title: Unusual presentation of Middle East respiratory syndrome coronavirus leading to a large outbreak in Riyadh during 2017

text: BACKGROUND: The hallmark of Middle East respiratory syndrome coronavirus (MERS-CoV) disease is the ability to cause major health care-associated nosocomial outbreaks with superspreading events leading to massive numbers of cases and excessive morbidity and mortality. In this report, we describe a patient who presented with acute renal failure requiring hemodialysis and became a MERS-CoV superspreader, igniting a recent multihospital outbreak in Riyadh. MATERIAL AND RESULTS: Between May 31 and June 15, 2017, 44 cases of MERS-CoV infection were reported from 3 simultaneous clusters from 3 health care facilities in Riyadh, Saudi Arabia, including 11 fatal cases. Out of the total reported cases, 29 cases were reported from King Saud Medical City. The cluster at King Saud Medical City was ignited by a single superspreader patient who presented with acute renal failure. After 14 hours in the open area of the emergency department and 2 hemodialysis sessions he was diagnosed with MERS-CoV. One hundred twenty contacts who had direct unprotected exposure were screened. Among those contacts, 9 out of 107 health care workers (5 nurses, 3 physicians, and 1 paramedic) and 7 out of 13 patients tested positive for MERS-CoV. CONCLUSIONS: This hospital outbreak demonstrated the difficulties in diagnosing pneumonia in patients with renal and cardiac failure, which leads to delayed suspicion of MERS-CoV and hence delay in applying the proper infection control procedures. In MERS-CoV endemic countries there is an urgent need for developing rapid point-of-care testing that would assist emergency department staff in triaging suspected cases of MERS-CoV to ensure timely isolation and management of their primary illness and prevent major MERS-CoV outbreaks.


Diagnóstico de virus respiratorios en la unidad de cuidados intensivos neonatales: ¿listos para el prime time?


The global pandemic involving severe acute respiratory syndrome–coronavirus-2 (SARS-COV-2) has stretched the limits of science. Ever since it emerged from the Wuhan province in China, it has spread across the world and has been fatal to about 4% of the victims. This position statement of the Indian Society of Critical Care Medicine represents the collective opinion of the experts chosen by the society. HOW TO CITE THIS ARTICLE: Mehta Y, Chaudhry D, Abraham OC, Chacko J, Divatia J, Jagiasi B, et al. Critical Care for COVID-19 Affected Patients: Position Statement of the Indian Society of Critical Care Medicine. Indian J Crit Care Med 2020;24(4):222–241.


title: Incidence of Hajj-associated febrile cough episodes among French pilgrims: a prospective cohort study on the influence of statin use and risk factors

text: Abstract A prospective epidemiological study was conducted to evaluate the incidence of febrile cough episodes among adult Muslims travelling from Marseille to Saudi Arabia during the Hajj pilgrimage and to assess if use of statin had an influence on this incidence. In total, 580 individuals were presented with a questionnaire. A significant proportion of individuals had chronic medical disorders, e.g. diabetes mellitus (132, 22.8%) and hypertension (147, 25.3%). Pilgrims had a low level of education and a low employment rate. Sixty (10.3%) were treated with statins for hypercholesterolemia. Four hundred and fourty-seven pilgrims were presented a questionnaire on returning home. A total of 74 travellers (16.6%) experienced fever during their stay in Saudi Arabia (67 attended a doctor) and 271 (60.6%) had cough (259 attended a doctor); 70 travellers with cough were febrile (25.9%). Seventy per cent of the travellers who suffered cough episodes developed their first symptoms within 3 days, suggesting a human to human transmission of the responsible pathogen, with short incubation time as evidenced by a bimodal distribution of cough in two peaks at a 24 h interval. None of demographical and socioeconomic characteristics, underlying diseases or vaccination against influenza significantly affected the occurrence of cough. Diabetes correlated with an increased risk of febrile cough (OR = 2.02 (1.05–3.89)) as well as unemployment (OR = 2.22 (0.91–5.53)). Use of statins had no significant influence on the occurrence of cough and/or fever during the pilgrimage. This result suggests that while treatment with a statin has been demonstrated to reduce the mortality from severe sepsis associated with respiratory tract infections, it probably does not play a role in the outcome of regular febrile cough episodes as observed in the cohort studied here.


Corrigendum to: Relationship Between Odor Intensity Estimates and COVID-19 Prevalence Prediction in a Swedish Population


title: Enhance immune response to DNA vaccine based on a novel multicomponent supramolecular assembly

text: Abstract DNA vaccination has tremendous potential for treating or preventing numerous diseases for which traditional vaccines are ineffective but the technique can be limited by low immunogenicity. Current synthetic DNA delivery systems are versatile and safe, but substantially less efficient than viruses. Here, a novel multicomponent supramolecular system involving the preparation of mannose-bearing chitosan oligomers microspheres with entrapping complexes of DNA vaccine and polyethylenimine was developed to mimic many of the beneficial properties of the viruses. After delivery by intramuscular immunization in BALB/c mice, the microspheres induced an enhanced serum antibody responses two orders of magnitude greater than naked DNA vaccine. Additionally, in contrast to naked DNA, the microspheres induced potent cytotoxic T lymphocyte responses at a low dose. Consequently, formulation of DNA vaccines into multicomponent vectors is a powerful means of increasing vaccine potency.


title: Viral mechanisms of immune evasion

text: During the millions of years they have coexisted with their hosts, viruses have learned how to manipulate host immune control mechanisms. Viral gene functions provide an overview of many relevant principles in cell biology and immunology. Our knowledge of viral gene functions must be integrated into virus–host interaction networks to understand viral pathogenesis, and could lead to new anti-viral strategies and the ability to exploit viral functions as tools in medicine.


title: Olfaction and anosmia in rhinosinusitis

text: Olfactory disorders can cause serious consequences from the inability to detect many olfactory warning signals (eg, smoke, spoiled food, and gas leaks) and can significantly impact nutritional status, eating satisfaction, and many other issues related to quality of life. More than 200,000 people a year seek treatment for impaired olfactory ability, and available evidence suggests this figure is a significant underestimate of those affected. Rhinitis and rhinosinusitis are the primary etiologies for olfactory loss or distortion among patients presenting to chemosensory clinics, and they are among the most common chronic medical conditions in the United States, affecting an estimated 33 million people. Both allergic and nonallergic rhinitis/rhinosinusitis can result in diminished, distorted, or absent olfactory ability. Current therapies are only partially or transiently effective in reversing olfactory loss. The underlying mechanisms by which rhinitis/rhinosinusitis impact olfactory ability are likely to be multifactorial and might include altered air flow and odor deposition, changes in mucus composition, and effects of inflammatory mediators on receptor cell differentiation, maturation, or function.


title: MERS-CoV 4b protein interferes with the NF-κB-dependent innate immune response during infection

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel human coronavirus that emerged in 2012, causing severe pneumonia and acute respiratory distress syndrome (ARDS), with a case fatality rate of ~36%. When expressed in isolation, CoV accessory proteins have been shown to interfere with innate antiviral signaling pathways. However, there is limited information on the specific contribution of MERS-CoV accessory protein 4b to the repression of the innate antiviral response in the context of infection. We found that MERS-CoV 4b was required to prevent a robust NF-κB dependent response during infection. In wild-type virus infected cells, 4b localized to the nucleus, while NF-κB was retained in the cytoplasm. In contrast, in the absence of 4b or in the presence of cytoplasmic 4b mutants lacking a nuclear localization signal (NLS), NF-κB was translocated to the nucleus leading to the expression of pro-inflammatory cytokines. This indicates that NF-κB repression required the nuclear import of 4b mediated by a specific NLS. Interestingly, we also found that both in isolation and during infection, 4b interacted with α-karyopherin proteins in an NLS-dependent manner. In particular, 4b had a strong preference for binding karyopherin-α4 (KPNA4), which is known to translocate the NF-κB protein complex into the nucleus. Binding of 4b to KPNA4 during infection inhibited its interaction with NF-κB-p65 subunit. Thereby we propose a model where 4b outcompetes NF-κB for KPNA4 binding and translocation into the nucleus as a mechanism of interference with the NF-κB-mediated innate immune response.


title: Future Challenges for Vaccinologists

text: Vaccination is one of the cheapest health-care interventions that have saved more lives than any other drugs or therapies. Due to successful immunization programs we rarely hear about some of the common diseases of the early twentieth century including small pox and polio. Vaccination programs have also helped to increase food production notably poultry, cattle, and milk production due to lower incidence of infectious diseases in farm animals. Though vaccination programs have eradicated several diseases and increased the quality of life there are several diseases that have no effective vaccines. Currently there are no vaccines for cancer, neurodegenerative diseases, autoimmune diseases, as well as infectious diseases like tuberculosis, AIDS, and parasitic diseases including malaria. Abuse of antibiotics has resulted in the generation of several antibiotic-resistant bacterial strains; hence there is a need to develop novel vaccines for antibiotic-resistant microorganisms. Changes in climate is another concern for vaccinologists. Climate change could lead to generation of new strains of infectious microorganisms that would require development of novel vaccines. Use of conventional vaccination strategies to develop vaccines has severe limitations; hence innovative strategies are essential in the development of novel and effective vaccines.


title: Molecular surveillance of respiratory viruses with bioaerosol sampling in an airport

text: Recognizing that crowded, high-traffic airports and airplanes have been implicated in respiratory disease transmission, we partnered with administrators of Raleigh Durham International Airport (RDU) in conducting a pilot study of aerosol surveillance for respiratory viruses at RDU. From January to March 2018 we used NIOSH 2-stage samplers to collect 150 min aerosol samples in crowded areas at RDU. Four (17%) of the 24 samples were positive for known respiratory pathogens including influenza D virus and adenovirus. These results suggest the feasibility of employing bioaerosol surveillance techniques in public transportation areas, such as airports, as a noninvasive way to detect and characterize novel respiratory viruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40794-018-0071-7) contains supplementary material, which is available to authorized users.


title: A Middle East respiratory syndrome screening clinic for health care personnel during the 2015 Middle East respiratory syndrome outbreak in South Korea: A single-center experience

text: BACKGROUND: Transmission of Middle East respiratory syndrome (MERS) to health care personnel (HCP) is a major concern. This study aimed to review cases of MERS-related events, such as development of MERS-like symptoms or exposure to patients. METHODS: A MERS screening clinic (MSC) for HCP was setup in the National Medical Center during the MERS outbreak in 2015. Clinical and laboratory data from HCP who visited the MSC were retrospectively reviewed. Additionally, these data were compared with the results of postoutbreak questionnaire surveys and interviews about MERS-related symptoms and risk-related events. RESULTS: Of the 333 HCP who participated in MERS patient care, 35 HCP (10.5%) visited the MSC for MERS-like symptoms. No one was infected with MERS, and the most common symptom was fever (68.6%) followed by cough (34.3%). However, 106 of 285 postoutbreak survey participants experienced at least 1 MERS-related symptom and 26 reported exposure to patients without appropriate personal protective equipment, whereas only 4 HCP visited the MSC to report exposure events. CONCLUSIONS: Although a considerable number of HCP experienced MERS-related symptoms or unprotected exposure during MERS patient care, some did not take appropriate action. These findings imply that for infection control strategy to be properly performed, education should be strengthened so that HCP can accurately recognize the risk situation and properly notify the infection control officer.


title: Hypothalamic digoxin – central role in conscious perception, neuroimmunoendocrine integration and coordination of cellular function – relation to hemispheric dominance

text: Abstract A family with a high prevalence of Parkinson’s disease, schizophrenia, neoplasms, syndrome-X, rheumatoid arthritis and epilepsy has been described. The psychological behavioural patterns of the family were as follows – creativity and high IQ, hypersexual behaviour, reduced appetite and eating behaviour, insomnia and reduced sleep patterns, increased tendency for spirituality, increased tendency for addiction, less of bonding and affectionate behaviour and left handedness. Digoxin, an endogenous Na+–K+ ATPase inhibitor secreted by the hypothalamus, was found to be elevated and RBC membrane Na+–K+ ATPase activity was found to be reduced in all the disorders and in the indexed family studied. Hypothalamic digoxin can modulate conscious perception and its dysfunction may lead to schizophrenia. Digoxin can also preferentially upregulate tryptophan transport over tyrosine resulting in increased levels of depolarising tryptophan catabolites – serotonin, quinolinic acid, strychnine and nicotine and decreased levels of hyperpolarising tyrosine catabolites dopamine, noradrenaline and morphine contributing to membrane Na+–K+ ATPase inhibition in all the above disorders and the indexed family. Digoxin induced membrane Na+–K+ ATPase inhibition can result in increased intracellular Ca2+ and reduced Mg++ levels leading to glutamate excitotoxicity, oncogene activation and immune activation. Digoxin induced altered Ca++/Mg++ ratios, reduced ubiquinone and increased dolichol can affect glycoconjugate metabolism, membrane formation and structure and mitochondrial function leading to the diverse disorders described above including those in the indexed family. The isoprenoid pathway and neurotransmitter patterns were compared in right-handed/left hemispheric dominant and left-handed/right hemispheric dominant individuals. The biochemical patterns in the indexed family and the diverse disorders studied correlated with those obtained in right hemispheric dominance. The hyperdigoxinemic state indicates right hemispheric dominance. Hypothalamic digoxin can thus function as the master conductor of the neuroimmunoendocrine orchestra and co-ordinate the functions of various cellular organelles.


title: Infections in Heart and Lung Transplant Recipients

text: Patients undergoing thoracic organ transplantation procedures involving the heart or lung are at increased risk for developing a wide variety of infections due to their underlying immunosuppression and/or other factors. Lung transplant recipients are at high risk for developing infections caused by bacteria, viruses, and opportunistic fungi, whereas heart transplant recipients are at risk for developing infections caused by these same microorganisms, as well as parasitic infections, including toxoplasmosis and New World trypanosomiasis. This review will highlight the various infections that thoracic organ transplant recipients may develop following their procedures.


title: Innate immunity modulation in virus entry

text: Entry into a cell submits viruses to detection by pattern recognition receptors (PRRs) leading to an early innate anti-viral response. Several viruses evolved strategies to avoid or subvert PRR recognition at the step of virus entry to promote infection. Whereas viruses mostly escape from soluble PRR detection, endocytic/phagocytic PRRs, such as the mannose receptor or DC-SIGN, are commonly used for virus entry. Moreover, virion-incorporated proteins may also offer viruses a way to dampen anti-viral innate immunity upon virus entry, and entering viruses might usurp autophagy to improve their own infectivity.


title: Circular RNAs in Sepsis: Biogenesis, Function, and Clinical Significance

text: Sepsis is a life-threatening condition that occurs when the body responds to an infection that damages it is own tissues. The major problem in sepsis is rapid, vital status deterioration in patients, which can progress to septic shock with multiple organ failure if not properly treated. As there are no specific treatments, early diagnosis is mandatory to reduce high mortality. Despite more than 170 different biomarkers being postulated, early sepsis diagnosis and prognosis remain a challenge for clinicians. Recent findings propose that circular RNAs (circRNAs) may play a prominent role in regulating the patients’ immune system against different pathogens, including bacteria and viruses. Mounting evidence also suggests that the misregulation of circRNAs is an early event in a wide range of diseases, including sepsis. Despite circRNA levels being altered in sepsis, the specific mechanisms controlling the dysregulation of these noncoding RNAs are not completely elucidated, although many factors are known to affect circRNA biogenesis. Therefore, there is a need to explore the molecular pathways that lead to this disorder. This review describes the role of this new class of regulatory RNAs in sepsis and the feasibility of using circRNAs as diagnostic biomarkers for sepsis, opening up new avenues for circRNA-based medicine.


title: Practical recommendations for the management of diabetes in patients with COVID-19

text: Summary Diabetes is one of the most important comorbidities linked to the severity of all three known human pathogenic coronavirus infections, including severe acute respiratory syndrome coronavirus 2. Patients with diabetes have an increased risk of severe complications including Adult Respiratory Distress Syndrome and multi-organ failure. Depending on the global region, 20–50% of patients in the coronavirus disease 2019 (COVID-19) pandemic had diabetes. Given the importance of the link between COVID-19 and diabetes, we have formed an international panel of experts in the field of diabetes and endocrinology to provide some guidance and practical recommendations for the management of diabetes during the pandemic. We aim to briefly provide insight into potential mechanistic links between the novel coronavirus infection and diabetes, present practical management recommendations, and elaborate on the differential needs of several patient groups.


title: Secular trends of healthcare-associated infections at a teaching hospital in Taiwan, 1981–2007

text: Summary The National Taiwan University Hospital (NTUH) adopted international guidelines for surveillance and control of healthcare-associated infection (HCAI) in 1981. This report describes the secular trends in HCAI at the NTUH over the past 27 years according to site of infection, aetiological agents and control measures. Clinical and microbiological data were collected by infection prevention and control nurses using a standardised case-record form. Specific control programmes were implemented and/or intensified as needed. Poisson or negative binomial regression analysis was used to quantify time trends of the incidence of HCAI. The annual number of discharges increased from 25 074 to 91 234 with a parallel increase in the Charlson comorbidity index. Active HCAI surveillance and periodic feedback were associated with a marked decrease in surgical site infections from 1981 to 2007 (2.5 vs 0.5 episodes per 100 procedures, P <0.0001). On the other hand, there was a 4.8-fold increase in bloodstream infections (BSIs) (0.39 vs 1.88 episodes per 100 discharges, P <0.0001). The average annual increase of pathogen-specific HCAI incidence during 1981–2007 was 11.4% for meticillin-resistant Staphylococcus aureus (MRSA), 75.4% for extensively drug-resistant A. baumannii (XDRAB), and 7.5% for Candida albicans (P <0.0001, respectively). The infection prevention and control programme was upgraded in 2004 by implementing annual, intensive, project-based control programmes, and decreases in rates of HCAI, BSI, MRSA and XDRAB were observed. This long term study demonstrates the need to couple surveillance of HCAI with focused control programmes. Hospitals must invest in adequate manpower to accomplish these goals.


title: Infection of Human Airway Epithelia with H1N1, H2N2, and H3N2 Influenza A Virus Strains

text: Abstract Three subtypes of influenza A virus cause human disease: H1N1, H2N2, and H3N2. Although all result in respiratory illness, little is known about how these subtypes infect differentiated airway epithelia. Therefore, we assayed A/PR/8/34 (H1N1), A/Japan/305/57 (H2N2), and X31 (H3N2) influenza virus strains for binding and infection on fully differentiated primary cultures of airway epithelia isolated from human bronchus, grown on semiporous filters at an air–liquid interface. In this model system, viral infectivity was highest when virus was applied to the apical versus the basolateral surface; Japan was most infectious, followed by PR8. The X31 strain showed very low levels of infectivity. Confocal microscopy and fluorescence-resonance energy transfer studies indicated that Japan virus could enter and fuse with cellular membranes, while infection with X31 virions was greatly inhibited. Japan virus could also productively infect human trachea explant tissues. These data show that influenza viruses with SAα2,3Gal binding specificity, like Japan, productively infect differentiated human airway epithelia from the apical surface. These data are important to consider in the development of pseudotyped recombinant viral vectors for gene transfer to human airway epithelia for gene therapy.


title: Evidence for Trans splicing in trypanosomes

text: Abstract The 5′ ends of trypanosome mRNAs consist of an identical sequence of 35 nucleotides. This “mini-exon” sequence is derived from the 5′ end of a 137 nucleotide RNA (medRNA). The remainder of each mRNA is derived from a protein-coding exon that is not linked to the mini-exon. We propose that medRNA is spliced in trans to de-novo-initiated transcripts of protein-coding genes. This trans splicing model predicts that the downstream portion of medRNA will be part of a branched structure and then be released as a free product (minRNA). We demonstrate that significant levels of minRNA exist in trypanosome RNA. Furthermore, minRNA can be released from high molecular weight RNA by a HeLa cell S100 “debranching” extract. We conclude that trnas splicing is the physiological process by which mature mRNA molecules are synthesized in trypanosomes.


title: Targeting strategies for delivery of anti-HIV drugs

text: Abstract Human Immunodeficiency Virus (HIV) infection remains a significant cause of mortality globally. Though antiretroviral therapy has significantly reduced AIDS-related morbidity and mortality, there are several drawbacks in the current therapy, including toxicity, drug–drug interactions, development of drug resistance, necessity for long-term drug therapy, poor bio-availability and lack of access to tissues and reservoirs. To circumvent these problems, recent anti-HIV therapeutic research has focused on improving drug delivery systems through drug delivery targeted specifically to host cells infected with HIV or could potentially get infected with HIV. In this regard, several surface molecules of both viral and host cell origin have been described in recent years, that would enable targeted drug delivery in HIV infection. In the present review, we provide a comprehensive overview of the need for novel drug delivery systems, and the successes and challenges in the identification of novel viral and host-cell molecules for the targeted drug delivery of anti-HIV drugs. Such targeted anti-retroviral drug delivery approaches could pave the way for effective treatment and eradication of HIV from the body.


News Feature: To counter the pandemic, clinicians bank on repurposed drugs


title: China’s local governments are combating COVID-19 with unprecedented responses — from a Wenzhou governance perspective

text: The COVID-19 caused by a novel strain of Coronavirus has been spreading rapidly since its onset in Wuhan, the capital city of central China’s Hubei Province, in December 2019. It is highly communicable through human-to-human transmission. China has been making unprecedented efforts in treating the confirmed cases, identifying and isolating their close contacts and suspected cases to control the source of infection and cut the route of transmission. China’s devotion in handling this epidemic has effectively and efficiently curbed communication domestically and across the border. Representative measures adopted by Wenzhou, the worst hit city out of Hubei Province, are examined to elucidate those massive undertakings with the aim of enhancing international understanding and building global rapport in fighting this evolving epidemic situation.


The accuracy of “Preliminary estimation of the novel coronavirus disease (COVID-19) cases in Iran: A modelling analysis based on overseas cases and air travel data”


title: Has SARS infected the property market? Evidence from Hong Kong

text: Abstract This paper uses the 2003 Hong Kong Severe Acute Respiratory Syndrome (SARS) epidemic as a natural experiment to investigate how housing markets react to extreme events. A panel data set of large-scale housing complexes (estates) is used to exploit the cross-sectional variation in the spread of SARS to estimate the effect of the disease on real estate prices and sales. SARS risk is measured by: (1) the estate-level SARS infection rate, (2) news reports, and (3) government announcements of infections. The average price declines by 1–3 percent if an estate is directly affected by SARS, and by 1.6 percent for all estates as a result of the outbreak of the disease. A back-of-the-envelope calculation of the expected price fall under the rational asset-pricing model implies that the economic value of life consistent with the SARS-related price movement was less than $1 million. This low figure contrasts with the predictions of overreaction from psychological and behavioral economics theories. An analysis of transaction volume suggests that the absence of price overreaction is likely to be related to housing market characteristics, including transaction costs, credit constraints and loss aversion.


title: Chapter 19 Membrane Transport

text: Abstract Life depends on a membrane's ability to precisely control the level of solutes in the aqueous compartments, inside and outside, bathing the membrane. The membrane determines what solutes enter and leave a cell. Transmembrane transport is controlled by complex interactions between membrane lipids, proteins, and carbohydrates. How the membrane accomplishes these tasks is the topic of this chapter.


Children and Fecal SARS-CoV-2 shedding: Just the Tip of the Iceberg of Italian COVID-19 outbreak?


Personal protective equipment and concerns over airborne transmission of COVID‐19: a reply


title: Effects of COVID-19 on Business and Research

text: Abstract The COVID-19 outbreak is a sharp reminder that pandemics, like other rarely occurring catastrophes, have happened in the past and will continue to happen in the future. Even if we cannot prevent dangerous viruses from emerging, we should prepare to dampen their effects on society. The current outbreak has had severe economic consequences across the globe, and it does not look like any country will be unaffected. This not only has consequences for the economy; all of society is affected, which has led to dramatic changes in how businesses act and consumers behave. This special issue is a global effort to address some of the pandemic-related issues affecting society. In total, there are 12 papers that cover different industry sectors (e.g., tourism, retail, higher education), changes in consumer behavior and businesses, ethical issues, and aspects related to employees and leadership.


Viral disease prevention after hematopoietic cell transplantation


title: Viral Diversity in Asthma

text: Asthma exacerbations are precipitated primarily by respiratory virus infection and frequently require immediate medical intervention. Studies of childhood and adult asthma have implicated a wide variety of respiratory viruses in exacerbations. By focusing on both RNA and DNA respiratory viruses and some newly identified viruses, this review illustrates the diversity and highlights some of the uncertainties that exist in our understanding of virus-related asthma exacerbations.


title: Hemagglutination with transmissible gastroenteritis virus

text: Transmissible gastroenteritis virus grown in primary swine kidney cell cultures agglutinated erythrocytes from chicken, guinea pig and cattle but not erythrocytes from mouse and goose. The optimal incubation temperature was at 4°C. The hemagglutination (HA) reaction was inhibited by specific antiserum. Some factors involved in the HA and HA-inhibition (HI) were investigated and standard HA and HI tests were established. HI antibody titers of individual pig sera showed a significant positive correlation with their neutralizing antibody titers.


title: Interferon lambda 1–3 expression in infants hospitalized for RSV or HRV associated bronchiolitis

text: Summary Objectives The airway expression of type III interferons (IFNs) was evaluated in infants hospitalized for respiratory syncytial virus (RSV) or rhinovirus (HRV) bronchiolitis. As an additional objective we sought to determine whether a different expression of IFN lambda 1–3 was associated with different harboring viruses, the clinical course of bronchiolitis or with the levels of well established IFN stimulated genes (ISGs), such as mixovirus resistance A (MxA) and ISG56. Methods The analysis was undertaken in 118 infants with RSV or HRV bronchiolitis. Nasopharyngeal washes were collected for virological studies and molecular analysis of type III IFN responses. Results RSV elicited higher levels of IFN lambda subtypes when compared with HRV. A similar expression of type III IFN was found in RSVA or RSVB infected infants and in those infected with HRVA or HRVC viruses. Results also indicate that IFN lambda 1 and IFN lambda 2–3 levels were correlated with each other and with MxA and ISG56-mRNAs. In addition, a positive correlation exists between the IFN lambda1 levels and the clinical score index during RSV infection. In particular, higher IFN lambda 1 levels are associated to an increase of respiratory rate. Conclusions These findings show that differences in the IFN lambda 1–3 levels in infants with RSV or HRV infections are present and that the expression of IFN lambda 1 correlates with the severity of RSV bronchiolitis.


title: Knowledge management systems in support of disasters management: A two decade review

text: Abstract Humans are increasingly being challenged with numerous forms of man-made and natural emergency situations. Emergencies cannot be prevented, but they can be better managed. The successful management of emergency situations requires proper planning, guided response, and well-coordinated efforts across the emergency management life cycle. Literature suggests that emergency management efforts benefit from well-integrated knowledge-based emergency management information systems (EMIS). This study presents a systematic review of papers pertaining to the application of knowledge-driven systems in support of emergency management that have been published in the last two decades. Our review presents two major findings. First, only limited work has been done in three EMIS-knowledge management system (KMS) subdomains: (i) definition, (ii) use, and (iii) methods. Second, only limited research has been done in embedding roles in KM systems. We highlight role alignment to the 12 fundamental roles, as called for by Turoff et al. (2004), in the context of creating dynamic systems in aid of emergency management efforts. We believe that these two findings warrant the attention of the research community.


title: Contingency management strategies of the Nursing Department in centralized rescue of patients with coronavirus disease 2019

text: Abstract Objectives This article aims to summarize a series of contingency management strategies of the Nursing Department in the centralized treatment of patients with coronavirus disease 2019 (COVID-19). Methods The strategies of the Nursing Department included an early warning for prevention and control, taking functions of vertically commanding and horizontally coordinating, and reasonably allocating nursing workforce, to facilitate centralized treatment work in the in-hospital fever clinic, isolation wards and ICU, and referral and admission of critical patients. Five special groups were established in charge of training and examination, management and supervision, psychological support, logistical support, and reporting and publicity, respectively. Results It was achieved that no deaths from critical patients and no medical staff, no other patients were infected. Conclusion Through the implementation of these strategies, safe and efficient centralized treatment was ensured timely, orderly and sustainably.


Chapter 41 Virus Infection of Epithelial Cells


“MoRPHEE” fighting COVID-19


title: Distribución temporal, geográfica y por población de la nueva enfermedad por coronavirus (COVID-19) desde el 20 de enero hasta el 10 de febrero del 2020, en China

text: Resumen Antecedentes y objetivo: Desde diciembre del 2019, se está detectando en el mundo un incremento de casos de una nueva enfermedad causada por el coronavirus 2019 (COVID-19). El objetivo de este artículo es proporcionar recomendaciones científicas para la prevención y el control de la COVID-19 en todo el mundo. Métodos: Se han recopilado características demográficas generales, antecedentes epidemiológicos y síntomas clínicos de la COVID-19 recogidos en los sitios web de múltiples Comisiones Municipales de Salud en China. Aquí describimos las distribuciones temporales, geográficas y de población de la COVID-19. Resultados: Hasta la medianoche del 10 de febrero del 2020, el número de casos confirmados de COVID-19 en China fue de 42.638, siendo Hubei la provincia con un mayor número de casos confirmados (31.728), seguida por Guangdong (1.177), Zhejiang (1.117) y la provincia de Henan (1.105), en China. El número de casos y la velocidad de confirmación en otras provincias fue más moderada que en la provincia de Hubei. La mediana (rango intecuartílico) de edad de 1.740 pacientes de COVID-19 fue de 44 años (33, 54), con un rango desde los 10 meses a los 89 años. Conclusiones: La epidemia de COVID-19 se ha de considerar como una amenaza mundial, y los pasos encaminados para su control incluyen el diagnóstico temprano y su tratamiento, así como el aislamiento. Summary Background and objective: Since December 2019, increasing cases of novel coronavirus disease 2019 (COVID-19) are being detected worldwide. The purpose of this paper is to provide a scientific reference for the global prevention and control of COVID-19. Methods: General demographic characteristics, epidemiological history, and clinical symptoms of COVID-19 were collected that had been reported on the websites of multiple Municipal Health Commissions in China. We herein describe distributions in time, place, and population of COVID-19. Results: As of midnight on February 10, 2020, the number of confirmed cases of COVID-19 in China was 42,638, and the province with the largest number of confirmed cases was Hubei (31728), followed by Guangdong (1177), Zhejiang (1117), and Henan (1105) province. The number of cases and the speed of confirmed cases in provinces other than Hubei were more moderate than those of the Hubei province. The median (interquartile range) age of 1740 patients with COVID-19 was 44 (33, 54) years, with a range of 10 months to 89 years. Conclusions: The COVID-19 epidemic should be considered a global threat and the steps for control include early diagnosis and treatment, as well as isolation.


Literature Highlights in Combinatorial Science: Solid‐phase Synthesis


title: Evaluation and mechanism for outcomes exploration of providing public health care in contract service in Rural China: a multiple-case study with complex adaptive systems design

text: BACKGROUND: The Chinese government has increased the funding for public health in 2009 and experimentally applied a contract service policy (could be seen as a counterpart to family medicine) in 15 counties to promote public health services in the rural areas in 2013. The contract service aimed to convert village doctors, who had privately practiced for decades, into general practitioners under the government management, and better control the rampant chronic diseases. This study made a rare attempt to assess the effectiveness of public health services delivered under the contract service policy, explore the influencing mechanism and draw the implications for the policy extension in the future. METHODS: Three pilot counties and a non-pilot one with heterogeneity in economic and health development from east to west of China were selected by a purposive sampling method. The case study methods by document collection, non-participant observation and interviews (including key informant interview and focus group interview) with 84 health providers and 20 demanders in multiple level were applied in this study. A thematic approach was used to compare diverse outcomes and analyze mechanism in the complex adaptive systems framework. RESULTS: Without sufficient incentives, the public health services were not conducted effectively, regardless of the implementation of the contract policy. To appropriately increase the funding for public health by local finance and properly allocate subsidy to village doctors was one of the most effective approaches to stimulate health providers and demanders’ positivity and promote the policy implementation. County health bureaus acted as the most crucial agents among the complex public health systems. Their mental models influenced by the compound and various environments around them led to the diverse outcomes. If they could provide extra incentives and make the contexts of the systems ripe enough for change, the health providers and demanders would be receptive to the transition of the policy. CONCLUSIONS: The innovative fund raising measures could be taken by relatively developed counties of China to conduct public health services. Policymakers could take systems thinking as a useful tool to design plans and predict the unintended outcomes during the process of public health reforms.


title: Evolution of COVID-19 Guidelines for University of Washington Oral and Maxillofacial Surgery Patient Care

text: Abstract The emergence of coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 (SC2) virus, in late December 2019 has placed an overwhelming strain on healthcare institutions nationwide. The modern healthcare system has never dealt with a pandemic of this magnitude, the ramifications of which will undoubtedly lead to lasting changes in policy and protocol development for viral testing guidelines, personal protective equipment (PPE), surgical scheduling, and residency education and training. The State of Washington (WA) had the first reported case and death related to COVID 19 in the United States (US). Oral and maxillofacial surgeons are at a unique risk of exposure to SC2 and developing COVID-19 due to our proximity of working in and around the oro- and nasopharynx. This article summarizes the evolution of COVID-19 guidelines in four key areas: 1. preoperative SARS-CoV-2 (SC2) testing, 2. personal protective equipment (PPE) stewardship, 3. surgical scheduling guidelines, and 4. resident education and training for oral and maxillofacial surgery (OMS) at the University of Washington, Seattle, WA.


title: COVID-19 and the food system: setback or opportunity for gender equality?

text: Agriculture and the food sector are critical to food and nutrition security because they not only produce food but also contribute to economic empowerment by employing a large share of female and male workers, especially in developing countries. Food systems at all levels―globally, domestically, locally, and in the home― are expected to be highly affected by the COVID-19 crisis. Women and men work as food producers, processors, and traders and will likely be impacted differently. Shocks or crises can exacerbate or reduce gender gaps, and so can policy responses to mitigate the impact of these crises or shocks. We offer some perspectives and available country examples on how the COVID-19 crisis and responses to the crisis could be a setback or offer opportunities for gender equality in the food system.


title: Chronicling changes to the chronic disease prevention landscape in Canada's public health system 2004–2010

text: The collective impact of major shifts in public health infrastructure and numerous new chronic disease prevention (CDP) capacity-building initiatives that have taken place in Canada over the last decade is unknown. The objective of this study was to determine if CDP capacity (i.e., skills and resources) and involvement in CDP programming improved in public health organizations in Canada from 2004 to 2010. Data for this repeated cross-sectional study were drawn from two waves of a national census of organizations mandated to carry out primary prevention of chronic disease and/or promotion of healthy eating, physical activity and tobacco control. Medians for continuous variables and frequencies for categorical variables were compared across time. Neither resources nor level of priority for CDP increased over time. There was little difference in the proportion of organizations with high levels of skills and involvement in core CDP practices (i.e., needs assessment, identification of relevant practices, planning, evaluation). Skills and involvement in CDP risk factor programming showed some gains, some steady states and some losses. Specifically, skill and involvement in tobacco control programming declined markedly while the proportion of organizations involved in healthy eating and physical activity programming increased. Skills to address and involvement in programming related to social determinants of health remained low over time as did involvement in programming addressing multiple risk factors concurrently. The lack of marked improvement in CDP capacity between 2004 and 2010 against a backdrop of initiatives favourable to strengthening the preventive health system in Canada suggests that efforts may have fallen short.


title: Emerging roles for RNA degradation in viral replication and antiviral defense

text: Abstract Viral replication significantly alters the gene expression landscape of infected cells. Many of these changes are driven by viral manipulation of host transcription or translation machinery. Several mammalian viruses encode factors that broadly dampen gene expression by directly targeting messenger RNA (mRNA). Here, we highlight how these factors promote mRNA degradation to globally regulate both host and viral gene expression. Although these viral factors are not homologous and use distinct mechanisms to target mRNA, many of them display striking parallels in their strategies for executing RNA degradation and invoke key features of cellular RNA quality control pathways. In some cases, there is a lack of selectivity for degradation of host versus viral mRNA, indicating that the purposes of virus-induced mRNA degradation extend beyond redirecting cellular resources towards viral gene expression. In addition, several antiviral pathways use RNA degradation as a viral restriction mechanism, and we will summarize new findings related to how these host-encoded ribonucleases target and destroy viral RNA.


title: Identification of two liver proteins recognized by autoantibodies elicited in mice infected with mouse hepatitis virus A59

text: Western blot experiments showed that sera from mice infected with the mouse hepatitis virus strain A59 (MHV‐A59) contained autoantibodies (autoAb) that bound to a 40‐kDa protein present in liver and kidney extracts. No reaction was observed with extracts of the heart, muscles, spleen, brain and lung. The Ab cross‐reacted with a 40‐kDa protein from human, rat and sheep liver, but not withliver extracts from the silver side fish (Odontesthes bonariensis). No correlation was found between the development of the hypergammaglobulinemia that followed the viral infection and theoccurrence of the autoAb. Reactive immunoglobulins pertained to the IgG1, IgG2a and IgG2b subclasses, recognized cryptic epitopes and were detected from 10 days up to 8 weeks after MHV‐infection. The 40‐kDa protein was purified from mouse liver extracts by ion‐exchange chromatography, gel filtration and SDS‐PAGE. Because the N‐terminal was blocked, we digested the protein in‐gel with trypsin and sequenced various peptides. Results indicated a 100% homology of sequence between the protein recognized by the autoAb and liver fumarylacetoacetate hydrolase (FAH), the enzyme that mediates the last step of tyrosine catabolism. Additionally, a second protein recognized by the autoAb was detected during FAH purification steps and was identified as liver alcohol dehydrogenase.


title: Genetic, antigenic and pathogenic characterization of avian coronaviruses isolated from pheasants (Phasianus colchicus) in China

text: Abstract Two viruses were isolated in 2017 from commercial pheasants with severe clinical signs and mortality in Shandong and Anhui provinces, China, respectively. We examined the pathogenic effects of the viruses in chicken embryos and the size and morphology of the virus particles, performed phylogenetic analysis based on the S1 gene and complete genomic sequences, and examined the antibody responses against infectious bronchitis virus (IBV). The results suggested that the viruses I0623/17 and I0710/17 were avian coronaviruses and were identified as pheasant coronaviruses (PhCoV), with greatest similarity to IBV. Further investigations of the antigenicity, complete genome organization, substitutions in multiple genes, and viral pathogenicity, replication, and shedding in chickens and pheasants showed obvious differences between PhCoV and IBV in terms of antigenicity, and viral pathogenicity, replication, and shedding in chickens and pheasants. The close genetic relationship, but obvious differences between PhCoVs and IBVs suggested the IBVs could be the ancestors of PhCoVs, and that PhCoVs isolated from different outbreaks may have evolved independently from IBVs circulating in the specific region by adaption in pheasants. This hypothesis was supported by analysis of the S1 gene fragments of the two PhCoVs isolated in the current study, as well as PhCoVs isolated in the UK and selected IBV strains. Such analyses indicated different evolution patterns and different tissue tropisms between PhCoVs isolated in different outbreaks. Further studies are needed to confirm this hypothesis by studying the complete genomic sequences of PhCoVs from different outbreaks and the pathogenicity of IBVs in pheasants to compare and clarify the relationships between PhCoVs and IBVs.


title: Continuous porcine cell lines developed from alveolar macrophages Partial characterization and virus susceptibility

text: Abstract Porcine monomyeloid cell lines were established following transfection of primary porcine alveolar macrophage cultures with plasmid pSV3neo, carrying genes for neomycin resistance and SV40 large T antigen. The parental clone 3D4 exhibited a relatively rapid doubling time (25.5 h), high plating efficiency and mixed phenotype with respect to growth on a solid support. Single cell cloning of the 3D4 parent resulted in establishment of several cell lines; three of them designated 3D4/2, 3D4/21 and 3D4/31 were selected for further characterization. All three clones supported the replication of vesicular stomatitis virus (VSV), pseudorabies virus (PRV), classical swine fever virus (CSFV), swine vesicular disease virus (SVDV), swine poxvirus, African swine fever virus (ASFV), herpes simplex virus (HSV), parainfluenza virus, bovine adenovirus (BAV), vaccinia virus (VV), and porcine adenovirus (PAV). Under the conditions tested the cells did not support replication of porcine reproductive and respiratory syndrome virus (PRRSV). The swine myeloid character was confirmed for all three clones by fluorescence activated cell scanning (FACS) analysis using monoclonal antibodies 74-22-15 and DH59B, which recognize the pan-myeloid antigen cluster SWC3a. A subpopulation of each cell line was positive for nonspecific esterase activity and phagocytic activity to varying degrees depending on the media formulation. Cells from all three lines exhibited anchorage dependent growth when maintained in RPMI 1640 medium supplemented with 5–15% fetal bovine serum (FBS) and nonessential amino acids. Propagation in commercially formulated serum free media resulted in colony formation and growth in suspension. The addition of dimethyl sulfoxide (DMSO) or phorbol 12-myristate 13-acetate (PMA) to serum free media restored cell attachment. DMSO was also able to induce expression of CD14 monocyte marker in the 3D4/31 cell line maintained in FBS containing medium, as determined by FACS with monoclonal antibody CAM36A. Supplementation of RPMI medium with 10% porcine serum upregulated the expression of CD14 and induced expression of porcine macrophage markers recognized by antibodies 2B10 and 2G6 (Vet. Immunol. Immunopathol. 74 (2000) 163) in all three cell lines. The porcine myelomonocytic cell lines obtained may have a wide variety of applications in porcine virology and immunology.


title: Innate immune response and bronchiolitis and preschool recurrent wheeze

text: Summary Bronchiolitis and preschool recurrent wheeze (PSRW) are common paediatric problems causing significant morbidity and mortality in the first years of life. Respiratory syncytial virus (RSV) and rhinoviruses are the commonest pathogens associated with these illnesses. Why some infants are severely affected, requiring admission to hospital, whilst others experience a simple cold is not fully understood: research has suggested that the innate immune response to these viruses is important. The innate immune system has many components and activation or deficiency in one or many areas may explain the different clinical presentations and disease severities that can occur in these infants. This review will summarize the recent evidence highlighting how RSV and rhinoviruses may modulate the innate immune response in both bronchiolitis and PSRW, and discuss how these illnesses affect the long-term development of the infant lung and the possible susceptibility to persistent airway disease.


title: Adverse immunological imprinting by cytomegalovirus sensitizing for allergic airway disease

text: Cytomegalovirus (CMV) infection has a profound impact on the host’s immune system. Immunological imprinting by CMV is not restricted to immunity against CMV itself, but can affect immunity against other viral or non-viral infectious agents and also immunopathological responses. One category is heterologous immunity based on molecular mimicry, where antigen recognition receptors specific for a CMV antigen with broad avidity distribution also bind with some avidity to unrelated antigens and exert effector functions against target structures other than those linked to CMV. Another category is induction of cytokines by CMV infection that inhibit or drive immune responses to bystander antigens unrelated to CMV, and a third category is the activation of antigen-presenting cells by CMV from which unrelated antigens profit as “stowaways”. A striking example of the “stowaway” category, actually one that is of medical importance, has been published recently and will be discussed here for the more general reader. Specifically, in a murine model, CMV airway infection and inhaled environmental antigen of poor intrinsic allergenic potential were found to sensitize for allergic airway disease (AAD) only when combined. As to the mechanism, viral activation of CD11b(+) conventional dendritic cells (CD11b(+) cDC) that localize to airway mucosa facilitates uptake and processing of inhaled antigen. Thus, CMV serves as a “door opener” for otherwise harmless environmental antigens that have no intrinsic property to activate DC. Antigen-laden CD11b(+) cDC migrate selectively to the airway draining lymph nodes, where they prime type-2 CD4(+) T helper (Th-2) cells. Upon airway re-exposure to the inhaled antigen, Th-2 cells secrete interleukins (IL-4, IL-5, IL-9, and IL-25) known to induce goblet cell metaplasia, the lead histopathological manifestation of AAD that is characterized by thickening of airway epithelia and increased numbers of mucus-producing goblet cells, resulting in enhanced mucus secretion and airflow obstruction.


Covid-19: One in 10 cases in England occurred in frontline health and social care staff.


title: Viral Respiratory Tract Infections in Adult Patients Attending Outpatient and Emergency Departments, Taiwan, 2012–2013: A PCR/Electrospray Ionization Mass Spectrometry Study

text: Viral etiologies of respiratory tract infections (RTIs) have been less studied in adult than in pediatric populations. Furthermore, the ability of PCR/electrospray ionization mass spectrometry (PCR/ESI-MS) to detect enteroviruses and rhinoviruses in respiratory samples has not been well evaluated. We sought to use PCR/ESI-MS to comprehensively investigate the viral epidemiology of adult RTIs, including testing for rhinoviruses and enteroviruses. Nasopharyngeal or throat swabs from 267 adults with acute RTIs (212 upper RTIs and 55 lower RTIs) who visited a local clinic or the outpatient or emergency departments of a medical center in Taiwan between October 2012 and June 2013 were tested for respiratory viruses by both virus isolation and PCR/ESI-MS. Throat swabs from 15 patients with bacterial infections and 27 individuals without active infections were included as control samples. Respiratory viruses were found in 23.6%, 47.2%, and 47.9% of the 267 cases by virus isolation, PCR/ESI-MS, and both methods, respectively. When both methods were used, the influenza A virus (24.3%) and rhinoviruses (9.4%) were the most frequently identified viruses, whereas human coronaviruses, human metapneumovirus (hMPV), enteroviruses, adenoviruses, respiratory syncytial virus, and parainfluenza viruses were identified in small proportions of cases (<5% of cases for each type of virus). Coinfection was observed in 4.1% of cases. In the control group, only 1 (2.4%) sample tested positive for a respiratory virus by PCR/ESI-MS. Patients who were undergoing steroid treatment, had an active malignancy, or suffered from chronic obstructive pulmonary disease (COPD) were at risk for rhinovirus, hMPV, or parainfluenza infections, respectively. Overall, immunocompromised patients, patients with COPD, and patients receiving dialysis were at risk for noninfluenza respiratory virus infection. Rhinoviruses (12.7%), influenza A virus (10.9%), and parainfluenza viruses (7.3%) were the most common viruses involved in the 55 cases of lower RTIs. The factors of parainfluenza infection, old age, and immunosuppression were independently associated with lower RTIs. In conclusion, PCR/ESI-MS improved the diagnostic yield for viral RTIs. Non-influenza respiratory virus infections were associated with patients with comorbidities and with lower RTIs. Additional studies that delineate the clinical need for including non-influenza respiratory viruses in the diagnostic work-up in these populations are warranted.


Necrotizing enterocolitis


title: Immunotherapeutic strategies for sexually transmitted viral infections: HIV, HSV and HPV

text: Abstract More than 1 million sexually transmitted infections (STIs) are acquired each day globally. Etiotropic drugs cannot effectively control infectious diseases therefore, there is a dire need to explore alternative strategies especially those based on the regulation of immune system. The review discusses all rational approaches to develop better understanding towards immunotherapeutic strategies based on modulation of immune system in an attempt to curb the elevating risk of infectious diseases such as HIV, HPV and HSV because of their high prevalence. Development of monoclonal antibodies, vaccines and several other immune based treatments are promising alternative strategies that are offering new opportunities to eradicate pathogens.


title: Concurrent Measurement of Dynamic Changes in Viral Load, Serum Enzymes, T Cell Subsets, and Cytokines in Patients with Severe Fever with Thrombocytopenia Syndrome

text: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infection caused by a novel Bunyavirus. Analysis on the dynamic changes of clinical, laboratory, and immunological abnormalities associated with SFTS in a concurrent study is lacking. Thirty-three SFTS patients were admitted to Jiangsu People's Hospital, Nanjing, China, and diagnosis was made based on the clinical symptoms and positive viral RNA detected by RT-PCR. Four patients deceased and twenty-nine survived. Blood samples were collected every other day between Day 5 and Day 15 from the onset of fever. Samples from healthy volunteers were used as normal controls. Peak viral RNA load, serum enzymes, IL-6, and IL-10 were significantly higher in deceased patients compared to survivors. Viral load, serum enzymes, and cytokines declined in survivors within 2 weeks from onset of fever. CD69+ T cells were elevated early after infection while HLA-DR+ and CTLA4+ T cells were elevated during the recovery phase of those who survived. High level SFTSV viral load was concurrently observed with reduced PLT, elevated serum enzymes, elevated pro-inflammatory and anti-inflammatory cytokines, and activation of CD69+ T cells. The degree and pattern of changes in these parameters may indicate the clinical outcome in SFTSV-infected patients.


title: Ictus isquémico e infección por SARS-CoV-2, ¿asociación casual o causal?

text: Resumen Introducción: Se ha comunicado la asociación de ictus isquémico y COVID-19, con mayor frecuencia en aquellos pacientes más graves. Sin embargo, se desconoce en qué medida podría estar en relación con la inflamación sistémica e hipercoagulabilidad producidas en el contexto de la infección. Métodos: Descripción de cuatro pacientes atendidos en nuestro Centro por ictus isquémico y diagnóstico de COVID-19, clasificándolos según el grado de probabilidad causal entre el estado de hipercoagulabilidad y el ictus isquémico. Revisión de la literatura sobre los posibles mecanismos implicados en la etiopatogenia del ictus isquémico en este contexto. Resultados: Dos pacientes se consideraron con alta probabilidad causal: presentaban infartos corticales, sin patología cardioembólica ni arterial significativa, con parámetros de inflamación sistémica e hipercoagulabilidad; las otras dos pacientes eran de edad avanzada y el ictus isquémico se consideró cardioembólico, con una probable asociación casual de COVID-19. Conclusiones: La inflamación sistémica, junto con la posible acción directa del virus, provocaría disfunción endotelial, generando un estado de hipercoagulabilidad que podría considerarse una causa potencial de ictus isquémico. Sin embargo, puesto que los mecanismos del ictus pueden ser múltiples, se precisan estudios más amplios que evalúen esta hipótesis. Mientras tanto, el estudio etiológico del ictus en pacientes con COVID-19 debe ser sistemático atendiendo a los protocolos vigentes, con las adaptaciones necesarias en relación con las circunstancias clínicas y epidemiológicas de la actual pandemia. Abstract Introduction: Ischaemic stroke has been reported in patients with COVID-19, particularly in more severe cases. However, it is unclear to what extent this is linked to systemic inflammation and hypercoagulability secondary to the infection. Materials and methods: We describe the cases of 4 patients with ischaemic stroke and COVID-19 who were attended at our hospital. Patients are classified according to the likelihood of a causal relationship between the hypercoagulable state and ischaemic stroke. We also conducted a review of studies addressing the possible mechanisms involved in the aetiopathogenesis of ischaemic stroke in these patients. Results: The association between COVID-19 and stroke was probably causal in 2 patients, who presented cortical infarcts and had no relevant arterial or cardioembolic disease, but did show signs of hypercoagulability and systemic inflammation in laboratory analyses. The other 2 patients were of advanced age and presented cardioembolic ischaemic stroke; the association in these patients was probably incidental. Conclusions: Systemic inflammation and the potential direct action of the virus may cause endothelial dysfunction, resulting in a hypercoagulable state that could be considered a potential cause of ischaemic stroke. However, stroke involves multiple pathophysiological mechanisms; studies with larger samples are therefore needed to confirm our hypothesis. The management protocol for patients with stroke and COVID-19 should include a complete aetiological study, with the appropriate safety precautions always being observed.


title: Role of respiratory pathogens in infants hospitalized for a first episode of wheezing and their impact on recurrences

text: ABSTRACT In order to evaluate the infectious agents associated with the first episode of severe acute wheezing in otherwise healthy infants and to define the role of each of them in recurrences, 85 patients in Italy, aged <12 months, hospitalized because of a first acute episode of wheezing, were prospectively enrolled between 1 October 2005 and 31 March 2006. Upon enrolment, nasopharyngeal swabs were collected for the real-time PCR detection of respiratory syncytial virus (RSV) types A and B, influenza virus types A and B, adenovirus, parainfluenza viruses types 1, 2, 3 and 4, rhinovirus, human metapneumovirus, human coronavirus types 229E, OC43, NL63, and HKU1, bocavirus, enterovirus, and paraechovirus; nasopharyngeal aspirates were also obtained to detect atypical bacteria. At least one infectious agent was identified in 76 children (89.4%). RSV was the most frequently detected pathogen and its prevalence was significantly higher than that of the other pathogens in both age groups, and significantly higher in the children aged 3–12 months than in those aged <3 months. Only the children with RSV infection experienced recurrent wheezing. Viral load was significantly higher in children with than in those without recurrent wheezing. This study shows that RSV is the main reason for hospitalization during the first wheezing episode in infants, and that it appears to be the only pathogen associated with a high frequency of recurrences. A high viral load seems to be strictly related to the likelihood of recurrence.


title: Description et place des techniques bactériologiques dans la prise en charge des infections pulmonaires

text: Résumé Les pneumopathies aiguës recouvrent des contextes cliniques variés et les étiologies bactériennes impliquées le sont tout autant. Aucun outil microbiologique n’est 100 % sensible ni 100 % spécifique et malgré les investigations, plus de 30 % des pneumopathies restent sans étiologie identifiée. Si aucun prélèvement n’est indiqué pour les patients traités en ambulatoire, les prélèvements respiratoires non invasifs sont à privilégier pour les pneumopathies aiguës hospitalisées (communautaires ou associées aux soins), tandis que les prélèvements invasifs sont indiqués en seconde ligne pour les pneumopathies aiguës communautaires en réanimation, et en première ligne pour les pneumopathies aiguës de l’immunodéprimé. La culture microbiologique garde une place importante, à condition que le malade soit prélevé avant instauration de l’antibiothérapie. Certains contextes peuvent justifier le recours aux hémocultures, à la recherche d’antigènes urinaires ou aux sérologies. Les PCR rendent déjà service au quotidien mais l’avenir à court terme appartient probablement aux panels moléculaires multiplex capables de détecter de nombreux micro-organismes en quelques heures, surtout dans les pneumopathies communautaires sévères de réanimation et les pneumopathies aiguës de l’immunodéprimé. Le séquençage nucléotidique haut débit révolutionnera bientôt le diagnostic microbiologique, en pneumologie comme dans les autres domaines de l’infectiologie. Summary Acute pneumonias occur in a variety of clinical settings and accurate identification of bacterial causes is extremely important. No microbiological tool is either 100 % sensitive or 100 % specific, and despite investigations, aetiology remains unanswered in more than 30 % of pneumonia. No sample may be necessary for patients treated as outpatients, non invasive respiratory specimens are preferred in hospitalised individuals (community or healthcare associated), while invasive specimens are used as second line for community acquired pneumonia (CAP) in intensive care, and in the first line where pneumonia occurs in immunosuppressed patients. Bacterial cultures have an important place, if the sample is taken before the introduction of antibiotic therapy. Some contexts may justify the use of blood cultures, testing for urinary antigens or serology. PCR is already becoming available as a daily service but the short-term future probably belongs to molecular multiplex panels capable of detecting many microorganisms within hours, especially in severe CAP resuscitation and in pneumonia in the immunosuppressed. High-throughput sequencing nucleotide techniques will soon revolutionize microbiological diagnosis in respiratory medicine, as in other areas of infectious diseases.


Triage of scarce critical care resources in COVID-19: an implementation guide for regional allocation An expert panel report of the Task Force for Mass Critical Care and the American College of Chest Physicians


title: Detection of human rhinovirus C in fecal samples of children with gastroenteritis

text: Abstract Background Despite recent discovery of the novel human rhinovirus species, HRV-C, little is known about the association of HRV-C in diseases other than respiratory tract infections. Objectives To investigate the presence of HRV-C in fecal samples of children with gastroenteritis. Study design 734 fecal samples from hospitalized children with gastroenteritis were subject to picornavirus detection by RT-PCR of the conserved 5′-NCR. Positive samples were subject to VP4 and 3Dpol gene analysis for species determination. The clinical and molecular epidemiology of HRV-C and other picornaviruses was analyzed. Results Picornaviruses were detected in 113 (15.4%) of 734 fecal samples from children with gastroenteritis by RT-PCR of 5′-NCR, with 58 containing potential HRVs and 55 containing other enteroviruses. PCR of the VP4 and 3Dpol regions was positive in 21 and 19 samples respectively (both regions positive in 8 samples). Sequencing analysis showed the presence of HRV-C in four samples, and diverse picornaviruses including HRV-A (n =2), HEV-A (n =2), HEV-B (n =2), HEV-C (n =21) and HPeV (n =2) in other samples, with co-detection of HRV-C and HPeV in one sample. Of the four children with HRV-C detected in fecal samples, three presented with diarrhea in the absence of respiratory symptoms, while one also had acute bronchiolitis. The four HRV-C strains from fecal samples belonged to the existing clade of diverse HRV-C genotypes, indistinguishable from previous respiratory strains. Conclusions HRV-C can be detected in fecal samples of children with gastroenteritis, in the absence of respiratory symptoms. This study also represented the first to detect HPeV in our population.


title: Subcutaneous tocilizumab treatment in patients with severe COVID-19–related cytokine release syndrome: An observational cohort study

text: BACKGROUND: Patients with severe coronavirus disease 2019 (COVID-19) have elevated levels of acute phase reactants and inflammatory cytokines, including interleukin-6, indicative of cytokine release syndrome (CRS). The interleukin-6 receptor inhibitor tocilizumab is used for the treatment of chimeric antigen receptor T-cell therapy–induced CRS. METHODS: Patients aged 18 years or older with laboratory-confirmed COVID-19 admitted to the Annunziata Hospital in Cosenza, Italy, through March 7, 2020, who received at least one dose of tocilizumab 162 mg subcutaneously for the treatment of COVID-19–related CRS in addition to standard care were included in this retrospective observational study. The primary observation was the incidence of grade 4 CRS after tocilizumab treatment. Chest computed tomography (CT) scans were evaluated to investigate lung manifestations. FINDINGS: Twelve patients were included; all had fever, cough, and fatigue at presentation, and all had at least one comorbidity (hypertension, six patients; diabetes, five patients; chronic obstructive lung disease, four patients). Seven patients received high-flow nasal cannula oxygen therapy and five received non-invasive mechanical ventilation for lung complications of COVID-19. No incidence of grade 4 CRS was observed within 1 week of tocilizumab administration in all 12 patients (100%) and within 2 days of tocilizumab administration in 5 patients (42%). The predominant pattern on chest CT scans at presentation was ground-glass opacity, air bronchograms, smooth or irregular interlobular or septal thickening, and thickening of the adjacent pleura. Follow-up CT scans 7 to 10 days after tocilizumab treatment showed improvement of lung manifestations in all patients. No adverse events or new safety concerns attributable to tocilizumab were reported. INTERPRETATION: Tocilizumab administered subcutaneously to patients with COVID-19 and CRS is a promising treatment for reduction in disease activity and improvement in lung function. The effect of tocilizumab should be confirmed in a randomised controlled trial.


title: Differential susceptibility of macrophages to serotype II feline coronaviruses correlates with differences in the viral spike protein

text: Abstract The ability to infect and replicate in monocytes/macrophages is a critically distinguishing feature between the two feline coronavirus (FCoV) pathotypes: feline enteric coronavirus (FECV; low-virulent) and feline infectious peritonitis virus (FIPV; lethal). Previously, by comparing serotype II strains FIPV 79-1146 and FECV 79-1683 and recombinant chimeric forms thereof in cultured feline bone marrow macrophages, we mapped this difference to the C-terminal part of the viral spike (S) protein (S2). In view of the later identified diagnostic difference in this very part of the S protein of serotype I FCoV pathotypes, the present study aimed to further define the contribution of the earlier observed ten amino acids difference to the serotype II virus phenotype in macrophages. Using targeted RNA recombination as a reverse genetics system we introduced the mutations singly and in combinations into the S gene and evaluated their effects on the infection characteristics of the mutant viruses in macrophages. While some of the single mutations had a significant effect, none of them fully reverted the infection phenotype. Only by combining five specific mutations the infections mediated by the FIPV and FECV spike proteins could be fully blocked or potentiated, respectively. Hence, the differential macrophage infection phenotype is caused by the cooperative effect of five mutations, which occur in five functionally different domains of the spike fusion subunit S2. The significance of these observations will be discussed, taking into account also some questions related to the identity of the virus strains used.


title: Transmission of viruses through shellfish: when specific ligands come into play

text: Shellfish are known as vectors for human pathogens and despite regulation based on enteric bacteria they are still implicated in viral outbreaks. Among shellfish, oysters are the most common vector of contamination, and the pathogens most frequently involved in these outbreaks are noroviruses, responsible for acute gastroenteritis in humans. Analysis of shellfish-related outbreak data worldwide show an unexpected high proportion of NoV GI strains. Recent studies performed in vitro, in vivo and in the environment indicate that oysters are not just passive filters, but can selectively accumulate norovirus strains based on viral carbohydrate ligands shared with humans. These observations contribute to explain the GI bias observed in shellfish-related outbreaks compared to other outbreaks.


title: Planning and preparing for public health threats at airports

text: The ever-increasing speed and scope of human mobility by international air travel has led to a global transport network for infectious diseases with the potential to introduce pathogens into non-endemic areas, and to facilitate rapid spread of novel or mutated zoonotic agents. Robust national emergency preparedness is vital to mitigate the transmission of infectious diseases agents domestically and to prevent onward spread to other countries. Given the complex range of stakeholders who respond to an infectious disease threat being transmitted through air travel, it is important that protocols be tested and practised extensively in advance of a real emergency. Simulation exercises include the identification of possible scenarios based on the probability of hazards and the vulnerability of populations as a basis for planning, and provide a useful measure of preparedness efforts and capabilities. In October 2016, a live simulation exercise was conducted at a major airport in Ireland incorporating a public health threat for the first time, with the notification of a possible case of MERS-CoV aboard an aircraft plus an undercarriage fire. Strengths of the response to the communicable disease threat included appropriate public health risk assessment, case management, passenger information gathering, notification to relevant parties, and communication to passengers and multiple agencies. Lessons learned include: o Exercise planning should not be overly ambitious. In testing too many facets of emergency response, the public health response could be deprioritised. o The practical implementation of communication protocols in a real-time exercise of this scope proved challenging. These protocols should continue to be checked and tested by desk-top exercises to ensure that all staff concerned are familiar with them, especially in the context of staff turn-over. o The roles and responsibilities of the various agencies must be clear to avoid role confusion. o Equipment and infrastructure capacities must be considered and in place in advance of an actual incident or test, for example whether or not cell phone signals require boosting during a major event. Importantly, exercises bring together individuals representing organisations with different roles and perspectives allowing identification of capabilities and limitations, and problem solving about how to address the gaps and overlaps in a low-threat collaborative setting.


title: Did Location-based Games Motivate Players to Socialize During COVID-19?

text: Abstract Location-based games (LBGs) are typically played outdoors, as moving in the game is done by moving in the real world. However, during the COVID-19 pandemic, people were advised and even forced by governments to stay home and avoid social contact to slow down the spreading of the virus. The major LBG developers reacted by making in-game adjustments that allow playing from home, while still maintaining some incentives for players to go outdoors and socialise. For investigating factors influencing intention to play LBGs socially during the on-going pandemic, we collected cross-sectional survey data (N=855) from Finnish players of the most popular LBG, Pokémon GO. The results showed that perceived severity of the pandemic and a positive attitude towards both governmental measures and in-game changes for combatting COVID-19 predicted intention to reduce social playing. Fear of missing out and deficient self-regulation increased playing intensity, which in turn negatively correlated with the intention to reduce social playing. Our findings demonstrate the influence that LBGs can have on human behaviour even during global crises such as COVID-19. As such, LBGs can be considered a resource in designing interventions for influencing movement at a population level.


title: Small Molecule Inhibitors of CRM1

text: The transport through the nuclear pore complex is used by cancer cells to evade tumor-suppressive mechanisms. Several tumor-suppressors have been shown to be excluded from the cell nucleus in cancer cells by the nuclear export receptor CRM1 and abnormal expression of CRM1 is oncogenic. Inhibition of CRM1 has long been postulated as potential approach for the treatment of cancer and to overcome therapy resistance. Furthermore, the nuclear export of viral components mediated by the CRM1 is crucial in various stages of the viral lifecycle and assembly of many viruses from diverse families, including coronavirus. However, the first nuclear export inhibitors failed or never entered into clinical trials. More recently CRM1 reemerged as a cancer target and a successful proof of concept was achieved with the clinical approval of Selinexor. The chemical complexity of natural products is a promising perspective for the discovery of new nuclear export inhibitors with a favorable toxicity profile. Several screening campaigns have been performed and several natural product-based nuclear export inhibitors have been identified. With this review we give an overview over the role of CRM1-mediated nuclear export in cancer and the effort made to identify and develop nuclear export inhibitors in particular from natural sources.


title: Simultaneous determination of six flavonoids from Paulownia tomentosa flower extract in rat plasma by LC–MS/MS and its application to a pharmacokinetic study

text: Abstract A simple, rapid and sensitive liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed and validated for simultaneous determination of six components including apigenin, quercetin, apigenin-7-O-β-d-glucoside, quercetin-3-O-β-d-glucoside, 3′-methoxyluteolin-7-O-β-d-glucoside, and tricin-7-O-β-d-glucopyranoside in rat plasma using formononetin as the internal standard (IS). The plasma samples were pretreated by a one-step liquid–liquid extraction with dichloromethane. The chromatographic separation was carried out on a ZORBAX SB-Aq column with a gradient mobile phase consisting of acetonitrile and 2mM aqueous ammonium acetate. All analytes and IS were quantitated through electrospray ionization in negative ion multiple reaction monitoring mode. The mass transitions were as follows: m/z 269.1→117.2 for apigenin, m/z 301.2→151.2 for quercetin, m/z 431.3→311.2 for apigenin-7-O-β-d-glucoside, m/z 463.2→300.2 for quercetin-3-O-β-d-glucoside, m/z 461.3→283.1 for 3′-methoxyluteolin-7-O-β-d-glucoside, m/z 491.3→313.1 for tricin-7-O-β-d-glucopyranoside, and m/z 267.2→252.2 for IS, respectively. All calibration curves exhibited good linearity with correlation coefficient (r)>0.995. The intra-day and inter-day precisions (RSD) at three QC levels were both less than 14.0% and the accuracies ranged from 89.8% to 113.8%. The extraction recoveries of six compounds ranged from 82.3% to 92.5%. The validated method was successfully applied to pharmacokinetic study of the six components in male rat plasma after oral administration of Paulownia tomentosa flower extract.


title: Application of RNA interference for inhibiting the replication of feline immunodeficiency virus in chronically infected cell lines

text: Abstract RNA interference (RNAi) is a process in which double-stranded RNA induces the post-transcriptional sequence-specific degradation of homologous messenger RNA. The present study was carried out to apply the RNAi technology to inhibit the replication of feline immunodeficiency virus (FIV). Four small interfering RNAs (siRNAs) homologous to the FIV gag gene were synthesized and transfected into a feline fibroblastic cell line chronically infected with FIV (CRFK/FIV). These synthetic siRNAs efficiently inhibited the replication of FIV. Next, we examined the effect of retroviral vector-mediated transfer of FIV-specific short hairpin RNA (shRNA) on the replication of FIV in a feline T-cell line chronically infected with FIV (FL4). The retroviral vector-mediated transfer of FIV-specific shRNA was shown to markedly inhibit the replication of FIV in the FL4 cells. These results provide useful information for the development of RNAi-based gene therapy strategy to control FIV infection.


title: Evaluation of two-stage weaning and trace mineral injection on receiving cattle growth performance and behavior

text: The objective was to evaluate the effects of two-stage weaning and injectable trace mineral (ITM) on receiving cattle growth performance and behavior. Angus and Simmental × Angus steers (n = 136; body weight [BW] = 200 ± 26 kg) were utilized in a 2 × 2 factorial design. Calves were blocked by source, and assigned to one of four treatments: 1) two-stage weaning and ITM (2MM), 2) two-stage weaning and saline injection (2SAL), 3) abrupt weaning and ITM (AbtMM), or 4) abrupt weaning and saline injection (AbtSAL). On d−6, calves were weighed, plastic calf weaner devices (used to prevent calf from nursing) were inserted in two-stage weaned calves, and ITM or saline injections (1 mL/45.4 kg BW) were administered. On day 0, plastic calf weaner devices were removed, and calves were weighed and shipped 272 km to Urbana, IL. Steer behavior was observed the 2 d following separation from dam. Receiving period was day 0 to 42 and growing period was day 42 to 124. Data were analyzed using the MIXED procedure of SAS and pen (six per treatment) was the experimental unit. Abruptly weaned calves had greater (P < 0.01) preweaning average daily gain (ADG) than two-stage weaned calves. Treatment did not affect (P ≥ 0.16) ADG during the receiving or growing period; however, calves that received ITM tended (P 0.06) to have greater ADG from day 0 to 124. During the receiving period, abruptly weaned calves tended (P = 0.08) to eat more than two-stage calves and ITM calves ate more (P = 0.03) than calves that received saline. There was a weaning strategy × ITM interaction (P < 0.01) for dry matter intake (DMI) from day 0 to 124; 2MM calves ate more (P < 0.01) than 2SAL, but DMI was not different (P = 0.58) between AbtMM and AbtSAL calves. There was a weaning strategy × ITM interaction (P < 0.01) for gain-to-feed ratio (G:F) from day 0 to 124; 2SAL calves had greater (P = 0.05) G:F than AbtSAL, with 2MM and AbtMM calves being intermediate and not different (P = 0.38) than each other. Two-stage weaning decreased (P ≤ 0.02) the percentage of calves walking, standing, and vocalizing, and increased (P ≤ 0.02) the percentage of calves lying and eating following separation from dam. Two-stage weaning decreased preweaning ADG and behavioral signs of stress at feedlot arrival, but had no effect on overall growth. In addition, ITM had no effect on calf BW or behavior, but increased overall DMI in two-stage weaned calves compared to abruptly weaned calves and tended to increase overall ADG regardless of weaning strategy.


title: One time intranasal vaccination with a modified vaccinia Tiantan strain MVTTZCI protects animals against pathogenic viral challenge

text: Abstract To combat variola virus in bioterrorist attacks, it is desirable to develop a noninvasive vaccine. Based on the vaccinia Tiantan (VTT) strain, which was historically used to eradicate the smallpox in China, we generated a modified VTT (MVTTZCI) by removing the hemagglutinin gene and an 11,944bp genomic region from HindIII fragment C2L to F3L. MVTTZCI was characterized for its host cell range in vitro and preclinical safety and efficacy profiles in mice. Despite replication-competency in some cell lines, unlike VTT, MVTTZCI did not cause death after intracranial injection or body weight loss after intranasal inoculation. MVTTZCI did not replicate in mouse brain and was safe in immunodeficient mice. MVTTZCI induced neutralizing antibodies via the intranasal route of immunization. One time intranasal immunization protected animals from the challenge of the pathogenic vaccinia WR strain. This study established proof-of-concept that the attenuated replicating MVTTZCI may serve as a safe noninvasive smallpox vaccine candidate.


COVID-19 diagnostic process in mainland China: the math beyond pneumonia


China uses mass surveillance tech to fight spread of coronavirus


title: STING is required for host defense against neuropathological West Nile virus infection

text: West Nile Virus (WNV), an emerging and re-emerging RNA virus, is the leading source of arboviral encephalitic morbidity and mortality in the United States. WNV infections are acutely controlled by innate immunity in peripheral tissues outside of the central nervous system (CNS) but WNV can evade the actions of interferon (IFN) to facilitate CNS invasion, causing encephalitis, encephalomyelitis, and death. Recent studies indicate that STimulator of INterferon Gene (STING), canonically known for initiating a type I IFN production and innate immune response to cytosolic DNA, is required for host defense against neurotropic RNA viruses. We evaluated the role of STING in host defense to control WNV infection and pathology in a murine model of infection. When challenged with WNV, STING knock out (-/-) mice displayed increased morbidity and mortality compared to wild type (WT) mice. Virologic analysis and assessment of STING activation revealed that STING signaling was not required for control of WNV in the spleen nor was WNV sufficient to mediate canonical STING activation in vitro. However, STING-/- mice exhibited a clear trend of increased viral load and virus dissemination in the CNS. We found that STING-/- mice exhibited increased and prolonged neurological signs compared to WT mice. Pathological examination revealed increased lesions, mononuclear cellular infiltration and neuronal death in the CNS of STING-/- mice, with sustained pathology after viral clearance. We found that STING was required in bone marrow derived macrophages for early control of WNV replication and innate immune activation. In vivo, STING-/- mice developed an aberrant T cell response in both the spleen and brain during WNV infection that linked with increased and sustained CNS pathology compared to WT mice. Our findings demonstrate that STING plays a critical role in immune programming for the control of neurotropic WNV infection and CNS disease.


title: Guidelines, law, and governance: disconnects in the global control of airline-associated infectious diseases

text: Summary International air travel is increasingly affecting the epidemiology of infectious diseases. A particular public health, economic, and political concern is the role of air travel in bringing infectious passengers or vectors to previously non-endemic areas. Yet, little research has been done to investigate either the infection risks associated with air travel or the empirical evidence for the effectiveness of infection control measures on aircraft and at borders. We briefly review the interface between international and national legislation, policy, and guidelines in the context of existing infection risks and possible scenarios. We have found that public health guidance and legislation, which airlines are required to follow, are often contradictory and confusing. Infection control measures for air travel need to be underpinned by coherent and enforceable national and international legislation that is based on solid epidemiological evidence. We recommend further research investment into more effective on-board vector control, health screening, and risk communications strategies, and the development of enforceable and harmonised international legislation.


title: Improved Molecular Diagnosis of COVID-19 by the Novel, Highly Sensitive and Specific COVID-19-RdRp/Hel Real-Time Reverse Transcription-PCR Assay Validated In Vitro and with Clinical Specimens

text: On 31 December 2019, the World Health Organization was informed of a cluster of cases of pneumonia of unknown etiology in Wuhan, China. Subsequent investigations identified a novel coronavirus, now named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), from the affected patients. Highly sensitive and specific laboratory diagnostics are important for controlling the rapidly evolving SARS-CoV-2-associated coronavirus disease 2019 (COVID-19) epidemic. In this study, we developed and compared the performance of three novel real-time reverse transcription-PCR (RT-PCR) assays targeting the RNA-dependent RNA polymerase (RdRp)/helicase (Hel), spike (S), and nucleocapsid (N) genes of SARS-CoV-2 with that of the reported RdRp-P2 assay, which is used in >30 European laboratories. Among the three novel assays, the COVID-19-RdRp/Hel assay had the lowest limit of detection in vitro (1.8 50% tissue culture infective doses [TCID(50)]/ml with genomic RNA and 11.2 RNA copies/reaction with in vitro RNA transcripts). Among 273 specimens from 15 patients with laboratory-confirmed COVID-19 in Hong Kong, 77 (28.2%) were positive by both the COVID-19-RdRp/Hel and RdRp-P2 assays. The COVID-19-RdRp/Hel assay was positive for an additional 42 RdRp-P2-negative specimens (119/273 [43.6%] versus 77/273 [28.2%]; P < 0.001), including 29/120 (24.2%) respiratory tract specimens and 13/153 (8.5%) non-respiratory tract specimens. The mean viral load of these specimens was 3.21 × 10(4) RNA copies/ml (range, 2.21 × 10(2) to 4.71 × 10(5) RNA copies/ml). The COVID-19-RdRp/Hel assay did not cross-react with other human-pathogenic coronaviruses and respiratory pathogens in cell culture and clinical specimens, whereas the RdRp-P2 assay cross-reacted with SARS-CoV in cell culture. The highly sensitive and specific COVID-19-RdRp/Hel assay may help to improve the laboratory diagnosis of COVID-19.


title: THE IMPACT OF COVID-19 ON SOLID ORGAN DONATION: The North Italy Transplantation program (NITp) EXPERIENCE

text: Introduction coronavirus disease 2019 (COVID-19) outbreak has unfavourably influenced the overall donation activity. Aim the aim of this study was to investigate effect of COVID-19 on transplantation in the North Italy Transplant program (NITp). Material and methods this was a cross-sectional study in which all consecutive potential deceased donors proposed in the NITp during 6 weeks from February 21, 2020 (period A) were included and compared to all potential donors during the same time frame of the previous years (period B) and all potential donors during six weeks before February 20, 2020 (period C). Results fifty-eight deceased donors were proposed during period A, 95 during Period B and 128 Period C. After evaluation process 32/58 (55.2%), 60/95 (63.2%) and 79/128 (61.7%) donors were used for organ donation in period A, B and C, respectively (p-value 0.595). Results: this study showed an important reduction of donations and transplants during the COVID-19 pandemic. A strict monitoring should be mandatory to ensure a safety procedure.


ECONOMIC RECESSION FROM THE COVID-19 PANDEMIC SIGNALS RECRUITING DIFFICULTY AHEAD FOR RADIOLOGY RESIDENCY PROGRAMS


title: Direct observation of distinct A/P hybrid-state tRNAs in translocating ribosomes

text: Transfer RNAs (tRNAs) link the genetic code in the form of messenger RNA (mRNA) to protein sequence. Translocation of tRNAs through the ribosome from aminoacyl (A) site to peptidyl (P) site, and from P-site to exit (E) site is catalysed in eukaryotes by the translocase elongation factor 2 (EF-2), and in prokaryotes by its homologue EF-G. During tRNA movement one or more “hybrid” states (A/P) is occupied, but molecular details of them and of the translocation process are limited. Here we show by cryo-electron microscopy (cryo-EM) that a population of mammalian ribosomes stalled at an mRNA pseudoknot structure contains structurally-distorted tRNAs in two different A/P hybrid states. In one (A/P’) the tRNA is in contact with the translocase EF-2 which induces it. In the other (A/P”) the translocase is absent. The existence of these alternative A/P intermediate states has relevance to our understanding of the mechanics and kinetics of translocation.


title: COVID‐19 and End Stage Renal Disease

text: The new coronavirus disease, named by World Health Organization (WHO) as COVID‐19 brought great challenges to patients with end‐stage renal disease (ESRD). In general, ESRD patients have higher number of comorbidities and are at age‐risk for severe pulmonary presentation of this disease. Another important issue is that hemodialysis (HD) clinics are usually not located in small towns, and these frail patients often travel to their dialysis center in groups and also cannot keep the 6‐feet safe distance during their HD session


title: Evaluation of two chimeric bovine-human parainfluenza virus type 3 vaccines in infants and young children

text: Human parainfluenza virus type 3 (HPIV3) is an important cause of lower respiratory tract illness in children, yet a licensed vaccine or antiviral drug is not available. We evaluated the safety, tolerability, infectivity, and immunogenicity of two intranasal, live-attenuated HPIV3 vaccines, designated rHPIV3-N(B) and rB/HPIV3, that were cDNA-derived chimeras of HPIV3 and bovine PIV3 (BPIV3). These were evaluated in adults, HPIV3 seropositive children, and HPIV3 seronegative children. A total of 112 subjects participated in these studies. Both rB/HPIV3 and rHPIV3-N(B) were highly restricted in replication in adults and seropositive children but readily infected seronegative children, who shed mean peak virus titers of 10(2.8) vs. 10(3.7) pfu/mL, respectively. Although rB/HPIV3 was more restricted in replication in seronegative children than rHPIV3-N(B), it induced significantly higher titers of hemagglutination inhibition (HAI) antibodies against HPIV3. Taken together, these data suggest that the rB/HPIV3 vaccine is the preferred candidate for further clinical development.


title: Benefits of Exercise on Influenza or Pneumonia in Older Adults: A Systematic Review

text: A coronavirus pandemic has recently become one of the greatest threats the world is facing. Older adults are under a high risk of infection because of weaker immune systems. Therefore, the purpose of this review is to summarize the recent scientific evidence that outlines the effects of exercise on influenza or pneumonia in older adults. An electronic literature search was conducted using the WEB OF SCIENCE, SCIENCEDIRECT and GOOGLE SCHOLAR databases using the following keywords, “Exercise,” “Older adult,” “Influenza,” and “Pneumonia.” Any randomized control trials, cross-sectional and observational studies that related to this topic were all included. Twenty studies met the eligibility criteria for this review. Thirteen randomized control trials investigated the effects of exercise on the immune responses to influenza or pneumonia vaccination: seven trials employed moderate aerobic exercise, three employed resistance exercise, and the remaining three used Asian martial arts or special home-based exercises. Five cross-sectional and two observational studies examined the associations between exercise/physical condition and influenza/pneumonia. Most of the current studies suggested that prolonged moderate aerobic exercise may help to reduce the risk of influenza-related infection and improve the immune responses to influenza or pneumonia vaccination in older adults. In addition, training in traditional Asian martial arts was also found to be beneficial. Future research should focus on the different effects of moderate and vigorous exercise on influenza-related diseases.


title: Prevalence of human metapneumovirus in adults with acute respiratory tract infection in Beijing, China

text: Summary Objective To evaluate the prevalence and clinical manifestations of human metapneumovirus (hMPV) in immunocompetent Chinese adults with acute respiratory tract infections (ARTIs). Methods A reverse transcription PCR (RT-PCR) assay targeting the P gene was developed in this study and used to detect hMPV in nasal and throat swabs collected from 2936 immunocompetent adult patients with ARTIs in Beijing, China between July 2008 and June 2010. Results Among the 2936 patients studied, 49 (1.7%) were positive for hMPV, of whom 14 (28.6%) were positive for hMPV_A2b, 19 (38.8%) for hMPV_B1, and 16 (32.6%) for hMPV_B2. hMPV_A1 was not detected. An average detection rate of 6.6% was observed in the peak months of the two epidemic seasons studied. The hMPV prevalence was higher in the sampled elderly (>65 years, 3.2%) than in middle aged adults (25–65 years; 2.0%) and teenagers (14–25 years; 0.9%). During the study period, hMPV infections showed a biennial rhythm of seasonality, peaking from November to March in 2008/09 and from March to June in 2010. Conclusion hMPV infection plays an important role in immunocompetent adults in its epidemic season. The demographic and clinical data presented in this study improves our understanding of the pathogenesis and clinical burden of hMPV infection in adults.