Nirsevimab binding-site conservation in respiratory syncytial virus fusion glycoprotein worldwide between 1956 and 2021: an analysis of observational study sequencing data

BACKGROUND: Nirsevimab is an extended half-life monoclonal antibody to the respiratory syncytial virus (RSV) fusion protein that has been developed to protect infants for an entire RSV season. Previous studies have shown that the nirsevimab binding site is highly conserved. However, investigations of the geotemporal evolution of potential escape variants in recent (ie, 2015-2021) RSV seasons have been minimal. Here, we examine prospective RSV surveillance data to assess the geotemporal prevalence of RSV A and B, and functionally characterise the effect of the nirsevimab binding-site substitutions identified between 2015 and 2021. METHOD(S): We assessed the geotemporal prevalence of RSV A and B and nirsevimab binding-site conservation between 2015 and 2021 from three prospective RSV molecular surveillance studies (the US-based OUTSMART-RSV, the global INFORM-RSV, and a pilot study in South Africa). Nirsevimab binding-site substitutions were assessed in an RSV microneutralisation susceptibility assay. We contextualised our findings by assessing fusion-protein sequence diversity from 1956 to 2021 relative to other respiratory-virus envelope glycoproteins using RSV fusion protein sequences published in NCBI GenBank. FINDINGS: We identified 5675 RSV A and RSV B fusion protein sequences (2875 RSV A and 2800 RSV B) from the three surveillance studies (2015-2021). Nearly all (25 [100%] of 25 positions of RSV A fusion proteins and 22 [88%] of 25 positions of RSV B fusion proteins) amino acids within the nirsevimab binding site remained highly conserved between 2015 and 2021. A highly prevalent (ie, >40.0% of all sequences) nirsevimab binding-site Ile206Met:Gln209Arg RSV B polymorphism arose between 2016 and 2021. Nirsevimab neutralised a diverse set of recombinant RSV viruses, including new variants containing binding-site substitutions. RSV B variants with reduced susceptibility to nirsevimab neutralisation were detected at low frequencies (ie, prevalence <1.0%) between 2015 and 2021. We used 3626 RSV fusion-protein sequences published in NCBI GenBank between 1956 and 2021 (2024 RSV and 1602 RSV B) to show that the RSV fusion protein had lower genetic diversity than influenza haemagglutinin and SARS-CoV-2 spike proteins. INTERPRETATION: The nirsevimab binding site was highly conserved between 1956 and 2021. Nirsevimab escape variants were rare and have not increased over time. FUNDING: AstraZeneca and Sanofi.Copyright © 2023 Elsevier Ltd. All rights reserved.

Nitric-oxide enriched plasma-activated water inactivates 229E coronavirus and alters antiviral response genes in human lung host cells

The ongoing pandemic caused by the novel coronavirus, SARS-CoV-2, is influencing global health. Moreover, there is a major threat of future coronaviruses affecting the entire world in a similar, or even more dreadful, manner. Therefore, effective and biocompatible therapeutic options against coronaviruses are urgently needed. To address this challenge, medical specialists require a well-informed and safe approach to treating human coronaviruses (HCoVs). Herein, an environmental friendly approach for viral inactivation, based on plasma technology, was considered. A microwave plasma system was employed for the generation of the high amount of gaseous nitric oxide to prepare nitric oxide enriched plasma-activated water (NO-PAW), the effects of which on coronaviruses, have not been reported to date. To determine these effects, alpha-HCoV-229E was used in an experimental model. We found that NO-PAW treatment effectively inhibited coronavirus infection in host lung cells, visualized by evaluating the cytopathic effect and expression level of spike proteins. Interestingly, NO-PAW showed minimal toxicity towards lung host cells, suggesting its potential for therapeutic application. Moreover, this new approach resulted in viral inactivation and greatly improved the gene levels involved in host antiviral responses. Together, our findings provide evidence of an initiation point for further progress toward the clinical development of antiviral treatments, including such coronaviruses. © 2022 The Authors

Water-soluble inclusion complexes for a novel anti-viral agent with low toxicity;Oseltamivir with the β-cyclodextrins

An innovative sonication method has been developed to produce inclusion complexes (ICs) of Oseltamivir (OTV) which is a potentially water-soluble anti-viral agent with lesser cytotoxicity. Proton signals and chemical shifts of OTV without any ambiguity confirm the formation of ICs with β-Cyclodextrin (B-CD) and Hydroxypropyl-β-cyclodextrin (H-CD). ICs are also supported by their atomic percentages as secondary evidence using XPS analysis. Analysis of drug release at three pH levels revealed the slow release of the OTV from ICs and also suitable for viral inactivation. A very less cytotoxic ability on cancer cell lines and enhanced the viral inactivation of OTV after being made into water-soluble ICs. © 2022 Elsevier B.V.

The 2022 Plasma Roadmap: low temperature plasma science and technology

The 2022 Roadmap is the next update in the series of Plasma Roadmaps published by Journal of Physics D with the intent to identify important outstanding challenges in the field of low-temperature plasma (LTP) physics and technology. The format of the Roadmap is the same as the previous Roadmaps representing the visions of 41 leading experts representing 21 countries and five continents in the various sub-fields of LTP science and technology. In recognition of the evolution in the field, several new topics have been introduced or given more prominence. These new topics and emphasis highlight increased interests in plasma-enabled additive manufacturing, soft materials, electrification of chemical conversions, plasma propulsion, extreme plasma regimes, plasmas in hypersonics, data-driven plasma science and technology and the contribution of LTP to combat COVID-19. In the last few decades, LTP science and technology has made a tremendously positive impact on our society. It is our hope that this roadmap will help continue this excellent track record over the next 5â€"10 years. [ FROM AUTHOR] Copyright of Journal of Physics: D Applied Physics is the property of IOP Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Inflammatory Bowel Disease Is Associated With Significantly Worsened Clinical Outcomes Of Covid-19 Infection In A Retrospective Analysis Of 78,756 Patients Across 143 Hospitals

Coronavirus Disease 2019 (Covid-19) Has Been Diagnosed In Over 50 Million Individuals And Resulted In Greater Than 1 Million Deaths Since Its Discovery In December 2019. Currently, It Is Understood That Cardiovascular Disease, Diabetes, Hypertension, Chronic Lung Disease, Malignancy, Chronic Renal Disease, Obesity, And Smoking Confer Worse Outcomes In Those Afflicted With Covid-19. The Role Of Underlying Gastrointestinal Comorbidities On Covid-19 Prognosis Has Not Been Well Studied. Patients With Inflammatory Bowel Disease (Ibd) Have A Slightly Higher Overall Mortality Than The General Population. While The Pathogenesis Of Ibd Is Not Completely Understood, It Is Thought To Be The Consequence Of Dysregulated Immune Response. A Pair Of Small International Studies Demonstrated That Patients With Ibd Are At Increased Risk Of Covid-19 Infection, Especially When They Have Active Disease And Are Taking Immunosuppressive Therapy. However, The Characteristics And Outcomes Of Covid-19 In Patients With Ibd Remain Unclear. We Conducted A Large-Scale, Multicenter, Retrospective Study To Examine The Outcomes In Ibd Patients Hospitalized For Covid-19. Using Hca Healthcare’S Physician Services Clinical Data Warehouse, We Reviewed 78,756 Adult Patients Across 143 Hospitals Between January Through August 2020 With Covid-19, Yielding 78,572 Covid-19 Patients Without Ibd And 184 With Ibd. Unpaired T-Tests Of Covid-19 Patients With Ibd Compared To Those Without Ibd Showed That Patients With Both Covid-19 And Ibd Experienced Significantly Higher Mortality (8.15% Vs 6.10%, P=0.004), Significantly Higher Rates Of Icu Admission (25.54% Vs 16.49%, P=0.001), Significantly Higher Rates Of Ventilation (13.04% Vs 7%, P=0.002), And Significantly Longer Lengths Of Stay (Los) (7.92 ± 9.84 Vs 4.57 ± 7.87 Days, P<0.001). The Outcomes Of Length Of Stay Remained Significant On Paired T-Test When The 184 Patients With Covid-19 And Ibd Were Age-Matched To Covid-19 Patients Without Ibd. However, There Was No Statistical Significance In Mortality, Icu Admission, And Need For Ventilation When Age-Matched. Ibd Was Independently Associated With Increased Icu Admission (Or 1.5, Ci 1.04 – 2.117, P=0.026) And Need For Ventilation (Or 1.8, Ci 1.124 – 2.775, P=0.010) On Multivariable Regression Analysis, And Los (Or 2.337, Se 0.531, P<0.001) In Linear Regression Analysis. Our Data Corroborates Previous Studies Suggesting Protective Effects Of Female Sex, And Deleterious Effects Of Increasing Age, Myocardial Infarction, Congestive Heart Failure, Cerebrovascular Disease, Chronic Pulmonary Disease, Diabetes, And Cancer. In Summary, Based On Our Study, Patients With Both Ibd And Covid-19 Experienced Significantly Increased Rates Icu Admission, Ventilation, And Lengths Of Stay Compared To Patients With Covid-19 Alone (Table Presented) (Table Presented) (Table Presented) (Table Presented)

CIRRHOSIS IS ASSOCIATED WITH SIGNIFICANTLY WORSENED CLINICAL OUTCOMES OF COVID-19 INFECTION IN A RETROSPECTIVE ANALYSIS OF 23,474 PATIENTS ACROSS 143 HOSPITALS

Coronavirus disease 2019 (COVID-19) has been diagnosed in at least 63.5 million individuals and resulted in 1.4 million deaths as of December 2020 since its discovery. Various risk factors for severe illness have been investigated;currently it is understood that cardiovascular disease, diabetes mellitus, hypertension, chronic lung disease, malignancy, chronic renal disease, obesity, and smoking confer worse outcomes. Liver cirrhosis is understood to be a significant source of general morbidity and mortality due, in part, to compromise of the immune system. A multicenter, retrospective examination of 50 patients with both COVID-19 and cirrhosis showed that patients with cirrhosis were at increased risk for mortality from COVID-19 than those without cirrhosis. To our knowledge, there exists no large study to examine the effect of cirrhosis on COVID-19 outcomes. We performed a multicenter, retrospective study to further examine outcomes in cirrhotic patients hospitalized for COVID-19 infection. Using the HCA Healthcare Physician Services clinical data warehouse, we reviewed 23,474 adult patients across 143 hospitals admitted from January through August 2020 with COVID-19, yielding 22,467 COVID-19 patients without cirrhosis and 1,007 with cirrhosis. Unpaired T-tests of COVID-19 patients with cirrhosis compared to those without cirrhosis showed that patients with both COVID-19 and cirrhosis experienced significantly higher mortality (17.97% vs 12.96%, p<0.001), significantly higher rates of ICU admission (45.58% vs 33.90%, p<0.001), significantly higher rates of ventilation (24.43% vs 16.07%, p<0.001), and significantly longer lengths of stay (LOS) (11.05 ± 10.86 vs 8.46 ± 10.05 days, p<0.001). The outcomes of ICU admission and length of stay remained significant on paired T-test when the 1,007 patients with COVID-19 and cirrhosis were age-matched to COVID-19 patients without cirrhosis. Cirrhosis was independently associated with increased mortality (OR 1.33, CI 1.11-1.58, p=0.002), ICU admission (OR 2.08, CI 1.16-1.52, p<0.001), and ventilation (OR 1.32, CI 1.13-1.54, p<0.001) on multivariable regression analysis. Our dataset corroborates previous studies suggesting protective effects of female sex;and deleterious effects of increasing age, myocardial infarction, cerebrovascular disease, diabetes, cancer, and obesity. Chronic pulmonary disease was significantly associated with poor outcomes of all measures except mortality. Additionally, length of stay among patients with both COVID and cirrhosis is estimated to increase by 1.65 (SE 0.31, p<0.001) on linear regression analysis. In summary, patients with both cirrhosis and COVID-19 experienced significantly increased rates of mortality, ICU admission, ventilation, and lengths of stay compared to patients with COVID-19 alone. (Table presented.)

Plasma bioscience and medicines

The nonthermal atmospheric biocompatible plasma, also called cold plasma, is the fourth state of matter, is a partially ionized gas consisting cocktail of gas’s molecules, free radicals, ions, electrons, and physical components such as photons, electric field and some heat. It has been successfully used in the biomedical, agricultural food safety, environment applications including industrial application for the processing of materials and etc. for not mentioned here. The recent discovery of its efficacy in sterilization of microorganisms has trigged a large quantity of research in the biomedical field. Here we review configurations and electrode layouts of typical plasma device for applications to biomedical such as cancer treatment and virus inactivation technology. Cocktail of reactive oxygen and nitrogen species (RONS) would be efficient and effective to several biomedical applications such as inactivation of drug-resistant bacteria, cancer treatment, inactivation of viruses, skin and dental applications. This detailed review provides an outline of typical plasma sources, their physical and chemical (RONS) characteristics based on their diagnostic methods, including cancer treatment strategies and inactivation of viruses. This review also emphasizing on strategises to control and inactivation of SARS-COV2 (COVID19) and rejuvenate lung cells. Plasma bioscience and medicine technologies will deliver a new model of therapeutic clinical systems along with sustainable application to environmental issues. © 2021, Korean Vacuum Society. All rights reserved.

Clinical and epidemiological characteristics of common human coronaviruses in children: A single center study, 2015–2019

Purpose: Common human coronaviruses (HCoVs) are relatively understudied due to the mild nature of HCoV infection. Given the lack of local epidemiology data on common HCoVs, we aimed to describe clinical and epidemiological characteristics of common HCoVs in children. Methods: Respiratory viral test results from 9,589 respiratory samples from Seoul National University Children's Hospital were analyzed from January 2015 to December 2019. Viral detection was done by the multiplex reverse transcription polymerase chain reaction. Demographics and clinical diagnosis were collected for previously healthy children tested positive for HCoVs. Results: Of the 9,589 samples tested, 1 or more respiratory viruses were detected from 5,017 (52.3%) samples and 463 (4.8%) samples were positive for HCoVs (OC43 2.8%, NL63 1.4%, 229E 0.7%). All 3 types co-circulated during winter months (November to February) with some variation by type. HCoV-OC43 was the most prevalent every winter season. HCoV-NL63 showed alternate peaks in late winter (January to March) and early winter (November to February). HCoV-229E had smaller peaks every other winter. Forty-one percent of HCoV-positive samples were co-detected with additional viruses;human rhinovirus 13.2%, respiratory syncytial virus 13.0%, influenza virus 4.3%. Common clinical diagnosis was upper respiratory tract infection (60.0%) followed by pneumonia (14.8%), croup (8.1%), and bronchiolitis (6.7%). Croup accounted for 17.0% of HCoV-NL63-positive children. Conclusions: This study described clinical and epidemiological characteristics of common HCoVs (OC43, NL63, 229E) in children. Continuing surveillance, perhaps by adding HKU1 in the diagnostic panel can further elucidate the spectrum of common HCoV infections in children. © 2021 The Korean Society of Pediatric Infectious Diseases.

Updates on coronavirus disease-2019 vaccine and consideration in children

As of March 2021, humanity has been suffering from the global severe acute respiratory syndrome coronavirus 2 pandemic that began late 2019. In 2020, new vaccine platforms— including mRNA vaccines and viral vector-based DNA vaccines—have been given emergency use authorization (EUA), leading to rolling out the vaccines for global mass vaccinations. The purpose of this article is to review the currently most widely used coronavirus disease 2019 vaccines: their action mechanisms and efficacy and safety data from clinical trials that have been published to date. In addition, the current status of clinical trials in the pediatric population was summarized, and further consideration for them was discussed.

Ethical considerations and patient safety concerns for cancelling non-urgent surgeries during the COVID-19 pandemic: a review

At the time of writing of this article, there have been over 110 million cases and 2.4 million deaths worldwide since the start of the Coronavirus Disease 2019 (COVID-19) pandemic, postponing millions of non-urgent surgeries. Existing literature explores the complexities of rationing medical care. However, implications of non-urgent surgery postponement during the COVID-19 pandemic have not yet been analyzed within the context of the four pillars of medical ethics. The objective of this review is to discuss the ethics of elective surgery cancellation during the COVID-19 pandemic in relation to beneficence, non-maleficence, justice, and autonomy. This review hypothesizes that a more equitable decision-making algorithm can be formulated by analyzing the ethical dilemmas of elective surgical care during the pandemic through the lens of these four pillars. This paper's analysis shows that non-urgent surgeries treat conditions that can become urgent if left untreated. Postponement of these surgeries can cause cumulative harm downstream. An improved algorithm can address these issues of beneficence by weighing local pandemic stressors within predictive algorithms to appropriately increase surgeries. Additionally, the potential harms of performing non-urgent surgeries extend beyond the patient. Non-maleficence is maintained through using enhanced screening protocols and modifying surgical techniques to reduce risks to patients and clinicians. This model proposes a system to transfer patients from areas of high to low burden, addressing the challenge of justice by considering facility burden rather than value judgments concerning the nature of a particular surgery, such as cosmetic surgeries. Autonomy can be respected by giving patients the option to cancel or postpone non-urgent surgeries. However, in the context of limited resources in a global pandemic, autonomy is not absolute. Non-urgent surgeries can ethically be postponed in opposition to the patient's preference. The proposed algorithm attempts to uphold the four principles of medical ethics in rationing non-urgent surgical care by building upon existing decision models, using additional measures of resource burden and surgical safety to increase health care access and decrease long-term harm as much as possible. The next global health crisis will undoubtedly present its own unique challenges. This model may serve as a comprehensive starting point in determining future guidelines for non-urgent surgical care.