title: Avian Influenza Risk Perception, Hong Kong

text: A telephone survey of 986 Hong Kong households determined exposure and risk perception of avian influenza from live chicken sales. Householders bought 38,370,000 live chickens; 11% touched them when buying, generating 4,220,000 exposures annually; 36% (95% confidence interval [CI] 33%–39%) perceived this as risky, 9% (7%–11%) estimated >50% likelihood of resultant sickness, whereas 46% (43%–49%) said friends worried about such sickness. Recent China travel (adjusted odds ratio 0.35; CI 0.13–0.91), traditional beliefs (1.20, 1.06–1.13), willingness to change (0.29, 0.11–0.81) and believing cooking protects against avian influenza (8.66, 1.61-46.68) predicted buying. Birth in China (2.79, 1.43–5.44) or overseas (4.23, 1.43–12.53) and unemployment (3.87, 1.24–12.07) predicted touching. Age, avian influenza contagion worries, husbandry threat, avian influenza threat, and avian influenza anxiety predicted perceived sickness risk. High population exposures to live chickens and low perceived risk are potentially important health threats in avian influenza.


title: Environmental factors, immune changes and respiratory diseases in troops during military activities

text: Abstract Combat operations in contemporary theaters of war, as well as combat training, are carried out in all parts of the world, typically in a harsh environment. Specific environmental conditions, such as heat, cold, high-altitudes, desert climates, as well as chemical and biological pollution of both the atmosphere and soil, together with over-exertion, food restrictions, sleep deprivation, and psychological stress can all result in changes in the immune system and the occurrence of associated diseases. Respiratory diseases are one of the most common health problems among military personnel participating in combat training or deployed to operations in areas characterized by difficult climatic and sanitary conditions. They are, therefore, one of the main reasons for military personnel requiring ambulant and hospital treatment. The aim of the study was to discuss the influence of environmental factors and the conditions in which active duty is performed on changes in the immune system and the occurrence of respiratory tract diseases in a military environment.


title: The role of risk perception in willingness to respond to the 2014–2016 West African Ebola outbreak: a qualitative study of international health care workers.

text: BACKGROUND: The 2014–2016 West Africa Ebola Virus Disease (EVD) outbreak was an unprecedented public health event, and in addition to claiming over 11,000 lives, it resulted in the deaths of more healthcare workers than any outbreak in recent history. While a cadre of willing and able health workers is essential for an effective epidemic response, health workforce capacity in times of crisis may be significantly impacted by how risks are perceived by health staff. This study aimed to explore how risk perceptions influenced healthcare workers’ willingness to respond during this outbreak. METHODS: Through in-depth interviews with 11 front-line international health care workers who chose to respond to the West Africa outbreak, this qualitative study explores how perceptions of risk developed and subsequently mediated the decision to respond to the outbreak. Data was thematically organized using NVivo 10. RESULTS: We found that numerous individual and social-level factors played a role in modifying risk perception in health workers. Institutional trust emerged as a key risk attenuator, as did past experience, self-efficacy, duty of care, humanitarian ethos, and cognitive heuristics. Feelings of risk were amplified by infections of co-workers, and risk perceptions of family members and the public, which were mainly informed by media reports, also hampered willingness to respond in some cases. CONCLUSIONS: Understanding the risk perceptions of health workers, institutions, and the public, while complex and interdependent, are each crucial to understand for an effective public health response to epidemics, and as such should be taken into consideration in future program planning and research.


title: Calf-Level Factors Associated with Bovine Neonatal Pancytopenia – A Multi-Country Case-Control Study

text: Bovine neonatal pancytopenia (BNP), a high fatality condition causing haemorrhages in calves aged less than 4 weeks, was first reported in 2007 in Germany and subsequently observed at low incidence in other European countries and New Zealand. A multi-country matched case-control study was conducted in 2011 to identify calf-level risk factors for BNP. 405 BNP cases were recruited from 330 farms in Belgium, France, Germany and the Netherlands by laboratory confirmation of farmer-reported cases. Up to four calves of similar age from the same farm were selected as controls (1154 calves). Risk factor data were collected by questionnaire. Multivariable modelling using conditional logistic regression indicated that PregSure®BVD (PregSure, Pfizer Animal Health) vaccination of the dam was strongly associated with BNP cases (adjusted matched Odds Ratio - amOR 17.8 first lactation dams; 95% confidence interval – ci 2.4, 134.4; p = 0.005), and second or more lactation PregSure-vaccinated dams were more likely to have a case than first lactation vaccinated dams (amOR 2.2 second lactation; ci 1.1, 4.3; p = 0.024; amOR 5.3 third or more lactation; ci 2.9, 9.8; p = <0.001). Feeding colostrum from other cows was strongly associated with BNP if the dam was not PregSure-vaccinated (amOR 30.5; ci 2.1, 440.5; p = 0.012), but the effect was less if the dam was PregSure-vaccinated (amOR 2.1; ci 1.1, 4.0; p = 0.024). Feeding exclusively dam’s milk was a higher risk than other types of milk (amOR 3.4; ci 1.6, 7.5; p = 0.002). The population attributable fractions were 0.84 (ci 0.68, 0.92) for PregSure vaccination, 0.13 (ci 0.06, 0.19) for feeding other cows’ colostrum, and 0.15 (ci 0.08, 0.22) for feeding dam’s milk. No other calf-level factors were identified, suggesting that there are other important factors that are outside the scope of this study, such as genetics, which explain why BNP develops in some PregSure-colostrum-exposed calves but not in others.


title: Mental Health Outcomes Among Frontline and Second-Line Health Care Workers During the Coronavirus Disease 2019 (COVID-19) Pandemic in Italy

text: This cross-sectional study reports on symptoms of posttraumatic stress disorder, depression, anxiety, and insomnia among health care workers in Italy during the coronavirus disease 2019 (COVID-19) pandemic.


Androgenetic Alopecia Present in the Majority of Hospitalized COVID-19 Patients – the “Gabrin sign”


title: Knowledge and practices of primary health care physicians regarding updated guidelines of MERS-CoV infection in Abha city

text: BACKGROUND: Human coronaviruses (hCoV) usually cause mild to moderate upper respiratory tract illnesses. The novel coronavirus (nCoV), or Middle East respiratory syndrome coronavirus (MERS-CoV), is a particular strain different from any other known hCoV with the possibility of human and also zoonotic transmissions. The aim of the study to assess primary health care (PHC) physicians’ knowledge and adherence regarding Saudi Ministry of Health guidelines regarding MERS-CoV. MATERIALS AND METHODS: A cross-sectional study design was followed to include 85 PHC physicians in Abha city. An interview questionnaire has been designed by the researcher that was used to assess knowledge and practices of PHC physicians regarding diagnosis and management of MERS-CoV. It includes personal characteristics, the MERS-CoV knowledge assessment questionnaire, and practices related to adherence toward guidelines regarding MERS-CoV. RESULTS: PHC physicians’ knowledge gaps regarding MERS-CoV included protected exposure (32.9%), highest seasonal incidence of MERS-CoV in Saudi Arabia (60%), relation between incidence of MERS-CoV and overcrowding (62.4%), case fatality of MERS-CoV cases (63.5%), and collecting specimens from MERS-CoV patients (64.7%). The knowledge of PHC physicians about MERS-CoV was poor among 5.9%, good among 63.5%, and excellent among 30.6%. Personal protective equipment to be used when seeing suspected cases of MERS-CoV infection were mainly the mask (94.1%), gloves (78.8%), the gown (60%), goggles (31.8%), and the cap (22.4%). All participants stated that the most important standard precaution that should be applied when seeing a case of MERS-CoV infection is hand washing, whereas 97.6% stated that the most important respiratory precaution to prevent transmission of respiratory infections in PHC setting when seeing a case of MERS-CoV infection is masking and separation of suspected MERS-CoV patients, and 81.2% stated that upon exit from the room of a MERS-CoV patient, the physician should remove and discard personal protective equipment. PHC physicians’ knowledge about MERS-CoV differed significantly according to their nationality (P = 0.038), with non-Saudi physicians expressing higher percent of excellent knowledge than Saudi physicians (40% and 20%, respectively). Those who attended continuing medical education (CME) activities had significantly higher percent of excellent knowledge than those who did not attend a CME activity (55.6% and 23.9%, respectively, P = 0.011). PHC physicians’ knowledge did not differ significantly according to their age, gender, qualification, experience in PHC, and practice-related adherence to guidelines. PHC physicians’ practice-related adherence to guidelines about MERS-CoV differed significantly according to their position (P = 0.035), with specialists having the highest percent of excellent practice (13%). CONCLUSIONS: There are knowledge gaps among PHC physicians in Abha city, and their practice is suboptimal regarding MERS-CoV infection. Less than one-fourth of PHC physicians attend CME activities about MERS-CoV infection. However, significantly less practice-related adherence to guidelines are associated with Saudi PHC physicians, those who did not attend a related CME activity, and MBBS qualified physicians’ general practitioners. To increase awareness, more CME activities related to MERS-CoV infection management needs to be organized.


Letter to the Editor—Behavioral Health Implications of Inmate Release During COVID‐19


title: COVID-19 Pandemic Shifts Inpatient Imaging Utilization

text: The results from this study provide real-world data to inform Radiology practices regarding not only the decline in inpatient imaging volumes, but more importantly the significant shift in the imaging composition mix during the COVID-19 pandemic.


title: Multiplex cytokine profiling with highly pathogenic material: Use of formalin solution in luminex analysis

text: Abstract Work with highly pathogenic material mandates the use of biological containment facilities, involving microbiological safety cabinets and specialist laboratory engineering structures typified by containment level 3 (CL3) and CL4 laboratories. Consequences of working in high containment are the practical difficulties associated with containing specialist assays and equipment often essential for experimental analyses. In an era of increased interest in biodefence pathogens and emerging diseases, immunological analysis has developed rapidly alongside traditional techniques in virology and molecular biology. For example, in order to maximise the use of small sample volumes, multiplexing has become a more popular and widespread approach to quantify multiple analytes simultaneously, such as cytokines and chemokines. The luminex microsphere system allows for the detection of many cytokines and chemokines in a single sample, but the detection method of using aligned lasers and fluidics means that samples often have to be analysed in low containment facilities. In order to perform cytokine analysis in materials from high containment (CL3 and CL4 laboratories), we have developed an appropriate inactivation methodology after staining steps, which although results in a reduction of median fluorescent intensity, produces statistically comparable outcomes when judged against non-inactivated samples. This methodology thus extends the use of luminex technology for material that contains highly pathogenic biological agents.


title: Epidemiology and etiology of community-acquired pneumonia

text: The seriousness of community-acquired pneumonia (CAP), despite being a reasonably common and potentially lethal disease, often is under estimated by physicians and patients alike. CAP results in more than 10 million visits to physicians, 64 million days of restricted activity, and 600,000 hospitalizations. This article discusses the epidemiology and bacterial causes of CAP in immunocompetent adults and the severe acute respiratory syndrome coronavirus.


title: Acute life threatening event (ALTE) in an infant with human coronavirus HCoV‐229E infection

text: In this short report we discuss the temporal association between an acute life threatening event (ALTE) and a RT‐PCR confirmed coronavirus HCoV‐229E infection in a 4 months old otherwise healthy infant. More detailed microbiological investigations of affected children even without apparent signs of a respiratory tract infection may help to clarify the etiology in some patients and extend our understanding of the pathogenesis. PCR‐based techniques should be utilized to increase the sensitivity of detection for old and new respiratory viral pathogens in comparable cases. Pediatr Pulmonol. 2007; 42:393–396. © 2007 Wiley‐Liss, Inc.


title: Viral Etiology of acute respiratory tract infections in hospitalized children and adults in Shandong Province, China

text: BACKGROUND: The dominant viral etiologies responsible for acute respiratory infections (ARIs) are poorly understood, particularly among hospitalized patients. Improved etiological insight is needed to improve clinical management and prevention of ARIs. METHODS: Clinical and demographic information and throat swabs were collected from 607 patients from 2011 to 2013 in Shandong Province, China. Multiplex RT-PCR (SeeplexTM RV detection, Seegene) was performed to detected 12 respiratory viral pathogens. RESULTS: A total of 607 hospitalized patients were enrolled from 2011 to 2013. Viruses were identified in 35.75 % (217/607) of cases, including 78 influenza virus A and B (IVA and IVB), 47 para-influenza viruses (PIVs), 41 respiratory syncytial virus (RSV) and 38 adenovirus (ADV). For the children under 15 year old, the common detected viruses were influenza viruses, RSV, PIVS and ADV, while the principal respiratory viruses were human coronaviruses (HCoV), PIVs, influenza viruses for the old adults. Co-infections with multiple viruses were detected in 15.67 % of patients. Children under 5 years were more likely to have one or more detectable virus associated with their ARI. The peak of ARI caused by the respiratory viruses occurred in winter. CONCLUSION: This study demonstrated respiratory viruses were the major cause of hospitalized ARI patients in Shandong Province, influenza virus was the most common detected, RSV was the highest incidence among the young children (≤5 years). These findings also gave a better understand of virus distribution among different age and seasons, which help to consider potential therapeutic approaches and develop effective prevention strategies for respiratory virus infection.


title: Intracranial Administration of P Gene siRNA Protects Mice from Lethal Chandipura Virus Encephalitis

text: BACKGROUND: In parts of India, Chandipura Virus (CHPV) has emerged as an encephalitis causing pathogen in both epidemic and sporadic forms. This pediatric disease follows rapid course leading to 55–75% mortality. In the absence of specific treatment, effectiveness of RNA interference (RNAi) was evaluated. METHODS AND FINDINGS: Efficacy of synthetic short interfering RNA (siRNA) or short hairpin RNA (shRNA) in protecting mice from CHPV infection was assessed. The target genes were P and M genes primarily because important role of the former in viral replication and lethal nature of the latter. Real time one step RT-PCR and plaque assay were used for the assessment of gene silencing. Using pAcGFP1N1-CHPV-P, we showed that P-2 siRNA was most efficient in reducing the expression of P gene in-vitro. Both quantitative assays documented 2logs reduction in the virus titer when P-2, M-5 or M-6 siRNAs were transfected 2hr post infection (PI). Use of these siRNAs in combination did not result in enhanced efficiency. P-2 siRNA was found to tolerate four mismatches in the center. As compared to five different shRNAs, P-2 siRNA was most effective in inhibiting CHPV replication. An extended survival was noted when mice infected intracranially with 100 LD(50) CHPV were treated with cationic lipid complexed 5 µg P-2 siRNA simultaneously. Infection with 10LD(50) and treatment with two doses of siRNA first, simultaneously and second 24 hr PI, resulted in 70% survival. Surviving mice showed 4logs less CHPV titers in brain without histopathological changes or antibody response. Gene expression profiles of P-2 siRNA treated mice showed no interferon response. First dose of siRNA at 2hr or 4hr PI with second dose at 24hr resulted in 40% and 20% survival respectively suggesting potential application in therapy. CONCLUSIONS: The results highlight therapeutic potential of siRNA in treating rapid and fatal Chandipura encephalitis.


title: Human mastadenovirus-B (HAdV-B)-specific E3-CR1β and E3-CR1γ glycoproteins interact with each other and localize at the plasma membrane of non-polarized airway epithelial cells

text: Abstract The E3 region of all simian and human types classified within species Human mastadenovirus B (HAdV-B) encodes two unique highly conserved ORFs of unknown function designated E3-CR1β and E3-CR1γ. We generated a HAdV-3 mutant encoding small epitope tags at the N-termini of both E3-CR1β and E3-CR1γ (HAdV-3 N-tag wt) and a double knock out (HAdV-3 N-tag DKO) mutant virus that does not express either protein. Our studies show that HAdV-3 E3-CR1β and E3-CR1γ are type I transmembrane proteins that are produced predominantly at late times post infection, are glycosylated, co-localize at the plasma membrane of non-polarized epithelial cells, and interact with each other. At their extreme C-termini HAdV-B E3-CR1β and E3-CR1γ possess a conserved di-leucine motif followed by a class II PDZ domain binding motif (PBM). HAdV-3 E3-CR1β and E3-CR1γ are dispensable for virus growth, progeny release, spread, and plaque formation in A549 cells.


title: Recombinant adenovirus carrying a core neutralizing epitope of porcine epidemic diarrhea virus and heat-labile enterotoxin B of Escherichia coli as a mucosal vaccine

text: Porcine epidemic diarrhea virus (PEDV) targets the intestinal mucosa in pigs. To protect against PEDV invasion, a mucosal vaccine is utilized effectively. In this study, we generated a recombinant adenovirus vaccine encoding the heat-labile enterotoxin B (LTB) and the core neutralizing epitope (COE) of PEDV (rAd-LTB-COE). The fusion protein LTB-COE was successfully expressed by the recombinant adenovirus in HEK293 cells, and the immunogenicity of the vaccine candidate was assessed in BALB/c mice and piglets. Three intramuscular or oral vaccinations with rAd-LTB-COE at two-week intervals induced robust humoral and mucosal immune responses. Moreover, a cell-mediated immune response was promoted in immunized mice, and the neutralizing antibody inhibited both the vaccine strain and the emerging PEDV isolate. Immunization experiments in piglets revealed that rAd-LTB-COE was immunogenic and induced good immune responses in piglets. Further studies are required to evaluate the efficacy of rAd-LTB-COE against a highly virulent PEDV challenge.


title: Do Paramedics Have a Professional Obligation to Work During a Pandemic? A Qualitative Exploration of Community Member Expectations

text: OBJECTIVES: Previous research has identified a lack of clarification regarding paramedic professional obligation to work. Understanding community expectations of paramedics will provide some clarity around this issue. The objective of this research was to explore the expectations of a sample of Australian community members regarding the professional obligation of paramedics to respond during pandemics. METHODS: The authors used qualitative methods to gather Australian community member perspectives immediately before the onset of the coronavirus disease 2019 (COVID-19) pandemic. Focus groups were used for data collection, and a thematic analysis was conducted. RESULTS: The findings revealed 9 key themes: context of obligation (normal operations versus crisis situation), hierarchy of obligation (individual versus organizational obligation), risk acceptability, acceptable occupational risk (it’s part of the job), access to personal protective equipment, legal and ethical guidelines, education and training, safety, and acceptable limitations to obligation. The factors identified as being acceptable limitations to professional obligation are presented as further sub-themes: physical health, mental health, and competing personal obligations. CONCLUSIONS: The issue of professional obligation must be addressed by ambulance services as a matter of urgency, especially in light of the COVID-19 coronavirus pandemic. Further research is recommended to understand how community member expectations evolve during and after the COVID-19 coronavirus pandemic.


title: The role of infection in the aetiology of inflammatory bowel disease

text: We have greatly increased our understanding of the genetics of inflammatory bowel disease (IBD) in the last decade; however, migrant studies highlight the importance of environment in disease risk. The possibility that IBD is an infection has been debated since the first description of Crohn’s disease. Mycobacterium avium paratuberculosis was the first organism to be suggested as an IBD pathogen, and it has been argued that it fulfils Koch’s postulates and could be designated the cause of Crohn’s disease. Other organisms have been postulated as possible IBD pathogens, including various Helicobacter species, one of which has been identified in primate colitis; others are widely used in animal models of IBD. Adherent-invasive Escherichia coli appear specific to ileal Crohn’s disease and have been shown to induce the release of TNF-α, a key cytokine in IBD inflammation. The aim of this article is to give a concise overview of the infections postulated as being relevant to the onset of IBD. We will also briefly cover the immunology underpinning IBD, in addition to reviewing current knowledge regarding other microorganisms that are associated with modifying the risk of developing IBD. It may be that infectious organisms have an orchestrator role in the development of dysbiosis and subsequently IBD.


title: Cutaneous lesions in a patient with COVID‐19: are they related?

text: A previously healthy 57‐year‐old woman presented with fever (39 °C) lasting for 4 days, and dry cough and rash appeared 2 days before. Diffuse fixed erythematous blanching maculopapular lesions were present, asymptomatic over the limbs and trunk, with burning sensation over the palms (a, b). She denied any drug intake, excepting paracetamol for fever. Thorax computed tomography scan was typical of COVID‐19; nasopharyngeal swab polymerase chain reaction (PCR) confirmed SARS‐CoV‐2. Infectious enquiry was otherwise negative. Skin biopsy specimen showed slight spongiosis, basal cell vacuolation and mild perivascular lymphocytic infiltrate (c).


title: Returning to Clinics Amidst COVID‐19: A Student Response to Compton et al

text: As U.K based medical students, we read with great interest the article by Compton et al (1) exploring the various factors influencing students’ motivation to return to clinical practice amidst the ongoing COVID‐19 pandemic. Despite the study exploring several convincing factors in explaining the hesitance of medical students in returning to clinical placement, social vulnerability is often overlooked when explaining this reluctance. Many black and minority ethnic (BME) groups, who experience higher rates of mortality and live in multi‐generational households, may risk the health of their own family members by returning to placement prematurely, or without adequate protection.


title: Personal Protective Equipment (PPE) for Surgeons during COVID‐19 Pandemic: A Systematic Review of Availability, Usage, and Rationing

text: BACKGROUND: Surgeons need guidance regarding appropriate personal protective equipment (PPE) during the COVID‐19 pandemic based on scientific evidence rather than availability. The aim of this paper is to inform surgeons of appropriate PPE requirements, and to discuss usage, availability, rationing and future solutions. METHODS: A systematic review was undertaken in accordance with the PRISMA guidelines using the MEDLINE, EMBASE, & WHO COVID‐19 Databases. Newspaper and internet article sources were identified using NEXIS. The search was complemented by bibliographic secondary linkage. The findings were analysed alongside guidelines from the World Health Organisation (WHO), Public Health England (PHE), the Royal College of Surgeons & Specialty Associations. RESULTS: Of a total 1329 articles identified, 305 were removed (duplicates etc), and finally, 95 studies met the inclusion criteria. Recommendations made by the WHO regarding the use of PPE in the COVID‐19 pandemic have evolved alongside emerging evidence. Medical resources including PPE have been rapidly overwhelmed. There is a global effort to overcome this by combining the most effective use of existing PPE in combination with innovative strategies to produce more. Practical advice on all aspects of PPE are detailed in this systematic review. CONCLUSION: Although there is a need to balance limited supplies with staff and patient safety, this should not leave surgeons treating patients with inadequate PPE. This article is protected by copyright. All rights reserved.


title: Influenza, respiratory syncytial virus and SARS

text: Abstract Acute lower respiratory tract infections (LRTIs) are a major worldwide health problem, particularly in childhood. About 30–50% of acute LRTIs are viral in origin; of these, influenza and respiratory syncytial virus are associated with the greatest disease burden in humans. Many different influenza A viruses occur naturally in animal reservoirs, and present a constant threat of zoonotic infections and global pandemics. The pandemic (H1N1) influenza virus that emerged in humans in 2009 contained a unique combination of genes originating in swine and the global human population was highly susceptible to the novel strain. The emergence of the severe acute respiratory syndrome coronavirus in 2003, and the ensuing worldwide epidemic, highlights the fact that respiratory viral infections in humans may originate in animals. Preventative measures for influenza include annual vaccination and treatment with antiviral drugs such as the neuraminidase inhibitors oseltamivir and zanamivir. Subtype-dependent resistance to antivirals can develop and should be closely monitored.


title: Does virus–bacteria coinfection increase the clinical severity of acute respiratory infection?

text: This retrospective cohort study investigated the presence of bacteria in respiratory secretions of patients hospitalized with acute respiratory infections and analyzed the impact of viral and bacterial coinfection on severity and the mortality rate. A total of 169 patients with acute respiratory infections were included, viruses and bacteria in respiratory samples were detected using molecular methods. Among all samples, 73.3% and 59.7% were positive for viruses and bacteria, respectively; 45% contained both virus and bacteria. Bacterial coinfection was more frequent in patients infected by community respiratory viruses than influenza A H1N1pdm (83.3% vs. 40.6%). The most frequently bacteria detected were Streptococcus pneumoniae and Haemophilus influenzae. Both species were co‐detected in 54 patients and identified alone in 22 and 21 patients, respectively. Overall, there were no significant differences in the period of hospitalization, severity, or mortality rate between patients infected with respiratory viruses alone and those coinfected by viruses and bacteria. The detection of mixed respiratory pathogens is frequent in hospitalized patients with acute respiratory infections, but its impact on the clinical outcome does not appear substantial. However, it should be noted that most of the patients received broad‐spectrum antibiotic therapy, which may have contributed to this favorable outcome. J. Med. Virol. 87:1456–1461, 2015. © 2015 Wiley Periodicals, Inc.


title: Erythema multiforme‐like eruption in patients with COVID‐19 infection: clinical and histological findings

text: Cutaneous manifestations in patients with COVID‐19 infection are being increasingly reported. Several patterns have been described since the initial report by Recalcati,(1) including erythematous maculo‐papular,(1) urticarial,(1,2) chickenpox‐like,(1,3) purpuric peri‐flexural,(4) transient livedo reticularis,(5) and acro‐ischemic or chilblain‐like lesions.(6,7) Herein we report the observation a new pattern with erythema multiforme‐like lesions in 4 hospitalized patients with COVID‐19 infection. All of them were women, and the mean age was 66.75 years (range 58 – 77). The mean time period between the onset of COVID‐19 symptoms to the appearance of cutaneous lesions was 19.5 days (range 16 – 24). One patient developed the skin rash during hospitalization. The remaining 3 patients had been previously discharged after clinical, analytical and radiologic improvement, and negativization of COVID‐19 PCR test. These 3 patients returned to the Emergency department consulting for skin rashes 6, 7 and 4 days after discharge, respectively. Laboratory tests at the time of skin lesions showed worsening of one or more parameters, compared to those at the time of discharge (CRP, D‐dimer and lymphocyte count). However, none of the patients presented recurrence of clinical symptoms of COVID‐19. Microbiological studies were performed in 2 patients, excluding other infectious diseases (Table 1). In all patients, skin lesions begun as erythematous papules in upper trunk, that progressively turned to erythemato‐violaceous patches with a dusky center, and a pseudo‐vesicle in the middle. Typical target lesions were observed in two patients. Lesions were markedly coalescing in the back, and then spread to the face and limbs within 1 week, without involvement of palms and soles (Figure 1). Three patient had their oral cavity examined, showing palatal macules and petechiae. Histological examination was similar in all patients, revealing a normal basket‐weave stratum corneum, and mild to moderate spongiosis in epidermis. The dermis showed dilated vessels filled with neutrophils, extravasation of red blood cells, and lymphocytic perivascular and interstitial infiltrate. Basal vacuolar changes with interface dermatitis was observed in 1 patient, and lymphocytic exocytosis in another (Figure 2). All patients were treated with systemic corticosteroids with progressive resolution of the skin lesions within 2‐3 weeks. We are facing challenging times in Dermatology. New information and cutaneous manifestations possibly related to COVID‐19 are emerging every day. Further studies are needed to evaluate whether these lesions are associated with the virus, the drug intake or any other conditions. Erythema multiforme (EM) is linked to infectious agents in 90% of the cases, while drug‐associated EM is reported in less than 10% of cases. Herpes simplex virus (HSV) and Mycoplasma pneumoniae are the main agents, but other viruses have been reported, such as Adenovirus, Coxsackie, Parvovirus B19.(8) We suggest that this EM‐like or target‐like exanthem might be another pattern of exanthem associated with COVID‐19 infection. Recent articles also report targetoid lesions in exanthems of patients with COVID‐19 infection.(9,10) In addition, the presence of pseudo‐vesicles and enanthem are two clues that suggest an infectious cause rather than a drug reaction. However, we cannot positively exclude the involvement of the various drugs administered to the patients. This is a first observation that will require further investigations.


title: COVID-19 infection can cause chemotherapy resistance development in patients with breast cancer and tamoxifen may cause susceptibility to COVID-19 infection

text: Breast cancer is the most common cancer in women and is the second most common cause of death in women. Estrogen plays an important role in breast tumor etiopathogenesis. Tamoxifen and other anti-estrogen drugs are used in breast cancer patients who have a positive estrogen receptor (ER). While angiotensin II plays a key role in breast cancer etiology and causes tamoxifen resistance, angiotensin 1–7 has been reported to may reduce the spread and invasion of breast cancer. During the COVID-19 infection, the virus blocks ACE2, and angiotensin 1–7 production discontinued. Angiotensin III production may increase as angiotensin II destruction is reduced. Thus, aminopeptidase upregulation may occur. Increased aminopeptidase may develop resistance to chemotherapy in breast cancer patients receiving chemotherapy. Estrogen can have a protective effect against COVID-19. Estrogen increase causes ER-α upregulation in T lymphocytes. Thus, estrogen increases the release of interferon I and III from T lymphocytes. Increasing interferon I and III alleviates COVID-19 infection. Tamoxifen treatment causes down-regulation, mutation, or loss in estrogen receptors. In the long-term use of tamoxifen, its effects on estrogen receptors can be permanent. Thus, since estrogen receptors are damaged or downregulated, estrogen may not act by binding to these receptors. Tamoxifen is a P-glycoprotein inhibitor, independent of its effect on estrogen receptors. It suppresses T cell functions and interferon release. We think tamoxifen may increase the COVID-19 risk due to its antiestrogen and P-glycoprotein inhibitory effects.


title: Phosphoantigen-Expanded Human γδ T Cells Display Potent Cytotoxicity against Monocyte-Derived Macrophages Infected with Human and Avian Influenza Viruses

text: BackgroundInfluenza virus is a cause of substantial annual morbidity and mortality worldwide. The potential emergence of a new pandemic strain (eg, avian influenza virus) is a major concern. Currently available vaccines and anti-influenza drugs have limited effectiveness for influenza virus infections, especially for new pandemic strains. Therefore, there is an acute need to develop alternative strategies for influenza therapy. γδ T cells have potent antiviral activities against different viruses, but no data are available concerning their antiviral activity against influenza viruses MethodsIn this study, we used virus-infected primary human monocyte-derived macrophages (MDMs) to examine the antiviral activity of phosphoantigen isopentenyl pyrophosphate (IPP)–expanded human Vγ9Vδ2 T cells against influenza viruses ResultsVγ9Vδ2 T cells were selectively activated and expanded by IPP from peripheral blood mononuclear cells. IPP-expanded Vγ9Vδ2 T cells efficiently killed MDMs infected with human (H1N1) or avian (H9N2 or H5N1) influenza virus and significantly inhibited viral replication. The cytotoxicity of Vγ9Vδ2 T cells against influenza virus–infected MDMs was dependent on NKG2D activation and was mediated by Fas–Fas ligand and perforin–granzyme B pathways ConclusionOur findings suggest a potentially novel therapeutic approach to seasonal, zoonotic avian, and pandemic influenza—the use of phosphoantigens to activate γδ T cells against influenza virus infections


title: Sources and symptoms of stress among nurses in the first Chinese anti-Ebola medical team during the Sierra Leone aid mission: A qualitative study

text: OBJECTIVE: This study investigated the sources of stress, corresponding symptoms, and stress relief among nurses of the first Chinese anti-Ebola medical team during the Sierra Leone aid mission. METHOD: A purposive sampling method was used and 10 nurses were selected from the first Chinese anti-Ebola medical team that was dispatched to Sierra Leone. Data were collected via phone and semi-structured interviews, then analyzed using Colaizzi's seven-step method. RESULTS: The data showed three major themes: (1) The causes of stress during the Sierra Leone aid mission mainly related to unsafety, responsibility, and unfamiliarity; (2) Physical, cognitive, emotional, and behavioral symptoms were documented; (3) Nurses experienced relief from stress after the mission. CONCLUSION: Targeted measures, proper responses and good community support can effectively lower stress among nurses on anti-Ebola missions.


title: Viral Shedding and Antibody Response in 37 Patients With Middle East Respiratory Syndrome Coronavirus Infection

text: Background. The Middle East respiratory syndrome (MERS) coronavirus causes isolated cases and outbreaks of severe respiratory disease. Essential features of the natural history of disease are poorly understood. Methods. We studied 37 adult patients infected with MERS coronavirus for viral load in the lower and upper respiratory tracts (LRT and URT, respectively), blood, stool, and urine. Antibodies and serum neutralizing activities were determined over the course of disease. Results. One hundred ninety-nine LRT samples collected during the 3 weeks following diagnosis yielded virus RNA in 93% of tests. Average (maximum) viral loads were 5 × 10(6) (6 × 10(10)) copies/mL. Viral loads (positive detection frequencies) in 84 URT samples were 1.9 × 10(4) copies/mL (47.6%). Thirty-three percent of all 108 serum samples tested yielded viral RNA. Only 14.6% of stool and 2.4% of urine samples yielded viral RNA. All seroconversions occurred during the first 2 weeks after diagnosis, which corresponds to the second and third week after symptom onset. Immunoglobulin M detection provided no advantage in sensitivity over immunoglobulin G (IgG) detection. All surviving patients, but only slightly more than half of all fatal cases, produced IgG and neutralizing antibodies. The levels of IgG and neutralizing antibodies were weakly and inversely correlated with LRT viral loads. Presence of antibodies did not lead to the elimination of virus from LRT. Conclusions. The timing and intensity of respiratory viral shedding in patients with MERS closely matches that of those with severe acute respiratory syndrome. Blood viral RNA does not seem to be infectious. Extrapulmonary loci of virus replication seem possible. Neutralizing antibodies do not suffice to clear the infection.


title: The Spectrum of Non-asthmatic Airway Diseases Contributing to Cough in the Adult

text: PURPOSE OF REVIEW: Cough becomes a pathologic reflex when the airways are inflamed and overwhelmed with excessive mucus. The goal of this review is to discuss acute and chronic cough syndromes caused by non-asthmatic airway diseases. RECENT FINDINGS: Acute cough syndrome is short-lived and self-limited. Acute bronchitis and diffuse acute infectious bronchiolitis (DAIB) are examples. The former is usually caused by a viral illness; the latter by Mycoplasma pneumoniae, influenza, and Haemophilus influenzae. Causes of chronic cough in the adult include chronic bronchitis, non-infectious bronchiolitis, and non-cystic fibrosis bronchiectasis. SUMMARY: Supportive measures are recommended for acute bronchitis and antibiotic use is discouraged. Antibiotics may be needed for DAIB. Smoking cessation and bronchodilators can control cough in chronic bronchitis. Therapeutic approaches for non-infectious bronchiolitis depend on the varied etiology. The hallmark of bronchiectasis is a chronic infection of the airways, and antibiotics, mucus clearance measures, and bronchodilators are all supportive.


title: Searching immunodominant epitopes prior to epidemic: HLA class II-restricted SARS-CoV spike protein epitopes in unexposed individuals

text: Identification of dominant T cell epitopes within newly emerging and re-emerging infectious organisms is valuable in understanding pathogenic immune responses and potential vaccine designs. However, difficulties in obtaining samples from patients or convalescent subjects have hampered research in this direction. We demonstrated a strategy, tetramer-guided epitope mapping, that specific CD4+ T cell epitopes can be identified by using PBMC from subjects that have not been exposed to the infectious organism. Sixteen HLA-DR0401- and 14 HLA-DR0701-restricted epitopes within spike protein of severe acute respiratory syndrome-coronavirus (SARS-CoV) were identified. Among these, spike protein residues 159–171, 166–178, 449–461 and 1083–1097 were identified to contain naturally processed immunodominant epitopes based on strong in vitro T cell responses of PBMC (as assayed by tetramer staining) to intact spike protein stimulation. These immunodominant epitopes were confirmed in vivo in HLA-DR0401 transgenic mice by immunizing with spike protein. Furthermore, the epitope-specific T cells from naive donors secreted IFN-γ and IL-13 upon re-stimulation with corresponding tetramers. Our study demonstrates a strategy to determine potential immunodominant epitopes for emerging infectious pathogens prior to their epidemic circulation.


We need each other: Social supports during COVID 19


title: Molecular characterisation of a bovine-like rotavirus detected from a giraffe

text: BACKGROUND: Rotavirus (RV), is a member of the Reoviridae family and an important etiological agent of acute viral gastroenteritis in the young. Rotaviruses have a wide host range infecting a broad range of animal species, however little is known about rotavirus infection in exotic animals. In this paper we report the first characterisation of a RV strain from a giraffe calf. RESULTS: This report describes the identification and detailed molecular characterisation of a rotavirus strain detected from a 14-day-old Giraffe (Giraffa camelopardalis), presenting with acute diarrhea. The RV strain detected from the giraffe was characterized molecularly as G10P[11]. Detailed sequence analysis of VP4 and VP7 revealed significant identity at the amino acid sequence level to Bovine RV (BoRV). CONCLUSION: This study demonstrates the need for continuous surveillance of RV strains in various animal populations, which will facilitate the identification of rotavirus hosts not previously reported. Furthermore, extending typical epidemiology studies to a broader host range will contribute to the timely identification of new emerging strain types.


title: A Monoclonal Antibody-Based Copro-ELISA Kit for Canine Echinococcosis to Support the PAHO Effort for Hydatid Disease Control in South America

text: Cystic echinococcosis is still a major concern in South America. While some regions show advances in the control of the disease, others have among the highest incidence in the world. To reverse this situation the Pan American Health Organization (PAHO) has launched a regional project on cystic echinococcosis control and surveillance. An early concern of the program was the lack of a standardized diagnostic tool to monitor infection in dogs, a key target of control programs. Under this premise, we have developed a new copro-ELISA test after extensive screening of a large panel of monoclonal antibodies (MAbs) and polyclonal sera, which performs with high standards of sensitivity (92.6%) and specificity (86.4%) as established by necropsy diagnosis of dogs. The key component of the test, MAbEg9 has a convenient IgG isotype and reacts with a periodate-resistant epitope found in high molecular weight components of the worm. Time-course analysis of experimentally infected dogs showed that even animals with a very low number of parasites could be detected as early as day 20 post infection. The test was formulated in a ready-to-use kit format with proven stability of each component for a minimum of 3 months at room temperature. This characteristic facilitates its standardized use and shipping to other laboratories, which was demonstrated by the identical results obtained by two different laboratories in Peru and our own laboratory when a large number of field samples were analyzed independently in a blind fashion.


title: Is the COVID-19 pandemic masking dengue epidemic in Bangladesh?

text: COVID-19 is now a pandemic. Like other countries, Bangladesh is putting all its efforts to combat this pandemic. Dengue is a mosquito-borne viral infection causing a severe flu-like illness and, sometimes causing a potentially lethal complication called severe dengue. At this very crisis moment, there are reports on new cases of dengue in Bangladesh. More efforts now need to be taken for the control of dengue along with COVID-19 control measures.


title: Activation of the autophagy pathway by Torovirus infection is irrelevant for virus replication

text: Autophagy is a conserved eukaryotic process that mediates lysosomal degradation of cytoplasmic macromolecules and damaged organelles, also exerting an important role in the elimination of intracellular pathogens. Despite the antiviral role of autophagy, many studies suggest that some positive-stranded RNA viruses exploit this pathway to facilitate their own replication. In this study, we demonstrate that the equine torovirus Berne virus (BEV), the prototype member of the Torovirus genus (Coronaviridae Family, Nidovirales Order), induces autophagy at late times post-infection. Conversion of microtubule associated protein 1B light chain 3 (LC3) from cytosolic (LC3 I) to the membrane associated form (LC3 II), a canonical marker of autophagosome formation, is enhanced in BEV infected cells. However, neither autophagy induction, via starvation, nor pharmacological blockade significantly affect BEV replication. Similarly, BEV infection is not altered in autophagy deficient cells lacking either Beclin 1 or LC3B protein expression. Unexpectedly, the cargo receptor p62, a selective autophagy receptor, aggregates within the region where the BEV main protease (M(pro)) localizes. This finding, coupled with observation that BEV replication also induces ER stress at the time when selective autophagy is taking place, suggests that the autophagy pathway is activated in response to the hefty accumulation of virus-encoded polypeptides during the late phase of BEV infection.


title: IFNΛ3/4 locus polymorphisms and IFNΛ3 circulating levels are associated with COPD severity and outcomes

text: BACKGROUND: Interferon lambdas (IFNLs) have important anti-viral/bacterial and immunomodulatory functions in the respiratory tract. How do IFNLs impact COPD and its exacerbations? METHODS: Five hundred twenty eight patients were recruited in a prospective observational multicentre cohort (PROMISE) study. The genetic polymorphisms (rs8099917 and rs12979860) within the IFNL3/4 gene region and circulating levels of IFNL3 in COPD patients were determined and associated with disease activity and outcome during a median follow-up of 24 months. RESULTS: The GG genotype significantly influenced severe exacerbation rate (42 vs. 23%; p = 0.032) and time to severe exacerbation (HR = 2.260; p = 0.012). Compared to the TT or TG genotypes, the GG genotype was associated with severe dyspnoea (modified medical research council score ≥ median 3; 22 vs 42%, p = 0.030). The CC genotype of the rs12979860 SNP was associated with a poorer prognosis (body mass index, airflow obstruction, dyspnea and exercise capacity index ≥ median 4; 46 vs. 36% TC vs. 20.5% TT; p = 0.031). Patients with stable COPD and at exacerbation had significantly lower circulating IFNL3 compared to healthy controls (p < 0.001 and p < 0.001, respectively). Circulating IFNL3 correlated to post-bronchodilator FEV(1)%predicted and the tissue maturation biomarker Pro-collagen 3. CONCLUSION: IFNL3/4 polymorphisms and circulating IFNL3 may be associated with disease activity and outcomes in COPD. TRIAL REGISTRATION: Clinical Trial registration http://www.isrctn.com/ identifier ISRCTN99586989 on 16 April 2008.


title: A relative Lempel–Ziv complexity: Application to comparing biological sequences

text: Abstract One of the main tasks in biological sequence analysis is biological sequence comparison. Numerous efficient methods have been developed for sequence comparison. Traditional sequence comparison is based on sequence alignment. In this report, we propose a novel alignment-free method based on the relative Lempel–Ziv complexity to compare biological sequences. The vertebrate transferring genomes and the spike protein sequences are prepared and tested to evaluate the validity of the method. We use this method to build phylogenetic tree of two groups of the sequences. The result demonstrates that our method is powerful and efficient.


title: Bayesian Evaluation of Temporal Signal in Measurably Evolving Populations

text: Phylogenetic methods can use the sampling times of molecular sequence data to calibrate the molecular clock, enabling the estimation of evolutionary rates and timescales for rapidly evolving pathogens and data sets containing ancient DNA samples. A key aspect of such calibrations is whether a sufficient amount of molecular evolution has occurred over the sampling time window, that is, whether the data can be treated as having come from a measurably evolving population. Here we investigate the performance of a fully Bayesian evaluation of temporal signal (BETS) in sequence data. The method involves comparing the fit to the data of two models: a model in which the data are accompanied by the actual (heterochronous) sampling times, and a model in which the samples are constrained to be contemporaneous (isochronous). We conducted simulations under a wide range of conditions to demonstrate that BETS accurately classifies data sets according to whether they contain temporal signal or not, even when there is substantial among-lineage rate variation. We explore the behaviour of this classification in analyses of five empirical data sets: modern samples of A/H1N1 influenza virus, the bacterium Bordetella pertussis, coronaviruses from mammalian hosts, ancient DNA from Hepatitis B virus and mitochondrial genomes of dog species. Our results indicate that BETS is an effective alternative to other tests of temporal signal. In particular, this method has the key advantage of allowing a coherent assessment of the entire model, including the molecular clock and tree prior which are essential aspects of Bayesian phylodynamic analyses.


title: Smell and taste symptom‐based predictive model for COVID‐19 diagnosis

text: BACKGROUND: The presentation of COVID‐19 overlaps with common influenza symptoms. There is limited data on whether a specific symptom or collection of symptoms may be useful to predict test positivity. METHODS: An anonymous electronic survey was publicized through social media to query participants with COVID‐19 testing. Respondents were questioned regarding 10 presenting symptoms, demographic information, comorbidities and COVID‐19 test results. Stepwise logistic regression was used to identify predictors for COVID positivity. Selected classifiers were assessed for prediction performance using receiver operating characteristic analysis (ROC). RESULTS: One‐hundred and forty‐five participants with positive COVID‐19 testing and 157 with negative results were included. Participants had a mean age of 39 years, and 214 (72%) were female. Smell or taste change, fever, and body ache were associated with COVID‐19 positivity, and shortness of breath and sore throat were associated with a negative test result (p<0.05). A model using all 5 diagnostic symptoms had the highest accuracy with a predictive ability of 82% in discriminating between COVID‐19 results. To maximize sensitivity and maintain fair diagnostic accuracy, a combination of 2 symptoms, change in sense of smell or taste and fever was found to have a sensitivity of 70% and overall discrimination accuracy of 75%. CONCLUSION: Smell or taste change is a strong predictor for a COVID‐19 positive test result. Using the presence of smell or taste change with fever, this parsimonious classifier correctly predicts 75% of COVID‐19 test results. A larger cohort of respondents will be necessary to refine classifier performance. This article is protected by copyright. All rights reserved


title: Cholesterol‐conjugated peptide antivirals: a path to a rapid response to emerging viral diseases

text: While it is now possible to identify and genetically fingerprint the causative agents of emerging viral diseases, often with extraordinary speed, suitable therapies cannot be developed with equivalent speed, because drug discovery requires information that goes beyond knowledge of the viral genome. Peptides, however, may represent a special opportunity. For all enveloped viruses, fusion between the viral and the target cell membrane is an obligatory step of the life cycle. Class I fusion proteins harbor regions with a repeating pattern of amino acids, the heptad repeats (HRs), that play a key role in fusion, and HR‐derived peptides such as enfuvirtide, in clinical use for HIV, can block the process. Because of their characteristic sequence pattern, HRs are easily identified in the genome by means of computer programs, providing the sequence of candidate peptide inhibitors directly from genomic information. Moreover, a simple chemical modification, the attachment of a cholesterol group, can dramatically increase the antiviral potency of HR‐derived inhibitors and simultaneously improve their pharmacokinetics. Further enhancement can be provided by dimerization of the cholesterol‐conjugated peptide. The examples reported so far include inhibitors of retroviruses, paramyxoviruses, orthomyxoviruses, henipaviruses, coronaviruses, and filoviruses. For some of these viruses, in vivo efficacy has been demonstrated in suitable animal models. The combination of bioinformatic lead identification and potency/pharmacokinetics improvement provided by cholesterol conjugation may form the basis for a rapid response strategy, where development of an emergency cholesterol‐conjugated therapeutic would immediately follow the availability of the genetic information of a new enveloped virus. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.


title: COVID-19 vaccine development: Time to consider SARS-CoV-2 challenge studies?

text: Abstract While a human challenge study holds the prospect of accelerating the development of a vaccine for the coronavirus SARS-CoV-2, it may be opposed due to risks of harm to participants and researchers. Given the increasing number of human deaths and severe disruption to lives worldwide, we argue that a SARS-CoV-2 challenge study is ethically justifiable as its social value substantially outweighs the risks. Such a study should therefore be seriously considered as part of the global research response towards the COVID-19 pandemic. In this paper, we contribute to the debate by addressing the misperception that a challenge study for the coronavirus would lower scientific and ethical standards for vaccine research and development, and examine how it could be ethically conducted. We also set out information that needs to be disclosed to prospective participants to obtain their consent.


title: Hospitalization and Mortality among Black Patients and White Patients with Covid-19

text: BACKGROUND: Many reports on coronavirus disease 2019 (Covid-19) have highlighted age- and sex-related differences in health outcomes. More information is needed about racial and ethnic differences in outcomes from Covid-19. METHODS: In this retrospective cohort study, we analyzed data from patients seen within an integrated-delivery health system (Ochsner Health) in Louisiana between March 1 and April 11, 2020, who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the virus that causes Covid-19) on qualitative polymerase-chain-reaction assay. The Ochsner Health population is 31% black non-Hispanic and 65% white non-Hispanic. The primary outcomes were hospitalization and in-hospital death. RESULTS: A total of 3626 patients tested positive, of whom 145 were excluded (84 had missing data on race or ethnic group, 9 were Hispanic, and 52 were Asian or of another race or ethnic group). Of the 3481 Covid-19–positive patients included in our analyses, 60.0% were female, 70.4% were black non-Hispanic, and 29.6% were white non-Hispanic. Black patients had higher prevalences of obesity, diabetes, hypertension, and chronic kidney disease than white patients. A total of 39.7% of Covid-19–positive patients (1382 patients) were hospitalized, 76.9% of whom were black. In multivariable analyses, black race, increasing age, a higher score on the Charlson Comorbidity Index (indicating a greater burden of illness), public insurance (Medicare or Medicaid), residence in a low-income area, and obesity were associated with increased odds of hospital admission. Among the 326 patients who died from Covid-19, 70.6% were black. In adjusted time-to-event analyses, variables that were associated with higher in-hospital mortality were increasing age and presentation with an elevated respiratory rate; elevated levels of venous lactate, creatinine, or procalcitonin; or low platelet or lymphocyte counts. However, black race was not independently associated with higher mortality (hazard ratio for death vs. white race, 0.89; 95% confidence interval, 0.68 to 1.17). CONCLUSIONS: In a large cohort in Louisiana, 76.9% of the patients who were hospitalized with Covid-19 and 70.6% of those who died were black, whereas blacks comprise only 31% of the Ochsner Health population. Black race was not associated with higher in-hospital mortality than white race, after adjustment for differences in sociodemographic and clinical characteristics on admission.


title: Pathways to zoonotic spillover

text: Zoonotic spillover, which is the transmission of a pathogen from a vertebrate animal to a human, presents a global public health burden but is a poorly understood phenomenon. Zoonotic spillover requires several factors to align, including the ecological, epidemiological and behavioural determinants of pathogen exposure, and the within-human factors that affect susceptibility to infection. In this Opinion article, we propose a synthetic framework for animal-to-human transmission that integrates the relevant mechanisms. This framework reveals that all zoonotic pathogens must overcome a hierarchical series of barriers to cause spillover infections in humans. Understanding how these barriers are functionally and quantitatively linked, and how they interact in space and time, will substantially improve our ability to predict or prevent spillover events. This work provides a foundation for transdisciplinary investigation of spillover and synthetic theory on zoonotic transmission.


title: Targeting the NO‐cGMP‐PDE5 pathway in COVID‐19 infection

text: A pandemic outbreak of COVID‐19 has been sweeping the world since December. It begins as a respiratory infection that, mainly in men with diabetes or renal impairment, evolves into a systemic disease, with SARDS, progressive endothelial cell damage, abnormal clotting and impaired cardiovascular and liver function. Some clinical trials are testing biological drugs to limit the immune system dysregulation, “cytokines storm”, that causes the systemic complications of COVID‐19. The contraindications of these drugs and their cost raise concerns over the implications of their widespread availability. Numerous clinical and experimental studies have revealed a role for the nitric oxide (NO)‐cyclic GMP‐phosphodiesterase type 5 (PDE5) pathway in modulating low‐grade inflammation in patients with metabolic diseases, offering cardiovascular protection. PDE5 inhibition favors an anti‐inflammatory response by modulating activated T cells, reducing cytokine release, lowering fibrosis, increasing oxygen diffusion, stimulating vascular repair. PDE5 is highly expressed in the lungs, where its inhibition improves pulmonary fibrosis, a complication of severe COVID‐19 disease. We performed a systematic review of all evidence documenting any involvement of the NO‐cGMP‐PDE5 axis in the pathophysiology of COVID‐19, presenting the ongoing clinical trials aimed at modulating this axis, including our own “silDEnafil administration in DiAbetic and dysmetaboLic patients with COVID‐19 (DEDALO trial)”. The reviewed evidence suggests that PDE5 inhibitors could offer a new strategy in managing COVID‐19 by (i) counteracting the Ang‐II‐mediated downregulation of AT‐1 receptor; (ii) acting on monocyte switching, thus reducing pro‐inflammatory cytokines, interstitial infiltration and the vessel damage responsible for alveolar hemorrhage‐necrosis; (iii) inhibiting the transition of endothelial and smooth muscle cells to mesenchymal cells in the pulmonary artery, preventing clotting and thrombotic complications. If the ongoing trials presented herein should provide positive findings, the low cost, wide availability and temperature stability of PDE5 inhibitors could make them a major resource to combat COVID‐19 in developing countries.


Immune-related pneumonitis with nivolumab and ipilimumab during the COVID-19 pandemic


title: Glucose and Galactose Absorption after Ingestion of Milk Containing Hydrolysed Lactose in Calves with Diarrhoea

text: Ten calves which had contracted acute diarrhoea caused by rotavirus, coronavirus and Cryptosporidium were used to test the hypothesis that feeding lactose‐hydrolysed cow's milk instead of unprocessed cow's milk improves sugar absorption in diarrhoeic calves. The animals were rehydrated with an orally administered solution containing electrolytes and glucose. Thereafter the calves received one test meal of whole fresh cow's milk whose lactose had been hydrolysed by added lactase and one test meal of unprocessed cow's milk at an interval of 24 h in a cross‐over design trial. In comparison with unprocessed milk, the intake of milk containing hydrolysed lactose resulted in a slight decrease of mean breath hydrogen concentration (P = 0.18), but also a slight decrease of mean blood galactose concentration (P = 0.14). There was no treatment effect on mean plasma glucose concentration. Peak plasma glucose and blood galactose concentration tended to be delayed after the intake of lactose‐hydrolysed milk, which implies that gastric emptying was probably delayed. The results show that feeding milk which contains hydrolysed lactose does not significantly improve lactose utilization in calves that are suffering from benign infectious diarrhoea.


title: Molecular advances in the cell biology of SARS-CoV and current disease prevention strategies

text: In the aftermath of the SARS epidemic, there has been significant progress in understanding the molecular and cell biology of SARS-CoV. Some of the milestones are the availability of viral genome sequence, identification of the viral receptor, development of an infectious cDNA clone, and the identification of viral antigens that elicit neutralizing antibodies. However, there is still a large gap in our understanding of how SARS-CoV interacts with the host cell and the rapidly changing viral genome adds another variable to this equation. Now the SARS-CoV story has entered a new phase, a search for preventive strategies and a cure for the disease. This review highlights the progress made in identifying molecular aspects of SARS-CoV biology that is relevant in developing disease prevention strategies. Authors conclude that development of successful SARS-CoV vaccines and antivirals depends on the progress we make in these areas in the immediate future.


title: Medication for COVID-19—an Overview of Approaches Currently Under Study

text: BACKGROUND: With the worldwide spread of SARS-CoV-2 infection, it is becoming increasingly urgent to develop a vaccine to prevent COVID-19, as well as effective drugs to treat it. METHODS: This article is based on a selective literature search in PubMed and ClinicalTrials.gov, followed by an assessment of the ongoing clinical trials that were revealed by the search. RESULTS: A number of substances have been found to prevent the reproduction of SARS-CoV-2 in vitro. These include virustatic agents that have already been approved for the treatment of other types of viral infection, as well as drugs that are currently used for entirely different purposes. High in vitro activity has been found for the nucleotide analogue remdesivir, for the antimalarial drug chloroquine, and for nitazoxanide, a drug used to treat protozoan infections. Because the virus enters human cells by way of the membrane-associated angiotensin converting enzyme 2 (ACE2), keeping the virus from docking to this receptor is a conceivable treatment approach. Transmembrane protease serine 2 (TMPRSS2) plays a role in the fusion of the virus with cells; inhibitors of this enzyme are known as well. The potential therapeutic efficacy and tolerability of these and other active substances remain to be investigated in clinical trials. At present, more than 80 trials on COVID-10 have already been registered with ClinicalTrials.gov. Some initial findings should already be available in late April 2020. CONCLUSION: Clinical trials are now indispensable in order to determine the true clinical benefits and risks of the substances that have been found to be active against SARS-CoV-2 in vitro. There is not yet any recommendation for the therapeutic use of any particular agent beyond standard supportive treatment.


title: DUSP1 regulates apoptosis and cell migration, but not the JIP1-protected cytokine response, during Respiratory Syncytial Virus and Sendai Virus infection

text: The host antiviral response involves the induction of interferons and proinflammatory cytokines, but also the activation of cell death pathways, including apoptosis, to limit viral replication and spreading. This host defense is strictly regulated to eliminate the infection while limiting tissue damage that is associated with virus pathogenesis. Post-translational modifications, most notably phosphorylation, are key regulators of the antiviral defense implying an important role of protein phosphatases. Here, we investigated the role of the dual-specificity phosphatase 1 (DUSP1) in the host defense against human respiratory syncytial virus (RSV), a pathogenic virus of the Pneumoviridae family, and Sendai virus (SeV), a model virus being developed as a vector for anti-RSV vaccine. We found that DUSP1 is upregulated before being subjected to proteasomal degradation. DUSP1 does not inhibit the antiviral response, but negatively regulates virus-induced JNK/p38 MAPK phosphorylation. Interaction with the JNK-interacting protein 1 scaffold protein prevents dephosphorylation of JNK by DUSP1, likely explaining that AP-1 activation and downstream cytokine production are protected from DUSP1 inhibition. Importantly, DUSP1 promotes SeV-induced apoptosis and suppresses cell migration in RSV-infected cells. Collectively, our data unveil a previously unrecognized selective role of DUSP1 in the regulation of tissue damage and repair during infections by RSV and SeV.


title: Démarche diagnostique devant une lymphopénie : quand penser à la lymphopénie CD4(+) idiopathique ?

text: Lymphocytopenia is defined by a lymphocyte count less than 1500/mm(3) in adults and less than 4500/mm(3) in children before the age of 8 months. Lymphocytopenia can be global or selectively affect a peculiar lymphocyte subpopulation. The patient's age, the context as well as the associated clinical manifestations and treatment prescribed must be taken into account in order to identify the etiology of lymphocytopenia. In adults, lymphocytopenia can be caused by: (1) insufficient thymic output (primary immune deficiencies, corticosteroid treatment, zinc deficiency, etc.), (2) increased lymphocyte catabolism (radiotherapy, chemotherapy, immunosuppressant, HIV infection, systemic lupus, etc.), (3) modified lymphocyte distribution (viral infections, septic shock, extensive burns, splenomegaly, granulomatosis, etc.), (4) multifactorial or unknown etiology (end-stage renal disease, lymphoid malignancies, solid tumor, ethnicity, etc.). In children, in addition to these etiologies, other immune deficiencies may be responsible for severe lymphocytopenia (thymocytes apoptosis, cytokine deficiencies, altered B-cell and T-cell receptor synthesis, signal transduction and cellular interactions deficiencies). Idiopathic CD4(+) lymphocytopenia is a rare disorder. It is defined by a persisting lymphocyte CD4(+) count less or equal to 300/mm(3) or less or equal to 20% of total lymphocytes in the absence of alternative diagnosis. Clinical symptoms can be absent or include opportunistic infections, auto-immune manifestations, lymphoma or solid tumors. Treatment is similar to that of HIV-infected patients and sometimes relies on specific immunotherapy even though clinical benefit has not been evaluated.


title: DPP4, the Middle East Respiratory Syndrome Coronavirus Receptor, is Upregulated in Lungs of Smokers and Chronic Obstructive Pulmonary Disease Patients

text: BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) causes pneumonia with a relatively high case fatality rate in humans. Smokers and chronic obstructive pulmonary disease (COPD) patients have been reported to be more susceptible to MERS-CoV infection. Here, we determined the expression of MERS-CoV receptor, dipeptidyl peptidase IV (DPP4), in lung tissues of smokers without airflow limitation and COPD patients in comparison to nonsmoking individuals (never-smokers). METHODS: DPP4 expression was measured in lung tissue of lung resection specimens of never-smokers, smokers without airflow limitation, COPD GOLD stage II patients and in lung explants of end-stage COPD patients. Both control subjects and COPD patients were well phenotyped and age-matched. The mRNA expression was determined using qRT-PCR and protein expression was quantified using immunohistochemistry. RESULTS: In smokers and subjects with COPD, both DPP4 mRNA and protein expression were significantly higher compared to never-smokers. Additionally, we found that both DPP4 mRNA and protein expression were inversely correlated with lung function and diffusing capacity parameters. CONCLUSIONS: We provide evidence that DPP4 is upregulated in the lungs of smokers and COPD patients, which could partially explain why these individuals are more susceptible to MERS-CoV infection. These data also highlight a possible role of DPP4 in COPD pathogenesis.


title: COVID‐19 multisystem inflammatory syndrome in three teenagers with confirmed SARS‐CoV‐2 infection

text: Coronavirus disease 2019 (COVID‐19) is generally a relatively mild illness in children. An emerging disease entity coined as pediatric inflammatory multisystem syndrome temporally associated with SARS‐CoV‐2 (PIMS‐TS) has been reported recently, but is very rare and only affects a very small minority of children. Here we describe the clinical presentations and outcomes of three teenagers with serologically‐confirmed SARS‐CoV‐2 infection admitted to a pediatric intensive care unit for PIMS‐TS. Although their initial presentations were very similar, their COVID‐19‐related disease varied in severity.


title: How We Do It: Modified Residency Programming and Adoption of Remote Didactic Curriculum During the COVID-19 Pandemic

text: ABSTRACT Objective To describe the modified operational plan we implemented for residents and faculty in our orthopaedic surgery department to allow continuation of resident education and other core activities during the novel coronavirus (COVID-19) pandemic. Design Description of educational augmentation and programming modifications Setting The Johns Hopkins Hospital and Johns Hopkins Bayview Medical Center, Baltimore, MD Participants Residents and faculty, Department of Orthopaedic Surgery Methods In response to the COVID-19 pandemic, we developed and implemented a modified operational schedule and remote curriculum in the orthopaedic surgery department of our health system. Our plan was guided by the following principles: protecting the workforce while providing essential clinical care; maintaining continuity of education and research; and promoting social distancing while minimizing the impact on team psychosocial well-being. Results The operational schedule and remote curriculum have been implemented successfully and allow resident education and other core departmental functions to continue as our health care system responds to the pandemic. Conclusions We have been proactive and deliberate in implementing these operational changes, without compromise of our workforce. This experience provides residents exposure to real-life systems-based practice. We hope that our early experience will provide a framework for other surgical residency programs facing this crisis.


title: Genome Wide Identification of SARS-CoV Susceptibility Loci Using the Collaborative Cross

text: New systems genetics approaches are needed to rapidly identify host genes and genetic networks that regulate complex disease outcomes. Using genetically diverse animals from incipient lines of the Collaborative Cross mouse panel, we demonstrate a greatly expanded range of phenotypes relative to classical mouse models of SARS-CoV infection including lung pathology, weight loss and viral titer. Genetic mapping revealed several loci contributing to differential disease responses, including an 8.5Mb locus associated with vascular cuffing on chromosome 3 that contained 23 genes and 13 noncoding RNAs. Integrating phenotypic and genetic data narrowed this region to a single gene, Trim55, an E3 ubiquitin ligase with a role in muscle fiber maintenance. Lung pathology and transcriptomic data from mice genetically deficient in Trim55 were used to validate its role in SARS-CoV-induced vascular cuffing and inflammation. These data establish the Collaborative Cross platform as a powerful genetic resource for uncovering genetic contributions of complex traits in microbial disease severity, inflammation and virus replication in models of outbred populations.


title: Middle East respiratory syndrome coronavirus: a comprehensive review

text: The Middle East respiratory syndrome coronavirus was first identified in 2012 and has since then remained uncontrolled. Cases have been mostly reported in the Middle East, however travel-associated cases and outbreaks have also occurred. Nosocomial and zoonotic transmission of the virus appear to be the most important routes. The infection is severe and highly fatal thus necessitating rapid and efficacious interventions. Here, we performed a comprehensive review of published literature and summarized the epidemiology of the virus. In addition, we summarized the virological aspects of the infection and reviewed the animal models used as well as vaccination and antiviral tested against it.


LA ATENCIÓN PRIMARIA Y COMUNITARIA (APyC) Y LA ESTRATEGIA DE ABORDAJE DE LA PANDEMIA COVID19


title: Personal Protective Equipment (PPE) Guidelines, Adaptations and Lessons During the COVID-19 Pandemic

text: Abstract The COVID-19 pandemic has placed unprecedented strain on the American healthcare system. Personal protective equipment (PPE) remains critical in keeping healthcare providers healthy and safe. The sudden increase in demand as well as the limited availability places increased risk on providers which may inhibit their ability to effectively manage patients. The purpose of this brief article is to review the recommended guidelines for PPE usage and compare them to how medical societies have adapted and responded to decreased supply, as well as public response.


Editorial 58(1)


title: A geographic analysis of population density thresholds in the influenza pandemic of 1918–19

text: BACKGROUND: Geographic variables play an important role in the study of epidemics. The role of one such variable, population density, in the spread of influenza is controversial. Prior studies have tested for such a role using arbitrary thresholds for population density above or below which places are hypothesized to have higher or lower mortality. The results of such studies are mixed. The objective of this study is to estimate, rather than assume, a threshold level of population density that separates low-density regions from high-density regions on the basis of population loss during an influenza pandemic. We study the case of the influenza pandemic of 1918–19 in India, where over 15 million people died in the short span of less than one year. METHODS: Using data from six censuses for 199 districts of India (n=1194), the country with the largest number of deaths from the influenza of 1918–19, we use a sample-splitting method embedded within a population growth model that explicitly quantifies population loss from the pandemic to estimate a threshold level of population density that separates low-density districts from high-density districts. RESULTS: The results demonstrate a threshold level of population density of 175 people per square mile. A concurrent finding is that districts on the low side of the threshold experienced rates of population loss (3.72%) that were lower than districts on the high side of the threshold (4.69%). CONCLUSIONS: This paper introduces a useful analytic tool to the health geographic literature. It illustrates an application of the tool to demonstrate that it can be useful for pandemic awareness and preparedness efforts. Specifically, it estimates a level of population density above which policies to socially distance, redistribute or quarantine populations are likely to be more effective than they are for areas with population densities that lie below the threshold.


title: Does Rapid and Sustained Economic Growth Lead to Convergence in Health Resources: The Case of China From 1980 to 2010

text: China’s rapid and sustained economic growth offers an opportunity to ask whether the advantages of growth diffuse throughout an economy, or remain localized in areas where the growth has been the greatest. A critical policy area in China has been the health system, and health inequality has become an issue that has led the government to broaden national health insurance programs. This study investigates whether health system resources and performance have converged over the past 30 years across China’s 31 provinces. To examine geographic variation of health system resources and performance at the provincial level, we measure the degree of sigma convergence and beta convergence in indicators of health system resources (structure), health services utilization (process), and outcome. All data are from officially published sources: the China Health Statistics Year Book and the China Statistics Year Book. Sigma convergence is found for resource indicators, whereas it is not observed for either process or outcome indicators, indicating that disparities only narrowed in health system resources. Beta convergence is found in most indicators, except for 2 procedure indicators, reflecting that provinces with poorer resources were catching up. Convergence found in this study probably reflects the mixed outcome of government input, and market forces. Thus, left alone, the equitable distribution of health care resources may not occur naturally during a period of economic growth. Governmental and societal efforts are needed to reduce geographic health variation and promote health equity.


title: A role for human leucocyte antigens in the susceptibility to SARS‐Cov‐2 infection observed in transplant patients

text: We analysed data from 80 patients who tested positive for SARS‐CoV‐2 RNA who had previously been HLA typed to support transplantation. Data were combined from two adjacent centres in Manchester and Leeds to achieve a sufficient number for early analysis. HLA frequencies observed were compared against two control populations: first, against published frequencies in a UK deceased donor population (n = 10,000) representing the target population of the virus, and second, using a cohort of individuals from the combined transplant waiting lists of both centres (n = 308), representing a comparator group of unaffected individuals of the same demographic. We report a significant HLA association with HLA‐ DQB1*06 (53% vs. 36%; p < .012; OR 1.96; 95% CI 1.94–3.22) and infection. A bias towards an increased representation of HLA‐A*26, HLA‐DRB1*15, HLA‐DRB1*10 and DRB1*11 was also noted but these were either only significant using the UK donor controls, or did not remain significant after correction for multiple tests. Likewise, HLA‐A*02, HLA‐B*44 and HLA‐C*05 may exert a protective effect, but these associations did not remain significant after correction for multiple tests. This is relevant information for the clinical management of patients in the setting of the current SARS‐CoV‐2 pandemic and potentially in risk‐assessing staff interactions with infected patients.


title: Human Norovirus Infection in Dogs, Thailand

text: In July 2018, recombinant norovirus GII.Pe-GII.4 Sydney was detected in dogs who had diarrhea in a kennel and in children living on the same premises in Thailand. Whole-genome sequencing and phylogenetic analysis of 4 noroviruses from Thailand showed that the canine norovirus was closely related to human norovirus GII.Pe-GII.4 Sydney, suggesting human-to-canine transmission.


title: Prevalence and Clinical Presentation of Health Care Workers With Symptoms of Coronavirus Disease 2019 in 2 Dutch Hospitals During an Early Phase of the Pandemic

text: IMPORTANCE: On February 27, 2020, the first patient with coronavirus disease 2019 (COVID-19) was reported in the Netherlands. During the following weeks, at 2 Dutch teaching hospitals, 9 health care workers (HCWs) received a diagnosis of COVID-19, 8 of whom had no history of travel to China or northern Italy, raising the question of whether undetected community circulation was occurring. OBJECTIVE: To determine the prevalence and clinical presentation of COVID-19 among HCWs with self-reported fever or respiratory symptoms. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was performed in 2 teaching hospitals in the southern part of the Netherlands in March 2020, during the early phase of the COVID-19 pandemic. Health care workers employed in the participating hospitals who experienced fever or respiratory symptoms were asked to voluntarily participate in a screening for infection with the severe acute respiratory syndrome coronavirus 2. Data analysis was performed in March 2020. MAIN OUTCOMES AND MEASURES: The prevalence of severe acute respiratory syndrome coronavirus 2 infection was determined by semiquantitative real-time reverse transcriptase–polymerase chain reaction on oropharyngeal samples. Structured interviews were conducted to document symptoms for all HCWs with confirmed COVID-19. RESULTS: Of 9705 HCWs employed (1722 male [18%]), 1353 (14%) reported fever or respiratory symptoms and were tested. Of those, 86 HCWs (6%) were infected with severe acute respiratory syndrome coronavirus 2 (median age, 49 years [range, 22-66 years]; 15 [17%] male), representing 1% of all HCWs employed. Most HCWs experienced mild disease, and only 46 (53%) reported fever. Eighty HCWs (93%) met a case definition of fever and/or coughing and/or shortness of breath. Only 3 (3%) of the HCWs identified through the screening had a history of travel to China or northern Italy, and 3 (3%) reported having been exposed to an inpatient with a known diagnosis of COVID-19 before the onset of symptoms. CONCLUSIONS AND RELEVANCE: Within 2 weeks after the first Dutch case was detected, a substantial proportion of HCWs with self-reported fever or respiratory symptoms were infected with severe acute respiratory syndrome coronavirus 2, likely as a result of acquisition of the virus in the community during the early phase of local spread. The high prevalence of mild clinical presentations, frequently not including fever, suggests that the currently recommended case definition for suspected COVID-19 should be used less stringently.


title: COVID-19: to be or not to be; that is the diagnostic question

text: Since the first cases in December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread across the globe, resulting in the COVID-19 pandemic. Early clinical experiences have demonstrated the wide spectrum of SARS-CoV-2 presentations, including various reports of atypical presentations of COVID-19 and possible mimic conditions. This article summarises the current evidence surrounding atypical presentations of COVID-19 including neurological, cardiovascular, gastrointestinal, otorhinolaryngology and geriatric features. A case from our hospital of pneumocystis pneumonia initially suspected to be COVID-19 forms the basis for a discussion surrounding mimic conditions of COVID-19. The dual-process model of clinical reasoning is used to analyse the thought processes used to make a diagnosis of COVID-19, including consideration of the variety of differential diagnoses. While SARS-CoV-2 is likely to remain on the differential diagnostic list for a plethora of presentations for the foreseeable future, clinicians should be cautious of ignoring other potential diagnoses due to availability bias. An awareness of atypical presentations allows SARS-CoV-2 to be a differential so that it can be appropriately investigated. A knowledge of infectious mimics prevents COVID-19 from overshadowing other diagnoses, hence preventing delayed diagnosis or even misdiagnosis and consequent adverse outcomes for patients.


title: Bacterial and viral pathogen spectra of acute respiratory infections in under-5 children in hospital settings in Dhaka city

text: The study aimed to examine for the first time the spectra of viral and bacterial pathogens along with the antibiotic susceptibility of the isolated bacteria in under-5 children with acute respiratory infections (ARIs) in hospital settings of Dhaka, Bangladesh. Nasal swabs were collected from 200 under-five children hospitalized with clinical signs of ARIs. Nasal swabs from 30 asymptomatic children were also collected. Screening of viral pathogens targeted ten respiratory viruses using RT-qPCR. Bacterial pathogens were identified by bacteriological culture methods and antimicrobial susceptibility of the isolates was determined following CLSI guidelines. About 82.5% (n = 165) of specimens were positive for pathogens. Of 165 infected cases, 3% (n = 6) had only single bacterial pathogens, whereas 43.5% (n = 87) cases had only single viral pathogens. The remaining 36% (n = 72) cases had coinfections. In symptomatic cases, human rhinovirus was detected as the predominant virus (31.5%), followed by RSV (31%), HMPV (13%), HBoV (11%), HPIV-3 (10.5%), and adenovirus (7%). Streptococcus pneumoniae was the most frequently isolated bacterial pathogen (9%), whereas Klebsiella pneumaniae, Streptococcus spp., Enterobacter agglomerans, and Haemophilus influenzae were 5.5%, 5%, 2%, and 1.5%, respectively. Of 15 multidrug-resistant bacteria, a Klebsiella pneumoniae isolate and an Enterobacter agglomerans isolate exhibited resistance against more than 10 different antibiotics. Both ARI incidence and predominant pathogen detection rates were higher during post-monsoon and winter, peaking in September. Pathogen detection rates and coinfection incidence in less than 1-year group were significantly higher (P = 0.0034 and 0.049, respectively) than in 1–5 years age group. Pathogen detection rate (43%) in asymptomatic cases was significantly lower compared to symptomatic group (P<0.0001). Human rhinovirus, HPIV-3, adenovirus, Streptococcus pneumonia, and Klebsiella pneumaniae had significant involvement in coinfections with P values of 0.0001, 0.009 and 0.0001, 0.0001 and 0.001 respectively. Further investigations are required to better understand the clinical roles of the isolated pathogens and their seasonality.


Atrial Arrhythmias in COVID-19 Patients


title: The C-terminal domain of the MERS coronavirus M protein contains a trans-Golgi network localization signal

text: Coronavirus M proteins represent the major protein component of the viral envelope. They play an essential role during viral assembly by interacting with all of the other structural proteins. Coronaviruses bud into the endoplasmic reticulum (ER)–Golgi intermediate compartment (ERGIC), but the mechanisms by which M proteins are transported from their site of synthesis, the ER, to the budding site remain poorly understood. Here, we investigated the intracellular trafficking of the Middle East respiratory syndrome coronavirus (MERS-CoV) M protein. Subcellular localization analyses revealed that the MERS-CoV M protein is retained intracellularly in the trans-Golgi network (TGN), and we identified two motifs in the distal part of the C-terminal domain as being important for this specific localization. We identified the first motif as a functional diacidic DxE ER export signal, because substituting Asp-211 and Glu-213 with alanine induced retention of the MERS-CoV M in the ER. The second motif, (199)KxGxYR(204), was responsible for retaining the M protein in the TGN. Substitution of this motif resulted in MERS-CoV M leakage toward the plasma membrane. We further confirmed the role of (199)KxGxYR(204) as a TGN retention signal by using chimeras between MERS-CoV M and the M protein of infectious bronchitis virus (IBV). Our results indicated that the C-terminal domains of both proteins determine their specific localization, namely TGN and ERGIC/cis-Golgi for MERS-M and IBV-M, respectively. Our findings indicate that MERS-CoV M protein localizes to the TGN because of the combined presence of an ER export signal and a TGN retention motif.


title: Vaccination in Hajj: An Overview of the Recent Findings

text: BACKGROUND: About two million people annually travel to Kingdom of Saudi Arabia to perform Hajj. The pilgrims may be at risk of exposure to communicable diseases in this mass gathering and their vaccination against contagious diseases can prevent many morbidities and mortalities. The aim of our study was to review the papers which evaluated effectiveness and compliance of the vaccines applied in Hajj. METHODS: We used PubMed and Scopus to search international medical databases. The key words were as follows: Hajj, Haj, vaccine, vaccination, and immunization. The time interval of the search was from the beginning of 2010 to May 23, 2016. One hundred and thirty papers were extracted, and their contents were subsequently reviewed after title and abstract screenings. The original articles were included in the study and non-English articles were excluded from the study. RESULTS: Considering the extracted papers, almost all pilgrims were vaccinated against meningococcal diseases. Using of influenza and pneumococcal vaccine rates were different among the pilgrims. The other vaccines have been taking according to specific conditions. CONCLUSIONS: The findings regarding influenza vaccine effectiveness are contradictory. A few studies confirmed the flu vaccine effectiveness while some others rejected its usefulness. Meningococcal immunization is an effective preventive tool with high compliance for Hajj pilgrims. Further investigations are recommended for the other vaccines.


title: Chest computed tomography in children with COVID-19 respiratory infection

text: BACKGROUND: Infection with COVID-19 is currently rare in children. OBJECTIVE: To describe chest CT findings in children with COVID-19. MATERIALS AND METHODS: We studied children at a large tertiary-care hospital in China, during the period from 28 January 2019 to 8 February 2020, who had positive reverse transcriptase polymerase chain reaction (RT-PCR) for COVID-19. We recorded findings at any chest CT performed in the included children, along with core clinical observations. RESULTS: We included five children from 10 months to 6 years of age (mean 3.4 years). All had had at least one CT scan after admission. Three of these five had CT abnormality on the first CT scan (at 2 days, 4 days and 9 days, respectively, after onset of symptoms) in the form of patchy ground-glass opacities; all normalised during treatment. CONCLUSION: Compared to reports in adults, we found similar but more modest lung abnormalities at CT in our small paediatric cohort.


title: Neuropathy target esterase (NTE/PNPLA6) and organophosphorus compound-induced delayed neurotoxicity (OPIDN)()

text: Systemic inhibition of neuropathy target esterase (NTE) with certain organophosphorus (OP) compounds produces OP compound-induced delayed neurotoxicity (OPIDN), a distal degeneration of axons in the central nervous system (CNS) and peripheral nervous system (PNS), thereby providing a powerful model for studying a spectrum of neurodegenerative diseases. Axonopathies are important medical entities in their own right, but in addition, illnesses once considered primary neuronopathies are now thought to begin with axonal degeneration. These disorders include Alzheimer's disease, Parkinson's disease, and motor neuron diseases such as amyotrophic lateral sclerosis (ALS). Moreover, conditional knockout of NTE in the mouse CNS produces vacuolation and other degenerative changes in large neurons in the hippocampus, thalamus, and cerebellum, along with degeneration and swelling of axons in ascending and descending spinal cord tracts. In humans, NTE mutations cause a variety of neurodegenerative conditions resulting in a range of deficits including spastic paraplegia and blindness. Mutations in the Drosophila NTE orthologue SwissCheese (SWS) produce neurodegeneration characterized by vacuolization that can be partially rescued by expression of wild-type human NTE, suggesting a potential therapeutic approach for certain human neurological disorders. This chapter defines NTE and OPIDN, presents an overview of OP compounds, provides a rationale for NTE research, and traces the history of discovery of NTE and its relationship to OPIDN. It then briefly describes subsequent studies of NTE, including practical applications of the assay; aspects of its domain structure, subcellular localization, and tissue expression; abnormalities associated with NTE mutations, knockdown, and conventional or conditional knockout; and hypothetical models to help guide future research on elucidating the role of NTE in OPIDN.


Symptoms of Infection Caused by SARS Coronavirus in Laboratory Mice and Guinea Pigs


title: CIRUGÍA LAPAROSCÓPICA EN TIEMPOS DE COVID-19

text: Resumen La convivencia con la infección por el COVID -19 (Coronavirus Disease 2019) en todos los entornos hospitalarios y de salud supone un reto actual de adaptación, creación de circuitos, protocolos y nuevos modelos de asistencia. Son todavía bastantes las incógnitas a resolver sobre esta infección en la actualidad, y mucho más desconocido es el impacto que el mismo supone si lo trasladamos al terreno quirúrgico. La evidencia respecto al efecto del SARS-CoV-2 y cirugía laparoscópica es escasa y de calidad limitada, pero aún así, la laparoscopia ha sido considerada de elección por las distintas sociedades científicas en pacientes COVID para la mayoría de indicaciones en ginecología, por las conocidas ventajas hacia el paciente respecto a la vía abierta: menor morbilidad y estancia hospitalaria y porque comporta procedimientos quirúrgicos autónomos y contenidos respecto a la liberación de humo y donde además, el instrumental y la disposición en quirófano permiten, un alejamiento del cirujano y del resto de profesionales en el área quirúrgica respecto al paciente. A modo global, las dos recomendaciones fundamentales en quirófano de cirugía laparoscópica en esta época COVID incluyen: el uso de equipo de protección personal adecuado para el personal de quirófano y la adopción de precauciones para reducir la exposición al CO2 y del humo quirúrgico que puede producirse en estos procedimientos. Abstract Coexistence with COVID-19 infection (Coronavirus Disease 2019) in all hospital and health care settings is a current challenge of adaptation, as well as the creation of new protocols and care models. At present, there are still many unknowns about this infection, and much more unknown is the impact into the surgical field. Although evidence regarding the effect of SARS-CoV-2 and laparoscopic surgery is scarce, laparoscopy has been considered the method of choice by different scientific societies for most indications in gynaecology during the COVID-19 pandemic. This is due to the advantages over the open route. There is less morbidity and hospital stay, and in addition, as it involves autonomous and contained surgical procedures with respect to smoke release. Moreover, the instruments and the setting in the operating room means that there can be safe distance from the surgeon and other staff to the patient. Overall, the main recommendations in laparoscopic surgery during the COVID era include: the use of Personal Protective Equipment (PPE) for operating room personnel, and the adoption of safety measures to reduce CO2 exposure and surgical smoke release.


title: Acceptability of A/H1N1 vaccination during pandemic phase of influenza A/H1N1 in Hong Kong: population based cross sectional survey

text: Objective To investigate the intention of the Hong Kong general population to take up vaccination against influenza A/H1N1. Setting Cross sectional population based anonymous survey. Participants Random sample of 301 adults interviewed by telephone (response rate 80%). Main outcome measure Intention to take up vaccination against influenza A/H1N1 under five hypothetical scenarios: vaccination is free; vaccination per dosage costs less than $HK100 (£8; €9; $13), $HK101-200, or more than $HK200; and no data are available on the efficacy and safety of the vaccine. Results 45% (n=135) of the participants reported that they would be highly likely take up vaccination if it was free. When vaccination incurred a cost, however, the prevalence of uptake decreased: 36% (n=108) would take up vaccination if it cost less than $HK100, 24% (n=72) if it cost $HK101-200, and 15% (n=45) if it cost more than $HK200; and in absence of proved efficacy and safety decreased to 5% (n=14). Moreover, 32% (n=95) considered universal A/H1N1 vaccination unnecessary. Overall, 39% (n=117) of participants believed that A/H1N1 vaccination would prevent the virus being contracted; 63% (n=189) erroneously believed that efficacy of the vaccine had been confirmed by clinical trials, and 16% (n=49) believed that it is necessary for everyone in Hong Kong to take up vaccination against influenza A/H1N1. Conclusions The uptake of vaccination against influenza A/H1N1 by the general population of Hong Kong is unlikely to be high and would be sensitive to personal cost. Evidence about safety and efficacy is critical in determining the prevalence of uptake of vaccination.