title: Infection of Human Immunodeficiency Virus and Intracellular Viral Tat Protein Exert a Pro-survival Effect in a Human Microglial Cell Line

text: Abstract The interaction of human immunodeficiency virus type 1 (HIV-1) with CD4+ T lymphocytes is well studied and typically results in virally induced cytolysis. In contrast, relatively little is known concerning the interplay between HIV-1 and microglia. Recent findings suggest that, counter-intuitively, HIV-1 infection may extend the lifespan of microglia. We developed a novel cell line model system to confirm and mechanistically study this phenomenon. We found that transduction of a human microglial cell line with an HIV-1 vector results in a powerful cytoprotective effect following apoptotic challenge. This effect was reproduced by ectopic expression of a single virus-encoded protein, Tat. Subsequent studies showed that the pro-survival effects of intracellular Tat could be attributed to activation of the PI-3-kinase (PI3K)/Akt pathway in the microglial cell line. Furthermore, we found that expression of Tat led to decreased expression of PTEN, a negative regulator of the PI-3-K pathway. Consistent with this, decreased p53 activity and increased E2F activity were observed. Based on these findings, a model of possible regulatory circuits that intracellular Tat and HIV-1 infection engage during the cytoprotective event in microglia has been suggested. We propose that the expression of Tat may enable HIV-1 infected microglia to survive throughout the course of infection, leading to persistent HIV-1 production and infection in the central nervous system.


title: 17 A guide to no-touch automated room disinfection (NTD) systems

text: Abstract: Conventional disinfection methods are limited by reliance on the operator to ensure appropriate selection, formulation, distribution and contact time of the agent. ‘No-touch’ automated room disinfection (NTD) systems remove or reduce reliance on operators and so they have the potential to improve the efficacy of terminal disinfection. The most commonly used systems are hydrogen peroxide vapour (H2O2 vapour), aerosolised hydrogen peroxide (aHP) and ultraviolet (UV) radiation. These systems have important differences in their active agent, delivery mechanism, efficacy, process time and ease of use. The choice of NTD system should be influenced by the intended application, the evidence base for effectiveness, practicalities of implementation and cost constraints.


title: Genome-wide data inferring the evolution and population demography of the novel pneumonia coronavirus (SARS-CoV-2)

text: Since December 2019, coronavirus disease 2019 (COVID-19) emerged in Wuhan, Central China and rapidly spread throughout China. Up to March 3, 2020, SARS-CoV-2 has infected more than 89,000 people in China and other 66 countries across six continents. In this study, we used 10 new sequenced genomes of SARS-CoV-2 and combined 136 genomes from GISAID database to investigate the genetic variation and population demography through different analysis approaches (e.g. Network, EBSP, Mismatch, and neutrality tests). The results showed that 80 haplotypes had 183 substitution sites, including 27 parsimony-informative and 156 singletons. Sliding window analyses of genetic diversity suggested a certain mutations abundance in the genomes of SARS-CoV-2, which may be explaining the existing widespread and high adaptation of the deadly virus. Phylogenetic analysis showed that the view, pangolin acted as an intermediate host, may be controversial. The network indicated that, in the original haplotype (H14), one patient sample lived near the Huanan seafood market (approximate 2 km), indicating high possibility of the patient having a history of unconscious contact with this market. However, based on this clue, we cannot accurately concluded that whether this market was the origin center of SARS-CoV-2. Additionally, 16 genomes, collected from this market, assigned to 10 haplotypes, indicated a circulating infection within the market in a short term and then leading to the outbreak of SARS-CoV-2 in Wuhan and other areas. The EBSP results showed that the first estimated expansion date of SARS-CoV-2 began from 7 December 2019, which may indicated that the transmission could have begun from person to person in mid to late November.


title: Neurovirulence of six different murine coronavirus JHMV variants for rats

text: Abstract Six variant viruses of the JHMV strain of murine coronavirus with large (cl-2, CNSV, DL and DS) or small (sp-4 and JHM-X) S proteins were compared in terms of their relative neurovirulence in weanling Lewis rats. Inoculation of various doses of the variants revealed that the cl-2 and CNSV were highly virulent and DL and DS were low-virulent, while sp-4 and JHM-X were avirulent. Pathological examination of rats infected with variants cl-2, DL and sp-4 showed that the cl-2 and DL induced severe and mild acute encephalomyelitis, respectively, while no lesions were observed in the central nervous system of rats infected with sp-4. Virus growth and distribution of antigen in rat brains correlated strongly with neurovirulence. These results suggest that S protein plays a role in neurovirulence in rats. In addition, these variant viruses were shown to be useful tools for further analysis of JHMV neurovirulence in animals as well as in cultured cells.


Mayo Clinic Strategies for COVID-19 Diagnostic Stewardship: An Essential Element in a Rapidly Evolving COVID-19 Pandemic


title: A sporadic COVID-19 pneumonia treated with extracorporeal membrane oxygenation in Tokyo, Japan: A case report

text: Abstract Introduction An ongoing outbreak of a novel coronavirus disease (coronavirus disease 2019, COVID-19) has become a global threat. While clinical reports from China to date demonstrate that the majority of cases remain relatively mild and recover with supportive care, it is also crucial to be well prepared for severe cases warranting intensive care. Initiating appropriate infection control measures may not always be achievable in primary care or in acute-care settings. Case A 45-year-old man was admitted to the intensive care unit due to severe pneumonia, later confirmed as COVID-19. His initial evaluation in the resuscitation room and treatments in the intensive care unit was performed under droplet and contact precaution with additional airborne protection using the N95 respirator mask. He was successfully treated in the intensive care unit with mechanical ventilation and extracorporeal membrane oxygenation for respiratory support; and antiretroviral treatment with lopinavir/ritonavir. His total intensive care unit stay was 15 days and was discharged on hospital day 24. Conclusions Strict infection control precautions are not always an easy task, especially under urgent care in an intensive care unit. However, severe cases of COVID-19 pneumonia, or another novel infectious disease, could present at any moment and would be a continuing challenge to pursue appropriate measures. We need to be well prepared to secure healthcare workers from exposure to infectious diseases and nosocomial spread, as well as to provide necessary intensive care.


title: Analysis using canine peripheral blood for establishing in vitro conditions for monocyte differentiation into macrophages for Leishmania chagasi infection and T-cell subset purification

text: Abstract Canine visceral leishmaniasis (CVL) is a parasitic disease endemic in many countries, and dogs present as the major natural reservoir of the parasite, Leishmania chagasi (syn. L. infantum). Biomarkers in the canine immune system is an important technique in the course of developing vaccines and treatment strategies against CVL. New methodologies for studying the immune response of dogs during Leishmania infection and after receiving vaccines and treatments against CVL would be useful. In this context, we used peripheral blood mononuclear cells (PBMCs) from healthy dogs to evaluate procedures related to (i) establishment of in vitro conditions of monocytes differentiated into macrophages infected with L. chagasi and (ii) purification procedures of T-cell subsets (CD4+ and CD8+) using microbeads. Our data demonstrated that after 5 days of differentiation, macrophages were able to induce significant phagocytic and microbicidal activity after L. chagasi infection and also showed increased frequency of parasitism and a higher parasite load. Although N-acetyl-β-d-glucosaminidase (NAG) levels presented similar levels of macrophage culture and L. chagasi infection, a progressive decrease in myeloperoxidase (MPO) levels was a hallmark over 5 days of culture. High purity levels (>90%) of CD4 and CD8 T cells were obtained on a magnetic separation column. We concluded that monocytes differentiated into macrophages at 5 days and displayed an intermediate frequency of parasitism and parasite load 72h after L. chagasi infection. Furthermore, the purification system using canine T-lymphocyte subsets obtained after 5 days of monocyte differentiation proved efficient for CD4 or CD8 T-cell purification (≥90%). The in vitro analysis using L. chagasi-infected macrophages and purified T cells presented a prospective methodology that could be incorporated in CVL vaccine and treatment studies that aim to analyze the microbicidal potential induced by specific CD4+ and/or CD8+ T cells.


docid: nbeuevwc

title: Antibodies to an Interfering Epitope in Hepatitis C Virus E2 Can Mask Vaccine-Induced Neutralizing Activity

text: Hepatitis C virus (HCV) neutralization occurring at the E2 region 412–426 (EP-I) could be enhanced when antibodies directed specifically to the E2 region 434–446 (EP-II) were removed from serum samples of persistently infected patients and vaccinated chimpanzees, a phenomenon of so-called antibody interference. Here we show that this type of interference can be observed in individuals after immunization with recombinant E1E2 proteins. One hundred and twelve blinded serum samples from a Phase I, placebo-controlled, dose escalation trial using recombinant HCV E1E2 with MF59C.1 adjuvant in healthy HCV-negative adults were tested in ELISA for binding reactivity to peptides representing the E2 regions 412–426 (EP-I) and 434–446 (EP-II). All samples were subsequently tested for neutralizing activity using HCVcc 1a(H77)/2a chimera, HCVpp H77 and HCVpp HCV-1 after treatment to remove EP-II-specific antibodies or mock treatment with a control peptide. Among the 112 serum samples we found 22 double positive (EP-I and EP-II), 6 EP-II positive only, 14 EP-I positive only and 70 double negative. Depleting EP-II antibodies from double positive serum samples increased ID(50) neutralizing antibody titers (up to 4.9-fold) in up to 72% of samples (p≤0.0005) contrasting with ID(50) neutralization titer increases in 2 of 70 double negative samples (2.9%) (p>0.5). In addition, EP-I-specific antibody levels in serum samples showed a significant correlation with ID(50) neutralization titers when EP-II antibodies were removed (p<0.0003). CONCLUSION: These data show that antibodies to the region 434–446 are induced during immunization of individuals with recombinant E1E2 proteins and that these antibodies can mask effective neutralizing activity from EP-I-specific antibodies. Elicitation of EP-II-specific antibodies with interfering capacity should be avoided in producing an effective cross-neutralizing vaccine aimed at the HCV envelope proteins.


title: A Rabbit Model of Hormone-induced Early Avascular Necrosis of the Femoral Head

text: Abstract Objective To establish an experimental model of early stage avascular necrosis of the femoral head (ANFH) caused by corticosteroid in adult rabbits and to observe the pathological changes with various imaging techniques. Methods ANFH was induced by a combination of hypersensitivity vasculitis caused by injection of horse serum and subsequent administration of a high dose of corticosteroid. The pathological changes were detected with digital radiography (DR), computed tomography (CT), magnetic resonance imaging (MRI), ink artery infusion angiography, hematoxylin–eosin staining, and immunohistochemistry. Results The imageological and pathological changes corresponded to the clinical characteristics of early stage ANFH. DR showed bilaterally increased bone density, an unclear epiphyseal line, and blurred texture of cancellous bone. CT showed spot-like low-density imaging of cancellous bone, thinner cortical bone, osteoporosis, and an unclear epiphyseal line. MRI showed bone marrow edema and spot-like high signals in T2-weighted imaging in cancellous bone. Ink artery infusion angiography showed fewer obstructed blood vessels in the femoral head. HE staining of pathological sections showed fewer trabeculae and thin bone, an increased proportion of empty osteocyte lacunae, decreased hematopoiesis, thrombosis, and fat cell hypertrophy. Immunohistochemistry showed attenuated expression of vascular endothelial growth factor in osteoblasts and chondrocytes, and on the inner membrane of blood vessels. Conclusion Experimental rabbit model of early stage ANFH caused by corticosteroid can be successfully established and provide the foundation for developing effective methods to treat early stage ANFH.


title: Does Eating Chicken Feet With Pickled Peppers Cause Avian Influenza? Observational Case Study on Chinese Social Media During the Avian Influenza A (H7N9) Outbreak

text: BACKGROUND: A hot topic on the relationship between a popular avian-origin food and avian influenza occurred on social media during the outbreak of the emerging avian influenza A (H7N9). The misinformation generated from this topic had caused great confusion and public concern. OBJECTIVE: Our goals were to analyze the trend and contents of the relevant posts during the outbreak. We also aimed to understand the characteristics of the misinformation and to provide suggestions to reduce public misconception on social media during the emerging disease outbreak. METHODS: The original microblog posts were collected from China’s Sina Weibo and Tencent Weibo using a combination of keywords between April 1, 2013 and June 2, 2013. We analyzed the weekly and daily trend of the relevant posts. Content analyses were applied to categorize the posts into 4 types with unified sorting criteria. The posts’ characteristics and geographic locations were also analyzed in each category. We conducted further analysis on the top 5 most popular misleading posts. RESULTS: A total of 1680 original microblog posts on the topic were retrieved and 341 (20.30%) of these posts were categorized as misleading messages. The number of relevant posts had not increased much during the first 2 weeks but rose to a high level in the next 2 weeks after the sudden increase in number of reported cases at the beginning of week 3. The posts under “misleading messages” occurred and increased from the beginning of week 3, but their daily posting number decreased when the daily number of posts under “refuting messages” outnumbered them. The microbloggers of the misleading posts had the lowest mean rank of followers and previous posts, but their posts had a highest mean rank of posts. The proportion of “misleading messages” in places with no reported cases was significantly higher than that in the epidemic areas (23.6% vs 13.8%). The popular misleading posts appeared to be short and consisted of personal narratives, which were easily disseminated on social media. CONCLUSIONS: Our findings suggested the importance of responding to common questions and misconceptions on social media platforms from the beginning of disease outbreaks. Authorities need to release clear and reliable information related to the popular topics early on. The microbloggers posting correct information should be empowered and their posts could be promoted to clarify false information. Equal importance should be attached to clarify misinformation in both the outbreak and nonoutbreak areas.


Cerebral Venous Thrombosis associated with COVID-19 infection: causality or coincidence?


title: Varying presentations of COVID‐19 in young heart transplant recipients: A case series

text: BACKGROUND: Immunosuppression is considered a risk factor for more severe clinical presentation of COVID‐19. Limited data regarding clinical outcome exist in adults, whereas very little is known about the spectrum of the disease in pediatric heart transplant recipients. METHODS: We retrospectively reviewed the charts of young heart transplant patients from our tertiary care center during the coronavirus pandemic in New York City and identified patients infected with SARS‐CoV‐2. RESULTS: We present four cases with COVID‐19 disease and elaborate on their presentation and clinical course. CONCLUSIONS: Although far from conclusive and limited by the small sample size and selection bias, these cases demonstrate mild and self‐limited disease despite immunosuppressive therapy and various comorbidities that are expected to increase the severity of the clinical picture based on extrapolation from the adult experience with this novel disease.


The Use of Point of Care Lung Ultrasound and Echocardiography in the Management of COVID-19


title: Preventing infections in non-hospital settings: long-term care.

text: Infection concerns in long-term care facilities include endemic infections, outbreaks, and colonization and infection with antimicrobial-drug resistant microorganisms. Infection control programs are now used in most long-term care facilities, but their impact on infections has not been rigorously evaluated. Preventive strategies need to address the changing complexity of care in these facilities, e.g., the increased use of invasive devices. The anticipated increase in the elderly population in the next several decades makes prevention of infection in long-term care facilities a priority.


title: Pulmonary manifestation of Plasmodium falciparum malaria: Case reports and review of the literature

text: Pulmonary complications, including acute respiratory distress syndrome (ARDS), are well described in P. falciparum (PF) and to a lesser extent in other malaria species. In non-endemic areas, malaria diagnosis may be overlooked; if a thorough travel history is not obtained on all patients with acute febrile illness. Three patients with malaria associated respiratory distress were admitted to our intensive care unit. The diagnosis was delayed; however, all patients received artesunate and intensive therapy with a satisfactory outcome. One patient presented with respiratory disease while the others developed ARDS during or following appropriate therapy. Similarly, level of parasitemia was variable ranging from undetectable to over 5%. Variability in timing and severity of illness is exciting and gives emphasis to the different pathological processes contemplated in this complication.


title: Identification and molecular cloning of a novel porcine parvovirus

text: A novel porcine parvovirus, PPV4, was identified in the lung lavage of a diseased pig coinfected with porcine circovirus type 2. This virus exhibits limited similarity to its closest relative, bovine parvovirus 2, but resembles viruses of the genus Bocavirus (bovine parvovirus, canine minute virus and human bocavirus) that encode an additional ORF3. The ORF3 of PPV4 is predicted to encode a protein of 204 amino acid residues, which is similar in size to the ORF3-encoded proteins of the bocaviruses. Whereas the ORF3-encoded proteins of bocaviruses share significant similarity with each other, the PPV4 ORF3 encoded protein does not exhibit homology with any protein in the GenBank non-redundant database.


title: Respiratory Protection against Pandemic and Epidemic Diseases

text: Respiratory protection against airborne pathogens is crucial for pandemic/epidemic preparedness in the context of personal protection, healthcare systems, and governance. We expect that the development of technologies that overcome the existing challenges in current respiratory protective devices will lead to a timely and effective response to the next outbreak.


Rapid diagnostics urgently needed for killer infections


title: Phylogenetic Analysis of Human Rhinovirus Isolates Collected from Otherwise Healthy Children with Community-Acquired Pneumonia during Five Successive Years

text: In order to evaluate the circulation of the different human rhinovirus (HRV) species and genotypes in Italian children with radiographically confirmed community-acquired pneumonia (CAP), a nasopharyngeal swab was obtained from 643 children admitted to hospital because of CAP during five consecutive winter and early spring seasons (2007-2012). Real-time reverse transcriptase polymerase chain reaction (RT-PCR) was used to identify HRV, and the HRV-positive samples were used for sequencing analysis and to reconstruct the phylogenetic tree. HRV was identified in 198 samples (42.2%), and the VP4/VP2 region was successfully amplified in 151 (76.3%). HRV-A was identified in 78 samples (51.6%), HRV-B in 14 (9.3%) and HRV-C in 59 (39.1%). Forty-seven (31.1%) of the children with HRV infection were aged <1 year, 71 (47.0%) were aged 1-3 years, and 33 (21.9%) were aged ≥4 years. Blast and phylogenetic analyses showed that the HRV strains were closely related to a total of 66 reference genotypes, corresponding to 29 HRV-A, 9 HRV-B and 28 HRV-C strains. Nucleotide variability was 37% between HRV-A and HRV-B, 37.3% between HRV-A and HRV-C, and 39.9% between HRV-B and HRV-C. A number of sequences clustered with known serotypes and, within these clusters, there were strains circulating during several seasons. The most frequently detected genotypes were HRV-A78 (n=17), HRV-A12 (n=9) and HRV-C2 (n=5). This study shows that, although it is mainly associated with HRV-A, pediatric CAP can also be diagnosed in subjects infected by HRV-C and, more rarely, by HRV-B. Moreover, a large number of genotypes may be involved in causing pediatric CAP and can be different from year to year. Although the prolonged circulation of the same genotypes can sometimes be associated with a number of CAP episodes in different years.


A novel human mAb (MERS-GD27) provides prophylactic and postexposure efficacy in MERS-CoV susceptible mice


Reply to: “COVID-19, syphilis, and biologic therapies for psoriasis and psoriatic arthritis: A word of caution”


title: Psychological intervention on COVID-19: A protocol for systematic review and meta-analysis

text: INTRODUCTION: COVID-19 is novel coronavirus infection in 2019. Many reports suggested that psychological intervention is playing a positive role in COVID-19 treatment, but there is no high-quality evidence to prove its effects. This paper reports the protocol of a systematic review and meta-analysis to clarify effectiveness of psychological intervention during the treatment of COVID-19. METHODS AND ANALYSIS: The following electronic databases will be used by 2 independent reviewers: Web of Science, Embase, Cochrane Library, PubMed, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, Chinese Scientific Journal Database, Wan fang Database, ClinicalTrials, WHO Trials, and Chinese Clinical Trial Registry. The randomised controlled trials of psychological intervention on COVID-19 will be searched in the databases by 2 researchers independently. Clinical recovery time and effective rate will be assessed as the primary outcomes. Changes of patients physical condition (1. Time until COVID-19 RT-PCR negative in upper respiratory tract specimen; 2. Time until cough reported as mild or absent; 3. Time until dyspnea reported as mild or absent; 4. Frequency of requiring supplemental oxygen or non-invasive ventilation; 5. Frequency of requiring respiratory; 6. Incidence of severe cases; 7. Proportion of re-hospitalization or admission to ICU; 8. All-cause mortality; 9. Frequency of seriously adverse events) and changes of psychological condition (such as: SRQ-20, PHQ-9, GAD-7, Hamilton Depression Scale, Hamilton Anxiety Scale) will be assessed as the secondary outcomes. For dichotomous outcomes, such as effective rate, data will be expressed as risk ratio (RR) with 95% confidence intervals (CIs). For continuous outcomes, weighted mean differences (WMD) or standardized mean differences (SMD) will be calculated. Fixed effect model will be used for evaluating efficiency. Considering clinical heterogeneity, random effect model will be used for continuous outcomes. RESULTS: Relevant studies will be used to evaluate whether psychological intervention is effective for COVID-19. CONCLUSION: This study will provide reliable evidence for psychological intervention on COVID-19. PROSPERO REGISTRATION NUMBER: CRD42020178699


Breast Milk and COVID-19: What Do We Know?


title: Molecular profile of reactive astrocytes—Implications for their role in neurologic disease

text: Abstract The central nervous system responds to diverse neurologic injuries with a vigorous activation of astrocytes. While this phenomenon is found in many different species, its function is obscure. Understanding the molecular profile characteristic of reactive astrocytes should help define their function. The purpose of this review is to provide a summary of molecules whose levels of expression differentiate activated from resting astrocytes and to use the molecular profile of reactive astrocytes as the basis for speculations on the functions of these cells. At present, reactive astrocytosis is defined primarily as an increase in the number and size of cells expressing glial fibrillary acidic protein. In vivo, this increase in glial fibrillary acidic protein-positive cells reflects predominantly phenotypic changes of resident astroglia rather than migration or proliferation of such cells. Upon activation, astrocytes upmodulate the expression of a large number of molecules. From this molecular profile it becomes apparent that reactive astrocytes may benefit the injured nervous system by participating in diverse biological processes. For example, upregulation of proteases and protease inhibitors could help remodel the extracellular matrix, regulate the concentration of different proteins in the neuropil and clear up debris from degenerating cells. Cytokines are key mediators of immunity and inflammation and could play a critical role in the regulation of the blood-central nervous system interface. Neurotrophic factors, transporter molecules and enzymes involved in the metabolism of excitotoxic amino acids or in the antioxidant pathway may help protect neurons and other brain cells by controlling neurotoxin levels and contributing to homeostasis within the central nervous system. Therefore, an impairment of astroglial performance has the potential to exacerbate neuronal dysfunction. Based on the synopsis of studies presented, a number of issues become apparent that deserve a more extensive analysis. Among them are the relative contribution of microglia and astrocytes to early wound repair, the characterization of astroglial subpopulations, the specificity of the astroglial response in different diseases as well as the analysis of reactive astrocytes with techniques that can resolve fast physiologic processes. Differences between reactive astrocytes in vivo and primary astrocytes in culture are discussed and underline the need for the development and exploitation of models that will allow the analysis of reactive astrocytes in the intact organism.


title: Brief Report: Anti‐phospholipid antibodies in critically ill patients with Coronavirus Disease 2019 (COVID‐19)

text: OBJECTIVES: Coagulopathy is one of the characteristics of critically ill patients with Coronavirus Disease 2019 (COVID‐19). Antiphospholipid antibodies (aPLs) contribute to coagulopathy, but their role in COVID‐19 remains unclear. We aimed to determine the prevalence and characteristics of aPLs in patients with COVID‐19. METHODS: Sera collected from 66 critically ill and 13 non‐critically ill patients with COVID‐19 were tested for anti‐cardiolipin (aCL) and anti‐β2‐glycoprotein 1 (aβ2GP1) (IgG, IgM, and IgA) and IgG aβ2GP1‐D1 by the chemiluminescence assay (CIA) and IgM and IgG anti‐phosphatidylserine/prothrombin (aPS/PT) by ELISA. RESULTS: aPLs were detected in 47.0% of critically ill patients (31/66), but not in patients with non‐critical conditions. IgA aβ2GP1 was the most common aPL, present in 28.8% (19/66) critically ill patients, followed by IgA aCL (25.8%,17/66) and IgG aβ2GP1 (18.2%,12/66). For multiple aPLs, IgA aβ2GP1+IgA aCL was the most common type (22.7%, 15/66), followed by IgA aβ2GP1+IgA aCL+ IgG aβ2GP1 (15.2%, 10/66). aPLs emerge around 35‐39 days post‐disease onset. Dynamic analysis of aPLs revealed 4 patterns based on persistence or transient appearance of the aPLs. Patients with multiple aPLs displayed significantly higher incidence of cerebral infarction (p=0.023). CONCLUSIONS: aPLs were common in critically ill patients. Multiple medium or high levels aPLs may help identify patients at risk of developing cerebral infarction. aPLs may be transient and disappear within a few weeks, but in genetically predisposed patients, COVID‐19 may trigger the development of “COVID‐19‐induced‐APS‐like‐syndrome”. Long‐term follow‐up on COVID‐19 patients positive for aPLs would be of great importance.


title: The Immune Response to Astrovirus Infection

text: Astroviruses are one of the leading causes of pediatric gastroenteritis worldwide and are clinically importantly pathogens in the elderly and immunocompromised populations. Although the use of cell culture systems and small animal models have enhanced our understanding of astrovirus infection and pathogenesis, little is known about the immune response to astrovirus infection. Studies from humans and animals suggest that adaptive immunity is important in restricting classic and novel astrovirus infections, while studies from animal models and cell culture systems suggest that an innate immune system plays a role in limiting astrovirus replication. The relative contribution of each arm of the immune system in restricting astrovirus infection remains unknown. This review summarizes our current understanding of the immune response to astrovirus infection and highlights some of the key questions that stem from these studies. A full understanding of the immune response to astrovirus infection is required to be able to treat and control astrovirus-induced gastroenteritis.


title: A recombinant baculovirus-expressed S glycoprotein vaccine elicits high titers of SARS-associated coronavirus (SARS-CoV) neutralizing antibodies in mice

text: A recombinant SARS-CoV spike (S) glycoprotein vaccine produced in insect cells in a pre-clinical development stage is described. A truncated version of S glycoprotein, containing only the ecto-domain, as well as a His-tagged full-length version were cloned and expressed in a serum-free insect cell line, ExpresSF+(®). The proteins, purified to apparent homogeneity by liquid column chromatography, were formulated without adjuvant at 3, 9, 27, and 50 μg per dose in phosphate saline and used to immunize mice. Both antigens in each formulation elicited a strong immune response after two or three vaccinations with the antigen. Neutralizing antibody titers correlated closely with standard ELISA reactivity against the S glycoprotein. The truncated S protein was also formulated with an adjuvant, aluminum hydroxide, at 1 μg per dose (±adjuvant), and 5 μg per dose (±adjuvant). Significantly enhanced immune responses, manifested by higher titers of serum ELISA and viral neutralizing antibodies, were achieved in adjuvanted groups with fewer doses and lower concentration of S glycoprotein. These findings indicate that the ecto-domain of SARS-CoV S glycoprotein vaccine, with or without adjuvant, is immunogenic and induces high titers of virus neutralizing antibodies to levels similar to those achieved with the full S glycoprotein vaccine.


title: Hemiacetal stabilization in a chymotrypsin inhibitor complex and the reactivity of the hydroxyl group of the catalytic serine residue of chymotrypsin

text: Abstract The aldehyde inhibitor Z-Ala-Ala-Phe-CHO has been synthesized and shown by 13C-NMR to react with the active site serine hydroxyl group of alpha-chymotrypsin to form two diastereomeric hemiacetals. For both hemiacetals oxyanion formation occurs with a pKa value of ~7 showing that chymotrypsin reduces the oxyanion pKa values by ~5.6 pKa units and stabilizes the oxyanions of both diastereoisomers by ~32kJmol−1. As pH has only a small effect on binding we conclude that oxyanion formation does not have a significant effect on binding the aldehyde inhibitor. By comparing the binding of Z-Ala-Ala-Phe-CHO with that of Z-Ala-Ala-Phe-H we estimate that the aldehyde group increases binding ~100 fold. At pH7.2 the effective molarity of the active site serine hydroxy group is ~6000 which is ~7× less effective than with the corresponding glyoxal inhibitor. Using 1H-NMR we have shown that at both 4 and 25°C the histidine pKa is ~7.3 in free chymotrypsin and it is raised to ~8 when Z-Ala-Ala-Phe-CHO is bound. We conclude that oxyanion formation only has a minor role in raising the histidine pKa and that the aldehyde hydrogen must be replaced by a larger group to raise the histidine pKa >10 and give stereospecific formation of tetrahedral intermediates. The results show that a large increase in the pKa of the active site histidine is not needed for the active site serine hydroxyl group to have an effective molarity of 6000.


title: Identification and evaluation of potent Middle East respiratory syndrome coronavirus (MERS-CoV) 3CLPro inhibitors

text: Abstract Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe acute respiratory illness with fever, cough and shortness of breath. Up to date, it has resulted in 1826 human infections, including 649 deaths. Analogous to picornavirus 3C protease (3Cpro), 3C-like protease (3CLpro) is critical for initiation of the MERS-CoV replication cycle and is thus regarded as a validated drug target. As presented here, our peptidomimetic inhibitors of enterovirus 3Cpro (6b, 6c and 6d) inhibited 3CLpro of MERS-CoV and severe acute respiratory syndrome coronavirus (SARS-CoV) with IC50 values ranging from 1.7 to 4.7 μM and from 0.2 to 0.7 μM, respectively. In MERS-CoV-infected cells, the inhibitors showed antiviral activity with EC50 values ranging from 0.6 to 1.4 μM, by downregulating the viral protein production in cells as well as reducing secretion of infectious viral particles into culture supernatants. They also suppressed other α- and β-CoVs from human and feline origin. These compounds exhibited good selectivity index (over 70 against MERS-CoV) and could lead to the development of broad-spectrum antiviral drugs against emerging CoVs and picornaviruses.


title: Detection of feline coronaviruses by culture and reverse transcriptase-polymerase chain reaction of blood samples from healthy cats and cats with clinical feline infectious peritonitis

text: Abstract A reverse transcriptase-polymerase chain reaction (RT-PCR) assay for the detection of the feline coronavirus (FCoV) genome and a co-cultivation method for the isolation of field strains of FCoV are described. Using the RT-PCR assay to assess blood samples from cats with feline infectious peritonitis (FIP) (n=47) and healthy cats from households with endemic FCoV (n=69) it was shown that approximately 80% of the cats were viraemic, irrespective of their health status. It was also shown that, over a 12-month period, a similar percentage of healthy cats remained viraemic, and that the presence of viraemia did not appear to predispose the cats to the development of FIP. The co-cultivation system proved to be a suitable method for the culture of field strains of FCoV from blood samples, so long as the cultures were maintained for at least 4 weeks. Using this system, followed by the RT-PCR, viraemia was detected as frequently as by RT-PCR on RNA extracted directly from peripheral blood mononuclear cells.


title: Coevolution of paired receptors in Xenopus carcinoembryonic antigen-related cell adhesion molecule families suggests appropriation as pathogen receptors

text: BACKGROUND: In mammals, CEACAM1 and closely related members represent paired receptors with similar extracellular ligand-binding regions and cytoplasmic domains with opposing functions. Human CEACAM1 and CEACAM3 which have inhibitory ITIM/ITSM and activating ITAM-like motifs, respectively, in their cytoplasmic regions are such paired receptors. Various bacterial pathogens bind to CEACAM1 on epithelial and immune cells facilitating both entry into the host and down-regulation of the immune response whereas interaction with granulocyte-specific CEACAM3 leads to their uptake and destruction. It is unclear whether paired CEACAM receptors also exist in other vertebrate clades. RESULTS: We identified more than 80 ceacam genes in Xenopus tropicalis and X. laevis. They consist of two subgroups containing one or two putative paired receptor pairs each. Analysis of genomic sequences of paired receptors provide evidence that their highly similar ligand binding domains were adjusted by recent gene conversion events. In contrast, selection for diversification is observed among inhibitory receptor orthologs of the two frogs which split some 60 million years ago. The allotetraploid X. laevis arose later by hybridization of two closely related species. Interestingly, despite the conservation of the genomic landscape surrounding the homeologous ceacam loci only one locus resembles the one found in X. tropicalis. From the second X. laevis locus more than 80 % of the ceacam genes were lost including 5 of the 6 paired receptor genes. This suggests that once the gene for one of the paired receptors is lost the remaining gene cluster degrades rapidly probably due to lack of selection pressure exerted by pathogens. CONCLUSIONS: The presence of paired receptors and selection for diversification suggests that also in amphibians CEACAM1-related inhibitory proteins are or were used as pathogen receptors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-3279-9) contains supplementary material, which is available to authorized users.


India’s COVID-19 Testing Strategy: Why Pediatric Hospitals Need to Focus More on ILI than SARI?


docid: cwkwnydk

title: Rationally designed ligand‐independent peptide inhibitors of TREM‐1 ameliorate collagen‐induced arthritis

text: Triggering receptor expressed on myeloid cells 1 (TREM‐1) is critically involved in the pathogenesis of rheumatoid arthritis (RA). In contrast to cytokine blockers, therapeutic blockade of TREM‐1 can blunt excessive inflammation while preserving the capacity for microbial control. However, the nature of the TREM‐1 ligand(s) and mechanisms of TREM‐1 signalling are still not yet well understood, impeding the development of clinically relevant inhibitors of TREM‐1. The aim of this study was to evaluate the anti‐arthritic activity of a novel, ligand‐independent TREM‐1 inhibitory nonapeptide GF9 that was rationally designed using the signalling chain homo oligomerization (SCHOOL) model of cell signalling. Free GF9 and GF9 bound to macrophage‐targeted nanoparticles that mimic human high‐density lipoproteins (GF9‐HDL) were used to treat collagen‐induced arthritis (CIA). We also tested if 31‐mer peptides with sequences from GF9 and helices 4 (GE31) and 6 (GA31) of the major HDL protein, apolipoprotein A‐I, are able to perform three functions: assist in the self‐assembly of GA/E31‐HDL, target these particles to macrophages and block TREM‐1 signalling. We showed that GF9, but not control peptide, ameliorated CIA and protected against bone and cartilage damage. The therapeutic effect of GF9 was accompanied by a reduction in the plasma levels of macrophage colony‐stimulating factor and pro‐inflammatory cytokines such as tumour necrosis factor‐α, interleukin (IL)‐1 and IL‐6. Incorporation of GF9 alone or as a part of GE31 and GA31 peptides into HDL significantly increased its therapeutic efficacy. Collectively, our findings suggest that TREM‐1 inhibitory SCHOOL sequences may be promising alternatives for the treatment of RA.


title: Cystatin C is a disease‐associated protein subject to multiple regulation

text: A protease inhibitor, cystatin C (Cst C), is a secreted cysteine protease inhibitor abundantly expressed in body fluids. Clinically, it is mostly used to measure glomerular filtration rate as a marker for kidney function due to its relatively small molecular weight and easy detection. However, recent findings suggest that Cst C is regulated at both transcriptional and post‐translational levels, and Cst C production from haematopoietic cell lineages contributes significantly to the systematic pools of Cst C. Furthermore, Cst C is directly linked to many pathologic processes through various mechanisms. Thus fluctuation of Cst C levels might have serious clinical implications rather than a mere reflection of kidney functions. Here, we summarize the pathophysiological roles of Cst C dependent and independent on its inhibition of proteases, outline its change of expression by various stimuli, and elucidate the regulatory mechanisms to control this disease‐related protease inhibitor. Finally, we discuss the clinical implications of these findings for translational gains.


Age, frailty and diabetes – triple jeopardy for vulnerability to COVID-19 infection


title: Rapid detection of a highly virulent Chinese-type isolate of Porcine Reproductive and Respiratory Syndrome virus by real-time reverse transcriptase PCR

text: An outbreak of highly virulent Chinese-type of Porcine Reproductive and Respiratory Syndrome Virus (H-PRRSV) in most areas of China recently has led to huge economic losses and drawn great attention to its diagnosis and disease control. To facilitate rapid identification of H-PRRSV, a fluorogenic-probe hydrolysis (TaqMan)-reverse transcriptase PCR for H-PRRSV has been developed. Primers and probe specificity were evaluated with RNA extracted from 5 strains of H-PRRSV and 24 strains of other viruses, the results showed 100% specificity for the selected panel. The assay met the sensitivity of 1 50% tissue culture infective dose (TCID(50)) per ml of samples from infected pigs. Analysis with 10(5)–1 TCID(50)/ml H-PRRSV samples demonstrated high reproducibility with a coefficient of variation (CV) of 0.5–2.5%. More than two hundred samples from lung, spleen, blood serum specimens obtained from 22 outbreaks of suspected H-PRRS from March to June in 2007 were verified using this assay. The results showed that 68.5% (146 out of 213) of these samples were positive which is 100% consistent with that of the sequencing method. The assay can be performed in less than 3 h and thus provide a rapid method for the diagnosis of H-PRRSV as well as for elucidation of the epidemiology of H-PRRSV infections.


title: What can health care professionals in the United Kingdom learn from Malawi?

text: Debate on how resource-rich countries and their health care professionals should help the plight of sub-Saharan Africa appears locked in a mind-set dominated by gloomy statistics and one-way monetary aid. Having established a project to link primary care clinics based on two-way sharing of education rather than one-way aid, our United Kingdom colleagues often ask us: "But what can we learn from Malawi?" A recent fact-finding visit to Malawi helped us clarify some aspects of health care that may be of relevance to health care professionals in the developed world, including the United Kingdom. This commentary article is focused on encouraging debate and discussion as to how we might wish to re-think our relationship with colleagues in other health care environments and consider how we can work together on a theme of two-way shared learning rather than one-way aid.


title: Antibodies against H10N8 avian influenza virus among animal workers in Guangdong Province before November 30, 2013, when the first human H10N8 case was recognized

text: BACKGROUND: Considered an epicenter of pandemic influenza virus generation, southern China has recently seen an increasing number of human H7N9 infections. However, it is not the only threat. On 30 November 2013, a human H10N8 infection case was first described in China. The origin and genetic diversity of this novel virus is similar to that of H7N9 virus. As H10N8 avian influenza virus (AIV) was first identified from a duck in Guangdong Province during 2012 and there is also evidence of H10N8 infected dogs in this region, we sought to examine archived sera from animal workers to see if there was evidence of subclinical human infections before the first human H10N8 cases. METHODS: We studied archived serum samples (cross-sectional study, convenience sample) collected between May and September 2013 from 710 animal workers and 107 non-animal exposed volunteers living in five cities of Guangdong Province. Study participants’ sera were tested by horse red blood cells (RBCs) hemagglutination inhibition (HI) and microneutralization (MN) assays according to World Health Organization guidelines. The A/Jiangxi-Donghu/346-1/2013(H10N8) virus was used. Sera which have an HI assay ≥1:20 were further tested with the MN assay. Questionnaire data were examined for risk factor associations with positive serological assays. Risk factor analyses failed to identify specific factors associated with probable H10N8 infections. RESULTS: Among the 827 sera, only 21 animal workers had an HI titer ≥1:20 (18 had an HI titer of 1:20 and 3 had an HI titer of 1:40). None of these 21 subjects reported experiencing any influenza symptoms during the three months before enrollment. Among the three subjects with HI titers of 1:40, two had MN antibody titers of 1:40, and one had a MN antibody titer of 1:80 (probable H10N8 infections). CONCLUSIONS: Study data suggest that animal workers may have been infected with the H10N8 virus before the first recognized H10N8 human infection cases. It seems prudent to continue surveillance for H10N8 viruses among animal workers.


title: Protection from infection with influenza A H7N9 virus in a mouse model by equine neutralizing F(ab′)2

text: Abstract Influenza A H7N9 virus has demonstrated considerable pandemic potential in China ever since early spring 2013. Until now, there have been no specific medicines to treat influenza A H7N9 virus infected patients. Development of a safe and effective H7N9 therapeutic preparation is urgently needed. To this end, we prepared and evaluated the pepsin-digested F(ab′)2 fragments of serum IgGs from the horses inoculated with a inactivated influenza A H7N9 whole virus antigens. The protective effects of the F(ab′)2 fragments against H7N9 virus infection were determined in cultured MDCK cells by cytopathic effect (CPE) and evaluated in a BALB/c mouse model by observing death, weight loss and viral load. The in vitro results showed that the F(ab′)2 fragments had an HI titer of 1:2048 and a neutralization titer of 1: 31,623. The in vivo assays suggested that 600U of the preparations could efficiently protect BALB/c mice from a lethal dose of A/Anhui/01/2013 (H7N9) infection even when administered two days post infection. Thus, this highly purified preparation should be a potential candidate for treating severe patients suffering from influenza A H7N9.


title: Cyclophilins as Modulators of Viral Replication

text: Cyclophilins are peptidyl‐prolyl cis/trans isomerases important in the proper folding of certain proteins. Mounting evidence supports varied roles of cyclophilins, either positive or negative, in the life cycles of diverse viruses, but the nature and mechanisms of these roles are yet to be defined. The potential for cyclophilins to serve as a drug target for antiviral therapy is evidenced by the success of non-immunosuppressive cyclophilin inhibitors (CPIs), including Alisporivir, in clinical trials targeting hepatitis C virus infection. In addition, as cyclophilins are implicated in the predisposition to, or severity of, various diseases, the ability to specifically and effectively modulate their function will prove increasingly useful for disease intervention. In this review, we will summarize the evidence of cyclophilins as key mediators of viral infection and prospective drug targets.


title: Strengthening health care research and academics during and after COVID19 pandemic- an Indian perspective

text: The world-wide crisis of COVID-19 pandemic has disrupted daily lives, global economies, intra/inter-countries political outlook and educational systems. Schools and colleges in India and abroad are under lock-down to maximize social distancing and minimize the spread of infection amongst students and teaching staff. Health sciences related universities and researchers are forced to adopt non-contact teaching and research. Present article highlights the positive impact and opportunities provided by COVID-19 crisis to health care research and academic set-up. We have compiled ethical, effective and practical guidelines and policies to mitigate the impact on health care related research and academic front during these pandemic times in an Indian perspective. These guidelines and management suggestions can be modified to suit region based cases and can be applied in global perspective also. The suggestions in the current article provide a working collaboration of students and teachers to effectively connect on virtual platforms to strengthen their research output, giving suggestions of data-sharing and rapid review of proposals by online review ethical boards. This time is proposed to be used for generating a positive impact on health and research sector to use each adversity as an opportunity.


Evaluation on different non-pharmaceutical interventions during COVID-19 pandemic: an analysis of 139 countries


title: Avian and human influenza virus compatible sialic acid receptors in little brown bats

text: Influenza A viruses (IAVs) continue to threaten animal and human health globally. Bats are asymptomatic reservoirs for many zoonotic viruses. Recent reports of two novel IAVs in fruit bats and serological evidence of avian influenza virus (AIV) H9 infection in frugivorous bats raise questions about the role of bats in IAV epidemiology. IAVs bind to sialic acid (SA) receptors on host cells, and it is widely believed that hosts expressing both SA α2,3-Gal and SA α2,6-Gal receptors could facilitate genetic reassortment of avian and human IAVs. We found abundant co-expression of both avian (SA α2,3-Gal) and human (SA α2,6-Gal) type SA receptors in little brown bats (LBBs) that were compatible with avian and human IAV binding. This first ever study of IAV receptors in a bat species suggest that LBBs, a widely-distributed bat species in North America, could potentially be co-infected with avian and human IAVs, facilitating the emergence of zoonotic strains.


docid: lxgofvye

title: Factors associated with duration of viral shedding in adults with COVID-19 outside of Wuhan, China: A retrospective cohort study

text: Abstract Objectives To investigate factors associated with the duration of viral shedding in patients with COVID-19 outside of Wuhan. Methods In this retrospective cohort study, patients with laboratory-confirmed COVID-19 in Changsha, China were included. Clinical characteristics, laboratory findings, treatment and outcome were retrieved. Univariable and multivariable analysis were performed to explore potential factors. Results Totally 147 patients with COVID-19 were included. The median duration of viral shedding (the number of days from symptoms onset till the successive negative detection of SARS-CoV-2 RNA) was 17 days (interquartile range [IQR], 12 to 21). Multivariable Logistic regression analysis indicated that the highest temperature at admission (odds ratio [OR], 5.200; 95% confidence interval [CI]: 1.190-22.726; p = 0.028) and time from symptom onset to admission (OR, 1.740; 95% CI: 1.296-2.337; p < 0.001) and hospital length of stay (OR, 1.604; 95% CI: 1.262-2.040; p < 0.001) were risk factors for prolonged duration of viral shedding. Conclusions This is the study with relatively large sample size that mainly focused on the duration of viral shedding and relevant factors in patients with COVID-19 outside of Wuhan, China. Potential risk factors were identified and should be taken into consideration for the strategy of quarantine of infected patients.


title: Proposed Clinical Indicators for Efficient Screening and Testing for COVID-19 Infection from Classification and Regression Trees (CART) Analysis

text: Background: The introduction and rapid transmission of SARS CoV2 in the United States resulted in implementation of methods to assess, mitigate and contain the resulting COVID-19 disease based on limited knowledge. Screening for testing has been based on symptoms typically observed in inpatients, yet outpatient symptom complexes may differ. Methods: Classification and regression trees (CART) recursive partitioning created a decision tree classifying enrollees into laboratory-confirmed cases and non-cases. Demographic and symptom data from patients ages 18-87 years who were enrolled from March 29-April 26, 2020 were included. Presence or absence of SARSCoV2 was the target variable. Results: Of 736 tested, 55 were positive for SARS-CoV2. Cases significantly more often reported chills, loss of taste/smell, diarrhea, fever, nausea/vomiting and contact with a COVID-19 case, but less frequently reported shortness of breath and sore throat. A 7-terminal node tree with a sensitivity of 96% and specificity of 53%, and an AUC of 78% was developed. The positive predictive value for this tree was 14% while the negative predictive value was 99%. Almost half (44%) of the participants could be ruled out as likely non-cases without testing. Discussion: Among those referred for testing, negative responses to three questions could classify about half of tested persons with low risk for SARS-CoV2 and would save limited testing resources. These questions are: was the patient in contact with a COVID-19 case? Has the patient experienced 1) a loss of taste or smell; or 2) nausea or vomiting? The outpatient symptoms of COVID-19 appear to be broader than the well-known inpatient syndrome.


title: Understanding TGEV–ETEC Coinfection through the Lens of Proteomics: A Tale of Porcine Diarrhea

text: Porcine diarrhea and gastroenteritis are major causes of piglet mortality that result in devastating economic losses to the industry. A plethora of pathogens can cause these diseases, with the transmissible gastroenteritis virus (TGEV) and enterotoxigenic Escherichia coli K88 (ETEC) being two of the most salient. In the December 2017 issue of Proteomics Clinical Aplications, Xia and colleagues used comparative proteomics to shed light on how these microbes interact to cause severe disease 1. The authors discovered that TGEV induces an epithelial‐mesenchymal transition‐like phenotype that augments cell adhesion proteins mediating the attachment of ETEC to intestinal epithelial cells. Moreover, coinfection was found to modulate several host proteins that could bolster pathogen persistence. Importantly, the authors observed that ETEC suppresses the production of inflammatory cytokines induced by TGEV, which may in turn promote the long‐term survival of both microbes.


docid: tdagpcbk

title: Perspectives on Surgery in the time of COVID-19: Safety First


title: We shouldn’t worry when a virus mutates during disease outbreaks

text: Mutation. The word naturally conjures fears of unexpected and freakish changes. Ill-informed discussions of mutations thrive during virus outbreaks, including the ongoing spread of SARS-CoV-2. In reality, mutations are a natural part of the virus life cycle and rarely impact outbreaks dramatically.


title: Lung base CT findings in COVID-19 adult patients presenting with acute abdominal complaints: case series from a major New York City health system

text: OBJECTIVE: To describe demographic, clinical, and lung base CT findings in COVID-19 patients presenting with abdominal complaints. METHODS: In this retrospective study, 76 COVID-19 patients who underwent abdominal CT for abdominal complaints from March 1 to April 15, 2020, in a large urban multihospital Health System were included. Those with positive abdominal CT findings (n = 14) were then excluded, with 62 patients undergoing final analysis (30M/32F; median age 63 years, interquartile range (IQR) 52–75 years, range 30–90 years). Demographic and clinical data were extracted. CT lung base assessment was performed by a cardiothoracic radiologist. Data were compared between discharged and hospitalised patients using Wilcoxon or Fisher’s exact tests. RESULTS: The majority of the population was non-elderly (56.4%, < 65 years) and most (81%) had underlying health conditions. Nineteen percent were discharged and 81% were hospitalised. The most frequent abdominal symptoms were pain (83.9%) and nausea/vomiting/anorexia (46.8%). Lung base CT findings included ground-glass opacities (95.2%) in a multifocal (95.2%) and peripheral (66.1%) distribution. Elevated laboratory values (when available) included C-reactive protein (CRP) (97.3%), D-dimer (79.4%), and ferritin (68.8% of males and 81.8% of females). Older age (p = 0.045), hypertension (p = 0.019), and lower haemoglobin in women (p = 0.042) were more frequent in hospitalised patients. There was no difference in lung base CT findings between discharged and hospitalised patients (p > 0.165). CONCLUSIONS: COVID-19 patients can present with abdominal symptoms, especially in non-elderly patients with underlying health conditions. Lung base findings on abdominal CT are consistent with published reports. Radiologists should be aware of atypical presentations of COVID-19. KEY POINTS: • COVID-19 infected patients can present with acute abdominal symptoms, especially in non-elderly patients with underlying health conditions, and may frequently require hospitalisation (81%). • There was no difference in lung base CT findings between patients who were discharged and those who were hospitalised. • Lung base CT findings included multifocal and peripheral ground-glass opacities, consistent with published reports.


PESTE NOIRE (1347-1352) ET COVID-19 (2019-20-- ?) LES SIMILITUDES


title: Porcine epidemic diarrhea virus infection blocks Cell cycle and induces apoptosis in pig intestinal epithelial cells

text: Porcine epidemic diarrhea virus (PEDV) is responsible for the acute infectious swine disease porcine epidemic diarrhea (PED). PED causes damage to the intestine, including villus atrophy and shedding, leading to serious economic losses to the pig industry worldwide. We carried out an in vitro study to investigate cell apoptosis and the cell cycle in a PEDV-infected host using transcriptomic shotgun sequencing (RNA-Seq) to study gene responses to PEDV infection. Results revealed that the PEDV infection reduced proliferation activity, blocked the cell cycle at S-phase and induced apoptosis in IPEC-J2 cells. The expression of gene levels related to ribosome proteins and oxidative phosphorylation were significantly up-regulated post-PEDV infection. Although the significantly down-regulated on PI3K/Akt signaling pathway post-PEDV infection, the regulator–related genes of mTOR signaling pathway exerted significantly up-regulated or down-regulated in IPEC-J2 cells. These results indicated that ribosome proteins and oxidative phosphorylation process were widely involved in the pathological changes and regulation of host cells caused by PEDV infection, and PI3K/AKT and mTOR signaling pathways played a vital role in antiviral regulation in IPEC-J2 cells. These data might provide new insights into the specific pathogenesis of PEDV infection and pave the way for the development of effective therapeutic strategies.


title: Introductory histopathological findings may shed light on COVID‐19 paediatric hyperinflammatory shock syndrome

text: Numerous pediatric cases of hyperinflammatory shock syndrome (demonstrating features reminiscent of Kawasaki vasculitis) were recently associated with infection by COVID-19. Clinical presentation includes unrelenting fever, variable rash, conjunctivitis and abdominal pain, progressing to hemodynamic shock with severe myocardial involvement. Recent report from Italy reported a 30 time increase in the rate of Kawasaki-like presentation during the COVID-19 pandemic among children, In many cases the nasopharyngeal swabs taken from these children were negative for COVID-19, and the association with COVID-19 infection is unclear.


title: Adamantanes might be protective from COVID-19 in patients with neurological diseases: multiple sclerosis, parkinsonism and cognitive impairment

text: Abstract Facing the outbreak of coronavirus disease 2019 (COVID-19) pandemic, there is an urgent need to find protective or curable drugs to prevent or to stop the course of the coronavirus SARS-CoV-2 infection. Recent evidence accumulates that adamantanes, widely used in different neurological diseases, could be repurposed for COVID-19. We hereby report on a questionnaire-based study performed to assess severity of COVID-19 in patients suffering from multiple sclerosis (n=10), Parkinson's disease (n=5) or cognitive impairment (n=7). In all patients infection with SARS-CoV-2 was confirmed by rtPCR of nasopharyngeal swabs. They were receiving treatment with either amantadine (n=15) or memantine (n=7) in stable registered doses. All of them had two-week quarantine since documented exposure and none of them developed clinical manifestations of infectious disease. They also did not report any significant changes in neurological status in the course of primary nervous system disease. Above results warrant further studies on protective effects of adamantanes against COVID-19 manifestation, especially in subjects suffering from neurological disease.


Taking matters into our own hands: reflections on the COVID‐19 pandemic in the Philippines


title: Immunogenicity and Protective Effect of a Virus-Like Particle Containing the SAG1 Antigen of Toxoplasma gondii as a Potential Vaccine Candidate for Toxoplasmosis

text: This study was carried out to evaluate the vaccination effect of a virus-like particle (VLP) including the surface antigen 1 (SAG1) of Toxoplasma gondii as a potential vaccine for toxoplasmosis. The SAG1 virus-like particles (SAG1-VLPs) were expressed by Sf9 cells, and their expression was confirmed through cloning, RT-PCR analysis, and western blot method. The immunogenicity and vaccine efficacy of SAG1-VLPs were assessed by the antibody response, cytokine analysis, neutralization activity, splenocyte assay, and survival rates through a mouse model. In particular, IgG, IgG1, IgG2a, and IgA were markedly increased after immunization, and the survival rates of T. gondii were strongly inhibited by the immunized sera. Furthermore, the immunization of SAG1-VLPs effectively decreased the production of specific cytokines, such as IL-1β, IL-6, TNF-α, and IFN-γ, after parasite infection. In particular, the immunized group showed strong activity and viability compared with the non-immunized infection group, and their survival rate was 75%. These results demonstrate that SAG1-VLP not only has the immunogenicity to block T. gondii infection by effectively inducing the generation of specific antibodies against T. gondii, but is also an effective antigen delivery system for preventing toxoplasmosis. This study indicates that SAG1-VLP can be effectively utilized as a promising vaccine candidate for preventing or inhibiting T. gondii infection.


title: Model for Vaccine Design by Prediction of B-Epitopes of IEDB Given Perturbations in Peptide Sequence, In Vivo Process, Experimental Techniques, and Source or Host Organisms

text: Perturbation methods add variation terms to a known experimental solution of one problem to approach a solution for a related problem without known exact solution. One problem of this type in immunology is the prediction of the possible action of epitope of one peptide after a perturbation or variation in the structure of a known peptide and/or other boundary conditions (host organism, biological process, and experimental assay). However, to the best of our knowledge, there are no reports of general-purpose perturbation models to solve this problem. In a recent work, we introduced a new quantitative structure-property relationship theory for the study of perturbations in complex biomolecular systems. In this work, we developed the first model able to classify more than 200,000 cases of perturbations with accuracy, sensitivity, and specificity >90% both in training and validation series. The perturbations include structural changes in >50000 peptides determined in experimental assays with boundary conditions involving >500 source organisms, >50 host organisms, >10 biological process, and >30 experimental techniques. The model may be useful for the prediction of new epitopes or the optimization of known peptides towards computational vaccine design.


title: Exposure to air pollution and COVID-19 mortality in the United States: A nationwide cross-sectional study

text: Objectives: United States government scientists estimate that COVID-19 may kill tens of thousands of Americans. Many of the pre-existing conditions that increase the risk of death in those with COVID-19 are the same diseases that are affected by long-term exposure to air pollution. We investigated whether long-term average exposure to fine particulate matter (PM2.5) is associated with an increased risk of COVID-19 death in the United States. Design: A nationwide, cross-sectional study using county-level data. Data sources: COVID-19 death counts were collected for more than 3,000 counties in the United States (representing 98% of the population) up to April 22, 2020 from Johns Hopkins University, Center for Systems Science and Engineering Coronavirus Resource Center. Main outcome measures: We fit negative binomial mixed models using county-level COVID-19 deaths as the outcome and county-level long-term average of PM2.5 as the exposure. In the main analysis, we adjusted by 20 potential confounding factors including population size, age distribution, population density, time since the beginning of the outbreak, time since state issuance of the stay-at-home order, hospital beds, number of individuals tested, weather, and socioeconomic and behavioral variables such as obesity and smoking. We included a random intercept by state to account for potential correlation in counties within the same state. We conducted more than 68 additional sensitivity analyses. Results: We found that an increase of only 1 μg/m3 in PM2.5 is associated with an 8% increase in the COVID-19 death rate (95% confidence interval [CI]: 2%, 15%). The results were statistically significant and robust to secondary and sensitivity analyses. Conclusions: A small increase in long-term exposure to PM2.5 leads to a large increase in the COVID-19 death rate. Despite the inherent limitations of the ecological study design, our results underscore the importance of continuing to enforce existing air pollution regulations to protect human health both during and after the COVID-19 crisis. The data and code are publicly available so our analyses can be updated routinely.


title: Respiratory Viruses and Eosinophils: exploring the connections

text: In this review, we consider the role played by eosinophilic leukocytes in the pathogenesis and pathophysiology of respiratory virus infection. The vast majority of the available information on this topic focuses on respiratory syncytial virus (RSV; Family Paramyxoviridae, genus Pneumovirus), an important pediatric pathogen that infects infants worldwide. There is no vaccine currently available for RSV. A formalininactivated RSV vaccine used in a trial in the 1960s elicited immunopathology in response to natural RSV infection; this has been modeled experimentally, primarily in inbred mice and cotton rats. Eosinophils are recruited to the lung tissue in response to formalin-inactivated RSV vaccine antigens in humans and in experimental models, but they may or may not be involved in promoting the severe clinical sequelae observed. Pulmonary eosinophilia elicited in response to primary RSV infection has also been explored; this response is particularly evident in the youngest human infants and in neonatal mouse models. Although pulmonary eosinophilia is nearly always perceived in a negative light, the specific role played by virus-elicited eosinophils - negative, positive or neutral bystander - remain unclear. Lastly, we consider the data that focus on the role of eosinophils in promoting virus clearance and antiviral host defense, and conclude with a recent study that explores the role of eosinophils themselves as targets of virus infection. (215 words)


Selected mosquito-borne illnesses—Chikungunya


title: The Epitope Study on the SARS-CoV Nucleocapsid Protein

text: The nucleocapsid protein (N protein) has been found to be an antigenic protein in a number of coronaviruses. Whether the N protein in severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is antigenic remains to be elucidated. Using Western blot and Enzyme-linked Immunosorbent Assay (ELISA), the recombinant N proteins and the synthesized peptides derived from the N protein were screened in sera from SARS patients. All patient sera in this study displayed strong positive immunoreactivities against the recombinant N proteins, whereas normal sera gave negative immunoresponses to these proteins, indicating that the N protein of SARS-CoV is an antigenic protein. Furthermore, the epitope sites in the N protein were determined by competition experiments, in which the recombinant proteins or the synthesized peptides competed against the SARS-CoV proteins to bind to the antibodies raised in SARS sera. One epitope site located at the C-terminus was confirmed as the most antigenic region in this protein. A detailed screening of peptide with ELISA demonstrated that the amino sequence from Codons 371 to 407 was the epitope site at the C-terminus of the N protein. Understanding of the epitope sites could be very significant for developing an effective diagnostic approach to SARS.


Ebola vaccines line up while industry calls for change


title: Heightened innate immune responses in the respiratory tract of COVID-19 patients

text: Summary The outbreaks of 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV-2 infection has posed a severe threat to global public health. It is unclear how the human immune system responds to this infection. Here, we used metatranscriptomic sequencing to profile immune signatures in the bronchoalveolar lavage fluid of eight COVID-19 cases. The expression of proinflammatory genes, especially chemokines, was markedly elevated in COVID-19 cases compared to community-acquired pneumonia patients and healthy controls, suggesting that SARS-CoV-2 infection causes hypercytokinemia. Compared to SARS-CoV, which is thought to induce inadequate interferon (IFN) responses, SARS-CoV-2 robustly triggered expression of numerous IFN-inducible genes (ISGs). These ISGs exhibit immunopathogenic potential, with overrepresentation of genes involved in inflammation. The transcriptome data was also used to estimate immune cell populations, revealing increases in activated dendritic cells and neutrophils. Collectively, these host responses to SARS-CoV-2 infection could further our understanding of disease pathogenesis and point towards antiviral strategies.


title: Chapter 65 Mucosal Vaccines from Plant Biotechnology

text: Abstract The use of plants for production of recombinant proteins has evolved over the past 25years. The first plant-based vaccines were expressed in stably transgenic plants, with the idea to conveniently deliver “edible vaccines” by ingestion of the antigen-containing plant material. These systems provided a proof of concept that oral delivery of vaccines in crude plant material could stimulate antigen-specific serum and mucosal antibodies. Transgenic grains like rice in particular provide a stable and robust vehicle for antigen delivery. However, some issues exist with stably transgenic plants, including relatively low expression levels and regulatory issues. Thus, many recent studies use transient expression with plant viral vectors to achieve rapid high expression in Nicotiana benthamiana, followed by purification of antigen and intranasal delivery for effective stimulation of mucosal immune responses.


title: The Neurologic Manifestations of Coronavirus Disease 2019 Pandemic: A Systemic Review

text: Objective: Review and integrate the neurologic manifestations of the Coronavirus Disease 2019 (COVID-19) pandemic, to aid medical practitioners who are combating the newly derived infectious disease. Methods: We reviewed the clinical research, consisting of mainly case series, on reported neurologic manifestations of COVID-19. We also reviewed basic studies to understand the mechanism of these neurologic symptoms and signs. Results: We included 79 studies for qualitative synthesis and 63 studies for meta-analysis. The reported neurologic manifestations were olfactory/taste disorders (35.6%), myalgia (18.5%), headache (10.7%), acute cerebral vascular disease (8.1%), dizziness (7.9%), altered mental status (7.8%), seizure (1.5%), encephalitis, neuralgia, ataxia, Guillain-Barre syndrome, Miller Fisher syndrome, intracerebral hemorrhage, polyneuritis cranialis, and dystonic posture. Conclusions: Neurologic manifestations in COVID-19 may alert physicians and medical practitioners to rule in high-risk patients. The increasing incidence of olfactory/taste disorders, myalgia, headache, and acute cerebral vascular disease renders a possibility that COVID-19 could attack the nervous system. The cytokine secretion and bloodstream circulation (viremia) are among the most possible routes into the nervous system.


docid: jenwsert

title: The role of respiratory viruses in cystic fibrosis

text: Abstract Background Previous studies have suggested a role played by respiratory viruses in the exacerbation of cystic fibrosis (CF). However, the impact of respiratory viruses could have been underestimated because of the low detection rate by conventional laboratory methods. Methods Children with CF had nasal swabs and sputum samples obtained on a routine basis and when they developed respiratory exacerbations. Nucleic Acid Sequence Based Amplification (NASBA) was used to detect respiratory viruses from nasal swabs. The definition of a respiratory exacerbation was when the symptom score totalled to 4 or more, or if the peak expiratory flow fell by more than 50 l/min from the child's usual best value, or if the parent subjectively felt that the child was developing a cold. Results 71 patients had 165 reported episodes of respiratory exacerbations. 138 exacerbation samples were obtained of which 63 (46%) were positive for respiratory viruses. In contrast, 23 of 136 asymptomatic nasal swabs (16.9%) were positive for respiratory viruses. There was significantly more viruses being detected during respiratory exacerbations, in particular influenza A, influenza B and rhinovirus (p <0.05). Upper respiratory symptoms significantly correlated with positive respiratory viral detection (p <0.05). This study also showed that viral respiratory exacerbations in CF could be independent from bacterial infections. Conclusions Respiratory viruses are associated with exacerbations in CF and upper respiratory symptoms are strong predictors for their presence. ‘Real-time’ NASBA has a rapid turn-around time and has the potential to aid clinical decision making, such as the use of anti-virals and administration of antibiotics.


title: Navigating the Clean Energy Transition in the COVID-19 Crisis

text: Bjarne Steffen is a senior researcher at ETH Zurich’s Energy Politics Group. His research addresses policies related to energy innovation and the role of finance in the energy transition. He previously worked at MIT’s Center for Energy and Environmental Policy Research, the World Economic Forum, and a strategy consultancy. Bjarne holds a Master’s in economics from the University of Mannheim and a PhD in energy economics from the University of Duisburg-Essen. Florian Egli is a PhD candidate at ETH Zurich’s Energy Politics Group. His research focuses on the role of finance in the energy transition and climate finance more generally. He is a World Economic Forum Global Shaper, is associated with the think tank foraus as its former vice president, and held a Mercator Fellowship on International Affairs in 2015 and 2016. Florian holds a Master’s in International Economics from the Graduate Institute of International and Development Studies (IHEID) in Geneva. Michael Pahle is head of the working group “Climate and Energy Policy” at the Potsdam-Institute for Climate Impact Research. His research focuses on carbon pricing and power market design. He holds a Master’s in Physics from Potsdam University and a PhD in economics from TU Berlin. Tobias S. Schmidt is Assistant Professor and the head of ETH Zurich’s Energy Politics Group, an interdisciplinary group analyzing the interaction of energy policy and its underlying politics with technological change in the energy sector. His research covers both developed and developing countries. Tobias holds a Bachelor’s and Master’s of Science in electrical engineering (energy focus) from the Technical University Munich and a PhD from ETH Zurich in management, technology, and economics.


title: Macrolides and viral infections: focus on azithromycin in COVID-19 pathology

text: The emergence of the new disease COVID-19, is posing the challenge of seeking effective therapies. Since the most severe clinical manifestation of COVID-19 appeared to be a severe acute respiratory syndrome, azithromycin has been proposed as a potential treatment. Azithromycin is known to have immunomodulating and antiviral properties. In vitro studies have demonstrated the capacity of azithromycin to reduce production of pro-inflammatory cytokines such as IL-8, IL-6, TNF alpha, reduce oxidative stress and modulate T-helper functions. At the same time there are multiple clinical evidences of the role of azithromycin in acute respiratory distress syndrome and against MERS. Some preliminary evidences have demonstrated controversial results regarding efficacy of azithromycin in combination with hydroxychloroquine in COVID-19. Firstly, a French trial demonstrated 100% of virological negativization of six patients treated with azithromycin plus hydroxychloroquine vs 57.1% of patients treated with only hydroxychloroquine and 12.5% of the control group (p<0.05). On the other hand, another case series revealed no efficacy at all on eleven patients treated with same combination and doses. Furthermore, there are some concerns regarding the association of azithromycin and hydroxychloroquine because of the potential Qt prolongation. In fact, both drugs have this as potential side effect and evidences regarding the safety use of this combination are controversial. Despite the necessity to quickly find solutions for COVID-19, extreme caution must be used in evaluating the risk-benefit balance. However, based on preclinical and clinical evidences and some preliminary results in COVID-19, azithromycin could have a potential in the fight against this new disease.


title: Adapting vascular surgery practice to the current COVID-19 era at a tertiary academic center in Madrid.

text: INTRODUCTION: The epidemic potential of Coronavirus infection is now a reality. Since the first case detected in late 2019 in China a fast-world-wide expansion confirms it. The vascular patient is at a higher risk of developing a severe form of the disease due to its nature associating several comorbid states and thus, some Vascular Surgery communities from many countries have tried to stratify patients into those requiring care during these uncertain times. METHODS: Observational study describing the current daily vascular surgery practice at one tertiary academic hospital in Madrid region, Spain; one of the most affected regions worldwide due to the COVID-19 outbreak. We analyzed our surgical practice since March 14(th) when the lockdown was declared up to date, May 14(th) (2 months). Procedural surgical practice, organizational issues, early outcomes and all the troubles encountered during this new situation are described. RESULTS: Our department is composed of 10 vascular surgeons and 4 trainees. Surgical practice has been reduced to only urgent care, totaling 50 repairs on 45 patients during the time period. Five surgeries were performed on 3 COVID-19 positive patients. Sixty percent were due to CLI, 45% of them performed by complete endovascular approach; whereas less than 10% of repairs were aorta related. We were allocated to use a total of 5 surgical rooms in different locations, none our usual, as it was converted into an ICU room while performing 50% of those repairs with unusual nursery staff. CONCLUSIONS: The COVID-19 outbreak has dramatically changed our organization and practice in favor of urgent or semi-urgent surgical care alone. The lack for in-hospital/ICU beds and changing nursery staff changed the whole availability organization at our hospital and was a key factor in surgical decision making in some cases.


title: Pregnancy and postpartum outcomes in a universally tested population for SARS‐CoV‐2 in New York City: A prospective cohort study

text: OBJECTIVE: To describe differences in outcomes between pregnant women with and without COVID‐19 DESIGN: Prospective cohort study of pregnant women consecutively admitted for delivery, and universally tested via nasopharyngeal (NP) swab for SARS‐CoV‐2 using reverse transcriptase polymerase chain reaction (RT‐PCR). All infants of mothers with COVID‐19 underwent SARS‐CoV‐2 testing. SETTING: Three New York City hospitals POPULATION: Pregnant women > 20 weeks’ gestation admitted for delivery METHODS: Data were stratified by SARS‐CoV‐2 result and symptomatic status, and summarized using parametric and nonparametric tests. MAIN OUTCOME MEASURES: Prevalence and outcomes of maternal COVID‐19; obstetric outcomes; neonatal SARS‐CoV‐2; placental pathology. RESULTS: Of 675 women admitted for delivery, 10.4% were positive for SARS‐CoV‐2, of whom 78.6% were asymptomatic. We observed differences in sociodemographics and comorbidities between women with symptomatic vs. asymptomatic vs. no COVID‐19. Cesarean delivery rates were 46.7% in symptomatic COVID‐19, 45.5% in asymptomatic COVID‐19, and 30.9% without COVID‐19 (p=0.044). Postpartum complications (fever, hypoxia, readmission) occurred in 12.9% of women with COVID‐19 vs 4.5% of women without COVID‐19 (p<0.001). No woman required mechanical ventilation, and no maternal deaths occurred. Among 71 infants tested, none were positive for SARS‐CoV‐2. Placental pathology demonstrated increased frequency of fetal vascular malperfusion, indicative of thrombi in fetal vessels, in women with vs. without COVID‐19 (48.3% vs 11.3%, p <0.001). CONCLUSION: Among pregnant women with COVID‐19 at delivery, we observed increased cesarean delivery rates and increased frequency of maternal complications in the postpartum period. Additionally, intraplacental thrombi may have maternal and fetal implications for COVID‐19 infections remote from delivery.


title: A framework for open tracheostomy in COVID‐19 patients

text: The COVID-19 pandemic is causing untold disruption across the globe and all countries irrespective of the strength and resilience of their health systems are feeling the burden. Intensive care units are facing a surge of patients requiring invasive ventilation.It is likely that requests for a tracheostomy in COVID-19 ventilated patients will soon come our way. It is difficult to predict the burden, but it would be remiss not to be prepared.


title: Magnetic Lateral Flow Immunoassays

text: A new generation of magnetic lateral flow immunoassays is emerging as powerful tool for diagnostics. They rely on the use of magnetic nanoparticles (MNP) as detecting label, replacing conventional gold or latex beads. MNPs can be sensed and quantified by means of external devices, allowing the development of immunochromatographic tests with a quantitative capability. Moreover, they have an added advantage because they can be used for immunomagnetic separation (IMS), with improvements in selectivity and sensitivity. In this paper, we have reviewed the current knowledge on magnetic-lateral flow immunoassay (LFIA), coupled with both research and commercially available instruments. The work in the literature has been classified in two categories: optical and magnetic sensing. We have analysed the type of magnetic nanoparticles used in each case, their size, coating, crystal structure and the functional groups for their conjugation with biomolecules. We have also taken into account the analytical characteristics and the type of transduction. Magnetic LFIA have been used for the determination of biomarkers, pathogens, toxins, allergens and drugs. Nanocomposites have been developed as alternative to MNP with the purpose of sensitivity enhancement. Moreover, IMS in combination with other detection principles could also improve sensitivity and limit of detection. The critical analysis in this review could have an impact for the future development of magnetic LFIA in fields requiring both rapid separation and quantification.


title: The 5′-end sequence of the murine coronavirus genome: Implications for multiple fusion sites in leader-primed transcription

text: Abstract The coronavirus leader-primed transcription model proposes that free leader RNA species derived from the 5′-end of the genomic RNA are utilized as a primer for the transcription of subgenomic mRNAs. To elucidate the precise mechanism of leader-priming, we cloned and sequenced the 5′-end of the mouse hepatitis virus genomic RNA. The 5′-terminal sequences are identical to the leader sequences present at the 5′-end of the subgenomic mRNAs. Two possible hairpin loop structures and an AU-rich region around the 3′-end of the leader sequence may provide the termination site for leader RNA synthesis. The comparison of 5′-end genomic sequences and the intergenic start sites for mRNA transcription revealed that there are homologous regions of 7–18 nucleotides at the putative leader/body junction sites. Some intergenic regions contain a mismatching nucleotide within this homologous region. We propose that free leader RNA binds to the intergenic region due to this homology and is cleaved at the mismatching nucleotide before serving as a primer. Thus, the free leader RNA species may be longer than the leader sequences in the subgenomic mRNAs and different mRNAs may have different leader/body junction sites.


title: Antibody-dependent infection of human macrophages by severe acute respiratory syndrome coronavirus

text: BACKGROUND: Public health risks associated to infection by human coronaviruses remain considerable and vaccination is a key option for preventing the resurgence of severe acute respiratory syndrome coronavirus (SARS-CoV). We have previously reported that antibodies elicited by a SARS-CoV vaccine candidate based on recombinant, full-length SARS-CoV Spike-protein trimers, trigger infection of immune cell lines. These observations prompted us to investigate the molecular mechanisms and responses to antibody-mediated infection in human macrophages. METHODS: We have used primary human immune cells to evaluate their susceptibility to infection by SARS-CoV in the presence of anti-Spike antibodies. Fluorescence microscopy and real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) were utilized to assess occurrence and consequences of infection. To gain insight into the underlying molecular mechanism, we performed mutational analysis with a series of truncated and chimeric constructs of fragment crystallizable γ receptors (FcγR), which bind antibody-coated pathogens. RESULTS: We show here that anti-Spike immune serum increased infection of human monocyte-derived macrophages by replication-competent SARS-CoV as well as Spike-pseudotyped lentiviral particles (SARS-CoVpp). Macrophages infected with SARS-CoV, however, did not support productive replication of the virus. Purified anti-viral IgGs, but not other soluble factor(s) from heat-inactivated mouse immune serum, were sufficient to enhance infection. Antibody-mediated infection was dependent on signaling-competent members of the human FcγRII family, which were shown to confer susceptibility to otherwise naïve ST486 cells, as binding of immune complexes to cell surface FcγRII was necessary but not sufficient to trigger antibody-dependent enhancement (ADE) of infection. Furthermore, only FcγRII with intact cytoplasmic signaling domains were competent to sustain ADE of SARS-CoVpp infection, thus providing additional information on the role of downstream signaling by FcγRII. CONCLUSIONS: These results demonstrate that human macrophages can be infected by SARS-CoV as a result of IgG-mediated ADE and indicate that this infection route requires signaling pathways activated downstream of binding to FcγRII receptors.


title: Influenza early warning model based on Yunqi theory

text: OBJECTIVE: To establish an early warning model to simulate the outbreak of influenza based on weather conditions and Yunqi theory, an ancient calendar theory of Chinese medicine (CM). METHODS: Tianjin, a northeastern city in China, was chosen as the region of research and applied the influenza-like illness attack rate (ILI)% as the baseline and warning line to determine the severity of influenza epidemic. Then, an influenza early warning model was constructed based on the theory of rough set and support vector machines (RS-SVM), and the relationship between influenza and meteorology was explored through analyzing the monitoring data. RESULTS: The predictive performance of the model was good, which had achieved 81.8% accuracy when grouping the obtained data into three levels that represent no danger, danger of a light epidemic, and danger of a severe epidemic. The test results showed that if the host qi and guest qi were not balanced, this kind of situation was more likely to cause influenza outbreaks. CONCLUSIONS: The outbreak of influenza closely relates to temperature, humidity, visibility, and wind speed and is consistent with some part of CM doctrine. The result also indicates that there is some reasonable evidence in the Yunqi theory.


Impact of the Covid-19 Pandemic and Lung Transplantation Program in France


title: Contribution of the FilmArray Respiratory Panel in the management of adult and pediatric patients attending the emergency room during 2015–2016 influenza epidemics: An interventional study

text: Abstract Aim To evaluate the contribution of a multiplex PCR for respiratory viruses on antibiotic and antiviral prescription, ancillary test prescription, admission and length of stay of patients. Methods Two hundred ninety-one adult and pediatric patients visiting the emergency department during the 2015–2016 influenza epidemic were prospectively included and immediately tested 24/7 using the FilmArray Respiratory Panel. The results were communicated to the practitioner in charge as soon as they became available. Clinical and biological data were gathered and analyzed. Findings Results from the FilmArray Respiratory Panel do not appear to impact admission or antibiotic prescription, with the exception of a lower admission rate for children who tested positive for influenza B. Parameters that account for the clinical decisions evaluated are CRP level, white blood cell count, suspected or proven bacterial infection and, for adult patients only, signs of respiratory distress. Length of stay is also not significantly different between patients with a positive and a negative result. A rapid influenza test result permits a more appropriate prescription of oseltamivir.


title: Addressing the Gaps in Preparation for Quarantine

text: INTRODUCTION: In the event of an outbreak of a communicable respiratory illness, quarantine may become necessary. The New York Institute for All Hazard Preparedness (NYIAHP) of the State University of New York (SUNY) Downstate Medical Center, in cooperation with the New York City Department of Health and Mental Hygiene's Healthcare Emergency Preparedness Program, (NYC DOHMH-HEPP) quarantine working group, has developed a series of clinical protocols to help health care facilities respond to such an event. PROBLEM: Two full-scale exercises (FSEs) were designed and conducted a year apart in the quarantine unit at Kings County Hospital Center (KCHC) to test the efficacy and feasibility of these quarantine protocols. The goal of these exercises was to identify the gaps in preparedness for quarantine and increase hospital readiness for such an event. METHODS: Evaluators monitored for efficient management of critical physical plants, personnel and material resources. Players were expected to integrate and practice emergency response plans and protocols specific to quarantine. In developing the exercise objectives, five activities were selected for evaluation: Activation of the Unit, Staffing, Charting/Admission, Symptom Monitoring and Infection Control, and Client Management. RESULTS: The results of the initial FSE found that there were incomplete critical tasks within all five protocols: These deficiencies were detailed in an After Action Report and an Improvement Plan was presented to the KCHC Disaster Preparedness Committee a month after the initial FSE. In the second FSE a year later, all critical tasks for Activation of the unit, Staffing and Charting/Admission were achieved. Completion of critical tasks related to Symptom Monitoring and Infection Control and Client Management was improved in the second FSE, but some tasks were still not performed appropriately. CONCLUSION: In short, these exercises identified critical needs in disaster preparedness of the KCHC Quarantine Unit. The lessons learned from this logistical exercise enabled the planning group to have a better understanding of leadership needs, communication capabilities, and infection control procedures. Kings County Hospital Center performed well during these exercises. It was clear that performance in the second exercise was improved, and many problems noted in the first exercise were corrected. Staff also felt better prepared the second time. This supports the idea that frequent exercises are vital to maintain disaster readiness. R Nathawad, PM Roblin, D Pruitt, B Arquilla. Addressing the gaps in preparation for quarantine. Prehosp Disaster Med. 2013;28(2):1-7 23158909.


title: Exploration of alternative supply chains and distributed manufacturing in response to COVID-19; a case study of medical face shields

text: Abstract Quarantine conditions arising as a result of the coronavirus (COVID-19) have had a significant impact on global production-rates and supply chains. This has coincided with increased demands for medical and personal protective equipment such as face shields. Shortages have been particularly prevalent in western countries which typically rely upon global supply chains to obtain these types of device from low-cost economies. National calls for the repurposing of domestic mass-production facilities have the potential to meet medical requirements in coming weeks, however the immediate demand associated with the virus has led to the mobilisation of a diverse distributed workforce. Selection of appropriate manufacturing processes and underused supply chains is paramount to the success of these operations. A simplified medical face shield design is presented which repurposes an assortment of existing alternative supply chains. The device is easy to produce with minimal equipment and training. It is hoped that the methodology and approach presented is of use to the wider community at this critical time.


title: Identification of α-fodrin as an autoantigen in experimental coronavirus retinopathy (ECOR)

text: Abstract The coronavirus, mouse hepatitis virus (MHV), JHM strain induces a biphasic disease in BALB/c mice that consists of an acute retinitis followed by progression to a chronic retinal degeneration with autoimmune reactivity. Retinal degeneration resistant CD-1 mice do not develop either the late phase or autoimmune reactivity. A mouse RPE/choroid DNA expression library was screened using sera from virus infected BALB/c mice. Two clones were identified, villin-2 protein and α-fodrin protein. α-Fodrin protein was used for further analysis and western blot reactivity was seen only in sera from virus infected BALB/c mice. CD4 T cells were shown to specifically react with MHV antigens and with α-fodrin protein. These studies clearly identified both antibody and CD4 T cell reactivities to α-fodrin in sera from virus infected, retinal degenerative susceptible BALB/c mice.


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title: The Role of the Laboratory and Transfusion Service in the Management of Ebola Virus Disease

text: Abstract The Ebola outbreak that began in 2013 infected and killed record numbers of individuals and created unprecedented challenges, including containment and treatment of the virus in resource-strained West Africa as well as the repatriation and treatment for patients in the United States and Europe. Valuable lessons were learned, especially the important role that the laboratory and transfusion service plays in the treatment for patients with Ebola virus disease (EVD) by providing data for supportive care and fluid resuscitation as well as the generation of investigational therapies such as convalescent plasma (CP). To provide treatment support, laboratories had to evaluate and update procedures to ensure the safety of laboratory personnel. Because there is no licensed EVD-specific treatment, CP was used in more than 99 patients with only 1 possible severe adverse event reported. However, given the biologic variability inherent in CP as well as the small number of patient treated in a nonrandomized fashion, the efficacy of CP in the treatment of EVD remains unknown.