Predictors of poor outcomes in patients with pandemic viral infections (influenza AH1N1pdm09, COVID-19) on a ventilator.

Considering the commonality of the pathogenetic links of the critical forms of COVID-19 and influenza AH1N1pdm09 (cytokine over-release syndrome), the question arises: will the predictors of an unfavorable outcome in patients on mechanical ventilation and, accordingly, the universal tactics of respiratory support in these diseases be identical? Objective. In a comparative aspect, to characterize patients with influenza AH1N1pdm09 and COVID-19 who were on mechanical ventilation, to identify additional clinical and laboratory risk factors for death, to determine the degree of influence of respiratory support (RP) tactics on an unfavorable outcome in the studied category of patients. Patients and methods. Patients treated on the basis of resuscitation and intensive care departments of the State Budgetary Healthcare Institution "SKIB" in Krasnodar and the State Budgetary Healthcare Institution "IB No 2" in Sochi were studied: group 1 - 31 people with influenza AH1N1pdm09 (21 people died - subgroup 1A;10 people survived - subgroup 1B) and group 2 - 50 people with COVID-19 (29 patients died - subgroup 2A;21 people survived - subgroup 2B). All patients developed hypoxemic ARF. All patients received step-by-step tactics of respiratory support, starting with oxygen therapy and ending with the use of "traditional" mechanical ventilation. Continuous variables were compared in subgroups of deceased and surviving patients for both nosologies at the stages: hospital admission;registration of hypoxemia and the use of various methods of respiratory therapy;development of multiple organ dysfunctions. With regard to the criteria for which a statistically significant difference was found (p < 0.05), we calculated a simple correlation, the relative risk of an event (RR [CI 25-75%]), the cut-off point, which corresponded to the best combination of sensitivity and specificity. Results. Risk factors for death of patients with influenza AH1N1pdm09 on mechanical ventilation: admission to the hospital later than the 8th day of illness;the fact of transfer from another hospital;leukocytosis >=10.0 x 109/l, granulocytosis >=5.5 x 109/l and LDH level >=700.0 U/l at admission;transfer of patients to mechanical ventilation on the 9th day of illness and later;SOFA score >=8;the need for pressor amines and replacement of kidney function. Predictors of poor outcome in ventilated COVID-19 patients: platelet count <=210 x 109/L on admission;the duration of oxygen therapy for more than 4.5 days;the use of HPNO and NIV as the 2nd step of RP for more than 2 days;transfer of patients to mechanical ventilation on the 14th day of illness and later;oxygenation index <=80;the need for pressors;SOFA score >=8. Conclusion. When comparing the identified predictors of death for patients with influenza and COVID-19 who needed mechanical ventilation, there are both some commonality and differences due to the peculiarities of the course of the disease. A step-by-step approach to the application of respiratory support methods is effective both in the case of patients with influenza AH1N1pdm09 and patients with COVID-19, provided that the respiratory support method used is consistent with the current state of the patient and his respiratory system, timely identification of markers of ineffectiveness of the respiratory support stage being carried out and determining the optimal moment escalation of respiratory therapy.Copyright © 2022, Dynasty Publishing House. All rights reserved.

Reddit and Google Activity Related to Non-COVID Epidemic Diseases Surged at Start of COVID-19 Pandemic: Retrospective Study.

BACKGROUND: Resources such as Google Trends and Reddit provide opportunities to gauge real-time popular interest in public health issues. Despite the potential for these publicly available and free resources to help optimize public health campaigns, use for this purpose has been limited. OBJECTIVE: The purpose of this study is to determine whether early public awareness of COVID-19 correlated with elevated public interest in other infectious diseases of public health importance. METHODS: Google Trends search data and Reddit comment data were analyzed from 2018 through 2020 for the frequency of keywords "chikungunya," "Ebola," "H1N1," "MERS," "SARS," and "Zika," 6 highly publicized epidemic diseases in recent decades. After collecting Google Trends relative popularity scores for each of these 6 terms, unpaired 2-tailed t tests were used to compare the 2020 weekly scores for each term to their average level over the 3-year study period. The number of Reddit comments per month with each of these 6 terms was collected and then adjusted for the total estimated Reddit monthly comment volume to derive a measure of relative use, analogous to the Google Trends popularity score. The relative monthly incidence of comments with each search term was then compared to the corresponding search term's pre-COVID monthly comment data, again using unpaired 2-tailed t tests. P value cutoffs for statistical significance were determined a priori with a Bonferroni correction. RESULTS: Google Trends and Reddit data both demonstrate large and statistically significant increases in the usage of each evaluated disease term through at least the initial months of the pandemic. Google searches and Reddit comments that included any of the evaluated infectious disease search terms rose significantly in the first months of 2020 above their baseline usage, peaking in March 2020. Google searches for "SARS" and "MERS" remained elevated for the entirety of the 2020 calendar year, as did Reddit comments with the words "Ebola," "H1N1," "MERS," and "SARS" (P<.001, for each weekly or monthly comparison, respectively). CONCLUSIONS: Google Trends and Reddit can readily be used to evaluate real-time general interest levels in public health-related topics, providing a tool to better time and direct public health initiatives that require a receptive target audience. The start of the COVID-19 pandemic correlated with increased public interest in other epidemic infectious diseases. We have demonstrated that for 6 distinct infectious causes of epidemics over the last 2 decades, public interest rose substantially and rapidly with the outbreak of COVID-19. Our data suggests that for at least several months after the initial outbreak, the public may have been particularly receptive to dialogue on these topics. Public health officials should consider using Google Trends and social media data to identify patterns of engagement with public health topics in real time and to optimize the timing of public health campaigns.

Exploring nanoselenium to tackle mutated SARS-CoV-2 for efficient COVID-19 management

Despite ongoing public health measures and increasing vaccination rates, deaths and disease severity caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its new emergent variants continue to threaten the health of people around the world. Therefore, there is an urgent need to develop novel strategies for research, diagnosis, treatment, and government policies to combat the variant strains of SARS-CoV-2. Since the state-of-the-art COVID-19 pandemic, the role of selenium in dealing with COVID-19 disease has been widely discussed due to its importance as an essential micronutrient. This review aims at providing all antiviral activities of nanoselenium (Nano-Se) ever explored using different methods in the literature. We systematically summarize the studied antiviral activities of Nano-Se required to project it as an efficient antiviral system as a function of shape, size, and synthesis method. The outcomes of this article not only introduce Nano-Se to the scientific community but also motivate scholars to adopt Nano-Se to tackle any serious virus such as mutated SARS-CoV-2 to achieve an effective antiviral activity in a desired manner.

Impact of Influenza in South-East Asia

Influenza infection is asymptomatic in up to 75% of cases, but outbreaks result in significant morbidity. Reports found that severe influenza complications tend to occur among the very young (<5 years) and very old (>65 years), especially those with underlying co-morbidities like diabetes mellitus and heart disease. Even with no co-morbidity, some older persons with severe influenza may require hospitalisation or intensive care, with increased risk of myocardial infarction and stroke. In South-East Asia, influenza was often seen as a mild problem and was not deemed notifiable until the appearance of the Influenza A(H1N1) pandemic in 2009. For decades the data made available were based on extrapolated estimates collected mainly from paediatric populations, resulting in inconsistent findings. Following expanded surveillance across the region using national surveillance systems for influenza-like illness (ILI) and severe acute respiratory illness (SARI), and better diagnostic methods, improved estimates of disease burden was achieved in South-East Asia. However, two studies conducted in 2008-2010 reported findings ranging from 2-3% to 11%. With regards to increased risk of complications, the estimated global annual attack rates for influenza were 5-10% in adults and 20-30% in children, resulting in 3-5 million cases of severe illness and 290,000-650,000 deaths. A study In Singapore reported that influenza is associated with annual excess mortality rates (EMR) of 11-14.8 per 100 000 person-years, especially affecting the elderly;these rates are comparable to that of the USA. As for hospitalisation rates of children under 5 years with seasonal influenza, the USA estimated a rate of 1.4 per 100,000. Comparable rates were reported in Singapore (0.7-0.9), Thailand (2.4), Viet Nam (3.9-4.7), and the Philippines (4.7). In 2018, an updated study reported a mean annual influenza-associated respiratory EMR of 4.0-8.8 per 100 000 individuals, with South-East Asia showing a high mortality rate of 3.5-9.2 per 100,000 individuals. It was already estimated in Thailand in 2004 that influenza resulted in USD23-63 million in economic costs, with the main contribution from lost productivity due to missed workdays. Thus, comparable to countries in temperate climate, the clinical and socioeconomic impact of influenza in South-East Asia appear to be just as substantial. With the emergence of the COVID-19 pandemic in 2020, global influenza incidence dropped dramatically. In South-East Asia, the trend in influenza detections was similar to the rest of the world, with numbers slightly higher than average in early 2020, followed by a quick drop-off by the end of April 2020. After April 2020, the detection rate remained low until late July 2020, when Influenza A(H3N2) predominated in Cambodia, Malaysia, the Philippines, Singapore, Thailand and Timor-Leste;influenza B in Lao People's Democratic Republic but with an upsurge in A(H3N2) activity. Following a two-year hiatus, influenza outbreaks began to re-emerge significantly since early 2022. From February through August 2022, influenza activity in the southern hemisphere remained lower than in pre-COVID-19 pandemic years, but was at the highest level compared to similar periods since the start of the COVID-19 pandemic. Reasons for the reduction during the COVID-19 pandemic include non-pharmaceutical interventions (NPIs), reduced population mixing and reduced travel, and possibly viral interference between SARS-CoV-2 and influenza virus in the same host. In general, the reduction in influenza detections however does not appear to be associated with lack of testing. The World Health Organisation (WHO) continues to recommend that vaccination is the most effective way to prevent infection and severe outcomes caused by influenza viruses. Although influenza vaccine is not commonly used in most countries in South-East Asia, its burden is similar in other parts of the world where influenza vaccine is now routinely used. Currently, the countries in South-East Asia that are providing free influenza vacc na ion for those at high risk include Thailand, Singapore, the Philippines and Lao People's Democratic Republic.Copyright © 2023

Applications of the One Health concept: Current status in the Middle East

Background: The One Health concept (OHC) seeks to improve the health of plants, animals, and humans because improving animal and plant health will increase the capacity for improving human health. Many risks such as plant and animal biotechnology applications have the potential to generate new diseases that can be transmitted to humans. In this way, the health of humans, animals, and plants is interrelated and depends on one another. However, it has been difficult to apply the OHC in some countries, such as those in the Middle East. The absence of financial support in the region is a major hindrance to applying this concept in the region. The application of the OHC requires the support of specialists who can advocate the government for support in launching OHC-related projects. Here, we discuss the OHC in the context of antimicrobial resistance, zoonotic diseases, and biosafety/biosecurity, which are important public health issues. Furthermore, we describe the current status of the OHC in the Middle East and recent research conducted related to this concept. There has been recent international solidarity in the application of the OHC to reduce risks that threaten the health of organisms. Several countries jointly launched the Global Health Security Agenda in 2014 with the aim of realizing a world that is free of infectious disease-related health risks. However, no previous review articles have examined the applications of the OHC in the Middle East region. This article discusses the OHC in terms of its needs and current applications in the Middle East. Methodology: The following keywords were used in the search: "One Health," "Middle East," "medicinal plants," "viruses," "rabies," "MERS," and "antimicrobial resistance." Related papers were obtained by searching for these keywords using available search engines, such as PubMed, Google Scholar, and Google search, as well as international organization websites. Conclusion(s): The concept of One Health is relatively new and has not been applied in most countries, possibly because the value of this concept for improving human health is not well understood. The key principle defining this concept and its importance is the interdependency of plants, animals, and human health. By applying the OHC, humans can benefit from healthy plants and animals by enhancing their growing conditions, medications, and environments. This would in turn improve general human health by allowing the safe extraction of therapeutics and food resources.Copyright © 2023

Respiratory Syncytial Virus (RSV) infections in children: recent concepts in immunopathogenesis and diagnostic dilemma

Respiratory viral infections are important cause of morbidity and mortality in early life. The relative influence of host and viral factors possibly contribute to the disease pathogenesis. Predisposing conditions like prematurity, Low birth weight and congenital heart diseases etc. have been incriminated in the disease progression. The development of cough, wheezing, and tachypnea, usually peaking on days 4 to 5, go parallel with host cytokine responses and viral load. Various host cytokines, chemokines and molecules involved in the immune response against RSV infection might be responsible for the outcome of the disease process. Nasopharyngeal aspirates (NPAs) from children (n = 349) between 2013-2017 were subjected for IL-17A, IFN-gamma, TNF-alpha, IL-10, IL-6 levels by CBA and MMP-9 and TIMP-1 levels by ELISA. The viral load in RSV positive samples and cytokine levels were correlated with the WHO criteria for acute lower respiratory tract illness (ALRTI). RSV viral load, Pro-inflammatory cytokine (TNF-alpha) levels in severe ALRTI patients were significantly higher than the ALRTI patients [p<0.001]. Whereas Th17 cytokine (IL-17) was found to be significantly higher (p<0.05) in ALRTI patients than severe patients. MMP-9 is secreted in higher levels in severe ALRTI patients (n = 77) in comparison to Acute LRTI patients (n = 35) with an increase of thirty seven fold (p<0.001). Thus, the study highlights the role of TNF -alpha, IL-17 and Th2 cytokine biasness in the pathogenesis of RSV disease with the possible contribution of higher MMP-9/TIMP-1 ratio as a bad prognostic marker towards disease severity. To study the gene expression of autophagy and mTOR signalling pathways in RSV infected children with ALRTI. Nasopharyngeal aspirate (NPA) samples (n = 145) from children suffering from ALRTI were subjected for detection of RSV (Oct 2019 to March 2020). Semi-quantitative gene expression analysis for 5 representative genes each of mTOR signalling and autophagy pathway were performed in respiratory tract epithelial cells using 25 RSV positive cases and 10 healthy controls subjects. Autophagy gene expression analysis revealed significant upregulation in NPC1 and ATG3 autophagy genes. mTOR, AKT1 and TSC1 genes of mTOR pathway were significantly down-regulated in RSV positive patients except RICTOR gene which was significantly upregulated. Thus, survival of RSV within autophagosome might have been facilitated by upregulation of autophagy and downregulation of mTOR signalling genes. To assess the impact of SARS-CoV2 pandemic on RSV, samples were collected from children with ALRTIs admitted to emergency, PICU and indoor admissions during pre-pandemic period (October 2019 to February 2020;n = 166) and during COVID-19 Pandemic (July 2021 to July 2022;n = 189, SARS-CoV2 negative). These NP swabs were analyzed for pdm InfA H1N1, InfA H3N2, Inf B, RSV, hMPV, hBoV, hRV, PIV-2 and PIV-3 by PCR. Higher proportion of children with ALRTIs have had virus/es isolated during pre-pandemic period than during pandemic period (p<0.001). During pre-pandemic period, significantly higher proportion of children had RSV positivity (p<0.001);and significantly lower positivity for hRV (p<0.05), hMPV (p<0.05), and hBoV (p <= 0.005). The occurrence of COVID-19 pandemic has significantly impacted the frequency and pattern of detection of RSV among hospitalized children with LRTIs. RSV Fusion protein plays a critical role in the entry of the virus into the host cell by initiating the fusion of host and viral membranes. It happens to be a target of neutralizing antibodies paving the way as a vaccine candidate. Hence effort was made to introduce point mutation in hRSV fusion protein which can confer stability in its prefusion form. In-silico a stable structure of RSV fusion protein was generated making it a potential vaccine candidate. The timely diagnosis of RSV infection in this population is important for initiating therapy and instituting appropriate infection prevention measures. Serological testing is not widely used for the diagnosis of RSV. C ll Cultures including shell vial culture were used for RSV diagnosis. However, culture approaches lack sensitivity, often quite significantly, compared to nucleic acid amplification assays for the diagnosis of RSV infections. Molecular multiplex assays now offer increased sensitivity for a more accurate diagnosis. However issues with the use of these types of commercial panel assays include the requirement for substantial training, quality systems, and infrastructure to maintain and run these assays and many a times identification of viruses where the true pathogenic potential of those multiple viruses are debatable. Studies are available with laboratory- developed nucleic acid amplification test systems for the detection of RSVA and RSVB in clinical specimens either by PCRbased technologies or RT-LAMP. Gene targets of laboratory-developed molecular assays point towards M gene and the N gene in RSVA and -B with the benefits of flexibility to modify assays when targets are under evolutionary pressure to change, as well as a perceived initial low cost to carry out testing.

Immunogenetic studies on SARS-CoV-2: Our experience at SKIMS

Background: The pathophysiology of viral-infections is highly complex and involves host immunocompetence, host genetics, and gene-environment interactions. We hypothesized that polymorphic variants in host genes, blood group and previous vaccination status against H1N1 may affect the clinical course of covid-19 infection. Method(s): A total of 202 subjects who were RT-PCR negative after Covid-19 infection were recruited. We investigated association between Covid-19 infection (Severity and recovery period) and multiple factors including ABO and Rh blood groups, H1N1 vaccination, polymorphism in Viral susceptibility genes (ACE2 G8790A), and polymorphism in host response genes (ACE I/D rs4646994, IL6- 174G/C, GSTT1/GSTM1 I/D and GSTP1 Ile 105 Val). Result(s): B-ve and O-ve ABO and Rh blood groups had significantly higher Covid-19 recovery period applied on one-vs.-all in a nonparametric t-test (p<0.05). Subjects who had vaccinated themselves against H1N1 presented with a lower recovery-period (p<0.05). Both variables (blood group and H1N1 vaccination) were not however associated with Covid-19 severity. Out of the studied polymorphisms, ACE2 G8790A and GSTT1/GSTM1 were significantly associated with covid-19 infection. Our results indicated that G/G genotype of ACE2 G8790A (OR 3.52, P 0.007) and GSTT1/ GSTM1 null (M1 - / - OR = 3.98, P = 0.0004;T1 - / - OR 3.84, P = 0.004) and double null (M1 - / - /T1 - / - OR = 9.66, P = 0.001) are likely to be associated with an increased risk for severe-critical outcomes in individuals with COVID-19. Other polymorphisms analyzed in this study were found to have no significant association with Covid-19 outcome. Conclusion(s): This study suggests that outcome of Covid-19 infection is affected by both clinical and genetic factors. Thus it seems plausible to utilize these factors as prediction and susceptibility markers in the prognosis of COVID-19, which may help to personalize the treatment.

Influenza surveillance in Ezhou city, Hubei Province, 2016-2021

ObjectiveTo analyze the influenza surveillance data in Ezhou City, Hubei Province from 2016 to 2021, determine the epidemiological characteristics and etiological trend of influenza like illness (ILI), and to provide scientific evidence for influenza prevention and control. MethodsThe ILI surveillance data were reported by Ezhou influenza sentinel hospitals and etiological examination results were collected by network laboratory. Influenza surveillance data from 2016 to 2021 were analyzed. ResultsFrom 2016 to 2021, the percentage of ILI visits (ILI%) in Ezhou city was 2.81% and increased over years. Majority (55.55%) of ILI cases were 0-4 years. A total of 7 716 ILI samples were examined from 2016 to 2021, of which 1 467 tested positive with a positive rate of 19.01%. Influenza A H1N1 was mainly concentrated in January-April, A H3N2 mainly in August-December, B Victoria mainly in April-July and December-March, and B Yamagata mainly in December-February. Influenza network laboratory isolated influenza virus from the 1 467 positive samples by using MDCK cells and SPF chicken embryos. The overall isolation rate was 32.78%, which was 26.93% by MDCK cells and 5.86% by SPF chicken embryos. From 2016 to 2021, a total of 13 ILI outbreaks were reported in Ezhou City. Temporally, the outbreaks mainly occurred in winter and spring. Spatially, they were mainly in primary schools, middle schools and kindergartens. ConclusionThe winter and spring are the key time period of influenza prevention and control in Ezhou City, as they are susceptible to influenza outbreaks. Children aged 0-14 are the key population of prevention and control. Diverse subtypes of influenza virus alternate by years, which warrants continually strengthening monitoring. Additionally, certain countermeasures against COVID-19 may be recommended in the prevention and control of influenza.

Convalescent plasma therapy for managing infectious diseases: A narrative review

The coronavirus disease 2019 (COVID-19) pandemic in 2020 is one of the worst catastrophic events in human history. A number of therapeutic modalities have been utilized in order to fight the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), although the majority of them failed to demonstrate a beneficial clinical effect. Among the anti-COVID-19 agents being investigated, the convalescent plasma collected from recovered donors has gained a growing interest. Convalescent plasma has been employed for over a hundred years to treat severe acute viral infections when a vaccine or a specific antiviral treatment was not yet available. In this narrative review, we summarize the literature data on the use of convalescent plasma during previous viral outbreaks and pandemics, including influenza viruses, coronaviruses other than SARS-CoV-2 and Ebola virus. A literature search, using the Medline and PubMed electronic database, was performed to retrieve publications on the use of convalescent plasma in previous viral epidemics. In conclusion, the available literature data suggest the safety profile of convalescent plasma and its potential benefit in treating emerging viral infectious diseases. In addition, these data retrieved from previous viral epidemics provide a solid rationale for the employment of plasma from convalescent donors also in COVID-19 patients.Copyright © 2021 AME Publishing Company. All rights reserved.

Extracellular vesicles as delivery vectors to enhance killing of bacteria and viruses by airway-recruited human neutrophils

Background: Polymorphonuclear neutrophils (PMNs) recruited to the airway lumen in cystic fibrosis (CF) undergo a rapid transcriptional program, resulting in exocytosis of granules and inhibition of bacterial killing. As a result, chronic infection, feed-forward inflammation, and structural tissue damage occur. Because CF airway PMNs are also highly pinocytic, we hypothesized that we could deliver protein- and ribonucleic acid (RNA)-based therapies to modulate their function to benefit patients. We elected to use extracellular vesicles (EVs) as a delivery vector because they are highly customizable, and airway PMNs have previously been shown by our group to process and use their cargo efficiently [1]. Furthermore, our prior work on CF airway PMNs [2] led to identification of the long noncoding RNA MALAT1, the transcription factor Ehf, and the histone deacetylase/long-chain fatty deacylase HDAC11 as potential targets to modulate CF airway PMN dysfunction. Method(s): H441 human club epithelial cells were chosen for EV production because they efficiently communicate with lung-recruited primary human PMNs [1]. Relevant constructs were cloned into an expression plasmid downstream of a constitutive cytomegalovirus or U6 promoter with an additional puromycin selection cassette. EVs were generated in serumdepleted media and purified by differential centrifugation. Quality and concentration of EVs was determined by electron microscopy and nanoparticle tracking analysis and cargo content by western blot (protein) or qualitative reverse transcription polymerase chain reaction (RNA). Enhanced green fluorescent protein and messenger ribonucleic acid (mRNA) were used as controls. To test delivery to primary human PMNs, generated EVs were applied in the apical fluid of an airway transmigration model [2]. PMN activation was assessed by flow cytometry, and bacterial (PA01 and Staphylococcus aureus 8325-4) killing and viral (influenza Avirus [IAV] H1N1/PR/8/34;SARS-CoV-2/Washington) clearance assays were conducted. Result(s): To package protein, we used EV-loading motifs such as the tetraspanin CD63, Basp1 amino acids 1-9, and the palmitoylation signal of Lyn kinase. To load mRNA, a C'D box motif recognized by the RNA-binding protein L7Ae was included in the 3' untranslated region of the expressed RNA, and CD63-L7Ae was co-expressed. Airway-recruited PMNs treated with EVs containing small interfering RNAs against MALAT1 or HDAC11 showed greater ability to clear bacteria. Conversely, PMNs treated with constructs encasing MALAT1 or HDAC11 efficiently cleared IAV and SARSCoV- 2. PMNs expressing Ehf showed greater clearance of bacteria and viruses. Conclusion(s): Our findings suggest mutually exclusive roles of MALAT-1 and HDAC11 in regulating bacterial and viral clearance by airway-recruited PMNs. Expression of Ehf in airway PMNs may be a pathogen-agnostic approach to enhancing clearance by airway-recruited PMNs. Overall, our study brings proof-of-concept data for therapeutic RNA/protein transfer to airway-recruited PMNs in CF and other lung diseases and for use of EVs as a promising method for cargo delivery to these cells. It is our expectation that, by treating the immune compartment of CF airway disease, pathogentherapies, such as antibiotics will be more effective, and epithelial-targeted therapies, such as CFTR modulators, will have greater penetrance into the cell types of interest.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

In-silico molecular modelling studies of some camphor imine based compounds as anti-influenza A (H1N1) pdm09 virus agents.

The advent of influenza A (H1N1) drug-resistant strains led to the search quest for more potent inhibitors of the influenza A virus, especially in this devastating COVID-19 pandemic era. Hence, the present research utilized some molecular modelling strategies to unveil new camphor imine-based compounds as anti-influenza A (H1N1) pdm09 agents. The 2D-QSAR results revealed GFA-MLR (R2train = 0.9158, Q2=0.8475) and GFA-ANN (R2train = 0.9264, Q2=0.9238) models for the anti-influenza A (H1N1) pdm09 activity prediction which have passed the QSAR model acceptability thresholds. The results from the 3D-QSAR studies also revealed CoMFA (R2train =0.977, Q2=0.509) and CoMSIA_S (R2train =0.976, Q2=0.527) models for activity predictions. Based on the notable information derived from the 2D-QSAR, 3D-QSAR, and docking analysis, ten (10) new camphor imine-based compounds (22a-22j) were designed using the most active compound 22 as the template. Furthermore, the high predicted activity and binding scores of compound 22j were further justified by the high reactive sites shown in the electrostatic potential maps and other quantum chemical calculations. The MD simulation of 22j in the active site of the influenza hemagglutinin (HA) receptor confirmed the dynamic stability of the complex. Moreover, the appraisals of drug-likeness and ADMET properties of the proposed compounds showed zero violation of Lipinski's criteria with good pharmacokinetic profiles. Hence, the outcomes in this work recommend further in-depth in vivo and in-vitro investigations to validate these theoretical findings.Communicated by Ramaswamy H. Sarma.

Guidelines on epidemics in Mexico. Historical perspective.

A perspective of epidemics and pandemics in Mexico is offered, focusing on three time periods, namely, end of the 18th century, the 20th century, and the 21st century, in order to analyze how they were approached by health and government authorities, as well as the challenges they have represented. Historical documentary sources were consulted and, in current cases, participation in them was analyzed. Epidemiological and social historical methodologies were combined. The presence of epidemics in Mexico is a constant on its evolution, which highlights the need for the epidemiological surveillance system to be updated, the importance of being prepared to face an epidemic and to develop a contingency plan.

Se ofrece una perspectiva de las epidemias y pandemias en México en tres periodos: fines del siglo XVIII y siglos XX y XXI, con el fin de analizar cómo las autoridades sanitarias y gubernamentales abordaron estos problemas, así como los desafíos que han representado. Se consultaron fuentes históricas documentales y, en los casos actuales, la participación en ellos. Se combinó metodología epidemiológica e histórica social. La presencia de las epidemias en México es una constante, lo cual evidencia la necesidad de actualizar el sistema de vigilancia epidemiológica, de estar preparados para enfrentar una epidemia y de elaborar un plan de contingencia.

Proteome2virus: Shotgun mass spectrometry data analysis pipeline for virus identification

Objectives: Shotgun proteomics is a generic method enabling detection of multiple viral species in one assay. The reliable and accurate identification of these viral species by analyzing peptides from MS-spectra is a challenging task. The aim of this study was to develop an easy accessible proteome analysis approach for the identification of viruses that cause respiratory and gastrointestinal infections. Method(s): For this purpose, a shotgun proteomics based method and a web application, 'proteome2virus', were developed. Identified peptides were searched in a database comprising proteomic data of 46 viruses known to be infectious to humans. Result(s): The method was successfully tested for cultured viruses and eight fecal samples consisting of ten different viral species from seven different virus families, including SARS-CoV-2. The samples were prepared with two different sample preparation methods and were measured with two different mass spectrometers. Conclusion(s): The results demonstrate that the developed web application is applicable to different MS data sets, generated from two different instruments, and that with this approach a high variety of clinically relevant viral species can be identified. This emphasizes the potential and feasibility for the diagnosis of a wide range of viruses in clinical samples with a single shotgun proteomics analysis.Copyright © 2023

Remote working after lockdown

In order to quickly adapt to the Covid-19 crisis, many companies set up remote working solutions, as an emergency for some and with a procedure studied on the occasion of the 2009 A-H1N1 flu epidemic for others. The Covid-19 crisis has also shown that, when faced with a critical situation, companies were able to drastically shorten their decision-making processes, as well as break years of taboos on certain subjects. Parisian transport system in the middle of winter did not see the remote working approaches put in place at the time. The hierarchical relationships will also have to be rethought, and relationship between performance and time worked on as well. Companies that have structured their knowledge will use this data to build and distribute continuous online training, with assistance, coaching, tutorials, etc. © ISTE Ltd 2022.

Acute encephalitis following COVID-19 vaccines: A case series

Case report Background: Neurological adverse effects (NAE) as headache and dizziness are commonly reported with COVID-19 vaccines but are transient and self-limited. However, few serious NAE have been recently described which can be fatal. Here we report two rare cases of encephalitis related to COVID-19vaccination BNT162b2 (Pfizer) and mRNA-1273 (Moderna) and the inherent challenges in their diagnosis. Method(s): We report two cases of acute encephalitis notified to the department of pharmacovigilance in the University Hospital of Monastir Results: Case n'1: Three weeks after receiving her first dose of mRNA-1273, a 35-year- old female, with a medical history of hypothyroidism and eczema was admitted to the intensive care unit as she had confusion and a febrile tonic-clonic seizure complicated with a status epilepticus and dysautonomia. CSF investigations were nonspecific, and the MRI head did not detect any abnormality. Common causes were excluded by an extensive workup (neoplastic, neuro-vascular, autoimmune and infectious causes). She received cefotaxime and acyclovir without any recovery. However, a spectacular recovery was noticed when receiving methylprednisolone. Case n'2: Three days after receiving her first dose of BNT162b2, a-40- year- old female, with a medical history of rheumatoid arthritis was admitted to the medical care unit as she had experienced a three-day history of headache, memory disturbance, severe cognitive disorders and 4 febrile tonic-clonic seizures. MRI head showed signs of bitemporal encephalitis and CSF investigations was with no findings. Extensive laboratory studies ran out alternative causes as neoplastic, autoimmune and infectious diseases. A twenty-one- day acyclovir regimen was administrated with no recovery. As the cognitive deficit is getting more severe, she got intravenous immunoglobulin therapy with a spectacular improvement. Conclusion(s): Based on the Naranjo Algorithm, this adverse NAR can be possibly (score = 6) induced by COVID-19 vaccines. The dramatic improvement after receiving either corticoids or immunoglobulin therapy supports an immune-mediated mechanism behind this acute presentation. Cases of acute encephalitis secondary to H1N1 influenza and poliomyelitis vaccines have been previously reported but those related to COVID-19 vaccines are still not yet elucidated due to the unproven causality. Further prospective studies are needed to evaluate the causal association between vaccine and NAE occurring vaccination.

Narcolepsy due to a medical condition

"Narcolepsy due to a medical condition” (symptomatic or secondary narcolepsy) results from a specific underlying medical or neurological condition. Common causes are inherited disorders, tumors, head trauma, demyelinating diseases and stroke. Similar to idiopathic narcolepsy, aberrant T cell mediated cytotoxicity to host antigens in hypocretin neurons might be the underlying pathophysiology. Secondary narcolepsy cases have varying ages of onset, typically following a specific underlying medical or neurological disorder. Primary sleep disorders, mental disorders, or drug/substance use needs to be ruled out. Although the main treatment should be controlling underlying pathologic processes, use of wake promoting medications are often warranted. © 2023 Elsevier Inc. All rights reserved

A novel isothermal digital amplification system and its application for absolute quantification of respiratory infectious virus

Herein, we establish a novel isothermal digital amplification system termed digital nicking and extension chain reaction system-based amplification (dNESBA) by utilizing the isothermal NESBA technique and the newly developed miniaturized fluorescence monitoring system (mFMS). dNESBA enables parallel isothermal NESBA reactions in more than 10,000 localized droplet microreactors and read the fluorescence signals rapidly in 150 s by mFMS. This system could identify the genomic RNA (gRNA) extracted from target respiratory syncytial virus A (RSV A) as low as 10 copies with remarkable specificity. The practical applicability of dNESBA was also successfully verified by reliably detecting the gRNA in the artificial sputum samples with excellent reproducibility and accuracy. Due to the intrinsic advantages of isothermal amplifying technique including the elimination of the requirement of thermocycling device and the enhanced portability of the miniaturized read-out equipment, the dNESBA technique equipped with mFMS could serve as a promising platform system to achieve point-of-care (POC) digital molecular diagnostics, enabling absolute and ultra-sensitive quantification of various infectious pathogens even in an early stage.Copyright © 2023

Hypothesis of a potential antiviral drug

The approval of mRNA vaccine technique against COVID-19 opens a door to research and the creation of new drugs against different infectious pathologies or even cancer, since for several diseases the therapeutic options are limited, and different viral diseases are treated only symptomatically. For these reasons, this study proposed a hypothesis supported by biological studies, that it provides a theoretical basis for the possible development of a drug that used the mRNA technique and the ribonucleolytic action of a ribonuclease for a possible antiviral therapy, and analyzed a future perspective of this technique in order to provide a bibliographic basis on this hypothesis and motivate researchers to carry out biological studies on this topic.Copyright © 2022, Health Biotechnology and Biopharma. All rights reserved.

Risk assessment of public health emergencies concerned in China, February 2023

Objective: To assess the risk of public health emergencies occurring in China (except Hong Kong, Macao Special Administrative Regions and Taiwan Province, the same below) or possibly imported from outside China in February 2023. Methods: Based on various data and departmental notification information on domestic and foreign public health emergencies reports and surveillance of key infectious diseases, the expert consultation method was used and experts from provincial (autonomous regions and municipalities directly under the central government) centers for disease prevention and control were invited to participate in the assessment by video conference. Results: The number of public health emergencies to be reported in February 2023 is expected to increase compared to former month. In February 2023, affected by immune escape and reinfection of Omicron variants XBB, CH and other possible emerging subtypes, it is expected that the COVID-19 may become endemic in more areas of the world. In China, because of the increased flow of people after the Spring Festival and the opening of schools, the possibility of the spread of the virus will increase. The influenza viruses activity level may increase in February, and influenza A (H1N1) is more likely to be the main influenza virus. Conclusion: Special attention is given to COVID-19, and general attention is given to seasonal influenza.