title: Human Natural Antibodies to Mammalian Carbohydrate Antigens as Unsung Heroes Protecting against Past, Present, and Future Viral Infections

text: Human natural antibodies to mammalian carbohydrate antigens (MCA) bind to carbohydrate-antigens synthesized in other mammalian species and protect against zoonotic virus infections. Three such anti-MCA antibodies are: (1) anti-Gal, also produced in Old-World monkeys and apes, binds to α-gal epitopes synthesized in non-primate mammals, lemurs, and New-World monkeys; (2) anti-Neu5Gc binds to Neu5Gc (N-glycolyl-neuraminic acid) synthesized in apes, Old-World monkeys, and many non-primate mammals; and (3) anti-Forssman binds to Forssman-antigen synthesized in various mammals. Anti-viral protection by anti-MCA antibodies is feasible because carbohydrate chains of virus envelopes are synthesized by host glycosylation machinery and thus are similar to those of their mammalian hosts. Analysis of MCA glycosyltransferase genes suggests that anti-Gal appeared in ancestral Old-World primates following catastrophic selection processes in which parental populations synthesizing α-gal epitopes were eliminated in enveloped virus epidemics. However, few mutated offspring in which the α1,3galactosyltransferase gene was accidentally inactivated produced natural anti-Gal that destroyed viruses presenting α-gal epitopes, thereby preventing extinction of mutated offspring. Similarly, few mutated hominin offspring that ceased to synthesize Neu5Gc produced anti-Neu5Gc, which destroyed viruses presenting Neu5Gc synthesized in parental hominin populations. A present-day example for few humans having mutations that prevent synthesis of a common carbohydrate antigen (produced in >99.99% of humans) is blood-group Bombay individuals with mutations inactivating H-transferase; thus, they cannot synthesize blood-group O (H-antigen) but produce anti-H antibody. Anti-MCA antibodies prevented past extinctions mediated by enveloped virus epidemics, presently protect against zoonotic-viruses, and may protect in future epidemics. Travelers to regions with endemic zoonotic viruses may benefit from vaccinations elevating protective anti-MCA antibody titers.


title: The antiviral activity of naturally occurring proteins and their peptide fragments after chemical modification

text: Abstract Chemical modification of the proteins bovine serum albumin, α-lactalbumin, β-lactoglobulin and chicken lysozyme by 3-hydroxyphthalic anhydride (3-HP) yielded compounds which exerted antiviral activity in vitro as compared with the native unmodified proteins. Of the three enveloped viruses tested, human herpes simplex virus type 1 (HSV-1), bovine parainfluenza virus type 3 and porcine respiratory corona virus, only HSV-1 proved sensitive to the 3-HP-proteins. All of the chemically modified proteins presented antiviral activity against HSV-1 when assayed before, during or after infection. However, to achieve HSV-1 inhibition, significantly higher concentrations of the modified proteins were required if present before infection as compared to during or after infection. Our results suggest that multiple mechanisms are involved in the inhibition of HSV-1 infection. Proteolytical digestion of albumin, α-lactalbumin, β-lactoglobulin and lysozyme by trypsin, chymotrypsin and pepsin yielded several peptide fragments with antiherpetic activity. Chemical modification of these peptide fragments by 3-HP generated peptides with antiviral activity, however, this was almost always combined with a cytotoxic effect on the Vero cells. Overall, our results suggest that targeted chemical modification of some natural products might provide compounds effective against HSV-1 infection.


title: Avian defensins

text: Abstract Modulation of defensin expression may be one way to improve animal health and to reduce zoonotic diseases. Defensins are small, cationic, and amphipathic cysteine-rich antibiotic peptides found in plants, insects, mammals and birds. Whereas α- and θ-defensins appear to be absent in birds, several β-defensins have been isolated from avian heterophils. In addition, β-defensins were found to be constitutively or inducibly expressed at mucosal surfaces of the respiratory, intestinal and urogenital tracts. In this review the current knowledge of the defensin repertoire of birds, their tissue-specific expression, regulation and corresponding biological functions are described.


title: High‐immunological risk living donor renal transplant during the COVID‐19 outbreak: Uncertainties and ethical dilemmas

text: We describe the challenges of performing a high-immunological risk living donor renal transplant during the COVID-19 outbreak. A 42-year-old lady with end-stage renal disease from lupus nephritis had failed peritoneal dialysis due to pleuro-peritoneal leak, failed vascular access creation due to early thrombosis and had recurrent dialysis catheter malfunction. The transplant from her husband was ABO-incompatible and had positive B cell flow crossmatch with multiple donor-specific antibodies. Neither alternative donors nor paired exchange candidates were available. Priority access to deceased donors is limited and unpredictable.


title: Trials and tribulations: so many potential treatments, so few answers

text: PURPOSE: The purpose of this review is to quantify the landscape of current clinical trials ongoing for therapies in the treatment of COVID-19. A secondary purpose is to examine the relationship between public and scientific interests in potential therapies for COVID-19. METHODS: A systematic search of clinicaltrials.gov was undertaken on April 22, 2020, to identify all currently registered clinical trials investigating potential therapies for patients with COVID-19. Public interest in the various therapies was quantified utilizing Google Trends. Public interest in hydroxychloroquine and chloroquine was plotted against the cumulative number of active clinical trials evaluating antimalarials as potential COVID-19 therapies over time. RESULTS: There were 341 interventional studies and 208 different therapies actively registered on clinicaltrials.gov whose primary aim is the treatment of COVID-19. The median sample size was 120 patients (range 4–6000) with 154 (45%) trials reporting a planned sample size of 100 patients or less. There was a strong positive correlation (r = 0.76, p = 0.01) between the number of registered clinical trials and the public interest in the top ten proposed therapies. Following the spike in public interest, the average number of new trials increased tenfold with respect to antimalarial therapies. CONCLUSIONS: The relatively small sample sizes and the number of independent trials investigating similar therapies are concerning. Resources may not be being allocated based on scientific merit and may be driven by public consciousness and speculation. Moving forward, a concerted effort focused on implementing large, well-coordinated and carefully designed multi-armed clinical trials will help to ensure that the most promising therapeutic options are rigorously studied and clinically meaningful results produced.


title: Severe Acute Respiratory Syndrome–associated Coronavirus Infection

text: Whether severe acute respiratory syndrome–associated coronavirus (SARS-CoV) infection can be asymptomatic is unclear. We examined the seroprevalence of SARS-CoV among 674 healthcare workers from a hospital in which a SARS outbreak had occurred. A total of 353 (52%) experienced mild self-limiting illnesses, and 321 (48%) were asymptomatic throughout the course of these observations. None of these healthcare workers had antibody to SARS CoV, indicating that subclinical or mild infection attributable to SARS CoV in adults is rare.


title: Respiratory Pathogens in Children with and without Respiratory Symptoms

text: Objectives To investigate the occurrence of respiratory pathogens in samples from children with and without respiratory symptoms and to identify whether age and/ or coinfections modify the impact of respiratory pathogens on symptoms. Study design In a prospective longitudinal study, 18 children were sampled biweekly for respiratory pathogens, irrespective of respiratory symptoms. Polymerase chain reaction was performed for 13 respiratory pathogens. Episodes were defined “asymptomatic” if no symptoms of any respiratory tract illness were present between 1 week before and 1 week after sampling. Results A total of 230 samples were collected. In 56% of the symptomatic episodes, a pathogen was detected, compared with 40% of the asymptomatic episodes (P = .03). Rhinovirus and coronaviruses were most prevalent in both symptomatic and asymptomatic episodes. In the youngest children, 9% of the pathogen-positive episodes were asymptomatic, compared with 36% in the oldest children (P = .01). Multiple pathogens were found in 17% of the symptomatic episodes and in 3% of the asymptomatic episodes (P = .02). Conclusions Respiratory pathogens are frequently detected in samples from children with no respiratory symptoms. Symptomatic cases occurred more often in younger children and with detections of more than 1 respiratory pathogen.


Clinical Signs, Computed Tomographic Imaging, and Management of Chronic Otitis Media/Interna in Dairy Calves


title: Covid‐19 and UK Universities

text: Universities UK (UUK) has suggested that there may be very significant losses to higher education as a consequence of Covid‐19. However, losses are likely to be substantially lower than the potential losses estimated by UUK. But the magnitude of losses is very uncertain. The UUK’s proposal to restrict undergraduate enrolment per university to stop institutions poaching students is not in the interests of the most highly regarded universities, or that of students. Some rationalisation of the sector should be the price of further government support. Now is also the time to reconsider how university research is funded.


title: Viral zoonoses in Europe

text: Abstract A number of new virus infections have emerged or re-emerged during the past 15 years. Some viruses are spreading to new areas along with climate and environmental changes. The majority of these infections are transmitted from animals to humans, and thus called zoonoses. Zoonotic viruses are, as compared to human-only viruses, much more difficult to eradicate. Infections by several of these viruses may lead to high mortality and also attract attention because they are potential bioweapons. This review will focus on zoonotic virus infections occurring in Europe.


title: Report of fatal mixed infection with Cryptosporidium parvum and Giardia intestinalis in neonatal calves

text: In the production and management of beef and dairy cattle, controlling diarrhea is one of the important concerns. Pathogenic agents of the disease, protozoan parasites including Cryptosporidium spp., are difficult to control, making prevention, diagnoses, and treatment of diarrhea. In the present study, we investigated a farm with a history of calf deaths over a period of 10 years in order to determine the cause of disease and to clarify the detailed distribution of the pathogens. In four examined calves that were reared in calf pens, all were positive with Cryptosporidium and/or Giardia, while the other breeding stock and adult cattle were negative. Molecular analyses revealed that the isolates from calves were C. parvum subtype IIaA15G2R1 as a zoonotic and G. intestinalis assemblage E. Other pathogenic bacteria and diarrhea-causing viruses were not detected. After treating the calf pens with boiling water and milk of lime (Ca[OH](2)), oocysts of C. parvum and cysts of G. intestinalis were not found and no additional calves died. This is the first report to describe the mixed infection of both parasites in Japan.


title: Comparative models for human nasal infections and immunity

text: Abstract The human olfactory system is a mucosal surface and a major portal of entry for respiratory and neurotropic pathogens into the body. Understanding how the human nasopharynx-associated lymphoid tissue (NALT) halts the progression of pathogens into the lower respiratory tract or the central nervous system is key for developing effective cures. Although traditionally mice have been used as the gold-standard model for the study of human nasal diseases, mouse models present important caveats due to major anatomical and functional differences of the human and murine olfactory system and NALT. We summarize the NALT anatomy of different animal groups that have thus far been used to study host-pathogen interactions at the olfactory mucosa and to test nasal vaccines. The goal of this review is to highlight the strengths and limitations of each animal model of nasal immunity and to identify the areas of research that require further investigation to advance human health.


title: Impact of Covid-19 Lockdown on Characteristics of Autopsy Cases in Greece. Comparison between 2019 and 2020

text: In order to reduce transmission of COVID-19, social distancing measures were proposed, including spatial distancing (2 m distance), or even generalized lockdown. Main concern was to prevent overwhelming of the healthcare systems, mainly of the intensive care units (ICUs) by decreasing the spreading of the disease. In Greece, the Government, after consulting with experts in the fields of infectious disease and epidemiology, implemented a rather aggressive stance with an early lockdown. Aim of our study, is to identify and compare the characteristics of cases referred for autopsy during the first month of the lockdown period for the COVID-19 outbreak, versus the cases referred during the same period in 2019. 231 autopsy cases were included in our study, 125 in 2019 and 106 in 2020. Regarding gender, age and nationality, no significant differences were detected between the two time periods. Age subgroup analysis demonstrated increased number of cases within the age group 70-79 years, in 2020. As to the place of death, the increase in the percentage of out-of-hospital deaths was not confirmed as statistically significant. Regarding type of death (violent, sudden/unexpected), the drop of violent deaths in the 2020 examined period, was not confirmed as statistically significant; however, further subgroup analysis showed a significant drop of fatal injuries resulting from road traffic accidents in the 2020 period. The slight increase of sudden/unexpected deaths, especially myocardial infarction cases, did not reach statistical significance. One month after lockdown, we cannot detect significant differences in the two time periods examined. Further study should be conducted soon when more data will become available. Frequency of fatal myocardial infarction seems to remain unaffected by the COVID-19 pandemic while deaths resulting from road traffic accidents exhibit a significant decrease. Homicides and suicides remain at low levels, in our jurisdiction area, seemingly unaffected by the COVID-19 outbreak and the subsequent lockdown. It appears that since sudden/unexpected deaths, statistically remain unaffected, the preventive measures taken by the Greek authorities prevented overwhelming of the healthcare system, which could function properly.


title: Evaluation of rapid and simple techniques for the enrichment of viruses prior to metagenomic virus discovery

text: Abstract The discovery of new or divergent viruses using metagenomics and high-throughput sequencing has become more commonplace. The preparation of a sample is known to have an effect on the representation of virus sequences within the metagenomic dataset yet comparatively little attention has been given to this. Physical enrichment techniques are often applied to samples to increase the number of viral sequences and therefore enhance the probability of detection. With the exception of virus ecology studies, there is a paucity of information available to researchers on the type of sample preparation required for a viral metagenomic study that seeks to identify an aetiological virus in an animal or human diagnostic sample. A review of published virus discovery studies revealed the most commonly used enrichment methods, that were usually quick and simple to implement, namely low-speed centrifugation, filtration, nuclease-treatment (or combinations of these) which have been routinely used but often without justification. These were applied to a simple and well-characterised artificial sample composed of bacterial and human cells, as well as DNA (adenovirus) and RNA viruses (influenza A and human enterovirus), being either non-enveloped capsid or enveloped viruses. The effect of the enrichment method was assessed by both quantitative real-time PCR and metagenomic analysis that incorporated an amplification step. Reductions in the absolute quantities of bacteria and human cells were observed for each method as determined by qPCR, but the relative abundance of viral sequences in the metagenomic dataset remained largely unchanged. A 3-step method of centrifugation, filtration and nuclease-treatment showed the greatest increase in the proportion of viral sequences. This study provides a starting point for the selection of a purification method in future virus discovery studies, and highlights the need for more data to validate the effect of enrichment methods on different sample types, amplification, bioinformatics approaches and sequencing platforms. This study also highlights the potential risks that may attend selection of a virus enrichment method without any consideration for the sample type being investigated.


title: Development and optimized pairing of mouse monoclonal antibodies for detecting hemagglutinin in novel H7 subtype influenza viruses

text: The H7 subtype avian influenza threatens public health with respect to poultry and humans. Thus, a specific and sensitive diagnostic test is essential for the management of H7 subtype influenza infections. In this study, five mouse monoclonal antibodies (mAbs) against hemagglutinin (HA) of influenza A/Anhui/1/2013 (H7N9) were produced and characterized by the Western blot, immunofluorescence, and hemagglutination inhibition assays. All five specific mAbs reacted with the HA protein of H7N9 but not with that of H1N1, H3N2, or H5N1. With the combination arrays of capture and detection antibodies, the matched pair mAbs (1C4-coated and 2D7-labeled) were selected and employed in a double-antibody sandwich ELISA (DAS-ELISA). Detection limits of the sandwich ELISA were 0.45 ng mL(−1) for the HA protein derived from A/Anhui/1/2013 (H7N9); or 1 and 2 HA units/50 µL for A/Anhui/1/2013 (H7N9) and A/GD/17SF003/2016 (H7N9), respectively. These anti-HA mAbs against subtype H7 and the novel DAS-ELISA provide a valuable approach for specific detection of the H7 subtype influenza virus and quantification of its HA protein, especially for the novel epidemic H7N9.


title: Body Mass Index, Weight Discrimination, and Psychological, Behavioral, and Interpersonal Responses to the Coronavirus Pandemic

text: OBJECTIVE: To examine whether body mass index (BMI) and weight discrimination are associated with psychological, behavioral, and interpersonal responses to the coronavirus pandemic. METHODS: Using a prospective design, participants (N=2,094) were first assessed in early February 2020 before the coronavirus crisis in the United States and again in mid‐March 2020 during the President’s 15 Days to Slow the Spread guidelines. Weight, height, and weight discrimination were assessed in the February survey. Psychological, behavioral, and interpersonal responses to the coronavirus were assessed in the March survey. RESULTS: Pre‐pandemic experiences with weight discrimination were associated with greater concerns about the virus, engaging in more preventative behaviors, less trust in people and institutions to manage the outbreak, and greater perceived declines in connection to one’s community. BMI tended to be unrelated to these responses. CONCLUSIONS: Despite the risks of complications of COVID‐19 associated with obesity, individuals with higher BMI were neither more concerned about the virus nor taking more behavioral precautions than individuals in other weight categories. Weight discrimination, in contrast, may heighten vigilance to threat, which may have contributed to both positive (greater concern, more precautionary behavior) and negative (less trust, declines community connection) responses to the pandemic.


Keeping alive enterprises while embracing unprecedented COVID-19 restrictions


title: Anti-MHV3 state induced by IFN gamma in macrophages is not related to arginine metabolism

text: In contrast to BALB/c mouse macrophages, the A/J macrophages after activation by interferon gamma (IFN gamma) develop an anti-MHV3 effect which correlates with the resistance to virus infection. To understand the cellular basis of this antiviral effect, we studied the possible involvement of arginine metabolism through nitric oxide (NO) and arginase induction, since these metabolic pathways have been described as implicated in antiviral activities of macrophages. The studies were performed by activating macrophages with inducers of NO (IFN gamma) and arginase (IL4 IL10). NO synthase (iNOS) and arginase inhibitors (N-methyl-arginine, NMA, and hydroxyarginine, OH-ARG) were used. The results show that in both macrophage populations, no spontaneous synthesis of NO occurred and the MHV3 enhanced the NO release induced by IFN gamma. After activation with IFN gamma, BALB/c macrophages released higher amounts of NO than the A/J macrophages. The inhibition of IFN gamma-induced NO-synthesis with NMA or with arginine free medium did not affect the virus replication. In BALB/c macrophages, IL4 or IL10, induced higher amounts of arginase than in A/J macrophages. In both macrophage populations the MHV3 infection had no influence on the arginase synthesized, and the inhibition of the arginase with OH-ARG had no influence on the virus growth. The level of MHV3 replication or inhibition was also not influenced when we used macrophages from knockout mice for the iNOS gene, and as a consequence were unable of synthesizing NO. These data indicate that NO and arginase do not participate in the anti-MHV3 state induced by IFN gamma in macrophages.


title: Contraception in the Era of COVID-19

text: As global health systems and communities prepare to meet an unprecedented threat causing increased demands for the care of people with COVID-19, health care providers should strive to ensure continuity of reproductive health care to women and girls in the face of facility service disruption.


How well prepared are dermatologists redeployed to COVID‐19 wards?


Abstracts of papers presented at the 5th workshop of the virology section of the deutsche gesellschaft für hygiene und mikrobiologie


title: The heterogeneous age-mixing model of estimating the covid cases of different local government units in the National Capital Region, Philippines

text: OBJECTIVES: The objective of the study is to investigate the effects of transmission control efforts of the Philippine Government through implementation of Enhanced Community Quarantine (ECQ) on curtailing the exponential growth of the Corona Virus (Covid-19). Also, this study provides forecast of transmission rate of Covid-19 incorporating the heterogeneous characteristics of the group of population according to age. METHODS: The heterogeneous-mixing model was used to forecast the transmission rate of Covid-19 and effect of Enhanced Community Quarantine in various Local Government Units (LGUs) in the National Capital Region (NCR), Philippines. RESULTS: The result of the study revealed that the mobility of people has significant contribution to the transmission rate of Covid-19. The result of the study revealed that the mobilization of workers, who are exempted in ECQ, would greatly affect the transmission of disease to those who are in the senior citizen group. The increase in the confirmed cases of Covid-19 is associated with the transmission from those workers, who are exempted from ECQ to senior citizens and the young age group. LGUs in the NCR, Philippines will experience a different pattern of peak periods ranging from the third week of April to the last week of May. CONCLUSIONS: This study concluded that in order to achieve the containment of the spread of Covid-19 in the Philippines, the government should be stricter in implementation of the ECQ and incorporate the different pattern of transmission of Covid-19 in deciding whether to extend or to lift the ECQ.


title: Synthetic surfactin analogues have improved anti-PEDV properties

text: Surfactin has antiviral activity against various enveloped viruses by inhibiting viral membrane fusion. However, the potential utility of surfactin as an antiviral drug is limited by its cytotoxicity. In this study, 10 surfactin analogues were obtained by chemical synthesis and evaluated to determine their anti-PEDV activities, hemolytic activities, and critical micelle concentrations. The main goal of our study was to develop a safer drug; a surfactin analogue with high anti-PEDV activity and low hemolytic activity. Compared with surfactin, one of the analogues we developed, SLP5, has lower hemolytic activity, with the same antiviral activity. The selectivity index of SLP5 is 52, while the SI for surfactin is 4, in other words, the safe and effective concentration range of SLP5 is 12 times greater than that of surfactin. Like surfactin, SLP5 has a direct antiviral effect on PEDV. Structurally, SLP5 is a linear lipopeptide with three carboxyl groups. Surfactin derivatives similar to SLP5 could be obtained by lactone bond hydrolyzation of surfactin, as well as total synthesis.


title: Immunology of Bats and Their Viruses: Challenges and Opportunities

text: Bats are reservoir hosts of several high-impact viruses that cause significant human diseases, including Nipah virus, Marburg virus and rabies virus. They also harbor many other viruses that are thought to have caused disease in humans after spillover into intermediate hosts, including SARS and MERS coronaviruses. As is usual with reservoir hosts, these viruses apparently cause little or no pathology in bats. Despite the importance of bats as reservoir hosts of zoonotic and potentially zoonotic agents, virtually nothing is known about the host/virus relationships; principally because few colonies of bats are available for experimental infections, a lack of reagents, methods and expertise for studying bat antiviral responses and immunology, and the difficulty of conducting meaningful field work. These challenges can be addressed, in part, with new technologies that are species-independent that can provide insight into the interactions of bats and viruses, which should clarify how the viruses persist in nature, and what risk factors might facilitate transmission to humans and livestock.


title: Crosstalk Between Mammalian Antiviral Pathways

text: As part of their innate immune response against viral infections, mammals activate the expression of type I interferons to prevent viral replication and dissemination. An antiviral RNAi-based response can be also activated in mammals, suggesting that several mechanisms can co-occur in the same cell and that these pathways must interact to enable the best antiviral response. Here, we will review how the classical type I interferon response and the recently described antiviral RNAi pathways interact in mammalian cells. Specifically, we will uncover how the small RNA biogenesis pathway, composed by the nucleases Drosha and Dicer can act as direct antiviral factors, and how the type-I interferon response regulates the function of these. We will also describe how the factors involved in small RNA biogenesis and specific small RNAs impact the activation of the type I interferon response and antiviral activity. With this, we aim to expose the complex and intricate network of interactions between the different antiviral pathways in mammals.


title: Complete Genome of Hepatitis E Virus from Laboratory Ferrets

text: The complete genome of hepatitis E virus (HEV) from laboratory ferrets imported from the United States was identified. This virus shared only 82.4%–82.5% nt sequence identities with strains from the Netherlands, which indicated that the ferret HEV genome is genetically diverse. Some laboratory ferrets were contaminated with HEV.


title: Coronavirus Disease of 2019: a Mimicker of Dengue Infection?

text: At the beginning of 2020, the national health system and medical communities are faced with unprecedented public health challenges. A novel strain of coronavirus, later identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread globally, marking another pandemic of coronaviruses. This viral disease is responsible for devastating pneumonia, named coronavirus disease of 2019 (COVID-19), and projected to persist until the end of the year. In tropical countries, however, concerns arise regarding the similarities of COVID-19 with other infectious diseases due to the same chief complaint, which is fever. One of the infectious disease of a primary concern is dengue infection, which its peak season is approaching. Others report that there are cases of serological cross-reaction of COVID-19 and dengue infection. In this comprehensive review, we underscore the importance of knowing similar clinical presentations of both diseases and emphasize why excluding COVID-19 in the differentials in the setting of a pandemic is imprudent.


title: Viral Takeover of the Host Ubiquitin System

text: Like the other more well-characterized post-translational modifications (phosphorylation, methylation, acetylation, acylation, etc.), the attachment of the 76 amino acid ubiquitin (Ub) protein to substrates has been shown to govern countless cellular processes. As obligate intracellular parasites, viruses have evolved the capability to commandeer many host processes in order to maximize their own survival, whether it be to increase viral production or to ensure the long-term survival of latently infected host cells. The first evidence that viruses could usurp the Ub system came from the DNA tumor viruses and Adenoviruses, each of which use Ub to dysregulate the host cell cycle (Scheffner et al., 1990; Querido et al., 2001). Today, the list of viruses that utilize Ub includes members from almost every viral class, encompassing both RNA and DNA viruses. Among these, there are examples of Ub usage at every stage of the viral life cycle, involving both ubiquitination and de-ubiquitination. In addition to viruses that merely modify the host Ub system, many of the large DNA viruses encode their own Ub modifying machinery. In this review, we highlight the latest discoveries regarding the myriad ways that viruses utilize Ub to their advantage.


title: Multiplex bioanalytical methods for food and environmental monitoring

text: Abstract Recent advances in miniaturization of analytical systems and newly emerging technologies offer platforms with greater automation and multiplexing capabilities than traditional biological binding assays. Multiplexed bioanalytical techniques provide control agencies and food industries with new possibilities for improved, more efficient monitoring of food and environmental contaminants. This review deals with recent developments in planar-array and suspension-array technologies, and their applications in detecting pathogens, food allergens and adulterants, toxins, antibiotics and environmental contaminants.


SGLT-2 inhibitors for COVID-19 — A miracle waiting to happen or just another beat around the bush?


Society and the reception of imaging technology: The American experience


Subject index Veterinary Microbioloy, volumes 26–50, 1991–1996


AIR tent for airway management of SARS patients


title: Women in Neuroscience: A Short Time Travel

text: About half of graduate and postgraduate students and one-third of faculty in the field of neuroscience are women. The proportion of women neuroscientists tend to decrease as they progress through the career ladder. Their responsibilities and their opportunities to secure research funding also tend to be lower compared to men, as in most scientific disciplines and professions. The multiple factors contributing to the under-representation of women in higher-level roles have historical, social, and cultural roots. A process of forgetfulness of pioneer women from the last century prevented the field from having role models in which upcoming generations of women neuroscientists could have identified. Maria Manasseina, Cécile Vogt, Augusta Dejerine Klumpke are only some early pioneers who have recently been rediscovered. The available data show that the profiles of women neuroscientists are overlooked and their remarkable findings receive less recognition. Conscious and unconscious gender biases also affect the evaluation and recruitment process. The presence of cultural and institutional barriers continues to hinder equal opportunities in all aspects of the scientific and academic career. The initiatives launched so far to increase awareness of such barriers and diversity in the workplace have produced a slight improvement but further action should be taken and supported to improve the condition of women in neuroscience.


title: Can N95 Respirators Be Reused after Disinfection? How Many Times?

text: [Image: see text] The coronavirus disease 2019 (COVID-19) pandemic has led to a major shortage of N95 respirators, which are essential for protecting healthcare professionals and the general public who may come into contact with the virus. Thus, it is essential to determine how we can reuse respirators and other personal protective equipment in these urgent times. We investigated multiple commonly used disinfection schemes on media with particle filtration efficiency of 95%. Heating was recently found to inactivate the virus in solution within 5 min at 70 °C and is among the most scalable, user-friendly methods for viral disinfection. We found that heat (≤85 °C) under various humidities (≤100% relative humidity, RH) was the most promising, nondestructive method for the preservation of filtration properties in meltblown fabrics as well as N95-grade respirators. At 85 °C, 30% RH, we were able to perform 50 cycles of heat treatment without significant changes in the filtration efficiency. At low humidity or dry conditions, temperatures up to 100 °C were not found to alter the filtration efficiency significantly within 20 cycles of treatment. Ultraviolet (UV) irradiation was a secondary choice, which was able to withstand 10 cycles of treatment and showed small degradation by 20 cycles. However, UV can potentially impact the material strength and subsequent sealing of respirators. Finally, treatments involving liquids and vapors require caution, as steam, alcohol, and household bleach all may lead to degradation of the filtration efficiency, leaving the user vulnerable to the viral aerosols.


title: Ultrastructure and protein A-gold immunolabelling of HRT-18 cells infected with turkey enteric coronavirus

text: Abstract The Minnesota strain of turkey enteric coronavirus (TCV) was propagated in HRT-18 cells, a cell line derived from human rectum adenocarcinoma. A productive non-cytopathic infection was established, without a previous adaptation, in these cells as shown by the specific hemagglutinating activity in cell culture supernatants. A post-embedding immunochemical technique, using specific antiserum directed against the original egg-adapted virus and colloidal-gold-labelled protein A as the electron-dense marker, was used for the identification of the virus and related antigens in the cells by electron microscopy. Budding of typical coronavirus particles, through intracytoplasmic membranes and accumulation of complete virus within cytoplasmic vesicles or the lumen of rough endoplasmic reticulum, were the main features of the viral morphogenesis. Late in infection, numerous progeny viral particles were shown at the outer surface of infected cells, but budding could not be demonstrated at this level. Two different types of surface projections were observed on the extracellular particles of this avian coronavirus. These morphological characteristics have been thus far described only for mammalian hemagglutinating coronaviruses.


Severe Acute Respiratory Syndrome : An Update


title: Universal Mask Usage for Reduction of Respiratory Viral Infections After Stem Cell Transplant: A Prospective Trial

text: Background. Respiratory viral infections (RVIs) are frequent complications of hematopoietic stem cell transplant (HSCT). Surgical masks are a simple and inexpensive intervention that may reduce nosocomial spread. Methods. In this prospective single-center study, we instituted a universal surgical mask policy requiring all individuals with direct contact with HSCT patients to wear a surgical mask, regardless of symptoms or season. The primary endpoint was the incidence of RVIs in the mask period (2010–2014) compared with the premask period (2003–2009). Results. RVIs decreased from 10.3% (95/920 patients) in the premask period to 4.4% (40/911) in the mask period (P < .001). Significant decreases occurred after both allogeneic (64/378 [16.9%] to 24/289 [8.3%], P = .001) and autologous (31/542 [5.7%] to 16/622 [2.6%], P = .007) transplants. After adjusting for multiple covariates including season and year in a segmented longitudinal analysis, the decrease in RVIs remained significant, with risk of RVI of 0.4 in patients in the mask group compared with the premask group (0.19–0.85, P = .02). In contrast, no decrease was observed during this same period in an adjacent hematologic malignancy unit, which followed the same infection control practices except for the mask policy. The majority of this decrease was in parainfluenza virus 3 (PIV3) (8.3% to 2.2%, P < .001). Conclusions. Requiring all individuals with direct patient contact to wear a surgical mask is associated with a reduction in RVIs, particularly PIV3, during the most vulnerable period following HSCT.


title: Antibody therapies for the prevention and treatment of viral infections

text: Antibodies are an important component in host immune responses to viral pathogens. Because of their unique maturation process, antibodies can evolve to be highly specific to viral antigens. Physicians and researchers have been relying on such high specificity in their quest to understand host–viral interaction and viral pathogenesis mechanisms and to find potential cures for viral infection and disease. With more than 60 recombinant monoclonal antibodies developed for human use in the last 20 years, monoclonal antibodies are now considered a viable therapeutic modality for infectious disease targets, including newly emerging viral pathogens such as Ebola representing heightened public health concerns, as well as pathogens that have long been known, such as human cytomegalovirus. Here, we summarize some recent advances in identification and characterization of monoclonal antibodies suitable as drug candidates for clinical evaluation, and review some promising candidates in the development pipeline.


title: COVID-19 and Kidney Disease Disparities in the United States

text: Abstract Racial, ethnic, socioeconomic, age, and sex-related health disparities in kidney disease are prominent in the United States. The Coronavirus Disease 2019 (COVID-19) pandemic has disproportionately affected marginalized populations. Older adults, people experiencing unstable housing, racial and ethnic minorities and immigrants are potentially at increased risk for infection and severe complications from COVID-19. The direct and societal effects of the pandemic may increase risk of incident kidney disease and lead to worse outcomes for those with kidney disease. The rapid transition to telemedicine potentially limits access to care for older adults, immigrants, and people experiencing unstable housing. The economic impact of the pandemic has had a disproportionate effect on women, minorities and immigrants, which may limit their ability to manage kidney disease, and lead to complications or kidney disease progression. We describe the impact of COVID-19 on marginalized populations and highlight how the pandemic may exacerbate existing disparities in kidney disease.


title: Two Amino Acid Changes at the N-Terminus of Transmissible Gastroenteritis Coronavirus Spike Protein Result in the Loss of Enteric Tropism

text: Abstract To study the molecular basis of TGEV tropism, a collection of recombinants between the PUR46-MAD strain of transmissible gastroenteritis coronavirus (TGEV) infecting the enteric and respiratory tracts and the PTV strain, which only infects the respiratory tract, was generated. The recombinant isolation frequency was about 10−9recombinants per nucleotide and was 3.7-fold higher at the 5′-end of the S gene than in other areas of the genome. Thirty recombinants were plaque purified and characterized phenotypically and genetically. All recombinant viruses had a single crossover and had inherited the 5′- and 3′-halves of their genome from the enteric and respiratory parents, respectively. Recombinant viruses were classified into three groups, named 1 to 3, according to the location of the crossover. Group 1 recombinants had the crossover in the S gene, while in Groups 2 and 3 the crossovers were located in ORF1b and ORF1a, respectively. The tropism of the recombinants was studied. Recombinants of Group 1 had enteric and respiratory tropism, while Group 2 recombinants infected the respiratory, but not the enteric, tract. Viruses of both groups differed by two nucleotide changes at positions 214 and 655. Both changes may be in principle responsible for the loss of enteric tropism but only the change in nucleotide 655 was specifically found in the respiratory isolates and most likely this single nucleotide change, which leads to a substitution in amino acid 219 of the S protein, was responsible for the loss of enteric tropism in the closely related PUR-46 isolates. The available data indicate that in order to infect enteric tract cells with TGEV, two different domains of the S protein, mapping between amino acids 522 and 744 and around amino acid 219, respectively, are involved. The first domain binds to porcine aminopeptidase N, the cellular receptor for TGEV. In the other domain maps a second factor of undefined nature but which may be the binding site for a coreceptor essential for the enteric tropism of TGEV.


title: Discovery of N-(benzo[1,2,3]triazol-1-yl)-N-(benzyl)acetamido)phenyl) carboxamides as severe acute respiratory syndrome coronavirus (SARS-CoV) 3CLpro inhibitors: identification of ML300 and non-covalent nanomolar inhibitors with an induced-fit binding

text: Herein we report the discovery and SAR of a novel series of SARS-CoV 3CLpro inhibitors identified through the NIH Molecular Libraries Probe Production Centers Network (MLPCN). In addition to ML188, ML300 represents the second probe declared for 3CLpro from this collaborative effort. The X-ray structure of SARS-CoV 3CLpro bound with a ML300 analog highlights a unique induced-fit reorganization of the S(2)-S(4) binding pockets leading to the first sub-micromolar non-covalent 3CLpro inhibitors retaining a single amide bond.


title: Human metapneumovirus prevalence and molecular epidemiology in respiratory outbreaks in Ontario, Canada

text: Human metapneumovirus (hMPV) has been identified previously as a cause of respiratory outbreaks in adults, including the elderly. The objective of this study was to document respiratory outbreaks that were caused by hMPV in Ontario, Canada and to identify the various circulating genotypes during April 2009–February 2012. The majority of the outbreaks that were part of this study were in adults (>65 years). Total nucleic acid extraction was done on 123 residual anonymized clinical specimens from 51 different respiratory outbreaks. Specimens were subjected to PCR amplification and Sanger sequencing targeting the F and G genes of hMPV. Phylogenetic analysis was performed to identify genotypes. HMPV accounted for 195 (8.5%) of 2,292 respiratory outbreaks. Genotype A2b was most prevalent, detected in 28 (54.9%) of 51 typed hMPV‐positive outbreaks. The genotype A2b2 that was described recently was also identified. In earlier reports, subtype A1 was reported in Canada which was absent in the specimens typed in this study. This shift in genotype may be significant in terms of disease severity, and for any future vaccine considerations. Regular testing for hMPV should be done as part of outbreak investigation. J. Med. Virol. 87:269–274, 2015. © 2014 Wiley Periodicals, Inc.


title: Rapid Detection of COVID-19 Causative Virus (SARS-CoV-2) in Human Nasopharyngeal Swab Specimens Using Field-Effect Transistor-Based Biosensor

text: [Image: see text] Coronavirus disease 2019 (COVID-19) is a newly emerging human infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, previously called 2019-nCoV). Based on the rapid increase in the rate of human infection, the World Health Organization (WHO) has classified the COVID-19 outbreak as a pandemic. Because no specific drugs or vaccines for COVID-19 are yet available, early diagnosis and management are crucial for containing the outbreak. Here, we report a field-effect transistor (FET)-based biosensing device for detecting SARS-CoV-2 in clinical samples. The sensor was produced by coating graphene sheets of the FET with a specific antibody against SARS-CoV-2 spike protein. The performance of the sensor was determined using antigen protein, cultured virus, and nasopharyngeal swab specimens from COVID-19 patients. Our FET device could detect the SARS-CoV-2 spike protein at concentrations of 1 fg/mL in phosphate-buffered saline and 100 fg/mL clinical transport medium. In addition, the FET sensor successfully detected SARS-CoV-2 in culture medium (limit of detection [LOD]: 1.6 × 10(1) pfu/mL) and clinical samples (LOD: 2.42 × 10(2) copies/mL). Thus, we have successfully fabricated a promising FET biosensor for SARS-CoV-2; our device is a highly sensitive immunological diagnostic method for COVID-19 that requires no sample pretreatment or labeling.


title: Management of Critically Ill Patients with Severe Acute Respiratory Syndrome (SARS)

text: Severe acute respiratory syndrome (SARS) is frequently complicated with acute respiratory failure. In this article, we aim to focus on the management of the subgroup of SARS patients who are critically ill. Most SARS patients would require high flow oxygen supplementation, 20–30% required intensive care unit (ICU) or high dependency care, and 13–26% developed acute respiratory distress syndrome (ARDS). In some of these patients, the clinical course can progress relentlessly to septic shock and/or multiple organ dysfunction syndrome (MODS). The management of critically ill SARS patients requires timely institution of pharmacotherapy where applicable and supportive treatment (oxygen therapy, noninvasive and invasive ventilation). Superimposed bacterial and other opportunistic infections are common, especially in those treated with mechanical ventilation. Subcutaneous emphysema, pneumothoraces and pneumomediastinum may arise spontaneously or as a result of positive ventilatory assistance. Older age is a consistently a poor prognostic factor. Appropriate use of personal protection equipment and adherence to infection control measures is mandatory for effective infection control. Much of the knowledge about the clinical aspects of SARS is based on retrospective observational data and randomized-controlled trials are required for confirmation. Physicians and scientists all over the world should collaborate to study this condition which may potentially threaten human existence.


title: Identification and functional characterization of regions that can be crosslinked to RNA in the helicase-like domain of BaMV replicase

text: Abstract The helicase-like domain of the Bamboo mosaic virus replicase catalyzes the release of 5′-γ-phosphate from both ATP and 5′-triphosphated RNA by an identical set of catalytic residues with a presumably larger binding pocket for RNA. In this study, the peptidyl regions involved in RNA binding were mapped by reversible formaldehyde crosslinking and mass spectrometry. Eleven residues within these regions were examined by mutational analysis. H636A, Y704A, and K706A greatly diminished the enzymatic activities and were unable to support the viral replication in Nicotiana benthamiana protoplasts. K843A decreased activity toward the RNA substrate to 17% of WT, and ∼20% replication efficiency was retained in protoplasts. R597A and K610A retained ∼50 and ∼90% of the enzymatic activities, respectively. However, replication in protoplasts of these mutants was extremely limited. Proteins with the mutations K603A, R628A, R645A, H794A, and R799A were present at levels 30–69% of WT in protoplasts. However, the fates of these mutations in plants were different. Viral cell-to-cell movement was limited by the K603A and R628A mutations, while systemic movement was restricted by R645A and H794A. The implications of the helicase-like domain in the viral replication and movement are discussed.


title: Call to action for advocacy of immigrant nurses during COVID‐19 pandemic

text: The increase in the migration of nurses has a global effect on the healthcare system (Li et al., 2014). Immigrant nurses are essential team players of the global nursing workforce and play a vital role in improving the global health care system and providing culturally sensitive care. According to the Trines (2018), the global immigrant population of nurses is 15.2% in the UK, 23.3% in Australia, 26.7% in New Zealand, 18.7% in Switzerland, and 7.7% in Canada. Patel et al., (2018) determined that 1.3% to 23.1% registered nurses, nurse practitioners, licensed practice nurses, and nursing aids in the US are immigrants (non-US born and non- US citizens). Possibly, the actual number of immigrant nurses in the developed countries cannot be estimated accurately because many of these nurses have not obtained the practicing license and are working as personal care attendants, home, and developmental support workers.


title: Identification of human metapneumovirus genotypes A and B from clinical specimens by reverse transcription loop-mediated isothermal amplification

text: Abstract Human metapneumovirus (hMPV) has been recognized as an important pathogen for acute respiratory infections in children worldwide and classified into genotypes A and B. Reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay is a rapid diagnostic method for detecting nucleic acids with a single step under isothermal conditions in less than 1h. RT-LAMP targeting the M gene of hMPV was developed for detecting and identifying hMPV genotypes A and B. The detection limit of the genotype-specific hMPV RT-LAMP assay was 10 times greater than that of conventional reverse transcription polymerase chain reaction (RT-PCR). No cross-reactivity was found with respiratory syncytial virus, parainfluenza virus 1–3, adenovirus, human bocavirus, human rhinovirus, influenza virus A and B, human coronaviruses and enteroviruses. One hundred and fifteen clinical specimens were detected for hMPV genotypes A and B with RT-LAMP, RT-PCR and real-time SYBR PCR. Kappa coefficients showed that there was a good agreement among these three methods. Compared with RT-PCR and real-time SYBR PCR, the genotype-specific RT-LAMP showed better specificity, sensitivity and is more convenient to perform with reduced turn-around time.


Regarding "Understanding the "Scope" of the Problem: Why Laparoscopy is Considered Safe During the COVID-19 Pandemic"


title: Influenza and Viral Pneumonia

text: Influenza and other respiratory viruses are commonly identified in patients with community-acquired pneumonia, hospital-acquired pneumonia, and in immunocompromised patients with pneumonia. Clinically, it is difficult to differentiate viral from bacterial pneumonia. Similarly, the radiological findings of viral infection are nonspecific. The advent of polymerase chain reaction testing has enormously facilitated the identification of respiratory viruses, which has important implications for infection control measures and treatment. Currently, treatment options for patients with viral infection are limited, but there is ongoing research on the development and clinical testing of new treatment regimens and strategies.


title: Characterization of the Viral Microbiome in Patients with Severe Lower Respiratory Tract Infections, Using Metagenomic Sequencing

text: The human respiratory tract is heavily exposed to microorganisms. Viral respiratory tract pathogens, like RSV, influenza and rhinoviruses cause major morbidity and mortality from respiratory tract disease. Furthermore, as viruses have limited means of transmission, viruses that cause pathogenicity in other tissues may be transmitted through the respiratory tract. It is therefore important to chart the human virome in this compartment. We have studied nasopharyngeal aspirate samples submitted to the Karolinska University Laboratory, Stockholm, Sweden from March 2004 to May 2005 for diagnosis of respiratory tract infections. We have used a metagenomic sequencing strategy to characterize viruses, as this provides the most unbiased view of the samples. Virus enrichment followed by 454 sequencing resulted in totally 703,790 reads and 110,931 of these were found to be of viral origin by using an automated classification pipeline. The snapshot of the respiratory tract virome of these 210 patients revealed 39 species and many more strains of viruses. Most of the viral sequences were classified into one of three major families; Paramyxoviridae, Picornaviridae or Orthomyxoviridae. The study also identified one novel type of Rhinovirus C, and identified a number of previously undescribed viral genetic fragments of unknown origin.


title: Theranostics Aspects of Various Nanoparticles in Veterinary Medicine

text: Nanoscience and nanotechnology shows immense interest in various areas of research and applications, including biotechnology, biomedical sciences, nanomedicine, and veterinary medicine. Studies and application of nanotechnology was explored very extensively in the human medical field and also studies undertaken in rodents extensively, still either studies or applications in veterinary medicine is not up to the level when compared to applications to human beings. The application in veterinary medicine and animal production is still relatively innovative. Recently, in the era of health care technologies, Veterinary Medicine also entered into a new phase and incredible transformations. Nanotechnology has tremendous and potential influence not only the way we live, but also on the way that we practice veterinary medicine and increase the safety of domestic animals, production, and income to the farmers through use of nanomaterials. The current status and advancements of nanotechnology is being used to enhance the animal growth promotion, and production. To achieve these, nanoparticles are used as alternative antimicrobial agents to overcome the usage alarming rate of antibiotics, detection of pathogenic bacteria, and also nanoparticles being used as drug delivery agents as new drug and vaccine candidates with improved characteristics and performance, diagnostic, therapeutic, feed additive, nutrient delivery, biocidal agents, reproductive aids, and finally to increase the quality of food using various kinds of functionalized nanoparticles, such as liposomes, polymeric nanoparticles, dendrimers, micellar nanoparticles, and metal nanoparticles. It seems that nanotechnology is ideal for veterinary applications in terms of cost and the availability of resources. The main focus of this review is describes some of the important current and future principal aspects of involvement of nanotechnology in Veterinary Medicine. However, we are not intended to cover the entire scenario of Veterinary Medicine, despite this review is to provide a glimpse at potential important targets of nanotechnology in the field of Veterinary Medicine. Considering the strong potential of the interaction between the nanotechnology and Veterinary Medicine, the aim of this review is to provide a concise description of the advances of nanotechnology in Veterinary Medicine, in terms of their potential application of various kinds of nanoparticles, secondly we discussed role of nanomaterials in animal health and production, and finally we discussed conclusion and future perspectives of nanotechnology in veterinary medicine.


title: INSMA: An integrated system for multimodal data acquisition and analysis in the intensive care unit

text: Modern intensive care units (ICU) are equipped with a variety of different medical devices to monitor the physiological status of patients. These devices can generate large amounts of multimodal data daily that include physiological waveform signals (arterial blood pressure, electrocardiogram, respiration), patient alarm messages, numeric vitals data, etc. In order to provide opportunities for increasingly improved patient care, it is necessary to develop an effective data acquisition and analysis system that can assist clinicians and provide decision support at the patient bedside. Previous research has discussed various data collection methods, but a comprehensive solution for bedside data acquisition to analysis has not been achieved. In this paper, we proposed a multimodal data acquisition and analysis system called INSMA, with the ability to acquire, store, process, and visualize multiple types of data from the Philips IntelliVue patient monitor. We also discuss how the acquired data can be used for patient state tracking. INSMA is being tested in the ICU at University Hospitals Cleveland Medical Center.


title: Chapter 25 ACE2 Cell Biology, Regulation, and Physiological Functions

text: Abstract Angiotensin-converting enzyme 2 (ACE2), discovered as a homologue of ACE, acts as its physiological counterbalance providing homeostatic regulation of circulating angiotensin II (Ang II) levels. ACE2 is a zinc metalloenzyme and carboxypeptidase located as an ectoenzyme on the surface of endothelial and other cells. While its primary substrate appears to be Ang II, it can hydrolyze a number of other physiological substrates. Additionally, ACE2 functions in other noncatalytic cellular roles including the regulation of intestinal neutral amino acid transport. It also serendipitously acts as the receptor for the severe acute respiratory syndrome virus. Upregulation of ACE2 expression and function is increasingly recognized as a potential therapeutic strategy in hypertension and cardiovascular disease, diabetes, lung injury, and fibrotic disorders. ACE2 is regulated at multiple levels including transcriptional, posttranscriptional (miRNA and epigenetic), and posttranslational through its shedding from the cell surface.


title: Viral metagenomic analysis of feces of wild small carnivores

text: BACKGROUND: Recent studies have clearly demonstrated the enormous virus diversity that exists among wild animals. This exemplifies the required expansion of our knowledge of the virus diversity present in wildlife, as well as the potential transmission of these viruses to domestic animals or humans. METHODS: In the present study we evaluated the viral diversity of fecal samples (n = 42) collected from 10 different species of wild small carnivores inhabiting the northern part of Spain using random PCR in combination with next-generation sequencing. Samples were collected from American mink (Neovison vison), European mink (Mustela lutreola), European polecat (Mustela putorius), European pine marten (Martes martes), stone marten (Martes foina), Eurasian otter (Lutra lutra) and Eurasian badger (Meles meles) of the family of Mustelidae; common genet (Genetta genetta) of the family of Viverridae; red fox (Vulpes vulpes) of the family of Canidae and European wild cat (Felis silvestris) of the family of Felidae. RESULTS: A number of sequences of possible novel viruses or virus variants were detected, including a theilovirus, phleboviruses, an amdovirus, a kobuvirus and picobirnaviruses. CONCLUSIONS: Using random PCR in combination with next generation sequencing, sequences of various novel viruses or virus variants were detected in fecal samples collected from Spanish carnivores. Detected novel viruses highlight the viral diversity that is present in fecal material of wild carnivores.


title: BCG-induced trained immunity: can it offer protection against COVID-19?

text: Bacillus Calmette–Guérin (BCG) vaccination has been reported to decrease susceptibility to respiratory tract infections, an effect proposed to be mediated by the general long-term boosting of innate immune mechanisms, also termed trained immunity. Here, we discuss the non-specific beneficial effects of BCG against viral infections and whether this vaccine may afford protection to COVID-19.


title: Enhanced Replication of Virulent Newcastle Disease Virus in Chicken Macrophages Is due to Polarized Activation of Cells by Inhibition of TLR7

text: Newcastle disease (ND), caused by infections with virulent strains of Newcastle disease virus (NDV), is one of the most important infectious disease affecting wild, peridomestic, and domestic birds worldwide. Vaccines constructed from live, low-virulence (lentogenic) viruses are the most accepted prevention and control strategies for combating ND in poultry across the globe. Avian macrophages are one of the first cell lines of defense against microbial infection, responding to signals in the microenvironment. Although macrophages are considered to be one of the main target cells for NDV infection in vivo, very little is known about the ability of NDV to infect chicken macrophages, and virulence mechanisms of NDV as well as the polarized activation patterns of macrophages and correlation with viral infection and replication. In the present study, a cell culture model (chicken bone marrow macrophage cell line HD11) and three different virulence and genotypes of NDV (including class II virulent NA-1, class II lentogenic LaSota, and class I lentogenic F55) were used to solve the above underlying questions. Our data indicated that all three NDV strains had similar replication rates during the early stages of infection. Virulent NDV titers were shown to increase compared to the other lentogenic strains, and this growth was associated with a strong upregulation of both pro-inflammatory M1-like markers/cytokines and anti-inflammatory M2-like markers/cytokines in chicken macrophages. Virulent NDV was found to block toll-like receptor (TLR) 7 expression, inducing higher expression of type I interferons in chicken macrophages at the late stage of viral infection. Only virulent NDV replication can be inhibited by pretreatment with TLR7 ligand. Overall, this study demonstrated that virulent NDV activates a M1-/M2-like mixed polarized activation of chicken macrophages by inhibition of TLR7, resulting in enhanced replication compared to lentogenic viruses.


title: 35 Humanitarian Aid Workers

text: Abstract Traveling to extreme environments for humanitarian aid mission is now common. Humanitarian aid workers (HAWs) typically travel for extended periods, work in close proximity to local populations, and work in high-risk environments in low-resource regions. Owing to the nature of their work, HAWs are often unable to avoid high-risk behaviors and frequently encounter stressful conditions, leading to psychologic repercussions. Although morbidity might be high, death during volunteer missions is not common and it is usually not attributable to infectious diseases. Medical evacuations are also not common. One unique aspect of ill-returning HAWs might be their threat to public health in their home countries, as was demonstrated in the 2014–2015 Ebola outbreak in West Africa. Thus pretravel and posttravel physical and psychologic screening evaluations, in addition to routine health care, are essential for this population.


title: Structure-based drug designing towards the identification of potential anti-viral for COVID-19 by targeting endoribonuclease NSP15

text: The world is facing health and economic havoc due to the Corona Virus Disease-2019 (COVID-19) pandemic. Given the number of affected people and the mortality rate, the virus is undoubtedly a serious threat to humanity. By analogy with earlier reports about Severe Acute Respiratory Syndrome (SARS-CoV) and Middle East Respiratory Syndrome (MERS-CoV) - viruses, the novel Coronavirus’ replication mechanism is likely well understood. The structure of an endoribonuclease (NSP15) of SARS-CoV-2 was reported recently. This enzyme is expected to play a crucial role in replication. In this work, attempts were made to identify inhibitors of this enzyme. To achieve the goal, high throughput in silico screening and molecular docking procedures were performed. From an Enamine database of a billion compounds, 3978 compounds with potential antiviral activity were selected for screening and induced fit docking that funneled down to eight compounds with good docking score and docking energy. Detailed analysis of non-covalent interactions at the active site and the apparent match of the molecule with the shape of the binding pocket were assessed. All the compounds show significant interactions for tight binding. Since all the compounds are synthetic with favorable drug-like properties, these may be considered for immediate optimization and downstream applications.


Foodomics and COVID-19


The common cold and asthma


Association between respiratory viruses and asthma exacerbations


title: Inhibition of viral protein translation by indomethacin in vesicular stomatitis virus infection: role of eIF2α kinase PKR

text: Indomethacin, a cyclooxygenase‐1 and ‐2 inhibitor widely used in the clinic for its potent anti‐inflammatory/analgesic properties, possesses antiviral activity against several viral pathogens; however, the mechanism of antiviral action remains elusive. We have recently shown that indomethacin activates the double‐stranded RNA (dsRNA)‐dependent protein kinase R (PKR) in human colon cancer cells. Because of the important role of PKR in the cellular defence response against viral infection, herein we investigated the effect of indomethacin on PKR activity during infection with the prototype rhabdovirus vesicular stomatitis virus. Indomethacin was found to activate PKR in an interferon‐ and dsRNA‐independent manner, causing rapid (< 5 min) phosphorylation of eukaryotic initiation factor‐2 α‐subunit (eIF2α). These events resulted in shutting off viral protein translation and blocking viral replication (IC (50) = 2 μM) while protecting host cells from virus‐induced damage. Indomethacin did not affect eIF2α kinases PKR‐like endoplasmic reticulum‐resident protein kinase (PERK) and general control non‐derepressible‐2 (GCN2) kinase, and was unable to trigger eIF2α phosphorylation in the presence of PKR inhibitor 2‐aminopurine. In addition, small‐interfering RNA‐mediated PKR gene silencing dampened the antiviral effect in indomethacin‐treated cells. The results identify PKR as a critical target for the antiviral activity of indomethacin and indicate that eIF2α phosphorylation could be a key element in the broad spectrum antiviral activity of the drug.


title: Diffusion‐weighted MRI abnormalities in an outbreak of Streptococcus agalactiae Serotype III, multilocus sequence type 283 meningitis

text: PURPOSE: In 2015, an outbreak of group B streptococcal (GBS) infection caused by Streptococcus agalactiae Serotype III, multilocus sequence type 283, related to consuming infected raw freshwater fish, affected more than 200 patients in Singapore. We describe the clinical, laboratory, and neuroimaging features of a subgroup of adults with central nervous system (CNS) infections caused by GBS. MATERIALS AND METHODS: The database of the Singapore Neurologic Infections Program (SNIP), a national multicenter study for surveillance of infectious neurologic disease, was reviewed to select patients with GBS CNS infection during the outbreak. Cases were diagnosed on the basis of clinical features, cerebrospinal fluid (CSF) findings and identification or isolation of Streptococcus agalactiae in the blood or CSF. Demographic, clinical and neuroradiological information was obtained prospectively and retrospectively abstracted. RESULTS: Fourteen patients (6 male, 8 female; median age, 58 years) presented with fever, meningism, headache, encephalopathy, focal neurological deficits, and/or seizures. All except two were previously healthy. Diffusion‐weighted imaging (DWI) on admission was abnormal in 13 patients, showing tiny hyperintensities in the subarachnoid space (7 patients), ventricles (6 patients) and brain parenchyma (8 patients); 5 patients had cerebellar abnormalities. CONCLUSION: Among healthy non‐pregnant adults infected with Serotype III, multilocus sequence type 283 GBS meningitis linked to eating infected raw freshwater fish, DWI detected small pus collections and unusual cerebellar involvement. A collaborative national surveillance system that includes MRI can be helpful during unusual food‐borne zoonotic infectious disease outbreaks. Level of Evidence: 4 J. Magn. Reson. Imaging 2017;45:507–514.


title: Lived experiences of the Corona Survivors (patients admitted in COVID wards): A Narrative real-life documented summaries of internalized guilt, shame, stigma, anger

text: COVID-19 pandemic has emerged as a disaster for the human beings. All the Governments across the globe have been preparing to deal with this medical emergency, which is known to be associated with mortality in about 5% of the sufferers. Gradually, it is seen that, many patients with COVID-19 infection have mild symptoms or are asymptomatic. Due to the risk of infecting others, persons with COVID-19 infection are kept in isolation wards. Because of the isolation, the fear of death, and associated stigma, many patients with COVID-19 infection go through mental distress. In this report, we discuss the experience of 3 persons diagnosed with COVId-19 infection and admitted to the COVID ward.


Commentary: This Port’s for YOU!


title: Analysis and control of an SEIR epidemic system with nonlinear transmission rate

text: Abstract In this paper, the dynamical behaviors of an SEIR epidemic system governed by differential and algebraic equations with seasonal forcing in transmission rate are studied. The cases of only one varying parameter, two varying parameters and three varying parameters are considered to analyze the dynamical behaviors of the system. For the case of one varying parameter, the periodic, chaotic and hyperchaotic dynamical behaviors are investigated via the bifurcation diagrams, Lyapunov exponent spectrum diagram and Poincare section. For the cases of two and three varying parameters, a Lyapunov diagram is applied. A tracking controller is designed to eliminate the hyperchaotic dynamical behavior of the system, such that the disease gradually disappears. In particular, the stability and bifurcation of the system for the case which is the degree of seasonality β 1 = 0 are considered. Then taking isolation control, the aim of elimination of the disease can be reached. Finally, numerical simulations are given to illustrate the validity of the proposed results.


title: Clinical manifestations of mannan-binding lectin deficiency

text: Abstract Mannan-binding lectin (MBL) is a plasma protein of the innate immune system with the ability to initiate antimicrobial and inflammatory actions. MBL deficiency is common. More than 10% of the general population may, depending on definition, be classified as MBL deficient, underlining the redundancy of the immune system. Ongoing research attempt to illuminate at which conditions MBL deficiency may lead to disease. With examples, this review illustrates the diversity of results obtained so far.


title: The diversity, evolution and origins of vertebrate RNA viruses

text: Despite a substantial increase in our knowledge of the biodiversity and evolution of vertebrate RNA viruses, far less is known about the diversity, evolution and origin of RNA viruses across the diverse phylogenetic range of viruses, and particularly in healthy animals that are often only rarely utilized for virological sampling. Fortunately, recent advances in virus discovery using metagenomic approaches are beginning to reveal a multitude of RNA viruses in vertebrates other than birds and mammals. In particular, fish harbor a remarkable array of RNA viruses, including the relatives of important pathogens. In addition, despite frequent cross-species transmission, the RNA viruses in vertebrates generally follow the evolutionary history of their hosts, which began in the oceans and then moved to terrestrial habitats over timescales covering hundreds of millions of years.


title: Clinical Features, Diagnosis, and Treatment of COVID-19 in Hospitalized Patients: A Systematic Review of Case Reports and Case Series

text: Introduction: The 2019 novel coronavirus (COVID-19) has been declared a public health emergency worldwide. The objective of this systematic review was to characterize the clinical, diagnostic, and treatment characteristics of hospitalized patients presenting with COVID-19. Methods: We conducted a structured search using PubMed/Medline, Embase, and Web of Science to collect both case reports and case series on COVID-19 published up to April 24, 2020. There were no restrictions regarding publication language. Results: Eighty articles were included analyzing a total of 417 patients with a mean age of 48 years. The most common presenting symptom in patients who tested positive for COVID-19 was fever, reported in up to 62% of patients from 82% of the analyzed studies. Other symptoms including rhinorrhea, dizziness, and chills were less frequently reported. Additionally, in studies that reported C-reactive protein (CRP) measurements, a large majority of patients displayed an elevated CRP (60%). Progression to acute respiratory distress syndrome (ARDS) was the most common complication of patients testing positive for COVID-19 (21%). CT images displayed ground-glass opacification (GGO) patterns (80%) as well as bilateral lung involvement (69%). The most commonly used antiviral treatment modalities included, lopinavir (HIV protease inhibitor), arbidiol hydrochloride (influenza fusion inhibitor), and oseltamivir (neuraminidase inhibitor). Conclusions: Development of ARDS may play a role in estimating disease progression and mortality risk. Early detection of elevations in serum CRP, combined with a clinical COVID-19 symptom presentation may be used as a surrogate marker for the presence and severity of the disease. There is a paucity of data surrounding the efficacy of treatments. There is currently not a well-established gold standard therapy for the treatment of diagnosed COVID-19. Further prospective investigations are necessary.


Controlling Middle East Respiratory Syndrome: Lessons Learned From Severe Acute Respiratory Syndrome


title: Frequent Asymptomatic Respiratory Syncytial Virus Infections During an Epidemic in a Rural Kenyan Household Cohort

text: Background. The characteristics, determinants, and potential contribution to transmission of asymptomatic cases of respiratory syncytial virus (RSV) infection have not been well described. Methods. A cohort of 47 households (493 individuals) in coastal Kenya was recruited and followed for a 26-week period spanning a complete RSV season. Nasopharyngeal swab specimens were requested weekly, during the first 4 weeks, and twice weekly thereafter from all household members, regardless of illness status. The samples were screened for a range of respiratory viruses by multiplex real-time polymerase chain reaction. Results. Tests on 16 928 samples yielded 205 RSV infection episodes in 179 individuals (37.1%) from 40 different households. Eighty-six episodes (42.0%) were asymptomatic. Factors independently associated with an increased risk of asymptomatic RSV infection episodes were higher age, shorter duration of infection, bigger household size, lower peak viral load, absence of concurrent RSV infections within the household, infection by RSV group B, and no prior human rhinovirus infections. The propensity of RSV spread in households was dependent on symptom status and amount (duration and load) of virus shed. Conclusions. While asymptomatic RSV was less likely to spread, the high frequency of symptomless RSV infection episodes highlights a potentially important role of asymptomatic infections in the community transmission of RSV.


title: Co‐infection of respiratory bacterium with severe acute respiratory syndrome coronavirus induces an exacerbated pneumonia in mice

text: SARS‐CoV grows in a variety of tissues that express its receptor, although the mechanism for high replication in the lungs and severe respiratory illness is not well understood. We recently showed that elastase enhances SARS‐CoV infection in cultured cells, which suggests that SARS development may be due to elastase‐mediated, enhanced SARS‐CoV infection in the lungs. To explore this possibility, we examined whether co‐infection of mice with SARS‐CoV and Pp, a low‐pathogenic bacterium which elicits elastase production in the lungs, induces exacerbation of pneumonia. Mice co‐infected with SARS‐CoV and Pp developed severe respiratory disease with extensive weight loss, resulting in a 33∼90% mortality rate. Mice with exacerbated pneumonia showed enhanced virus infection in the lungs and histopathological lesions similar to those found in human SARS cases. Intranasal administration of LPS, another elastase inducer, showed an effect similar to that of Pp infection. Thus, this study shows that exacerbated pneumonia in mice results from co‐infection with SARS‐CoV and a respiratory bacterium that induces elastase production in the lungs, suggesting a possible role for elastase in the exacerbation of pneumonia.


Family Therapy Across the Gamut: Working with COVID‐19, Paediatric Trauma, Engaging Parents, Dialogical Supervision, Training Novice Therapists and Narrative Therapy in Iran


title: Pediatric Seizure Disorders in Dogs and Cats

text: Seizure disorders in young animals pose different considerations as to cause and therapeutic decisions compared with adult animals. Infectious diseases of the nervous system are more likely in puppies and kittens compared with adults. The diagnosis of canine distemper is often based on clinical signs. Idiopathic epilepsy typically occurs in dogs between 1 and 5 years of age; however, inflammatory brain diseases such as necrotizing encephalitis and granulomatous meningoencephalomyelitis also commonly occur in young to middle-aged small-breed dogs. The choice of which anticonvulsant to administer for maintenance therapy is tailored to each individual patient.


title: Outbreak of Necrotizing Enterocolitis Caused by Norovirus in a Neonatal Intensive Care Unit

text: Objectives To investigate an outbreak of necrotizing enterocolitis (NEC) in a neonatal intensive care unit (NICU) and to identify the etiology, describe illness risk factors, and develop control measures. Study design A retrospective case-control study was performed including newborns with NEC and newborns without NEC, examining demographic factors and exposures to medications, staff members, and procedures before illness. Stool samples from affected newborns were collected and tested for bacteria, parasites, and viruses. Results We confirmed a NEC outbreak in the NICU in January 1998 with 8 cases, including 2 deaths, clustered in time and space. Norovirus-like particles were identified in all available stools from cases; norovirus (NoV) was confirmed with reverse transcriptase polymerase chain reaction in 4 of 6 samples. NEC cases were younger, had lower Apgar scores, and received antibiotics longer than 25 control subjects. Three NICU health care personnel had more contact with cases than control subjects; 1 staff member recalled having gastroenteritis symptoms around the time of the outbreak. Conclusions This report associates NoV with NEC. NoV appeared to precipitate NEC in predisposed infants. Spatial clustering and epidemiologic links between cases and a health care worker with gastroenteritis suggests that NoV should be investigated among the etiologies of NEC outbreaks and that interventions targeted to interruption of NoV transmission should be considered.


title: Respiratory failure

text: Abstract The respiratory system has two principal purposes – to maintain adequate arterial Pao2, and to regulate arterial Paco2 and thereby maintain a stable acid-base state. Both are necessary to sustain normal tissue metabolism. Respiratory failure can be defined in two ways: • failure of oxygenation, resulting in Pao2 < 8.0 kPa • failure of ventilation, resulting in Paco2 > 6.7 kPa with accompanying acid-base changes.


title: Famotidine use and quantitative symptom tracking for COVID-19 in non-hospitalised patients: a case series

text: OBJECTIVE: Treatment options for non-hospitalised patients with coronavirus disease 2019 (COVID-19) to reduce morbidity, mortality and spread of the disease are an urgent global need. The over-the-counter histamine-2 receptor antagonist famotidine is a putative therapy for COVID-19. We quantitively assessed longitudinal changes in patient reported outcome measures in non-hospitalised patients with COVID-19 who self-administered high-dose famotidine orally. DESIGN: Patients were enrolled consecutively after signing written informed consent. Data on demographics, COVID-19 diagnosis, famotidine use, drug-related side effects, temperature measurements, oxygen saturations and symptom scores were obtained using questionnaires and telephone interviews. Based on a National Institute of Health (NIH)-endorsed Protocol to research Patient Experience of COVID-19, we collected longitudinal severity scores of five symptoms (cough, shortness of breath, fatigue, headaches and anosmia) and general unwellness on a four-point ordinal scale modelled on performance status scoring. All data are reported at the patient level. Longitudinal combined normalised symptom scores were statistically compared. RESULTS: Ten consecutive patients with COVID-19 who self-administered high-dose oral famotidine were identified. The most frequently used famotidine regimen was 80 mg three times daily (n=6) for a median of 11 days (range: 5–21 days). Famotidine was well tolerated. All patients reported marked improvements of disease related symptoms after starting famotidine. The combined symptom score improved significantly within 24 hours of starting famotidine and peripheral oxygen saturation (n=2) and device recorded activity (n=1) increased. CONCLUSIONS: The results of this case series suggest that high-dose oral famotidine is well tolerated and associated with improved patient-reported outcomes in non-hospitalised patients with COVID-19.


The emergence of novel sparrow deltacoronaviruses in the United States more closely related to porcine deltacoronaviruses than sparrow deltacoronavirus HKU17


title: Recent advances in the detection of base modifications using the Nanopore sequencer

text: DNA and RNA modifications have important functions, including the regulation of gene expression. Existing methods based on short-read sequencing for the detection of modifications show difficulty in determining the modification patterns of single chromosomes or an entire transcript sequence. Furthermore, the kinds of modifications for which detection methods are available are very limited. The Nanopore sequencer is a single-molecule, long-read sequencer that can directly sequence RNA as well as DNA. Moreover, the Nanopore sequencer detects modifications on long DNA and RNA molecules. In this review, we mainly focus on base modification detection in the DNA and RNA of mammals using the Nanopore sequencer. We summarize current studies of modifications using the Nanopore sequencer, detection tools using statistical tests or machine learning, and applications of this technology, such as analyses of open chromatin, DNA replication, and RNA metabolism.


title: Use of a portable forced air system to convert existing hospital space into a mass casualty isolation area

text: STUDY OBJECTIVE: Patients with communicable diseases may require respiratory isolation to reduce the chance of transmission to health care workers and the public. This project was conducted to determine whether negative-pressure isolation for multiple patients can be achieved quickly and effectively using general hospital space not previously dedicated to respiratory isolation. METHODS: The physical therapy gymnasium was the area designated to test the ability to create a negative-pressure isolation environment in a large space. The conversion was planned in advance of an unscheduled drill to convert the space. Four high-efficiency particulate air (HEPA) filtered forced air machines were used to generate negative pressure. The units were vented to the outside air by a 25-foot length of 10-inch-diameter reusable duct. We evaluated the time needed for equipment setup and room conversion and noted any subjective difficulty with either setup or operation of the equipment. We measured the ability of the equipment to generate a negative air pressure relative to adjacent areas and determined the noise levels created during the use of different combinations of machines at various power settings. RESULTS: After drill activation and the request for equipment setup, 1 hour was required to convert the physical therapy gymnasium into an operational negative-pressure environment. The room pressure readings “high” power ranged from −1.5 to −13 Pa (−0.006 to −0.052 inches of water), and noise levels ranged from 70 to 76 dB. Calculated air changes per hour using 1, 2, 3, or 4 units running simultaneously at “high” power were 4.1, 8.2, 12.3, and 16.4, respectively. Using 4 units at once running at “low” power setting yielded 8.2 air changes per hour and generated a room pressure reading of −8.0 Pa, or −0.032 inches of water. CONCLUSION: Portable HEPA filtered forced air units are an effective means of creating large patient care areas with the negative-pressure environment required for respiratory isolation. This design results in a significantly lower-cost alternative compared with construction of individual rooms or units with similar capability and can be retrofitted to existing space. This type of unit would allow treatment of many more patients than current hospital capability would permit and would be an important asset in meeting the needs created by bioterrorism or a naturally occurring epidemic.


title: Determinants of QTL Mapping Power in the Realized Collaborative Cross

text: The Collaborative Cross (CC) is a mouse genetic reference population whose range of applications includes quantitative trait loci (QTL) mapping. The design of a CC QTL mapping study involves multiple decisions, including which and how many strains to use, and how many replicates per strain to phenotype, all viewed within the context of hypothesized QTL architecture. Until now, these decisions have been informed largely by early power analyses that were based on simulated, hypothetical CC genomes. Now that more than 50 CC strains are available and more than 70 CC genomes have been observed, it is possible to characterize power based on realized CC genomes. We report power analyses from extensive simulations and examine several key considerations: 1) the number of strains and biological replicates, 2) the QTL effect size, 3) the presence of population structure, and 4) the distribution of functionally distinct alleles among the founder strains at the QTL. We also provide general power estimates to aide in the design of future experiments. All analyses were conducted with our R package, SPARCC (Simulated Power Analysis in the Realized Collaborative Cross), developed for performing either large scale power analyses or those tailored to particular CC experiments.


title: Distributed mobile ultraviolet light sources driven by ambient mechanical stimuli

text: Abstract Due to the natural characteristics of high voltage output, Triboelectric nanogenerators (TENGs) have huge advantages in many fields. Here, we have proposed a concept of Mobile ultraviolet light sources (Mobile-UV) driven by TENG, without any additional circuits. For this system, analysis of electric characteristics, optical emission spectra, and COMSOL simulation were carried out to promote the performance. Subsequently, we have developed exploratory applications in the fields of bio-sterilization, chemical detection, and UV-curing, which proved the versatility and effectiveness. This work offers a promising, portable, effective, and safe supplement to traditional ultraviolet light sources, and will enrich the diversity of the ultraviolet application based on the reach of existing technologies.


title: Descriptive review of geographic mapping of severe acute respiratory syndrome (SARS) on the Internet

text: From geographic mapping at different scales to location-based alerting services, geoinformatics plays an important role in the study and control of global outbreaks like severe acute respiratory syndrome (SARS). This paper reviews several geographic mapping efforts of SARS on the Internet that employ a variety of techniques like choropleth rendering, graduated circles, graduated pie charts, buffering, overlay analysis and animation. The aim of these mapping services is to educate the public (especially travellers to potentially at-risk areas) and assist public health authorities in analysing the spatial and temporal trends and patterns of SARS and in assessing/revising current control measures.


title: Nucleotide Sequence of the Human Coronavirus 229E RNA Polymerase Locus

text: Abstract The nucleotide sequence of the human coronavirus 229E (HCV 229E) RNA polymerase gene and the 5′ region of the genome has been determined. The polymerase gene is comprised of two large open reading frames, ORF1a and ORF1b, that contain 4086 and 2687 codons, respectively. ORF1b overlaps ORF1a by 43 bases in the (-1) reading frame. The in vitro translation of SP6 transcripts which include HCV 229E sequences encompassing the ORF1a/ORF1b junction show that expression of ORF1b can be mediated by ribosomal frame-shifting. The predicted translation products of ORF1a (454,200 molecular weight) and ORF1a/1b (754,200 molecular weight) have been compared to the predicted RNA polymerase gene products of infectious bronchitis virus (IBV) and murine hepatitis virus (MHV) and conserved structural features and putative functional domains have been identified. This analysis completes the nucleotide sequence of the HCV 229E genome.


title: First Reported Use of Highly Adsorptive Hemofilter in Critically Ill COVID-19 Patients in the USA

text: Critically ill patients with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop respiratory failure and septic shock. Extracorporeal blood purification is proposed as an adjuvant therapy for sepsis and aims at controlling the dysregulated autoimmune system. We describe our experience in treating COVID-19 patients with the oXiris(®) hemofilter which adsorbs both cytokines and endotoxins, provides renal replacement therapy and has anti-thrombogenic properties. It was approved by the US Food and Drug Administration (FDA) under emergency use authorization for COVID-19 patients in April 2020. In our study, the use of the oXiris(®) filter decreased levels of inflammatory markers including interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), and improved clinical outcomes in two out of three patients.


title: The Role of FGL2 in the Pathogenesis and Treatment of Hepatitis C Virus Infection

text: Chronic hepatitis C virus (HCV) infection is a leading cause of liver disease worldwide and remains the most common indication for liver transplantation. The current standard of care leads to a sustained viral response of roughly 50% of treated patients at best. Furthermore, anti-viral therapy is expensive, prolonged, and associated with serious side-effects. Evidence suggests that a poor response to treatment may be the result of a suppressed anti-viral immunity due to the presence of increased numbers and activity of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg cells). We and others have recently identified fibrinogen-like protein 2 (FGL2) as a putative effector of Treg cells, which accounts for their suppressive function through binding to Fc gamma receptors (FcγR). In an experimental model of fulminant viral hepatitis, our laboratory showed that increased plasma levels of FGL2 pre- and post-viral infection were predictive of susceptibility and severity of disease. Moreover, treatment with antibody to FGL2 fully protected susceptible animals from the lethality of the virus, and adoptive transfer of wild-type Treg cells into resistant fgl2-deficient animals accelerated their mortality post-infection. In patients with HCV infection, plasma levels of FGL2 and expression of FGL2 in the liver correlated with the course and severity of the disease. Collectively, these studies suggest that FGL2 may be used as a biomarker to predict disease progression in HCV patients and be a logical target for the development of novel therapeutic approaches for the treatment of patients with HCV infection.


Reflections on the impact of coronavirus on public affairs


title: In vitro Acquisition and Retention of Low-Pathogenic Avian Influenza H9N2 by Musca domestica (Diptera: Muscidae)

text: Avian influenza virus (AIV) H9N2 emerged in the 1990s as an economically important disease in poultry and occasionally infects humans and other mammals. The aim of this study was to evaluate the acquisition and retention of H9N2 AIV on and within the house fly, Musca domestica (Linnaeus 1758), under laboratory conditions. In first experiment, 100 adult house flies were divided into control and treatment groups equally. Treatment group was fed with a meal containing H9N2 virus, while control group was supplied with an identical meal without virus. Fifteen minutes after exposure in each group, flies were washed twice to remove surface particles, disinfected and then homogenized for testing. The two external body surface washes and the homogenate samples were tested for H9N2 to distinguish exterior from interior viral load. Second experiment was performed likewise but five flies from each group were taken at 0, 6, 24, 48, 72, 96, and 120 h post-exposure. All samples were subjected to real-time reverse-transcription polymerase chain reaction (RRT-PCR) for detecting H9-Specific viral RNA. Results of the first experiment showed that viral RNA was detectable in both of external surface and homogenates samples. Second experiment revealed that persistence of H9N2 AIVs on external body surface and within the body of M. domestica were 24 and 96 h, respectively. Moreover, viral RNAs concentration declined during the time after exposure to AIV H9N2 either outside or within house flies. Overall, house fly was able to acquire and preserve H9N2 AIV experimentally, which may contribute the spread of virus among poultry farms.


Que déduire des études évaluant l’effet du climat sur la COVID-19 ?


title: Systemic Immunobiological, Immunosuppressant and Oncologic Agents for the Treatment of Dermatologic Diseases during the SARS‐Cov‐2 (COVID19) Pandemic Emergency: a Quick Review for a Quick Consultation

text: The Precision Medicine Era has helped to better manage patients with immunological and oncological disease, improving the quality of life of this class of patients. Regarding the management of these patients and positivity to SARS‐Cov2, currently, limited data is available and information is evolving. In this quick review we have analyzed the mechanisms of action and related infective risk of drugs used for the treatment of immune‐mediated and oncologic skin conditions during the daily clinical practice. In general immunosuppressant and antineoplastic agents for dermatologic treatments do not require suspension and do not require special measures, if not those commonly observed. In the case of a COVID19 patient with complication (such as pneumonia, respiratory failure), treatment suspension should always be considered after taking into account the general condition of the patient, the risk‐benefit ratio and the pathophysiology of COVID19 infection. The COVID19 emergency pandemic does not imply an under‐treatment of existing skin conditions, which together with the SARS‐Cov2 infection may jeopardize the patient's life. This article is protected by copyright. All rights reserved.


title: Pathogenicity of three genetically diverse strains of PRRSV Type 1 in specific pathogen free pigs

text: Abstract Studies from Eastern European countries proved that porcine reproductive and respiratory syndrome virus Type 1 (PRRSV-1) harbours high genetic diversity and that genetically divergent subtypes 2–4 circulate in this area. In the present study, we compared the pathogenicity of two different PRRSV-1 subtype 2 strains and a strain representing PRRSV-1 subtype 1. Four groups of 8-week-old specific pathogen free pigs were either infected with subtype 2 strain ILI6, subtype 2 strain or BOR59, subtype 1 strain 18794, or mock inoculated. The most pronounced clinical signs were observed in pigs infected with BOR59. Pigs from both subtype 2 strain infected groups exhibited significantly elevated mean body temperatures on DPI 2 compared to the other two groups, the difference remaining significant up to DPI 13 for the BOR59 group, only. The pigs in the latter group also displayed significantly highest levels of early viremia together with the most rapid APP response. Overall, the results indicated that BOR59 strain can be considered a highly pathogenic strain, similarly to subtype 3 strains Lena and SU1-bel, while the virulence of the other subtype 2 strain ILI6 was intermediate between BOR59 and subtype 1 strain.


Struggling with COVID: Every Cancer Patient is Unique, and Needs Their Own Plan