title: Contact Transmission of COVID-19 in South Korea: Novel Investigation Techniques for Tracing Contacts

text: In the epidemiological investigation of an infectious disease, investigating, classifying, tracking, and managing contacts by identifying the patient’s route are important for preventing further transmission of the disease. However, omissions and errors in previous activities can occur when the investigation is performed through only a proxy interview with the patient. To overcome these limitations, methods that can objectively verify the patient’s claims (medical facility records, Global Positioning System, card transactions, and closed-circuit television) were used for the recent ongoing coronavirus disease 2019 contact investigations in South Korea.


title: Translating old drugs into new treatments: ribosomal frameshifting as a target for antiviral agents

text: Abstract Programmed ribosomal frameshifting is used by many viruses to regulate the production of structural and enzymatic proteins. Altering the frameshifting efficiencies disrupts the virus life cycle and eliminates or reduces virus production. Ribosomal frameshifting therefore provides a unique target on which antiviral agents can function. This article describes a series of rapid assay strategies that have been developed and used to identify potential antiviral agents that target programmed −1 ribosomal frameshifting.


title: Nasal delivery of Protollin-adjuvanted H5N1 vaccine induces enhanced systemic as well as mucosal immunity in mice

text: Abstract Sporadic, yet frequent human infections with avian H5N1 influenza A viruses continue to pose a potential pandemic threat. Poor immunogenicity of unadjuvanted H5N1 vaccines warrants developing novel adjuvants and formulations as well as alternate delivery systems to improve their immunogenicity and efficacy. Here, we show that Protollin, a nasal adjuvant composed of Neisseria meningitides outer membrane proteins non-covalently linked to Shigella flexneri 2a lipopolysaccharide, is a potent nasal adjuvant for an inactivated split virion H5N1 clade 1 A/Viet Nam1203/2004 (A/VN/1203/04) vaccine in a mouse model. Protollin-adjuvanted vaccines elicited enhanced serum protective hemagglutination inhibition titers, mucosal IgA responses, and H5N1-specific cell-mediated immunity that resulted in complete protection against a lethal challenge with a homologous virus as well as a heterologous clade 2 virus A/Indonesia/05/2005 (A/IN/05/05). Detailed analysis of adaptive immunity revealed that Protollin increased the frequency of lymphoid- as well as local tissue-resident antibody-secreting cells, local germinal center reaction of B cells, broad-spectrum of CD4 T cell response. Our findings suggest that nasal delivery of H5N1 vaccine with Protollin adjuvant can overcome the poor immunogenicity of H5N1 vaccines, induce both cellular and humoral immune responses, enhance protection against challenge with clade 1 and clade 2 H5N1 viruses and achieve significant antigen dose-sparing.


title: Influence of plant origin on propagation capacity and alkaloid biosynthesis during long-term in vitro cultivation of Leucojum aestivum L.

text: The investigation deals with in vitro clonal propagation of L. aestivum L. (summer snowflake), a threatened Amaryllidaceae plant species in Bulgaria used in the pharmaceutical industry as raw material for production of galanthamine-based medicines. Plants of known origin and with different alkaloid profile were taken from the living collection of the Institute of Botany, Sofia. Bulbs were used to initiate in vitro cultures and 24 clones were multiplied. The influence of the clone origin on the propagation coefficient, shoot and bulblet morphology, alkaloid profile and content of galanthamine, lycorine, and four related alkaloids was evaluated. Clones kept stable alkaloid profiles and for most of them, high regeneration rates were noted. Galanthamine content of some clones was commensurable with that of Bulgarian populations of L. aestivum of commercial importance. Five clones: four galanthamine-type and one lycorine-type were selected as promising for further investigation.


title: Social network analysis on a topic‐based navigation guidance system in a public health portal

text: We investigated a topic‐based navigation guidance system in the World Health Organization portal, compared the link connection network and the semantic connection network derived from the guidance system, analyzed the characteristics of the 2 networks from the perspective of the node centrality (in_closeness, out_closeness, betweenness, in_degree, and out_degree), and provided the suggestions to optimize and enhance the topic‐based navigation guidance system. A mixed research method that combines the social network analysis method, clustering analysis method, and inferential analysis methods was used. The clustering analysis results of the link connection network were quite different from those of the semantic connection network. There were significant differences between the link connection network and the semantic network in terms of density and centrality. Inferential analysis results show that there were no strong correlations between the centrality of a node and its topic information characteristics. Suggestions for enhancing the navigation guidance system are discussed in detail. Future research directions, such as application of the same research method presented in this study to other similar public health portals, are also included.


title: Témoignage: Expérience d’un étudiant en Masso-Kinésithérapie en renfort dans un EPHAD touché par le COVID-19

text: Abstract As a physiotherapist student, I was asked by the ARS to reinforce the care team of a nursing home welcoming residents affected by Covid-19. I had to acquire the specific hygiene and protection rules for this situation in addition to nursing work. Whenever necessary, I applied my physiotherapist knowledge’s to serve residents and carers. This disease is exhausting for the patients; their respiratory and general condition can fluctuate quickly. Without treatment to cure them, we have to accompany them as comfortably as possible.


title: Availability of COVID-19 Information from National and International Aesthetic Surgery Society Websites

text: BACKGROUND: National and international aesthetic surgery society websites are an important source of information for patients and aesthetic surgeons. The current COVID-19 pandemic represents an unprecedented global health crisis. The aim of this study was to assess the information available on national and international aesthetic surgery society websites on the current pandemic of COVID-19. METHODS: National and international aesthetic surgery society websites were assessed with regard to COVID-19 information. RESULTS: Thirty-one per cent of nations had aesthetic surgery society websites. Twenty-two per cent of national society websites had a specific COVID-19 section. Seventeen per cent of these websites had COVID-19-specific guidelines available; of these websites with guidelines, 77% had a specific COVID-19 section advising to provide only urgent or emergent care and 46% provided their sovereign state’s directives to provide only urgent or emergent care. Two international aesthetic surgery society websites had COVID-19-specific guidelines, and one of the two had significant educational resources. CONCLUSION: The availability of COVID-19 clinical guidelines and patient information sheets on national plastic surgery society websites is sparse. In contrast, one international society website carefully analysed national and international recommendations and guidelines and made general recommendations for its members with regularly updated resources. This study suggests that improvement and increase in COVID-19 information provided by many national aesthetic surgery society websites may be improved by links to the ISAPS website. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.


title: Histopathological characterization of the naturally occurring hepatotropic virus infections of nude mice

text: In the last ten years the mutant athymic nude mouse has been used by many researchers as a model for studying pathological conditions in an immunodeficient host. A major problem with such mice is their susceptibility to viral infections indigenous to murine stocks, such as the hepatotropic mouse coronaviruses. In an effort to define the hepatotropic virus diseases indigenous to nude mice this paper details the pathogenesis and associated comparative histopathology of three common strains of mouse hepatitis virus, reovirus 3 and murine cytomegalovirus in the nude mouse.


title: Structural and molecular basis of mismatch correction and ribavirin excision from coronavirus RNA

text: Coronaviruses (CoVs) stand out among RNA viruses because of their unusually large genomes (∼30 kb) associated with low mutation rates. CoVs code for nsp14, a bifunctional enzyme carrying RNA cap guanine N7-methyltransferase (MTase) and 3′-5′ exoribonuclease (ExoN) activities. ExoN excises nucleotide mismatches at the RNA 3′-end in vitro, and its inactivation in vivo jeopardizes viral genetic stability. Here, we demonstrate for severe acute respiratory syndrome (SARS)-CoV an RNA synthesis and proofreading pathway through association of nsp14 with the low-fidelity nsp12 viral RNA polymerase. Through this pathway, the antiviral compound ribavirin 5′-monophosphate is significantly incorporated but also readily excised from RNA, which may explain its limited efficacy in vivo. The crystal structure at 3.38 Å resolution of SARS-CoV nsp14 in complex with its cofactor nsp10 adds to the uniqueness of CoVs among RNA viruses: The MTase domain presents a new fold that differs sharply from the canonical Rossmann fold.


title: Case Report: Clinical Treatment of the First Critical Patient With Coronavirus Disease (COVID-19) in Liaocheng, Shandong Province

text: This paper reports the clinical characteristics, diagnosis, and treatment of the first critical COVID-19 patient in Liaocheng City, who was admitted to the intensive care unit isolation ward of Liaocheng People's Hospital on February 11, 2020. On admission, the patient had difficulty breathing, the oxygenation index was 135 mmHg, and the blood lactate was 5.6 mmol/L. After comprehensive treatment including high-flow nasal cannula oxygen therapy, plasma exchange, antiviral and anti-infection therapies, immune regulation, liquid volume management, glucocorticoid, enteral nutrition support, analgesia and sedation, blood glucose control, anticoagulation and thrombus prevention, and electrolyte balance maintenance, the patient was finally cured, and discharged. The purpose of this case report is to provide a reference for the clinical diagnosis and treatment of critical COVID-19 patients.


title: Review of group A rotavirus strains reported in swine and cattle

text: Abstract Group A rotavirus (RVA) infections cause severe economic losses in intensively reared livestock animals, particularly in herds of swine and cattle. RVA strains are antigenically heterogeneous, and are classified in multiple G and P types defined by the two outer capsid proteins, VP7 and VP4, respectively. This study summarizes published literature on the genetic and antigenic diversity of porcine and bovine RVA strains published over the last 3 decades. The single most prevalent genotype combination among porcine RVA strains was G5P[7], whereas the predominant genotype combination among bovine RVA strains was G6P[5], although spatiotemporal differences in RVA strain distribution were observed. These data provide important baseline data on epidemiologically important RVA strains in swine and cattle and may guide the development of more effective vaccines for veterinary use.


title: Aerosol-generating procedures in head and neck surgery – can we improve practice after COVID-19?

text: The COVID-19 pandemic has had a dramatic impact on international medicine practice. The propensity for head and neck surgery to generate aerosols needs special consideration over and above simply adopting personal protective equipment. This study sought to interrogate the literature and evaluate whether which additional measures might provide benefit if routinely adopted in minimising viral transmission.


title: Learning from the Italian experience in coping with COVID-19

text: INTRODUCTION: In March 2020, the rapid increase in COVID-19 cases overburdened the Italian health system, with the country becoming the pandemic’s epicenter. METHODS: We present a narrative review based on manuscripts, official documents, and newspaper articles regarding COVID-19 in Italy. RESULTS: Characteristics of the epidemic, possible causes for its worsening, and the measures adopted across Italian regions are presented. CONCLUSIONS: In the early stages of an epidemic, effective decision-making is essential to contain the number of cases. Medical support for patients and social isolation measures are the most appropriate strategies currently available to reduce the spread and lethality of COVID-19.


title: Investigation of Anti–Middle East Respiratory Syndrome Antibodies in Blood Donors and Slaughterhouse Workers in Jeddah and Makkah, Saudi Arabia, Fall 2012

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel, potentially zoonotic human coronavirus (HCoV). We investigated MERS-CoV antibodies using a staged approach involving an immunofluorescence assay (IFA), a differential recombinant IFA, and a plaque-reduction serum neutralization assay. In 130 blood donors sampled during 2012 in Jeddah and 226 slaughterhouse workers sampled in October 2012 in Jeddah and Makkah, Saudi Arabia, 8 reactive sera were seen in IFA but were resolved to be specific for established HCoVs by discriminative testing. There is no evidence that MERS-CoV circulated widely in the study region in fall 2012, matching an apparent absence of exported disease during the 2012 Hajj.


title: Detection of a novel astrovirus from a black-naped monarch (Hypothymis azurea) in Cambodia

text: BACKGROUND: Astroviruses are comprised of two genera with Avastrovirus infecting birds and Mamastrovirus infecting mammals. Avastroviruses have primarily been associated with infections of poultry, especially chicken, turkey, duck, and guineafowl production systems, but also infect wading birds and doves. Outcomes result in a spectrum of disease, ranging from asymptomatic shedding to gastroenteritis with diarrhea, stunting, failure to thrive and death. FINDINGS: Virological surveillance was conducted in birds from two sites in Cambodia in 2010. Samples were screened for influenza, astroviruses, coronaviruses, flaviviruses, and paramyxoviruses. A total of 199 birds were tested and an astrovirus was detected in a black-naped monarch (Hypothymis azurea). CONCLUSIONS: This is the first astrovirus detection in a passerine bird. Phylogenetic analysis and nucleotide distances suggest that this avastrovirus forms a distinct lineage and may constitute a fourth avastrovirus group. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-015-0413-2) contains supplementary material, which is available to authorized users.


title: Enveloped Virus Inactivation on Personal Protective Equipment by Exposure to Ozone

text: Ozone is a highly oxidizing gas easily generated from atmospheric oxygen with inexpensive equipment and is commonly used for the disinfection of municipal water, foods, and surfaces. We report tests of the ability of ozone to inactivate enveloped respiratory viruses (influenza A virus and respiratory syncytial virus), chosen as more easily handled surrogates for SARS-CoV-2, on N95 respirators and other personal protective equipment (PPE) commonly used in hospitals. At 20 ppm, an ozone concentration easily achieved by standard commercial equipment, the viruses were inactivated with high efficiency as long as the relative humidity was above a threshold value of approximately 50%. In the absence of humidity control, disinfection is more variable and requires considerably longer exposure under relatively dry conditions. This report extends the observations of a previous publication (http://doi.org/10.1080/01919510902747969) to hospital-relevant materials and provides additional details about the relationship of humidity to the antiviral activity of ozone. Home CPAP disinfection devices using ozone can provide effective results for individuals. Ozone did not appear to degrade any of the materials tested except for elastic bands if strained during treatment (such as by the pressure exerted by stapled attachment to N95 respirators). The filtration efficiency of N95 respirator material was not compromised. Overall, we recommend exposures of at least 40 minutes to 20 ppm ozone and >70% relative humidity at ambient temperatures (21-24°C) for 4-log (99.99%) reduction of viral infectivity on a variety of PPE, including gowns, face shields, and respirators. Shorter exposure times are likely to be effective under these conditions, but at the risk of some variability for different materials. Higher ozone concentrations and higher humidity levels promoted faster inactivation of viruses. Our work suggests that ozone exposure can be a widely accessible method for disinfecting PPE, permitting safer re-use for healthcare workers and patients alike in times of shortage.


title: Risk communication in times of crisis: Pitfalls and challenges in ensuring preparedness instead of hysterics

text: The Ebola outbreak in West Africa is an instructive lesson on the difficulties of risk communication in times of crisis. The most effective strategy to improve communication during a crisis is to build public trust in officials and academics long before disaster strikes. [Image: see text]


title: Virus and virus‐like particles in the faeces of cats with and without diarrhoea

text: SUMMARY: Negative staining electron microscopy was used to identify viruses in 166 normal and 62 diarrhoeal faecal samples from 208 cats admitted to an animal shelter during a 16‐month period (March 1984 to June 1985). On the basis of size and shape 7 distinct viral types were detected: 24 nm parvovirus‐like particles, 30 nm astrovirus, 30 nm picornavirus‐like particles, reovirus, rotavirus, coronavirus and a 75 nm “togavirus‐like” particle. The incidence of these particles in the 208 cats was 11%, 7%, 6%, 0.4%, 5%, 1% and 1% respectively. Virus isolation studies using 40 of the faecal samples succeeded in isolating reovirus 1 in 2 cases. Immune electron microscope studies demonstrated the presence of antibody in a human serum to cat astrovirus, but failed to clarify the identity of the parvovirus‐like particles and picornavirus‐like particles, other than showing that some of the parvovirus‐like particles were not related to feline panleukopenia virus. It was found that parvovirus‐like particles, astrovirus, picornavirus‐like particles, reovirus and rotavirus could be excreted by cats with normal faeces as well as cats with diarrhoeal faeces. Parvovirus‐like particles, astrovirus, picornavirus‐like particles and rotavirus could be excreted in high concentration in normal faeces. There was no simple relationship between age and diarrhoea in the population of cats studied. Age was not a critical factor in the excretion of parvovirus‐like particles, astrovirus, picornavirus‐like particles and rotavirus. The incidence of diarrhoea was not clearly associated with the seasons.


title: On the 2-Row Rule for Infectious Disease Transmission on Aircraft

text: Abstract Background With over two billion airline passengers annually, in-flight transmission of infectious diseases is an important global health concern. Many instances of in-flight transmission have been documented, but the relative influence of the many factors (see below) affecting in-flight transmission has not been quantified. Long-standing guidance by public health agencies is that the primary transmission risk associated with air travel for most respiratory infectious diseases is associated with sitting within two rows of an infectious passenger. The effect of proximity may be one of these factors. Objective The aim of this study was to determine the risk of infection within and beyond the 2-row rule given by public health guidance. Methods We searched the literature for reports of in-flight transmission of infection which included seat maps indicating where the infectious and infected passengers were seated. Findings There is a ∼ 6% risk to passengers seated within the 2-rows of infected individual(s) and there is ∼ 2% risk to passengers seated beyond 2-rows from the infectious individual. Discussion Contact tracing limited to passengers within 2-rows of the infectious individual(s) could fail to detect other cases of infections. This has important consequences for assessing the spread of infectious diseases. Conclusions Infection at a distance from the index case indicates other factors, such as airflow, movement of passenger/crew members, fomites and contacts between passengers in the departure gate before boarding, or after deplaning, are involved.


title: Recent Advances in AIV Biosensors Composed of Nanobio Hybrid Material

text: Since the beginning of the 2000s, globalization has accelerated because of the development of transportation systems that allow for human and material exchanges throughout the world. However, this globalization has brought with it the rise of various pathogenic viral agents, such as Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), Zika virus, and Dengue virus. In particular, avian influenza virus (AIV) is highly infectious and causes economic, health, ethnical, and social problems to human beings, which has necessitated the development of an ultrasensitive and selective rapid-detection system of AIV. To prevent the damage associated with the spread of AIV, early detection and adequate treatment of AIV is key. There are traditional techniques that have been used to detect AIV in chickens, ducks, humans, and other living organisms. However, the development of a technique that allows for the more rapid diagnosis of AIV is still necessary. To achieve this goal, the present article reviews the use of an AIV biosensor employing nanobio hybrid materials to enhance the sensitivity and selectivity of the technique while also reducing the detection time and high-throughput process time. This review mainly focused on four techniques: the electrochemical detection system, electrical detection method, optical detection methods based on localized surface plasmon resonance, and fluorescence.


title: Bibliometric method for mapping the state of the art of scientific production in Covid-19

text: Global scientific production around the Covid-19 pandemic, in the various disciplines on the various international scientific bibliographic databases, has grown exponentially. The latter builds a source of scientific enrichment and an important lever for most researchers around the world, each of its field and its position with an ultimate aim of overcoming this pandemic. In this direction, bibliometric data constitute a fundamental source in the process of evaluation of scientific production in the academic world; bibliometrics provides researchers and institutions with crucial strategic information for the enhancement of their research results with the local and international scientific community, especially in this international pandemic.


title: On fractional order differential equations model for nonlocal epidemics

text: Abstract A fractional order model for nonlocal epidemics is given. Stability of fractional order equations is studied. The results are expected to be relevant to foot-and-mouth disease, SARS and avian flu.


title: The Ribavirin Pregnancy Registry: An Interim Analysis of Potential Teratogenicity at the Mid-Point of Enrollment

text: INTRODUCTION: Significant teratogenic effects have been demonstrated in all animal species exposed to ribavirin. Ribavirin is prescribed for chronic hepatitis C and is contraindicated in women who are pregnant and in the male sexual partners of women who are pregnant. Both sexes are advised to avoid pregnancy for 6 months after exposure. The Ribavirin Pregnancy Registry was established in 2003 to monitor pregnancy exposures to ribavirin for signals of possible human teratogenicity. METHODS: This voluntary registry enrolls pregnant women with prenatal exposure to ribavirin. Exposure is classified as direct—women taking ribavirin during pregnancy or the 6 months prior to conception—or indirect—women exposed through sexual contact, 6 months prior to or during pregnancy, with a man who is taking or has taken ribavirin in the past 6 months. Women are followed until delivery and infants for 1 year. When enrollment is complete, birth defect rates will be compared with the Metropolitan Atlanta Congenital Defects Program’s published rate of 2.67. Using data collected since inception in 2003 through February 2016, preliminary rates were calculated. RESULTS: The registry has enrolled 272 pregnant women, with 180 live births: there were seven birth defect cases among 85 directly exposed women [7/85 (8.2%) (95% confidence interval (CI) 3.4–16.2)] and four birth defect cases among 95 indirectly exposed women [4/95 (4.2%) (95% CI 1.2–10.4)]. Of the 11 infants, nine had structural defects and two had chromosomal anomalies. Patterns suggesting a common etiology or relationship with ribavirin exposure are not seen. CONCLUSION: Based on the patterns of birth defects reported, preliminary findings do not suggest a clear signal of human teratogenicity for ribavirin. However, the current sample size is insufficient for definitive conclusions, and ribavirin exposure should be avoided during pregnancy and during the 6 months prior to pregnancy, in accordance with prescribing information. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00114712.


title: Development of cell-mediated immunity to porcine circovirus type 2 (PCV2) in caesarean-derived, colostrum-deprived piglets

text: Abstract The interaction between porcine circovirus type 2 (PCV2) and the pig immune system has been suggested to be a determinant event for the pathogenesis of postweaning multisystemic wasting syndrome (PMWS). To gain insight into the host immune mechanisms developed upon PCV2 infection, early innate and adaptive immune responses were examined in 1-week-old, caesarean-derived, colostrum-deprived piglets using a subclinical infection model of PCV2 in combination with lipopolysaccharide (LPS) as a potential immunostimulation factor. The use of LPS did not show any significant effect on the course of PCV2 infection, nor did in the evolution of the immunological parameters evaluated. Ex vivo responses were detected as early as 1 day post-infection (PI) and consisted of an elevation of the plasmatic levels of interleukin (IL)-8 in PCV2-inoculated pigs followed by an increase on plasmatic IFN-α at day 5 PI. Regarding IL-10, only one PCV2-inoculated pig was positive (day 7 PI); this pig was the only one in which viremia persisted until the end of the study. In vitro cytokine determination showed that, regardless of the treatment administrated to the pigs, an IL-10 release was observed when peripheral blood mononuclear cells (PBMC) cultures were stimulated with PCV2. Seroconvertion to PCV2 measured by an immunoperoxidase monolayer assay (IPMA) occurred between 7 and 14 days PI, whereas neutralizing antibodies (NA) did not appear until day 29 PI. PCV2 DNA was first detected in serum at day 7 PI, reaching the peak of viremia between days 14 and 21 PI, followed by a drop in viral load that was found coincident with the appearance of PCV2-specific IFN-γ-secreting cells (PCV2-IFN-γ-SC) and NA. Results from the present work suggest that viral clearance might be mediated by the development of PCV2-IFN-γ-SC in contribution to the PCV2-specific NA.


title: Pitfalls in SARS‐CoV‐2 PCR diagnostics

text: To combat the COVID‐19 pandemic, millions of PCR tests are performed worldwide. Any deviation of the diagnostic sensitivity and specificity will reduce the predictive values of the test. Here, we report the occurrence of contaminations of commercial primers/probe sets with the SARS‐CoV‐2 target sequence of the RT‐qPCR as an example for pitfalls during PCR diagnostics affecting diagnostic specificity. In several purchased in‐house primers/probe sets, quantification cycle values as low as 17 were measured for negative control samples. However, there were also primers/probe sets that displayed very low‐level contaminations, which were detected only during thorough internal validation. Hence, it appears imperative to pre‐test each batch of reagents extensively before use in routine diagnosis, to avoid false‐positive results and low positive predictive value in low‐prevalence situations. As such, contaminations may have happened more widely, COVID‐19 diagnostic results should be re‐assessed retrospectively to validate the epidemiological basis for control measures.


title: Detained during a pandemic: A postcard from the Midwest

text: The last time I was on the veterans' tier in Cook County Jail, one of the men detained sitting on the aluminum benches reached up to shake my hand. "Next time you come, can you bring me a container of fresh air?" That was before we all became wary of the air we breathe, in the days when we still grasped extended hands.


title: Sequestration by IFIT1 Impairs Translation of 2′O-unmethylated Capped RNA

text: Viruses that generate capped RNA lacking 2′O methylation on the first ribose are severely affected by the antiviral activity of Type I interferons. We used proteome-wide affinity purification coupled to mass spectrometry to identify human and mouse proteins specifically binding to capped RNA with different methylation states. This analysis, complemented with functional validation experiments, revealed that IFIT1 is the sole interferon-induced protein displaying higher affinity for unmethylated than for methylated capped RNA. IFIT1 tethers a species-specific protein complex consisting of other IFITs to RNA. Pulsed stable isotope labelling with amino acids in cell culture coupled to mass spectrometry as well as in vitro competition assays indicate that IFIT1 sequesters 2′O-unmethylated capped RNA and thereby impairs binding of eukaryotic translation initiation factors to 2′O-unmethylated RNA template, which results in inhibition of translation. The specificity of IFIT1 for 2′O-unmethylated RNA serves as potent antiviral mechanism against viruses lacking 2′O-methyltransferase activity and at the same time allows unperturbed progression of the antiviral program in infected cells.


title: Severe Acute Respiratory Syndrome: Temporal Stability and Geographic Variation in Death Rates and Doubling Times

text: We analyzed temporal stability and geographic trends in cumulative case-fatality rates and average doubling times of severe acute respiratory syndrome (SARS). In part, we account for correlations between case-fatality rates and doubling times through differences in control measures. Factors that may alter future estimates of case-fatality rates, reasons for heterogeneity in doubling times among countries, and implications for the control of SARS are discussed.


title: Airway Memory CD4(+) T Cells Mediate Protective Immunity against Emerging Respiratory Coronaviruses

text: Two zoonotic coronaviruses (CoV), SARS-CoV and MERS-CoV have crossed species to cause severe human respiratory disease. Here, we showed that induction of airway memory CD4(+) T cells specific for a conserved epitope shared by SARS-CoV and MERS-CoV is a potential strategy for developing pan-coronavirus vaccines. Airway memory CD4(+) T cells differed phenotypically and functionally from lung-derived cells and were crucial for protection against both CoVs in mice. Protection was interferon-γ-dependent and required early induction of robust innate and virus-specific CD8(+) T cell responses. The conserved epitope was also recognized in SARS-CoV and MERS-CoV-infected human leukocyte antigen DR2 and DR3 transgenic mice, indicating potential relevance in human populations. Additionally, this epitope was cross-protective between human and bat CoVs, the progenitors for many human CoVs. Vaccine strategies that induce airway memory CD4(+) T cells targeting conserved epitopes may have broad applicability in the context of new CoV and other respiratory virus outbreaks.


title: Phyloevolutionary analysis of SARS-CoV-2 in Nigeria

text: Abstract Background Phyloepidemiologic approaches have given specific insight to understanding emergence and evolution of infection. Knowledge on the outbreak and spread of SARS-CoV-2 in Nigeria would assist in providing preventive measures to reduce transmission among populations at risk. Therefore, this study aimed at investigating the evolution of SARS-CoV-2 in Nigeria. Materials and Method A total of 39 complete genomes of SARS-CoV-2 were retrieved from the GISAID EpiFluTM database on March 29th 2020 to investigate its evolution in Nigeria. Sequences were selected based on the travel history of the patient and the collection date. Other sequences were not selected because they were short, contained artefacts, not from original source or had insufficient information. Evolutionary history was inferred using Maximum Likelihood method based on the General Time Reversible model. Phylogenetic tree was constructed to determine the common ancestor of each strain. Results The phylogenetic analysis showed the strain in Nigeria clustered in a monophyletic clade with a Wuhan sublineage. Nucleotide alignment also showed a 100% similarity indicating a common origin of evolution. Comparative analysis showed 27,972 (93.6%) identical sites and 97.6% pairwise identity with the consensus. Conclusion The study evidently showed the entire outbreak of COVID-19 infection in Nigeria stemmed from a single introduction sharing consensus similarity with the reference SARS-CoV-2 human genome from Wuhan. Preventive measures that can limit the spread of the infection among populations at risk should be implemented.


title: Expression of feline angiotensin converting enzyme 2 and its interaction with SARS-CoV S1 protein

text: Abstract Feline angiotensin converting enzyme 2 (fACE2) gene was amplified from domestic cat lung with RT-PCR, cloned and sequenced. The complete coding region is 2418bp in length and is the closest to human ACE2 among known ACE2 homologs of non-primate animals. The N terminal fragment 19– 367 aa was expressed in Escherishia coli. Both Western blotting and ELISA demonstrated that fACE2 could react with SARS-CoV S1 protein as efficiently as ACE2 of Vero E6 cells did.


title: Prevalence and characteristics of hypoxic hepatitis in the largest single-centre cohort of avian influenza A(H7N9) virus-infected patients with severe liver impairment in the intensive care unit

text: Avian influenza A(H7N9) virus (A(H7N9)) emerged in February 2013. Liver impairment of unknown cause is present in 29% of patients with A(H7N9) infection, some of whom experience severe liver injury. Hypoxic hepatitis (HH) is a type of acute severe liver injury characterized by an abrupt, massive increase in serum aminotransferases resulting from anoxic centrilobular necrosis of liver cells. In the intensive care unit (ICU), the prevalence of HH is ∼1%–2%. Here, we report a 1.8% (2/112) incidence of HH in the largest single-centre cohort of ICU patients with A(H7N9) infection. Both HH patients presented with multiple organ failure (MOF) involving respiratory, cardiac, circulatory and renal failure and had a history of chronic heart disease. On admission, severe liver impairment was found. Peak alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values were 937 and 1281 U/L, and 3117 and 3029 U/L, respectively, in the two patients. Unfortunately, both patients died due to deterioration of MOF. A post-mortem biopsy in case 1 confirmed the presence of centrilobular necrosis of the liver, and real-time reverse transcription polymerase chain reaction of A(H7N9)-specific genes was negative, which excluded A(H7N9)-related hepatitis. The incidence of HH in A(H7N9) patients is similar to that in ICU patients with other aetiologies. It seems that patients with A(H7N9) infection and a history of chronic heart disease with a low left ventricular ejection fraction on admission are susceptible to HH, which presents as a marked elevation in ALT at the time of admission.


title: Influenza and Endemic Viral Pneumonia

text: Viruses are a common and important cause of severe community-acquired pneumonia, and may lead to severe respiratory disease and admission to the intensive care unit. Influenza is the most common virus associated with severe viral pneumonia, although other important causes include respiratory syncytial virus, adenovirus, metapneumonia virus, and coronaviruses. Viral pneumonias tend to have a seasonal predilection and are often preceded by a typical viral prodrome. This article focuses on severe influenza pneumonia, including the 2009 H1N1 pandemic, and briefly discusses other causes of severe respiratory disease of viral etiology.


title: Harnessing the Power of T Cells: The Promising Hope for a Universal Influenza Vaccine

text: Next-generation vaccines that utilize T cells could potentially overcome the limitations of current influenza vaccines that rely on antibodies to provide narrow subtype-specific protection and are prone to antigenic mismatch with circulating strains. Evidence from animal models shows that T cells can provide heterosubtypic protection and are crucial for immune control of influenza virus infections. This has provided hope for the design of a universal vaccine able to prime against diverse influenza virus strains and subtypes. However, multiple hurdles exist for the realisation of a universal T cell vaccine. Overall primary concerns are: extrapolating human clinical studies, seeding durable effective T cell resident memory (Trm), population human leucocyte antigen (HLA) coverage, and the potential for T cell-mediated immune escape. Further comprehensive human clinical data is needed during natural infection to validate the protective role T cells play during infection in the absence of antibodies. Furthermore, fundamental questions still exist regarding the site, longevity and duration, quantity, and phenotype of T cells needed for optimal protection. Standardised experimental methods, and eventually simplified commercial assays, to assess peripheral influenza-specific T cell responses are needed for larger-scale clinical studies of T cells as a correlate of protection against influenza infection. The design and implementation of a T cell-inducing vaccine will require a consensus on the level of protection acceptable in the community, which may not provide sterilizing immunity but could protect the individual from severe disease, reduce the length of infection, and potentially reduce transmission in the community. Therefore, increasing the standard of care potentially offered by T cell vaccines should be considered in the context of pandemic preparedness and zoonotic infections, and in combination with improved antibody vaccine targeting methods. Current pandemic vaccine preparedness measures and ongoing clinical trials under-utilise T cell-inducing vaccines, reflecting the myriad questions that remain about how, when, where, and which T cells are needed to fight influenza virus infection. This review aims to bring together basic fundamentals of T cell biology with human clinical data, which need to be considered for the implementation of a universal vaccine against influenza that harnesses the power of T cells.


title: Psoriasis and COVID 19: A narrative review with treatment considerations

text: COVID‐19 is a highly contagious respiratory infection caused by severe acute respiratory syndrome coronavirus 2. COVID‐19 outbreak, has been declared a pandemic by the World Health Organization on March, 2020. The pandemic has affected the management of psoriasis, not only for those who are under treatment but also for those who are about to begin a new therapy to control their disease. An increasing number of studies in the current literature have focused on the relationship between psoriasis and COVID 19 from different perspectives. This narrative review includes searching the PubMed and Web of Science databases using the keywords "psoriasis,”, “psoriatic arthritis”, "coronavirus", "COVID 19" and "SARS‐Cov‐2". The search was supplemented by manual searching of reference lists of included articles. A total of 11 relevant original investigations and 6 case studies was identified. The search was updated in May 2019. Due to the absence of randomized controlled trials, it is not likely to have a robust evidence‐based approach to psoriasis management in the era of COVID‐19. However, current literature may provide some clues for safety considerations. Conventional immunosuppressive therapies such as methotrexate and cyclosporine, and anti TNF agents should not be preferred due to increased risk of infection, especially in high‐risk areas. The use of cyclosporine may pose additional risk due to the side effect of hypertension, which has been reported to be associated with susceptibility to severe COVID‐19. Considering that current literature has provide no conclusive evidence that biologics increase the risk of COVID‐19, withdrawal of these agents should be reserved for patients with COVID 19 symptoms. The treatment approach should be personalized, considering the advantages and disadvantages for each case separately. This article is protected by copyright. All rights reserved.


title: Thiopurine analogs and mycophenolic acid synergistically inhibit the papain-like protease of Middle East respiratory syndrome coronavirus

text: Abstract Middle East respiratory syndrome coronavirus (MERS-CoV) is a new highly pathogenic human coronaviruses that emerged in Jeddah and Saudi Arabia and has quickly spread to other countries in Middle East, Europe and North Africa since 2012. Up to 17 December 2014, it has infected at least 938 people with a fatality rate of about 36% globally. This has resulted in an urgent need to identify antiviral drugs that are active against MERS-CoV. The papain-like protease (PLpro) of MERS-CoV represents an important antiviral target as it is not only essential for viral maturation, but also antagonizes interferon stimulation of the host via its deubiquitination activity. Here, we report the discovery that two SARS-CoV PLpro inhibitors, 6-mercaptopurine (6MP) and 6-thioguanine (6TG), as well as the immunosuppressive drug mycophenolic acid, are able to inhibit MERS-CoV PLpro. Their inhibition mechanisms and mutually binding synergistic effect were also investigated. Our results identify for the first time three inhibitors targeting MERS-CoV PLpro and these can now be used as lead compounds for further antiviral drug development.


title: Pulmonary embolism in patients with COVID-19: Time to change the paradigm of computed tomography

text: Abstract Objective To raise awareness for possible benefits of examining known COVID-19 patients presenting sudden clinical worsening with CT pulmonary angiography instead of standard non-contrast chest CT.


title: Cats under the shadow of the SARS‐CoV‐2 pandemic

text: I have some comments on the recently published paper in Transboundary and Emerging Diseases titled "Serological survey of SARS-CoV-2 for experimental, domestic, companion and wild animals excludes intermediate hosts of 35 different species of animals" by Deng JH, et al.


title: Amphotropic murine leukemia virus is preferentially attached to cholesterol-rich microdomains after binding to mouse fibroblasts

text: BACKGROUND: We have recently shown that amphotropic murine leukemia virus (A-MLV) can enter the mouse fibroblast cell line NIH3T3 via caveola-dependent endocytosis. But due to the size and omega-like shape of caveolae it is possible that A-MLV initially binds cells outside of caveolae. Rafts have been suggested to be pre-caveolae and we here investigate whether A-MLV initially binds to its receptor Pit2, a sodium-dependent phosphate transporter, in rafts or caveolae or outside these cholesterol-rich microdomains. RESULTS: Here, we show that a high amount of cell-bound A-MLV was attached to large rafts of NIH3T3 at the time of investigation. These large rafts were not enriched in caveolin-1, a major structural component of caveolae. In addition, they are rather of natural occurrence in NIH3T3 cells than a result of patching of smaller rafts by A-MLV. Thus cells incubated in parallel with vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped MLV particles showed the same pattern of large rafts as cells incubated with A-MLV, but VSV-G pseudotyped MLV particles did not show any preference to attach to these large microdomains. CONCLUSION: The high concentration of A-MLV particles bound to large rafts of NIH3T3 cells suggests a role of these microdomains in early A-MLV binding events.


title: Coronavirus phylogeny based on a geometric approach

text: Abstract A novel coronavirus has been identified as the cause of the outbreak of severe acute respiratory syndrome (SARS). Previous phylogenetic analyses based on sequence alignments show that SARS-CoVs form a new group distantly related to the other three groups of previously characterized coronaviruses. In this paper, a geometric approach based on the Z-curve representation of the whole genome sequence is proposed to analyze the phylogenetic relationships of coronaviruses. The evolutionary distances are obtained through measuring the differences among the three-dimensional Z-curves. The Z-curve is approximately described by its geometric center and the associated three eigenvectors, which indicate the center position and the trend of the Z-curve, respectively. Although some information is lost due to the approximate description of the Z-curve, the phylogenetic tree constructed based on these parameters is consistent with those of previous analyses. The present method has the merits of simplicity and intuitiveness, but it is still in its premature stage. Because the phylogenetic relationships are inferred from the whole genome, instead of some individual genes, the present method represents a new direction of phylogeny study in the post-genome era.


title: A new isolation method for rat intraepithelial lymphocytes

text: Abstract Intraepithelial lymphocytes (IELs) play critical roles in gut immunity. In mice, γδ T cells are a large component of the IEL population. In the rat, γδ IELs are reportedly much less common, but technical issues suggest that previous analyses should be interpreted cautiously. The study of IELs in rats has been impeded by isolation procedures that are lengthy and complex, leading to small cell yields. For this reason, it is possible that rat IELs analyzed in previous studies have not been representative of the entire IEL compartment. We report a new method for the isolation of rat IELs that is based on the selective removal of intestinal epithelial cells under conditions that leave the basement membrane undisturbed. The method is rapid and requires neither enzymatic digestion, nor surgical removal of Peyer's patches, nor vigorous mechanical manipulation of the intestine. The yield of rat IELs using this method is 5- to 10-fold greater than that reported for other methods. Morphological and phenotypic analyses demonstrated that the purified cell population is comprised of IELs and is not contaminated with lamina propria or Peyer's patch lymphocytes. Phenotypic analysis revealed five major subsets of IELs based on differential cell surface expression of CD4, CD8, and αβ T cell receptor (TcR). Among the αβTcR− cells was a population of γδ T cells present at levels not previously detected. The isolation of IEL sub-populations using this methodology should facilitate studies of the function of these cells in gut immunity.


title: Venezuelan equine encephalitis virus non-structural protein 3 (nsP3) interacts with RNA helicases DDX1 and DDX3 in infected cells

text: Abstract The mosquito-borne New World alphavirus, Venezuelan equine encephalitis virus (VEEV) is a Category B select agent with no approved vaccines or therapies to treat infected humans. Therefore it is imperative to identify novel targets that can be targeted for effective therapeutic intervention. We aimed to identify and validate interactions of VEEV nonstructural protein 3 (nsP3) with host proteins and determine the consequences of these interactions to viral multiplication. We used a HA tagged nsP3 infectious clone (rTC-83-nsP3-HA) to identify and validate two RNA helicases: DDX1 and DDX3 that interacted with VEEV-nsP3. In addition, DDX1 and DDX3 knockdown resulted in a decrease in infectious viral titers. Furthermore, we propose a functional model where the nsP3:DDX3 complex interacts with the host translational machinery and is essential in the viral life cycle. This study will lead to future investigations in understanding the importance of VEEV-nsP3 to viral multiplication and apply the information for the discovery of novel host targets as therapeutic options.


title: Disruptive Innovation Can Prevent the Next Pandemic

text: Public health surveillance (PHS) is at a tipping point, where the application of novel processes, technologies, and tools promise to vastly improve efficiency and effectiveness. Yet twentieth century, entrenched ideology and lack of training results in slow uptake and resistance to change. The term disruptive innovation – used to describe advances in technology and processes that change existing markets – is useful to describe the transformation of PHS. Past disruptive innovations used in PHS, such as distance learning, the smart phone, and field-based laboratory testing have outpaced older services, practices, and technologies used in the traditional classroom, governmental offices, and personal communication, respectively. Arguably, the greatest of these is the Internet – an infrastructural innovation that continues to enable exponential benefits in seemingly limitless ways. Considering the Global Health Security Agenda and facing emerging and reemerging infectious disease threats, evolving environmental and behavioral risks, and ever changing epidemiologic trends, PHS must transform. Embracing disruptive innovation in the structures and processes of PHS can be unpredictable. However, it is necessary to strengthen and unlock the potential to prevent, detect, and respond.


title: The Challenge of Respiratory Virus Infections in Hematopoietic Cell Transplant Recipients

text: Respiratory virus infections in hematopoietic cell transplant (HCT) recipients are a major cause of morbidity and mortality. While respiratory syncytial virus (RSV), human metapneumonvirus, parainfluenzaviruses, and influenza viruses are well known for their potential to cause fatal pneumonia, information is emerging only recently on the significance of the newly discovered viruses such as human coronaviruses NL63 and HKU1, and human bocavirus. Lymphopenia seems to be the most recent risk factors for progression to lower respiratory tract disease. Airflow obstruction is another complication of respiratory virus infections after HCT, and data to date indicate this complication may occur following parainfluenza virus and RSV infection. Infection control procedures are key for prevention. Unfortunately, there are no randomized treatment studies, which make the interpretation of the literature on interventions difficult. This article reviews the spectrum of pathogens, epidemiology, risk factors and clinical manifestations of infection, as well as recent advances in diagnostic and clinical management.


title: A New Framework and Software to Estimate Time-Varying Reproduction Numbers During Epidemics

text: The quantification of transmissibility during epidemics is essential to designing and adjusting public health responses. Transmissibility can be measured by the reproduction number R, the average number of secondary cases caused by an infected individual. Several methods have been proposed to estimate R over the course of an epidemic; however, they are usually difficult to implement for people without a strong background in statistical modeling. Here, we present a ready-to-use tool for estimating R from incidence time series, which is implemented in popular software including Microsoft Excel (Microsoft Corporation, Redmond, Washington). This tool produces novel, statistically robust analytical estimates of R and incorporates uncertainty in the distribution of the serial interval (the time between the onset of symptoms in a primary case and the onset of symptoms in secondary cases). We applied the method to 5 historical outbreaks; the resulting estimates of R are consistent with those presented in the literature. This tool should help epidemiologists quantify temporal changes in the transmission intensity of future epidemics by using surveillance data.


title: Structural Basis of Inhibition Specificities of 3C and 3C-like Proteases by Zinc-coordinating and Peptidomimetic Compounds

text: Human coxsackievirus (CV) belongs to the picornavirus family, which consists of over 200 medically relevant viruses. In picornavirus, a chymotrypsin-like protease (3C(pro)) is required for viral replication by processing the polyproteins, and thus it is regarded as an antiviral drug target. A 3C-like protease (3CL(pro)) also exists in human coronaviruses (CoV) such as 229E and the one causing severe acute respiratory syndrome (SARS). To combat SARS, we previously had developed peptidomimetic and zinc-coordinating inhibitors of 3CL(pro). As shown in the present study, some of these compounds were also found to be active against 3C(pro) of CV strain B3 (CVB3). Several crystal structures of 3C(pro) from CVB3 and 3CL(pro) from CoV-229E and SARS-CoV in complex with the inhibitors were solved. The zinc-coordinating inhibitor is tetrahedrally coordinated to the His(40)-Cys(147) catalytic dyad of CVB3 3C(pro). The presence of specific binding pockets for the residues of peptidomimetic inhibitors explains the binding specificity. Our results provide a structural basis for inhibitor optimization and development of potential drugs for antiviral therapies.


title: Planning for Pandemics: Lessons From the Past Decade

text: It is now 10 years since the disease we now know as SARS—severe acute respiratory syndrome—caused more than 700 deaths around the world and made more than 8,000 people ill. More recently, in 2009 the global community experienced the first influenza pandemic of the 21st century—the 2009 H1N1 influenza pandemic. This paper analyses the major developments in international public health law relating to infectious diseases in the period since SARS and considers their implications for pandemic planning.


title: Avian infectious bronchitis virus disrupts the melanoma differentiation associated gene 5 (MDA5) signaling pathway by cleavage of the adaptor protein MAVS

text: BACKGROUND: Melanoma differentiation associated gene 5 (MDA5) and retinoic acid-inducible gene-I (RIG-I) selectively sense cytoplasmic viral RNA to induce an antiviral immune response. Infectious bronchitis virus (IBV) is one of the most important infectious agents in chickens, and in chicken cells, it can be recognized by MDA5 to activate interferon production. RIG-I is considered to be absent in chickens. However, the absence of RIG-I in chickens raises the question of whether this protein influences the antiviral immune response against IBV infection. RESULTS: Here, we showed that chicken cells transfected with domestic goose RIG-I (dgRIG-I) exhibited increased IFN-β activity after IBV infection. We also found that IBV can cleave MAVS, an adaptor protein downstream of RIG-I and MDA5 that acts as a platform for antiviral innate immunity at an early stage of infection. CONCLUSIONS: Although chicken MDA5 (chMDA5) is functionally active during IBV infection, the absence of RIG-I may increase the susceptibility of chickens to IBV infection, and IBV may disrupt the activation of the host antiviral response through the cleavage of MAVS. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi: 10.1186/s12917-017-1253-7) contains supplementary material, which is available to authorized users.


title: Comparison of SYBR green I real-time RT-PCR with conventional agarose gel-based RT-PCR for the diagnosis of infectious bronchitis virus infection in chickens in Morocco

text: BACKGROUND: A rapid, sensitive, and specific molecular method for the diagnosis of infectious bronchitis virus (IBV) infection is important in curbing infectious bronchitis outbreaks in Morocco and other countries. METHODS: In this study, an easy-to-perform SYBR green I real-time reverse transcriptase polymerase chain reaction (RT-PCR) targeting the nucleocapsid gene of IBV was developed and compared with conventional agarose gel-based RT-PCR for the detection of IBV infection. RESULTS: We found that the SYBR green I real-time RT-PCR was at least 10 times more sensitive than the agarose gel electrophoresis detection method. The assay exhibited high specificity for IBV infection. All negative controls, such as Newcastle disease virus, infectious bursal disease virus, and avian influenza virus, were not detected. CONCLUSION: The SYBR green I real-time RT-PCR test described herein can be used to rapidly distinguish IBV from other respiratory pathogens, which is important for diagnosis and control of infectious bronchitis outbreaks in Morocco. The test is a valuable and useful method as a routine assay for diagnosis of clinical IBV infection in commercial chickens.


title: COVID‐19 pandemic and Zagreb earthquakes as stressors in patients with temporomandibular disorders

text: Stress refers to situations in which one feels that the demands imposed on them exceed the limitations of their ability to adapt. This causes a series of adverse consequences among which is compromised health (Lazarus and Folkman, 1984). On 11th March 2020, the World Health Organization declared the pandemic status of COVID‐19 diseases, leading to the European Union states imposing the lockdown, Croatia being one among them. Infection prevention became the nation's most important goal, and people had to change their day‐to‐day habits.


title: Dialectical behavior therapy-based psychological intervention for woman in late pregnancy and early postpartum suffering from COVID-19: a case report

text: 目 的: 孕产妇的心理健康风险较为突出, 但尚未有文献说明何种心理干预方式对患有新冠肺炎的围产期孕妇有效. 本文报告了一例确诊新冠肺炎的 35 周 2 天孕妇在入住隔离病房后, 使用辩证行为治疗 (DBT) 相关技术对其存在的抑郁和焦虑症状在围产期进行持续心理干预的案例, 旨在探究以 DBT 为基础的短程心理治疗对围产期新冠肺炎患者的抑郁和焦虑症状的改善作用. 创新点: 首例对确诊新冠肺炎的孕产妇进行产前及产后心理评估及干预的案例. 也是首次报道在公共卫生危机事件的个体干预中使用了 DBT 相关技术. 方 法: 患者, 女, 30 岁, 孕 35 周 +2 天, 干咳两天就诊, 在当地医院进行新型冠状病毒核酸测验提示阳性后转入浙江大学医学院附属第一医院住院治疗. 2020 年 2 月 8 日行剖腹产, 产后继续在隔离病房治疗. 入院后精神科访谈及心理测量均提示存在抑郁和焦虑症状, 于 2 月 7 日、 10 日、 16 日进行三次心理干预, 主要使用 DBT 相关干预技术, 包括放松训练、 正念练习、 情绪控制技巧训练、 人际支持等. 期间根据患者的需要及时调整干预策略. 通过三次心理干预, 患者的抑郁、 焦虑症状得到改善, 抑郁和焦虑量表评分与基线比显著下降. 结 论: 本报告显示了对确诊新冠肺炎的隔离病房患者及时进行心理干预的必要性. 心理干预能有效改善患者的抑郁、 焦虑症状, 减少或避免了精神类药物的使用, 为新冠肺炎的临床治疗提供了支持. 此报告也为以 DBT 为基础的心理治疗在危机干预中的应用提供了临床证据.


title: Mapping the neutralizing epitopes of F18 fimbrial adhesin subunit FedF of enterotoxigenic Escherichia coli (ETEC)

text: Abstract K88 and F18 fimbrial enterotoxigenic Escherichia coli (ETEC) are the major causes of post-weaning diarrhea (PWD) in pigs. A vaccine that induces broad immunity to prevent K88 and F18 fimbrial ETEC bacterial attachment and colonization in pig small intestines and to neutralize enterotoxin enterotoxicity would be effective for PWD. Structure-based multiepitope-fusion-antigen (MEFA) technology using a backbone immunogen to present neutralizing epitopes of representing virulence factors capacitates development of broadly protective ETEC vaccines. Neutralizing epitopes have been identified from K88 fimbrial adhesin (FaeG) and enterotoxins but not F18 fimbrial adhesin. In this study, we in silico identified immunodominant epitopes from F18ac fimbrial subunit FedF which plays a critical role in F18 fimbrial adherence, genetically fused each epitope to a carrier, examined immunogenicity of each epitope fusion, and determined epitope-derived antibodies neutralizing activities against F18 fimbrial adherence. Data showed that seven immune-dominant epitopes were identified from FedF subunit. Fused to heterologous human ETEC adhesin subunit CfaB, epitope fusions induced anti-F18 antibodies in subcutaneously immunized mice. Moreover, antibodies derived from each fusion significantly blocked adherence of a F18-fimbrial E. coli bacteria to pig intestinal cell line IPEC-J2. While all seven epitopes exhibited neutralizing activity, results from this study identified FedF epitopes #3 (IPSSSGTLTCQAGT) and #7 (QPDATGSWYD) the most effective for antibodies against F18 fimbrial adherence, and suggested their future application in PWD vaccine development.


title: STEMI care during COVID-19: losing sight of the forest for the trees

text: [Figure: see text]


The Importance of Virology at a Time of Great Need and Great Jeopardy


title: Naturally occurring recombination between distant strains of infectious bronchitis virus

text: New variants of infectious bronchitis virus (IBV) have emerged in Australia despite its geographical isolation and intensive vaccination programs. In the present study, the 3′ terminal 7.2 kb of the genome of a recently isolated variant of IBV (N1/03) was sequenced and compared with the sequences of classical and novel strains of IBV, the two main groups of these viruses in Australia. The comparison revealed that recombination between classical and novel IBVs was responsible for the emergence of the new variant. It was concluded that novel IBVs, which have not been detected since 1993, and which are phylogenically more distant from classical IBVs than turkey coronaviruses, might still be circulating and contributing to the evolution of IBV in Australia.


Normativas para el diagnóstico y el tratamiento de la neumonía adquirida en la comunidad. Sociedad Española de Neumología y Cirugía Torácica (SEPAR)


title: High Prevalence of Cryptococcal Infection Among HIV-Infected Patients Hospitalized With Pneumonia in Thailand

text: Background. Cryptococcal meningitis (CM) is a major cause of death among HIV-infected patients. Cryptococcal antigenemia (CrAg+) in the absence of CM can represent early-stage cryptococcosis during which antifungal treatment might improve outcomes. However, patients without meningitis are rarely tested for cryptococcal infection. We evaluated Cryptococcus species as a cause of acute respiratory infection in hospitalized patients in Thailand and evaluated clinical characteristics associated with CrAg+. Methods. We tested banked serum samples from 704 human immunodeficiency virus (HIV)–infected and 730 HIV-uninfected patients hospitalized with acute respiratory infection from 2004 through 2009 in 2 rural provinces in Thailand for the presence of CrAg+. Retrospective chart reviews were conducted for CrAg+ patients to distinguish meningeal and nonmeningeal cryptococcosis and to identify clinical characteristics associated with CrAg+ in patients with and without evidence of CM. Results. CrAg+ was found in 92 HIV-infected patients (13.1%); only tuberculosis (19.3%) and rhinovirus (16.5%) were identified more frequently. No HIV-uninfected patients were CrAg+. Of 70 CrAg+ patients with medical charts available, 37 (52.9%) had no evidence of past or existing CM at hospitalization; 30 of those patients (42.9% of all CrAg+) had neither past nor existing CM, nor any alternate etiology of infection identified. Dyspnea was more frequent among CrAg+ patients without CM than among CrAg– patients (P = .0002). Conclusions. Cryptococcus species were the most common pathogens detected in HIV-infected patients hospitalized with acute respiratory infection in Thailand. Few clinical differences were found between antigenemic and nonantigenemic HIV-infected patients. Health care providers in Thailand should evaluate HIV-infected patients hospitalized with acute respiratory infection for cryptococcal antigenemia, even in the absence of meningitis.


title: SARS-CoV-2 and the COVID-19 disease: a mini review on diagnostic methods

text: Coronavirus disease 2019 (COVID-19) is an infectious disease initially reported in China and currently worldwide dispersed caused by a new coronavirus (SARS-CoV-2 or 2019-nCoV) affecting more than seven million people around the world causing more than 400 thousand deaths (on June 8(th), 2020). The diagnosis of COVID-19 is based on the clinical and epidemiological history of the patient. However, the gold standard for COVID-19 diagnosis is the viral detection through the amplification of nucleic acids. Although the quantitative Reverse-Transcription Polymerase Chain Reaction (RT-PCR) has been described as the gold standard for diagnosing COVID-19, there are several difficulties involving its use. Here we comment on RT-PCR and describe alternative tests developed for the diagnosis of COVID-19.


title: Expression of SARS-CoV-2 Receptor ACE2 and Coincident Host Response Signature Varies by Asthma Inflammatory Phenotype

text: Abstract Background Over 300 million people carry a diagnosis of asthma with data to suggest they are at higher risk for infection or adverse outcomes from SARS-CoV-2. Asthma is remarkably heterogenous and it is currently unclear how patient intrinsic factors may relate to COVID-19. Objective Identify and characterize subsets of asthmatics at increased risk for SARS-CoV-2 infection. Methods Participants from 2 large asthma cohorts were stratified using clinically relevant parameters to identify factors related to ACE2 expression within bronchial epithelium. ACE-2 correlated gene signatures were used to interrogate publicly available databases to identify upstream signaling events and novel therapeutic targets. Results Stratifying by Type 2 inflammatory biomarkers, we identified subjects who demonstrated low peripheral blood eosinophils accompanied by increased expression of the SARS-CoV-2 receptor ACE2 in bronchial epithelium. Genes highly correlated with ACE2 overlapped with Type 1 and 2 interferon signatures, normally induced by viral infections. T cell recruitment and activation within bronchoalveolar lavage cells of ACE2-high subjects was reciprocally increased. These patients demonstrated characteristics corresponding to risk factors for severe COVID-19, including male sex, history of hypertension, low peripheral blood and elevated BAL lymphocytes. Conclusion ACE2 expression is linked to upregulation of viral response genes in a subset of Type-2 low asthmatics with characteristics resembling known risk factors for severe COVID-19. Therapies targeting the interferon family and T cell activating factors may therefore be of benefit in a subset of patients. Clinical Implication Type-2 low asthmatics may be at increased risk for adverse outcome from COVID-19 and deserve increased vigilance upon developing symptoms.


title: Testing the modularity of the N-terminal amphipathic helix conserved in picornavirus 2C proteins and hepatitis C NS5A protein

text: Abstract The N-terminal region of the picornaviral 2C protein is predicted to fold into an amphipathic α-helix that is responsible for the protein's association with membranes in the viral RNA replication complex. We have identified a similar sequence in the N-terminal region of NS5A of hepaciviruses that was recently shown to form an amphipathic α-helix. The conservation of the N-terminal region in two apparently unrelated proteins of two different RNA virus families suggested that this helix might represent an independent module. To test this hypothesis, we constructed chimeric poliovirus (PV) genomes in which the sequence encoding the N-terminal 2C amphipathic helix was replaced by orthologous sequences from other picornaviral genomes or a similar sequence from NS5A of HCV. Effects of the mutations were assessed by measuring the accumulation of viable virus and viral RNA in HeLa cells after transfection, examining membrane morphology in cells expressing chimeric proteins and by in vitro analysis of RNA translation, protein processing and negative strand RNA synthesis in HeLa cell extracts. The chimeras manifested a wide range of growth and RNA synthesis phenotypes. The results are compatible with our hypothesis, although they demonstrate that helix exchangeability may be restricted due to requirements for interactions with other viral components involved in virus replication.


title: Factors associated with recovery delay in a sample of patients diagnosed by MERS‐CoV rRT‐PCR: A Saudi Arabian multicenter retrospective study

text: BACKGROUND: Research evidence exists that poor prognosis is common in Middle East respiratory syndrome coronavirus (MERS‐CoV) patients. OBJECTIVES: This study estimates recovery delay intervals and identifies associated factors in a sample of Saudi Arabian patients admitted for suspected MERS‐CoV and diagnosed by rRT‐PCR assay. METHODS: A multicenter retrospective study was conducted on 829 patients admitted between September 2012 and June 2016 and diagnosed by rRT‐PCR procedures to have MERS‐CoV and non‐MERS‐CoV infection in which 396 achieved recovery. Detailed medical charts were reviewed for each patient who achieved recovery. Time intervals in days were calculated from presentation to the initial rRT‐PCR diagnosis (diagnosis delay) and from the initial rRT‐PCR diagnosis to recovery (recovery delay). RESULTS: The median recovery delay in our sample was 5 days. According to the multivariate negative binomial model, elderly (age ≥ 65), MERS‐CoV infection, ICU admission, and abnormal radiology findings were associated with longer recovery delay (adjusted relative risk (aRR): 1.741, 2.138, 2.048, and 1.473, respectively). Camel contact and the presence of respiratory symptoms at presentation were associated with a shorter recovery delay (expedited recovery) (aRR: 0.267 and 0.537, respectively). Diagnosis delay is a positive predictor for recovery delay (r = .421; P = .001). CONCLUSIONS: The study evidence supports that longer recovery delay was seen in patients of older age, MERS‐CoV infection, ICU admission, and abnormal radiology findings. Shorter recovery delay was found in patients who had camel contact and respiratory symptoms at presentation. These findings may help us understand clinical decision making on directing hospital resources toward prompt screening, monitoring, and implementing clinical recovery and treatment strategies.


title: Human infectious diseases in the genomics era: where do we go from here?

text: Ripudaman K Bains is the editor of the Genome Biology special issue content on the ‘genomics of infectious diseases’, and introduces the collection in this editorial.


title: Clinical usefulness of serum procalcitonin level in distinguishing between Kawasaki disease and other infections in febrile children

text: PURPOSE: The aims of this study were to compare serum procalcitonin (PCT) levels between febrile children with Kawasaki disease (KD) and those with bacterial or viral infections, and assess the clinical usefulness of PCT level in predicting KD. METHODS: Serum PCT levels were examined in febrile pediatric patients admitted between August 2013 and August 2014. The patients were divided into 3 groups as follows: 49 with KD, 111 with viral infections, and 24 with bacterial infections. RESULTS: The mean PCT level in the KD group was significantly lower than that in the bacterial infection group (0.82±1.73 ng/mL vs. 3.11±6.10 ng/mL, P=0.002) and insignificantly different from that in the viral infection group (0.23±0.34 ng/mL,P=0.457). The mean erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level in the KD group were significantly higher than those in the viral and bacterial infection groups (P<0.001 and P<0.001 for ESR, P<0.001 and P=0.005 for CRP, respectively). The proportion of patients in the KD group with PCT levels of >1.0 ng/mL was significantly higher in the nonresponders to the initial intravenous immunoglobulin treatment than in the responders (36% vs. 8%, P=0.01). CONCLUSION: PCT levels may help to differentiate KD from bacterial infections. A combination of disease markers, including ESR, CRP, and PCT, may be useful for differentiating between KD and viral/bacterial infections.


Postdigital Living in the Age of Covid-19: Unsettling What We See as Possible


title: Newcastle disease virus induces G0/G1 cell cycle arrest in asynchronously growing cells

text: Abstract The cell cycle, as a basic cellular process, is conservatively regulated. Consequently, subversion of the host cell replication cycle is a common strategy employed by many viruses to create a cellular environment favorable for viral replication. Newcastle disease virus (NDV) causes disease in poultry and is also an effective oncolytic agent. However, the effects of NDV infection on cell cycle progression are unknown. In this study, we showed that NDV replication in asynchronized cells resulted in the accumulation of infected cells in the G0/G1 phase of the cell cycle, which benefitted the proliferation of NDV. Examination of various cell cycle-regulatory proteins showed that expression of cyclin D1, was significantly reduced following NDV infection. Importantly, the decreased expression of cyclin D1 was reversed by inhibition of CHOP expression, indicating that induction of the PERK-eIF-2a-ATF4-CHOP signaling pathway was involved in the G0/G1 phase cell cycle arrest observed following NDV infection.


title: Characteristics of Group A Streptococcus Strains Circulating during Scarlet Fever Epidemic, Beijing, China, 2011

text: Scarlet fever is one of a variety of diseases caused by group A Streptococcus (GAS). During 2011, a scarlet fever epidemic characterized by peak monthly incidence rates 2.9–6.7 times higher than those in 2006–2010 occurred in Beijing, China. During the epidemic, hospital-based enhanced surveillance for scarlet fever and pharyngitis was conducted to determine characteristics of circulating GAS strains. The surveillance identified 3,359 clinical cases of scarlet fever or pharyngitis. GAS was isolated from 647 of the patients; 76.4% of the strains were type emm12, and 17.1% were emm1. Almost all isolates harbored superantigens speC and ssa. All isolates were susceptible to penicillin, and resistance rates were 96.1% to erythromycin, 93.7% to tetracycline, and 79.4% to clindamycin. Because emm12 type GAS is not the predominant type in other countries, wider surveillance for the possible spread of emm12 type GAS from China to other countries is warranted.


title: Core Outcome Set for Clinical Trials of COVID-19 Based on Traditional Chinese and Western Medicine

text: BACKGROUND: Development of a core outcome set (COS) for clinical trials for COVID-19 is urgent because of the pandemic wreaking havoc worldwide and the heterogeneity of outcomes in clinical trials. METHODS: A preliminary list of outcomes was developed after a systematic review of protocols of clinical trials for COVID-19. Then, two rounds of the Delphi survey were conducted. Stakeholders were traditional Chinese medicine (TCM) experts, Western medicine (WM) experts, nurses, and the public. Patients with confirmed COVID-19 were also invited to participate in a questionnaire written in understandable language. Then different stakeholders participated in a consensus meeting by video conference to vote. RESULTS: Ninety-seven eligible study protocols were identified from 160 clinical trials. Seventy-six outcomes were identified from TCM clinical trials and 126 outcomes were identified from WM clinical trials. Finally, 145 outcomes were included in the first round of the Delphi survey. Then, a COS for clinical trials of TCM and WM was developed. The COS included clinical outcomes (recovery/improvement/progression/death), etiology (SARS-CoV-2 nucleic-acid tests, viral load), inflammatory factor (C-reactive protein), vital signs (temperature, respiration), blood and lymphatic-system parameters (lymphocytes, virus antibody), respiratory outcomes (pulmonary imaging, blood oxygen saturation, PaO2/FiO2 ratio, arterial blood gas analysis, mechanical ventilation, oxygen intake, pneumonia severity index), clinical efficacy (prevalence of preventing patients with mild-to-moderate disease progressing to severe disease), and symptoms (clinical symptom score). Outcomes were recommended according to different types of disease. Outcome measurement instruments/definitions were also recommended. CONCLUSION: Though there are some limitations for the research, such as insufficient patients and the public involvement, and the unbalanced stakeholders' region, the COS for COVID-19 may improve consistency of outcome reporting in clinical trials. It also should be updated with research progression.


title: Schinus terebenthifolius Raddi extracts: from sunscreen activity toward protection of the placenta to Zika virus infection, new uses for a well-known medicinal plant

text: Abstract Schinus terebinthifolius Raddi is a well-known medicinal plant native of South America. This species has demonstrated important biological activities such as antihypertensive and vasodilator, antimicrobial, anti-inflammatory and antioxidant. However, no studies have been, so far, reported with the fruits of S. terebinthifolius as a protector of the placenta against Zika virus infection and as sunscreen agents. The present study aimed to investigate new uses for the ethanolic fruit extracts of S. terebinthifolius, from fruits’peel (STPE) and from the whole fruits (STWFE). Zika virus (ZIKV) has been linked to several fetal malformations, such as microcephaly and other central nervous system abnormalities. Thus, the potential of these natural extracts against ZIKV infection was evaluated, using an in vitro method. The photoprotective potential, determined by spectrometry, along with phenolic content, antioxidant capacity, and chemical composition of both extracts were also evaluated. The chemical composition of the extracts was evaluated by HPLC-UV / vis. The cytotoxicity of peel and whole fruit extracts in vero E6 cell lines, in placental cell lines and placental explant cultures were evaluated by the MTT assay. The infectivity of placental cells and explants was evaluated by qRT-PCR and the effects of extracts on ZIKV infection were investigated using HTR-8/SVneo cells, pre-treated with 100 μg mL-1 of STWFE for 1 h, and infected with MR766 (AD) or PE243 (EH) ZIKV strains. STFE and STWFE were well-tolerated by both placental-derived trophoblast cell line HTR-8/SVneo as well as by term placental chorionic villi explants, which indicate absence of cytotoxicity in all analysed concentrations. Two strains of ZIKV were tested to access if pre-treatment of trophoblast cells with the STWFE would protect them against infection. Flow cytometry analysis revealed that STWFE extract greatly reduced ZIKV infection. The extracts were also photoprotective with SPF values equivalent to the standard, benzophenone-3. The formulations prepared in different concentrations of the extracts (5-10%) had shown maximum SPF values of 32.21. STWFE represents a potential natural mixture to be used in pregnancy in order to restrain placental infection by ZIKV and might potentially protect fetus against ZIKV-related malformations. The extracts exhibited photoprotective activity and some of the phenolic compounds, mainly resveratrol, catechin and epicatechin, are active ingredients in all assayed activities. The development of biotechnological/medical products, giving extra value to products from family farming, is expected, with strong prospects for success.


title: Marine compounds and their antiviral activities

text: Abstract Available treatments for many infectious diseases are limited. In particular, diseases caused by viral pathogens have demonstrated the need for new medicines, due to the increasing appearance of resistance to these available treatments. Thousands of novel compounds have been isolated from various marine organisms and tested for pharmacological properties, many of which are commercially available. The screening of natural products derived from marine species for antiviral activity has yielded a considerable number of active crude aqueous and organic solvent extracts. Today, over 40 compounds are commercially available in pharmacological markets, including alternative antiviral medicines or those being tested as potential antiviral drugs. Many more are being tested as potential antiviral drugs at the preclinical and clinical stages. The growing interest in marine-derived antiviral compounds, along with the development of new technology in marine cultures and extraction, will significantly expedite the current exploration of the marine environment for compounds with significant pharmacological applications, which will continue to be a promising strategy and new trend for modern medicine.


Rationing of Medical Supplies Including Ventilators in Patients With Kidney Disease


Research News: COVID-19


title: Dynamics of transmissible gastroenteritis virus internalization unraveled by single‐virus tracking in live cells

text: Transmissible gastroenteritis virus (TGEV) is a swine enteropathogenic coronavirus that causes significant economic losses in swine industry. Current studies on TGEV internalization mainly focus on viral receptors, but the internalization mechanism is still unclear. In this study, we used single‐virus tracking to obtain the detailed insights into the dynamic events of the TGEV internalization and depict the whole sequential process. We observed that TGEVs could be internalized through clathrin‐ and caveolae‐mediated endocytosis, and the internalization of TGEVs was almost completed within ~2 minutes after TGEVs attached to the cell membrane. Furthermore, the interactions of TGEVs with actin and dynamin 2 in real time during the TGEV internalization were visualized. To our knowledge, this is the first report that single‐virus tracking technique is used to visualize the entire dynamic process of the TGEV internalization: before the TGEV internalization, with the assistance of actin, clathrin, and caveolin 1 would gather around the virus to form the vesicle containing the TGEV, and after ~60 seconds, dynamin 2 would be recruited to promote membrane fission. These results demonstrate that TGEVs enter ST cells via clathrin‐ and caveolae‐mediated endocytic, actin‐dependent, and dynamin 2‐dependent pathways.


Reallocating Ventilators During the COVID-19 Pandemic: Is it Ethical?


title: Impact of quarantine measures on chemical compositions of PM2.5 during the COVID-19 epidemic in Shanghai, China

text: Abstract The COVID-19 epidemic broke out in Wuhan, Hubei in December 2019 and in January 2020 and was later transmitted to the entire country. Quarantine measures during Chinese New Year effectively alleviated the spread of the epidemic, but they simultaneously resulted in a decline in anthropogenic emissions from industry, transportation, and import and export of goods. Herein, we present the major chemical composition of non-refractory PM2.5 (NR-PM2.5) and the concentrations of gaseous pollutants in an urban site in Shanghai before and during the quarantine period of the COVID-19 epidemic, which was Jan. 8―23 and Jan. 24―Feb. 8, respectively. The observed results show that the reduction in PM2.5 can be mainly attributed to decreasing concentrations of nitrate and primary aerosols. Nitrate accounted for 37% of NR-PM2.5 before the quarantine period when there was no emission reduction. During the quarantine period, the nitrate concentration decreased by approximately 60%, which is attributed to a reduction in the NOx concentration. Ammonium, as the main balancing cation, showed an approximately 45% simultaneous decrease in concentration. The concentrations of chloride and hydrocarbon-like organic aerosols from primary emissions also declined due to limited human activities. By contrast, sulphate and oxygenated organic aerosols showed a slight decrease in concentration, with their contributions increasing to 27% and 18%, respectively, during the quarantine period, which resulted in two pollution episodes with PM2.5 exceeding 100 μg/m3. This study provides a better understanding of the impact of quarantine measures on variations of the PM2.5 concentration and chemical compositions. Atmospheric oxidation capacities based on the oxidant (Ox = O3 + NO2) and oxidation ratios have been discussed for elucidating the source and formation of haze in an environment with lower anthropogenic emissions. With increasing contribution of secondary aerosols, lower NOx and nitrate concentrations did not completely avoid haze in Shanghai during the epidemic.


title: Bioaerosol Sampling at a Live Animal Market in Kunshan, China: A Noninvasive Approach for Detecting Emergent Viruses

text: From October to December 2018, periodic bioaerosol sampling was conducted at a live bird market in Kunshan, China. Sixty-six (55%) of 120 samples had molecular evidence of avian influenza viruses. Four yielded live H9N2 virus after egg culture.


Dysentery as a rare GI symptom found in COVID-19 patients


title: Impacto de la pandemia por SARS-CoV-2 sobre la actividad y profesionales de un Servicio de Cirugía General y del Aparato Digestivo en un hospital terciario

text: Resumen Introducción: La rápida expansión de la infección por SARS-CoV-2 ha supuesto una radical reorganización de los recursos sanitarios y la exposición de profesionales al contagio. Los servicios de Cirugía General y del Aparato Digestivo también necesitan adaptarse a este cambio. Pacientes y métodos: Se realiza un estudio observacional descriptivo prospectivo de los casos de COVID-19 en pacientes y cirujanos de un Servicio de Cirugía General en un área de alta incidencia de infección entre el 1 y el 31 de marzo de 2020. Resultados: Pacientes: La incidencia de infección por SARS-CoV-2 en los pacientes programados con hospitalización en el postoperatorio inmediato fue del 7%. Su edad media fue de 59,5 años y todos evolucionaron satisfactoriamente en planta. De 36 pacientes intervenidos de urgencia, dos fueron SARS-CoV-2+ y uno altamente sospechoso de COVID-19 (11,1%). Los tres pacientes fallecieron por insuficiencia respiratoria, su edad media era de 81 años. Cirujanos: Hubo un total de 12 casos SARS-CoV-2 + confirmados (24,4%) (8 de 34 adjuntos y 4 de 15 residentes). Actividad asistencial: El número medio de intervenciones quirúrgicas urgentes diarias bajó de 3,6 en febrero a 1,16 en el mes de marzo. El 42% de los pacientes intervenidos a partir de la entrada en vigor de las primeras medidas de aislamiento a nivel regional, presentaban cuadros evolucionados. Conclusiones: El aumento de casos en la población general de COVID-19 debe alertar a los Servicios de Cirugía General de la necesidad de tomar de medidas de forma precoz que garanticen la seguridad de los pacientes y de los cirujanos. Abstract Introduction: The rapid spread of SARS-CoV-2 infection has led to a radical reorganization of healthcare resources. Surgical Departments need to adapt to this change. Patients and methods: We performed a prospective descriptive observational study of the incidence of COVID-19 in patients and surgeons of a General Surgical Department in a high prevalence area, between the 1st and 31st of March 2020. Results: Patients: The incidence of SARS-CoV-2 infection in elective surgery patients was 7% (mean age 59.5 years). All survived. Of 36 patients who underwent emergency surgery, two of them were SARS-CoV-2 positive and one was clinically highly suspicious of COVID-19 (11.1%). All three patients died of respiratory failure (mean age 81 years). Surgeons: There were a total of 12 confirmed SARS-CoV-2+ cases among the surgical department staff (24.4%) (8 out of 34 consultants and 4 out of 15 residents). Healthcare activity: The average number of daily emergency surgical interventions declined from 3.6 in February to 1.16 in March. 42% of the patients who underwent emergency surgery had peritonitis upon presentation. Conclusions: The fast pace of COVID-19 pandemia, should alert surgical departments of the need of adopting early measures to ensure the safety of patients and staff.


title: Establishment of a novel ovine kidney cell line for isolation and propagation of viruses infecting domestic cloven-hoofed animal species

text: A sheep kidney-derived cell line, FLK-N3, was successfully established after serial (>100) passages. Persistent infection of this cell line with viruses and mycoplasma was not detected. The cells grew well and showed susceptibility to a wide variety of viruses derived from ovine, bovine, and porcine species, including orf virus, maedi visna virus, bovine herpesvirus 1, bovine parainfluenza virus 3, bovine viral diarrhea viruses 1 and 2, bovine coronavirus, bovine respiratory syncytial virus, bovine enterovirus, suid herpesvirus 1, and porcine enterovirus. These results suggest that the FLK-N3 cell line could be useful for isolation and propagation of viruses that affect cloven-hoofed animals.


title: Deposition of respiratory virus pathogens on frequently touched surfaces at airports

text: BACKGROUND: International and national travelling has made the rapid spread of infectious diseases possible. Little information is available on the role of major traffic hubs, such as airports, in the transmission of respiratory infections, including seasonal influenza and a pandemic threat. We investigated the presence of respiratory viruses in the passenger environment of a major airport in order to identify risk points and guide measures to minimize transmission. METHODS: Surface and air samples were collected weekly at three different time points during the peak period of seasonal influenza in 2015–16 in Finland. Swabs from surface samples, and air samples were tested by real-time PCR for influenza A and B viruses, respiratory syncytial virus, adenovirus, rhinovirus and coronaviruses (229E, HKU1, NL63 and OC43). RESULTS: Nucleic acid of at least one respiratory virus was detected in 9 out of 90 (10%) surface samples, including: a plastic toy dog in the children’s playground (2/3 swabs, 67%); hand-carried luggage trays at the security check area (4/8, 50%); the buttons of the payment terminal at the pharmacy (1/2, 50%); the handrails of stairs (1/7, 14%); and the passenger side desk and divider glass at a passport control point (1/3, 33%). Among the 10 respiratory virus findings at various sites, the viruses identified were: rhinovirus (4/10, 40%, from surfaces); coronavirus (3/10, 30%, from surfaces); adenovirus (2/10, 20%, 1 air sample, 1 surface sample); influenza A (1/10, 10%, surface sample). CONCLUSIONS: Detection of pathogen viral nucleic acids indicates respiratory viral surface contamination at multiple sites associated with high touch rates, and suggests a potential risk in the identified airport sites. Of the surfaces tested, plastic security screening trays appeared to pose the highest potential risk, and handling these is almost inevitable for all embarking passengers.


title: Epidemiology of respiratory infections among adults in Qatar (2012-2017)

text: BACKGROUND: Limited data is available about the etiology of influenza like illnesses (ILIs) in Qatar. OBJECTIVES: This study aimed at providing preliminary estimates of influenza and other respiratory infections circulating among adults in Qatar. METHODS: We retrospectively collected data of about 44,000 patients who visited Hamad General Hospital clinics, sentinel sites, and all primary healthcare centers in Qatar between 2012 and 2017. All samples were tested for influenza viruses, whereas about 38,000 samples were tested for influenza and a panel of respiratory viruses using Fast Track Diagnostics (FTD) RT-PCR kit. RESULTS: Among all ILIs cases, 20,278 (46.5%) tested positive for at least one respiratory pathogen. Influenza virus was predominating (22.6%), followed by human rhinoviruses (HRVs) (9.5%), and human coronaviruses (HCoVs) (5%). A detection rate of 2–3% was recorded for mycoplasma pneumonia, adenoviruses, human parainfluenza viruses (HPIVs), respiratory syncytial virus (RSV), and human metapneumovirus (HMPV). ILIs cases were reported throughout the year, however, influenza, RSV, and HMPV exhibited strong seasonal peaks in the winter, while HRVs circulated more during fall and spring. Elderly (>50 years) had the lowest rates of influenza A (13.9%) and B (4.2%), while presenting the highest rates of RSV (3.4%) and HMPV (3.3%). While males had higher rates of HRVs (11.9%), enteroviruses (1.1%) and MERS CoV (0.2%), females had higher proportions of influenza (26.3%), HPIVs (3.2%) and RSV (3.6%) infections. CONCLUSION: This report provides a comprehensive insight about the epidemiology of ILIs among adults in the Qatar, as a representative of Gulf States. These results would help in improvement and optimization of diagnostic procedures, as well as control and prevention of the respiratory infections.


title: Development of Mouse Hepatitis Virus and SARS-CoV Infectious cDNA Constructs

text: The genomes of transmissible gastroenteritis virus (TGEV) and mouse hepatitis virus (MHV) have been generated with a novel construction strategy that allows for the assembly of very large RNA and DNA genomes from a panel of contiguous cDNA subclones. Recombinant viruses generated from these methods contained the appropriate marker mutations and replicated as efficiently as wild-type virus. The MHV cloning strategy can also be used to generate recombinant viruses that contain foreign genes or mutations at virtually any given nucleotide. MHV molecular viruses were engineered to express green fluorescent protein (GFP), demonstrating the feasibility of the systematic assembly approach to create recombinant viruses expressing foreign genes. The systematic assembly approach was used to develop an infectious clone of the newly identified human coronavirus, the serve acute respiratory syndrome virus (SARS-CoV). Our cloning and assembly strategy generated an infectious clone within 2 months of identification of the causative agent of SARS, providing a critical tool to study coronavirus pathogenesis and replication. The availability of coronavirus infectious cDNAs heralds a new era in coronavirus genetics and genomic applications, especially within the replicase proteins whose functions in replication and pathogenesis are virtually unknown.


title: Symptomatic Respiratory Virus Infection and Chronic Lung Allograft Dysfunction

text: Background. Chronic lung allograft dysfunction (CLAD) is a major cause of allograft loss post-lung transplantation. Prior studies have examined the association between respiratory virus infection (RVI) and CLAD were limited by older diagnostic techniques, study design, and case numbers. We examined the association between symptomatic RVI and CLAD using modern diagnostic techniques in a large contemporary cohort of lung transplant recipients (LTRs). Methods. We retrospectively assessed clinical variables including acute rejection, cytomegalovirus pneumonia, upper and lower RVI, and the primary endpoint of CLAD (determined by 2 independent reviewers) in 250 LTRs in a single university transplantation program. Univariate and multivariate Cox models were used to analyze the relationship between RVI and CLAD in a time-dependent manner, incorporating different periods of risk following RVI diagnosis. Results. Fifty patients (20%) were diagnosed with CLAD at a median of 95 weeks post-transplantation, and 79 (32%) had 114 episodes of RVI. In multivariate analysis, rejection and RVI were independently associated with CLAD (adjusted hazard ratio [95% confidence interval]) 2.2 (1.2–3.9), P = .01 and 1.9 (1.1–3.5), P = .03, respectively. The association of RVI with CLAD was stronger the more proximate the RVI episode: 4.8 (1.9–11.6), P < .01; 3.4 (1.5–7.5), P < .01; and 2.4 (1.2–5.0), P = .02 in multivariate analysis for 3, 6, and 12 months following RVI, respectively. Conclusions. Symptomatic RVI is independently associated with development of CLAD, with increased risk at shorter time periods following RVI. Prospective studies to characterize the virologic determinants of CLAD and define the underlying mechanisms are warranted.


title: WHO should declare climate change a public health emergency

text: Rapid and potentially irreversible climate change poses a direct threat to global public health. Andrew Harmer and colleagues argue that WHO should recognise this in the same way as global threats from specific diseases


title: Lymphopenia in COVID‐19: Therapeutic opportunities

text: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is uncontrollably spread all over the world. The host immune responses strongly try to confront it with all the potential cells and cytokines. With chronically condition of SARS‐CoV‐2, natural killer cells and T cells become exhausted and decreasing their count leads to lymphopenia. Inability to eradicate the infected organ makes hyperinitiation of the immune system, which releases the excessive inflammatory cytokines to compensate the exhausted one as well as the low lymphocytes counts; it consequently leads to the cytokine storm syndrome. These mechanisms and the potential therapeutic targeting are discussed in this paper.


title: COVID-19 and Generalized Myasthenia Gravis Exacerbation: A Case Report

text: • MG treatment in the context of COVID-19 should be tailored to the patient. • Patient’s respiratory status should be closely monitored. • Concomitant COVID-19 and MG has a variable response to treatment.