared with the control group. Severe hypoxemic events (SpO2 < 80%) occurred less frequently in the NIV group than in controls (7.4% vs. 37.7%, respectively; p < .01). Conclusions Continuous NIV support during FOB-guided nasal intubation can prevent severe desaturation during intubation in critically ill patients with respiratory failure. Trial registration: ClinicalTrials.gov, NCT02462668. Registered on 25 May 2015, https://www.clinicaltrials.gov/ct2/results?term=NCT02462668.


Home healthcare services in communities during COVID‐19: Protecting against and mitigating the pandemics in Taiwan


Recommendations for Treatment of Nail Psoriasis During the COVID‐19 Pandemic


title: The context of host competence: a role for plasticity in host–parasite dynamics

text: Even apparently similar hosts can respond differently to the same parasites. Some individuals or specific groups of individuals disproportionately affect disease dynamics. Understanding the sources of among-host heterogeneity in the ability to transmit parasites would improve disease management. A major source of host variation might be phenotypic plasticity – the tendency for phenotypes to change across different environments. Plasticity might be as important as, or even more important than, genetic change, especially in light of human modifications of the environment, because it can occur on a more rapid timescale than evolution. We argue that variation in phenotypic plasticity among and within species strongly contributes to epidemiological dynamics when parasites are shared among multiple hosts, which is often the case.


title: Guidance on the use of antiviral drugs for influenza in acute care facilities in Canada, 2014–2015

text: This article represents the second update to the AMMI Canada Guidelines document on the use of antiviral drugs for influenza. The article aims to inform health care professionals of the increased risk for influenza in long-term care facilities due to a documented mismatch between the components chosen for this season’s vaccine and currently circulating influenza strains. Adjusted recommendations for the use of antiviral drugs for influenza in the acute care setting for this season are provided.


title: Glycyrrhizin inhibits influenza A virus uptake into the cell

text: Abstract We investigated the mechanism by which glycyrrhizin (GL), the main active component of licorice roots, protects cells from infection with influenza A virus (IAV). We found that GL treatment leads to a clear reduction in the number of IAV-infected human lung cells as well as a reduction in the CCID50 titer by 90%. The antiviral effect, however, was limited to one or two virus replication cycles. Analysis of different GL treatment protocols suggested that the antiviral effect of GL was limited to an early step in the virus replication cycle. A direct inhibitory action of GL on IAV particles could be excluded and GL did not interact with virus receptor binding either. The antiviral effect of GL was abolished by treatment 1h after virus infection, whereas pre-treatment and treatment during and after virus adsorption led to a reduction in the cytopathic effect, reduced viral RNA within the cells and in the cell supernatants, and reduced viral hemagglutination titers. Detailed virus uptake analyses unambiguously demonstrated reduced virus uptake in various GL-treated cells. These observations lead to the conclusion, that the antiviral activity of GL is mediated by an interaction with the cell membrane which most likely results in reduced endocytotic activity and hence reduced virus uptake. These insights might help in the design of structurally related compounds leading to potent anti-influenza therapeutics.


title: Autophagy sustains the replication of porcine reproductive and respiratory virus in host cells

text: Abstract In this study, we confirmed the autophagy induced by porcine reproductive and respiratory syndrome virus (PRRSV) in permissive cells and investigated the role of autophagy in the replication of PRRSV. We first demonstrated that PRRSV infection significantly results in the increased double-membrane vesicles, the accumulation of LC3 fluorescence puncta, and the raised ratio of LC3-II/β-actin, in MARC-145 cells. Then we discovered that induction of autophagy by rapamycin significantly enhances the viral titers of PRRSV, while inhibition of autophagy by 3-MA and silencing of LC3 gene by siRNA reduces the yield of PRRSV. The results showed functional autolysosomes can be formed after PRRSV infection and the autophagosome–lysosome-fusion inhibitor decreases the virus titers. We also examined the induction of autophagy by PRRSV infection in pulmonary alveolar macrophages. These findings indicate that autophagy induced by PRRSV infection plays a role in sustaining the replication of PRRSV in host cells.


Incidence, Severity and Impact of Influenza: a joint meeting organised by the ISIRV Epidemiology Group and ECDC, Stockholm, 2019


title: Forum article: The protective rather than prothrombotic fibrinogen in COVID‐19 and other inflammatory states

text: Hypercoagulability has been recognised as a common complication of COVID‐19. Exact mechanisms for this extreme coagulation activation have not yet been elucidated. However, one of the consistent laboratory finding is the increase in fibrinogen, in some cases, marked elevation. High circulating levels of fibrinogen have been linked to thrombosis for years and for this reason, hyper‐fibrinogenemia is considered one of the mechanisms for COVID‐19 coagulopathy. In this forum article, instead of the prothrombotic role, a protective function for fibrinogen is discussed. Fibrinogen, like the other well‐known acute phase reactants, is increased in COVID‐19 possibly to protect the host.


title: A review of licensed viral vaccines, some of their safety concerns, and the advances in the development of investigational viral vaccines

text: Abstract Viral vaccines could be considered among the most important medical achievements of the 20th century. They have prevented much suffering and saved many lives. Although some curative antiviral drugs exist, we desperately depend on efforts by academic, governmental and industrial scientists in the advancement of viral vaccines in the prevention and control of infectious diseases. In the next decade, we hope to see advancement in the development of current and investigational viral vaccines against childhood and adult infections. In this article, we will review the licensed viral vaccines, some of their safety concerns, and the advances in the development of investigational viral vaccines.


title: SAGES: A Suite of Freely-Available Software Tools for Electronic Disease Surveillance in Resource-Limited Settings

text: Public health surveillance is undergoing a revolution driven by advances in the field of information technology. Many countries have experienced vast improvements in the collection, ingestion, analysis, visualization, and dissemination of public health data. Resource-limited countries have lagged behind due to challenges in information technology infrastructure, public health resources, and the costs of proprietary software. The Suite for Automated Global Electronic bioSurveillance (SAGES) is a collection of modular, flexible, freely-available software tools for electronic disease surveillance in resource-limited settings. One or more SAGES tools may be used in concert with existing surveillance applications or the SAGES tools may be used en masse for an end-to-end biosurveillance capability. This flexibility allows for the development of an inexpensive, customized, and sustainable disease surveillance system. The ability to rapidly assess anomalous disease activity may lead to more efficient use of limited resources and better compliance with World Health Organization International Health Regulations.


title: Crowning Proteins: Modulating the Protein Surface Properties using Crown Ethers**

text: Crown ethers are small, cyclic polyethers that have found wide-spread use in phase-transfer catalysis and, to a certain degree, in protein chemistry. Crown ethers readily bind metallic and organic cations, including positively charged amino acid side chains. We elucidated the crystal structures of several protein-crown ether co-crystals grown in the presence of 18-crown-6. We then employed biophysical methods and molecular dynamics simulations to compare these complexes with the corresponding apoproteins and with similar complexes with ring-shaped low-molecular-weight polyethylene glycols. Our studies show that crown ethers can modify protein surface behavior dramatically by stabilizing either intra- or intermolecular interactions. Consequently, we propose that crown ethers can be used to modulate a wide variety of protein surface behaviors, such as oligomerization, domain–domain interactions, stabilization in organic solvents, and crystallization.


title: Viral and bacterial vectors of immunogenes

text: Abstract A recent development in the production of experimental vaccines has been the use of the smallpox vaccine virus (vaccinia virus) as a carrier (vector) of the genes (immunogenes) which code for the protection-inducing proteins (immunogens) of unrelated viruses. The potential of these vector vaccines lies in the hope that such a vaccine would be cheaper, safer and/or more effective than existing vaccines to some pathogens. Vaccinia virus as a vector has attracted most attention to date because: (a) several immunogenes can be inserted into its genome without destroying its infectivity; (b) the immunogens appear to be produced normally; (c) vaccinia virus has been used highly successfully to eradicate smallpox; and (d) it has a wide host-range and thus might find veterinary as well as human medical application. Experimental vaccines, successfully tested in animals, have been prepared using immunogenes from influenza virus, hepatitis B virus and herpes simplex virus. Apathogenic enteric bacteria have some potential as vectors, most probably against enteric pathogens, although the potential of viral vectors is likely to be realized first. Parasitic worms and protozoa devastate millions of people. When the immunogens of these organisms have been identified there will be added impetus to investigate the potential of vector vaccines against these pathogens.


title: Properties of Cordyceps Sinensis: A review

text: Abstract A great mystique and aura surrounds Cordyceps sinensis (syn.: Cephalosporium sinensis), an endoparasitic fungus which has claims of anti-cancer and anti-aging properties. Much research has been conducted over the years on crude extracts and its bioactivity. More research is now focused on culturing C. sinensis and on isolating and identifying pure compounds novel to C. sinensis in an attempt to alleviate strain on demand for the natural fungi. Several polysaccharides, nucleosides and sterols all have had reports of promoting health both in vitro and in vivo. Specific and novel compounds which are characteristic to C. sinensis are emerging with reports of two new epipolythiodioxopiperazines, gliocladicillins A and B capable of inhibiting growth of HeLa, HepG2 and MCF-7 tumor cells. Exclusive to natural C. sinensis, five constituents of cordysinin (A–E) has also been reported for the first time and has been linked to anti-inflammatory properties. Although it may still be premature to believe these results should translate into pharmaceutical use, there is sufficient evidence to warrant further research.


title: The immune responses of HLA-A*0201 restricted SARS-CoV S peptide-specific CD8+ T cells are augmented in varying degrees by CpG ODN, PolyI:C and R848

text: Abstract The induction of antigen specific memory CD8+ T cells in vivo is very important to new vaccines against infectious diseases. In the present study, we aimed to evaluate the immune responses of peptide-specific CD8+ T cells induced by HLA-A*0201 restricted severe acute respiratory syndrome-associated coronavirus (SARS-CoV) S epitopes plus CpG oligodeoxynucleotide (CpG ODN), PolyI:C and R848 as adjuvants. Furthermore, the generation, distribution and phenotype of long-lasting peptide-specific memory CD8+ T cells were assessed by ELISA, ELISPOT and flow cytometry. Our results showed that antigen specific CD8+ T cells were elicited by HLA-A*0201 restricted SARS-CoV S epitopes. Furthermore, the frequency of peptide-specific CD8+ T cells was dramatically increased after both prime and boost immunization with peptides plus CpG ODN, whereas slight enhancements were induced following boost vaccination with peptides plus PolyI:C or R848. SARS-CoV S peptide-specific IFN-γ+CD8+ T cells were distributed throughout the lymphoid and non-lymphoid tissues. Results also demonstrated that the HLA-A*0201 restricted peptide-specific CD8+ T cells induced by peptides plus CpG ODN carried a memory cell phenotype with CD45RB+ and CD62L− and possessed long-term survival ability in vivo. Taken together, our results implied that HLA-A*0201 restricted SARS-CoV S epitopes plus CpG ODN might be the superior candidates for SARS vaccine.


title: Systematic review for geo-authentic Lonicerae Japonicae Flos

text: In traditional Chinese medicine, Lonicerae Japonicae Flos is commonly used as anti-inflammatory, antiviral, and antipyretic herbal medicine, and geo-authentic herbs are believed to present the highest quality among all samples from different regions. To discuss the current situation and trend of geo-authentic Lonicerae Japonicae Flos, we searched Chinese Biomedicine Literature Database, Chinese Journal Full-text Database, Chinese Scientific Journal Full-text Database, Cochrane Central Register of Controlled Trials, Wanfang, and PubMed. We investigated all studies up to November 2015 pertaining to quality assessment, discrimination, pharmacological effects, planting or processing, or ecological system of geo-authentic Lonicerae Japonicae Flos. Sixty-five studies mainly discussing about chemical fingerprint, component analysis, planting and processing, discrimination between varieties, ecological system, pharmacological effects, and safety were systematically reviewed. By analyzing these studies, we found that the key points of geo-authentic Lonicerae Japonicae Flos research were quality and application. Further studies should focus on improving the quality by selecting the more superior of all varieties and evaluating clinical effectiveness.


title: De Novo Status Epilepticus in patients with COVID‐19

text: Neurological complications are increasingly recognized with SARS CoV‐2, the causative pathogen for COVID‐19. We present a single‐center retrospective case series reporting the EEG and outcome of de novo status epilepticus (SE) in two African‐American women with laboratory‐confirmed SARS CoV‐2 virus. SE was the initial presentation in one asymptomatic individual. Patient 2 had COVID‐19 pneumonia, and fluctuating mental status that raised the suspicion of subclinical SE. The patient with older age and higher comorbidities failed to recover from the viral illness that has no definitive treatment.


title: High IL‐6/IFN‐γ ratio could be associated with severe disease in COVID‐19 patients

text: Cytokines are important mediators of the inflammatory response, and during infection with SARS‐CoV‐2 it has been suggested that there is a cytokine storm syndrome. In this study, a meta‐analysis was performed to investigate whether the IL‐6/IFN‐γ ratio can help predict clinical severity in patients with COVID‐19. This article is protected by copyright. All rights reserved.


title: Bronchiectasis exacerbation study on azithromycin and amoxycillin-clavulanate for respiratory exacerbations in children (BEST-2): study protocol for a randomized controlled trial

text: BACKGROUND: Bronchiectasis unrelated to cystic fibrosis (CF) is being increasingly recognized in children and adults globally, both in resource-poor and in affluent countries. However, high-quality evidence to inform management is scarce. Oral amoxycillin-clavulanate is often the first antibiotic chosen for non-severe respiratory exacerbations, because of the antibiotic-susceptibility patterns detected in the respiratory pathogens commonly associated with bronchiectasis. Azithromycin has a prolonged half-life, and with its unique anti-bacterial, immunomodulatory, and anti-inflammatory properties, presents an attractive alternative. Our proposed study will test the hypothesis that oral azithromycin is non-inferior (within a 20% margin) to amoxycillin-clavulanate at achieving resolution of non-severe respiratory exacerbations by day 21 of treatment in children with non-CF bronchiectasis. METHODS: This will be a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel group trial involving six Australian and New Zealand centers. In total, 170 eligible children will be stratified by site and bronchiectasis etiology, and randomized (allocation concealed) to receive: 1) azithromycin (5 mg/kg daily) with placebo amoxycillin-clavulanate or 2) amoxycillin-clavulanate (22.5 mg/kg twice daily) with placebo azithromycin for 21 days as treatment for non-severe respiratory exacerbations. Clinical data and a parent-proxy cough-specific quality of life (PC-QOL) score will be obtained at baseline, at the start and resolution of exacerbations, and on day 21. In most children, blood and deep-nasal swabs will also be collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 21. The main secondary outcome is the PC-QOL score. Other outcomes are: time to next exacerbation; requirement for hospitalization; duration of exacerbation, and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood inflammatory markers will be reported where available. DISCUSSION: Currently, there are no published randomized controlled trials (RCT) to underpin effective, evidence-based management of acute respiratory exacerbations in children with non-CF bronchiectasis. To help address this information gap, we are conducting two RCTs. The first (bronchiectasis exacerbation study; BEST-1) evaluates the efficacy of azithromycin and amoxycillin-clavulanate compared with placebo, and the second RCT (BEST-2), described here, is designed to determine if azithromycin is non-inferior to amoxycillin-clavulanate in achieving symptom resolution by day 21 of treatment in children with acute respiratory exacerbations. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR) number http://ACTRN12612000010897. http://www.anzctr.org.au/trial_view.aspx?id=347879


title: China’s health assistance to Africa: opportunism or altruism?

text: China has made substantial health commitments to Africa in the past several decades. However, while much has been written regarding China-Africa aid overall, relatively little attention has been given to China’s health aid. To better understand these investments, we provide an overview of the current framework and characteristics of China’s health aid to Africa. China’s health assistance has been perceived by some as opportunistic, largely as a demonstration of China’s engagement in “soft power” and an attempt to enhance its access to natural resources and political favors by African countries. Others have attributed altruistic intent, aiming to support the advancement of the health of populations in the African continent with a “no strings attached” approach. Our overview demonstrated that despite the magnitude of China’s health assistance, many questions remain regarding the scope of this aid, its effectiveness and the governance mechanisms that guide the conceptualization and implementation of such efforts. We also identified the need for a systematic and rigorous evaluation of the various elements of China’s health assistance to African countries in order to gain a deeper understanding of how priorities and allocations for health aid are determined, how such aid fits within the specific African country’s health strategies and to assess the effectiveness of such aid. Insights garnered through such an assessment could help determine future priorities for investment as well as inform efforts to optimize the value of China's aid for the populations of the recipient countries.


title: Detection and genotyping of Korean porcine rotaviruses

text: Abstract Porcine group A rotavirus (GARV) is considered to be an important animal pathogen due to their economic impact in the swine industry and its potential to cause heterologous infections in humans. This study examined 475 fecal samples from 143 farms located in 6 provinces across South Korea. RT-PCR and nested PCR utilizing primer pairs specific for the GARV VP6 gene detected GARV-positive reactions in 182 (38.3%) diarrheic fecal samples. A total of 98 porcine GARV strains isolated from the GARV-positive feces were analyzed for G and P genotyping. Based on the sequence and phylogenetic analyses, the most predominant combination of G and P genotypes was G5P[7], found in 63 GARV strains (64.3%). The other combinations of G and P genotypes were G8P[7] (16 strains [16.3%]), G9P[7] (7 strains [7.1%]), G9P[23] (2 strains [2.0%]), and G8P[1] (1 strain [1.0%]). The counterparts of G or P genotypes were not determined in three G5, five P[7], and one P[1] strains. Interestingly, phylogenetic analysis indicated that all Korean G9 strains were more closely related to lineage VI porcine and human viruses than to other lineages (I–V) of GARVs and to Korean human G9 strains (lineage III). These results show that porcine GARV infections are common in diarrheic piglets in South Korea. The infecting strains are genetically diverse, and include homologous (G5P[7]), heterologous (G8P[1]), and reassortant (G8P[7]), as well as emerging G9 GARV strains.


title: Acquisition of respiratory viruses and presence of respiratory symptoms in French pilgrims during the 2016 Hajj: A prospective cohort study

text: Abstract Background Viral respiratory tract infections are frequent among Hajj pilgrims. However, it is still not known whether viruses are responsible for the symptoms observed in sick pilgrims or whether they only colonize sick and asymptomatic pilgrims. Patients and methods A prospective cohort study was conducted among French Hajj pilgrims in 2016. Medical follow-up and systematic nasal swabbing were performed pre- and post-Hajj. Additional samples were obtained per-Hajj, at symptom onset in ill pilgrims. Viruses were identified using the BioFire FilmArray® Respiratory multiplex qualitative PCR panel. Results 109 pilgrims were included. 83.5% presented respiratory symptoms during Hajj and 39.5% were still symptomatic on return. 5.5% of pre-Hajj, 95.2% of per-Hajj (at symptom onset) and 46.5% of post-Hajj samples tested positive (p < 0.0001). Acquisition rates of rhinovirus/enterovirus, coronavirus 229E and influenza A virus were respectively 38.6%, 19.8% and 2.0%. Although rhinovirus/enterovirus, coronavirus 229E and influenza A clearance were respectively 70.6%, 71.4% and 100% on return, overall virus carriage proportion on return was 75.0% in pilgrims with influenza-like illness and 44.0% in those who have never experienced this symptoms or resolved it (OR = 4.05, 95% CI [1.02–16.02]). Conclusions Viruses likely play some role in the pathogenesis of the respiratory tract infections at the Hajj. Point of care-rapid multiplex PCR assays are valuable diagnosis tools in this context when used at respiratory symptom onset or soon after.


title: A Graphene‐Based Platform for the Assay of Duplex‐DNA Unwinding by Helicase

text: Time to unwind: Graphene oxide (GO) enables the quantitative measurement of helicase‐dependent double‐stranded DNA (dsDNA) unwinding activity in real time. GO selectively binds to unwound fluorescent‐dye‐labeled single‐stranded DNA and quenches its fluorescence (see picture). The helicase activity is monitored by following the change in fluorescence.[Image: see text]


title: In vivo analysis of glial cell phenotypes during a viral demyelinating disease in mice

text: C57 BL/6N mice injected intracranially with the A59 strain of mouse hepatitis virus exhibit extensive viral replication in glial cells of the spinal cord and develop demyelinating lesions followed by virus clearing and remyelination. To study how different glial cell types are affected by the disease process, we combine three-color immunofluorescence labeling with tritiated thymidine autoradiography on 1-micron frozen sections of spinal cord. We use three different glial cell specific antibodies (a) to 2',3' cyclic-nucleotide 3' phosphohydrolase (CNP) expressed by oligodendrocytes, (b) to glial fibrillary acidic protein (GFAP) expressed by astrocytes, and (c) the O4 antibody which binds to O-2A progenitor cells in the rat. These progenitor cells, which give rise to oligodendrocytes and type 2 astrocytes and react with the O4 antibody in the adult central nervous system, were present but rare in the spinal cord of uninfected mice. In contrast, cells with the O-2A progenitor phenotype (O4 + only) were increased in number at one week post viral inoculation (1 WPI) and were the only immunostained cells labeled at that time by a 2-h in vivo pulse of tritiated thymidine. Both GFAP+ only and GFAP+, O4+ astrocytes were also increased in the spinal cord at 1 WPI. Between two and four WPI, the infected spinal cord was characterized by the loss of (CNP+, O4+) oligodendrocytes within demyelinating lesions and the presence of O-2A progenitor cells and O4+, GFAP+ astrocytes, both of which could be labeled with thymidine. As remyelination proceeded, CNP immunostaining returned to near normal and tritiated thymidine injected previously during the demyelinating phase now appeared in CNP+ oligodendrocytes. Thus O4 positive O-2A progenitor cells proliferate early in the course of the demyelinating disease, while CNP positive oligodendrocytes do not. The timing of events suggests that the O-2A progenitors may give rise to new oligodendrocytes and to type 2 astrocytes, both of which are likely to be instrumental in the remyelination process.


title: Cell adhesion as a novel approach to determining the cellular binding motif on the severe acute respiratory syndrome coronavirus spike protein

text: Abstract Emerging life threatening pathogens such as severe acute aspiratory syndrome-coronavirus (SARS-CoV), avian-origin influenzas H7N9, and the Middle East respiratory syndrome coronavirus (MERS-CoV) have caused a high case-fatality rate and psychological effects on society and the economy. Therefore, a simple, rapid, and safe method to investigate a therapeutic approach against these pathogens is required. In this study, a simple, quick, and safe cell adhesion inhibition assay was developed to determine the potential cellular binding site on the SARS-CoV spike protein. Various synthetic peptides covering the potential binding site helped to minimize further the binding motif to 10–25 residues. Following analyses, 2 peptides spanning the 436–445 and 437–461 amino acids of the spike protein were identified as peptide inhibitor or peptide vaccine candidates against SARS-CoV.


title: Infection control in paediatric office settings

text: Transmission of infection in the paediatric office is of increasing concern. The present document discusses routes of transmission of infection and the principles of current infection control measures. Prevention includes appropriate office design and administrative policies, triage, routine practices for the care of all patients (eg, hand hygiene; use of gloves, masks, eye protection and gowns for specific procedures; adequate cleaning, disinfection and sterilization of surfaces and equipment including toys, and aseptic technique for invasive procedures), and additional precautions for specific infections. Personnel should be adequately immunized, and those infected should follow work-restriction policies.


Aged patients with mental disorders in the COVID-19 era: the experience of Northern Italy


title: Viral and Bacterial Etiology of Acute Febrile Respiratory Syndrome among Patients in Qinghai, China

text: Abstract Objective This study was conducted to investigate the viral and bacterial etiology and epidemiology of patients with acute febrile respiratory syndrome (AFRS) in Qinghai using a commercial routine multiplex-ligation-nucleic acid amplification test (NAT)-based assay. Methods A total of 445 nasopharyngeal swabs specimens from patients with AFRS were analyzed using the RespiFinderSmart22kit (PathoFinder BV, Netherlands) and the LightCycler 480 real-time PCR system. Results Among the 225 (225/445, 51%) positive specimens, 329 positive pathogens were detected, including 298 (90.58%) viruses and 31 (9%) bacteria. The most commonly detected pathogens were influenza virus (IFV; 37.39%; 123/329), adenovirus (AdV; 17.02%; 56/329), human coronaviruses (HCoVs; 10.94%; 36/329), rhinovirus/enterovirus (RV/EV; 10.03%; 33/329), parainfluenza viruses (PIVs; 8.51%; 28/329), and Mycoplasma pneumoniae (M. pneu; 8.51%; 28/329), respectively. Among the co-infected cases (17.53%; 78/445), IFV/AdV and IFV/M. pneu were the most common co-infections. Most of the respiratory viruses were detected in summer and fall. Conclusion In our study, IFV-A was the most common respiratory pathogen among 22 detected pathogens, followed by AdV, HCoV, RV/EV, PIV, and M. pneu. Bacteria appeared less frequently than viruses, and co-infection was the most common phenomenon among viral pathogens. Pathogens were distributed among different age groups and respiratory viruses were generally active in July, September, and November. Enhanced surveillance and early detection can be useful in the diagnosis, treatment, and prevention of AFRS, as well as for guiding the development of appropriate public health strategies.


title: Assessment of the economic impacts of porcine epidemic diarrhea virus in the United States

text: Porcine epidemic diarrhea virus (PEDV), which first emerged in the United States in 2013, spread throughout the U.S. hog population. Limited preemptive knowledge impeded the understanding of PEDV introduction, spread, and prospective economic impacts in the United States. To assess these impacts, this article reviews the timeline of PEDV in the United States and the corresponding impacts. PEDV is a supply-impacting disease and is not demand inhibiting, as pork demand remained strong since PEDV first appeared. Pig losses reached significant levels during September 2013 through August 2014, with the majority of pork production impacts occurring in 2014. PEDV had differing impacts for subsectors of the pork industry. A budget model demonstrates that producers could have had pig losses and decreases in productivity proportionally smaller than price increases, resulting in net returns above what was expected before the major outbreak of PEDV. Previous literature is reviewed to identify the potential main industry beneficiaries of the PEDV outbreaks in the United States. As a result of reduced volumes of available pig and hog supplies, reductions in annual returns likely occurred for packers, processors, distributors, and retailers. In addition, pork consumers who experienced reduced-supply-induced pork-price increases were likely harmed directly by higher prices paid for pork and indirectly as prices of competing meats were also likely strengthened by PEDV. This article also identifies future considerations motivated by the appearance of PEDV in the United States, such as discussions of industry-wide efficiency and competitive advantage, the future role of PEDV vaccines, enhancement in biosecurity measures, and consumer perceptions of food safety and insecurity.


title: Zoonoses, One Health and complexity: wicked problems and constructive conflict

text: Infectious zoonoses emerge from complex interactions among social and ecological systems. Understanding this complexity requires the accommodation of multiple, often conflicting, perspectives and narratives, rooted in different value systems and temporal–spatial scales. Therefore, to be adaptive, successful and sustainable, One Health approaches necessarily entail conflicts among observers, practitioners and scholars. Nevertheless, these integrative approaches have, both implicitly and explicitly, tended to marginalize some perspectives and prioritize others, resulting in a kind of technocratic tyranny. An important function of One Health approaches should be to facilitate and manage those conflicts, rather than to impose solutions. This article is part of the themed issue ‘One Health for a changing world: zoonoses, ecosystems and human well-being’.


title: Support online students during campus closures

text: Students may have left your campus due to the COVID‐19 crisis, but they still need your support to succeed — now more than ever. To help student affairs professionals provide students with that support during campus closures, NASPA: Student Affairs Administrators in Higher Education presented a webinar featuring Alicia Battle, Assistant Professor and Director of the Online Master of Public Health Program at Tulane University; Jaimie Hoffman, Ed.D., Vice President for Student Affairs at Noodle Partners, which produces and runs online and hybrid higher ed programs; and James McGhee, Assistant Dean of Students at Randolph‐Macon College.


title: Pacing a small cage: mutation and RNA viruses

text: RNA viruses have an extremely high mutation rate, and we argue that the most plausible explanation for this is a trade-off with replication speed. We suggest that research into further increasing this mutation rate artificially as an antiviral treatment requires a theoretical reevaluation, especially relating to the so-called error threshold. The main evolutionary consequence of a high mutation rate appears to have been to restrict RNA viruses to a small genome; they thus rapidly exploit a limited array of possibilities. Investigating this constraint to their evolution, and how it is occasionally overcome, promises to be fruitful. We explain the many terms used in investigating RNA viral evolution and highlight the specific experimental and comparative work that needs to be done.


title: Chapter 18 Marine Metabolites Oceans of Opportunity

text: Abstract The marine environment provides an array of compounds often with unique molecular architectures boasting an equally wide array of bioactivities including anticancer, antiinflammatory, and antimicrobial activity. Typically without the benefit of folklore therapeutic knowledge, marine organisms are collected, extracted, and fractionated to afford compounds that undergo evaluation with in vivo and in vitro assays en route to clinical applications. The pharmaceutical industry has benefited from research into marine metabolites with the development of marine-derived drugs including cytarabine, vidarabine, and ziconotide along with the more recently developed formulation Carragelose, an antiviral spray. Cosmetic applications incorporating marine extracts include Abyssine and RefirMAR. Research with macroinvertebrates, macroalgae, and microorganisms continue in the hope that drugs of the future will be culled from the oceans of the world. While obtaining a consistent and adequate supply of the bioactive compounds remains a challenge to be overcome, synthetic methods are being employed along with the application of biotechnological techniques to ensure that the drugs, when developed, will be in sufficient quantities for distribution to those who are in need.


Auditoría inmunitaria de COVID-19 en el servicio de Oftalmología de un hospital de tercer nivel antes del desconfinamiento


title: SARS‐CoV‐2 may be related to conjunctivitis but not necessarily spread through the conjunctiva SARS‐CoV‐2 and conjunctiva

text: We appreciate the comments of Liu et al.(1) and Peng et al.(2) in relation to our previous study. Currently, the controversy on the relationship among SARS‐CoV‐2 infection, the ocular surface and conjunctivitis are reflected in two aspects as follows: (i) can SARS‐CoV‐2 infection cause conjunctivitis? (ii) can SARS‐CoV‐2 be transmitted through the ocular surface? This article is protected by copyright. All rights reserved.


title: Astrovirus evolution and emergence

text: Abstract Astroviruses are small, non-enveloped, positive-sense, single-stranded RNA viruses that belong to the Astroviridae family. Astroviruses infect diverse hosts and are typically associated with gastrointestinal illness; although disease can range from asymptomatic to encephalitis depending on the host and viral genotype. Astroviruses have high genetic variability due to an error prone polymerase and frequent recombination events between strains. Once thought to be species specific, recent evidence suggests astroviruses can spread between different host species, although the frequency with which this occurs and the restrictions that regulate the process are unknown. Recombination events can lead to drastic evolutionary changes and contribute to cross-species transmission events. This work reviews the current state of research on astrovirus evolution and emergence, especially as it relates to cross-species transmission and recombination of astroviruses.


Human bocavirus DNA detected by quantitative real-time PCR in two children hospitalized for lower respiratory tract infection


title: Molecular Characteristics, Functions, and Related Pathogenicity of MERS-CoV Proteins

text: Abstract Middle East respiratory syndrome (MERS) is a viral respiratory disease caused by a de novo coronavirus—MERS-CoV—that is associated with high mortality. However, the mechanism by which MERS-CoV infects humans remains unclear. To date, there is no effective vaccine or antibody for human immunity and treatment, other than the safety and tolerability of the fully human polyclonal Immunoglobulin G (IgG) antibody (SAB-301) as a putative therapeutic agent specific for MERS. Although rapid diagnostic and public health measures are currently being implemented, new cases of MERS-CoV infection are still being reported. Therefore, various effective measures should be taken to prevent the serious impact of similar epidemics in the future. Further investigation of the epidemiology and pathogenesis of the virus, as well as the development of effective therapeutic and prophylactic anti-MERS-CoV infections, is necessary. For this purpose, detailed information on MERS-CoV proteins is needed. In this review, we describe the major structural and nonstructural proteins of MERS-CoV and summarize different potential strategies for limiting the outbreak of MERS-CoV. The combination of computational biology and virology can accelerate the advanced design and development of effective peptide therapeutics against MERS-CoV. In summary, this review provides important information about the progress of the elimination of MERS, from prevention to treatment.


title: Gross Lesions of Alimentary Disease in Adult Cattle

text: The purpose of the gross necropsy examination of the gastrointestinal tract is to recognize the presence of lesions, thus requiring a basic understanding of its normal appearance and anatomy. This article highlights gross changes to the gastrointestinal tract of adult cattle that help place the disease processes into broad categories. Although few gross lesions reach the zenith of pathognomonic, there are numerous lesions that, when considered in aggregate with history (eg, number of animals affected, environment, duration of signs, time of onset relative to management changes, previous management) and clinical signs, can help narrow the spectrum of causes, provide a basis for a strong presumptive diagnosis, and focus diagnostic test selection.


title: Developments towards antiviral therapies against enterovirus 71

text: Enterovirus 71 (EV71) has emerged as a clinically important neurotropic virus that can cause acute flaccid paralysis and encephalitis, leading to cardiopulmonary failure and death. Recurring outbreaks of EV71 have been reported in several countries. The current lack of approved anti-EV71 therapy has prompted intense research into antiviral development. Several strategies – ranging from target-based chemical design to compound library screenings – have been employed, while others revisited compound series generated from antiviral developments against poliovirus and human rhinoviruses. These efforts have given rise to a diversity of antiviral candidates that include small molecules and non-conventional nucleic-acid-based strategies. This review aims to highlight candidates with potential for further clinical development based on their putative modes of action.


title: Synthesis and activity of an octapeptide inhibitor designed for SARS coronavirus main proteinase

text: The outbreak of SARS, a life-threatening disease, has spread over many countries around the world. So far there is no effective drug for the treatment of SARS. Stimulated by the binding mechanism of SARS-CoV M(pro) with the octapeptide AVLQSGFR reported recently as well as the “Chou's distorted key” theory, we synthesized the octapeptide AVLQSGFR for conducting various biochemical experiments to investigate the antiviral potential of the octapeptide against SARS coronavirus (BJ-01). The results demonstrate that, compared with other compounds reported so far, AVLQSGFR is the most active in inhibiting replication of the SARS coronavirus, and that no detectable toxicity is observed on Vero cells under the condition of experimental concentration.


title: Mechanisms of GII.4 Norovirus Persistence in Human Populations

text: BACKGROUND: Noroviruses are the leading cause of viral acute gastroenteritis in humans, noted for causing epidemic outbreaks in communities, the military, cruise ships, hospitals, and assisted living communities. The evolutionary mechanisms governing the persistence and emergence of new norovirus strains in human populations are unknown. Primarily organized by sequence homology into two major human genogroups defined by multiple genoclusters, the majority of norovirus outbreaks are caused by viruses from the GII.4 genocluster, which was first recognized as the major epidemic strain in the mid-1990s. Previous studies by our laboratory and others indicate that some noroviruses readily infect individuals who carry a gene encoding a functional alpha-1,2-fucosyltransferase (FUT2) and are designated “secretor-positive” to indicate that they express ABH histo-blood group antigens (HBGAs), a highly heterogeneous group of related carbohydrates on mucosal surfaces. Individuals with defects in the FUT2 gene are termed secretor-negative, do not express the appropriate HBGA necessary for docking, and are resistant to Norwalk infection. These data argue that FUT2 and other genes encoding enzymes that regulate processing of the HBGA carbohydrates function as susceptibility alleles. However, secretor-negative individuals can be infected with other norovirus strains, and reinfection with the GII.4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations. METHODS AND FINDINGS: Phylogenetic analyses of the GII.4 capsid sequences suggested an epochal evolution over the last 20 y with periods of stasis followed by rapid evolution of novel epidemic strains. The epidemic strains show a linear relationship in time, whereby serial replacements emerge from the previous cluster. Five major evolutionary clusters were identified, and representative ORF2 capsid genes for each cluster were expressed as virus-like particles (VLPs). Using salivary and carbohydrate-binding assays, we showed that GII.4 VLP-carbohydrate ligand binding patterns have changed over time and include carbohydrates regulated by the human FUT2 and FUT3 pathways, suggesting that strain sensitivity to human susceptibility alleles will vary. Variation in surface-exposed residues and in residues that surround the fucose ligand interaction domain suggests that antigenic drift may promote GII.4 persistence in human populations. Evidence supporting antigenic drift was obtained by measuring the antigenic relatedness of GII.4 VLPs using murine and human sera and demonstrating strain-specific serologic and carbohydrate-binding blockade responses. These data suggest that the GII.4 noroviruses persist by altering their HBGA carbohydrate-binding targets over time, which not only allows for escape from highly penetrant host susceptibility alleles, but simultaneously allows for immune-driven selection in the receptor-binding region to facilitate escape from protective herd immunity. CONCLUSIONS: Our data suggest that the surface-exposed carbohydrate ligand binding domain in the norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against norovirus infections, and that continued epidemiologic surveillance and reformulations of norovirus vaccines will be essential in the control of future outbreaks.


Immediate-use steam sterilization sterilizes N95 masks without mask damage


Essais cliniques au cours de la pandémie COVID-19


Aumento de la gravedad de las hemopatías malignas agudas diagnosticadas durante la pandemia COVID-19


title: Bioterrorism and children Unique concerns with infection control and vaccination

text: Treatment of child victims of a bioterrorism attack is complicated because they may be more vulnerable to the agents used and may suffer more complications from the treatment strategies. Isolation and other infection control measures can be psychologically harmful to young children and may require that they undergo sedation. Most of the recommended antibiotics and antiviral treatments for bioterror agents have not been approved for use in children, and children undergoing smallpox vaccination have a higher incidence of complications than adults. Pediatric anesthesiologists should expect to be part of the pediatric care team and must be careful to observe infection control procedures to limit the spread of disease caused by bioterror attack.


A New Symptom of COVID‐19: Loss of Taste and Smell


title: Social and political determinants of vaccine hesitancy: Lessons learned from the H1N1 pandemic of 2009-2010

text: BACKGROUND: Public acceptance of vaccination programs is essential for vaccine preventable diseases. However, increasing sectors of the population have expressed hesitancy about participating in such programs, leading to the re-emergence of vaccine preventable diseases. In this study we rely on a recreancy hypothesis to test the association between confidence in the government and local hospitals and the willingness to take the vaccine. METHODS: A secondary analysis of a survey that used a large sample of the U.S. population conducted in October 2009 was used (N = 968). RESULTS: The results indicate that 36.1% of the respondents expressed willingness to be vaccinated. Those with the greatest trust in the government were the most likely to be vaccinated (43.4%), and those least confident were the least willing (15.8%). From the ones reporting being confident in the local health system, 38.4% were willing to be vaccinated, and from those not confident, only 23.5% were willing to be vaccinated. CONCLUSION: The decision to get vaccinated in the midst of a contagious outbreak involves many considerations. Trust in the government's technical and organization skill to deal with the infectious outbreak along with trust in medical organizations predict the adoption of recommended protection measures. The results indicate that public compliance with vaccination plans in health crisis requires the development of social and institutional trust.


title: The Clinical Features and Outcomes of Discharged Coronavirus Disease 2019 Patients：A Prospective Cohort Study

text: BACKGROUND: COVID-19 is a global pandemic but the follow-up data of discharged patients was barely described. AIMS: To investigate clinical outcomes, distribution of quarantine locations, and the infection status of the contacts of COVID-19 patients after discharge. DESIGN: A prospective cohort study METHODS: Demographics, baseline characteristics of 131 COVID-19 patients discharged from February 3 to 21, 2020 in Wuhan, China were collected and analyzed by reviewing the medical records retrospectively. Post-hospitalization data related to clinical outcomes, quarantine locations and close contact history were obtained by following up the patients every week up to 4 weeks. RESULTS: 53 (40.05%) patients on discharge had cough (29.01%), fatigue (7.63%), expectoration (6.11%), chest tightness (6.11%), dyspnea (3.82%), chest pain (3.05%), and palpitation (1.53%). These symptoms constantly declined in 4 weeks post discharge. Transient fever recurred in 11 (8.4%) patients. 78 (59.5%) discharged patients underwent chest CT and 2 (1.53%) showed deterioration. 94 (71.8%) patients received SARS-CoV-2 retest and 8 (6.10%) reported positive. 7 (2.29%) patients were re-admitted because of fever or positive SARS-CoV-2 retest. 121 (92.37%) and 4 (3.05%) patients were self-quarantined at home or community spots following discharge, with totally 167 closely contacted persons free of COVID-19 at the endpoint of study. CONCLUSIONS: The majority of COVID-19 patients after discharge were in the course of recovery. Readmission was required in rare cases due to suspected recurrence of COVID-19. Although no contacted infection observed, appropriate self-quarantine and regular reexamination are necessary, particularly for those who have recurred symptoms.


title: Accounting for incomplete testing in the estimation of epidemic parameters

text: As the COVID-19 pandemic spreads across the world, it is important to understand its features and responses to public health interventions in real-time. The field of infectious diseases epidemiology has highly advanced modeling strategies that yield relevant estimates. These include the doubling time of the epidemic and various other representations of the numbers of cases identified over time. Crude estimates of these quantities suffer from dependence on the underlying testing strategies within communities. We clarify the functional relationship between testing and the epidemic parameters, and thereby derive sensitivity analyses that explore the range of possible truths under various testing dynamics. We derive the required adjustment to the estimates of interest for New York City. We demonstrate that crude estimates that assume stable testing or complete testing can be biased.


title: Immunology in wild nonmodel rodents: an ecological context for studies of health and disease

text: Transcriptomic methods are set to revolutionize the study of the immune system in naturally occurring nonmodel organisms. With this in mind, the present article focuses on ways in which the use of ‘nonmodel’ rodents (not the familiar laboratory species) can advance studies into the classical, but ever relevant, epidemiologic triad of immune defence, infectious disease and environment. For example, naturally occurring rodents are an interesting system in which to study the environmental stimuli that drive the development and homeostasis of the immune system and, by extension, to identify where these stimuli are altered in anthropogenic environments leading to the formation of immunopathological phenotypes. Measurement of immune expression may help define individual heterogeneity in infectious disease susceptibility and transmission and facilitate our understanding of infection dynamics and risk in the natural environment; furthermore, it may provide a means of surveillance that can filter individuals carrying previously unknown acute infections of potential ecological or zoonotic importance. Finally, the study of immunology in wild animals may reveal interactions within the immune system and between immunity and other organismal traits that are not observable under restricted laboratory conditions. Potentiating much of this is the possibility of combining gene expression profiles with analytical tools derived from ecology and systems biology to reverse engineer interaction networks between immune responses, other organismal traits and the environment (including symbiont exposures), revealing regulatory architecture. Such holistic studies promise to link ecology, epidemiology and immunology in natural systems in a unified approach that can illuminate important problems relevant to human health and animal welfare and production.


title: Chapter Four Parasites in Food: From a Neglected Position to an Emerging Issue

text: Abstract Foodborne parasites have long been a neglected group of pathogens, as they often have insidious, chronic effects, rather than being acute diseases, and they are often associated with impoverished or marginalized populations. In addition, due to the long incubation period for most foodborne parasites, source attribution is often difficult, if not impossible. However, global trends have enabled foodborne parasites to emerge in different populations in new locations, transmitted through different food types, and sometimes with unexpected symptoms. This emergence of foodborne parasites has brought them into focus. In this chapter, six foodborne parasites are used as examples on emergence: Echinococcus multilocularis is spreading to new locations; Cryptosporidium spp. are beginning to be associated not only with water, but also with salads; Trypanosoma cruzi is being manifest with acute disease due to foodborne transmission, particularly transmitted with juices; Trichinella spp. have become less of a burden regarding transmission via pork in many countries, but now game animals are becoming a concern; anisakiasis is becoming a global problem as the world develops a taste for sushi, and similarly for opisthorchiasis, which is increasingly being associated with cholangiocarcinoma. However, the emergence of these foodborne parasites provides an incentive for increased efforts being made toward control. In this chapter, having described how the parasites are emerging from their neglected position, the focus turns toward control. In addition to considering control measures that may be applied to the specific parasites, an overview is provided of some of the organized collaborations, projects, and consortia, as well as some of their outputs, that have in focus the control of these emerging and important pathogens.


title: In vitro exposure system for study of aerosolized influenza virus

text: Abstract Infection of adherent cell monolayers using a liquid inoculum represents an established method to reliably and quantitatively study virus infection, but poorly recapitulates the exposure and infection of cells in the respiratory tract that occurs during infection with aerosolized pathogens. To better simulate natural infection in vitro, we adapted a system that generates viral aerosols similar to those exhaled by infected humans to the inoculation of epithelial cell monolayers. Procedures for cellular infection and calculation of exposure dose were developed and tested using viruses characterized by distinct transmission and pathogenicity phenotypes: an HPAI H5N1, an LPAI H7N9, and a seasonal H3N2 virus. While all three aerosolized viruses were highly infectious in a human bronchial epithelial cell line (Calu-3) cultured submerged in media, differences between the viruses were observed in primary human alveolar epithelial cells and in Calu-3 cells cultured at air-liquid interface. This system provides a novel enhancement to traditional in vitro experiments, particularly those focused on the early stages of infection.


Using Telehealth Groups to Combat Loneliness in Older Adults Through COVID‐19


title: Local Food Systems and COVID-19: An Insight from China

text: • Effective governance and efficient coordination across multi-levels and multi-sectors are pivotal factors to ensure food supply during COVID-19. • Digital tools and innovative models provided valuable solutions to cope with the crisis in China, which can be further developed and contribute to the “New Normal”. • The pandemic implies the necessity to strengthen urban-rural linkages and foster local food production for more resilient local food systems.