title: HexaPrime: A novel method for detection of coronaviruses

text: Abstract Despite intense efforts to develop novel and better tools to identify known viruses and to discover new viruses, establishing etiological roles for viruses in human disease is challenging. In large part, this may be attributed to the high variability of viral species and the difficulties in developing broad-spectrum, yet specific, diagnostic assays. To overcome this problem, a novel method for the detection of viruses is described in the current manuscript. The technique relies on the addition of synthetic oligonucleotides to both termini of RNA fragments in a sequence-dependent manner during first- and second-strand DNA synthesis; these oligonucleotides are used subsequently for amplification of the viral nucleic acids of interest. The recognition of the target sequence by the oligonucleotides is mediated by short (6–8nt) conserved regions, which facilitates development of broad–spectrum assays. The method has been tested for coronaviruses, although it may be also adopted for other RNA viruses.


title: Genome sequencing of the first SARS-CoV-2 reported from patients with COVID-19 in Ecuador

text: SARS-CoV-2, the etiological agent of COVID-19 was first described in Wuhan in December 2019 and has now spread globally. Ecuador was the second country in South America to report confirmed cases. The first case reported in Quito, the capital city of Ecuador, was a tourist who came from the Netherlands and presented symptoms on March 10th, 2020 (index case). In this work we used the MinION platform (Oxford Nanopore Technologies) to sequence the metagenome of the bronchoalveolar lavage (BAL) from this case reported, and subsequently we sequenced the whole genome of the index case and other three patients using the ARTIC network protocols. Our data from the metagenomic approach confirmed the presence of SARS-CoV-2 coexisting with pathogenic bacteria suggesting coinfection. Relevant bacteria found in the BAL metagenome were Streptococcus pneumoniae, Mycobacterium tuberculosis, Staphylococcus aureus and Chlamydia spp. Lineage assignment of the four whole genomes revealed three different origins. The variant HEE-01 was imported from the Netherlands and was assigned to B lineage, HGSQ-USFQ-018, belongs to the B.1 lineage showing nine nucleotide differences with the reference strain and grouped with sequences from the United Kingdom, and HGSQ-USFQ-007 and HGSQ-USFQ-010 belong to the B lineage and grouped with sequences from Scotland. All genomes show mutations in their genomes compared to the reference strain, which could be important to understand the virulence, severity and transmissibility of the virus. Our findings also suggest that there were at least three independent introductions of SARS-CoV-2 to Ecuador.


Suggestions from Cremona, Italy - two months into the pandemic at the frontline of COVID-19 in Europe


title: An unfolded protein-induced conformational switch activates mammalian IRE1

text: The unfolded protein response (UPR) adjusts the cell’s protein folding capacity in the endoplasmic reticulum (ER) according to need. IRE1 is the most conserved UPR sensor in eukaryotic cells. It has remained controversial, however, whether mammalian and yeast IRE1 use a common mechanism for ER stress sensing. Here, we show that similar to yeast, human IRE1α’s ER-lumenal domain (hIRE1α LD) binds peptides with a characteristic amino acid bias. Peptides and unfolded proteins bind to hIRE1α LD’s MHC-like groove and induce allosteric changes that lead to its oligomerization. Mutation of a hydrophobic patch at the oligomerization interface decoupled peptide binding to hIRE1α LD from its oligomerization, yet retained peptide-induced allosteric coupling within the domain. Importantly, impairing oligomerization of hIRE1α LD abolished IRE1’s activity in living cells. Our results provide evidence for a unifying mechanism of IRE1 activation that relies on unfolded protein binding-induced oligomerization.


title: Sample descriptors linked to metagenomic sequencing data from human and animal enteric samples from Vietnam

text: There is still limited information on the diversity of viruses co-circulating in humans and animals. Here, we report data obtained from a large field collection of enteric samples taken from humans, pigs, rodents and other mammal hosts in Vietnam between 2012 and 2016. Each of 2100 stool or rectal swab samples was subjected to virally-enriched agnostic metagenomic sequencing; the short read sequence data are accessible from the European Nucleotide Archive (ENA). We link the sequence data to metadata on host type and demography and geographic location, distinguishing hospital patients, members of a cohort identified as a high risk of zoonotic infections (e.g. abattoir workers, rat traders) and animals. These data are suitable for further studies of virus diversity and virus discovery in humans and animals from Vietnam and to identify viruses found in multiple hosts that are potentially zoonotic.


title: Clinical Characteristics of Acute Lower Extremity Deep Venous Thrombosis Diagnosed by Duplex in Patients Hospitalized for Coronavirus Disease (COVID-19)

text: OBJECTIVE: Little is known about coronavirus disease (COVID-19)-associated hypercoagulability. We sought to characterize patients with deep venous thrombosis (DVT) identified after admission for COVID-19. METHODS: All adult patients admitted to Montefiore Medical Center (MMC) from March 1, 2020 to April 10, 2020 and undergoing lower extremity venous duplex for DVT evaluation were included. Patients admitted with suspicion of COVID-19 were divided into severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive and SARS-CoV-2 negative groups based on in-hospital test results. Patients without clinical suspicion for COVID-19 were not tested. A retrospective case-control study design was used to identify potential risk factors for DVT in patients with COVID-19. Demographic, radiographic and laboratory values were abstracted and analyzed. RESULTS: During the study period, 3,404 patients with confirmed COVID-19 were admitted to the hospital. Of the 135 SARS-CoV-2 patients who underwent duplex scanning, there were 18 (13.3%) noted to have DVT compared to 72 of the 711 patients (10.1%) who were either SARS-CoV-2 negative or untested. The odds ratio for DVT in COVID-19 was 1.35 (95% CI 0.78 – 2.34, p=0.289). Baseline characteristics for COVID-19 patients with and without DVT were overall similar. COVID-19 patients with DVT had an elevated median first D-dimer (18.88 mcg/mL [IQR 7.79, 20.00] versus 2.55 mcg/mL [IQR 1.45, 6.28], p=0.002, reference range <0.5 mcg/mL), average in-hospital D-dimer (median 11.93 mcg/mL [IQR 8.25, 16.97] versus 3.54 mcg/mL [IQR 2.05, 8.53] , p<0.001) and median fibrinogen level (501.0 (IQR 440.0, 629.0) versus 654.5 (IQR 535.8, 780.0), p= 0.002, reference range 187-502 mg/dL). There was a trend to significance for COVID-19 patients with DVT compared to without DVT in median D-dimer levels at the time of the duplex (13.61 mcg/mL [IQR 4.04, 19.97] versus 3.58 mcg/mL [IQR 2.51, 9.62], p=0.055) and median ferritin levels (1,679.0 ng/mL [IQR 1,168.0, 2,577.0] versus 1,103.0 ng/mL [IQR 703.5, 2,076.5], p=0.055, reference 25-270 ng/mL). Twelve of the 18 patients with COVID who developed DVT did so despite chemical thromboprophylaxis, and two developed DVT in spite of therapeutic anticoagulation CONCLUSIONS: We found only a modestly increased risk of DVT in patients with COVID-19, likely underestimated due to limitations in duplex testing early in the epidemic. Elevated D-dimer and a less elevated fibrinogen are associated with DVT in patients with COVID-19 who appear to form thrombus despite conventional chemical thromboprophylaxis. Additionally, an increasing D-dimer over time may be a reflection of the development of DVT in patients with COVID-19.


title: Knowledge, Perceptions, and Attitude of Egyptians Towards the Novel Coronavirus Disease (COVID-19)

text: Coronavirus disease 2019 (COVID-19) has been recognized as a pandemic by the World Health Organization. Global efforts have been exerted to prevent the spreading of the disease through political decisions together with personal behaviors, which depend on awareness of the public. The goal of this study is to assess the knowledge, perceptions and attitude of the Egyptian public towards the COVID-19 disease. We conducted a cross-sectional survey about these points, which was distributed among adult Egyptians. Five hundred and fifty nine persons completed the survey. The mean knowledge score was 16.39 out of 23, gained mainly though social media (66.9%), and the internet (58.3%). Knowledge was significantly lower among older, less educated, lower income participants, and rural residents. Most participants (86.9%) were concerned about the risk of infection. While 37.6% thought that their salary will be continued if they become isolated, 68.5% believed that it should be continued during this period. About 73.0% were looking forward to get the vaccine when available. In general, participants had a good knowledge about the disease and a positive attitude towards protective measures. This knowledge is gained mainly through novel media channels, which have pros and cons. Although the government has taken major steps to educate the public and limit the spread of the disease, more effort is needed to educate and support the lower economic strata. If a vaccine or a treatment is approved, we recommend a government control over its use to preserve the rights of the vulnerable and needy groups. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10900-020-00827-7) contains supplementary material, which is available to authorized users.


title: Identification and complete genome analysis of a novel bovine picornavirus in Japan

text: Abstract We identified novel viruses in feces from cattle with diarrhea collected in 2009 in Hokkaido Prefecture, Japan, by using a metagenomics approach and determined the (near) complete sequences of the virus. Sequence analyses revealed that they had a standard picornavirus genome organization, i.e. 5′ untranslated region (UTR) - L- P1 (VP4- VP3- VP2- VP1) - P2 (2A- 2B- 2C) - P3 (3A- 3B- 3C-3D) - 3′UTR- poly(A). They are closely related to other unclassified Chinese picornaviruses; bat picornaviruses group 1–3, feline picornavirus, and canine picornavirus, sharing 45.4–51.4% (P1), 38.0–44.9% (P2), and 49.6–53.3% (P3) amino acid identities, respectively. The phylogenetic analyses and detailed genome characterization showed that they, together with the unclassified Chinese picornaviruses, grouped as a cluster for the P1, 2C, 3CD and VP1 coding regions. These viruses had conserved features (e.g. predicted protein cleavage sites, presence of a leader protein, 2A, 2C, 3C, and 3D functional domains), suggesting they have a common ancestor. Reverse-transcription-PCR assays, using specific primers designed from the 5′UTR sequence of these viruses, showed that 23.0% (20/87) of fecal samples from cattle with diarrhea were positive, indicating the prevalence of these picornavirus in the Japanese cattle population in Hokkaido Prefecture. However, further studies are needed to investigate the pathogenic potential and etiological role of these viruses in cattle.


title: Chapter 5 Laboratory diagnosis of viral infection

text: Abstract Since the last Handbook of Clinical Neurology volume on this topic, viral diagnosis has made tremendous strides, moving from the margin to the mainstream of clinical care. For many years, conventional virus isolation was the mainstay of viral diagnosis since it was sensitive and “open-minded.” However, growth in conventional cell culture entails an inherent delay that limits its clinical impact. Although rapid culture and viral antigen methods detect fewer pathogens and are less sensitive than conventional culture, both require less expertise and have greatly reduced time to result. Polymerase chain reaction has ushered in a new era in virology, especially in the diagnosis of neurologic diseases. Molecular amplification methods are rapid, highly sensitive, can be automated, quantitative, and detect viruses not amenable to routine culture. User-friendly, walk-away tests with results in an hour, as well as multiplex tests that can detect 20 viruses in a single reaction, are now a reality. As the variety of test methods and commercial products proliferate, the challenges for clinicians and laboratories are selecting which tests to utilize in which clinical scenarios, and understanding how to interpret the results. The advantages and limitations of each method are discussed in this chapter, with special attention to neurologic disease.


title: Bovine coronavirus in naturally and experimentally exposed calves; viral shedding and the potential for transmission

text: BACKGROUND: Bovine coronavirus (BCoV) is a widely distributed pathogen, causing disease and economic losses in the cattle industry worldwide. Prevention of virus spread is impeded by a lack of basic knowledge concerning viral shedding and transmission potential in individual animals. The aims of the study were to investigate the duration and quantity of BCoV shedding in feces and nasal secretions related to clinical signs, the presence of virus in blood and tissues and to test the hypothesis that seropositive calves are not infectious to naïve in-contact calves three weeks after BCoV infection. METHODS: A live animal experiment was conducted, with direct contact between animal groups for 24 h as challenge procedure. Four naïve calves were commingled with a group of six naturally infected calves and sequentially euthanized. Two naïve sentinel calves were commingled with the experimentally exposed group three weeks after exposure. Nasal swabs, feces, blood and tissue samples were analyzed for viral RNA by RT-qPCR, and virus isolation was performed on nasal swabs. Serum was analyzed for BCoV antibodies. RESULTS: The calves showed mild general signs, and the most prominent signs were from the respiratory system. The overall clinical score corresponded well with the shedding of viral RNA the first three weeks after challenge. General depression and cough were the signs that correlated best with shedding of BCoV RNA, while peak respiratory rate and peak rectal temperature appeared more than a week later than the peak shedding. Nasal shedding preceded fecal shedding, and the calves had detectable amounts of viral RNA intermittently in feces through day 35 and in nasal secretions through day 28, however virus isolation was unsuccessful from day six and day 18 from the two calves investigated. Viral RNA was not detected in blood, but was found in lymphatic tissue through day 42 after challenge. Although the calves were shedding BCoV RNA 21 days after infection the sentinel animals were not infected. CONCLUSIONS: Prolonged shedding of BCoV RNA can occur, but detection of viral RNA does not necessarily indicate a transmission potential. The study provides valuable information with regard to producing scientifically based biosecurity advices. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0555-x) contains supplementary material, which is available to authorized users.


title: Antibody-mediated Neutralization of Ebola Virus Can Occur by Two Distinct Mechanisms

text: Human Ebola virus (EBOV) causes severe hemorrhagic fever disease with high mortality and there is no vaccine or treatment. Antibodies in survivors occur early, are sustained, and can delay infection when transferred into nonhuman primates. Monoclonal antibodies (mAbs) from survivors exhibit potent neutralizing activity in vitro and are protective in rodents. To better understand targets and mechanisms of neutralization, we investigated a panel of mAbs shown previously to react with the envelope glycoprotein (GP). While one non-neutralizing mAb recognized a GP epitope in the non-essential mucin-like domain, the rest were specific for GP1, were neutralizing, and could be further distinguished by reactivity with secreted GP. We show that survivor antibodies, human KZ52 and monkey JP3K11, were specific for conformation-dependent epitopes comprising residues in GP1 and GP2 and that neutralization occurred by two distinct mechanisms; KZ52 inhibited cathepsin cleavage of GP whereas JP3K11 recognized the cleaved, fusion-active form of GP.


title: Sequence motifs and prokaryotic expression of the reptilian paramyxovirus fusion protein

text: Fourteen reptilian paramyxovirus isolates were chosen to represent the known extent of genetic diversity among this novel group of viruses. Selected regions of the fusion (F) gene were sequenced, analyzed and compared. The F gene of all isolates contained conserved motifs homologous to those described for other members of the family Paramyxoviridae including: signal peptide, transmembrane domain, furin cleavage site, fusion peptide, N-linked glycosylation sites, and two heptad repeats, the second of which (HRB-LZ) had the characteristics of a leucine zipper. Selected regions of the fusion gene of isolate Gono-GER85 were inserted into a prokaryotic expression system to generate three recombinant protein fragments of various sizes. The longest recombinant protein was cleaved by furin into two fragments of predicted length. Western blot analysis with virus-neutralizing rabbit-antiserum against this isolate demonstrated that only the longest construct reacted with the antiserum. This construct was unique in containing 30 additional C-terminal amino acids that included most of the HRB-LZ. These results indicate that the F genes of reptilian paramyxoviruses contain highly conserved motifs typical of other members of the family and suggest that the HRB-LZ domain of the reptilian paramyxovirus F protein contains a linear antigenic epitope.


title: Intra-abdominal hypertension as a trigger of “gut failure” in SARS-CoV-2 infection: effect of open abdomen (OA) and negative pressure therapy (NPT) on respiratory and gastrointestinal (GI) function

text: COVID-19 gastrointestinal manifestations could be attributed to SARS-CoV-2-induced small vessel thrombosis. OA with NPT treatment may have a role in optimization of bowel microcirculation and in the reduction of the endothelial and the systemic cytokine-related damage, improving also respiratory function.


title: Is schizophrenia research relevant during the COVID-19 pandemic?

text: Abstract Schizophrenia researchers may ask themselves—or be asked by others—whether their research is relevant in the face of the COVID-19 pandemic. This commentary argues that schizophrenia research is more relevant than ever during this public health crisis, because of the likelihood that the COVID-19 pandemic may lead to increased incidence of psychotic disorders.


Epizootic Catarrhal Enteritis


title: Evolutionary trends of the COVID-19 epidemic and effectiveness of government interventions in Nigeria: A data-driven analysis.

text: BACKGROUND: Nigeria became the first sub Saharan African country to record a case of COVID-19 after an imported case from Italy was confirmed on February 27, 2020. Moving averages and the Epidemic Evaluation Indices (EEI) are two important but complementary methods useful in monitoring epidemic trends, they can also serve as a useful guide for policy makers and inform the timing of decisions on preventive measures. The objectives of this paper are to graphically depict the trends of new COVID-19 cases nationally and in two key States (Lagos and Kano) and the Federal Capital Territory (FCT) using the moving averages and the EEI. In addition, we examined the effects of government’s public health interventions on the spread of COVID-19 and appraise the progress made so far in addressing the challenges of COVID-19 in Nigeria. METHODS: We used data on new cases of COVID-19 from public sources released by the Nigeria Center for Disease Control (NCDC) from the 27(th) February 2020, when the first case was recorded, to 11(th) May, 2020, one week after the lockdowns in Lagos and the FCT were lifted. We computed moving averages of various orders, the log transformations of the moving averages and then the EEIs of new COVID-19 cases for Nigeria as a whole, and then for two of the most affected states i.e. Lagos and Kano, as well as the Federal Capital Territory (FCT). Then, we plotted graphs to depict these indices and show the epidemic trends for COVID-19 in each scenario. RESULTS: Nationally, the number of new cases of COVID-19 showed an initial gradual rise from the first reported case on the 27(th) February 2020. However, by the second week in April, these numbers began to show a relatively sharper increase and this trend has continued till date. Similar trends were observed in Lagos state and the FCT. The rate of growth of the logarithm-transformed moving average in the period leading to, and including the lockdowns reduced by a factor of 0.65. This suggests that the policies put in place by the government including the lockdown measures in Lagos and the FCT may have had a positive effect on the development of new cases of COVID-19 in Nigeria. Nationally and in Lagos, the EEIs of the COVID-19 cases started off on very high notes, however, the effects of the lockdown gradually became evident by the end of April and early May 2020, as the EEIs headed closer to 1.0. In all case scenarios, the EEIs are still above 1.0. CONCLUSIONS AND RECOMMENDATIONS: The number of new cases of COVID-19 has been on a steady rise since the first reported case. In Nigeria especially across the two states and the FCT, public health interventions including the lockdown measures appear to have played a role in reducing the rate of increase of new infections. The EEIs are still above 1.0, suggesting that despite the progress that appears to have been made, the epidemic is still evolving and Nigeria has not yet reached her peak for COVID-19 cases. We recommend that aggressive public health interventions and restrictions against mass gatherings should be sustained.


title: Can activation of NRF2 be a strategy against COVID-19?

text: Acute respiratory distress syndrome (ARDS) caused by SARS-CoV-2 is largely the result of a dysregulated host response, followed by damage to alveolar cells and lung fibrosis. Exacerbated pro-inflammatory cytokines release (cytokine storm) and loss of T-lymphocytes (leucopenia) characterize the most aggressive presentation. Here we propose that a multi-faceted anti-inflammatory strategy based on pharmacological activation of nuclear factor erythroid 2 p45-related factor 2 (NRF2), can be deployed against the virus. The strategy provides robust cytoprotection by restoring the redox and protein homeostasis, promoting resolution of inflammation, and facilitating repair. NRF2 activators such as sulforaphane and bardoxolone methyl are already in clinical trials. The safety and efficacy information of these modulators in humans, together with their well-documented cytoprotective and anti-inflammatory effects in preclinical models, highlight the potential of this armamentarium for deployment to the battlefield against COVID-19.


COVID-19 Outbreak in International Airport – Where the Incidence Case Occurs?


title: Current concepts in the prevention of pathogen transmission via blood/plasma-derived products for bleeding disorders()

text: The pathogen safety of blood/plasma-derived products has historically been a subject of significant concern to the medical community. Measures such as donor selection and blood screening have contributed to increase the safety of these products, but pathogen transmission does still occur. Reasons for this include lack of sensitivity/specificity of current screening methods, lack of reliable screening tests for some pathogens (e.g. prions) and the fact that many potentially harmful infectious agents are not routinely screened for. Methods for the purification/inactivation of blood/plasma-derived products have been developed in order to further reduce the residual risk, but low concentrations of pathogens do not necessarily imply a low level of risk for the patient and so the overall challenge of minimising risk remains. This review aims to discuss the variable level of pathogenic risk and describes the current screening methods used to prevent/detect the presence of pathogens in blood/plasma-derived products.


Covid-19 and thrombosis: beyond a casual association


title: Influenza D Virus of New Phylogenetic Lineage, Japan

text: Influenza D virus (IDV) can potentially cause respiratory diseases in livestock. We isolated a new IDV strain from diseased cattle in Japan; this strain is phylogenetically and antigenically distinguished from the previously described IDVs.


title: Appraisal of recommended respiratory infection control practices in primary care and emergency department settings

text: BACKGROUND: The severe acute respiratory syndrome (SARS) epidemic and concern about pandemic influenza prompted the Centers for Disease Control and Prevention (CDC) to develop guidelines to prevent the transmission of all respiratory infections in health care settings during first contact with a potentially infected person. The extent to which health care workers and institutions use these CDC recommended practices is uncertain. METHODS: The study examined health care worker adherence to CDC recommended respiratory infection control practices in primary care clinics and emergency departments of 5 medical centers in King County, Washington, using a self-administered questionnaire. All clinical, allied, and administrative health care workers in study settings were invited to participate: 653 (53%) responded, and 630 were included. RESULTS: The survey revealed important shortcomings in overall personal and institutional use of CDC recommended practices, including deficiencies in posted alerts, patient masking and separation, hand hygiene, personal protective equipment, staff training, and written procedures. Use of recommended measures was generally higher among nursing staff than medical practitioners. CONCLUSION: This study found significant gaps in adherence to CDC recommendations for the control of respiratory infections in ambulatory care clinical settings. Practical strategies are needed to identify and reduce barriers to implementation of recommended practices for control of respiratory infections.


title: Chronic treatment with hydroxychloroquine and SARS‐CoV‐2 infection

text: BACKGROUND: Hydroxychloroquine sulphate (HCQ) is being scrutinized for repositioning in the treatment and prevention of SARS‐Cov‐2 infection. This antimalarial drug is also chronically used to treat patients with autoimmune diseases. METHODS: By analysing the Portuguese anonymized data on private and public based medical prescriptions we have identified all cases chronically receiving HCQ for the management of diseases such as systemic lupus erythematosus, rheumatoid arthritis, and other autoimmune diseases. Additionally, we have detected all laboratory confirmed cases of SARS‐CoV‐2 infection and all laboratory confirmed negative cases in the Portuguese population (mandatorily registered in a centrally managed database). Cross linking the two sets of data has allowed us to compare the proportion of HCQ chronic treatment (at least 2 grams per month) in laboratory confirmed cases of SARS‐CoV‐2 infection with laboratory confirmed negative cases. RESULTS: Out of 26,815 SARS‐CoV‐2 positive patients, 77 (0.29%) were chronically treated with HCQ, while 1,215 (0.36%) out of 333,489 negative patients were receiving it chronically (P=0.04). After adjustment for age, sex, and chronic treatment with corticosteroids and/or immunosuppressants, the odds ratio of SARS‐CoV‐2 infection for chronic treatment with HCQ has been 0.51 (0.37‐0.70). CONCLUSIONS: Our data suggest that chronic treatment with HCQ confer protection against SARS‐CoV‐2 infection. This article is protected by copyright. All rights reserved.


title: Vacuolating encephalitis in mice infected by human coronavirus OC43

text: Abstract Involvement of viruses in human neurodegenerative diseases and the underlying pathologic mechanisms remain generally unclear. Human respiratory coronaviruses (HCoV) can infect neural cells, persist in human brain, and activate myelin-reactive T cells. As a means of understanding the human infection, we characterized in vivo the neurotropic and neuroinvasive properties of HCoV-OC43 through the development of an experimental animal model. Virus inoculation of 21-day postnatal C57BL/6 and BALB/c mice led to a generalized infection of the whole CNS, demonstrating HCoV-OC43 neuroinvasiveness and neurovirulence. This acute infection targeted neurons, which underwent vacuolation and degeneration while infected regions presented strong microglial reactivity and inflammatory reactions. Damage to the CNS was not immunologically mediated and microglial reactivity was instead a consequence of direct virus-mediated neuronal injury. Although this acute encephalitis appears generally similar to that induced by murine coronaviruses, an important difference rests in the prominent spongiform-like degeneration that could trigger neuropathology in surviving animals.


title: Cullin E3 Ligases and Their Rewiring by Viral Factors

text: The ability of viruses to subvert host pathways is central in disease pathogenesis. Over the past decade, a critical role for the Ubiquitin Proteasome System (UPS) in counteracting host immune factors during viral infection has emerged. This counteraction is commonly achieved by the expression of viral proteins capable of sequestering host ubiquitin E3 ligases and their regulators. In particular, many viruses hijack members of the Cullin-RING E3 Ligase (CRL) family. Viruses interact in many ways with CRLs in order to impact their ligase activity; one key recurring interaction involves re-directing CRL complexes to degrade host targets that are otherwise not degraded within host cells. Removal of host immune factors by this mechanism creates a more amenable cellular environment for viral propagation. To date, a small number of target host factors have been identified, many of which are degraded via a CRL-proteasome pathway. Substantial effort within the field is ongoing to uncover the identities of further host proteins targeted in this fashion and the underlying mechanisms driving their turnover by the UPS. Elucidation of these targets and mechanisms will provide appealing anti-viral therapeutic opportunities. This review is focused on the many methods used by viruses to perturb host CRLs, focusing on substrate sequestration and viral regulation of E3 activity.


title: Gauge field, strings, solitons, anomalies and the speed of life

text: It's been said that"mathematics is biology's next microscope, only better; biology is mathematics' next physics, only better". Here we aim for something even better. We try to combine mathematical physics and biology into a picoscope of life. For this we merge techniques which have been introduced and developed in modern mathematical physics, largely by Ludvig Faddeev to describe objects such as solitons and Higgs and to explain phenomena such as anomalies in gauge fields. We propose a synthesis that can help to resolve the protein folding problem, one of the most important conundrums in all of science. We apply the concept of gauge invariance to scrutinize the extrinsic geometry of strings in three dimensional space. We evoke general principles of symmetry in combination with Wilsonian universality and derive an essentially unique Landau-Ginzburg energy that describes the dynamics of a generic string-like configuration in the far infrared. We observe that the energy supports topological solitons, that pertain to an anomaly in the manner how a string is framed around its inflection points. We explain how the solitons operate as modular building blocks from which folded proteins are composed. We describe crystallographic protein structures by multi-solitons with experimental precision, and investigate the non-equilibrium dynamics of proteins under varying temperature. We simulate the folding process of a protein at in vivo speed and with close to pico-scale accuracy using a standard laptop computer: With pico-biology as mathematical physics' next pursuit, things can only get better.


title: Combating COVID-19 with Mesenchymal Stem Cell therapy

text: The COVID-19 disease is caused by a positive stranded RNA virus called SARS-CoV-2. The virus mainly targets the pulmonary epithelial cells as it’s initial site of infection by letting its surface spike protein interact and bind to the host ACE2 receptor. The internalization and gradual replication of the virus results in an exaggerated immune response triggering release of many pro-inflammatory cytokines and chemokines. This immune storm is responsible for multiple health hazards in the host ultimately leading to multiple organ failure. Mesenchymal stem cell therapy offers a promising approach towards mitigating the delirious effects of the infection in the COVID-19 patients. This therapy has shown to reduce the expression of pro-inflammatory cytokines as well as repair of damaged tissues in COVID-19 patients. This review has been organized to put forward the positive aruments and implications in support of mesenchymal stem cell therapy as a necessary approach for treating COVID-19 patients.


title: IFITM3 directly engages and shuttles incoming virus particles to lysosomes

text: Interferon-induced transmembrane proteins (IFITMs) (1, 2 and 3) have emerged as important innate immune effectors that prevent diverse virus infections in vertebrates. However, the cellular mechanisms and live cell imaging of these small membrane proteins have been challenging to evaluate during viral entry of mammalian cells. Using CRISPR-Cas9-mediated IFITM-mutant cell lines, we demonstrate that human IFITM1, 2 and 3 act cooperatively and function in dose-dependent fashion in interferon-stimulated cells. Through site-specific fluorophore tagging and live cell imaging studies, we show IFITM3 is on endocytic vesicles that fuse with incoming virus particles and enhances the trafficking of this pathogenic cargo to lysosomes. IFITM3 trafficking is specific to restricted viruses, requires S-palmitoylation and is abrogated with loss-of-function mutants. The site-specific protein labeling and live cell imaging approaches described here should facilitate the functional analysis of host factors involved in pathogen restriction as well as their mechanisms of regulation.


title: Survival of mechanically ventilated patients admitted to intensive care units: Results from a tertiary care center between 2016-2018

text: OBJECTIVES: To estimate the survival of adult and pediatric patients receiving mechanical ventilation and determine the associated risk factors METHODS: A retrospective cohort study was carried out in the intensive care unit (ICU) at King Abdulaziz Medical City (KAMC) and King Abdullah Children’s Specialist Hospital (KACSH), Riyadh, Saudi Arabia. The analysis includes data from medical records of all patients admitted to ICUs who received mechanical ventilation between 2016-2018. For each patient, potential risk factors were collected. The main outcome of this study was the mortality during the stay in ICU after receiving mechanical ventilation RESULTS: A total of 262 adults and 175 pediatric patients were admitted to ICUs and received mechanical ventilation during the study period. For adult patients, the overall mortality was 37%, with a median survival time of 11 days (interquartile range [IQR] 6-20 days). The main risk factors independently associated with the increased mortality rate were being aged 51-60 (odds ratio [OR] 2.6, 95% confidence interval [CI] 6.7-1.0) and factors related to ICU admission. For the pediatric population, the mortality rate was 17%, with a median survival time of 16 days (IQR 7-37 days). Prematurity with respiratory problems was the main recorded cause of initiation of mechanical ventilation (50% of patients). Neonates who had mechanical ventilation within one month of their birth and were born extremely preterm had a high mortality rate after the initiation of mechanical ventilation. CONCLUSION: Both patient age and the causes of the initiation of mechanical ventilation were influencing the survival of patients who required mechanical ventilation.


title: Covid‐19 in solid organ transplant recipients: A single center experience

text: BACKGROUND: Solid organ transplant (SOT) recipients may be at risk for severe COVID‐19. Data on the clinical course of COVID‐19 in immunosuppressed patients are limited and the effective treatment strategy for these patients is unknown. METHODS: We describe our institutional experience with COVID‐19 in SOT. Demographic, clinical and treatment data were extracted from the electronic patient files. RESULTS: A total of 23 SOT transplant recipients suffering from COVID‐19 were identified (n = 3 heart; n =15 kidney; n = 1 kidney‐after‐heart; n = 3 lung and n = 1 liver transplant recipient). The presenting symptoms were similar to non‐immunocompromised patients Eighty‐three percent (19/23) of the patients required hospitalization but only two of these were transferred to the intensive care unit. Five patients died from COVID‐19; all had high Clinical Frailty scores. In four of these patients, mechanical ventilation was deemed futile. In 57% of patients, the immunosuppressive therapy was not changed and only 3 patients were treated with chloroquine. Most patients recovered without experimental anti‐viral therapy. CONCLUSIONS: Modification of the immunosuppressive regimen alone could be a therapeutic option for SOT recipients suffering from moderate to severe COVID‐19. Pre‐existent frailty is associated with death from COVID‐19.


title: The Future of Emergency Medicine Public Health Research

text: This chapter addresses past successes and challenges and then elaborates on the potential for further advances in three areas that bridge emergency medicine and the broader public health and health services research agenda: (1) monitoring health care access; (2) surveillance of diseases, injuries, and health risks; and (3) delivering clinical preventive services. This article also suggests ways to advance policy-relevant research on systems of health and social welfare that impact the health of the public.


title: Nurses' participation in the Holocaust: A call to nursing educators

text: This year marks the 75th anniversary of the liberation of Auschwitz. The number of people able to provide first-person accounts of the atrocities of the Holocaust is dwindling in numbers. Prior to the mass extermination of Jews at Auschwitz and other extermination camps, nurses actively participated in the execution of tens of thousands of mentally, physically, and emotionally ill German citizens. Nursing educators must ensure that nursing students not only know about the Holocaust, but that they know that ordinary nurses were directly involved in the identification of vulnerable humans to be killed, and actually murdered them. Social, economic, and political pressures existed enabling the Nazi regime to involve nurses in this way. Similarly, social, economic, and political pressures today have the potential to encourage nurses to act in ways that violate personal or professional values. This paper provides four learning objectives that can be incorporated into existing nursing curricula to ensure that nurses do not forget how and why nurses in Germany came to murder more than 10,000 people in their care. With the passage of time comes the risk that the legacy of the Holocaust will be forgotten, nursing educators must participate in preventing that from happening.


title: Progress towards Health for All: Time to End Discrimination and Marginalization

text: Although it has been more than 40 years since "health for all" was presented as a focus in the Alma Ata declaration [...].


title: Single-dose treatment with a humanized neutralizing antibody affords full protection of a human transgenic mouse model from lethal Middle East respiratory syndrome (MERS)-coronavirus infection

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is continuously spreading and causing severe and fatal acute respiratory disease in humans. Prophylactic and therapeutic strategies are therefore urgently needed to control MERS-CoV infection. Here, we generated a humanized monoclonal antibody (mAb), designated hMS-1, which targeted the MERS-CoV receptor-binding domain (RBD) with high affinity. hMS-1 significantly blocked MERS-CoV RBD binding to its viral receptor, human dipeptidyl peptidase 4 (hDPP4), potently neutralized infection by a prototype MERS-CoV, and effectively cross-neutralized evolved MERS-CoV isolates through recognizing highly conserved RBD epitopes. Notably, single-dose treatment with hMS-1 completely protected hDPP4 transgenic (hDPP4-Tg) mice from lethal infection with MERS-CoV. Taken together, our data suggest that hMS-1 might be developed as an effective immunotherapeutic agent to treat patients infected with MERS-CoV, particularly in emergent cases.


title: Lesser Mealworm (Coleoptera: Tenebrionidae) Emergence After Mechanical Incorporation of Poultry Litter into Field Soils

text: Lesser mealworm, Alphitobius diaperinus (Panzer), emergence from North Carolina field soils was evaluated in a controlled experiment simulating land application of turkey litter and again in field studies. Adult lesser mealworms were buried in central North Carolina Cecil red clay at depths of 0, 8, 15, 23, and 30 cm and the beetles emerging from the soil counted 1, 3, 7, 10, 13, 17, 21, 24, and 28 d after burial. Beetles emerged from all depths and differences among depths were not significant. Beetles survived at least 28 d buried in the soil at depths ≤30 cm. In seasonal field studies, lesser mealworm emergence from clay soil with poultry litter incorporated by disk, mulch and plow was compared with emergence from plots with no incorporation. Incorporation significantly reduced beetle emergence when poultry litter containing large numbers of beetles was applied to clay field soils during the summer (F = 3.45; df = 3, 143; P = 0.018). Although mechanical incorporation of poultry litter reduced beetle emergence relative to the control, greatest reductions were seen in plowed treatments. Beetle activity was reduced after land application of litter during colder months. Generally, lesser mealworm emergence decreased with time and few beetles emerged from the soil 28 d after litter was applied. Similarly, mechanical incorporation of poultry litter into sandy soils reduced beetle emergence (F = 4.06; df = 3, 143; P < 0.008). In sandy soils typical of eastern North Carolina, disk and plow treatments significantly reduced beetle emergence compared with control.


title: Immunotherapy of SARS based on combinations of neutralizing human monoclonal antibodies

text: Evaluation of: Coughlin MM, Babcook J, Prabhakar BS: Human monoclonal antibodies to SARS-coronavirus inhibit infection by different mechanisms. Virology 394(1), 39–46 (2009). This work discusses passive immunotherapy based on neutralizing human monoclonal antibodies (mAbs) with different mechanisms of action. The authors have demonstrated that combining such mAbs, which target distinct epitopes, may greatly increase inhibition of virus infection and suppress the generation of neutralization escape mutants. The inhibition of human mAbs to SARS-coronavirus (CoV) may also act through different mechanisms of action, depending on their target epitopes or regions. Therefore, this approach could provide fast and effective prophylaxis and treatment of SARS-CoV infection during a SARS outbreak. Specifically, Coughlin et al. have indicated that most of the tested anti-S1 mAbs recognized epitopes within the receptor-binding domain and blocked virus attachment to its cellular receptor. These findings could provide a further step in understanding the mechanism of these mAbs in the prevention of SARS-CoV infection, as well as an insight into the design and development of novel therapeutic treatments.


Collaborative Delirium Prevention in the Age of COVID‐19


title: Feasibility of a 5G-based robot-assisted remote ultrasound system for cardiopulmonary assessment of COVID-19 patients

text: Abstract Background Traditional methods for cardiopulmonary assessment of Coronavirus Disease 2019 (COVID-19) patients pose risks to, both, patients and examiners. This necessitates a remote examination of such patients without sacrificing information quality. Research Question Assess the feasibility of a 5G-based robot-assisted remote ultrasound system in examining COVID-19 patients and establish an examination protocol for telerobotic ultrasound scanning. Study Design and Methods Twenty-three COVID-19 patients were included and divided into two groups. Twelve were non-severe cases, and 11 were severe cases. All patients underwent a 5G-based robot-assisted remote ultrasound system examination of the lungs and heart following an established protocol. Distribution characteristics and morphology of the lung and surrounding tissue lesions, left ventricular ejection fraction (LVEF), ventricular area ratio, pericardial effusion, and examination-related complications were recorded. Bilateral lung lesions were evaluated by lung ultrasound score (LUS). Results The remote ultrasound system successfully and safely performed cardiopulmonary examinations of all patients. Peripheral lung lesions were clearly evaluated. Severe cases had significantly more diseased regions [median (interquartile range), 6.0 (2.0-11.0) vs. 1.0 (0.0-2.8)] and higher LUSs [12.0 (4.0-24.0) vs. 2.0 (0.0-4.0)] than non-severe cases (both, P < 0.05 ). One non-severe case (8.3%, 95%CI, 1.5% to 35.4%) and three severe cases (27.3%, 95%CI, 9.7% to 56.6%) were complicated by pleural effusions. Four severe cases (36.4%, 95%CI, 15.2% to 64.6%) were complicated by pericardial effusions (vs 0% of non-severe cases, P < 0.05). No patients had significant examination-related complications. Interpretation 5G-based robot-assisted remote ultrasound system is feasible, and effectively obtains ultrasound characteristics for cardiopulmonary assessment of COVID-19 patients. By following established protocols and considering medical history, clinical manifestations, and laboratory markers, it might help to evaluate the severity of COVID-19 remotely.


title: Development of Autonomous Advanced Disinfection Tunnel to Tackle External Surface Disinfection of COVID-19 Virus in Public Places

text: This paper describes a robust autonomous disinfection tunnel to disinfect external surfaces of COVID-19 virus such as clothes and open body sections in public places such as airports, office complexes, schools, and malls. To make the tunnel effective and highly efficient, it has been provided with two chambers with three disinfection processes. Due to the multiple processes, the possibility of neutralizing the virus is quite high and higher than other solutions available at this point for this purpose. Chamber 1 sprays the solution of a disinfectant on the person. This solution can be either a dilute solution of approved chemical or any Ayurvedic/herbal disinfectant. Once the person enters chamber 2, he/she is exposed to hot air at 70 °C along with far-ultraviolet C rays (207–222 nm). Both chambers function autonomously by detecting a person in a chamber using ultrasonic sensors. The proposed tunnel is developed under industry–academia collaboration jointly by Technopark@iitk and ALIMCO under the ambit of the Ministry of Human Resources Development and the Ministry of Social Justice and Empowerment, respectively. The tunnel is referred to as the ‘Techno Advanced Disinfection Tunnel’ (TADT).


title: Evaluation of clinical applicability of reverse transcription-loop-mediated isothermal amplification assay for detection and subtyping of Influenza A viruses

text: Abstract Background Influenza A viruses (IAVs) have always remain a serious concern for the global economy and public health. A rapid, specific and sensitive detection method is always needed to control the influenza in its early stages by timely intervention of therapy and early clinical management. Objectives To develop RT-LAMP assays for detection of influenza A viruses, their further subtyping into seasonal (H1N1, H3N2) and novel pandemic H1N1 viruses and to evaluate clinical applicability of optimized RT-LAMP assays on patients’ samples. Study design In this study, we optimized RT-LAMP assay to detect IAVs by using primers against matrix gene and subtyping of IAVs was done by using primers against hemagglutinin gene. Optimized RT-LAMP assays were applied on clinical samples from patients having influenza like illness and results were compared with conventional one-step RT-PCR and real-time RT-PCR. Results RT-LAMP assays successfully detected and differentiated IAVs into H1N1, H3N2 and pdm09/H1N1 subtypes. One hundred and sixty seven clinical swab samples from influenza suspected patients were taken and tested with RT-LAMP assay, detecting 30 (17.9%) samples positive for Influenza A virus. Out of 30 samples, 21, 7 and 2 were found positive for pdm09/H1N1, H3N2 and seasonal H1 respectively. Conventional one-step RT-PCR detected a total of 27 (16.2%) samples for influenza A and further subtyping showed 20 and 7 samples positive for pdm09/H1N1 and H3N2 virus respectively whereas none was found positive for seasonal H1N1. RT-LAMP assay demonstrated higher sensitivity (93.8%) than conventional RT-PCR (84.4%) for influenza A viruses detection in clinical samples. Conclusions RT-LAMP assay is rapid, sensitive, specific and cost effective method for detection of influenza A viruses than conventional one-step RT-PCR and it can serve as a good alternate for diagnosis and surveillance studies during influenza outbreaks in resource-limited setups of developing countries.


Ventilatory support recommendations in children with Sars-CoV-2


title: Metagenomic analysis of viromes of dromedary camel fecal samples reveals large number and high diversity of circoviruses and picobirnaviruses

text: Abstract The recent discovery of Middle East Respiratory Coronavirus and another novel dromedary camel coronavirus UAE-HKU23 in dromedaries has boosted interest in search of novel viruses in dromedaries. In this study, fecal samples of 203 dromedaries in Dubai were pooled and deep sequenced. Among the 7330 assembled viral contigs, 1970 were assigned to mammalian viruses. The largest groups of these contigs matched to Picobirnaviridae, Circoviridae, Picornaviridae, Parvoviridae, Astroviridae and Hepeviridae. Many of these viral families were previously unknown to dromedaries. In addition to the high abundance of contigs from Circoviridae (n=598 with 14 complete genomes) and Picobirnaviridae (n=1236), a high diversity of contigs from these two families was found, with the 14 Circoviridae complete genomes forming at least five clusters and contigs from both genogroup I and genogroup II potentially novel picobirnaviruses. Further studies comparing the incidence of these viral families in healthy and sick dromedaries will reveal their pathogenic potential.


Sedation for critically ill patients with COVID-19: which specificities? One size does not fit all


title: Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19

text: Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis. In an analysis of a randomly collected cohort of 124 patients with Corona Virus Disease 2019 (COVID-19), we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. By virtual screening of a U.S. Food and Drug Administration (FDA) approved drug library, we identified an anticoagulation agent dipyridamole (DIP) in silico, which suppressed SARS-CoV-2 replication in vitro. In a proof-of-concept trial involving 31 patients with COVID-19, DIP supplementation was associated with significantly decreased concentrations of D-dimers (P<0.05), increased lymphocyte and platelet recovery in the circulation, and markedly improved clinical outcomes in comparison to the control patients. In particular, all 8 of the DIP-treated severely ill patients showed remarkable improvement: 7 patients (87.5%) achieved clinical cure and were discharged from the hospitals while the remaining 1 patient (12.5%) was in clinical remission.


Risk of transmission of severe acute respiratory syndrome to household contacts by infected health care workers and patients


A Case of COVID-19 Presenting after Coronary Artery Bypass Grafting


title: Viral and Developmental Cell Fusion Mechanisms: Conservation and Divergence

text: Membrane fusion is a fundamental requirement in numerous developmental, physiological, and pathological processes in eukaryotes. So far, only a limited number of viral and cellular fusogens, proteins that fuse membranes, have been isolated and characterized. Despite the diversity in structures and functions of known fusogens, some common principles of action apply to all fusion reactions. These can serve as guidelines in the search for new fusogens, and may allow the formulation of a cross-species, unified theory to explain divergent and convergent evolutionary principles of membrane fusion.


The Importance of Video Visits in the Time of COVID‐19


title: To recover faster from Covid-19, open up: Managerial implications from an open innovation perspective

text: Abstract Covid-19 has severely tested our public health systems. Recovering from Covid-19 will soon test our economic systems. Innovation will have an important role to play in recovering from the aftermath of the coronavirus. This article discusses both how to manage innovation as part of that recovery, and also derives some lessons from how we have responded to the virus so far, and what those lessons imply for managing innovation during the recovery.


title: New advances in CNS immunity against viral infection

text: The central nervous system (CNS) is an immunologically specialized organ where restrictive barrier structures protect the parenchyma from inflammation and infection. This protection is important in preventing damage to non-renewable resident cell populations, such as neurons, responsible for functions ranging from executive to autonomic. Despite these barriers, the CNS can be infected through several entry portals, giving rise to meningitis and encephalitis. Following infection, resident cells recruit peripherally derived immune cells to sites of viral infection. In this review, we discuss recent advances in immune recruitment and entry at barrier structures as well as current immunotherapeutic strategies for the treatment of persistent viral infections.


title: Detection and characterization of bovine torovirus from the respiratory tract in Japanese cattle

text: Abstract Bovine torovirus (BToV), a member of the Coronaviridae family, is a causative agent of diarrhea in cattle, but it may also possess tropism for the respiratory tract. However, no surveys concerning with the relation between respiratory symptoms and the detection of BToV have been conducted in wide range. Among 311 nasal samples, BToV gene products were detected in seven samples (rBToV-1 to -7) derived only from calves with respiratory symptoms, suggesting that BToV may be a predisposing factor and/or causative agent for bovine respiratory disease. Regarding the degree of similarity between the spike and hemagglutinin-esterase coding regions, the rBToVs showed over 90.8% similarity with one another and 73.5–99.0% similarity with fecal tract-derived BToVs. rBToV-1, -2, and -3 were identical despite their being collected during different seasons; in comparison, rBToV-4 and -5 were distinct despite the fact that they were collected from the same herd, suggesting the existence of diversity among domestic rBToVs. One animal with a BToV-positive nasal sample also shed the virus in its feces, suggesting dual tropisms for BToV.


Knowledge, attitudes, beliefs, and practices pertaining to camel-to-human disease risks among persons at camel farms, abattoirs, and meat markets in Jordan


Continues Renal Replacement Therapy (CRRT) With Disposable Hemoperfusion Cartridge: A Promising Option for Severe COVID-19


title: Prostate Cancer Radiotherapy Recommendations in Response to COVID-19

text: Abstract Purpose During a global pandemic the benefit of routine visits and treatment of cancer patients must be weighed against the risks to patients, staff, and society. Prostate cancer is one of the most common cancers Radiation Oncology departments treat, and efficient resource utilization is essential in the setting of a pandemic. Herein, we aim to establish recommendations and a framework by which to evaluate prostate radiotherapy management decisions. Patients and Methods Radiation Oncologists from the United States and United Kingdom rapidly conducted a systematic review and agreed upon recommendations to safely manage prostate cancer patients during the COVID-19 pandemic. A RADS framework was created: Remote visits, and Avoidance, Deferment, and Shortening of radiotherapy was applied to determine appropriate approaches. Results Recommendations are provided by National Comprehensive Cancer Network (NCCN) risk group, including clinical node positive, post-prostatectomy, oligometastatic, and low volume M1 disease. Across all prostate cancer stages, telemedicine consultations and return visits were recommended when resources/staff available. Delays in consultations and return visits was deemed safe based on stage of disease between 1-6 months. Treatment can be avoided or delayed until safe for very low, low, and favorable intermediate-risk disease. Unfavorable intermediate-risk, high-risk, clinical node positive, recurrence post-surgery, oligometastatic, and low-volume M1 disease can receive neoadjuvant hormone therapy for 4-6 months as necessary. Ultrahypofractionation was preferred for localized, oligometastatic, and low volume M1, and moderate hypofractionation was preferred for post-prostatectomy and clinical node positive disease. Salvage was preferred to adjuvant radiation. Conclusion Resources can be reduced for all identified stages of prostate cancer. The RADS (Remote visits, and Avoidance, Deferment, and Shortening of radiotherapy) framework can be applied to other disease sites to help with decision making in a global pandemic.


The importance of vaginal natural orifice surgeries in the era of COVID-19 pandemic


title: A mRNA PCR for the diagnosis of feline infectious peritonitis

text: Abstract A reverse transcriptase polymerase chain reaction (RT-PCR) for the detection of feline coronavirus (FCoV) messenger RNA in peripheral blood mononuclear cells (PBMCs) is described. The assay is evaluated as a diagnostic test for feline infectious peritonitis (FIP). It is based on a well-documented key event in the development of FIP: the replication of virulent FCoV mutants in monocytes/macrophages. To detect most feline coronavirus field strains, the test was designed to amplify subgenomic mRNA of the highly conserved M gene. The test was applied to 1075 feline blood samples (424 from healthy, 651 from sick cats suspected of FIP) and returned 46% of the diseased cats as positive for feline coronavirus mRNA in their peripheral blood cells; of the healthy cats, 5% tested positive. Of a group of 81 animals in which FIP had been confirmed by post-mortem examination, 75 (93%) tested positive, whereas 17 cats with different pathologies (non-FIP cases) all tested negative. In view of the low rate of false-positive results (high specificity) the mRNA RT-PCR may be a valuable addition to the diagnostic arsenal for FIP.


title: Microplastics in waters and soils: Occurrence, analytical methods and ecotoxicological effects

text: Microplastics (MPs) are ubiquitous in the environment and more abundant in the marine environment. Consequently, increasing focus has been put on MPs in oceans and seas, while little importance has been attached to their presence in freshwaters and soils. Therefore, this paper aimed to provide a comprehensive review of the occurrence, analysis and ecotoxicology of MPs. The abundance and distribution of MPs in several typical freshwater systems of China were summarized. It suggested that the surface water of Poyang Lake contained the highest concentration of 34 items/L MPs among all the 8 freshwater systems, and the content of MPs in sediments were higher than that of the surface water. Net-based zooplankton sampling methods are the most frequently utilized sampling methods for MPs, and density separation, elutriation and digestion are three major pretreatment methods. Fourier transform infrared spectroscopy, Raman spectroscopy and pyrolysis-gas chromatography coupled to mass spectrometry are often used to identify the polymer types of MPs. Besides, MPs might damage the digestive tract of various organisms and negatively inhibit their growth, feeding and reproduction. The ways of human exposure to MPs are by ingestion, inhalation and dermal exposure, digestive and respiratory system might be adversely influenced. However, potential health risks of MPs to humans are remained insufficiently researched. Overall, by showing the presence of MPs in freshwaters and soils as well as possible ecotoxicological effects on the environment and humans, this paper provided a framework for future research in this field.


Optometry in times of pandemic: Spanish flu (1919) versus COVID‐19 (2020)


title: Anti-influenza A virus effects of fructan from Welsh onion (Allium fistulosum L.)

text: Abstract A fructan that acts as an anti-influenza A virus substance was isolated from hot water extract of the green leafy part of a Welsh onion (Allium fistulosum L.). The structure of the fructan was characterised and elucidated by chemical and spectroscopic analyses. The fructan was composed of terminal (21.0%) and 2,1-linked β-d-Fruf residues (65.3%) with 1,6-linked β-d-Glcp residues (13.7%). The molecular weight of the polysaccharide and polydispersity was estimated to be 1.5×103 and 1.18, respectively. Although the fructan did not show anti-influenza A virus activity in vitro, it demonstrated an inhibitory effect on virus replication in vivo when it was orally administered to mice. In addition, the polysaccharide enhanced the production of neutralising antibodies against influenza A virus. Therefore, the antiviral mechanism of the polysaccharide seemed to be dependent on the host immune system, i.e., enhancement of the host immune function was achieved by the administration of the polysaccharide. From our observations, the fructan from Welsh onions is suggested to be one of the active principles which exert an anti-influenza virus effect.


title: Host Shutoff in Influenza A Virus: Many Means to an End

text: Influenza A virus carries few of its own proteins, but uses them effectively to take control of the infected cells and avoid immune responses. Over the years, host shutoff, the widespread down-regulation of host gene expression, has emerged as a key process that contributes to cellular takeover in infected cells. Interestingly, multiple mechanisms of host shutoff have been described in influenza A virus, involving changes in translation, RNA synthesis and stability. Several viral proteins, notably the non-structural protein NS1, the RNA-dependent RNA polymerase and the endoribonuclease PA-X have been implicated in host shutoff. This multitude of host shutoff mechanisms indicates that host shutoff is an important component of the influenza A virus replication cycle. Here we review the various mechanisms of host shutoff in influenza A virus and the evidence that they contribute to immune evasion and/or viral replication. We also discuss what the purpose of having multiple mechanisms may be.


Early preemptive immunomodulators (corticosteroids) for severe pneumonia patients infected with SARS-CoV-2


title: The behaviour of recent isolates of human respiratory coronavirus in vitro and in volunteers: Evidence of heterogeneity among 229E‐related strains

text: Strains of human coronavirus (HCV) isolated between 1974 and 1976 have been studied in vitro and in volunteers. All strains caused colds in volunteers, and those cultivable in tissue culture (TC) produced significantly more coryza and less sore throat than strains growing only in organ culture (OC). The TC strains were serologically related to 229E, but these isolates produced colds with a frequency and severity that contrasted with the effects of 229E itself. Tests on volunteers' preinfection sera showed that the prevalence of antibody to 229E had increased during the period 1961–1979 and that during 1977–1979 only 11% of subjects had no neutralising antibody against 229E. Susceptibility to the 229E‐related isolates PR and TO was associated with low preinfection serum neutralising antibody against the homologous virus, and paired sera frequently showed fourfold or greater antibody rises, most commonly against the homologous strain. Volunteers infected with TO were immune when reinoculated with the same strain approximately 1 year later, but other similar volunteers were at least partly susceptible to infection with a heterologous 229E‐related virus after similar time intervals. Although the strains of HCV that were grown in tissue culture were all related to the prototype 229E, they appeared not to be identical with it, and this heterogeneity is probably a significant factor in the epidemiology of HCV infections.


COVID–19, Journal de bord–18/02/2020–Questions à François Bricaire


title: Determination and analysis of complete coding sequence regions of new discovered human bocavirus types 2 and 3

text: In this study, two human bocaviruses (HBoV), HBoV2 and HBoV3, that were detected previously in enteric samples were characterized genetically. Nearly complete genome sequences of three HBoV2 variants and one HBoV3 variant originating from Thailand and the UK were compared to published HBoV sequences. HBoV2 showed divergence from HBoV1 throughout the genome, while the HBoV3 sequence grouped phylogenetically with HBoV1 in the non-structural region and with HBoV2 sequences in the structural gene, consistent with its proposed recombinant origin. Compared to HBoV1 and HBoV3, HBoV2 shows substantially greater intra-species diversity, consistent with a longer period of human circulation.


Kawasaki disease coincident with influenza A H1N1/09 infection


title: Comparison of respiratory virus shedding by conventional and molecular testing methods in patients with haematological malignancy

text: Respiratory viruses (RV) are a leading cause of infection-related morbidity and mortality for patients undergoing treatment for cancer. This analysis compared duration of RV shedding as detected by culture and PCR among patients in a high-risk oncology setting (adult patients with haematological malignancy and/or stem cell transplant and all paediatric oncology patients) and determined risk factors for extended shedding. RV infections due to influenza virus, parainfluenza virus (PIV), human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) from two study periods—January 2009–September 2011 (culture-based testing) and September 2011–April 2013 (PCR-based testing)—were reviewed retrospectively. Data were collected from patients in whom re-testing for viral clearance was carried out within 5–30 days after the most recent test. During the study period 456 patients were diagnosed with RV infection, 265 by PCR and 191 by culture. The median range for duration of shedding (days) by culture and PCR, respectively, were as follows—influenza virus: 13 days (5–38 days) versus 14 days (5–58 days), p 0.5; RSV: 11 days (5–35 days) versus 16 days (5–50 days), p 0.001; PIV: 9 days (5–41 days) versus 17 days (5–45 days), p ≤0.0001; HMPV 10.5 days (5–29 days) versus 14 days (5–42 days), p 0.2. In multivariable analysis, age and underlying disease or transplant were not independently associated with extended shedding regardless of testing method. In high-risk oncology settings for respiratory illness due to RSV and PIV, the virus is detectable by PCR for a longer period of time than by culture and extended shedding is observed.


title: Combating Antimicrobial Resistance in Singapore: A Qualitative Study Exploring the Policy Context, Challenges, Facilitators, and Proposed Strategies

text: Antimicrobial resistance (AMR) is a global public health threat that warrants urgent attention. However, the multifaceted nature of AMR often complicates the development and implementation of comprehensive policies. In this study, we describe the policy context and explore experts’ perspectives on the challenges, facilitators, and strategies for combating AMR in Singapore. We conducted semi-structured interviews with 21 participants. Interviews were transcribed verbatim and were analyzed thematically, adopting an interpretative approach. Participants reported that the Ministry of Health (MOH) has effectively funded AMR control programs and research in all public hospitals. In addition, a preexisting One Health platform, among MOH, Agri-Food & Veterinary Authority (restructured to form the Singapore Food Agency and the Animal & Veterinary Service under NParks in April 2019), National Environment Agency, and Singapore’s National Water Agency, was perceived to have facilitated the coordination and formulation of Singapore’s AMR strategies. Nonetheless, participants highlighted that the success of AMR strategies is compounded by various challenges such as surveillance in private clinics, resource constraints at community-level health facilities, sub-optimal public awareness, patchy regulation on antimicrobial use in animals, and environmental contamination. This study shows that the process of planning and executing AMR policies is complicated even in a well-resourced country such as Singapore. It has also highlighted the increasing need to address the social, political, cultural, and behavioral aspects influencing AMR. Ultimately, it will be difficult to design policy interventions that cater for the needs of individuals, families, and the community, unless we understand how all these aspects interact and shape the AMR response.


title: A qualitative study of the duty to care in communicable disease outbreaks

text: Abstract Health care providers’ (HCPs’) duty to care during communicable disease outbreaks has resurfaced as an important and contentious topic. This renewed interest follows the re-emergence of communicable diseases, largely thought to have disappeared and therefore irrelevant to modern day practitioners. The 2003 SARS outbreak particularly presented propitious circumstances for reconsidering this issue. This study seeks to characterize the views of individuals on the nature and limits of this duty. The authors employed qualitative methods to gather lay and expert perspectives. Individual interviews were conducted with 67 participants consisting of HCPs, spiritual leaders, regulators, and members of the public from the greater Toronto area. Participants’ views were analyzed and organized according to three main themes, constituting a framework that combines micro-, meso-, and macro-level structures and processes: the scope of obligations of HCPs, the roles of health care institutions, and the broader social context, respectively. Our data suggest that the duty to care must be placed in a wider context to include considerations that transcend individual provider obligations. It thus follows, based on our data, that the duty to care cannot be left to personal choice or an appeal to morality based on an ethic derived entirely from individual obligations. The micro-meso-macro analytical framework that we have developed can guide the articulation of accepted norms of duty to care during epidemics and the development of policy for public health crises. It can also enhance the focus of our current expectations of HCPs’ duty during epidemics. This can be achieved by informing regulatory bodies, collaborating with policy makers and engaging the public.


Multiplex polymerase chain reaction testing in pediatric inpatients with febrile seizures


title: Evaluation of Seegene Allplex Respiratory Panel 1 kit for the detection of influenza virus and human respiratory syncytial virus

text: Abstract Background Influenza (FLUV) and human respiratory syncytial (HRSV) viruses are etiological agents of respiratory infections that cause a significant morbidity and mortality worldwide. A rapid and accurate diagnosis of these respiratory viruses is essential for an appropriate patient management. Molecular tests are the best detection option due to their high sensitivity and specificity. Seegene’s Allplex™ Respiratory Panel 1 (Allplex RP1) is a real-time one-step RT-PCR assay for the simultaneous detection of FLUAV, FLUBV, HRSV-A and HRSV-B. In addition, it allows the determination of FLUAV subtype (H1, H3 and H1pdm09). Objectives This study aims to evaluate Allplex RP1 as a rapid molecular test for the detection of FLUAV, FLUBV, HRSV-A and HRSV-B viruses. Study design The Allplex RP1 assay will be compared with other two commercial molecular assays, Prodesse ProFlu+ and ProFAST+ (Hologic, Madison, WI, USA), and GeneXpert Flu/RSV XC (Cepheid, USA). Results Allplex RP1, ProFlu+ and GeneXpert tests showed 95%, 91% and 96% of accuracy; and 94%, 88% and 95% of sensitivity, respectively. Moreover, Allplex RP1 showed a FLUAV subtype sensitivity of 91% and 88% for FLUAV-H1pdm09 and FLUAV-H3 respectively, and ProFAST+ assay showed sensitivities of 100% for both targets. The three assays showed a 100% of specificity and PPV, while the NPV were 84%, 73% and 86% for Allplex RP1, Prodesse and GeneXpert, respectively. Conclusions In this study, Seegene’s Allplex RP1 assay showed to be highly sensitive, specific, and suitable for detection of FLUV and HRSV, including FLUAV subtyping. In addition, it is also a hands-on-time saving assay due to the automated nucleic acid extraction and PCR setup.


Men, Suicide, and Covid-19: Critical Masculinity Analyses and Interventions


title: Factors impacting compliance with standard precautions in nursing, China

text: Summary Objectives To evaluate registered nurse compliance with standard precautions and to analyze the factors that affect compliance. Methods Study data were collected over a 3-month period from June to September 2007. The survey research method was used. A total of 1500 randomly sampled registered nurses from 18 hospitals in Hunan, China completed self-report questionnaires. Results Of the 1500 nurses included in the study, 1444 returned valid self-report questionnaires. Compliance with standard precautions was found to be low in the surveyed nurses. With a maximum possible score of 80, the quartile range of the overall score for compliance for all nurses was 48.29 (upper quartile score 76.36, lower quartile score 28.07), which was occupied by 64.7% of the participants. The factors most affecting compliance were: standard precautions training (odds ratio (OR) 2.17, 95% confidence interval (CI) 1.85–2.55) and knowledge (OR 1.94, 95% CI 1.01–3.41), followed by hospital grade (OR 1.61, 95% CI 1.79–1.86), presence of sharps disposal box in the department (OR 1.43, 95% CI 1.10–3.41), general self-efficacy (OR 1.29, 95% CI 1.04–1.59), exposure experience (OR 0.69, 95% CI 0.56–0.85), and department in which the nurse worked (OR 1.24, 95% CI 1.05–1.46). Conclusions The relevant authorities and hospital infection control department should pay more attention to nurse compliance with standard precautions. Standard precautions training should be strengthened and sufficient practical personal protection equipment provided in order to reduce hospital infections and protect the health of patients and medical staff.


title: Respiratory Syncytial Virus and Other Respiratory Viral Infections in Older Adults With Moderate to Severe Influenza-like Illness

text: Background. Few studies have prospectively assessed viral etiologies of acute respiratory infections in community-based elderly individuals. We assessed viral respiratory pathogens in individuals ≥65 years with influenza-like illness (ILI). Methods. Multiplex reverse-transcriptase polymerase chain reaction identified viral pathogens in nasal/throat swabs from 556 episodes of moderate-to-severe ILI, defined as ILI with pneumonia, hospitalization, or maximum daily influenza symptom severity score (ISS) >2. Cases were selected from a randomized trial of an adjuvanted vs nonadjuvanted influenza vaccine conducted in elderly adults from 15 countries. Results. Respiratory syncytial virus (RSV) was detected in 7.4% (41/556) moderate-to-severe ILI episodes in elderly adults. Most (39/41) were single infections. There was a significant association between country and RSV detection (P = .004). RSV prevalence was 7.1% (2/28) in ILI with pneumonia, 12.5% (8/64) in ILI with hospitalization, and 6.7% (32/480) in ILI with maximum ISS > 2. Any virus was detected in 320/556 (57.6%) ILI episodes: influenza A (104/556, 18.7%), rhinovirus/enterovirus (82/556, 14.7%), coronavirus and human metapneumovirus (each 32/556, 5.6%). Conclusions. This first global study providing data on RSV disease in ≥65 year-olds confirms that RSV is an important respiratory pathogen in the elderly. Preventative measures such as vaccination could decrease severe respiratory illnesses and complications in the elderly.


title: Susceptibility to SARS coronavirus S protein-driven infection correlates with expression of angiotensin converting enzyme 2 and infection can be blocked by soluble receptor

text: Abstract The angiotensin converting enzyme 2 (ACE2) has been identified as a receptor for the severe acute respiratory syndrome associated coronavirus (SARS-CoV). Here we show that ACE2 expression on cell lines correlates with susceptibility to SARS-CoV S-driven infection, suggesting that ACE2 is a major receptor for SARS-CoV. The soluble ectodomain of ACE2 specifically abrogated S-mediated infection and might therefore be exploited for the generation of inhibitors. Deletion of a major portion of the cytoplasmic domain of ACE2 had no effect on S-driven infection, indicating that this domain is not important for receptor function. Our results point to a central role of ACE2 in SARS-CoV infection and suggest a minor contribution of the cytoplasmic domain to receptor function.


title: Dendritic cells: microbial clearance via autophagy and potential immunobiological consequences for periodontal disease

text: Dendritic cells are potent antigen-capture and -presenting cells that play a key role in the initiation and regulation of the adaptive immune response. This process of immune homeostasis, as maintained by dendritic cells, is susceptible to dysregulation by certain pathogens during chronic infections. Such dysregulation may lead to disease perpetuation with potentially severe systemic consequences. Here we discuss in detail how intracellular pathogens exploit dendritic cells and evade degradation by altering or evading autophagy. This novel mechanism explains in part the chronic, persistent nature observed in several immuno-inflammatory diseases, including periodontal disease. Also, here we propose a hypothetical model on the plausible role of autophagy in the context of periodontal disease. Promotion of autophagy may open new therapeutic strategies in the search for a “cure” for periodontal disease in humans.


title: SARS2-CoV-2 and Stroke in a New York Healthcare System

text: BACKGROUND AND PURPOSE: With the spread of coronavirus disease 2019 (COVID-19) during the current worldwide pandemic, there is mounting evidence that patients affected by the illness may develop clinically significant coagulopathy with thromboembolic complications including ischemic stroke. However, there is limited data on the clinical characteristics, stroke mechanism, and outcomes of patients who have a stroke and COVID-19. METHODS: We conducted a retrospective cohort study of consecutive patients with ischemic stroke who were hospitalized between March 15, 2020, and April 19, 2020, within a major health system in New York, the current global epicenter of the pandemic. We compared the clinical characteristics of stroke patients with a concurrent diagnosis of COVID-19 to stroke patients without COVID-19 (contemporary controls). In addition, we compared patients to a historical cohort of patients with ischemic stroke discharged from our hospital system between March 15, 2019, and April 15, 2019 (historical controls). RESULTS: During the study period in 2020, out of 3556 hospitalized patients with diagnosis of COVID-19 infection, 32 patients (0.9%) had imaging proven ischemic stroke. Cryptogenic stroke was more common in patients with COVID-19 (65.6%) as compared to contemporary controls (30.4%, P=0.003) and historical controls (25.0%, P<0.001). When compared with contemporary controls, COVID-19 positive patients had higher admission National Institutes of Health Stroke Scale score and higher peak D-dimer levels. When compared with historical controls, COVID-19 positive patients were more likely to be younger men with elevated troponin, higher admission National Institutes of Health Stroke Scale score, and higher erythrocyte sedimentation rate. Patients with COVID-19 and stroke had significantly higher mortality than historical and contemporary controls. CONCLUSIONS: We observed a low rate of imaging-confirmed ischemic stroke in hospitalized patients with COVID-19. Most strokes were cryptogenic, possibly related to an acquired hypercoagulability, and mortality was increased. Studies are needed to determine the utility of therapeutic anticoagulation for stroke and other thrombotic event prevention in patients with COVID-19.


title: Personal protective equipment induced facial dermatoses in healthcare workers managing Coronavirus disease 2019

text: During the COVID-19 pandemic, frontline healthcare workers (HCW) are working tirelessly for long hours to provide patient care. Although COVID is not dermatotropic, prolonged contact with personal protective equipment (PPE i.e. goggles, face-shield/visor, N 95 respirator, double layered gloves, coverall/gowns, head cover and shoe cover) may cause various dermatoses. Several dermatoses have been reported due to PPE, such as pressure injury, contact dermatitis, pressure urticaria, and exacerbation of pre-existing skin diseases, including seborrheic dermatitis and acne.


title: Novel genotype of infectious bronchitis virus isolated in China

text: Abstract Recombination events are known to contribute to the emergence of novel infectious bronchitis virus (IBV) genotypes. In this study, we carried out detailed phylogenetic analysis and sequence comparisons based on 74 complete nucleotide sequences of the IBV S1 gene, including strain I0636/16 and 73 representative sequences from each genotype and lineage. The results showed that strain I0636/16 represented a novel genotype, designated as lineage 1 within genotype VII (GVII-1). Further comparative genomic analysis revealed at least two recombination sites that replaced the spike gene in a lineage 18 within genotype I (GI-18)-like virus with an as-yet-unidentified sequence, likely derived from another IBV strain, resulting a novel serotype with a lower affinity to the respiratory tract in chickens. To the best of our knowledge, this provides the first evidence for recombination leading to replacement of the complete spike gene and the emergence of a novel genotype/serotype with a lower affinity to the respiratory tract in chickens comparing to one of its parental virus ck/CH/LGX/111119. These results emphasize the importance of limiting exposure to novel IBVs that may serve as a source of genetic material for emerging viruses, as well as the importance of IBV surveillance in chicken flocks.


title: Evidence for Cross-Protection Against Subsequent Febrile Respiratory Illness Episodes From Prior Infections by Different Viruses Among Singapore Military Recruits 2009–2014

text: BACKGROUND: Few studies have evaluated the relative cross-protection conferred by infection with different groups of viruses through studies of sequential infections in humans. We investigated the presence of short-lived relative cross-protection conferred by specific prior viral infections against subsequent febrile respiratory illness (FRI). METHODS: Men enlisted in basic military training between December 2009 and December 2014 were recruited, with the first FRI as the study entry point. ResPlex II assays and real-time polymerase chain reaction assays were used to detect viral pathogens in nasal wash samples, and survival analyses were performed to determine whether infection with particular viruses conferred short-lived relative cross-protection against FRI. RESULTS: Prior infection with adenovirus (hazard ratio [HR], 0.24; 95% confidence interval [CI], .14–.44) or influenza virus (HR, 0.52; 95% CI, .38–.73) conferred relative protection against subsequent FRI episode. Results were statistically significant even after adjustment for the interval between enlistment and FRI (P < .001). Adenovirus-positive participants with FRI episodes tended to be protected against subsequent infection with adenovirus, coronavirus, enterovirus/rhinovirus, and influenza virus (P = .062–.093), while men with influenza virus–positive FRI episodes tended be protected against subsequent infection with adenovirus (P = .044) and influenza virus (P = .081). CONCLUSION: Prior adenovirus or influenza virus infection conferred cross-protection against subsequent FRI episodes relative to prior infection due to other circulating viruses.


What’s the way out? Potential exit strategies from the COVID-19 lockdown


title: Community-acquired pneumonia

text: Summary This seminar reviews important features and management issues of community-acquired pneumonia (CAP) that are especially relevant to immunocompetent adults in light of new information about cause, clinical course, diagnostic testing, treatment, and prevention. Streptococcus pneumoniae remains the most important pathogen; however, emerging resistance of this organism to antimicrobial agents has affected empirical treatment of CAP. Atypical pathogens have been quite commonly identified in several prospective studies. The clinical significance of these pathogens (with the exception of Legionella spp) is not clear, partly because of the lack of rapid, standardised tests. Diagnostic evaluation of CAP is important for appropriate assessment of severity of illness and for establishment of the causative agent in the disease. Until better rapid diagnostic methods are developed, most patients will be treated empirically. Antimicrobials continue to be the mainstay of treatment, and decisions about specific agents are guided by several considerations that include spectrum of activity, and pharmacokinetic and pharmacodynamic principles. Several factors have been shown to be associated with a beneficial clinical outcome in patients with CAP. These factors include administration of antimicrobials in a timely manner, choice of antibiotic therapy, and the use of a critical pneumonia pathway. The appropriate use of vaccines against pneumococcal disease and influenza should be encouraged. Several guidelines for management of CAP have recently been published, the recommendations of which are reviewed.


title: Serial interval of novel coronavirus (COVID-19) infections

text: Abstract Objective To estimate the serial interval of novel coronavirus (COVID-19) from information on 28 infector-infectee pairs. Methods We collected dates of illness onset for primary cases (infectors) and secondary cases (infectees) from published research articles and case investigation reports. We subjectively ranked the credibility of the data and performed analyses on both the full dataset (n = 28) and a subset of pairs with highest certainty in reporting (n = 18). In addition, we adjust for right truncation of the data as the epidemic is still in its growth phase. Results Accounting for right truncation and analyzing all pairs, we estimated the median serial interval at 4.0 days (95% credible interval [CrI]: 3.1, 4.9). Limiting our data to only the most certain pairs, the median serial interval was estimated at 4.6 days (95% CrI: 3.5, 5.9). Conclusions The serial interval of COVID-19 is close to or shorter than its median incubation period. This suggests that a substantial proportion of secondary transmission may occur prior to illness onset. The COVID-19 serial interval is also shorter than the serial interval of severe acute respiratory syndrome (SARS), indicating that calculations made using the SARS serial interval may introduce bias.


title: Interferon, Mx, and viral countermeasures

text: Abstract The interferon system provides a powerful and universal intracellular defense mechanism against viruses. Knockout mice defective in IFN signaling quickly succumb to all kinds of viral infections. Likewise, humans with genetic defects in interferon signaling die of viral disease at an early age. Among the known interferon-induced antiviral mechanisms, the Mx pathway is one of the most powerful. Mx proteins belong to the dynamin superfamily of large GTPases and have direct antiviral activity. They inhibit a wide range of viruses by blocking an early stage of the viral replication cycle. Likewise, the protein kinase R (PKR), and the 2–5 OAS/RNaseL system represent major antiviral pathways and have been extensively studied. Viruses, in turn, have evolved multiple strategies to escape the IFN system. They try to go undetected, suppress IFN synthesis, bind and neutralize secreted IFN molecules, block IFN signaling, or inhibit the action of IFN-induced antiviral proteins. Here, we summarize recent findings about the astonishing interplay of viruses with the IFN response pathway.


title: A High-Throughput Yeast Two-Hybrid Protocol to Determine Virus-Host Protein Interactions

text: The yeast two-hybrid (Y2H) system is a powerful method to identify and analyze binary protein interactions. In the field of virology, the Y2H system has significantly increased our knowledge of structure and function of viral proteins by systematically assessing intraviral protein interactions. Several comprehensive approaches to determine virus-host interactions have provided insight into viral strategies to manipulate the host for efficient replication and to escape host-derived countermeasures. To expand our knowledge of intraviral and virus-host protein interactions, we here present a Y2H protocol that is well suited for high-throughput screening. Yeast mating followed by liquid handling in a 96-well format as well as fluorescent readout of the reporter system provides a highly standardized and fully automated screening situation. The protocol can either be applied to screen complex host cDNA libraries or protein pairs arrayed for cross-testing. The ease of use, the cost-effectiveness as well as the robotic handling allows for extensive and multiple rounds of screening providing high coverage of protein-protein interactions. Thus, this protocol represents an improved “deep” screening method for high-throughput Y2H assays.


Weaker together or weaker apart? Great power relations after the coronavirus


title: Analysis of the Microbiota of the Physiotherapist's Environment

text: ABSTRACT. Objetive To analyse the microbiota of the physiotherapist´s work environment to understand the existing potential risks in order to adopt appropriate preventive measures. Design Cross-sectional descriptive observational study. Setting Physiotherapist´s working environment. Participants 19 physiotherapy and rehabilitation centres. Intervention A microbiological sampling was carried out in the physiotherapy centers. The samples were studied using the usual culture and analysis methodology for characterization and isolation of a range of bacteria. Main outcome measures Absolute and relative frequency of microorganism isolation. Results In the analysis, pathogens normally responsible for nosocomial infections were detected, especially on instruments and equipment used by the physiotherapist like sponge electrodes, and were significantly more contaminated than the rest of the places studied (p<0.01). Conclusion This situation confirms the absence of measures and protocols for the prevention and control of such infections in the physiotherapist's environment, which is why they must be considered in order to protect both physiotherapy professionals and patients.


A case with psychotic disorder as a clinical presentation of COVID‐19


title: Targeting CCL5 in inflammation

text: Introduction: Chemokines play important roles in inflammation and in immune responses. This article will discuss the current literature on the C–C chemokine ligand 5 (CCL5), and whether it is a therapeutic target in the context of various allergic, autoimmune or infectious diseases. Areas covered: Small-molecule inhibitors, chemokine and chemokine receptor-deficient mice, antibodies and modified chemokines are the current tools available for CCL5 research, and there are several ongoing clinical trials targeting the CCL5 receptors, CCR1, CCR3 and CCR5. There are fewer studies specifically targeting the chemokine itself and clinical studies with anti-CCL5 antibodies are still to be carried out. Expert opinion: Although clinical trials are strongly biased toward HIV treatment and prevention with blockers of CCR5, the therapeutic potential for CCL5 and its receptors in other diseases is relevant. Overall, it is not likely that specific targeting of CCL5 will result in new adjunct strategies for the treatment of infectious diseases with a major inflammatory component. However, targeting CCL5 could result in novel therapies for chronic inflammatory diseases, where it may decrease inflammatory responses and fibrosis, and certain solid tumors, where it may have a role in angiogenesis.


title: Antiviral responses against chicken respiratory infections: Focus on avian influenza virus and infectious bronchitis virus

text: Abstract Some of the respiratory viral infections in chickens pose a significant threat to the poultry industry and public health. In response to viral infections, host innate responses provide the first line of defense against viruses, which often act even before the establishment of the infection. Host cells sense the presence of viral components through germinal encoded pattern recognition receptors (PRRs). The engagement of PRRs with pathogen-associated molecular patterns leads to the induction of pro-inflammatory and interferon productions. Induced antiviral responses play a critical role in the outcome of the infections. In order to improve current strategies for control of viral infections or to advance new strategies aimed against viral infections, a deep understanding of host-virus interaction and induction of antiviral responses is required. In this review, we summarized recent progress in understanding innate antiviral responses in chickens with a focus on the avian influenza virus and infectious bronchitis virus.


title: Effects of temperature variation and humidity on the death of COVID-19 in Wuhan, China

text: Abstract Meteorological parameters are the important factors influencing the infectious diseases such as severe acute respiratory syndrome (SARS) and influenza. This study aims to explore the association between Corona Virus Disease 2019 (COVID-19) deaths and weather parameters. In this study, we collected the daily death numbers of COVID-19, meteorological parameters and air pollutant data from 20 January 2020 to 29 February 2020 in Wuhan, China. Generalized additive model was applied to explore the effect of temperature, humidity and diurnal temperature range on the daily death counts of COVID-19. There were 2299 COVID-19 death counts in Wuhan during the study period. A positive association with COVID-19 daily death counts was observed for diurnal temperature range (r = 0.44), but negative association for relative humidity (r = −0.32). In addition, one unit increase in diurnal temperature range was only associated with a 2.92% (95% CI: 0.61%, 5.28%) increase in COVID-19 deaths in lag 3. However, both 1 unit increase of temperature and absolute humidity were related to the decreased COVID-19 death in lag 3 and lag 5, with the greatest decrease both in lag 3 [−7.50% (95% CI: −10.99%, −3.88%) and −11.41% (95% CI: −19.68%, −2.29%)]. In summary, this study suggests the temperature variation and humidity may also be important factors affecting the COVID-19 mortality.


title: Journey of cystatins from being mere thiol protease inhibitors to at heart of many pathological conditions

text: Abstract Cystatins are thiol proteinase inhibitors (TPI), present ubiquitously in animals, plants and micro-organisms. These are not merely inhibitors rather they are at heart of many pathological conditions ranging from diabetes to renal failure. These are essential for maintenance of protein balance of the cell; once this balance gets disturbed, it may lead to cell death. Thus, cystatins cannot be merely regarded as TPI’s as these have been found to play a pivotal role in tumorigenesis and neurodegenerative diseases. Many studies have reported the variation in cystatin level in incidences of different types of cancer; highlighting an important role played by these inhibitors in cancer development and progression. Cystatin C is increasingly replacing creatinine as a biomarker of glomerular filtration rate (GFR) thereby highlighting the importance of this important inhibitor. Some recent studies have also reported the interaction pattern of various anti-cancer drugs with cystatins in a bid to find how these drugs affect this important inhibitors and whether these drugs have any side effect on cystatins. Thus, in this growing disease era it can be said that cystatins are no more just inhibitors blocking the activity of thiol proteases rather they play a pivotal role in variety of pathological conditions.