title: COVID-19: laboratory diagnosis for clinicians. An updating article

text: COVID-19 (coronavirus disease 2019) is an infectious disease caused by the new coronavirus associated with severe acute respiratory syndrome 2 (SARS-CoV-2) Coronaviridae comprises a large family, of which at least seven members are known to cause respiratory diseases in humans Coronaviruses have the ability to infect virtually all major groups of animals and, eventually, can infect humans SARS-CoV-2 is the third coronavirus to cross the species barrier and infect humans This virus was identified in an outbreak of pneumonia cases in Wuhan city, Hubei province, China, in December 2019 Its entire genome is inscribed on a single strand of ribonucleic acid Some proteins present on the surface of the virus act as facilitators for its entry into host cells, while others, apparently, are related to its pathogenesis Coronaviruses are responsible for respiratory infections in humans and some animals The infection is often mild to moderate in intensity, but some coronaviruses may cause serious illnesses, such as severe acute respiratory syndrome (SARS), which occurred in 2002, and the Middle East respiratory syndrome (MERS) Coronaviruses can activate an excessive and unregulated immune response, which may promote SARS development Although the lungs are one of the target organs, the hypoxia mechanism is systemic and other organs begin to suffer both through lack of oxygen and through deregulation of inflammation control mechanisms


title: Nucleotide sequence of bovine rotavirus gene 1 and expression of the gene product in Baculovirus

text: Abstract The nucleotide sequence of the gene that encodes for the structural viral protein VP1 of bovine rotavirus (RF strain) has been determined. The sequence data indicate that segment 1 contains 3302 by and is A+T rich (65.3%). The positive strand of segment 1 contains a single open reading frame that extends 1088 codons and possesses 5′- and 3′-terminal untranslated regions of 18 and 20 bp, respectively. The first AUG conforms to the Kozak consensus sequence and if utilized, would yield a protein having a calculated molecular weight of 124–847, very close to the apparent molecular weight of VP1 (M.W. 125,000). The deduced amino acid sequence presents significant similarities with RNA-dependent RNA polymerase of several RNA viruses. VP1 was also synthesized in baculovirus using two transfer vecors: pAC461 and pVL941. Following infection of Sf9 cells with a recombinant baculovirus, a full-length nonfusion protein was synthesised which shares properties with authentic VP1 made in monkey kidney cells. The level of VP1 synthesis was about 10-fold higher when the baculovirus recombinant was derived from the pVL941 transfer vector. In that case, VP1 was expressed in yields approximately equivalent to 10% of the cellular protein. The recombinant protein was immunoprecipitated by hyperimmune serum raised against purified rotavirus. It also was immunogenic; a hyperimmune serum made in guinea pigs reacted with VP1 using immunoprecipitation and Western blot. This serum did not possess neutralization activity.


title: Charting the challenges behind the testing of COVID-19 in developing countries: Nepal as a case study

text: Abstract The infrastructure needed to detect SARS-CoV-2 infection (COVID-19) that complies completely with WHO guidelines is lacking across many parts of the globe, especially in developing countries, including Nepal. We outline the problems faced by such countries and suggest that the national and international community should collaborate in the development and adoption of novel protocols for the rapid detection of COVID-19 according to locally available infrastructure, in order to fight against the outbreak.


docid: rixiupem

title: Qualitative study on the shifting sociocultural meanings of the facemask in Hong Kong since the severe acute respiratory syndrome (SARS) outbreak: implications for infection control in the post-SARS era

text: BACKGROUND: The clinical importance and efficacy of facemasks in infection prevention have been documented in the international literature. Past studies have shown that the perceived susceptibility, the perceived severity of being afflicted with life-threatening diseases, and the perceived benefits of using a facemask are predictors of a person’s use of a facemask. However, I argue that people wear a facemask not merely for infection prevention, and various sociocultural reasons have been motivating people to wear (and not wear) a facemask. Facemasks thus have sociocultural implications for people. Research on the sociocultural meanings of facemasks is scant, and even less is known on how the shifting sociocultural meanings of facemasks are related to the changing social environment, which, I argue, serve as remarkable underlying factors for people using (and not using) facemasks. As new infectious diseases such as avian influenza and Middle East Respiratory Syndrome have been emerging, threatening people’s health worldwide, and because facemasks have been documented to have substantial efficacy in the prevention of infection transmission, understanding the sociocultural meanings of facemasks has significant implications for public health policymakers and health care providers in designing a socially and culturally responsive public health and infection control policy for the community. METHODS: A qualitative research design involving the use of 40 individual, in-depth semistructured interviews and a phenomenological analysis approach were adopted. RESULTS: The sociocultural meanings of the facemask have been undergoing constant change, from positive to negative, which resulted in the participants displaying hesitation in using a facemask in the post-SARS era. Because it represents a violation of societal ideologies and traditional Chinese cultural beliefs, the meanings of the facemask that had developed during the SARS outbreak failed to be sustained in the post-SARS era. CONCLUSION: The changes in meaning not only influenced the participants’ perceptions of the facemask but also influenced their perceptions of people who use facemasks, which ultimately influenced their health behavior, preventing them from using facemasks in the post-SARS era. These findings have critical implications for designing a culturally responsive infection prevention and facemask usage policy in the future.


Genomics of Emerging Infectious Disease: A PLoS Collection


title: Covid-19 pandemic by the “real-time” monitoring: the Tunisian case and lessons for global epidemics in the context of 3PM strategies

text: Covid-19 is neither the first nor the last viral epidemic which societies around the world are, were and will be affected by. Which lessons should be taken from the current pandemic situation? The Covid-19 disease is still not well characterised, and many research teams all over the world are working on prediction of the epidemic scenario, protective measures to populations and sub-populations, therapeutic and vaccination issues, amongst others. Contextually, countries with currently low numbers of Covid-19-infected individuals such as Tunisia are intended to take lessons from those countries which already reached the exponential phase of the infection distribution as well as from those which have the exponential phase behind them and record a minor number of new cases such as China. To this end, in Tunisia, the pandemic wave has started with a significant delay compared with Europe, the main economic partner of the country. In this paper, we do analyse the current pandemic situation in this country by studying the infection evolution and considering potential protective strategies to prevent a pandemic scenario. The model is predictive based on a large number of undetected Covid-19 cases that is particularly true for some country regions such as Sfax. Infection distribution and mortality rate analysis demonstrate a highly heterogeneous picture over the country. Qualitative and quantitative comparative analysis leads to a conclusion that the reliable “real-time” monitoring based on the randomised laboratory tests is the optimal predictive strategy to create the most effective evidence-based preventive measures. In contrast, lack of tests may lead to incorrect political decisions causing either unnecessary over-protection of the population that is risky for a long-term economic recession, or under-protection of the population leading to a post-containment pandemic rebound. Recommendations are provided in the context of advanced predictive, preventive and personalised (3P) medical approach.


title: COVID-19 in patients with rheumatic diseases in northern Italy: a single-centre observational and case–control study

text: BACKGROUND: The highest number of COVID-19 cases in Italy have been reported in Lombardy, a region in northern Italy. We aimed to analyse the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with rheumatic and musculoskeletal diseases living in a district of Lombardy with a high prevalence of COVID-19. METHODS: We did a single-centre observational study at the Azienda Socio Sanitaria Territoriale (ASST) Spedali Civili of Brescia, Italy. We collected data from patients with rheumatic and musculoskeletal diseases enrolled in our outpatient clinic to identify confirmed or possible cases of SARS-CoV-2 infection. Data were collected through a survey that was administered via telephone or in the outpatient clinic by rheumatologists. We also did a case–control study of all patients with confirmed COVID-19 pneumonia and rheumatic and musculoskeletal diseases who were admitted to the ASST Spedali Civili of Brescia during the study period. Cases were matched by age, sex, and month of hospital admission to at least two controls admitted to the same hospital for COVID-19 pneumonia during the study period. FINDINGS: Between Feb 24 and May 1, 2020, we collected data from 1525 patients with rheumatic and musculoskeletal diseases: 117 (8%) presented with symptoms that were compatible with COVID-19. 65 patients had a swab confirmation of SARS-CoV-2 infection, whereas 52 presented with a spectrum of symptoms indicative of COVID-19 but were not swab tested. Patients with confirmed COVID-19 were older than those with suspected COVID-19 (median age 68 [IQR 55–76] years vs 57 [49–67] years; p=0·0010) and more likely to have arterial hypertension (33 [51%] vs 14 [27%] patients; odds ratio [OR] 2·8 [95% CI 1·3–6·1]; p=0·031) and obesity (11 [17%] vs 1 [2%]; OR 11·0 [1·3–83·4]; p=0·0059). We found no differences in rheumatological disease or background therapy between confirmed and suspected COVID-19 cases. 47 (72%) of the 65 patients with confirmed COVID-19 developed pneumonia that required admission to hospital. 12 (10%) deaths occurred among the 117 patients with confirmed or suspected COVID-19 (ten in those with confirmed COVID-19 and two in those with suspected COVID-19). Deceased patients with confirmed COVID-19 were older than survivors (median age 78·8 years [IQR 75·3–81·3] vs 65·5 years [53·3–74·0]; p=0·0002). We observed no differences in sex, comorbidities, or therapies between the deceased patients and survivors. The case–control study comprised 26 patients with rheumatic and musculoskeletal diseases and COVID-19 pneumonia and 62 matched controls. We found no significant differences between cases and controls in duration of COVID-19 symptoms before admission, duration of stay in hospital, or the local chest X-ray scoring system. Glucocorticoids were used for severe respiratory manifestations related to lung involvement in 17 (65%) of 26 cases and tocilizumab in six (23%) of 26; thrombotic events occurred in four (15%) of 26 cases. Four (15%) of 26 cases and six (10%) of 62 controls died during the study period. INTERPRETATION: In this cohort of patients with rheumatic and musculoskeletal diseases in a geographical region with a high prevalence of COVID-19, a poor outcome from COVID-19 seems to be associated with older age and the presence of comorbidities rather than the type of rheumatic disease or the degree of pharmacological immunosuppression. FUNDING: None.


Therapeutic and prophylactic potential of anti-microbial peptides against coronaviruses


title: COVID-19 in Colombia endpoints. Are we different, like Europe?

text: Abstract The infection by the new coronavirus (SARS-CoV-2) has taken the dimension of a pandemic, affecting more than 160 countries in a few weeks. In Colombia, despite the implementation of the rules established by the national government, exists an elevate concern both for mortality and for the limited capacity of the health system to respond effectively to the needs of patients infected. For Colombia, assuming a case fatality rate among people infected with SARS-CoV-2 of 0.6% (average data from the information reported for Latin American countries for March 18) (Table 1), the number of deaths, in one or two weeks, could be 16 and 243, respectively. These estimates differ markedly from those documented in countries such as Spain and Italy, in which COVID-19 case fatality rates exceed 8% (case of Italy) and from the percentage of patients who have required intensive care, which has ranged from 9% to 11% of patients in Mediterranean European countries. These differences could be explained due to: a) the percentage of the population at risk (individuals older than 60 years); b) a higher epidemiological exposure to viral respiratory infections associated with more frequent exposure to them, due to geographic and climatic conditions; c) less spread of the virus by location in the tropical zone; and d) earlier preventive measures to contain the spread of SARS-CoV-2 infection. Therefore, it is possible to establish that the situation in this country will be different from in European Mediterranean and that Colombia could have different endpoints from Spain and Italy.


title: IBD in the time of corona — vigilance for immune-mediated diseases

text: The gastrointestinal tract represents a target organ for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), warranting a thorough discussion on the consequences, particularly regarding inflammatory bowel diseases. Here, aspects of gastrointestinal involvement with SARS-CoV-2, the role of viruses as modulators of mucosal immunity and as treatment-related safety hazards, and the current clinical evidence will be discussed.


title: Global analysis for spread of infectious diseases via transportation networks

text: We formulate an epidemic model for the spread of an infectious disease along with population dispersal over an arbitrary number of distinct regions. Structuring the population by the time elapsed since the start of travel, we describe the infectious disease dynamics during transportation as well as in the regions. As a result, we obtain a system of delay differential equations. We define the basic reproduction number [Formula: see text] as the spectral radius of a next generation matrix. For multi-regional systems with strongly connected transportation networks, we prove that if [Formula: see text] then the disease will be eradicated from each region, while if [Formula: see text] there is a globally asymptotically stable equilibrium, which is endemic in every region. If the transportation network is not strongly connected, then the model analysis shows that numerous endemic patterns can exist by admitting a globally asymptotically stable equilibrium, which may be disease free in some regions while endemic in other regions. We provide a procedure to detect the disease free and the endemic regions according to the network topology and local reproduction numbers. The main ingredients of the mathematical proofs are the inductive applications of the theory of asymptotically autonomous semiflows and cooperative dynamical systems. We visualise stability boundaries of equilibria in a parameter plane to illustrate the influence of the transportation network on the disease dynamics. For a system consisting of two regions, we find that due to spatial heterogeneity characterised by different local reproduction numbers, [Formula: see text] may depend non-monotonically on the dispersal rates, thus travel restrictions are not always beneficial.


title: Repurposing of FDA-approved antivirals, antibiotics, anthelmintics, antioxidants, and cell protectives against SARS-CoV-2 papain-like protease

text: SARS-CoV-2 or Coronavirus disease 19 (COVID-19) is a rapidly spreading, highly contagious, and sometimes fatal disease for which drug discovery and vaccine development are critical. SARS-CoV-2 papain-like protease (PL(pro)) was used to virtually screen 1697 clinical FDA-approved drugs. Among the top results expected to bind with SARS-CoV-2 PL(pro) strongly were three cell protectives and antioxidants (NAD+, quercitrin, and oxiglutatione), three antivirals (ritonavir, moroxydine, and zanamivir), two antimicrobials (doripenem and sulfaguanidine), two anticancer drugs, three benzimidazole anthelmintics, one antacid (famotidine), three anti-hypertensive ACE receptor blockers (candesartan, losartan, and valsartan) and other miscellaneous systemically or topically acting drugs. The binding patterns of these drugs were superior to the previously identified SARS CoV PL(pro) inhibitor, 6-mercaptopurine (6-MP), suggesting a potential for repurposing these drugs to treat COVID-19. The objective of drug repurposing is the rapid relocation of safe and approved drugs by bypassing the lengthy pharmacokinetic, toxicity, and preclinical phases. The ten drugs with the highest estimated docking scores with favorable pharmacokinetics were subjected to molecular dynamics (MD) simulations followed by molecular mechanics/generalized Born surface area (MM/GBSA) binding energy calculations. Phenformin, quercetin, and ritonavir all demonstrated prospective binding affinities for COVID-19 PL(pro) over 50 ns MD simulations, with binding energy values of −56.6, −40.9, and −37.6 kcal/mol, respectively. Energetic and structural analyses showed phenformin was more stable than quercetin and ritonavir. The list of the drugs provided herein constitutes a primer for clinical application in COVID-19 patients and guidance for further antiviral studies. Communicated by Ramaswamy H. Sarma


title: Personnel Training Course for Businesses Regarding the Response to Stranded Persons Focusing on Vulnerable People from the Perspective of Business Continuity

text: Businesses in urban areas have been required to accommodate stranded persons as temporary evacuation facilities during disasters. Regarding measures aimed at aiding stranded persons, aspects such as trust and the image of the business need to be considered. Therefore, in this study, a personnel training course was developed to smoothly take in stranded persons, and the outcomes of this training were evaluated by quizzes, entry sheets, and a questionnaire. This was a two-day and one-night course characterized by the use of role-play in which 20 participants experienced the series of processes that unfold during disasters, playing either the role of a stranded person or a facility member. This training included emergency food provision using real stockpiled food and accommodation training using actual bedding stored in a model facility. After the review, when the participants were taught the correct response for vulnerable people, their scores in the test regarding the points of caution in vulnerable people were significantly higher than those prior to the course, confirming that participants had acquired knowledge as a result. Furthermore, through training using real food and accommodation, the participants were able to understand victims’ requirements by experiencing the need for satisfactory emergency rations and comfortable bedding.


title: Modelling the Measles Outbreak at Hong Kong International Airport in 2019: A Data-Driven Analysis on the Effects of Timely Reporting and Public Awareness

text: BACKGROUND: Measles, a highly contagious disease, still poses a huge burden worldwide. Lately, a trend of resurgence threatened the developed countries. A measles outbreak occurred in the Hong Kong International Airport (HKIA) between March and April 2019, which infected 29 airport staff. During the outbreak, multiple measures were taken including daily situation updates, setting up a public enquiry platform on March 23, and an emergent vaccination program targeting unprotected staff. The outbreak was put out promptly. The effectiveness of these measures was unclear. METHODS: We quantified the transmissibility of outbreak in HKIA by the effective reproduction number, R(eff)(t), and basic reproduction number, R(0)(t). The reproduction number was modelled as a function of its determinants that were statistically examined, including lags in hospitalization, situation update, and level of public awareness. Then, we considered a hypothetical no-measure scenario when improvements in reporting and public enquiry were absent and calculated the number of infected airport staff. RESULTS: Our estimated average R(0) is 10.09 (95% CI: 1.73−36.50). We found that R(0)(t) was positively associated with lags in hospitalization and situation update, while negatively associated with the level of public awareness. The average predicted basic reproduction number, r(0), was 14.67 (95% CI: 9.01−45.32) under the no-measure scenario, which increased the average R(0) by 77.57% (95% CI: 1.71−111.15). The total number of infected staff would be 179 (IQR: 90−339, 95% CI: 23−821), namely the measure induced 8.42-fold (95% CI: 0.21−42.21) reduction in the total number of infected staff. CONCLUSION: Timely reporting on outbreak situation and public awareness measured by the number of public enquiries helped to control the outbreak.


title: The NF-κB-dependent and -independent transcriptome and chromatin landscapes of human coronavirus 229E-infected cells

text: Coronavirus replication takes place in the host cell cytoplasm and triggers inflammatory gene expression by poorly characterized mechanisms. To obtain more insight into the signals and molecular events that coordinate global host responses in the nucleus of coronavirus-infected cells, first, transcriptome dynamics was studied in human coronavirus 229E (HCoV-229E)-infected A549 and HuH7 cells, respectively, revealing a core signature of upregulated genes in these cells. Compared to treatment with the prototypical inflammatory cytokine interleukin(IL)-1, HCoV-229E replication was found to attenuate the inducible activity of the transcription factor (TF) NF-κB and to restrict the nuclear concentration of NF-κB subunits by (i) an unusual mechanism involving partial degradation of IKKβ, NEMO and IκBα and (ii) upregulation of TNFAIP3 (A20), although constitutive IKK activity and basal TNFAIP3 expression levels were shown to be required for efficient virus replication. Second, we characterized actively transcribed genomic regions and enhancers in HCoV-229E-infected cells and systematically correlated the genome-wide gene expression changes with the recruitment of Ser5-phosphorylated RNA polymerase II and prototypical histone modifications (H3K9ac, H3K36ac, H4K5ac, H3K27ac, H3K4me1). The data revealed that, in HCoV-infected (but not IL-1-treated) cells, an extensive set of genes was activated without inducible p65 NF-κB being recruited. Furthermore, both HCoV-229E replication and IL-1 were shown to upregulate a small set of genes encoding immunomodulatory factors that bind p65 at promoters and require IKKβ activity and p65 for expression. Also, HCoV-229E and IL-1 activated a common set of 440 p65-bound enhancers that differed from another 992 HCoV-229E-specific enhancer regions by distinct TF-binding motif combinations. Taken together, the study shows that cytoplasmic RNA viruses fine-tune NF-κB signaling at multiple levels and profoundly reprogram the host cellular chromatin landscape, thereby orchestrating the timely coordinated expression of genes involved in multiple signaling, immunoregulatory and metabolic processes.


title: Rotavirus vaccine efficacy: current status and areas for improvement

text: The difference noted in Rotavirus vaccine efficiency between high and low income countries correlates with the lack of universal access to clean water and higher standards of hygiene. Overcoming these obstacles will require great investment and also time, therefore more effective vaccines should be developed to meet the needs of those who would benefit the most from them. Increasing our current knowledge of mucosal immunity, response to Rotavirus infection and its modulation by circadian rhythms could point at actionable pathways to improve vaccination efficacy, especially in the case of individuals affected by environmental enteropathy. Also, a better understanding and validation of Rotavirus entry factors as well as the systematic monitoring of dominant strains could assist in tailoring vaccines to individual’s needs. Another aspect that could improve vaccine efficiency is targeting to M cells, for which new ligands could potentially be sought. Finally, alternative mucosal adjuvants and vaccine expression, storage and delivery systems could have a positive impact in the outcome of Rotavirus vaccination.


title: In vivo gene regulation using tetracycline-regulatable systems

text: Abstract Numerous preclinical studies have demonstrated the efficacy of viral gene delivery vectors, and recent clinical trials have shown promising results. However, the tight control of transgene expression is likely to be required for therapeutic applications and in some instances, for safety reasons. For this purpose, several ligand-dependent transcription regulatory systems have been developed. Among these, the tetracycline-regulatable system is by far the most frequently used and the most advanced towards gene therapy trials. This review will focus on this system and will describe the most recent progress in the regulation of transgene expression in various organs, including the muscle, the retina and the brain. Since the development of an immune response to the transactivator was observed following gene transfer in the muscle of nonhuman primate, focus will be therefore, given on the immune response to transgene products of the tetracycline inducible promoter.


“You Have to Wait a Little Longer”: Transgender (Mental) Health at Risk as a Consequence of Deferring Gender-Affirming Treatments During COVID-19


title: Correlation of Chest CT and RT-PCR Testing in Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases

text: BACKGROUND: Chest CT is used for diagnosis of 2019 novel coronavirus disease (COVID-19), as an important complement to the reverse-transcription polymerase chain reaction (RT-PCR) tests. PURPOSE: To investigate the diagnostic value and consistency of chest CT as compared with comparison to RT-PCR assay in COVID-19. METHODS: From January 6 to February 6, 2020, 1014 patients in Wuhan, China who underwent both chest CT and RT-PCR tests were included. With RT-PCR as reference standard, the performance of chest CT in diagnosing COVID-19 was assessed. Besides, for patients with multiple RT-PCR assays, the dynamic conversion of RT-PCR results (negative to positive, positive to negative, respectively) was analyzed as compared with serial chest CT scans for those with time-interval of 4 days or more. RESULTS: Of 1014 patients, 59% (601/1014) had positive RT-PCR results, and 88% (888/1014) had positive chest CT scans. The sensitivity of chest CT in suggesting COVID-19 was 97% (95%CI, 95-98%, 580/601 patients) based on positive RT-PCR results. In patients with negative RT-PCR results, 75% (308/413) had positive chest CT findings; of 308, 48% were considered as highly likely cases, with 33% as probable cases. By analysis of serial RT-PCR assays and CT scans, the mean interval time between the initial negative to positive RT-PCR results was 5.1 ± 1.5 days; the initial positive to subsequent negative RT-PCR result was 6.9 ± 2.3 days). 60% to 93% of cases had initial positive CT consistent with COVID-19 prior (or parallel) to the initial positive RT-PCR results. 42% (24/57) cases showed improvement in follow-up chest CT scans before the RT-PCR results turning negative. CONCLUSION: Chest CT has a high sensitivity for diagnosis of COVID-19. Chest CT may be considered as a primary tool for the current COVID-19 detection in epidemic areas. A translation of this abstract in Farsi is available in the supplement. - ترجمه چکیده این مقاله به فارسی، در ضمیمه موجود است.


Social Distancing in the Covid-19 Pandemic


docid: ycjzitlk

title: Potential for Introduction of Bat-Borne Zoonotic Viruses into the EU: A Review

text: Bat-borne viruses can pose a serious threat to human health, with examples including Nipah virus (NiV) in Bangladesh and Malaysia, and Marburg virus (MARV) in Africa. To date, significant human outbreaks of such viruses have not been reported in the European Union (EU). However, EU countries have strong historical links with many of the countries where NiV and MARV are present and a corresponding high volume of commercial trade and human travel, which poses a potential risk of introduction of these viruses into the EU. In assessing the risks of introduction of these bat-borne zoonotic viruses to the EU, it is important to consider the location and range of bat species known to be susceptible to infection, together with the virus prevalence, seasonality of viral pulses, duration of infection and titre of virus in different bat tissues. In this paper, we review the current scientific knowledge of all these factors, in relation to the introduction of NiV and MARV into the EU.


title: Detection of bovine coronavirus using a TaqMan-based real-time RT-PCR assay

text: Abstract A real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for the detection of bovine coronavirus (BCoV) RNA in clinical samples is described. The assay is based on TaqMan technology, consisting of two primers and one probe labeled with the reporter dye 6-carboxyfluorescein that binds selectively to the transmembrane-protein gene of BCoV. The BCoV real-time RT-PCR assay was able to detect the tested BCoV and BCoV-like viruses (canine respiratory coronavirus and bubaline coronavirus), whereas other common viral pathogens of cattle were not recognised by the established oligonucleotide set, thus showing that the test was specific for bovine-like CoVs. The detection limit of the assay was 20 BCoV RNA copies (1-log higher with respect to traditional gel-based RT-PCR) and the reproducibility was satisfactory, thus allowing for a sensitive and accurate measurement of the viral RNA load in clinical samples. Two hundred and twenty clinical specimens (92 rectal, 82 nasal and 46 ocular swabs) were subjected to gel-based and real-time RT-PCR. By conventional amplification, 43 rectal, 54 nasal and 34 ocular samples tested positive, whereas the TaqMan assay was able to detect the BCoV nucleic acid in 49 rectal, 60 nasal and 37 ocular swabs. The rapidity and high throughput of the BCoV TaqMan assay makes this method a powerful tool for a sensitive and specific diagnosis of BCoV infection in cattle.


title: Regulation of MAVS Expression and Signaling Function in the Antiviral Innate Immune Response

text: Viral infection is controlled by host innate immune cells that express specialized receptors for viral components. Engagement of these pattern recognition receptors triggers a series of signaling pathways that culminate in the production of antiviral mediators such as type I interferons. Mitochondrial antiviral-signaling protein (MAVS) acts as a central hub for signal transduction initiated by RIG-I-like receptors, which predominantly recognize viral RNA. MAVS expression and function are regulated by both post-transcriptional and post-translational mechanisms, of which ubiquitination and phosphorylation play the most important roles in modulating MAVS function. Increasing evidence indicates that viruses can escape the host antiviral response by interfering at multiple points in the MAVS signaling pathways, thereby maintaining viral survival and replication. This review summarizes recent studies on the mechanisms by which MAVS expression and signaling are normally regulated and on the various strategies employed by viruses to antagonize MAVS activity, which may provide new insights into the design of novel antiviral agents.


docid: fgxfvdis

title: Procalcitonin Identifies Bacterial Coinfections in Vietnamese Children with Severe Respiratory Syncytial Virus Pneumonia

text: This study assessed the diagnostic value of interleukin- (IL-) 6, high-sensitivity C-reactive protein (hs-CRP), and procalcitonin (PCT) in differentiating severe pneumonia caused by respiratory syncytial virus (RSV) alone and RSV with bacterial coinfections among Vietnamese children under 5 years old. A cross-sectional study on 70 children with severe RSV pneumonia was conducted. IL-6, hs-CRP, and PCT tests were performed. Receiver operating characteristic (ROC) analysis was employed to measure the diagnostic values of PCT, IL-6, and hs-CRP. Of 70 children, 11 children were confirmed to have bacterial coinfections. The most common bacterial coinfection was Haemophilus influenzae. This study underlined that inflammatory biomarkers such as PCT had a moderate-to-high capability of disseminating severe pneumonia children with RSV alone or RSV and bacterial coinfections. This may support clinicians in administrating appropriate antibiotics to children suffering from severe RSV pneumonia.


title: Low to medium-low risk perception for dengue, chikungunya and Zika outbreaks by infectious diseases physicians in France, Western Europe

text: BACKGROUND: Many tropical countries are currently experiencing dengue (DEN), chikungunya (CHIK) and also more recently Zika (ZIKA) epidemics (particularly in Latin America). Although the risk of transmission and spread of these infections in temperate regions remains a controversial issue, vector-borne diseases have been widely reported in the media and have been the focus of preventive strategies by national and international policy-makers and public health authorities. In this context, we wanted to determine the extent of risk perception in infectious diseases (ID) physicians of the current and future risk of arboviral disease introduction, autochthonous case development and epidemic scenarios in France, Western Europe. METHODS: To this aim, we developed an original standardized questionnaire survey which was disseminated by the French Infectious Diseases Society to ID physician members. RESULTS: We found that ID physicians perceived the risk of introduction and outbreak development of DEN, CHIK and ZIKA in France to be low to medium-low. Generalized Linear Model(s) identified medical school training, the extent of professional experience, and awareness of the French national plan regarding arboviral infections as significant predictors for lower risk perception among respondents. CONCLUSION: Despite the fact that arboviral diseases are increasingly being imported into France, sometimes resulting in sporadic autochtonous transmission, French ID physicians do not perceive the risk as high. Better communication and education targeting health professionals and citizens will be needed to enhance the effectiveness of the French national plan to prepare against arboviral diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12889-019-7317-9) contains supplementary material, which is available to authorized users.


title: Comparison of a dengue-2 virus and its candidate vaccine derivative: Sequence relationships with the flaviviruses and other viruses

text: Abstract A comparison of the sequence of the dengue-2 16681 virus with that of the candidate vaccine strain (16681-PDK53) derived from it identified 53 of the 10,723 nucleotides which differed between the strains. Nucleotide changes occurred in genes coding for all virion and nonvirion proteins, and in the 5′ and 3′ untranslated regions. Twenty-seven of the nucleotide changes resulted in amino acid alterations. The greatest amino acid sequence differences in the virion proteins occurred in prM (2.20%; 2 91 amino acids) followed by the M protein (1.33%; 1 75 amino acids), the C protein (0.88%; 1 114 amino acid), and the E protein (0.61%; 3 495 amino acids). Differences in the amino acid sequence of nonvirion proteins ranged from 1.51% ( 6 398 amino acids) in NS4 to 0.33% ( 3 900 amino acids) in NS5. The encoded protein sequences of 16681-PDK53 were also compared with the published sequences of other flaviviruses to obtain a detailed classification of 17 flaviviruses using the neighbor-joining tree method. The analyses of the sequence data produced dendrograms which supported the traditional groupings based on serological evidence, and they suggested that the flaviviruses have evolved by divergent mutational change and there was no evidence of genetic recombination between members of the group. Comparisons of the sequences of the flavivirus polymerase and helicase-like proteins (NS5 and NS3, respectively) with those from other viruses yielded a classification of the flaviviruses indicating that the primary division of the flaviviruses was between those transmitted by mosquitoes and those transmitted by ticks.


title: A re-organizing biosurveillance framework based on fog and mobile edge computing

text: Biological threats are becoming a serious security issue for many countries across the world. Effective biosurveillance systems can primarily support appropriate responses to biological threats and consequently save human lives. Nevertheless, biosurveillance systems are costly to implement and hard to operate. Furthermore, they rely on static infrastructures that might not cope with the evolving dynamics of the monitored environment. In this paper, we present a reorganizing biosurveillance framework for the detection and localization of biological threats with fog and mobile edge computing support. In the proposed framework, a hierarchy of fog nodes are responsible for aggregating monitoring data within their regions and detecting potential threats. Although fog nodes are deployed on a fixed base station infrastructure, the framework provides an innovative technique for reorganizing the monitored environment structure to adapt to the evolving environmental conditions and to overcome the limitations of the static base station infrastructure. Evaluation results illustrate the ability of the framework to localize biological threats and detect infected areas. Moreover, the results show the effectiveness of the reorganization mechanisms in adjusting the environment structure to cope with the highly dynamic environment.


title: China Tongxinluo study for myocardial protection in patients with acute myocardial infarction (CTS-AMI): Rationale and Design of a Randomized, double-blind, placebo-controlled, multi-center clinical trial

text: Abstract Background Acute ST-segment elevation myocardial infarction (STEMI) remains a serious life-threatening event. Despite coronary revascularization, patients might still suffer from poor outcomes caused by myocardial no-reflow and ischemic/reperfusion injury. Tongxinluo (TXL), a traditional Chinese medicine, has been preliminarily demonstrated to reduce myocardial no-reflow and ischemic/reperfusion injury. We further hypothesize that TXL treatment is also effective in reducing clinical endpoints for the patients with STEMI. Methods and Results. The CTS-AMI trial is a prospective, randomized, double-blind, placebo-controlled, multi-center clinical study in China. An estimated 3796 eligible patients with STEMI from about 120 centers are randomized 1:1 ratio to TXL or placebo groups. All enrolled patients are orally administrated a loading dose of 8 capsules of TXL or placebo together with dual anti-platelet agents on admission, followed by 4 capsules three times a day until 12months. The primary endpoint is 30-day major adverse cardiovascular and cerebrovascular events (MACCE), a composite of cardiac death, myocardial re-infarction, emergency coronary revascularization, and stroke. Secondary endpoints include each component of the primary endpoint, 1-year MACCE and other efficacy and safety parameters. Conclusion Results of CTS-AMI trial will determine the clinical efficacy and safety of traditional Chinese medicine TXL capsule in the treatment of STEMI patients in the reperfusion era.


title: Genetic associations of fatigue and other symptom domains of the acute sickness response to infection

text: Abstract The acute sickness response to infection is a conserved set of changes in physiology and behaviour, featuring fever, fatigue, musculo-skeletal pain, disturbed mood, and cognitive difficulties. The manifestations differ somewhat between individuals, including those infected with pathogens which do not have genetic variability – suggesting host determinants. Principal components analysis (PCA) was applied to acute phase, self-report symptom data from subjects in the Dubbo Infection Outcomes Study (n =296) to empirically derive indices of fatigue, pain, neurocognitive difficulties, and mood disturbance, as well as overall illness severity. Associations were sought with functional single nucleotide polymorphisms (SNPs) in the cytokine genes, interleukin (IL)-6, tumour necrosis factor (TNF)-α, interferon (IFN)-γ, and IL-10. The summed individual symptom indices correlated with overall severity and also with functional status. The relative contribution of individual symptom domains to the overall illness was stable over time within subjects, but varied between subjects with the same infection. The T allele of the IFN-γ +874 T/A SNP was associated with increased fatigue (p =0.0003; OR: 3.3). The C allele of the IL-10 −592 C/A SNP exerted a protective effect on neurocognitive difficulties (p =0.017; OR: 0.52); while the A allele for the IL-10 −592 SNP was associated with increased mood disturbance (p =0.044; OR: 1.83), as was the G allele of the IL-6 −174 G/C SNP (p =0.051; OR: 1.83). The acute sickness response has discrete symptom domains including fatigue, which have unique genetic associations. These data provide novel insights into the pathophysiology of fatigue states.


title: Online Mental Health Survey in a Medical College in China During the COVID-19 Outbreak

text: BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, Hubei province, has led to the quarantine of many residents in their homes, in order to mitigate its spread. Some of these people developed mental health problems, and many solutions have been put in place to address the mental health issues of patients and health professionals affected by the disease. However, not much attention has been given to students, particularly those from medical school. The present study aims to conduct an online survey to investigate the mental health status of students from a medical college in Hubei province. MATERIALS AND METHODS: The WeChat-based survey program Questionnaire Star, which contained questions from Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), was utilized for the present study. RESULTS: A total of 217 students participated in the survey. Among these students, 127 were female and 90 were male. Furthermore, 77 students (35.5%) who participated in the survey were in a state of depression, and 48 (22.1%) were in a state of anxiety. The majority of students who were in depressed (n=75) or anxiety (n=46) states had mild or moderate states. There were no significant differences in students in terms of gender, geographical location, and grade, for the prevalence of depression and anxiety. CONCLUSION: The present study implies that universities need to take measures to prevent, identify, and deal with mental health problems among students during large-scale stressors.


title: Human enteric Coronaviruses: Antigenic Relatedness to Human Coronavirus OC43 and Possible Etiologic Role in Viral Gastroenteritis

text: In a group of infants with acute nonbacterial gastroenteritis, examination of paired sera for antibody to human coronavirus (HCV) OC43 and neonatal calf diarrhea coronavirus showed a peculiar pattern of serological response, restricted only to HCV OC43 surface antigens, in a significantly higher proportion than among age-matched controls. In another group of infants and young children with acute nonbacterial gastroenteritis, fecal excretion of coronavirus-like particles was detected by electron microscopy in 34 (16.3%) of 208 patients as compared with three (1.6%) of 182 controls (P < .01). Two strains of human enteric coronavirus (HECV) were purified from stools of two patients, and immune sera were raised in mice and guinea pigs. Immune electron microscopy showed a two-way cross-reactivity between HECV and HCV OC43 when tested with immune sera and convalescent-phase sera from patients with infection due to HECV or HCV OC43.


title: Clinical Efficacy of Intravenous Hypertonic Saline Solution or Hypertonic Bicarbonate Solution in the Treatment of Inappetent Calves with Neonatal Diarrhea

text: Background: The clinical efficacy of IV administered hypertonic saline solution and hypertonic bicarbonate solution (HBS) in the treatment of inappetent diarrheic calves has not been compared yet. Hypothesis: HBS is more advantageous than hypertonic saline in the treatment of calves with severe metabolic acidosis. Animals: Twenty‐eight dehydrated, inappetent calves with neonatal diarrhea. Methods: In 2 consecutive clinical studies, calves were initially treated with saline (5.85%; 5 mL/kg body weight [BW] over 4 minutes; study I: N = 16) or bicarbonate solution (8.4%; 10 mL/kg BW over 8 minutes; study II: N = 12), respectively, followed by oral administration of 3 L isotonic electrolyte solution 5 minutes after injection. Clinical and laboratory variables were monitored for 72 hours. Results: Treatment failed in 6 calves of study I and in 1 calf of study II as indicated by a deterioration of the general condition. All treatment failures had more severe metabolic acidosis compared with successfully treated calves before treatment. In the latter, rehydration was completed within 18 hours after injection; metabolic acidosis was corrected within 24 hours (study I) and 6 hours (study II) after injection. Conclusions and Clinical Importance: Diarrheic calves with slight metabolic acidosis (base excess [BE] >−10 mM) can be treated successfully with hypertonic saline. HBS is appropriate in calves without respiratory problems with more severe metabolic acidosis (BE up to −20 mM). Intensive care of the calves is required to ensure a sufficient oral fluid intake after the initial IV treatment.


title: Predicting turning point, duration and attack rate of COVID-19 outbreaks in major Western countries

text: Abstract In this paper, we employed a segmented Poisson model to analyze the available daily new cases data of the COVID-19 outbreaks in the six Western countries of the Group of Seven, namely, Canada, France, Germany, Italy, UK and USA. We incorporated the governments’ interventions (stay-at-home advises/orders, lockdowns, quarantines and social distancing) against COVID-19 into consideration. Our analysis allowed us to make a statistical prediction on the turning point (the time that the daily new cases peak), the duration (the period that the outbreak lasts) and the attack rate (the percentage of the total population that will be infected over the course of the outbreak) for these countries.


title: SARS‐CoV‐2 variants: Relevance for symptom granularity, epidemiology, immunity (herd, vaccines), virus origin and containment?

text: The origin of the SARS‐CoV‐2 virus remains enigmatic. It is likely to be a continuum resulting from inevitable mutations and recombination events. These genetic changes keep developing in the present epidemic. Mutations tending to deplete the genome in its cytosine content will progressively lead to attenuation as a consequence of Muller's ratchet, but this is counteracted by recombination when different mutants co‐infect the same host, in particular, in clusters of infection. Monitoring as a function of time the genome sequences in closely related cases is critical to anticipate the future of SARS‐CoV‐2 and hence of COVID‐19.


title: Emerging Pathogens in Transfusion Medicine

text: Although the risk of infection with hepatitis and human immunodeficiency viruses from blood transfusions has been reduced to negligible levels, emerging infections continue to offer threats. Such threats occur with any infection that has an asymptomatic, blood-borne phase. In the past, it was thought that any emerging transfusion-transmitted disease would have epidemiologic properties similar to those of AIDS or viral hepatitis. Over the past 20 years, however, greatest concern has arisen from variant Creutzfeldt-Jakob disease, West Nile virus, and Babesia. These and other emerging infections are discussed in the context of blood safety.


title: Latent infection of human bocavirus accompanied by flare of chronic cough, fatigue and episodes of viral replication in an immunocompetent adult patient, Cologne, Germany

text: INTRODUCTION: The human bocavirus (HBoV) is a parvovirus and is associated with mild to life-threatening acute or persisting respiratory infections, frequently accompanied by further pathogens. So far, there is limited knowledge on the mechanisms of persistence, and no reports on chronic infections or latency have been published so far. CASE PRESENTATION: An immunocompetent male patient suffers from a chronic HBoV1 infection, i.e. viral DNA was detected in both serum and bronchoalveolar lavage (BAL) for >5 months without co-infections and with respiratory symptoms resolved spontaneously while receiving symptomatic treatment with montelukast and corticosteroids. Following the symptomatic medication of a chronic infection with HBoV1 viraemia indicating active viral replication lasting over 5 months, the patient cleared the viraemia and no further viral DNA was detectable in the BAL. However, by fluorescence in situ hybridization analyses of mucosal biopsies, it was shown that the virus genome still persisted in the absence of viral shedding but in a more compact manner possibly representing a supercoiled episomal form of this otherwise linear single-stranded DNA genome. This indicated the entry into a latency phase. Moreover, the cytokine profile and the IP-10/TARC ratio, a marker for fibrotization, seem to have been altered by HBoV1 replication. Although specific IgG antibodies were detectable during the whole observation period, they showed an apparently insufficient neutralising activity. CONCLUSION: On the one hand, these findings suggest that the symptomatic medication may have led to clearance of the virus from blood and airways and, moreover, that the viral DNA persists in the tissue as an altered episomal form favoured by lacking neutralising antibodies. This appears to be important in order to reduce possible long-term effects such as lung fibrosis.


title: Finding the Dose for Hydroxychloroquine Prophylaxis for COVID‐19: The Desperate Search for Effectiveness

text: Hydroxychloroquine is an antimalarial drug being tested as a potential treatment for the novel coronavirus disease 2019 (COVID‐19) pandemic caused by the severe acute respiratory syndrome coronavirus 2. Although the efficacy of hydroxychloroquine for COVID‐19 remains uncertain, it may serve as a potential prophylactic agent especially in those at high risk, such as healthcare workers, household contacts of infected patients, and the immunocompromised. Our aim was to identify possible hydroxychloroquine dosing regimens through simulation in those at high risk of infections by optimizing exposures above the in vitro generated half maximal effective concentration (EC(50)) and to help guide researchers in dose‐selection for COVID‐19 prophylactic studies. To maintain weekly troughs above EC(50) in > 50% of subjects at steady‐state in a pre‐exposure prophylaxis setting, an 800 mg loading dose followed by 400 mg twice or 3 times weekly is required. In an exposure driven, post‐exposure prophylaxis setting, 800 mg loading dose followed in 6 hours by 600 mg, then 600 mg daily for 4 more days achieved daily troughs above EC(50) in > 50% subjects. These doses are higher than recommended for malaria chemoprophylaxis, and clinical trials are needed to establish safety and efficacy.


title: Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2

text: Summary We have previously provided the first genetic evidence that angiotensin converting enzyme 2 (ACE2) is the critical receptor for severe acute respiratory syndrome coronavirus (SARS-CoV), and ACE2 protects the lung from injury, providing a molecular explanation for the severe lung failure and death due to SARS-CoV infections. ACE2 has now also been identified as a key receptor for SARS-CoV-2 infections, and it has been proposed that inhibiting this interaction might be used in treating patients with COVID-19. However, it is not known whether human recombinant soluble ACE2 (hrsACE2) blocks growth of SARS-CoV-2. Here, we show that clinical grade hrsACE2 reduced SARS-CoV-2 recovery from Vero cells by a factor of 1,000–5,000. An equivalent mouse rsACE2 had no effect. We also show that SARS-CoV-2 can directly infect engineered human blood vessel organoids and human kidney organoids, which can be inhibited by hrsACE2. These data demonstrate that hrsACE2 can significantly block early stages of SARS-CoV-2 infections.


title: Resolution of the major poliovirus capsid polypeptides into doublets

text: Abstract Using the pH gradient electrophoretic technique of Vrijsen and Boeyé, the coat protein of poliovirus types 1 and 2 was resolved into six components, Cl to C6, instead of the classical VP1-2-3 (the much smaller polypeptide VP4 was excluded from this study). The multiple components ran true upon reelectrophoresis, and there were no technical artifacts. Their resolution did not depend on a particular method for the preparation or disruption of the virion. The C1–C6 components of pH gradient electrophoresis and the classical VP1–VP3 polypeptides were examined with regard to (i) their migration in normal and pH gradient reelectrophoresis and (ii) their kinetics of leucine incorporation in emetine-stopped pulses. It is concluded that C1 and C2 were both derived from VPl, C3 and C4 from VP2, and C5 and C6 from VP3.


title: Type III interferons disrupt the lung epithelial barrier upon viral recognition

text: Lower respiratory tract viral infections are a leading cause of mortality. Mounting evidence indicates that most severe cases are characterized by aberrant immune responses and do not depend on viral burden. Here, we assessed how type III interferons (IFN-λ) contribute to the pathogenesis induced by RNA viruses. We report IFN-λ is present in the lower, but not upper, airways of COVID-19 patients. In mice, we demonstrate IFN-λ produced by lung dendritic cells in response to a synthetic viral RNA induces barrier damage, causing susceptibility to lethal bacterial superinfections. These findings provide a strong rationale for rethinking the pathophysiological role of IFN-λ and its possible use in the clinical practice against endemic viruses, such as influenza virus, as well as the emerging SARS-CoV-2 viral infection.


title: “You have to find a caring man, like your father!” Gendering sickle cell and refashioning women’s moral boundaries in Sierra Leone

text: Most research on sickle cell disorders has tended to be gender-blind. This qualitative study undertaken in 2018, explores if and how sickle cell disorders become gendered in Sierra Leone through the analytical framework of a feminist ethics of care. It argues that women have to navigate moral blame when they have children with the condition. At the same time women refashion moral boundaries so that gendered norms around childhood and parenting for such children become suspended, in favour of creation of careful spaces. Parental fears of physical and sexual violence mean that gendered sexual norms are enforced for teenage boys as they are encouraged into early adulthood. In contrast, girls are kept in enforced ignorance about the consequences of sickle cell for reproduction and are encouraged to delay motherhood. This is because, as women relate, relationships and giving birth are fraught with embodied dangers and risks of violence.


title: PATHOLOGICAL MANIFESTATIONS OF FELINE IMMUNODEFICIENCY VIRUS (FIV) INFECTION IN WILD AFRICAN LIONS

text: Feline immunodeficiency virus (FIV) causes AIDS in the domestic cat (Felis catus) but has not been explicitly associated with AIDS pathology in any of the eight free-ranging species of Felidae that are endemic with circulating FIV strains. African lion (Panthera leo) populations are infected with lion-specific FIV strains (FIVple), yet there remains uncertainty about the degree to which FIV infection impacts their health. Reported CD4+ T-lymphocyte depletion in FIVple infected lions and anecdotal reports of lion morbidity associated with FIV sero-prevalence emphasize the concern as to whether FIVple is innocuous or pathogenic. Here we monitored clinical, biochemical, histological and serological parameters among FIVple-positive (N=47) as compared to FIVple negative (N=17) lions anesthetized and sampled on multiple occasions between 1999 and 2006 in Botswana. Relative to uninfected lions, FIVple infected lions displayed a significant elevation in the prevalence of AIDS defining conditions: lymphandenopathy, gingivitis, tongue papillomas, dehydration, and poor coat condition, as well as displaying abnormal red blood cell parameters and elevated liver enzymes and serum proteins. Spleen and lymph node laparoscopic biopsies from free-ranging FIVple infected lions (N=8) revealed evidence of lymphoid depletion, the hallmark pathology documented in immunodefieciency virus infections of humans (HIV-1), macaques, and domestic cats. We conclude that over time FIVple infections in free-ranging lions can lead to adverse clinical, immunological, and pathological outcomes in some individuals that parallel sequelae caused by lentivirus infection in humans (HIV), Asian macaques (SIV) and domestic cats (FIVfca).


title: Rhinovirus infections in western Sweden: a four-year molecular epidemiology study comparing local and globally appearing types

text: Human rhinovirus (HRV) is a highly prevalent pathogen and a major cause of acute respiratory tract infection (ARTI). HRV express less seasonality than other viral ARTIs, which typically appear as seasonal epidemics lasting for 1–2 months. The aim of this study was to investigate the seasonal patterns of HRV types over four consecutive years in one geographic region. HRV identified in respiratory samples from 114 patients over a four-year period were analysed by VP4/VP2 sequencing. HRV-A was found in 64, HRV-B in 11 and HRV-C in 37 cases. Overall, 33 different HRV-A types, nine B types and 21 C types were found. As many as 21 of the HRV types appeared during several seasons, with a maximum time-span of four years. Some types appeared during successive seasons and, in some cases, phylogenetic analysis indicated extended periods of circulation locally. Most of the strains were closely related to HRV identified in other parts of the world during the same time period. HRV strains that circulate locally represent many types and seem to reflect that HRV infections are highly globalised. The existence of simultaneous or successive epidemics with different HRV types in combination with the ability of each type to remain in the local population over extended periods of time may contribute to explaining the high rate of HRV infections.


title: Functional and evolutionary analysis of viral proteins containing a Rossmann‐like fold

text: Viruses are the most abundant life form and infect practically all organisms. Consequently, these obligate parasites are a major cause of human suffering and economic loss. Rossmann‐like fold is the most populated fold among α/β‐folds in the Protein Data Bank and proteins containing Rossmann‐like fold constitute 22% of all known proteins 3D structures. Thus, analysis of viral proteins containing Rossmann‐like domains could provide an understanding of viral biology and evolution as well as could propose possible targets for antiviral therapy. We provide functional and evolutionary analysis of viral proteins containing a Rossmann‐like fold found in the evolutionary classification of protein domains (ECOD) database developed in our lab. We identified 81 protein families of bacterial, archeal, and eukaryotic viruses in light of their evolution‐based ECOD classification and Pfam taxonomy. We defined their functional significance using enzymatic EC number assignments as well as domain‐level family annotations.


title: Genetic Variants and Susceptibility to Neurological Complications Following West Nile Virus Infection

text: To determine genetic factors predisposing to neurological complications following West Nile virus infection, we analyzed a cohort of 560 neuroinvasive case patients and 950 control patients for 13 371 mostly nonsynonymous single-nucleotide polymorphisms (SNPs). The top 3 SNPs on the basis of statistical significance were also in genes of biological plausibility: rs2066786 in RFC1 (replication factor C1) (P = 1.88 × 10(−5); odds ratio [OR], 0.68 [95% confidence interval {CI}, .56–.81]); rs2298771 in SCN1A (sodium channel, neuronal type I α subunit) (P = 5.87 × 10(−5); OR, 1.47 [95% CI, 1.21–1.77]); and rs25651 in ANPEP (ananyl aminopeptidase) (P = 1.44 × 10(−4); OR, 0.69 [95% CI, .56–.83]). Additional genotyping of these SNPs in a separate sample of 264 case patients and 296 control patients resulted in a lack of significance in the replication cohort; joint significance was as follows: rs2066786, P = .0022; rs2298771, P = .005; rs25651, P = .042. Using mostly nonsynonymous variants, we therefore did not identify genetic variants associated with neuroinvasive disease.


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title: PEDV and PDCoV Pathogenesis: The Interplay Between Host Innate Immune Responses and Porcine Enteric Coronaviruses

text: Enteropathogenic porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV), members of the coronavirus family, account for the majority of lethal watery diarrhea in neonatal pigs in the past decade. These two viruses pose significant economic and public health burdens, even as both continue to emerge and reemerge worldwide. The ability to evade, circumvent or subvert the host’s first line of defense, namely the innate immune system, is the key determinant for pathogen virulence, survival, and the establishment of successful infection. Unfortunately, we have only started to unravel the underlying viral mechanisms used to manipulate host innate immune responses. In this review, we gather current knowledge concerning the interplay between these viruses and components of host innate immunity, focusing on type I interferon induction and signaling in particular, and the mechanisms by which virus-encoded gene products antagonize and subvert host innate immune responses. Finally, we provide some perspectives on the advantages gained from a better understanding of host-pathogen interactions. This includes their implications for the future development of PEDV and PDCoV vaccines and how we can further our knowledge of the molecular mechanisms underlying virus pathogenesis, virulence, and host coevolution.


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title: Development of a multiplex RT‐PCR for the detection of major diarrhoeal viruses in pig herds in China

text: The major enteric RNA viruses in pigs include porcine epidemic diarrhoea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine rotavirus A (PRV‐A), porcine kobuvirus (PKV), porcine sapovirus (PSaV) and porcine deltacoronavirus (PDCoV). For differential diagnosis, a multiplex RT‐PCR method was established on the basis of the N genes of TGEV, PEDV and PDCoV, the VP7 gene of PRV‐A, and the polyprotein genes of PKV and PSaV. This multiplex RT‐PCR could specifically detect TGEV, PEDV, PDCoV, PRV‐A, PKV and PSaV without cross‐reaction to any other major viruses circulating in Chinese pig farms. The limit of detection of this method was as low as 10(0)–10(1) ng cDNA of each virus. A total of 398 swine faecal samples collected from nine provinces of China between October 2015 and April 2017 were analysed by this established multiplex RT‐PCR. The results demonstrated that PDCoV (144/398), PSaV (114/398), PEDV (78/398) and PRV‐A (70/398) were the main pathogens, but TGEV was not found in the pig herds in China. In addition, dual infections, for example, PDCoV + PSaV, PDCoV + PRV‐A, PRA‐V + PSaV and PEDV + PDCoV, and triple infections, for example, PDCoV + PRV‐A + PSaV and PEDV + PDCoV + PKV, were found among the collected samples. The multiplex RT‐PCR provided a valuable tool for the differential diagnosis of swine enteric viruses circulating in Chinese pig farms and will facilitate the prevention and control of swine diarrhoea in China.


title: Adipocytokines: Are they the Theory of Everything?

text: INTRODUCTION: Adipose tissue secretes various bioactive peptides/proteins, immune molecules and inflammatory mediators which are known as adipokines or adipocytokines. Adipokines play important roles in the maintenance of energy homeostasis, appetite, glucose and lipid metabolism, insulin sensitivity, angiogenesis, immunity and inflammation. Enormous number of studies from all over the world proved that adipocytokines are involved in the pathogenesis of diseases affecting nearly all body systems, which raises the question whether we can always blame adipocytokines as the triggering factor of every disease that may hit the body. OBJECTIVE: Our review targeted the role played by adipocytokines in the pathogenesis of different diseases affecting different body systems including diabetes mellitus, kidney diseases, gynecological diseases, rheumatologic disorders, cancers, Alzheimer’s, depression, muscle disorders, liver diseases, cardiovascular and lung diseases. METHODOLOGY: We cited more than 33 recent literature reviews that discussed the role played by adipocytokines in the pathogenesis of different diseases affecting different body systems. CONCLUSION: More evidence is being discovered to date about the role played by adipocytokines in more diseases and extra research is needed to explore hidden roles played by adipokine imbalance on disease pathogenesis.


title: SARS coronavirus 8b reduces viral replication by down-regulating E via an ubiquitin-independent proteasome pathway

text: Abstract The severe acute respiratory syndrome coronavirus (SARS-CoV) 8b protein, which is not expressed by other known coronaviruses, can down-regulate the envelope (E) protein via a proteasome-dependent pathway. Here, we showed that the down-regulation of E is not dependent on the lysine residues on 8b and the reduction of polyubiquitination of E mutants is not correlated with their down-regulation by 8b, suggesting an ubiquitin-independent proteasome pathway is involved. A time-course study revealed that 8b was expressed at late-stages of SARS-CoV infection. By using Vero E6 cells stably expressing green fluorescence protein-tagged 8b, ectopic expression of 8b was shown to significantly reduce the production of progeny virus and down-regulate E expression. Taken together, these results suggest that 8b negatively modulates virus replication by down-regulating E via an ubiquitin-independent proteasome pathway.


title: Analyzing the interaction of a herbal compound Andrographolide from Andrographis paniculata as a folklore against swine flu (H1N1)

text: Abstract Objective To find new bioactive molecules for the treatment of swine flu. Methods The present study is an attempt to elucidate inhibition potential of andrographolide and its derivatives along with an associated binding mechanism through virtual screening and molecular docking simulation studies. Results Our findings revealed structural conformation changes in 150 loop, secondary sialic acid binding site residues of ACZ97474 {Neuraminidase (A/Blore/NIV236/2009(H1N1)}. Andrographolide have been identified as the highest binging energy of −10.88 Kcal/mol, 3 hydrogen bond interactions (Arg152, Lys150, and Gly197), total intermolecular energy of −12.07 Kcal/mol with bioactivity value (Ki) of 10.59 nmol/L, while the Food and Drug Admistraton approved drug Oseltamivir and Zanamivir have shown 2 and 4 hydrogen bond interactions with binding energies of −6.28 Kcal/mol and −7.73Kcal/mol, respectively, which is higher than andrographolide. The guanidine group of Arg152 has binding affinities to the hydrophilic nature of the inhibitors (-OH and =O groups), as identified by docking of andrographolide (CID: 5318517) on neuraminidase. Conclusions Hence, andrographolide has the potential to inhibit neuraminidase activity of H1N1 and may be used as an alternative medicinal therapy for swine flu positive patient. With potent antiviral activity and a potentially new mechanism of action, andrographolide may warrant further evaluation as a possible therapy for influenza.


title: Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China

text: BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been widely spread. We aim to investigate the clinical characteristic and allergy status of patients infected with SARS-CoV-2. METHODS: Electronic medical records including demographics, clinical manifestation, comorbidities, laboratory data, and radiological materials of 140 hospitalized COVID-19 patients, with confirmed result of SARS-CoV-2 viral infection, were extracted and analyzed. RESULTS: An approximately 1:1 ratio of male (50.7%) and female COVID-19 patients was found, with an overall median age of 57.0years. All patients were community-acquired cases. Fever (91.7%), cough (75.0%), fatigue (75.0%), and gastrointestinal symptoms (39.6%) were the most common clinical manifestations, whereas hypertension (30.0%) and diabetes mellitus (12.1%) were the most common comorbidities. Drug hypersensitivity (11.4%) and urticaria (1.4%) were self-reported by several patients. Asthma or other allergic diseases were not reported by any of the patients. Chronic obstructive pulmonary disease (COPD, 1.4%) patients and current smokers (1.4%) were rare. Bilateral ground-glass or patchy opacity (89.6%) was the most common sign of radiological finding. Lymphopenia (75.4%) and eosinopenia (52.9%) were observed in most patients. Blood eosinophil counts correlate positively with lymphocyte counts in severe (r=.486, P<.001) and nonsevere (r=.469, P<.001) patients after hospital admission. Significantly higher levels of D-dimer, C-reactive protein, and procalcitonin were associated with severe patients compared to nonsevere patients (all P<.001). CONCLUSION: Detailed clinical investigation of 140 hospitalized COVID-19 cases suggests eosinopenia together with lymphopenia may be a potential indicator for diagnosis. Allergic diseases, asthma, and COPD are not risk factors for SARS-CoV-2 infection. Older age, high number of comorbidities, and more prominent laboratory abnormalities were associated with severe patients.


title: Phylogenomic proximity and comparative proteomic analysis of SARS-CoV-2

text: The coronavirus disease (COVID-19) belongs to the family Severe Acute Respiratory Syndrome (SARS-CoV). It can be more severe for some persons and can lead to pneumonia or breathing difficulties resulting in the death of immune-compromised patients. We performed a phylogenomic and phylogeographic tree from the collected datasets. Phylogenomic analysis or sequence-based phylogeny showed an evolutionary relationship between the geographical strains. The phylogenomic tree grouped into two major clades consists of various isolates of SARS-CoV-2 and Bat SARS-like coronavirus, Bat coronavirus, and Pangolin coronavirus. The phylogenetic neighbor of newly sequenced Indian strains (Accession: MT012098.1, MT050493.1) was revealed to identify the variations between the nCoV-19 strains. The results showed keen evidence that SARS-CoV-2 has evolved from Bat SARS-like coronavirus. The evolutionary history and comparative proteomic analysis provide a new avenue for the current scientific research related to the coronavirus.


title: COVID-19 as a catalyst for educational change

text: The massive damages of COVID-19 may be incalculable. But in the spirit of never wasting a good crisis, COVID-19 represents an opportunity to rethink education. The rethinking should not be about improving schooling, but should focus on the what, how, and where of learning. This article highlights some of the questions that schools can ask as they reimagine post-COVID education.


title: Candidates in Astroviruses, Seadornaviruses, Cytorhabdoviruses and Coronaviruses for +1 frame overlapping genes accessed by leaky scanning

text: BACKGROUND: Overlapping genes are common in RNA viruses where they serve as a mechanism to optimize the coding potential of compact genomes. However, annotation of overlapping genes can be difficult using conventional gene-finding software. Recently we have been using a number of complementary approaches to systematically identify previously undetected overlapping genes in RNA virus genomes. In this article we gather together a number of promising candidate new overlapping genes that may be of interest to the community. RESULTS: Overlapping gene predictions are presented for the astroviruses, seadornaviruses, cytorhabdoviruses and coronaviruses (families Astroviridae, Reoviridae, Rhabdoviridae and Coronaviridae, respectively).


title: COVID-19 and Outpatient Parenteral Antimicrobial Therapy: The Need to Protect Vulnerable Medicare Beneficiaries

text: Home infusion therapy can provide a safer alternative for exposure to SARS-CoV-2 infection for many vulnerable patients who receive parenteral therapies on an outpatient basis, such as parenteral antimicrobial therapy. This article proposes changes to Medicare payment policy, which currently does not adequately reimburse for these services for many patients.


title: Viral Enhancement of Nasal Colonization with Haemophilus influenzae Type b in the Infant Rat

text: Summary: Infant rats infected with influenza A virus, Sendai (parainfluenza 1) virus or rat coronavirus were used to determine whether viral infection increases the intensity of nasal colonization with Haemophilus influenzae type b (HIB). Intranasal inoculation of HIB in rats previously infected with each of these viruses resulted in nasal HIB titers at least 100-fold higher than those for controls during the first 2 wk after HIB inoculation, and as much as 10,000-fold higher during the first week. Children with cough, sneezing, or rhinorrhea could be effective disseminators of HIB if they were as heavily and persistently colonized as these virus-infected animals.


title: Immunity after natural exposure to enteric canine coronavirus does not provide complete protection against infection with the new pantropic CB/05 strain

text: Abstract Recently, an outbreak of fatal infection caused by a pantropic variant (strain CB/05) of canine coronavirus (CCoV) has been reported. In this study, evidence is provided that immunity induced by natural exposure to enteric CCoV is not fully protective against strain CB/05. Twenty-two, 10-week-old beagles with a recent natural infection by enteric CCoV were randomly distributed in two experimental groups of eight (groups A and B) and one control group of six (group C) dogs. Dogs in groups A and B were inoculated oronasally with different doses (4×105 or 4×103 TCID50) of the pantropic strain CB/05, whereas dogs in group C were used as negative controls. Clinical, post-mortem and virological investigations showed that, despite the high serum antibody titres induced by the prior natural infection with enteric CCoV, dogs were susceptible to experimental infection with strain CB/05. This was shown by the occurrence of faecal shedding, and dogs displaying moderate clinical signs, mainly vomiting and diarrhoea. Involvement of the lymphoid tissues was evident as demonstrated by the acute lymphopenia (below 70% of the initial counts), gross lesions in spleen and lymph nodes and detection of CB/05 RNA in thymus, spleen and lymph nodes of some infected dogs. The presence of viral RNA in lymphoid tissues was observed only in dogs euthanised in the early stages of infection and the clinical course of the infection was unrelated to the viral dose administered. The present study demonstrates that strain CB/05 is able to induce infection and disease in dogs seropositive to enteric CCoV, thus highlighting the need for extensive epidemiological investigation and for the possible development of novel antigenically relevant vaccines.


title: Modeling COVID-19 and Its Impacts on U.S. Immigration and Customs Enforcement (ICE) Detention Facilities, 2020

text: U.S. Immigration and Customs Enforcement (ICE) facilities house thousands of undocumented immigrants in environments discordant with the public health recommendations to reduce the transmission of 2019 novel coronavirus (COVID-19). Using ICE detainee population data obtained from the ICE Enforcement and Removal Operations (ERO) website as of March 2, 2020, we implemented a simple stochastic susceptible-exposed-infected-recovered model to estimate the rate of COVID-19 transmission within 111 ICE detention facilities and then examined impacts on regional hospital intensive care unit (ICU) capacity. Models considered three scenarios of transmission (optimistic, moderate, pessimistic) over 30-, 60-, and 90-day time horizons across a range of facility sizes. We found that 72% of individuals are expected to be infected by day 90 under the optimistic scenario (R0 = 2.5), while nearly 100% of individuals are expected to be infected by day 90 under a more pessimistic (R0 = 7) scenario. Although asynchronous outbreaks are more likely, day 90 estimates provide an approximation of total positive cases after all ICE facility outbreaks. We determined that, in the most optimistic scenario, coronavirus outbreaks among a minimum of 65 ICE facilities (59%) would overwhelm ICU beds within a 10-mile radius and outbreaks among a minimum of 8 ICE facilities (7%) would overwhelm local ICU beds within a 50-mile radius over a 90-day period, provided every ICU bed was made available for sick detainees. As policymakers seek to rapidly implement interventions that ensure the continued availability of life-saving medical resources across the USA, they may be overlooking the pressing need to slow the spread of COVID-19 infection in ICE’s detention facilities. Preventing the rapid spread necessitates intervention measures such as granting ICE detainees widespread release from an unsafe environment by returning them to the community. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11524-020-00441-x) contains supplementary material, which is available to authorized users.


title: Validation of an Aptima-format Finnish new variant of Chlamydia trachomatis (FI-nvCT) surveillance assay, 2019

text: The Finnish new variant of Chlamydia trachomatis (FI-nvCT) is escaping diagnostics in Finland, Norway and Sweden. We have developed and validated an Aptima-format nucleic acid amplification test (NAAT) designed specifically to detect the FI-nvCT. This NAAT has high sensitivity (100%) and specificity (100%) for the FI-nvCT strain, enabling further investigation of the geographic distribution, prevalence and transmission of this diagnostic-escape mutant in screening populations in Europe.


title: Predator–prey model with disease infection in both populations

text: A predator–prey model with disease infection in both populations is proposed to account for the possibility of a contagious disease crossing species barrier from prey to predator. We obtain several threshold parameters from local analysis of various equilibria of the proposed system as well as coupled conditions on these threshold parameters which determine the stability of these equilibria. One of the coupled conditions, in the form of an ecological threshold number for the predator–prey ecosystem, always determines the coexistence of predators and prey. The other condition, in the form of a disease basic reproduction number, dictates whether the disease will become endemic in the ecosystem. Under one combination of these coupled conditions, a highly infectious disease could drive the predators to extinction when predators and prey would have coexisted without the disease. For another combination of the conditions, the predation of the more vulnerable infected prey could cause the disease to be eradicated in the ecosystem, in some case even approaching a disease-free periodic solution, when the disease would have otherwise remained endemic in the prey population in the absence of predation. This indicates that the presence of disease in both predators and prey could either promote or impair coexistence, and its precise impact needs to be explored specifically in each particular situation. By considering disease infection in both populations, our model also yields more complex dynamics, allowing for the possibility of bistability and periodic oscillation, in either disease-free or endemic states, in the ecosystem for which the conditions are obtained analytically and with the help of numerical simulations.


title: Going viral: A brief history of Chilblain-like skin lesions (“COVID toes”) amidst the COVID-19 pandemic

text: Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the respiratory illness COVID-19, has led to a global pandemic. In a rapidly evolving medical literature its manifestations are expanding and now include coagulopathies renal dysfunction, cardiac arrests, multisystem inflammatory syndrome in children as well as cutaneous manifestations commonly observed with viral illnesses and chilblain-like skin lesions often referred to as “COVID toes”. Driven in large part by the internet-facilitated communication, dermatologists around the world now report a marked increase in the frequency of chilblain-like diagnoses, not infrequently in members of the same family, amidst the COVID-19 pandemic. While a mechanistic explanation has yet to be proven a robust antiviral immune response in young patients that simultaneously truncates the clinical course and induces the microangiopathic changes could lead to chilblain-like skin lesions. This or a similar explanation would then posit that chilblain-like lesions would be most likely to appear only after a successful viral response is mounted with lesions detected only when symptoms are likely to be subsiding. We review the rapid evolution of the chilblain-like presentation in patients with COVID 19 beginning with its first description in early March 2020 and summarize the evolving but rapidly self-confirming data.


title: G-quadruplexes in viruses: function and potential therapeutic applications

text: G-rich nucleic acids can form non-canonical G-quadruplex structures (G4s) in which four guanines fold in a planar arrangement through Hoogsteen hydrogen bonds. Although many biochemical and structural studies have focused on DNA sequences containing successive, adjacent guanines that spontaneously fold into G4s, evidence for their in vivo relevance has recently begun to accumulate. Complete sequencing of the human genome highlighted the presence of ∼300 000 sequences that can potentially form G4s. Likewise, the presence of putative G4-sequences has been reported in various viruses genomes [e.g., Human immunodeficiency virus (HIV-1), Epstein–Barr virus (EBV), papillomavirus (HPV)]. Many studies have focused on telomeric G4s and how their dynamics are regulated to enable telomere synthesis. Moreover, a role for G4s has been proposed in cellular and viral replication, recombination and gene expression control. In parallel, DNA aptamers that form G4s have been described as inhibitors and diagnostic tools to detect viruses [e.g., hepatitis A virus (HAV), EBV, cauliflower mosaic virus (CaMV), severe acute respiratory syndrome virus (SARS), simian virus 40 (SV40)]. Here, special emphasis will be given to the possible role of these structures in a virus life cycle as well as the use of G4-forming oligonucleotides as potential antiviral agents and innovative tools.


title: Full-length title: Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: A retrospective analysis of 1061 cases in Marseille, France

text: Abstract Background In France, the combination hydroxychloroquine (HCQ) and azithromycin (AZ) is used in the treatment of COVID-19. Methods We retrospectively report on 1061 SARS-CoV-2 positive tested patients treated with HCQ (200 mg three times daily for ten days) + AZ (500 mg on day 1 followed by 250 mg daily for the next four days) for at least three days. Outcomes were death, clinical worsening (transfer to ICU, and >10 day hospitalization) and viral shedding persistence (>10 days). Results A total of 1061 patients were included in this analysis (46.4% male, mean age 43.6 years – range 14–95 years). Good clinical outcome and virological cure were obtained in 973 patients within 10 days (91.7%). Prolonged viral carriage was observed in 47 patients (4.4%) and was associated to a higher viral load at diagnosis (p < .001) but viral culture was negative at day 10. All but one, were PCR-cleared at day 15. A poor clinical outcome (PClinO) was observed for 46 patients (4.3%) and 8 died (0.75%) (74–95 years old). All deaths resulted from respiratory failure and not from cardiac toxicity. Five patients are still hospitalized (98.7% of patients cured so far). PClinO was associated with older age (OR 1.11), severity at admission (OR 10.05) and low HCQ serum concentration. PClinO was independently associated with the use of selective beta-blocking agents and angiotensin II receptor blockers (p < .05). A total of 2.3% of patients reported mild adverse events (gastrointestinal or skin symptoms, headache, insomnia and transient blurred vision). Conclusion Administration of the HCQ+AZ combination before COVID-19 complications occur is safe and associated with very low fatality rate in patients.


title: Full-length genome analysis of canine coronavirus type I

text: Abstract Canine coronavirus types I (CCoV-I) and II (CCoV-II) are usually responsible for mild enteritis in dogs. While the CCoV-II genome has been completely sequenced, to date there are no complete genomic sequence data available publicly for CCoV-I. Thus, the aim of the present study was to analyze the full-length genome of a CCoV-I prototype strain that had been recovered from a dog with diarrhea in Italy. CCoV-I strain 23/03 has a genome of 30,000 nucleotides, excluding the 3′ poly(A) tail, displaying the typical Alphacoronavirus-1 organization and the highest genetic relatedness to CCoV-II. However, two distinct features were observed in the CCoV-I genome: (i) the presence of an additional ORF between the spike (S) protein gene and ORF3a; (ii) the diversity of the S protein, which is more closely related to that of feline coronavirus type I and presents a furin cleavage site. The present study may contribute to a better understanding of the Alphacoronavirus-1 evolutionary pattern and may be paradigmatic of how coronaviruses evolve through gene losses, acquisition and exchanges among different members.


Challenge of managing patients with COVID‐19 and acute behavioural disturbances


title: Metagenomics and the molecular identification of novel viruses

text: Abstract There have been rapid recent developments in establishing methods for identifying and characterising viruses associated with animal and human diseases. These methodologies, commonly based on hybridisation or PCR techniques, are combined with advanced sequencing techniques termed ‘next generation sequencing’. Allied advances in data analysis, including the use of computational transcriptome subtraction, have also impacted the field of viral pathogen discovery. This review details these molecular detection techniques, discusses their application in viral discovery, and provides an overview of some of the novel viruses discovered. The problems encountered in attributing disease causality to a newly identified virus are also considered.


title: Tropical sprue in southern India

text: Abstract Tropical sprue, a primary malabsorption syndrome affecting residents and visitors to several tropical regions, occurs in southern India in endemic and epidemic forms. The stomach, the small intestine and colon are affected and malabsorption results in nutrient deficiency. Enterocyte damage, the primary lesion in southern Indian tropical sprue, is the result of a persistent lesion of the stem cell compartment. This lesion occurs on a background of tropical enteropathy and the available evidence suggests that an immunity conferring agent may be responsible for initiating the damage.


title: The economy-wide impact of pandemic influenza on the UK: a computable general equilibrium modelling experiment

text: Objectives To estimate the potential economic impact of pandemic influenza, associated behavioural responses, school closures, and vaccination on the United Kingdom. Design A computable general equilibrium model of the UK economy was specified for various combinations of mortality and morbidity from pandemic influenza, vaccine efficacy, school closures, and prophylactic absenteeism using published data. Setting The 2004 UK economy (the most up to date available with suitable economic data). Main outcome measures The economic impact of various scenarios with different pandemic severity, vaccination, school closure, and prophylactic absenteeism specified in terms of gross domestic product, output from different economic sectors, and equivalent variation. Results The costs related to illness alone ranged between 0.5% and 1.0% of gross domestic product (£8.4bn to £16.8bn) for low fatality scenarios, 3.3% and 4.3% (£55.5bn to £72.3bn) for high fatality scenarios, and larger still for an extreme pandemic. School closure increases the economic impact, particularly for mild pandemics. If widespread behavioural change takes place and there is large scale prophylactic absence from work, the economic impact would be notably increased with few health benefits. Vaccination with a pre-pandemic vaccine could save 0.13% to 2.3% of gross domestic product (£2.2bn to £38.6bn); a single dose of a matched vaccine could save 0.3% to 4.3% (£5.0bn to £72.3bn); and two doses of a matched vaccine could limit the overall economic impact to about 1% of gross domestic product for all disease scenarios. Conclusion Balancing school closure against “business as usual” and obtaining sufficient stocks of effective vaccine are more important factors in determining the economic impact of an influenza pandemic than is the disease itself. Prophylactic absence from work in response to fear of infection can add considerably to the economic impact.


title: Possible SARS Coronavirus Transmission during Cardiopulmonary Resuscitation

text: Infection of healthcare workers with the severe acute respiratory syndrome–associated coronavirus (SARS-CoV) is thought to occur primarily by either contact or large respiratory droplet transmission. However, infrequent healthcare worker infections occurred despite the use of contact and droplet precautions, particularly during certain aerosol-generating medical procedures. We investigated a possible cluster of SARS-CoV infections in healthcare workers who used contact and droplet precautions during attempted cardiopulmonary resuscitation of a SARS patient. Unlike previously reported instances of transmission during aerosol-generating procedures, the index case-patient was unresponsive, and the intubation procedure was performed quickly and without difficulty. However, before intubation, the patient was ventilated with a bag-valve-mask that may have contributed to aerosolization of SARS-CoV. On the basis of the results of this investigation and previous reports of SARS transmission during aerosol-generating procedures, a systematic approach to the problem is outlined, including the use of the following: 1) administrative controls, 2) environmental engineering controls, 3) personal protective equipment, and 4) quality control.


title: Jubanines F–J, cyclopeptide alkaloids from the roots of Ziziphus jujuba

text: Abstract Five Ib-type cyclopeptide alkaloids, jubanines F–J (1–5), and three known compounds, nummularine B (6), daechuine-S3 (7), and mucronine K (8) were isolated from the roots of Ziziphus jujuba. Their structures were fully characterized by spectroscopic analyses in combination with chemical derivatization. Compounds 1–3, and 6 were evaluated for their antiviral activity against the porcine epidemic diarrhea virus (PEDV). Compounds 2, 3, and 6 showed potent inhibitory effects on PEDV replication.


Citizenship after COVID‐19: thoughts from Poland


title: Randomly primed, strand-switching MinION-based sequencing for the detection and characterization of cultured RNA viruses

text: RNA viruses rapidly mutate, which can result in increased virulence, increased escape from vaccine protection, and false negative detection results. Targeted detection methods have a limited ability to detect unknown viruses and often provide insufficient data to detect coinfections or identify antigenic variants. Random, deep sequencing is a method that can more fully detect and characterize RNA viruses and is often coupled with molecular techniques or culture methods for viral enrichment. Viral culture coupled with third-generation sequencing were tested for the ability to detect and characterize RNA viruses. Cultures of bovine viral diarrhea virus, canine distemper virus, epizootic hemorrhagic disease virus, infectious bronchitis virus, two influenza A viruses, and porcine respiratory and reproductive syndrome virus were sequenced on the MinION platform using a random, reverse primer in a strand-switching reaction, coupled with PCR-based barcoding. Reads were taxonomically classified and used for reference-based sequence building using a stock personal computer. This method accurately detected and identified complete coding sequence genomes with a minimum of 20× coverage depth for all seven viruses, including a sample containing two viruses. Each lineage-typing region had at least 26× coverage depth for all viruses. Furthermore, analyzing the canine distemper virus sample through a pipeline devoid of canine distemper virus reference sequences modeled the ability of this protocol to detect unknown viruses. These results show the ability of this technique to detect and characterize dsRNA, negative- and positive-sense ssRNA, nonsegmented, and segmented RNA viruses.


title: Establishment of a panel of in‐house polyclonal antibodies for the diagnosis of enterovirus infections

text: The aim of this study was to establish a reliable method of virus detection for the diagnosis of critical enterovirus infections such as acute infective encephalitis, encephalomyelitis and myocarditis. Because histopathological and immunohistochemical analyses of paraffin‐embedded tissues play an important role in recognizing infectious agents in tissue samples, six in‐house polyclonal antibodies raised against three representative enteroviruses using an indirect immunofluorescence assay and immunohistochemistry were examined. This panel of polyclonal antibodies recognized three serotypes of enterovirus. Two of the polyclonal antibodies were raised against denatured virus particles from enterovirus A71, one was raised against the recombinant VP1 protein of coxsackievirus B3, and the other for poliovirus type 1 were raised against denatured virus particles, the recombinant VP1 protein and peptide 2C. Western blot analysis revealed that each of these antibodies recognized the corresponding viral antigen and none cross‐reacted with non‐enteroviruses within the family Picornaviridae. However, all cross‐reacted to some extent with the antigens derived from other serotypes of enterovirus. Indirect immunofluorescence assay and immunohistochemistry revealed that the virus capsid and non‐structural proteins were localized in the cytoplasm of affected culture cells, and skeletal muscles and neurons in neonatal mice experimentally‐infected with human enterovirus. The antibodies also recognized antigens derived from recent clinical isolates of enterovirus A71, coxsackievirus B3 and poliovirus. In addition, immunohistochemistry revealed that representative antibodies tested showed the same recognition pattern according to each serotype. Thus, the panel of in‐house anti‐enterovirus polyclonal antibodies described herein will be an important tool for the screening and pathological diagnosis for enterovirus infections, and may be useful for the classification of different enterovirus serotypes, including coxsackieviruses A and B, echoviruses, enterovirus A71 and poliovirus.


title: Data Analysis of Coronavirus CoVID‐19 Epidemic in South Korea Based on Recovered and Death Cases

text: Coronavirus epidemic caused announcing emergency case in South Korea. The virus started with one infected case by January 20, 2020, where 9583 announced cases were reported by March 29, 2020. This indicates that the number of confirmed cases is increasing rapidly, which can cause national crises for South Korea. The aim of this study is to fill a gap between previous studies and the current development of CoVID‐19 spreading, by extracting a relationship between independent variables and dependent variable. This research statistically analyzed the effect of sex, region, infection reasons, birth year, and released or diseased date on the reported numbers of recovered and deceased cases. The results found that sex, region, and infection reasons affected on both recovered and deceased cases, while birth year only affected on deceased cases. Besides, no deceased cases are reported for released cases, while 11.3% of deceased cases positive confirmed after their deceased. Unknown reason of infection is the main variable that detected in South Korea with more than 33% of total infected cases. This article is protected by copyright. All rights reserved.