title: Machine learning based approaches for detecting COVID-19 using clinical text data

text: Technology advancements have a rapid effect on every field of life, be it medical field or any other field. Artificial intelligence has shown the promising results in health care through its decision making by analysing the data. COVID-19 has affected more than 100 countries in a matter of no time. People all over the world are vulnerable to its consequences in future. It is imperative to develop a control system that will detect the coronavirus. One of the solution to control the current havoc can be the diagnosis of disease with the help of various AI tools. In this paper, we classified textual clinical reports into four classes by using classical and ensemble machine learning algorithms. Feature engineering was performed using techniques like Term frequency/inverse document frequency (TF/IDF), Bag of words (BOW) and report length. These features were supplied to traditional and ensemble machine learning classifiers. Logistic regression and Multinomial Naïve Bayes showed better results than other ML algorithms by having 96.2% testing accuracy. In future recurrent neural network can be used for better accuracy.


COVID-19 and social distancing


title: Influenza viruses and the evolution of avian influenza virus H5N1

text: Summary Although small in size and simple in structure, influenza viruses are sophisticated organisms with highly mutagenic genomes and wide antigenic diversity. They are species-specific organisms. Mutation and reassortment have resulted in newer viruses such as H5N1, with new resistance against anti-viral medications, and this might lead to the emergence of a fully transmissible strain, as occurred in the 1957 and 1968 pandemics. Influenza viruses are no longer just a cause of self-limited upper respiratory tract infections; the H5N1 avian influenza virus can cause severe human infection with a mortality rate exceeding 50%. The case death rate of H5N1 avian influenza infection is 20 times higher than that of the 1918 infection (50% versus 2.5%), which killed 675000 people in the USA and almost 40 million people worldwide. While the clock is still ticking towards what seems to be inevitable pandemic influenza, on April 17, 2007 the U.S. Food and Drug Administration (FDA) approved the first vaccine against the avian influenza virus H5N1 for humans at high risk. However, more research is needed to develop a more effective and affordable vaccine that can be given at lower doses.


title: Outbreak-Related Porcine Epidemic Diarrhea Virus Strains Similar to US Strains, South Korea, 2013

text: In late 2013, outbreaks of porcine epidemic diarrhea virus (PEDV) infection recurred in South Korea. Genetic and phylogenetic analyses showed that isolates from the outbreaks were most closely related to emergent US strains of PEDV. These US strain–like PEDV variants are prevalent in South Korea and responsible for recent outbreaks in the country.


title: Learning from the SARS outbreak

text: The appearance in south China and subsequent global epidemic of Sars in 2003, and its re-emergence this year, is focusing attention on the growing threat of animal diseases making the jump from their normal hosts to human populations. Nigel Williams reports.


title: Lessons from the Ebola Outbreak: Action Items for Emerging Infectious Disease Preparedness and Response

text: As the Ebola outbreak in West Africa wanes, it is time for the international scientific community to reflect on how to improve the detection of and coordinated response to future epidemics. Our interdisciplinary team identified key lessons learned from the Ebola outbreak that can be clustered into three areas: environmental conditions related to early warning systems, host characteristics related to public health, and agent issues that can be addressed through the laboratory sciences. In particular, we need to increase zoonotic surveillance activities, implement more effective ecological health interventions, expand prediction modeling, support medical and public health systems in order to improve local and international responses to epidemics, improve risk communication, better understand the role of social media in outbreak awareness and response, produce better diagnostic tools, create better therapeutic medications, and design better vaccines. This list highlights research priorities and policy actions the global community can take now to be better prepared for future emerging infectious disease outbreaks that threaten global public health and security.


title: Zwiesel bat banyangvirus, a potentially zoonotic Huaiyangshan banyangvirus (Formerly known as SFTS)–like banyangvirus in Northern bats from Germany

text: Bats are reservoir hosts for several emerging and re-emerging viral pathogens causing morbidity and mortality in wildlife, animal stocks and humans. Various viruses within the family Phenuiviridae have been detected in bats, including the highly pathogenic Rift Valley fever virus and Malsoor virus, a novel Banyangvirus with close genetic relation to Huaiyangshan banyangvirus (BHAV)(former known as Severe fever with thrombocytopenia syndrome virus, SFTSV) and Heartland virus (HRTV), both of which have caused severe disease with fatal casualties in humans. In this study we present the whole genome of a novel Banyangvirus, named Zwiesel bat banyangvirus, revealed through deep sequencing of the Eptesicus nilssonii bat virome. The detection of the novel bat banyangvirus, which is in close phylogenetic relationship with the pathogenic HRTV and BHAV, underlines the possible impact of emerging phenuiviruses on public health.


Allergic contact dermatitis caused by elastic bands from FFP2 mask


title: Functional assessment of cell entry and receptor usage for lineage B β-coronaviruses, including 2019-nCoV

text: Over the past 20 years, several coronaviruses have crossed the species barrier into humans, causing outbreaks of severe, and often fatal, respiratory illness. Since SARS- CoV was first identified in animal markets, global viromics projects have discovered thousands of coronavirus sequences in diverse animals and geographic regions. Unfortunately, there are few tools available to functionally test these novel viruses for their ability to infect humans, which has severely hampered efforts to predict the next zoonotic viral outbreak. Here we developed an approach to rapidly screen lineage B betacoronaviruses, such as SARS-CoV and the recent 2019-nCoV, for receptor usage and their ability to infect cell types from different species. We show that host protease processing during viral entry is a significant barrier for several lineage B viruses and that bypassing this barrier allows several lineage B viruses to enter human cells through an unknown receptor. We also demonstrate how different lineage B viruses can recombine to gain entry into human cells and confirm that human ACE2 is the receptor for the recently emerging 2019-nCoV.


Off-Site Radiology Workflow Changes Due to the COVID19 Pandemic


title: Endotracheal intubation with barrier protection

text: Given the high risk of healthcare worker (HCW) infection with COVID-19 during aerosol-generating medical procedures, the use of a box barrier during intubation for protection of HCWs has been examined. Previous simulation work has demonstrated its efficacy in protecting HCWs from cough-expelled droplets. Our objective was to assess its ability to protect HCWs against aerosols generated during aerosol-generating medical procedures. We used a battery-powered vapouriser to assess movement of vapour with: (1) no barrier; (2) a box barrier; and (3) a box barrier and a plastic sheet covering the box and patient’s body. We visualised the trajectory of vapour and saw that the vapour remained within the barrier space when the box barrier and plastic sheet were used. This is in contrast to the box barrier alone, where vapour diffused towards the feet of the patient and throughout the room, and to no barrier where the vapour immediately diffused to the laryngoscopist. This demonstrates that the box with the plastic sheet has the potential to limit the spread of aerosols towards the laryngoscopist, and thus may play a role in protecting HCWs during aerosol-generating medical procedures. This is of particular importance in the care of patients with suspected COVID-19.


title: Estimating Infection Attack Rates and Severity in Real Time during an Influenza Pandemic: Analysis of Serial Cross-Sectional Serologic Surveillance Data

text: BACKGROUND: In an emerging influenza pandemic, estimating severity (the probability of a severe outcome, such as hospitalization, if infected) is a public health priority. As many influenza infections are subclinical, sero-surveillance is needed to allow reliable real-time estimates of infection attack rate (IAR) and severity. METHODS AND FINDINGS: We tested 14,766 sera collected during the first wave of the 2009 pandemic in Hong Kong using viral microneutralization. We estimated IAR and infection-hospitalization probability (IHP) from the serial cross-sectional serologic data and hospitalization data. Had our serologic data been available weekly in real time, we would have obtained reliable IHP estimates 1 wk after, 1–2 wk before, and 3 wk after epidemic peak for individuals aged 5–14 y, 15–29 y, and 30–59 y. The ratio of IAR to pre-existing seroprevalence, which decreased with age, was a major determinant for the timeliness of reliable estimates. If we began sero-surveillance 3 wk after community transmission was confirmed, with 150, 350, and 500 specimens per week for individuals aged 5–14 y, 15–19 y, and 20–29 y, respectively, we would have obtained reliable IHP estimates for these age groups 4 wk before the peak. For 30–59 y olds, even 800 specimens per week would not have generated reliable estimates until the peak because the ratio of IAR to pre-existing seroprevalence for this age group was low. The performance of serial cross-sectional sero-surveillance substantially deteriorates if test specificity is not near 100% or pre-existing seroprevalence is not near zero. These potential limitations could be mitigated by choosing a higher titer cutoff for seropositivity. If the epidemic doubling time is longer than 6 d, then serial cross-sectional sero-surveillance with 300 specimens per week would yield reliable estimates when IAR reaches around 6%–10%. CONCLUSIONS: Serial cross-sectional serologic data together with clinical surveillance data can allow reliable real-time estimates of IAR and severity in an emerging pandemic. Sero-surveillance for pandemics should be considered. Please see later in the article for the Editors' Summary


title: Biosensors for Managing the COVID-19 Cytokine Storm: Challenges Ahead

text: [Image: see text] The global COVID-19 pandemic has oversaturated many intensive care units to the point of collapse, leading to enormous spikes in death counts. Before critical care becomes a necessity, identifying patients who are likely to become critically ill and providing prompt treatment is a strategy to avoid ICU oversaturation. There is a consensus that a hyperinflammatory syndrome or a “cytokine storm” is responsible for poor outcomes in COVID-19. Measuring cytokine levels at the point of care is required in order to better understand this process. In this Perspective, we summarize the main events behind the cytokine storm in COVID-19 as well as current experimental treatments. We advocate for a new biosensor-enabled paradigm to personalize the management of COVID-19 and stratify patients. Biosensor-guided dosing and timing of immunomodulatory therapies could maximize the benefits of these anti-inflammatory treatments while minimizing deleterious effects. Biosensors will also be essential in order to detect complications such as coinfections and sepsis, which are common in immunosuppressed patients. Finally, we propose the ideal features of these biosensors using some prototypes from the recent literature as examples. Multisensors, lateral flow tests, mobile biosensors, and wearable biosensors are seen as key players for precision medicine in COVID-19.


title: Virus-induced acute respiratory distress syndrome: Epidemiology, management and outcome

text: Summary The acute respiratory distress syndrome (ARDS) can be induced by viral diseases, with two virus types being responsible: respiratory viruses that cause community-acquired viral pneumonia and Herpesviridae that cause nosocomial viral pneumonia. Among the respiratory viruses that can affect the lung and cause ARDS, pandemic viruses head the list, with influenza viruses H5N1 and H1N1 2009 being the most recently identified. However, other viruses can cause severe ARDS. Notably, a novel coronavirus was responsible for the severe acute respiratory syndrome outbreak in 2003. Apart from these pandemic viruses, respiratory viruses are rarely responsible for viral pneumonia and ARDS. Other than antiviral drug (mainly oseltamivir) administration and avoidance of corticosteroids, management of ARDS due to these viruses does not differ from that for ARDS caused by other diseases. Among Herpesviridae, herpes simplex virus (HSV) and cytomegalovirus (CMV) are the two viruses causing nosocomial viral pneumonia that can evolve into ARDS. HSV is frequently recovered in the respiratory tract of mechanically ventilated patients and can sometimes be responsible for HSV bronchopneumonitis. Although not evaluated for this indication, acyclovir can be a therapeutic option for patients with HSV bronchopneumonitis and ARDS. CMV pneumonia can also occur in mechanically ventilated patients, but is difficult to diagnose because virus recovery does not necessarily mean viral disease. Ganciclovir can be considered for patients with ARDS and histology- or cytology-proven CMV pneumonia.


title: A six-year study on respiratory viral infections in a bull testing facility

text: Abstract Viral infection dynamics and bovine respiratory disease (BRD) treatment rates were studied over six years at a Swedish bull testing station with an ‘all in, all out’ management system. In August of each of the years 1998–2003, between 149 and 185 4–8-month-old calves arrived at the station from 99 to 124 different beef-breeding herds, and remained until March the following year. Only calves that tested free from bovine viral diarrhoea virus (BVDV) were allowed to enter the station and original animal groups were kept isolated from new cattle in their original herds for three weeks before admission. Although neither prophylactic antibiotics, nor BRD vaccines were used, less than 0.7–13.2% (mean 5%) of the calves (n =970) required treatment for BRD during the first five weeks following entry. This was probably due, at least in part, to the season (the summer months) when the animals were commingled. In the six-month period August–February, 38% of the animals were treated one or more times for BRD and mortality was 0.7%. Hereford and Aberdeen Angus calves had significantly higher treatment rates than Charolais, Simmental and Blonde d’Aquitaine. Serological testing on samples obtained in August, November and January indicated that bovine parainfluenza virus 3 (PIV-3) infections occurred each year before November after entry. Bovine coronavirus (BCoV) infections also occurred every year, but in 3/6 years this was not until after November. Bovine respiratory syncytial virus (BRSV) infections occurred only every second year and were associated with a treatment peak and one death on one occasion (December). The herd remained BVDV free during the entire study period. The infection patterns for PIV-3 and BCoV indicated a high level of infectivity amongst bovine calves, whereas the incidence for BRSV was observed at a lower level. Although the rearing of the animals differed from conventional beef production, the study has shown that commingling animals from many sources is not necessarily associated with high morbidity within the first few weeks after arrival. By preventing BRD soon after commingling the prerequisites for protective vaccination at entry might be improved. Applied management routines are discussed.


title: Pathophysiological Characteristics and Therapeutic Approaches for Pulmonary Injury and Cardiovascular Complications of Coronavirus Disease 2019

text: Abstract The pandemic of coronavirus disease 2019 (COVID-19) has emerged as a major health crisis, with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) having infected over a million people around the world within a few months of its identification as a human pathogen. Initially, SARS-CoV-2 infects cells in the respiratory system and causes inflammation and cell death. Subsequently, the virus spreads out and damages other vital organs and tissues, triggering a complicated spectrum of pathophysiological changes and symptoms, including cardiovascular complications. Acting as the receptor for SARS-CoV entering mammalian cells, angiotensin converting enzyme-2 (ACE2) plays a pivotal role in the regulation of cardiovascular cell function. Diverse clinical manifestations and laboratory abnormalities occur in patients with cardiovascular injury in COVID-19, characterizing the development of this complication, as well as providing clues to diagnosis and treatment. This review provides a summary of the rapidly appearing laboratory and clinical evidence for the pathophysiology and therapeutic approaches to COVID-19 pulmonary and cardiovascular complications.


May early intervention with intravenous immunoglobulin pose a potentially successful treatment for Ebola virus infection?


title: Characterization and pathogenicity of a novel mammalian orthoreovirus from wild short-nosed fruit bats

text: Abstract Mammalian orthoreoviruses (MRVs) have a wide range of geographic distribution and have been isolated from humans and various animals. This study describes the isolation, molecular characterization and analysis of pathogenicity of MRV variant B/03 from wild short-nosed fruit bats. Negative stain electron microscopy illustrated that the B/03 strain is a non-enveloped icosahedral virus with a diameter of 70nm. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) migration patterns showed that the B/03 viral genome contains 10 segments in a 3:3:4 arrangement. The isolate belongs to MRV serotype 1 based on S1 gene nucleotide sequence data. BALB/c mice experimentally infected with B/03 virus by intranasal inoculation developed severe respiratory distress with tissue damage and inflammation. Lastly, B/03 virus has an increased transmission risk between bats and humans or animals.


title: Feline Infectious Diarrhea

text: This article reviews the common infectious causes of diarrhea in cats and discusses selected diseases in greater depth. A systematic approach to a cat with possible infectious diarrhea is presented, along with a detailed description of the best way to perform an in-house fecal examination. The goal here is to provide the reader with a logical list of differentials and the information necessary to pursue a diagnosis in an efficient manner.


title: The Impact of Emerging Infectious Diseases on Chinese Blood Safety

text: Abstract Emerging infectious diseases (EIDs) have always been one of the major threats to public health. Although the implementation of mandatory testing for 4 classical transfusion-transmitted infectious—human immunodeficiency virus, hepatitis B virus, hepatitis C virus, and syphilis—has reduced the transfusion risk of these pathogens, the potential threat of various EID agents and their constantly evolving variants to blood safety in China is not fully understood. This review presents 9 representative EID agents that are autochthonous and epidemic nationally or regionally in China. The epidemiologic status and distribution of these EID agents among donors and/or healthy populations are summarized. The potential risks of these EID agents to blood safety are discussed. The review also explores strategies to strengthen hemovigilance systems and studies to further evaluate the impact of EID agents on blood safety.


title: RNA respiratory viral infections in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

text: These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of RNA respiratory viral infections in the pre‐ and post‐transplant period. Viruses reviewed include influenza, respiratory syncytial virus (RSV), parainfluenza, rhinovirus, human metapneumovirus (hMPV), and coronavirus. Diagnosis is by nucleic acid testing due to improved sensitivity, specificity, broad range of detection of viral pathogens, automatization, and turnaround time. Respiratory viral infections may be associated with acute rejection and chronic lung allograft dysfunction in lung transplant recipients. The cornerstone of influenza prevention is annual vaccination and in some cases antiviral prophylaxis. Treatment with neuraminidase inhibitors and other antivirals is reviewed. Prevention of RSV is limited to prophylaxis with palivizumab in select children. Therapy of RSV upper or lower tract disease is controversial but may include oral or aerosolized ribavirin in some populations. There are no approved vaccines or licensed antivirals for parainfluenza, rhinovirus, hMPV, and coronavirus. Potential management strategies for these viruses are given. Future studies should include prospective trials using contemporary molecular diagnostics to understand the true epidemiology, clinical spectrum, and long‐term consequences of respiratory viruses as well as to define preventative and therapeutic measures.


title: Middle East respiratory syndrome coronavirus intermittent positive cases: Implications for infection control

text: BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) continues to be reported from the Kingdom of Saudi Arabia. Data on the phenomenon of intermittent positive results for MERS-CoV on reverse-transcription polymerase chain reaction (RT-PCR) with negative results in between are lacking. Here we describe cases with intermittent positive MERS-CoV test results and highlight the required number of tests to rule out or rule in MERS-CoV infection based on a large retrospective cohort of patients with confirmed MERS-CoV. METHODS: This analysis included cases admitted between January 2014 and December 2017. The included patients had a minimum of 3 nasopharyngeal MERS-CoV RT-PCR tests for confirmation and needed 2 negative samples for MERS-CoV evaluated 48 hours apart with clinical improvement or stabilization apart to ensure clearance. RESULTS: A total of 408 patients with positive MERS-CoV test results were treated at the referring hospital. We excluded 72 patients who had only 1 swab result available in the system and were treated in the initial years of the disease. Of the remaining 336 patients, 300 (89%) had a positive result after 1 swab, 324 (96.5%) had a positive result after 2 consecutive swabs, and 328 (97.6%) had a positive result after 3 consecutive swabs. Of the total cases, 46 (13.7%) had a positive MERS-CoV test then a negative test, followed by positive test results. CONCLUSIONS: Our data indicate that 2 to 3 nasopharyngeal samples are needed to produce the highest yield of positive results for MERS-CoV. In addition, 2 negative results 48 hours apart with clinical improvement or stabilization are needed to clear patients from MERS-CoV. Evaluation of the yield of sputum samples is needed to assess the effectiveness against nasopharyngeal swabs.


title: Coronavirus Disease 2019 (COVID-19) Spread and Pharmacovigilance Implications: Expert Opinion

text: The Coronavirus Disease 2019 (COVID-19) is rapidly spreading throughout the world after emerging in China in December 2019. Currently, there are no approved treatments for COVID-19 based on large clinical trial data, and hence, management involves infection prevention and control measures and supportive care. With anecdotal reports and in vitro studies suggesting that certain medicines already in use for treatment of other conditions could be viable treatment options, there has been an increased demand for these therapies which could have adverse consequences on patients and healthcare systems. Toxicity from these medicines resulting from a mad rush for them at community pharmacies and pressure on physicians to prescribe for individuals who do not have the infection are worth noting. Furthermore, the indiscriminate use of these medicines could result in viral resistance as well as acute shortage such that patients who routinely take them for other conditions may not get them.


title: A compendium of reviews in biochemistry and molecular biology published in the second half of 1991

text: Abstract 1. 1. A compendium of reviews and mini-reviews in Biochemistry and Molecular Biology published in the second half of 1991 is presented. In all 880 titles are listed from 108 different publications. 2. 2. This compendium presents the references by Journal Name-the most suitable format for a hardcopy of this information. Keywords have been included with each reference to increase the value of the collection. Keyword and author cross-reference indexes are not included but are available in the electronic database from which this version was constructed. Should anyone wish to have this information in electronic form it can be distributed on MS-DOS formatted flopppy disks in either Reference Manager or Medline format. The author should be contacted for details of the number of pre-formatted floppy disks required.


title: Impact of the COVID‐19 outbreak on acute stroke pathways – insights from the Alsace region in France

text: BACKGROUND AND PURPOSE: To date, no study has attempted to quantify the impact of the COVID‐19 outbreak on the incidence and treatment of acute stroke. METHODS: This was a retrospective review of acute stroke pathway parameters in all three stroke units in the Alsace region during the first month of the outbreak (1–31 March 2020), using the similar period from 2019 as a comparator. A secondary detailed analysis of all stroke alerts and stroke unit admissions was performed in the centre with the largest case volume. RESULTS: Compared to the same period in 2019, in March 2020 there were 39.6% fewer stroke alerts and 33.3% fewer acute revascularization treatments [40.9% less intravenous thrombolysis (IVT) and 27.6% less mechanical thrombectomy (MT)]. No marked variation was observed in the number of stroke unit admissions (−0.6%). The proportion of patients with acute revascularization treatments (IVT or MT) out of the total number of stroke unit admissions was significantly lower in March 2020 (21.3%) compared to 2019 (31.8%), P = 0.034. There were no significant differences in time delays or severity of clinical symptoms for patients treated by IVT or MT, nor in the distribution of final diagnosis amongst stroke alerts and stroke unit admissions. CONCLUSION: These results suggest that the overall incidence of stroke remained the same, but fewer patients presented within the therapeutic time window. Increased public awareness and corrective measures are needed to mitigate the deleterious effects of the COVID‐19 outbreak on acute stroke care.


title: Anesthetic agents affect urodynamic parameters and anesthetic depth at doses necessary to facilitate preclinical testing in felines

text: Urodynamic studies, used to understand bladder function, diagnose bladder disease, and develop treatments for dysfunctions, are ideally performed with awake subjects. However, in animal models, especially cats (a common model of spinal cord injury and associated bladder pathology), anesthesia is often required for these procedures and can be a research confounder. This study compared the effects of select agents (dexmedetomidine, alfaxalone, propofol, isoflurane, and α-chloralose) on urodynamic (Δpressure, bladder capacity, bladder compliance, non-voiding contractions, bladder pressure slopes) and anesthetic (change in heart rate [ΔHR], average heart rate [HR], reflexes, induction/recovery times) parameters in repeated cystometrograms across five adult male cats. Δpressure was greatest with propofol, bladder capacity was highest with α-chloralose, non-voiding contractions were greatest with α-chloralose. Propofol and dexmedetomidine had the highest bladder pressure slopes during the initial and final portions of the cystometrograms respectively. Cats progressed to a deeper plane of anesthesia (lower HR, smaller ΔHR, decreased reflexes) under dexmedetomidine, compared to propofol and alfaxalone. Time to induction was shortest with propofol, and time to recovery was shortest with dexmedetomidine. These agent-specific differences in urodynamic and anesthetic parameters in cats will facilitate appropriate study-specific anesthetic choices.


title: Pharmacological Therapeutics Targeting RNA-Dependent RNA Polymerase, Proteinase and Spike Protein: From Mechanistic Studies to Clinical Trials for COVID-19

text: An outbreak of novel coronavirus-related pneumonia COVID-19, that was identified in December 2019, has expanded rapidly, with cases now confirmed in more than 211 countries or areas. This constant transmission of a novel coronavirus and its ability to spread from human to human have prompted scientists to develop new approaches for treatment of COVID-19. A recent study has shown that remdesivir and chloroquine effectively inhibit the replication and infection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, 2019-nCov) in vitro. In the United States, one case of COVID-19 was successfully treated with compassionate use of remdesivir in January of 2020. In addition, a clinically proven protease inhibitor, camostat mesylate, has been demonstrated to inhibit Calu-3 infection with SARS-CoV-2 and prevent SARS-2-spike protein (S protein)-mediated entry into primary human lung cells. Here, we systemically discuss the pharmacological therapeutics targeting RNA-dependent RNA polymerase (RdRp), proteinase and S protein for treatment of SARS-CoV-2 infection. This review should shed light on the fundamental rationale behind inhibition of SARS-CoV-2 enzymes RdRp as new therapeutic approaches for management of patients with COVID-19. In addition, we will discuss the viability and challenges in targeting RdRp and proteinase, and application of natural product quinoline and its analog chloroquine for treatment of coronavirus infection. Finally, determining the structural-functional relationships of the S protein of SARS-CoV-2 will provide new insights into inhibition of interactions between S protein and angiotensin-converting enzyme 2 (ACE2) and enable us to develop novel therapeutic approaches for novel coronavirus SARS-CoV-2.


title: Rabies DNA vaccine: No impact of MHC Class I and Class II targeting sequences on immune response and protection against lethal challenge

text: Rabies is progressive fatal encephalitis. WHO estimates 55,000 rabies deaths and more than 10 million PEP every year world-wide. A variety of cell-culture derived vaccines are available for prophylaxis against rabies. However, their high cost restricts their usage in developing countries, where such cases are most often encountered. This is driving the quest for newer vaccine formulations; DNA vaccines being most promising amongst them. Here, we explored strategies of antigen trafficking to various cellular compartments aiming at improving both humoral and cellular immunity. These strategies include use of signal sequences namely Tissue Plasminogen Activator (TPA), Ubiquitin (UQ) and Lysosomal-Associated Membrane Protein-1 (LAMP-1). TPA, LAMP-1 and their combination were aimed at enhancing the CD4(+) T cell and antibody response. In contrast, the UQ tag was utilized for enhancing CD8(+) response. The potency of modified DNA vaccines assessed by total antibody response, antibody isotypes, cytokine profile, neutralizing antibody titer and protection conferred against in vivo challenge; was enhanced in comparison to native unmodified vaccine, but the response elicited did not pertain to the type of target sequence and the directed arm of immunity. Interestingly, the DNA vaccines that had been designed to generate different type of immune responses yielded in effect similar response. In conclusion, our data indicate that the directing target sequence is not the exclusive deciding factor for type and extent of immune response elicited and emphasizes on the antigen dependence of immune enhancement strategies.


title: Anti-TNF-α therapy does not ameliorate disease in a model of acute virus-endotoxin mediated respiratory disease in pigs

text: Tumour necrosis factor-α (TNF-α) has been shown to play a role in many inflammatory conditions. Currently anti-TNF-α drugs (e.g. etanercept) are used in humans for treatment of autoimmune diseases. In this study we aimed to elucidate the role of TNF-α in the development of virus-endotoxin-induced respiratory disease. Twenty-two caesarean derived colostrum deprived pigs were used. Initially, the availability in the lungs and circulation, and possible clinical and inflammatory effects of etanercept alone were assessed in 4 pigs after intratracheal and intraperitoneal administration of 0.5 mg/per route/per pig. High anti-TNF-α activity was detected in bronchoalveolar lavage (BAL) fluids, peritoneal lavage fluids and serum of all animals for at least 8 hours post inoculation (HPI). No clinical symptoms, lung lesions, lung cell infiltration or induction of IFN-α, IL-1, IL-6, IL-12 and TNF-α in BAL were detected. Subsequently, the ability of etanercept to block porcine TNF-α and its effect on the above mentioned parameters and on lung virus titres were assessed in 8 pigs. They were inoculated intratracheally with porcine respiratory coronavirus (PRCV) followed by lipopolysaccharide (LPS) 24 hours later. Etanercept was administered at the time of LPS inoculation via the same routes and dose as in the initial experiment. The parameters were compared with a control group (n=8), receiving only PRCV-LPS. Half of the animals from each group were euthanized at 4 and the rest at 8 hours after LPS inoculation. TNF-α was completely neutralized in 3 of the 4 animals euthanized at 4 HPI and significantly lower than in the PRCV-LPS group at all times. No significant differences in disease severity, lung lesions, virus replication, lung cell infiltration or levels of IFN-α, IL-1, IL-6 and IL-12/IL-23 were observed between the two groups. Blocking of TNF-α alone was not sufficient to ameliorate disease in the PRCV-LPS model of respiratory disease, possibly due to the redundancy in the proinflammatory cytokine cascade, or the involvement of other unidentified disease mediators.


title: Modeling the dynamics of novel coronavirus (2019-nCov) with fractional derivative

text: Abstract The present paper describes the mathematical modeling and dynamics of a novel corona virus (2019-nCoV). We describe the brief details of interaction among the bats and unknown hosts, then among the peoples and the infections reservoir (seafood market). The seafood marked are considered the main source of infection when the bats and the unknown hosts (may be wild animals) leaves the infection there. The purchasing of items from the seafood market by peoples have the ability to infect either asymptomatically or symptomatically. We reduced the model with the assumptions that the seafood market has enough source of infection that can be effective to infect people. We present the mathematical results of the model and then formulate a fractional model. We consider the available infection cases for January 21, 2020, till January 28, 2020 and parameterized the model. We compute the basic reproduction number for the data is R 0 ≈ 2.4829 . The fractional model is then solved numerically by presenting many graphical results, which can be helpful for the infection minimization.


title: Psychological Symptoms During the Two Stages of Lockdown in Response to the COVID-19 Outbreak: An Investigation in a Sample of Citizens in Northern Spain

text: Spain has been in a state of emergency since 14th March due to the COVID-19 crisis. This state of emergency means that the population must comply with strict rules such as lockdown (confinement to their homes except for essential trips) and social distancing. The aim of this study was to examine the psychological state of the general population in a sample recruited in Northern Spain. Sociodemographic and psychological data were gathered, assessing variables such as stress, anxiety, and depression. A questionnaire was administered at the beginning of the lockdown and three weeks later. The sample was recruited using an online questionnaire by means of a non-probabilistic snowball sampling methodology. A total of 1,933 people participated in this study. The results reveal that more than a quarter of the participants have reported symptoms of depression (27.5%), anxiety (26.9%) and stress (26.5%) and as the time spent in lockdown has progressed, psychological symptoms have risen. In relation to gender, data indicate that men have higher levels of depression than women, and similar levels of anxiety and stress. Greater symptomatology has also been found among the younger population and in people with chronic diseases. We discuss the need to continue carrying out these types of studies to prevent and treat psychological problems that could emerge amidst this pandemic.


title: Antiviral immunity in crustaceans

text: Abstract Viral diseases of shrimp have caused negative effects on the economy in several countries in Asia, South America and America, where they have numerous shrimp culture industries. The studies on the immunity of shrimp and other crustaceans have mainly focused on general aspects of immunity and as a consequence little is known about the antiviral responses in crustaceans. The aim of this review is to update recent knowledge of innate immunity against viral infections in crustaceans. Several antiviral molecules have been isolated and characterized recently from decapods. Characterization and identification of these molecules might provide a promising strategy for protection and treatment of these viral diseases. In addition dsRNA-induced antiviral immunity is also included.


title: Recommendations from workshops of the second international feline coronavirus/feline infectious peritonitis symposium

text: Abstract In August 2002, scientists and veterinarians from all over the world met in Scotland to discuss feline coronavirus (FCoV) and feline infectious peritonitis (FIP). The conference ended with delegates dividing into three workshops to draw up recommendations for FCoV control, diagnosis and treatment and future research. The workshops were chaired by the three authors and the recommendations are presented in this paper.


title: Conducting Clinical Research During the COVID-19 Pandemic: Investigator and Participant Perspectives

text: As the medical landscape changes daily with the coronavirus disease (COVID-19) pandemic, clinical researchers are caught off-guard and are forced to make decisions on research visits in their ongoing clinical trials. Although there is some guidance from local and national organizations, the principal investigator (PI) is ultimately responsible for determining the risk-benefit ratio of conducting, rescheduling, or cancelling each research visit. The PI should take into consideration the ethical principles of research, local/national guidance, the community risk of the pandemic in their locale, staffing strain, and the risk involved to each participant, to ultimately decide on the course of action. While balancing the rights and protection of the human subject, we seldom examine patients’ views and opinions about their scheduled research visit(s). This article discusses the ethical principles of beneficence and autonomy in helping the decision-making process. We discuss ways to weigh-in local and national guidance, staffing strain, and institutional support into the decision-making process and outline potential changes needed for regulatory bodies depending on the decision. Further, we discuss the need to weigh-in the individual risk-benefit ratio for each participant and present a decision tree to navigate this complex process. Finally, we examine participant and caregiver perspectives on their fears, sense of preparedness, and factors that they consider before deciding whether to keep or postpone the research appointments. This entry also provides PIs ways to support their research participants in both scenarios, including provision of psychological support.


title: Données de vie réelle et Covid 19: la troisième voie

text: Abstract The analysis of real-life data from hospital information systems could make possible to decide on the efficacy and safety of covid19 treatments by avoiding the pitfalls of preliminary studies and randomized clinical trials. The different drugs tested in current clinical trials are already widely prescribed to patients by doctors in hospitals, and can therefore be immediately analysed according to validated methodological standards.


title: 56 Fever in Returned Travelers

text: Abstract Predominant causes of fever vary by different geographic areas of exposure. Malaria is the most common overall cause of systemic febrile illness in travelers returning from tropical areas; dengue is the most common cause in travelers to some regions. The approach to a febrile patient must consider travel and exposure history, incubation period, mode of exposure, and impact of pretravel vaccination. Initial symptoms of self-limited and life-threatening infections may be similar; focal signs and symptoms can help to limit the differential diagnosis. Routine laboratory results can provide clues to the final diagnosis.


title: Bilan étiologique de 403 gastro-entérites aiguës infantiles. Intérêt de la numération des leucocytes dans les selles

text: Summary Etiological agents of 403 acute infantile gastroenteritis were inventoried during a three years period. During the last 18 months, qualitative and quantitative evaluation of leukocytes in stools was tried. This examination correlates with the supposed causative agent of diarrhea. Therefore, we insist on difficulties of this test : some discordant examples are described. Leukocytes numeration must be performed by experienced technician. Stools must be very liquid and well homogeneized.


title: Optimizing Health Care Environmental Hygiene

text: This article presents a review and perspectives on aspects of optimizing health care environmental hygiene. The topics covered include the epidemiology of environmental surface contamination, a discussion of cleaning health care patient area surfaces, an overview of disinfecting health care surfaces, an overview of challenges in monitoring cleaning versus cleanliness, a description of an integrated approach to environmental hygiene and hand hygiene as interrelated disciplines, and an overview of the research opportunities and challenges related to health care environmental hygiene.


title: Changes in Police Calls for Service During the Early Months of the 2020 Coronavirus Pandemic

text: The coronavirus pandemic poses multiple challenges for policing, including the need to continue responding to calls from the public. Several contingency plans warned police to expect a large and potentially overwhelming increase in demand from the public during a pandemic, but (to the author’s knowledge) there is no empirical work on police demand during a major public health emergency. This study used calls-for-service data from 10 large cities in the USA to analyse how calls for service changed during the early months of the 2020 COVID-19 outbreak, compared to forecasts of call volume based on data from previous years. Contrary to previous warnings, overall the number of calls went down during the early weeks of the pandemic. There were substantial reductions in specific call types, such as traffic collisions, and significant increases in others, such as calls to dead bodies. Other types of calls, particularly those relating to crime and order maintenance, continued largely as before. Changes in the frequency of different call types present challenges to law enforcement agencies, particularly since many will themselves be suffering from reduced staffing due to the pandemic. Understanding changes to calls in detail will allow police leaders to put in place evidence-based plans to ensure they can continue to serve the public.


title: China, Hong Kong and Taiwan, Health Systems of

text: This article describes how health care has been and is currently financed, organized, and delivered in China, Hong Kong, and Taiwan. Each system's performance is assessed on the equity and efficiency axes in terms of how well it deals with important market failures. We conclude by drawing comparative lessons and showing how policymakers are trying or might attempt to rise up to and overcome key challenges.


title: Early Biomarkers of Inflammation in Dogs and Cats: The Acute Phase Proteins

text: Paltrinieri, S., 2007. Early biomarkers of inflammation in dogs and cats: the acute phase proteins. Veterinary Research Communications, 31(Suppl. 1), 125–129


title: Preparation of recombinant vaccines

text: Abstract Vaccination is one of the most efficient ways to eradicate some infectious diseases in humans and animals. The material traditionally used as vaccines is attenuated or inactivated pathogens. This approach is sometimes limited by the fact that the material for vaccination is not efficient, not available, or generating deleterious side effects. A possible theoretical alternative is the use of recombinant proteins from the pathogens. This implies that the proteins having the capacity to vaccinate have been identified and that they can be produced in sufficient quantity at a low cost. Genetically modified organisms harboring pathogen genes can fulfil these conditions. Microorganisms, animal cells as well as transgenic plants and animals can be the source of recombinant vaccines. Each of these systems that are all getting improved has advantages and limits. Adjuvants must generally be added to the recombinant proteins to enhance their vaccinating capacity. This implies that the proteins used to vaccinate have been purified to avoid any immunization against the contaminants. The efficiency of a recombinant vaccine is poorly predictable. Multiple proteins and various modes of administration must therefore be empirically evaluated on a case-by-case basis. The structure of the recombinant proteins, the composition of the adjuvants and the mode of administration of the vaccines have a strong and not fully predictable impact on the immune response as well as the protection level against pathogens. Recombinant proteins can theoretically also be used as carriers for epitopes from other pathogens. The increasing knowledge of pathogen genomes and the availability of efficient systems to prepare large amounts of recombinant proteins greatly facilitate the potential use of recombinant proteins as vaccines. The present review is a critical analysis of the state of the art in this field.


title: Rationnel pour le traitement antibiotique des infections bronchiques aiguës

text: Summary Acute bronchitis in healthy patient in mainly related to virus. Intra-cellular bacteria, Mycoplasma pneumonia are rarely involved. For these reasons, macrolides or cyclines (except for children) are justified in first line treatment. For patients with acute exacerbation of chronic bronchitis, the choice of the treatment needs to be discuss. At the initial stage, most of the pathogens involved are those of acute bronchitis. Antibiotic is only prescribes for the prevention of a superinfection; this kind of prophylaxis has to be evaluated. Few days after, histological due to modifications of bronchi, a superinfection can occur which needs a curative treatment. In most of the data reported the literature, there is no distinction between the two periods of the disease. It is interesting to point out that associated treatments such as kinesitherapy, corticosteroids can modify the natural course of bronchitis. There are not evaluated as associated treatment in the different clinical trials.


title: Development of a nasal spray containing xylometazoline hydrochloride and iota-carrageenan for the symptomatic relief of nasal congestion caused by rhinitis and sinusitis

text: INTRODUCTION: Xylometazoline hydrochloride (HCl) is a nasal decongestant that causes vasoconstriction in the nasal submucosa. It has been used for more than 50 years for the treatment of nasal congestion caused by rhinitis/sinusitis. Iota-carrageenan is effective against a broad variety of respiratory viruses, which are the most common cause of infections of the upper respiratory tract. Therefore, it is used as the active component in the antiviral nasal spray Coldamaris prophylactic (1.2 mg/mL iota-carrageenan in 0.5% NaCl) and other medical device nasal sprays that are approved and marketed in the EU. Recently, we developed a nasal spray formulation containing both xylometazoline HCl (0.05%) and iota-carrageenan (0.12%) that provides decongestion and antiviral protection of the nasal mucosa at the same time. RESULTS: A set of in vitro experiments revealed that the vasoconstrictive properties of xylometazoline HCl and the antiviral effectiveness of iota-carrageenan against human rhinovirus (hRV) 1a, hRV8 and human coronavirus OC43 were maintained in the formulation containing these two compounds. Permeation experiments using bovine nasal mucosa showed that iota-carrageenan had no significant influence on the permeation of xylometazoline HCl. Finally, in the local tolerance and toxicity study, it was shown that the formulation was well tolerated at the application site with no occurrence of erythema or edema in the nostrils of all rabbits or any signs of toxicity in any of the organs and tissues inspected. CONCLUSION: Investigations on compatibility of xylometazoline HCl and iota-carrageenan demonstrated that the substances do not influence each other, allowing both to fulfill their known specific clinical efficacy (xylometazoline HCl) and effectiveness (iota-carrageenan).


title: Genome characterization, antigenicity and pathogenicity of a novel infectious bronchitis virus type isolated from south China

text: Abstract In 2014, three infectious bronchitis virus (IBV) strains, designated as γCoV/ck/China/I0111/14, γCoV/ck/China/I0114/14 and γCoV/ck/China/I0118/14, were isolated and identified from chickens suspected to be infected with IBV in Guangxi province, China. Based upon data arising from S1 sequence and phylogenetic analyses, the three IBV isolates were genetically different from other known IBV types, which represented a novel genotype (GI-29). Virus cross-neutralization tests, using γCoV/ck/China/I0111/14 as a representative, showed that genotype GI-29 was antigenically different from all other known IBV types, thus representing a novel serotype. Complete genomic analysis showed that GI-29 type viruses were closely related to and might originate from a GX-YL5-like virus by accumulation of substitutions in multiple genes. These GI-29 viral genomes are still evolving and diverging, particularly in the 3′ region, although we cannot rule out the possibility of recombination events occurring. For isolate γCoV/ck/China/I0114/14, we found that recombination events had occurred between nsps 2 and 3 in gene 1 which led to the introduction of a 4/91 gene fragment into the γCoV/ck/China/I0114/14 viral genome. In addition, we found that the GI-29 type γCoV/ck/China/I0111/14 isolate was a nephropathogenic strain and high pathogenic to 1-day-old specific pathogen-free (SPF) chickens although cystic oviducts were not observed in the surviving layer chickens challenged with γCoV/ck/China/I0111/14 isolate.


title: Children hospitalized with rhinovirus bronchiolitis have asthma-like characteristics

text: Children with bronchiolitis often are considered a homogeneous group. However, in a multicenter, prospective study of 2,207 young children hospitalized for bronchiolitis, we found that children with respiratory syncytial virus detected differ from those with rhinovirus detected; the latter patients resemble older children with asthma, including more frequent treatment with corticosteroids.


A tribute to frontline corona warriors––Doctors who sacrificed their life while saving patients during the ongoing COVID-19 pandemic


title: Targeting and retention of HPV16 E7 to the endoplasmic reticulum enhances immune tumour protection

text: The endoplasmic reticulum (ER) is where the major histocompatibility complex (MHC) class I molecules are loaded with epitopes to cause an immune cellular response. Most of the protein antigens are degraded in the cytoplasm to amino acids and few epitopes reach the ER. Antigen targeting of this organelle by Calreticulin (CRT) fusion avoids this degradation and enhances the immune response. We constructed a recombinant adenovirus to express the E7 antigen with an ER-targeting signal peptide (SP) plus an ER retention signal (KDEL sequence). In cell-culture experiments we demonstrated that this new E7 antigen, SP-E7-KDEL, targeted the ER. Infection of mice with this recombinant adenovirus that expresses SP-E7-KDEL showed interferon induction and tumour-protection response, similar to that provided by an adenovirus expressing the E7 antigen fused to CRT. This work demonstrated that just by adding a SP and the KDEL sequence, antigens can be targeted and retained in the ER with a consequent enhancement of immune response and tumour protection. These results will have significant clinical applications.


title: Airline networks and the international diffusion of severe acute respiratory syndrome (SARS)

text: In fewer than four months in 2003, severe acute respiratory syndrome (SARS) spread from China to 25 countries and Taiwan, becoming the first new, easily transmissible infectious disease of the twenty‐first century. The role of air transport in the diffusion of the disease became obvious early in the crisis; to assess that role more carefully, this study relates the spatial‐temporal pattern of the SARS outbreak to a measure of airline network accessibility. Specifically, the accessibility from those countries that were infected by SARS, beginning with China, to other countries was measured using airline schedules. The country‐pair accessibility measure, along with other country‐level factors relevant to the disease, were tested as determinants of the speed with which SARS arrived in infected countries as well as its failure to arrive in most countries. The analyses indicate that airline network accessibility was an especially influential variable but also that the importance of this variable diminished in the latter weeks of the outbreak. The latter finding is partly attributable to public health measures, particularly health screening in airports. The timing and geography of those measures are reviewed using data from media reports and interim World Health Organization (WHO) documents during the outbreak. The uneven effort to curtail the international diffusion of SARS suggests further planning is needed to develop a concerted response to contain future epidemics.


title: Clinical Time Features and Chest Imaging of 85 Patients With COVID-19 in Zhuhai, China

text: Background: An outbreak of SARS-CoV-2 infections began in Wuhan, China, and quickly spread to the entire country. We sought to delineate the time features of clinical symptoms, virological conversion, and chest radiological abnormalities in individuals infected with this virus in Zhuhai, China. Methods: In this retrospective study, we assessed 85 confirmed cases of COVID-19 in the Fifth Hospital of Sun Yat-sen University, Zhuhai, from the 17th of January to the 11th of February 2020. Outcomes were followed up until the 24th of February 2020. Results: The median age of the 85 patients with COVID-19 was 43 years (range, 1–80); 56.5% (48/85) were female. The median time from the last known contact to the first SARS-CoV-2 positive test result was 8 days (0–18). The time to throat swab negativity for SARS-CoV-2 ranged from 5 to 36 days after illness onset. Patients with abnormal chest imaging findings on admission were older than those with normal imaging findings (median age, 50 [3-80] vs. 37 [1-69], P = 0.031). Among patients with lung changes on admission, the risk of lesions was 13.8 times greater in the left lower lobe than in the right middle lobe. Most lung lesions appeared within 2 weeks of onset (median 4–5 days). The overall rates of lesions in the right upper/middle/lower lobe and left upper/lower lobe were 47.1, 30.6, 62.4% as well as 49.4 and 63.5%, respectively. Conclusions: The incubation period of SARS-CoV-2 may be longer than 14 days; thus, medical surveillance after contact is required for longer than this. The predominant sites of lung lesions are both lower lungs, whereas the lowest risk region is the right middle lobe.


title: Pathophysiology of Clinical Symptoms in Acute Viral Respiratory Tract Infections

text: In this article we discuss the pathophysiology of common symptoms of acute viral respiratory infections (e.g., sneezing, nasal discharge, sore throat, cough, muscle pains, malaise, and mood changes). Since clinical symptoms are not sufficient to determine the etiology of viral respiratory tract infections, we believe that the host defense mechanisms are critical for the symptomatology. Consequently, this review of literature is focused on the pathophysiology of respiratory symptoms regardless of their etiology. We assume that despite a high prevalence of symptoms of respiratory infection, their pathogenesis is not widely known. A better understanding of the symptoms’ pathogenesis could improve the quality of care for patients with respiratory tract infections.


title: Evidence that high temperatures and intermediate relative humidity might favor the spread of COVID-19 in tropical climate: A case study for the most affected Brazilian cities

text: Abstract This study aimed to analyze how meteorological conditions such as temperature, humidity and rainfall can affect the spread of COVID-19 in five Brazilian (São Paulo, Rio de Janeiro, Brasília, Manaus and Fortaleza) cities. The cities selected were those with the largest number of confirmed cases considering data of April 18. Variables such as number of cumulative cases, new daily cases and contamination rate were employed for this study. Our results showed that higher mean temperatures and average relative humidity favored the COVID-19 transmission, differently from reports from coldest countries or periods of time under cool temperatures. Thus, considering the results obtained, intersectoral policies and actions are necessary, mainly in cities where the contamination rate is increasing rapidly. Thus, prevention and protection measures should be adopted in these cities aiming to reduce transmission and the possible collapse of the health system.


title: LIVE@Home.Path—innovating the clinical pathway for home-dwelling people with dementia and their caregivers: study protocol for a mixed-method, stepped-wedge, randomized controlled trial

text: BACKGROUND: The global health challenge of dementia is exceptional in size, cost and impact. It is the only top ten cause of death that cannot be prevented, cured or substantially slowed, leaving disease management, caregiver support and service innovation as the main targets for reduction of disease burden. Institutionalization of persons with dementia is common in western countries, despite patients preferring to live longer at home, supported by caregivers. Such complex health challenges warrant multicomponent interventions thoroughly implemented in daily clinical practice. This article describes the rationale, development, feasibility testing and implementation process of the LIVE@Home.Path trial. METHODS: The LIVE@Home.Path trial is a 2-year, multicenter, mixed-method, stepped-wedge randomized controlled trial, aiming to include 315 dyads of home-dwelling people with dementia and their caregivers, recruited from 3 municipalities in Norway. The stepped-wedge randomization implies that all dyads receive the intervention, but the timing is determined by randomization. The control group constitutes the dyads waiting for the intervention. The multicomponent intervention was developed in collaboration with user-representatives, researchers and stakeholders to meet the requirements from the national Dementia Plan 2020. During the 6-month intervention period, the participants will be allocated to a municipal coordinator, the core feature of the intervention, responsible for regular contact with the dyads to facilitate L: Learning, I: Innovation, V: Volunteering and E: Empowerment (LIVE). The primary outcome is resource utilization. This is measured by the Resource Utilization in Dementia (RUD) instrument and the Relative Stress Scale (RSS), reflecting that resource utilization is more than the actual time required for caring but also how burdensome the task is experienced by the caregiver. DISCUSSION: We expect the implementation of LIVE to lead to a pathway for dementia treatment and care which is cost-effective, compared to treatment as usual, and will support high-quality independent living, at home. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04043364. Registered on 15 March 2019.


title: Associations Between Fear of COVID-19, Mental Health, and Preventive Behaviours Across Pregnant Women and Husbands: An Actor-Partner Interdependence Modelling

text: The present cross-sectional study examined the actor-partner interdependence effect of fear of COVID-19 among Iranian pregnant women and their husbands and its association with their mental health and preventive behaviours during the first wave of the COVID-19 pandemic in 2020. A total of 290 pregnant women and their husbands (N = 580) were randomly selected from a list of pregnant women in the Iranian Integrated Health System and were invited to respond to psychometric scales assessing fear of COVID-19, depression, anxiety, suicidal intention, mental quality of life, and COVID-19 preventive behaviours. The findings demonstrated significant dyadic relationships between husbands and their pregnant wives' fear of COVID-19, mental health, and preventive behaviours. Pregnant wives’ actor effect of fear of COVID-19 was significantly associated with depression, suicidal intention, mental quality of life, and COVID-19 preventive behaviours but not anxiety. Moreover, a husband actor effect of fear of COVID-19 was significantly associated with depression, anxiety, suicidal intention, mental quality of life, and COVID-19 preventive behaviours. Additionally, there were significant partner effects observed for both the pregnant wives and their husbands concerning all outcomes. The present study used a cross-sectional design and so is unable to determine the mechanism or causal ordering of the effects. Also, the data are mainly based on self-reported measures which have some limitations due to its potential for social desirability and recall biases. Based on the findings, couples may benefit from psychoeducation that focuses on the effect of mental health problems on pregnant women and the foetus.


title: “To Rid Oneself of the Uninvited Guest”: Robert Koch, Sergei Winogradsky and Competing Styles of Practice in Medical Microbiology

text: Does an infectious disease have one, singular pathogenic cause, or many interacting causes? In the discipline of medical microbiology, there is no definitive theoretical answer to this question: there, the conditions of aetiological possibility exist in a curious tension. Ever since the late 19(th) century, the “germ theory of disease”–“one disease, one cause”– has co‐existed with a much less well known theory of “multifactorality”–“one disease, many interacting causes”. And yet, in practice, it is always a singular and never a multifactorial aetiology that emerges once the pathogenic world is brought into the field of medical perception. This paper seeks to understand why. Performing a detailed, genealogical reading of the 2003 severe acute respiratory syndrome (SARS) outbreak, it foregrounds a set of links that connect the practical diagnostic tools at work within contemporary, 21(st) century laboratories to the philosophical assumptions at work within late‐19(th) century understandings of the “germ theory of disease”.


title: Clearance of virus infection from the CNS

text: Viruses that cause encephalomyelitis infect neurons and recovery from infection requires noncytolytic clearance of virus from the nervous system to avoid damaging these irreplaceable cells. Several murine model systems of virus infection have been used to identify clearance mechanisms. Quantitative analysis of Sindbis virus clearance over 6 months shows three phases: day 5-7, clearance of infectious virus, but continued presence of viral RNA; day 8-60, decreasing levels of viral RNA; day 60-180, maintenance of viral RNA at low levels. Antiviral antibody and interferon-γ have major roles in clearance with a likely role for IgM as well as IgG antibody. Long-term residence of virus-specific immune cells in the nervous system is necessary to prevent virus reactivation.


title: Free-Form Deformation Approach for Registration of Visible and Infrared Facial Images in Fever Screening †

text: Fever screening based on infrared (IR) thermographs (IRTs) is an approach that has been implemented during infectious disease pandemics, such as Ebola and Severe Acute Respiratory Syndrome. A recently published international standard indicates that regions medially adjacent to the inner canthi provide accurate estimates of core body temperature and are preferred sites for fever screening. Therefore, rapid, automated identification of the canthi regions within facial IR images may greatly facilitate rapid fever screening of asymptomatic travelers. However, it is more difficult to accurately identify the canthi regions from IR images than from visible images that are rich with exploitable features. In this study, we developed and evaluated techniques for multi-modality image registration (MMIR) of simultaneously captured visible and IR facial images for fever screening. We used free form deformation (FFD) models based on edge maps to improve registration accuracy after an affine transformation. Two widely used FFD models in medical image registration based on the Demons and cubic B-spline algorithms were qualitatively compared. The results showed that the Demons algorithm outperformed the cubic B-spline algorithm, likely due to overfitting of outliers by the latter method. The quantitative measure of registration accuracy, obtained through selected control point correspondence, was within 2.8 ± 1.2 mm, which enables accurate and automatic localization of canthi regions in the IR images for temperature measurement.


title: Abuse, self-harm and suicidal ideation in the UK during the COVID-19 pandemic

text: This study explored patterns of abuse, self-harm and thoughts of suicide/self-harm in the UK during the first month of the COVID-19 pandemic using data from the COVID-19 Social Study (n=44 775), a non-probability sample weighted to population proportions. The reported frequency of abuse, self-harm and thoughts of suicide/self-harm was higher among women, Black, Asian and minority ethnic (BAME) groups and people experiencing socioeconomic disadvantage, unemployment, disability, chronic physical illnesses, mental disorders and COVID-19 diagnosis. Psychiatric medications were the most common type of support being used, but fewer than half of those affected were accessing formal or informal support.


title: Surveillance of Disease: Overview

text: This article discusses the role and methodology of disease surveillance, which provides epidemiological data to formulate actions to control or eliminate disease hazard, one of the indispensable systems in national and global public health intelligence services. The target diseases include not only infectious diseases but also noncommunicable diseases as well as accidents and injuries. Efficacy is increasing with ever-newer diagnostic technology as well as expanding information technology. A few experiences in how surveillance has played an essential role in disease control are illustrated.


title: Emerging Pathogens: Challenges and Successes of Molecular Diagnostics

text: More than 50 emerging and reemerging pathogens have been identified during the last 40 years. Until 1992 when the Institute of Medicine issued a report that defined emerging infectious diseases, medicine had been complacent about such infectious diseases despite the alarm bells of infections with human immunodeficiency virus. Molecular tools have proven useful in discovering and characterizing emerging viruses and bacteria such as Sin Nombre virus (hantaviral pulmonary syndrome), hepatitis C virus, Bartonella henselae (cat scratch disease, bacillary angiomatosis), and Anaplasma phagocytophilum (human granulocytotropic anaplasmosis). The feasibility of applying molecular diagnostics to dangerous, fastidious, and uncultivated agents for which conventional tests do not yield timely diagnoses has achieved proof of concept for many agents, but widespread use of cost-effective, validated commercial assays has yet to occur. This review presents representative emerging viral respiratory infections, hemorrhagic fevers, and hepatitides, as well as bacterial and parasitic zoonotic, gastrointestinal, and pulmonary infections. Agent characteristics, epidemiology, clinical manifestations, and diagnostic methods are tabulated for another 22 emerging viruses and five emerging bacteria. The ongoing challenge to the field of molecular diagnostics is to apply contemporary knowledge to facilitate agent diagnosis as well as to further discoveries of novel pathogens.


title: Inside out and outside in: How the COVID-19 pandemic affects self-disclosure on social media

text: As social distancing and lockdown orders grew more pervasive, individuals increasingly turned to social media for support, entertainment, and connection to others. We posit that global health emergencies - specifically, the COVID-19 pandemic - change how and what individuals self-disclose on social media. We argue that IS research needs to consider how privacy (self-focused) and social (other-focused) calculus have moved some issues outside in (caused by a shift in what is considered socially appropriate) and others inside out (caused by a shift in what information should be shared for the public good). We identify a series of directions for future research that hold potential for furthering our understanding of online self-disclosure and its factors during health emergencies.


title: Development of universal SYBR Green real-time RT-PCR for the rapid detection and quantitation of bovine and porcine toroviruses

text: Abstract Toroviruses (ToVs) are a group of emerging viruses that cause gastroenteritis in domestic animals and humans. Currently, methods such as real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) have not yet been developed for the rapid detection and quantitation of bovine (BToV) and porcine (PToV) toroviruses. Using BToV and PToV RNA standards generated by in vitro transcription, the detection limit of the SYBR Green real-time RT-PCR assay was 2.54×102 BToV and 2.17×103 PToV copies/reaction (correlation coefficiency=0.99 and 0.97, respectively), whereas those of RT-PCR and nested PCR were 2.54×105 and 2.54×104 (BToV) and 2.17×107 and 2.17×105 (PToV) cRNA viral copies/reaction, respectively. Archived diarrhea specimens of calves (n =121) and piglets (n =86) were subjected to RT-PCR, nested PCR and SYBR Green real-time RT-PCR. By conventional RT-PCR, 1 (0.8%) bovine and 7 (8.1%) porcine samples tested positive to BToV and PToV, respectively. With nested PCR, 13 (10.7%) bovine and 17 (19.8%) porcine samples tested positive. SYBR Green real-time RT-PCR assay detected BToV and PToV in 22 of 121 (18.2%) bovine and 31 of 86 (36.0%) porcine samples. These results indicate that SYBR Green real-time RT-PCR (P <0.05) is a more sensitive assay, which can be reproduced as a reliable, sensitive, and rapid tool for the detection and quantitation of toroviruses.


title: Clinical implication of radiographic scores in acute Middle East respiratory syndrome coronavirus pneumonia: Report from a single tertiary-referral center of South Korea

text: Abstract The aim of this study is to determine the earliest cutoff of radiographic score as a potential prognostic indicator of fatal outcomes in patients with acute Middle East respiratory syndrome coronavirus (MERS-CoV) pneumonia. The institutional review board approved this retrospective study. Serial chest radiographies (CXRs) were obtained from viral exposure until death or discharge in 35 patients with laboratory confirmed MERS-CoV infection. Radiographic scores were calculated by multiplying a four-point scale of involved lung area and three-point scale of abnormal opacification, in each of the six lung zones. Receiver operating characteristics (ROC) analyses were performed to identify optimal day and radiographic score for the prediction of respiratory distress, and univariate and multivariate logistic regression analyses were performed to assess significant predictive factors for intubation or tracheostomy. Among 35 patients (22 men, 13 women; median age: 48 years), 25 demonstrated abnormal opacity on CXR (MERS pneumonia), whereas no abnormality was detected in 10 patients (MERS upper respiratory tract infection). Seven patients required ventilator support (intubation group) and three of them eventually expired. The average incubation period was 5.4 days (standard deviation, ±2.8; range, 2–11). Patients in the intubation group had a higher incidence of diffuse lung involvement, higher radiographic scores, and fibrosing sequela on follow up study compared with those in the non-intubation group. However, patients’ age and comorbidity did not differ significantly between the two groups. The ROC analysis revealed an area under curve of 0.726 for the radiographic score on day 10 with an optimal cutoff score of 10 for prediction of intubation, with a sensitivity of 71% and specificity of 67%. Our study suggest that MERS patients with radiographic score > 10 on day 10 from viral exposure require aggressive therapy with careful surveillance and follow-up evaluation.


title: Marine lectins and their medicinal applications

text: Marine organisms have been extensively explored for the last several decades as potential sources of novel biologically active compounds, and extensive research has been conducted on lectins. Lectins derived from marine organisms are structurally diverse and also differ from those identified from terrestrial organisms. Marine lectins appear to be particularly useful in some biological applications. They seem to induce negligible immunogenicity because they have a relatively small size, are more stable due to extensive disulfide bridge formation, and have high specificity for complex glyco-conjugates and carbohydrates instead of simple sugars. It is clear that many of them have not yet been extensively studied when compared with their terrestrial counterparts. Marine lectins can be used to design and develop new potentially useful therapeutic agents. This review encompasses recent research on the isolation and identification of marine lectins with potential value in medicinal applications.


Physiology in Perspective: The New Normal—Life in a Pandemic


title: Release of Coronavirus E Protein in Membrane Vesicles from Virus-Infected Cells and E Protein-Expressing Cells

text: Abstract Coronavirus E protein is a small viral envelope protein that plays an essential role in coronavirus assembly; coexpression of coronavirus M and E proteins results in the production of virus-like particles. The present study demonstrated that mouse hepatitis virus (MHV) E protein was released as an integral membrane protein in lipid vesicles from E-protein-expressing mammalian cells, in the absence of other MHV proteins. Furthermore, our data indicated that the E-protein-containing vesicles, which had a slightly lighter buoyant density than that of MHV, were released from MHV-infected cells. These data implied that E protein alone can drive the production and release of coronavirus envelope in the absence of M protein.


Coronary artery dilatation in a child with hyperinflammatory syndrome with SARS-CoV-2-positive serology


title: Early diagnosis of SARS: lessons from the Toronto SARS outbreak

text: The clinical presentation of SARS is nonspecific and diagnostic tests do not provide accurate results early in the disease course. Initial diagnosis remains reliant on clinical assessment. To identify features of the clinical assessment that are useful in SARS diagnosis, the exposure status and the prevalence and timing of symptoms, signs, laboratory and radiographic findings were determined for all adult patients admitted with suspected SARS during the Toronto SARS outbreak. Findings were compared between patients with laboratory-confirmed SARS and those in whom SARS was excluded by laboratory or public health investigation. Of 364 cases, 273 (75%) had confirmed SARS, 30 (8%) were excluded, and 61 (17%) remained indeterminate. Among confirmed cases, exposure occurred in the healthcare environment (80%) or in the households of affected patients (17%); community or travel-related cases were rare (<3%). Fever occurred in 97% of patients by the time of admission. Respiratory findings including cough, dyspnea and pulmonary infiltrates evolved later and were present in only 59, 37 and 68% of patients, respectively, at admission. Direct exposure, fever on the first day of illness, and elevated temperature, pulmonary infiltrates, lymphopenia and thrombocytopenia at admission were associated with confirmed cases. Rhinorrhea, sore throat, and an elevated neutrophil count at admission were associated with excluded cases. In the absence of fever or significant exposure, SARS is unlikely. Other clinical, laboratory and radiographic findings further raise or lower the likelihood of SARS and provide a rational basis for estimating the likelihood of SARS and directing initial management.


title: Proportional morbidity rates of enteropathogens among diarrheic dairy calves in central Spain

text: Abstract Faecal samples from 218 diarrheic dairy calves in 65 dairy herds, selected by convenience, were screened for the presence of rotavirus, coronavirus, Cryptosporidium spp., F5+ Escherichia coli and Salmonella spp. Animals surveyed were from 1 to 30 days old. Cryptosporidium and rotavirus were the most commonly detected agents (52.3% and 42.7% of the samples positive, respectively). F5+ E. coli was detected in the faeces of 11.9% of the calves and bovine coronavirus was detected in the faeces of 7.3% of the calves. Salmonella spp. was only found in the faeces of two calves (0.9%). Mixed infections with two or more agents occurred in 28% of the calves. Concurrent infection of rotavirus and Cryptosporidium was found in 21.6% of the calves. Two tests were used for the detection of rotavirus (a commercial ELISA and PAGE), F5+ E. coli (ELISA and bacterial culture) and Cryptosporidium (ELISA and microscopy). The validity of the commercial ELISA for the detection of rotavirus, F5+ E. coli and Cryptosporidium in faeces from diarrheic calves was evaluated using PAGE, bacterial culture and microscopy as gold standard, respectively. The ELISA showed a very low sensitivity (28.6%) for the detection of F5+ E. coli compared to bacterial culture.


title: Transmissible gastroenteritis virus: Identification of M protein-binding peptide ligands with antiviral and diagnostic potential

text: Abstract The membrane (M) protein is one of the major structural proteins of coronavirus particles. In this study, the M protein of transmissible gastroenteritis virus (TGEV) was used to biopan a 12-mer phage display random peptide library. Three phages expressing TGEV-M-binding peptides were identified and characterized in more depth. A phage-based immunosorbent assay (phage-ELISA) capable of differentiating TGEV from other coronaviruses was developed using one phage, phTGEV-M7, as antigen. When the phage-ELISA was compared to conventional antibody-based ELISA for detecting infections, phage-ELISA exhibited greater sensitivity. A chemically synthesized, TGEV-M7 peptide (pepTGEV-M7; HALTPIKYIPPG) was evaluated for antiviral activity. Plaque-reduction assays revealed that pepTGEV-M7 was able to prevent TGEV infection in vitro (p <0.01) following pretreatment of the virus with the peptide. Indirect immunofluorescence and real-time RT-PCR confirmed the inhibitory effects of the peptide. These results indicate that pepTGEV-M7 might be utilized for virus-specific diagnostics and treatment.


Delirium and sleep disturbances in COVID–19: a possible role for melatonin in hospitalized patients?


title: The renin–angiotensin system in acute respiratory distress syndrome

text: Angiotensin-converting enzyme 2 (ACE2) counterbalances with ACE and functions as a negative regulator of the renin–angiotensin system (RAS). The importance of RAS in acute respiratory distress syndrome (ARDS) has recently re-emerged owing to the identification of ACE2 as a receptor for the SARS-coronavirus. Recent studies have demonstrated that ACE2 protects mice from acute lung injury as well as SARS-mediated lung injury. We review the role of the RAS, in particular ACE2, in the pathogenesis of ARDS. Section editors: Terry Delovitch – The John P. Robarts Research Institute, London, Ont., Canada David Scott – University of Maryland School of Medicine, Baltimore, MD, USA


title: Enterovirus-D68 (EV-D68) in pediatric patients with respiratory infection: The circulation of a new B3 clade in Italy

text: Abstract Background In recent years, several outbreaks due to Enterovirus D-68 (EV-D68) have been reported, and it was confirmed that the virus can cause upper and lower respiratory tract diseases and be associated with the development of neurological problems. Objectives The main aim of this research was to study the genetic characteristics of EV-D68 strains that were circulating in Italy identified during an outbreak of an EV-D68 infection that occurred in Italy during the period March-October 2016. Study design A retrospective study of the circulation of different types and subtypes of EV-D68 was performed. Nasopharyngeal swabs were collected from March 2016 through October 2016 in children admitted to the Emergency Room with respiratory diseases. Results Among 390 children, 22 (59.1% males; mean age 47 months) were found to be infected by EV-D68 and most of them were immunocompetent (72.7%). Pneumonia was diagnosed in 12 (54.5%) children. Phylogenetic analysis of the VP1 region showed that all the strains identified in this study belonged to clade B3. Within B3 subclade, the Italian EV-D68 strains were most closely related to strains detected in Southern China in 2015 as well as to strains detected in US and the Netherlands in 2016. Conclusions These results showed that EV-D68 infections are a common cause of lower respiratory illness in pediatric age. The circulation of one EV-D68 lineage has been proven in Italy and in the European region during 2016. However, further studies are required to investigate whether some strains or lineages may possess a higher affinity for the lower airway or central nervous system.


ACTIVITÉ DE LA SFMC PENDANT LA PANDÉMIE COVID-19


title: Detection of Severe Human Metapneumovirus Infection by Real-Time Polymerase Chain Reaction and Histopathological Assessment

text: BackgroundInfections with common respiratory tract viruses can cause high mortality, especially in immunocompromised hosts, but the impact of human metapneumovirus (hMPV) in this setting was previously unknown MethodsWe evaluated consecutive bronchoalveolar lavage and bronchial wash fluid samples from 688 patients—72% were immunocompromised and were predominantly lung transplant recipients—for hMPV by use of quantitative real-time polymerase chain reaction (PCR), and positive results were correlated with clinical outcome and results of viral cultures, in situ hybridization, and lung histopathological assessment ResultsSix cases of hMPV infection were identified, and they had a similar frequency and occurred in a similar age range as other paramyxoviral infections. Four of 6 infections occurred in immunocompromised patients. Infection was confirmed by in situ hybridization for the viral nucleocapsid gene. Histopathological assessment of lung tissue samples showed acute and organizing injury, and smudge cell formation was distinct from findings in infections with other paramyxoviruses. Each patient with high titers of hMPV exhibited a complicated clinical course requiring prolonged hospitalization ConclusionsOur results provide in situ evidence of hMPV infection in humans and suggest that hMPV is a cause of clinically severe lower respiratory tract infection that can be detected during bronchoscopy by use of real-time PCR and routine histopathological assessment


title: Toll/IL-1 domain-containing adaptor inducing IFN-β (TRIF) mediates innate immune responses in murine peritoneal mesothelial cells through TLR3 and TLR4 stimulation

text: Abstract Mesothelial cells are composed of monolayer of the entire surface of serosal cavities including pleural, pericardial, and peritoneal cavity. Although mesothelial cells are known to express multiple Toll-like receptors (TLRs) which contribute to trigger innate immune responses against infections, the precise molecular mechanism remains still unclear. In the present study, we investigated the role of Toll/IL-1 domain-containing adaptor inducing IFN-β (TRIF), one of the two major TLRs–adaptor molecules, on innate immune response induced by TLR3 and TLR4 stimulation in murine peritoneal mesothelial cells (PMCs). TRIF was strongly expressed in PMCs and its deficiency led to impaired production of cytokines and chemokines by poly I:C and LPS in the cells. Activation of NF-κB or MAPKs through poly I:C and LPS stimulation was reduced in TRIF-deficient PMCs as compared to the WT cells. TRIF was also necessary for optimal nitric oxide synthesis and gene expression of inducible nitric oxide synthase (iNOS) and IFN-β in PMCs in response to poly I:C and LPS. Furthermore, both Escherichia coli and Pseudomonas aeruginosa induced high level of IL-6, CXCL1, and CCL2 production in PMCs, which was significantly impaired by TRIF deficiency. These results demonstrated that TRIF is required for optimal activation of innate immune responses in mesothelial cells against microbial infections.


title: Chapter 28 Asthma

text: Abstract Asthma is a common respiratory disease with a complex etiology involving a combination of genetic and environmental components. Current asthma management involves a step-up and step-down approach based on asthma control with a large degree of heterogeneity in responses to the main drug classes currently in use: β2-adrenergic receptor agonists, corticosteroids, and leukotriene modifiers. Importantly, asthma is heterogeneous with respect to clinical presentation and the inflammatory mechanisms that underlie it. This heterogeneity likely contributes to variable results in clinical trials, particularly when targeting specific inflammatory mediators. These factors have motivated a drive toward stratified medicine in asthma based on clinical/cellular outcomes or genetics (i.e., pharmacogenetics). Significant progress has been made in identifying genetic polymorphisms that influence the efficacy and potential for adverse effects of all main classes of asthma drugs. Importantly an emerging role for genetics in phase II development of newer therapies has been demonstrated (e.g., anti-IL4). Similarly, the stratification of patients based on clinical characteristics (e.g., blood and sputum eosinophil levels) has been critical in evaluating newer therapies (e.g., anti-IL5). As a proof of concept, anti-IgE is the latest therapy to be introduced into clinical practice, although only for severe, allergic patients (i.e., in a stratified manner). As new asthma genes are identified using genome-wide association, among other technologies, new targets (e.g., IL33/IL33 receptor (IL1RL1)) will emerge and pharmacogenetics in these development programs will be essential. In this chapter we review the current understanding of asthma pathobiology and its clinical presentation, as well as the use of stratified medicine, which holds great promise for maximizing clinical outcomes and minimizing adverse effects in existing and new therapies.


title: Sensitive Commercial NASBA Assay for the Detection of Respiratory Syncytial Virus in Clinical Specimen

text: The aim of the study was to evaluate the usability of three diagnostic procedures for the detection of respiratory syncytial virus in clinical samples. Therefore, the FDA cleared CE marked NOW® RSV ELISA, the NucliSENS® EasyQ RSV A+B NASBA, and a literature based inhouse RT-PCR protocol were compared for their relative sensitivities. Thereby, NASBA turned out to be the most sensitive method with a total number of 80 RSV positive samples out of a cohort of 251 nasopharyngeal washings from patients suffering from clinical symptoms, followed by the inhouse RT-PCR (62/251) and ELISA (52/251). Thus, NASBA may serve as a rapid and highly sensitive alternative for RSV diagnostics.


COVID-19 related Kawasaki-like disease in an adult: a case report.


title: Epidemiology of severe acute respiratory syndrome (SARS): adults and children

text: Summary Severe acute respiratory syndrome (SARS) is a newly described respiratory infection with pandemic potential. The causative agent is a new strain of coronavirus most likely originating from wild animals. This disease first emerged in November 2002 in Guangdong Province, China. Early in the outbreak the infection had been transmitted primarily via household contacts and healthcare settings. In late February 2003 the infection was transmitted to Hong Kong when an infected doctor from the mainland visited there. During his stay in Hong Kong at least 17 guests and visitors were infected at the hotel at which he stayed. By modern day air travel, the infection was rapidly spread to other countries including Vietnam, Singapore and Canada by these infected guests. With the implementation of effective control strategies including early isolation of suspected cases, strict infection control measures in the hospital setting, meticulous contact tracing and quarantine, the outbreak was finally brought under control by July 2003. In addition, there were another two events of SARS in China between the end of December 2003 and January 2004 and from March to May 2004; both were readily controlled without significant patient spread.


title: Medication management and adherence during the COVID-19 pandemic: Perspectives and experiences from LMICs

text: Abstract The current coronavirus disease 2019 (COVID-19) pandemic is placing a huge strain on health systems worldwide. Suggested solutions like social distancing and lockdowns in some areas to help contain the spread of the virus may affect special patient populations like those with chronic illnesses who are unable to access healthcare facilities for their routine care and medicines management. Retail pharmacy outlets are the likely facilities for easy access by these patients. The contribution of community pharmacists in these facilities in managing chronic conditions and promoting medication adherence during this COVID-19 pandemic will be essential in easing the burden on already strained health systems. This paper highlights the pharmaceutical care practices of community pharmacists for patients with chronic diseases. during this pandemic. This would provide support for the call by the WHO to maintain essential services during the pandemic, in order to prevent non-COVID disease burden on healthcare systems particularly in low-and middle-income countries.


title: The Challenge of Viral Immunity

text: Bringing together discussion of innate immunity, B cell and T cell responses, vaccine design and efficacy, and the genetics of HIV and AIDS resistance allows us to access the extraordinary complexity of viral immunity and host responsiveness.


title: No Autopsies on COVID-19 Deaths: A Missed Opportunity and the Lockdown of Science

text: Background: The current outbreak of COVID-19 infection, which started in Wuhan, Hubei province, China, in December 2019, is an ongoing challenge and a significant threat to public health requiring surveillance, prompt diagnosis, and research efforts to understand a new, emergent, and unknown pathogen and to develop effective therapies. Despite the increasing number of published studies on COVID-19, in all the examined studies the lack of a well-defined pathophysiology of death among patients who died following COVID-19 infection is evident. Autopsy should be considered mandatory to define the exact cause of death, thus providing useful clinical and epidemiologic information as well as pathophysiological insights to further provide therapeutic tools. Methods: A literature review was performed on PubMed database, using the key terms: “COVID-19”, “nCov 19”, and “Sars Cov 2”. 9709 articles were retrieved; by excluding all duplicated articles, additional criteria were then applied: articles or abstracts in English and articles containing one of the following words: “death”, “died”, “comorbidity”, “cause of death”, “biopsy”, “autopsy”, or “pathological”. Results: A total of 50 articles met the inclusion criteria. However, only 7 of these studies reported autopsy-based data. Discussion: The analysis of the main data from the selected studies concerns the complete analysis of 12,954 patients, of whom 2269 died (with a mortality rate of 17.52%). Laboratory confirmation of COVID-19 infection was obtained in all cases and comorbidities were fully reported in 46 studies. The most common comorbidities were: cardiovascular diseases (hypertension and coronary artery disease), metabolic disorders (diabetes, overweight, or obesity), respiratory disorders (chronic obstructive pulmonary disease), and cancer. The most common reported complications were: acute respiratory distress syndrome (ARDS), acute kidney injury, cardiac injury, liver insufficiency, and septic shock. Only 7 papers reported histological investigations. Nevertheless, only two complete autopsies are described and the cause of death was listed as COVID-19 in only one of them. The lack of postmortem investigation did not allow a definition of the exact cause of death to determine the pathways of this infection. Based on the few histopathological findings reported in the analyzed studies, it seems to be a clear alteration of the coagulation system: frequently prothrombotic activity with consequent thromboembolism was described in COVID-19 patients. As a scientific community, we are called on to face this global threat, and to defeat it with all the available tools necessary. Despite the improvement and reinforcement of any method of study in every field of medicine and science, encouraging the autopsy practice as a tool of investigation could also therefore, help physicians to define an effective treatment to reduce mortality.


title: The immunity induced by recombinant spike proteins of SARS coronavirus in Balb/c mice

text: The immune effect of two recombinant protein fragments of spike protein in severe acute respiratory syndrome coronavirus (SARS CoV) was investigated in Balb/c mice. Two partial spike gene fragments S1 (322 1464 bp) and S2 (2170 2814 bp) of SARS coronavirus were amplified by RT-PCR, and cloned into pET-23a prokaryotic expression vector, then transformed into competent Escherichia E. coli BL21 (DE3)(pLysS) respectively. Recombinant proteins were expressed and purified by Ni(2+) immobilized metal ion affinity chromatography. The purified proteins mixed with complete Freund adjuvant were injected into Balb/c mice three times at a two-week interval. High titer antibody was detected in the serum of immunized Balb/c mice, and mice immunized with S1 protein produced high titer IgG1, IgG2a, IgG2b and IgG3, while those immunized with S2 protein produced high titer IgG1, IgG2a, but lower titer IgG2b and IgG3. Serum IFN-concentration was increased significantly but the concentrations of Il-2, IL-4 and IL-10 had no significant change. And a marked increase was observed in the number of spleen CD8+ T cells. The results showed that recombinant proteins of SARS coronavirus spike protein induced hormonal and cellular immune response in Balb/c mice.


Covering coronavirus—emerging tools for the fight against the common enemy


title: Molecular characterization of human coronaviruses and their circulation dynamics in Kenya, 2009–2012

text: BACKGROUND: Human Coronaviruses (HCoV) are a common cause of respiratory illnesses and are responsible for considerable morbidity and hospitalization across all age groups especially in individuals with compromised immunity. There are six known species of HCoV: HCoV-229E, HCoV-NL63, HCoV-HKU1, HCoV-OC43, MERS-CoV and SARS-HCoV. Although studies have shown evidence of global distribution of HCoVs, there is limited information on their presence and distribution in Kenya. METHODS: HCoV strains that circulated in Kenya were retrospectively diagnosed and molecularly characterized. A total of 417 nasopharyngeal specimens obtained between January 2009 and December 2012 from around Kenya were analyzed by a real time RT-PCR using HCoV-specific primers. HCoV-positive specimens were subsequently inoculated onto monolayers of LL-CMK2 cells. The isolated viruses were characterized by RT-PCR amplification and sequencing of the partial polymerase (pol) gene. RESULTS: The prevalence of HCoV infection was as follows: out of the 417 specimens, 35 (8.4 %) were positive for HCoV, comprising 10 (2.4 %) HCoV-NL63, 12 (2.9 %) HCoV-OC43, 9 (2.1 %) HCoV-HKU1, and 4 (1 %) HCoV-229E. The Kenyan HCoV strains displayed high sequence homology to the prototypes and contemporaneous strains. Evolution analysis showed that the Kenyan HCoV-OC43 and HCoV-NL63 isolates were under purifying selection. Phylogenetic evolutionary analyses confirmed the identities of three HCoV-HKU1, five HCoV-NL63, eight HCoV-OC43 and three HCoV-229E. CONCLUSIONS: There were yearly variations in the prevalence and circulation patterns of individual HCoVs in Kenya. This paper reports on the first molecular characterization of human Coronaviruses in Kenya, which play an important role in causing acute respiratory infections among children.