Passive immunotherapies for the next influenza pandemic.

Influenzavirus is among the most relevant candidates for a next pandemic. We review here the phylogeny of former influenza pandemics, and discuss candidate lineages. After briefly reviewing the other existing antiviral options, we discuss in detail the evidences supporting the efficacy of passive immunotherapies against influenzavirus, with a focus on convalescent plasma.

[The definition of pandemic: causes and consequences of its adjustment in 2009 and 2011].

The article considers results of the study evaluating historical and epidemiological events that preceded and accompanied adjustment of the pandemic description on the WHO website in 2009 and 2011. The analysis covered publications related to epidemics and pandemics issues, the WHO documents, the WHO website. The descriptions of pandemic mostly focused on "enormous numbers of cases and deaths". Since May 2009, new description of pandemic was published, focusing on disease prevalence. In 2011 it reverted to initial one with no comments. From perspective of the WHO document of 2009, declaration of swine flu pandemic in June 2009 seemed justified. However, considering previous pandemic history, common sense and consequences of declaring pandemic of disease with low both number of cases and mortality, it was premature move. Since primary factor hindering development of pandemic is effectiveness of infectious disease treatment, to minimize likelihood of new pandemic it is necessary to improve special medical education quality and to study and to adapt to modern conditions all effective medications and methods used in the past.

COVID-19 and H1N1 Influenza: Are They 2 Sides of the Same Coin?

Background: Swine flu (H1N1) and Coronavirus diseases (COVID-19) have been compared in the past few months. Both pandemics sparked a worldwide major panic. Although both have some common symptoms and diagnoses, they are quite different in many aspects. The current study aimed to investigate the differences in clinical and viral behaviors between H1N1 Influenza and COVID-19 pneumonia. Methods: This was a retrospective study of adult patients hospitalized with H1N1 influenza pneumonia between January 2019 and February 2020, and patients hospitalized with COVID-19 during the outbreak. A demographic and clinical characteristic of H1N1 influenza and COVID-19 patients were recorded. Both groups were compared-using an independent samples student t test for continuous variables and a chi-square test for categorical data-to identify significantly different parameters between the 2 diseases. Results: A total of 78 patients were included and divided into 2 groups: 33 patients (42.3%) with H1N1 and 45 patients (57.7%) with COVID-19. The mean age of the patients was 43.3 ± 10.6 years. Bronchial asthma was significantly higher among patients with H1N1, while diabetes mellitus was significantly higher among patients with COVID-19. Right lower lobe affection was significantly present among those with H1N1 than those with COVID (100% vs 0%). The monocytic count was significantly higher among those with H1N1 than COVID-19 (11.63 ± 1.50 vs 7.76 ± 1.68; P < 0.001). Respiratory rates of more than 22 c/min significantly increased in patients with HINI than in those with COVID-19 (18.2% vs 4.4%; P = 0.05). Mortality increased in patients with HINI than in those with COVID-19 (18.2% vs 6.7%). However, the difference did not reach statistical significance (P = 0.15). Conclusion: Clinically, it is difficult to distinguish between H1N1 and COVID-19. Thus, a polymerase chain reaction is recommended for all patients suffering from influenza-like symptoms to rule out influenza A subtype H1N1 and/or SARS-CoV2.

Determining Existing Human Population Immunity as Part of Assessing Influenza Pandemic Risk.

Zoonotic influenza infections continue to threaten human health. Ongoing surveillance and risk assessment of animal viruses are needed for pandemic preparedness, and population immunity is an important component of risk assessment. We determined age-stratified hemagglutinin inhibition seroprevalence against 5 swine influenza viruses circulating in Hong Kong and Guangzhou in China. Using hemagglutinin inhibition seroprevalence and titers, we modeled the effect of population immunity on the basic reproduction number (R0) if each virus were to become transmissible among humans. Among 353 individual serum samples, we reported low seroprevalence for triple-reassortant H1N2 and Eurasian avian-like H1N1 influenza viruses, which would reduce R0 by only 18%-20%. The smallest R0 needed to cause a pandemic was 1.22-1.24, meaning existing population immunity would be insufficient to block the spread of these H1N1 or H1N2 variants. For human-origin H3N2, existing population immunity could suppress R0 by 47%, thus reducing pandemic risk.

Potential Threats to Human Health from Eurasian Avian-Like Swine Influenza A(H1N1) Virus and Its Reassortants.

During 2018-2020, we isolated 32 Eurasian avian-like swine influenza A(H1N1) viruses and their reassortant viruses from pigs in China. Genomic testing identified a novel reassortant H3N1 virus, which emerged in late 2020. Derived from G4 Eurasian H1N1 and H3N2 swine influenza viruses. This virus poses a risk for zoonotic infection.

Gold, bonds, and epidemics: A safe haven study.

The COVID-19 pandemic raised the question whether gold and sovereign bonds are a safe haven during epidemics. We study the effectiveness as safe haven during the epidemics caused by SARS, Ebola, Zika, Swine Flu, and COVID-19. To this end, this study employs a DCC-GARCH model to analyze the conditional correlations between daily returns of S&P 500 and MSCI Emerging Markets Index with gold and the major sovereign bonds. Our results show that gold is a weak safe haven for stock market investors during the epidemics, and U.S. treasuries are the safest option, followed by Japanese sovereign bonds.

Reassortant Influenza A(H1N1)pdm09 Virus in Elderly Woman, Denmark, January 2021.

A case of human infection with influenza A(H1N1)pdm09 virus containing a nonstructural gene highly similar to Eurasian avian-like H1Nx swine influenza virus was detected in Denmark in January 2021. We describe the clinical case and report testing results of the genetic and antigenic characterizations of the virus.

An Eight-Year Profile of Children with Influenza A(H1N1) in a Large Hospital in India.

As influenza virus A(H1N1) continues to circulate, reports from India have documented mainly respiratory involvement in children. This retrospective chart review of children at a medical college found that from August 2009 to July 2017, 855 children aged 3 months to 15 years had H1N1 influenza of whom 310 (36.3%) were admitted and 29 (9.4% admissions) died. In 2009-12, 76.5% patients presented in August-October but from 2015 to 2017, 89.3% came in January-March. The proportion of under-fives increased from 54.0% in 2009-10 to 77.7% in 2015-17. Among admitted children, 82.6% were under 5 years, 96.1% had respiratory symptoms and 11% had seizures. Six children had encephalopathy of whom four died; two survivors had severe neurological sequelae. Other features included gastroenteritis, otitis media, myositis and hepatitis. Complications included shock (10.7%) and acute respiratory distress syndrome (6.1%). Evidence of bacterial/fungal infection was present in 71 (22.9%). Oxygen was required by 123 children (39.7%), high-dependency/intensive care by 47 (15.2%), 17 (5.5%) received high-flow oxygen and 29 (9.4%) required mechanical ventilation. There were no significantly increased odds of needing intensive care or of dying in children with underlying diseases or among different age groups but those with underlying central nervous system (CNS) diseases had higher odds of needing high-dependency/intensive care [odds ratio (OR) 2.35, p = 0.046]. Significantly, children with CNS symptoms had nearly seven times higher odds of needing mechanical ventilation (OR 6.85, p < 0.001) and over three times higher odds of dying (OR 3.31, p = 0.009).Lay summaryH1N1 Influenza ("swine flu") emerged as a global pandemic in 2009 and continues to affect children all over the world. This review of records from a medical college hospital in southern India found that 855 children aged 3 months to 15 years came with H1N1 influenza over 8 years from August 2009 to July 2017. In 2009-12, over three-quarters of them presented in the rainy season but from 2015-17, almost 90% came in the winter and spring, suggesting a change in the seasonality of the outbreaks, which could impact the choice of dates for annual influenza vaccination. The proportion under 5 years of age increased from 54% in 2009-10 to 78% in 2015-17, suggesting possible immunity in children exposed to earlier outbreaks. Over a third of the children needed admission of whom almost 40% needed oxygen, one-sixth needed high-dependency/intensive care and 1 in 11 admitted children died, emphasizing the severity of this disease. While most children had respiratory symptoms, all organs of the body were affected; 11% of those admitted had seizures and 6 had encephalitis. Children admitted with central nervous system symptoms had an almost 7-fold higher risk of needing high-dependency/intensive care and an over 3-fold higher risk of dying.

The Swine Flu Pandemic - Should We Be Concerned?

As I write this review, we are in the midst of the 2009 influenza A (H1N1) pandemic. The extent and impact of this pandemic is still unknown. Although daily reports on confirmed cases and deaths provide a constant stream of detailed information, it is not possible to predict with any degree of precision the impact the outbreak will have in society in general or on the life insurance industry in particular.1 The epidemiology of such disease outbreaks has been likened to a jigsaw puzzle, and we are now at the stage where the picture is intriguing even if we are not sure what we are seeing.2.

Pandemrix® vaccination is not associated with increased risk of islet autoimmunity or type 1 diabetes in the TEDDY study children.

AIMS/HYPOTHESIS: During the A/H1N1 2009 (A/California/04/2009) pandemic, mass vaccination with a squalene-containing vaccine, Pandemrix®, was performed in Sweden and Finland. The vaccination was found to cause narcolepsy in children and young adults with the HLA-DQ 6.2 haplotype. The aim of this study was to investigate if exposure to Pandemrix® similarly increased the risk of islet autoimmunity or type 1 diabetes. METHODS: In The Environmental Determinants of Diabetes in the Young (TEDDY) study, children are followed prospectively for the development of islet autoimmunity and type 1 diabetes. In October 2009, when the mass vaccination began, 3401 children at risk for islet autoimmunity and type 1 diabetes were followed in Sweden and Finland. Vaccinations were recorded and autoantibodies against insulin, GAD65 and insulinoma-associated protein 2 were ascertained quarterly before the age of 4 years and semi-annually thereafter. RESULTS: By 5 August 2010, 2413 of the 3401 (71%) children observed as at risk for an islet autoantibody or type 1 diabetes on 1 October 2009 had been vaccinated with Pandemrix®. By 31 July 2016, 232 children had at least one islet autoantibody before 10 years of age, 148 had multiple islet autoantibodies and 96 had developed type 1 diabetes. The risk of islet autoimmunity was not increased among vaccinated children. The HR (95% CI) for the appearance of at least one islet autoantibody was 0.75 (0.55, 1.03), at least two autoantibodies was 0.85 (0.57, 1.26) and type 1 diabetes was 0.67 (0.42, 1.07). In Finland, but not in Sweden, vaccinated children had a lower risk of islet autoimmunity (0.47 [0.29, 0.75]), multiple autoantibodies (0.50 [0.28, 0.90]) and type 1 diabetes (0.38 [0.20, 0.72]) compared with those who did not receive Pandemrix®. The analyses were adjusted for confounding factors. CONCLUSIONS/INTERPRETATION: Children with an increased genetic risk for type 1 diabetes who received the Pandemrix® vaccine during the A/H1N1 2009 pandemic had no increased risk of islet autoimmunity, multiple islet autoantibodies or type 1 diabetes. In Finland, the vaccine was associated with a reduced risk of islet autoimmunity and type 1 diabetes.

Population Responses during the Pandemic Phase of the Influenza A(H1N1)pdm09 Epidemic, Hong Kong, China.

During August 2009-July 2010, we conducted 7 longitudinal telephone surveys among 503 adults in Hong Kong, China, to explore changes in their behavioral and psychological responses to the influenza A(H1N1)pdm09 virus epidemic. Trends were examined using generalized estimating equations models. Findings showed that responses varied with the course of the pandemic.

The swine flu vaccine, public attitudes, and researcher interpretations: a systematic review of qualitative research.

BACKGROUND: During pandemics, health authorities may be uncertain about the spread and severity of the disease and the effectiveness and safety of available interventions. This was the case during the swine flu (H1N1) pandemic of 2009-2010, and governments were forced to make decisions despite these uncertainties. While many countries chose to implement wide scale vaccination programmes, few accomplished their vaccination goals. Many research studies aiming to explore barriers and facilitators to vaccine uptake have been conducted in the aftermath of the pandemic, including several qualitative studies. AIMS: 1. To explore public attitudes to the swine flu vaccine in different countries through a review of qualitative primary studies. 2. To describe and discuss the implications drawn by the primary study authors. METHODS: Systematic review of qualitative research studies, using a broadly comparative cross case-study approach. Study quality was appraised using an adaptation of the Critical Appraisal Skills Programme (CASP) quality assessment tool. RESULTS: The review indicates that the public had varying opinions about disease risk and prevalence and had concerns about vaccine safety. Most primary study authors concluded that participants were uninformed, and that more information about the disease and the vaccine would have led to an increase in vaccine uptake. We find these conclusions problematic. We suggest instead that people's questions and concerns were legitimate given the uncertainties of the situation at the time and the fact that the authorities did not have the necessary information to convince the public. Our quality assessment of the included studies points to a lack of reflexivity and a lack of information about study context. We suggest that these study weaknesses are tied to primary study authors' lack of acknowledgement of the uncertainties surrounding the disease and the vaccine. CONCLUSION: While primary study authors suggest that authorities could increase vaccine uptake through increased information, we suggest instead that health authorities should be more transparent in their information and decision-making processes in future pandemic situations.

Emergence of influenza A (H1N1)pdm09 genogroup 6B and drug resistant virus, India, January to May 2015.

To investigate the aetiology of the 2015 A(H1N1)pdm09 influenza outbreak in India, 1,083 nasopharyngeal swabs from suspect patients were screened for influenza A(H1N1)pdm09 in the state of Madhya Pradesh. Of 412 positive specimens, six were further characterised by phylogenetic analysis of haemagglutinin (HA) sequences revealing that they belonged to genogroup 6B. A new mutation (E164G) was observed in HA2 of two sequences. Neuraminidase genes in two of 12 isolates from fatal cases on prior oseltamivir treatment harboured the H275Y mutation.

The Evaluations of Swine Flu Magnitudes in TV News: A Comparative Analysis of Paired Influenza Pandemics.

This study examined how major TV news networks covered two flu pandemics in 1976 and 2009 in terms of news frames, mortality exemplars, mortality subject attributes, vaccination, evaluation approaches, and news sources. Results showed that the first pandemic was frequently framed with the medical/scientific and political/legal issues, while the second pandemic was emphasized with the health risk issue in TV news. Both flu pandemics were regularly reported with mortality exemplars, but the focus in the first pandemic was on the flu virus threat and vaccination side effects, while the vaccination shortage was frequently revealed in the second outbreak.

Contact tracing for influenza A(H1N1)pdm09 virus-infected passenger on international flight.

In April 2009, influenza A(H1N1)pdm09 virus infection was confirmed in a person who had been symptomatic while traveling on a commercial flight from Mexico to the United Kingdom. Retrospective public health investigation and contact tracing led to the identification of 8 additional confirmed cases among passengers and community contacts of passengers.

Perceptions and sociodemographic factors influencing vaccination uptake and precautionary behaviours in response to the A/H1N1 influenza in Sweden.

AIMS: In response to the 2009 outbreak of A/H1N1 influenza, Swedish authorities decided on a programme for universal vaccination. Over 60% of the population received at least one dose of vaccine. This study examines demographic factors and perceptions related to the decision whether or not to become vaccinated. METHODS: A combined web/postal survey was conducted (n = 1587, response rate 53%) in late spring 2010. Questions reported here concerned perceptions, precautionary behaviours and vaccination decision. RESULTS: Main reasons for becoming vaccinated were concerns about spreading the disease to relatives or in the community and confidence in the good effect of vaccination. Vaccination rates were higher among women, those with young children or belonging to a risk group. Main reasons for abstaining were belief that the flu was not a serious threat, low risk of spreading the disease, concern about side-effects and perceived uncertainties in information. Three profiles representing different patterns of thought and beliefs were identified by cluster analysis, respectively labelled as a vulnerable, a trusting and a sceptical group. Vaccination rates and precautionary behaviours were demonstrated to differ between these groups. CONCLUSIONS: Perceptions relating to the 2009 pandemic are likely to influence uptake of vaccination in the future. Authorities need to be aware of different patterns of beliefs and attitudes among the public, and that these may vary in different phases. Communication of risk needs to be dynamic and prepared to engage with the public before, during and even for some time after the acute risk period.

An experimental universal swine influenza a virus (IAV) vaccine candidate based on the M2 ectodomain (M2e) peptide does not provide protection against H1N1 IAV challenge in pigs.

Swine flu is a common disease problem in North American pig populations and swine influenza A viruses (IAV) are extremely diverse and the lack of cross protection between heterologous strains is impacting vaccine efficacy in the field. The objective of this study was to design and test a novel swine flu vaccine targeting the M2 ectodomain (M2e) of IAV, a highly conserved region within the IAV proteome. In brief, an M2e peptide was designed to match the predominant swine IAV M2 sequence based on global analysis of sequences from pigs and humans. The resulting sequence was used to synthesize the M2e peptide coupled to a carrier protein. The final vaccine concentration was 200 µg per dose, and a commercial, microemulsion-based aqueous adjuvant was added. Nine 3-week-old IAV negative piglets were randomly assigned to three groups and rooms including non-vaccinated pigs (NEG-CONTROLs) and vaccinated pigs using the intramuscular (M2e-IM) or the intranasal route (M2e-IN). Vaccinations were done at weaning and again at 2 weeks later. An in-house enzyme-linked immunosorbent assay (ELISA) was developed and validated to study the M2e IgG antibody response and demonstrated M2e-IM pigs had a higher systemic antibody response compared to M2e-IN pigs. Subsequently, an IAV challenge study was conducted. The results indicated that M2e-IM vaccinated pigs were not protected from H1N1 (US pandemic clade, global clade 1A.3.3.2) challenge despite having a strong humoral anti-M2e immune response. In conclusion, while the experimental IAV vaccine was able to induce anti-M2e antibodies, when challenged with H1N1, the vaccinated pigs were not protected, perhaps indicating that reactivity to the M2e antigen alone is not sufficient to reduce clinical signs, lesions or shedding associated with experimental IAV challenge.

A Dialogue about Vaccine Side Effects: Understanding Difficult Pandemic Experiences.

This paper investigates the relationship between the experiences of mass vaccinations against two pandemic viruses: the swine flu in 2009-2010 and COVID-19 in the early 2020s. We show how distressing memories from the swine flu vaccination, which led to the rare but severe adverse effect of narcolepsy in approximately 500 children in Sweden, were triggered by the COVID-19 pandemic. The narcolepsy illness story has rarely been told in academic contexts; therefore, we will provide space for this story. It is presented through a dialogue with the aim of shedding light on the interrelationship between pandemics-and between mass vaccinations-to investigate what could be termed cultural wounds that influence societies because they are characterized by the difficulty of talking about them. The paper explores the multiple shocks of illness in life and what can be learned from them by sharing them.

Homeopathic treatment of patients with influenza-like illness during the 2009 A/H1N1 influenza pandemic in India.

INTRODUCTION: We conducted a prospective, multi-centre, data collection survey of homeopathic practice in treatment of influenza-like illness in India during the 2009 pandemic of A/H1N1 influenza ('swine flu', SF). AIMS: To survey the practice of homeopathic practitioners in India in the management of SF, with respect to: (a) patients' symptoms at presentation and at follow-up (FU) consultation; (b) homeopathic medicines prescribed. METHODS: Data collection took place from October 2009 to February 2010, at the peak of the pandemic. All patients satisfying the minimum diagnostic symptoms of SF were eligible for inclusion. Data per appointment (in person or by telephone) were recorded by practitioners in spreadsheet format. All records were anonymised and included: whether patient was immunised against A/H1N1; influenza symptoms at consultation; the homeopathic medicine/s prescribed; whether antiviral medicine prescribed. RESULTS: Twenty-three homeopathic physicians contributed to data collection. At the first appointment, 1126 patients had valid SF symptoms. A total of 89 different combinations of SF symptoms was observed, the most common being temperature >38°C + cough + runny nose (n = 170; 15.1%). A total of 44 different remedies (or combinations of remedies) were used at these first appointments, the most frequently prescribed being Arsenicum album (n = 265; 23.5%). For a total of 99 FU appointments with valid SF symptoms, Arsenicum album was prescribed most frequently overall (n = 28; 28.0%). CONCLUSIONS: In our sample, the 2009 A/H1N1 influenza pandemic in India was characterised by several prominent symptoms and symptom/medicine associations, particularly temperature >38°C + cough + runny nose, associated with Arsenicum album. Future studies should collect additional keynote prescribing symptoms that influence the choice of homeopathic medicine.

Nanodot zirconium trisulfide modified conducting thread: A smart substrate for fabrication of next generation biosensor.

In present work, we report an eco-friendly, flexible and highly conducting cotton thread (CT) as a smart substrate for the development of biosensing platform towards ultrasensitive detection of swine flu serum amyloid A (SAA) biomarker. The biosensor was fabricated by optimized coating of CT with poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT:PSS) conductive ink followed by incorporation of nanodot zirconium trisulfide (nZrS3) which helped in enhancing the electrochemical properties and improving stability of PEDOT:PSS polymeric film. The fabricated nZrS3/PEDOT:PSS/CT electrode was then used for sequential immobilization of monoclonal antibodies of SAA (anti-SAA) and bovine serum albumin (BSA). The synthesized nanomaterials and fabricated electrodes were characterized through X-ray diffraction, Fourier-transform infrared spectroscopy, transmission electron microscopy, scanning electron microscopy and contact angle analyser techniques. The electrochemical response of the fabricated smart thread based biosensor (BSA/anti-SAA/ZrS3/PEDOT:PSS/CT) was recorded against SAA using chronoamperometry technique which revealed superior sensitivity {30.2 µA [log (µg mL-1)]-1 cm-2}, excellent lower detection limit (0.72 ng mL-1) and prolonged shelf life up to 48 days. The response of the biosensor was also validated by analysing the electrochemical response of SAA spiked serum samples and the obtained results showed good correlation with that of standard samples.