Severe Flu Research Articles

Molecular characterisation of influenza B virus from the 2017/18 season in primary models of the human lung reveals improved adaptation to the lower respiratory tract

ABSTRACT The 2017/18 influenza season was characterized by unusual high numbers of severe infections and hospitalizations. Instead of influenza A viruses, this season was dominated by infections with influenza B viruses of the Yamagata lineage. While this IBV/Yam dominance was associated with a vaccine mismatch, a contribution of virus intrinsic features to the clinical severity of the infections was speculated. Here, we performed a molecular and phenotypic characterization of three IBV isolates from patients with severe flu symptoms in 2018 and compared it to an IBV/Yam isolate from 2016 using experimental models of increasing complexity, including human lung explants, lung organoids, and alveolar macrophages. Viral genome sequencing revealed the presence of clade but also isolate specific mutations in all viral genes, except NP, M1, and NEP. Comparative replication kinetics in different cell lines provided further evidence for improved replication fitness, tolerance towards higher temperatures, and the development of immune evasion mechanisms by the 2018 IBV isolates. Most importantly, immunohistochemistry of infected human lung explants revealed an impressively altered cell tropism, extending from AT2 to AT1 cells and macrophages. Finally, transcriptomics of infected human lung explants demonstrated significantly reduced amounts of type I and type III IFNs by the 2018 IBV isolate, supporting the existence of additional immune evasion mechanisms. Our results show that the severeness of the 2017/18 Flu season was not only the result of a vaccine mismatch but was also facilitated by improved adaptation of the circulating IBV strains to the environment of the human lower respiratory tract.

Influenza A defective viral genomes and non-infectious particles are increased by host PI3K inhibition via anti-cancer drug alpelisib.

RNA viruses produce abundant defective viral genomes during replication, setting the stage for interactions between viral genomes that alter the course of pathogenesis. Harnessing these interactions to develop antivirals has become a recent goal of intense research focus. Despite decades of research, the mechanisms that regulate the production and interactions of Influenza A defective viral genomes are still unclear. The role of the host is essentially unexplored; specifically, it remains unknown whether host metabolism can influence the formation of defective viral genomes and the particles that house them. To address this question, we manipulated host cell anabolic signaling activity and monitored the production of defective viral genomes and particles by A/H1N1 and A/H3N2 strains, using a combination of single-cell immunofluorescence quantification, third-generation long-read sequencing, and the cluster-forming assay, a method we developed to titer defective and fully-infectious particles simultaneously. Here we show that alpelisib (Piqray), a highly selective inhibitor of mammalian Class 1a phosphoinositide-3 kinase (PI3K) receptors, significantly changed the proportion of defective particles and viral genomes (specifically deletion-containing viral genomes) in a strain-specific manner, under conditions that minimize multiple cycles of replication. Alpelisib pre-treatment of cells led to an increase in defective particles in the A/H3N2 strain, while the A/H1N1 strain showed a decrease in total viral particles. In the same infections, we found that defective viral genomes of polymerase and antigenic segments increased in the A/H1N1 strain, while the total particles decreased suggesting defective interference. We also found that the average deletion size in polymerase complex viral genomes increased in both the A/H3N2 and A/H1N1 strains. The A/H1N1 strain, additionally showed a dose-dependent increase in total number of defective viral genomes. In sum, we provide evidence that host cell metabolism can increase the production of defective viral genomes and particles at an early stage of infection, shifting the makeup of the infection and potential interactions among virions. Given that Influenza A defective viral genomes can inhibit pathogenesis, our study presents a new line of investigation into metabolic states associated with less severe flu infection and the potential induction of these states with metabolic drugs.

Exploring the Therapeutic Potential of Chrysanthemum morifolium: An Ethnopharmacological Perspective

Aim: The current manuscript aims to discuss the ethnopharmacological relevance of the common plant Chrysanthemum morifolium, also known as pot mums and its potential therapeutic applications. Methods: A bibliography survey was carried out using various electronic databases like google scholar, ScienceDirect, Springer, Scopus, PubMed, Wiley, etc. Other offline, as well as, online academic libraries were also used for the bibliography survey and compilation of data. Result and Discussion: Traditional remedies have grown in both therapeutic and economic importance around the world and are used by various groups of people. While the use of these medications has grown, there are still concerns about their consistency, safety, and efficacy in many areas. Chrysanthemum is the peak three of the world’s mainly significant cut flowers with an important herb of traditional Chinese medicine (TCM). It contains abundant volatile oil and flavonoids. It has been used for a long time to treat allergies, cardiovascular disease, severe flu, hypertension, and sore throat. It also has characteristics such as anti-inflammatory, antibacterial, aromatic, demulcent, febrifuge, hepatic, hypotensive, refrigerant, etc. Conclusion: It can be established from the complete study that various active constituents can be isolated from the plant which has potential therapeutic value and justifies its use on modern scientific parameters.

Lung microvascular occlusion by platelet-rich neutrophil-platelet aggregates promotes cigarette smoke-induced severe flu.

Cigarette smoking is associated with a higher risk of ICU admissions among patients with flu. However, the etiological mechanism by which cigarette smoke (CS) exacerbates flu remains poorly understood. Here, we show that a mild dose of influenza A virus promotes a severe lung injury in mice preexposed to CS but not room air for 4 weeks. Real-time intravital (in vivo) lung imaging revealed that the development of acute severe respiratory dysfunction in CS- and flu-exposed mice was associated with the accumulation of platelet-rich neutrophil-platelet aggregates (NPAs) in the lung microcirculation within 2 days following flu infection. These platelet-rich NPAs formed in situ and grew larger over time to occlude the lung microvasculature, leading to the development of pulmonary ischemia followed by the infiltration of NPAs and vascular leakage into the alveolar air space. These findings suggest, for the first time to our knowledge, that an acute onset of platelet-driven thrombo-inflammatory response in the lung contributes to the development of CS-induced severe flu.

Rapid detection of human influenza A viruses by HFman probe-based loop-mediated isothermal amplification assays

Since China abandoned the zero-COVID policy at the end of 2022, a wave of severe Flu pandemic emerged in China. Rapid and accurate diagnosis of Influenza A virus (IAV) is critical for clinical management and therapeutic decision-making of patients with fever. Here, we reported a novel IAV HF-LAMP assay, which can be performed with purified RNA or directly using clinical samples. The assays with purified RNA and clinical samples have high sensitivity with limit of detection (LOD) of 9.6 copies/reaction, 9900 copies/mL, and short sample-to-answer times of 36 and 50 min, respectively. Both assays showed high specificity and significantly higher IAV detection rate than the rapid antigen detection (RAD) assays. Furthermore, we found the vast majority (91.2 %) of children with fever during the pandemic were infected by IAV, and current IAV infection has a very narrow detectable window. The novel IVA HF-LAMP assays will provide robust tools to facilitate early diagnosis of IAV infection in current and future seasonal influenza epidemics.

Determinants of Flu Vaccine Uptake Among the General Population in Saudi Arabia: A Study Based on the Health Belief Model.

Background and objective Recently, influenza has emerged as a significant public health concern worldwide, including in Saudi Arabia. Vaccination against the flu is widely recognized as a crucial preventive measure to reduce morbidity and mortality associated with the virus. However, the uptake of flu vaccines among the general population in Saudi Arabia still remains low. In light of this, this study aimed to examine thedeterminants of influenza vaccine uptake in Saudi Arabia by using the Health Belief Model (HBM). Methods This cross-sectional study was conducted among adults living in all regions of Saudi Arabia by using an online self-administered questionnaire based on the HBM.The questionnaire inquired aboutdemographics, knowledge about influenza, knowledge about vaccines, and beliefs/barriers. It was distributed via social media platforms, including WhatsApp, Twitter, and Instagram. IBM SPSS Statistics softwareversion 29 (IBM Corp., Armonk, NY)was used for statistical analyses, and both the Chi-square test and logic regression analyses were applied to determine associations between explanatory and response variables, with the level ofsignificance set at p<0.05. Results This study enrolled a total of 1040 participants, and the majority were Saudi nationals (96.9%). Of note, 66.2% of the participants were males, and the rest were females. Most of the participants were employed by governmental institutions (42.0%), had bachelor's degrees (58.4%), had never worked in the health sector (70.2%), and earned above 10,000 Saudi riyals per month (62.1%). Over half (55.7%) of participants had taken the flu vaccine at the time of this study. Working in the healthcare sector was associated with increased flu vaccine uptake [adjusted odds ratio (aOR): 3.84, p<0.001]. The likelihood of getting the flu vaccines was greater among men (aOR: 1.38, p=0.027), and obesity was associated with lower flu vaccine uptake (aOR: 0.29, p=0.034). Having contact with people with flu, having had flu in the past, and experiencing severe flu complications (aOR: 4.71, p=0.029; aOR: 0.13, p=0.006; and aOR: 0.29, p=0.033, respectively)were significantly associated with the flu vaccine uptake among our studyparticipants. Perceived potential risks of the flu vaccine were also associated with taking the flu vaccine (aOR: 0.213, p=0.042). There was a significant association between seeing an advertisement for the flu vaccine and the likelihood of taking the vaccine (aOR: 5.488, p=0.042). Conclusion This study found that certain sociodemographic factors are associated withflu vaccine uptake. These factors included contact with flu-infected individuals, pastexperiences with flu, perceived risks, and exposure to flu vaccine advertisements. Improving healthcare accessibility, conducting awareness campaigns, and implementing workplace initiatives are recommended to address the issues related to flu vaccine uptake.

The perfect storm: An unseasonably early RSV annual epidemic, a severe annual flu epidemic, and a smoldering COVID-19 pandemic

The perfect storm: An unseasonably early RSV annual epidemic, a severe annual flu epidemic, and a smoldering COVID-19 pandemic

The evolution of the global COVID-19 epidemic in Morocco and understanding the different therapeutic approaches of chitosan in the control of the pandemic.

In 2020, Coronavirus disease (COVID-19), a new viral respiratory disease caused by a virus that belongs to Coronaviridae family, has been identified. It is a very severe flu that negatively affects the functions of the lung and other respiratory organs. COVID-19 virus can be transmitted between people either by touching an infected person or by direct contact with their respiratory droplets. Therefore, the COVID-19 virus has become a global concern due to its rapid spread and severity. Based on the World Health Organization report from 2 March 2020 to 24 October 2022, the total infected cases and deaths in Morocco are around 1,265,389 (3.46%) and 16,280 (0.04%), respectively. Recently, some scientists have found that chitosan, a polymer existed in nature, can inhibit COVID-19 infection and repair damaged tissue. Therefore, understanding chitosan mechanisms in controlling COVID-19, might lead to innovative strategies in the medical field, such as developing drugs against SARS-CoV-2, and replacing vaccines, which have negative side effects. This review aims to show the evolution of the COVID-19 pandemic worldwide, specifically in Morocco, its pathophysiology, and its ability to silence the immune system. This review also provides an overview of the treatments and measures applied to protect human beings and how chitosan acts and controls COVID-19.

Early and Severe Flu Season May Start After COVID-19

Early and Severe Flu Season May Start After COVID-19

Layered protein nanoparticles containing influenza B HA stalk induced sustained cross-protection against viruses spanning both viral lineages

The influenza epidemics pose a significant threat to public health. Of them, type B influenza coincided with several severe flu outbreaks. The efficacy of the current seasonal flu vaccine is limited due to the antigenicity changes of circulating strains. In this study, we generated structure-stabilized HA stalk antigens from influenza B and fabricated double-layered protein nanoparticles as universal influenza B vaccine candidates. In vitro studies found that the resulting protein nanoparticles were effectively taken up to activate dendritic cells. Nanoparticle immunization induced broadly reactive immune responses conferring robust and sustained cross-immune protection against influenza B virus strains of both lineages. The results reveal the potential of layered protein nanoparticles incorporated with structure-stabilized constant antigens as a universal influenza vaccine with improved immune protective potency and breadth.

Would Illness Representations of COVID-19 and COVID-19 Fears During Clinic Visits Promote or Reduce Behavioral Intention to Seek Medical Consultations for Flu Symptoms? A Random Telephone Survey in Hong Kong, China.

BackgroundThe study investigated the level of behavioral intention to consult doctors for flu symptoms (BICDFS) during the Coronavirus Disease 2019 (COVID-19) pandemic and examined its associations with illness representations of COVID-19 and fear of COVID-19 during clinic visits in a general Chinese adult population.MethodsA random telephone survey was conducted among 300 residents in Hong Kong, China in April 2020 when the second wave of COVID-19 was just ended in the region. The participants were asked about their intention to consult doctors if they had mild or severe flu symptoms in the next week (from 1 = definitely no to 5 = definitely yes). Illness representations of COVID-19 were measured by the Chinese version of the Brief Illness Perception Questionnaire (BIPQ). The fear of COVID-19 during clinic visits were assessed by two single items. Linear regression adjusted for background variables and hierarchical strategies were employed.ResultsOf the participants, 52.3 and 92.0% showed an intention to consult doctors for mild and severe flu symptoms, respectively. Adjusted for background factors, COVID-19-related cognitive representations (consequences: standardized b = 0.15, p = 0.010; understanding: standardized b = 0.21, p = 0.001) and emotional representations (concern: standardized b = 0.17, p = 0.001; negative emotions: standardized b = 0.19, p = 0.001) were positively associated with BICDFS. In the hierarchical model, independent significant factors of BICDFS included understanding (standardized b = 0.16, p = 0.013) and negative emotions (standardized b = 0.17, p = 0.008). The fear-related variables showed non-significant associations with the BICDFS.ConclusionsPromotion of care-seeking behaviors for flu symptoms during the COVID-19 pandemic should consider improving people's understanding of COVID-19 and providing advice on related coping strategies for emotional responses to COVID-19.

The impact of mental distress on influenza vaccine coverage.

Influenza is a major cause of morbidity and mortality worldwide. The flu vaccine is the most important strategy to prevent influenza. Studies indicate that individuals with mental health disorders are at an increased risk of comorbid health conditions that predispose them to severe flu complications. This study examined the association between mental distress and influenza vaccine coverage among non-institutionalized adults in the United States. Data was analyzed from the 2016 Behavioral Risk Factor Surveillance System (BRFSS). The analytic sample (453,924) included those with valid information on health-related quality of life (HRQOL) and flu vaccine coverage. Bivariate analysis and logistic regression were performed. Those with infrequent mental distress had 1% (95% confidence interval [CI] 0.96,1.03) lower odds and those with frequent mental distress had 21% (95% CI 0.75,0.82) decrease odds of receiving the flu shot in comparison to those with no mental distress, given all else equal. A negative effect on influenza vaccination rates was observed with frequent mental distress when compared to those with no mental distress. Further studies are warranted to better understand this association.

Detection of feline panleukopenia with antigen test kit

Feline panleukopenia is an infectious disease caused by the feline panleukopenia virus (FPV). The signs of infected cats in-clude fever, lethargy, anorexia, diarrhoea, and vomit. A secondary infection can exacerbate this condition, such as bacteria. The aim of this study to find out the diagnostic technique and the FPV detection method using the FPV antigen test kit. On August 2nd, 2021, the cat was brought to Griya Fauna Mojokerto with severe flu. In addition, based on the information, the cat has decreased appetite. The physical examination results that the temperature was 39.5 °C, bodyweight of 2.9 kg, and the cat looked weak when observed. Further, the FPV antigen test kit was used to confirm the diagnosis in this case. The FPV antigen test kit showed positive results that indicated by forming two lines on the test line (T) and the control line (C).

Experience with COVID-19 convalescent plasma provides vital guidance to future pandemics.

Experience with COVID-19 convalescent plasma provides vital guidance to future pandemics.

Thailand's Covid-19 Crisis: A Tale in Two Parts

Thailand's Covid-19 Crisis:A Tale in Two Parts Gregory V. Raymond (bio) By October 2021, Thailand had recorded over 17,000 deaths from Covid-19, and its target to have 70% of the public double-vaccinated was still months away.1 Like other countries, Thailand's Covid-19 story has had many chapters with twists, turns, and setbacks on the journey to "return to normal," and the myriad individual experiences of hardship and suffering among its most economically vulnerable populations will probably never be told. Partly because of its high reliance on tourism, Thailand—the second-largest economy in Southeast Asia and one of the more prosperous states there—will likely emerge from the pandemic as one of the worst-hit regional states by Covid-19. The Health Impact and Response to Covid-19 in Thailand Covid-19's health impact in Thailand was initially mild but changed dramatically in 2021. In fact, 2020 and 2021 offer a tale in two halves: the first showing the strength of Thailand's healthcare and disease-prevention infrastructure, and the second revealing weakness in planning for worst-case scenarios. Before the pandemic, the Johns Hopkins University rated Thailand as sixth in the world on pandemic preparedness.2 Over several decades, Thailand has created a decentralized health administration system that is capable of acting locally with autonomy, flexibility, and—due to prior experience of epidemics such as Severe Acute Respiratory Syndrome (SARS) and avian flu—effectiveness. When Covid-19 reached Thailand in January 2020, the system needed no direction from the national government. At the village level, Thailand's 1.04 million well-trained village health volunteers [End Page 10] swung into action, each reaching out to their ten to fifteen assigned households with relevant information on the virus.3 These volunteers managed close-contact cases, monitored individuals in quarantine, and manned checkpoints. At the municipal level, local governments also acted ahead of the national government, inviting local civil society groups to bid for funds in support of health projects, such as those that taught citizens to make masks and alcohol-based sanitizer and trained high school students in hygiene.4 These measures, together with restricting inbound international travel, bringing patients into facilities rather than keeping them at home, and closing all but essential businesses, were effective in containing the initial strain of the virus. By the end of September 2020, Thailand could claim that after 3,559 cases and 59 deaths, the only infected people were those who remained in quarantine.5 Tedros Ghebreyesus, director-general of the World Health Organization, was impressed, stating that, "Thailand's response to Covid-19 offers a powerful example of how investment in public health and all-of-society engagement can control outbreaks of deadly diseases, protect people's health, and allow economies to continue functioning."6 Sadly, this success in 2020—built on effective contact tracing, community compliance, and comprehensive social distancing measures—was not sufficient to arrest the spread of new variants of Covid-19 that emerged in 2021. Thailand experienced reasonable success in containing its second wave of Covid-19, which started at the end of 2020 among migrant workers at a seafood market in the province of Samut Sakhon on the outskirts of Bangkok. But with the third wave, which started in April 2021, the country entered a more desperate and dangerous struggle against Covid-19. This wave began its spread from the Krystal Club, an upscale nightclub frequented by politicians and diplomats. It thus initially spread among Thailand's elite, and soon there was a marked increase in daily cases and deaths.7 By May, Thailand was experiencing [End Page 11] five thousand new cases a day, as many as it had experienced in the whole of November 2020.8 The more infectious Alpha strain initially fueled the April 2021 surge, and its spread puzzled Thai virologists, who wondered how community transmission had occurred despite Thailand's border controls, quarantine system, and testing protocols.9 But worse was to come, because the even more infectious Delta strain was detected in Thailand by June.10 By July, Delta was the dominant variant in the country, with new cases reaching over ten...

National Institute for Health and Care Research to fund new phase of platform trial to assess treatments for severe flu

A platform trial used to assess treatments for COVID-19 during the pandemic will, for the first time, look at treatments for people hospitalised with severe influenza. The ‘Randomised, embedded, multi-factorial, adaptive platform trial for community-acquired pneumonia‘ (REMAP-CAP) was originally established in 2016 by researchers from several countries to assess treatments for community-acquired pneumonia during pandemics. […]

Cigarette Smoking Exacerbates Flu-Induced Thrombo-Inflammation

Rationale: Epidemiological evidence suggests that prior exposure to cigarette smoke (CS) or habitual smoking increases the risk of influenza A virus (IAV)-triggered respiratory failure (severe flu). Although emerging evidence supports the role of thrombo-inflammation in the development of CS and IAV-triggered lung injury, the innate immune mechanism that contributes to this morbidity remains poorly understood.Materials and methods: We have developed a two-hit model of CS-induced severe flu in mice. Mice were exposed to four weeks of room air (air) or CS followed by intra-nasal administration of A/PR/8/34 (H1N1) IAV. The body weight was measured every day for two weeks after IAV administration followed by assessment of lung injury at day 7 and 14. Lungs were harvested for histological assessment of lung injury and estimation of viral titer by RT-PCR. Quantitative fluorescence intravital lung microscopy (qFILM) was conducted at 2-, 3- and 4-days post IAV-infection to visualize dynamics of neutrophil and platelet recruitment in the lung of mice IV administered with fluorescent dextran, anti-Ly6G Ab and anti-CD49Ab.Results: Mice exposed to CS+IAV manifested significantly more weight loss, lung injury, lung congestion and alveolar hemorrhage compared to mice administered room-air+IAV. QFILM revealed that severity of lung injury was associated with significantly more entrapment of neutrophil-platelet aggregates within the pulmonary microcirculation and infiltration into the air spaces of CS+IAV than room-air+IAV administered mice.Conclusion: These initial results suggest that CS primes innate immune signaling in neutrophils and platelets to promote their recruitment in the lung following flu. Currently, studies are underway to identify innate immune pathways in neutrophils and platelets that drive this severe thrombo-inflammatory response. DisclosuresSundd: CSL Behring Inc: Research Funding; Bayer: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding.

A new drug formula for pneumonia and severe seasonal flu; a promising drug for eradicate COVID19.

World Health Organization (WHO) well-known pleiotropic antiviral compounds.This study was designed to evaluate the effects of herbal drug combination in treatment of pneumonia, severe respiratory distress, and severe flu and recently for COVID19.The treatment phase includes 12 days period of herbal drug mixture (X) . Results showed the activity of herbal drug in eradication of COVID19, pneumonia and severe seasonalful.

Clinical features and risk factors for severe influenza in children: A study from multiple hospitals in Shanghai

The incidence and mortality of influenza in children had risen, but data are limited on children with severe influenza virus infection in China. We conducted a retrospective case-control study and collected the patients' clinical data. Clinical data including demography, clinical presentation, laboratory findings, radiologic findings, treatment and outcomes were collected. Children were clinically confirmed to have virus infection in Shanghai in three hospitals from June 2014 to June 2019. During the study, 36,047 children were enrolled. Among them, 118 met the criteria for severe flu. Clinical symptoms such as fever, cough, gastrointestinal symptoms, coma and epilepsy were higher in the severe group. Complications such as pneumorrhagia, heart failure, septic shock, acute renal failure and influenza-associated encephalitis were higher in the severe influenza group than the death group. The laboratory findings including decreased hemoglobin, high alanine aminotransferase, high urea nitrogen and high lactate levels were risk factors for death in children with influenza. Influenza-associated encephalopathy (IAE), acute respiratory distress syndrome (ARDS) were the common clinical manifestations and complications for the severe influenza, and delayed use of oseltamivir was found to be associated with fatality.

Platelet-rich neutrophil-platelet micro-emboli contribute to cigarette smoke induced flu severity.

Abstract Epidemiological evidence suggests that prior exposure to cigarette smoke (CS) or habitual smoking increases the risk of influenza A virus (IAV)-triggered respiratory failure. Although emerging evidence supports the role of thrombo-inflammation in the development of CS and IAV-triggered lung injury, the innate immune mechanism remains poorly understood. We have developed a two-hit model of CS-induced severe flu in mice. Mice were exposed to four weeks of room air (air) or CS followed by intra-nasal administration of A/PR/8/34 IAV. The body weight was measured every day for two weeks after IAV administration followed by assessment of lung injury at day 7. Lungs were harvested for histological assessment and viral titration by qPCR. Quantitative fluorescence intravital lung microscopy (qFILM) was conducted at 2-, 3- and 4-days post IAV-infection to visualize dynamics of neutrophil and platelet recruitment in the lung of mice IV administered with fluorescent dextran, anti-Ly6G Ab and anti-CD49Abs. Mice exposed to CS+IAV manifested significantly more weight loss, lung injury, lung congestion, hemorrhage and hypoxemia compared to mice administered IAV only. QFILM revealed that severity of lung injury was associated with significantly larger area with impaired blood flow and more vascular leakage secondary to vascular occlusion by platelet-rich neutrophil-platelet aggregates in the lung of CS+IAV than IAV administered mice. These initial results suggest that CS primes innate immune signaling in neutrophils and platelets to promote their recruitment in the lung following flu, leading to severe acute lung injury. Currently, studies are underway to identify innate immune pathways that drive hyper thrombo-inflammatory response.