Tag: influenza

Categories : Cardiovascular Disease VaccinesTags :

Flu Vaccine Reduces Early Mortality in HF Patients

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In a study published in The Lancet Global Health, an international team of researchers has found that influenza vaccines greatly reduce both pneumonia and cardiovascular complications in people with heart failure.

“If you have heart failure, you should get your flu shot because it can save your life – that is what we found in this study,” said the study’s principal investigator Mark Loeb. “It is underappreciated that influenza vaccine can save people from cardiovascular death.”

The study showed that over the entire year the influenza vaccine reduced pneumonia by 40% and hospitalisation by 15% in patients with HF. During influenza season in autumn and winter, the influenza vaccine reduced deaths by 20% in these patients.

Data gathered during flu season also showed the vaccine helped protect against cardiovascular complications, such as heart attacks and strokes.

Trial investigators tracked more than 5000 patients with HF in 10 countries across Africa, Asia and the Middle East, where few people have regular influenza vaccination. They received either an influenza vaccine or a placebo annually between June 2015 and November 2021.

While the flu has long been associated with an increased risk of life-threatening cardiovascular events, Loeb said that people with heart failure are already vulnerable to poor health outcomes. Patients with the condition have a 50% chance of dying within five years, while 20% are hospitalised for cardiovascular complications every year.

“Importantly, we looked at low and middle-income countries where 80 per cent of cardiovascular disease occurs and where flu vaccination rates are low.”

Salim Yusuf, executive director of PHRI and an author of the study said: “The flu shot should be part of the standard practise in people with heart failure given how simple, inexpensive and safe it is. Avoiding one sixth of deaths from heart disease and preventing hospitalizations makes it very cost effective and that can have an important public health and clinical impact.”

The study from McMaster University and partners marks the first clinical trial of the flu vaccine’s effectiveness in patients with HF.

Source: McMaster University

Categories : AgeingTags :

Macrophages Explain Vulnerability to Influenza in Old Age

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Old man
Source: JD Mason on Unsplash

After being suppressed during the COVID pandemic, influenza is again circulating and threatening the health of over 65s. But why are older people so more susceptible to the flu? A new study from the University of Michigan, published in Nature Communications, offers clues.

The study, led by first author Judy Chen, a PhD candidate, senior author Professor Daniel Goldstein, MD, and their team investigates why cells called alveolar macrophages, the first line of defence in the lungs, appear to be compromised with age.

Macrophages attack pathogens like the flu virus and reside in alveoli. Importantly, these cells appear to be lost with ageing.

Previous research by another group showed that when macrophages from an old mouse were put into a young mouse, and cells looked young again. “This drove us to believe that something in the environment of the lungs is contributing to this,” said Chen.

Signs pointed to a lipid immune modulator known as prostaglandin E2 (PGE2) with wide ranging effects, from labour induction in pregnancy to inflammation with arthritis. The study team discovered there is more PGE2 in the lungs with age. This increase in PGE2, Chen explained, acts on the macrophages in the lung, limiting their overall health and ability to generate.

The team suspects that the buildup of PGE2 is yet another marker of a biological process called senescence, which is often seen with age. Senescence serves as insurance against the runaway division of damaged cells; cells that are senescent are no longer able to replicate.

“One of the interesting things about these cells is they secrete a lot of inflammatory factors,” said Chen.

The study showed that with age, the cells lining the air sacs in the lungs become senescent, and these cells lead to increased production of PGE2 and suppression of the immune response.

To test the link between PGE2 and increased susceptibility to influenza, they treated older mice with a drug that blocks a PGE2 receptor. “The old mice that got that drug actually ended up having more alveolar macrophages and had better survival from influenza infection than older mice that did not get the drug,” said Chen.

The team plans to next investigate the various ways PGE2 affects lung macrophages as well as its potential role in inflammation throughout the body. “As we get older, we become more susceptible not only to influenza, but to other infections, cancers, autoimmune diseases as well.”

Source: Michigan Medicine – University of Michigan

Categories : Respiratory DiseasesTags :

Scientists Witness the Creation of a Hybrid Virus

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In a world first, scientists have witnessed the fusion two viruses, influenza A virus (IAV) and respiratory syncytial virus (RSV), forming a single, hybrid virus particle (HVP). The discovery was published in Nature Microbiology.

Viruses often share tropism for the same system, such as respiratory viruses preferentially infecting the respiratory system. Coinfections by more than one virus represent between ~10–30% of all respiratory viral infections and are common among children. The clinical impact of viral coinfections is unclear: while some studies indicate that coinfections do not alter the outcome of disease, others report increased incidence of viral pneumonia.

Though evidence suggests virus–virus interactions play an important role in virus dynamics and transmission, viruses are typically studied in isolation. Recent work showed that interactions among respiratory viruses occur and have impacts at multiple levels, from populations, to individuals and tissues. However, studies characterising direct virus–virus interactions within cells are scarce. Here we report previously unknown interactions between IAV and RSV, two clinically important respiratory viruses that belong to different taxonomical families.

To investigate virus–virus interactions, the researchers infected human lung cells with both influenza A virus (IAV) and respiratory syncytial virus (RSV). Using super-resolution microscopy, live-cell imaging, scanning electron microscopy and cryo-electron tomography, the researchers found extracellular and membrane-associated filamentous structures consistent with hybrid viral particles (HVPs).

The researchers found that HVPs harbour surface glycoproteins and ribonucleoproteins of IAV and RSV. HVPs use the RSV fusion glycoprotein to evade anti-IAV neutralising antibodies and infect and spread among cells lacking IAV receptors. Finally, we show that IAV and RSV coinfection in primary cells of the bronchial epithelium results in viral proteins from both viruses latching on together at the apical cell surface.

“Our observations define a previously unknown interaction between respiratory viruses that might affect virus pathogenesis by expanding virus tropism and enabling immune evasion,” the researchers wrote.

“This kind of hybrid virus has never been described before,” virologist and senior author Pablo Murcia told The Guardian. “We are talking about viruses from two completely different families combining together with the genomes and the external proteins of both viruses. It is a new type of virus pathogen.”

When IAV and RSV coinfect, IAV becomes more infectious, infecting a wider array of human cells. Carrying the RSV surface proteins, IAV was able to better evade the immune system. The HVP also spread into cells lacking influenza receptors, letting it progress further down the respiratory tract.

The relationship is not mutually beneficial for the viruses as RSV loses potency. Overall though, pilfering another virus’s tools could play a role in viral pneumonia.

“RSV tends to go lower down into the lung than the seasonal flu virus, and you’re more likely to get more severe disease the further down the infection goes,” said Dr Stephen Griffin, a virologist at the University of Leeds who was not involved in the study.

“It is another reason to avoid getting infected with multiple viruses, because this [hybridisation] is likely to happen all the more if we don’t take precautions to protect our health,” he added.

The researchers also found that the combination of viruses was important; IAV did not form an effective hybrid with rhinovirus.

Categories : VaccinesTags :

One Step Close to a Universal Flu Vaccine

On By ModernMedia
Syringe withdrawing from vaccine vial
Photo by Mufid Majnun

A new universal flu vaccine protects against diverse variants of both influenza A and B viruses in mice, according to a new study published in the journal PLOS Pathogens.

The researchers designed a single, universal influenza vaccine candidate with key cross-protective, less variable parts of the influenza A and B viruses: multi-neuraminidase protein subtypes known to be major antiviral drug targets and the universally conserved M2 ectodomain protein.

The researchers, from the Institute for Biomedical Sciences at Georgia State University, report that mice vaccinated with an immune stimulating virus-like particle displaying multiple neuraminidase subtypes and conserved M2 portions of antigens were protected against influenza A seasonal variants and pandemic potential viruses (H1N1, H5N1, H3N2, H9N2 and H7N9) and influenza B (Yamagata and Victoria lineage) viruses containing substantial antigenic variations.

Viral variants emerge when flu pathogens change their major surface haemagglutinin protein that binds to host receptor molecules. Continuous mutational changes in the flu haemagglutinin proteins result in immune escape and sever disease.

Current influenza vaccines are based on strain-specific immunity to haemagglutinin, a highly variable target of immune protection. The effectiveness of the seasonal vaccine is unpredictable and could be below 20% because of continuous changes in haemagglutinin proteins. Influenza therefore remains a significant risk to human health worldwide.

“We developed a single, universal vaccine entity that induced immunity to conserved M2 ectodomain and multi subtype neuraminidase proteins and was found to be effective in conferring broad cross protection against antigenically diverse influenza A and B viruses in young and aged mice,” said Professor Sang-Moo Kang, senior author of the study. “This study provides impactful insight into developing a universal influenza vaccine inducing broad immunity against both flu A and B variants in young and aged populations.”

This study supports a novel strategy for creating a universal vaccine against influenza A and B viruses. A single construct displaying multiple cross protective proteins has the capacity to induce immunity to M2 and multi-subtype neuraminidase proteins of influenza A and B viruses, as well as offer broad cross protection against sickness and mortality under lethal flu virus challenges in mice, according to the study.

Vaccinating mice with this universal vaccine candidate induced broad neuraminidase inhibition, M2 ectodomain specific antibodies and T cell immune responses. Comparable cross protection was induced in aged mice.

The study warrants further testing of this unique, universal va ccine candidate in ferrets, which have similar respiratory tracts to humans.

Source: Georgia State University

Categories : VaccinesTags :

New Universal Flu Vaccine Offers Broad Protection, Study Finds

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Source: Pixabay CC0

By focusing on key parts which remain stable over time, scientists have created a universal flu vaccine that offers broad cross protection against different strains and subtypes of influenza A viruses in both young and old populations, according to a new study reported in npj Vaccines.

The researchers developed the universal flu vaccine by genetically linking two highly conserved portions of the virus: the extracellular domain of matrix 2 (M2e) and the stalk protein found in influenza A H3N2 viruses. The findings show that vaccinating against M2e-stalk protein induced broad protection against different influenza virus strains and subtypes by universal vaccine-mediated immunity in adult and aged mice.

Developing effective influenza vaccines has been a challenge because the head portion of the influenza virus is constantly mutating. When comparing the H1N1 and H3N2 influenza A viruses, particular challenges exist in H3N2 subtypes because of stalk mutations in circulating strains and the unstable structure of stalk proteins for H3N2 viruses. These drawbacks have been difficult to overcome in developing effective H3 stalk-based vaccines.

In the past decade, vaccine effectiveness against H3N2 hovered around 33%, and during the 2014–2015 flu season, it dropped to 6%. New mutations of H3N2 variants emerged with increased virulence. Also, the outbreak of H7N9, another influenza A subtype, caused concern for potential pandemics. Therefore, developing an effective vaccine to protect against these viruses is a high priority.

“The M2e-stalk protein, for the first time, could be easily produced in bacterial cell cultures at high yields and was found to confer protection against heterologous and heterosubtypic cross-group subtype viruses (H1N1, H5N1, H9N2, H3N2 and H7N9) at similar levels in adult and aged mice,” said Dr Sang-Moo Kang, senior author of the study and a professor in the Institute for Biomedical Sciences at Georgia State. “These results provide evidence that M2e-stalk genetic fusion proteins can be produced in a large scale at low cost and developed as a universal influenza A virus vaccine candidate for young and aged populations.”

The study found this novel M2e-stalk protein vaccine induced M2e and stalk-specific Immunoglobulin G (IgG) antibodies that recognised antigenically diverse influenza viral antigens on virus particles and on the infected cell surface. The vaccine also stimulated protective cellular T cell immunity and effective lung influenza viral clearance in mice.

Source: Georgia State University

Categories : Diseases, Syndromes and ConditionsTags :

Accuracy of Flu Self-tests Comparable to Clinical Tests

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Runny nose and sneezing symptoms
Photo by Britanny Colette on Unsplash

Home-based, self-administered tests for influenza are comparable in accuracy to rapid diagnostic tests in clinical settings, according to a study reported in JMIR Public Health and Surveillance.

“Home tests are a valuable tool to support the management of influenza and other respiratory infections,” explained senior author Matthew J. Thompson, professor at the University of Washington School of Medicine in Seattle.

“The tests facilitate earlier diagnoses and reduce the time from the onset of symptoms to patients seeking appropriate care,” he said.

More than 600 residents in the Seattle area participated in the 2020 study conducted between February and the end of May. Participants received influenza testing kits in the mail. After swabbing their noses, they either recorded the results through an app, or returned the kits to the lab of Lea Starita, assistant professor of genome sciences at the UW School of Medicine and a study co-author.

The researchers found that self-test’s sensitivity and specificity test were comparable with those of influenza rapid diagnostic tests used in clinical settings. They noted that false-negative results were more common when the self-test was administered after 72 hours of the appearance of symptoms, but were not related to inadequate swab collection or severity of illness.

“This study underscores the imperative of expanding access to testing and lowering the costs,” said Barry Lutz, associate professor of bioengineering and another co-author of the paper.

Source: UW Medicine

Categories : Genetics Immune SystemTags :

Differences in Influenza Responses According to Genetic Ancestries

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Photo by Andrea Piacquadio on Unsplash

Researchers have uncovered differences in immune pathway activation to influenza infection between individuals of European and African genetic ancestry, according to a study published in Science. Many of the genes that were associated with these immune response differences to influenza are also enriched among genes associated with COVID disease severity. 

“The lab has been interested in understanding how individuals from diverse populations respond differently to infectious diseases,” said first author Haley Randolph, a graduate student at the University of Chicago. “In this study, we wanted to look at the differences in how various cell types respond to viral infection.”

The researchers examined gene expression patterns in peripheral mononuclear blood cells, a diverse set of specialised immune cells that play important roles in the body’s response to infection. These cells were gathered from men of European and African ancestry and then exposed the cells to flu in a laboratory setting. This let the team examine the gene signatures of a variety of immune cell types, and observe how the flu virus affected each cell type’s gene expression.

The results showed that individuals of European ancestry showed an increase in type I interferon pathway activity during early influenza infection.

“Interferons are proteins that are critical for fighting viral infections,” said senior author Luis Barreiro, PhD, Associate Professor of Medicine at UChicago. “In COVID-19, for example, the type I interferon response has been associated with differences in the severity of the disease.”

This increased pathway activation hindered the replication of the virus more and limited viral replication later on. “Inducing a strong type I interferon pathway response early upon infection stops the virus from replicating and may therefore have a direct impact on the body’s ability to control the virus,” said Barreiro. “Unexpectedly, this central pathway to our defense against viruses appears to be amongst the most divergent between individuals from African and European ancestry.”

The researchers saw a variety of differences in gene expression across different cell types, suggesting a constellation of cells that work together to fight disease.

Such a difference in immune pathway activation could explain influenza outcome disparities between different racial groups; Non-Hispanic Black Americans are more likely to be hospitalised due to the flu than any other racial group.

However, these results are not evidence for genetic differences in disease susceptibility, the researchers point out. Rather, possible differences in environmental and lifestyle between racial groups could be influencing gene expression, and affecting the immune response.

“There’s a strong relationship between the interferon response and the proportion of the genome that is of African ancestry, which might make you think it’s genetic, but it’s not that simple,” said Barreiro. “Genetic ancestry also correlates with environmental differences. A lot of what we’re capturing could be the result of other disparities in our society, such as systemic racism and healthcare inequities. Although some of the differences we show in the paper can be linked to specific genetic variation, showing that genetics do play some role, such genetic differences are not enough to fully explain the differences in the interferon response.”

These differences in viral susceptibility may not be confined to just influenza. Comparing a list of genes associated with differences in COVID severity, the researchers found that many of the same genes showed significant differences in their expression after flu infection between individuals of African and European ancestry.

“We didn’t study COVID patient samples as part of this study, but the overlap between these gene sets suggests that there may be some underlying biological differences, influenced by genetic ancestry and environmental effects, that might explain the disparities we see in COVID outcomes,” said Barreiro.

As they explore this further, the researchers hope to figure out which factors contribute to the differences in the interferon response, and immune responses more broadly, to better predict individual disease risk.

Source: EurekAlert!

Categories : COVIDTags :

A Smaller Fourth Wave Predicted for South Africa as Flu Cases Spike

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Image by Quicknews

A fourth wave of infections is likely for South Africa but its impact probably won’t be as severe as during earlier surges, as shown by new modelling, according to BusinessTech.

Factoring in sero-prevalence surveys and other data, it appears that an estimated 60% to 70% of the population has already contracted COVID, which along with vaccinations will provide protection from severe disease, the South African COVID-19 Modelling Consortium said in an online presentation on Wednesday.

Even in its worst-case scenario, deaths and hospitalisations during a fourth wave were projected to be substantially lower than during previous surges.

Though current caseload for the country is “incredibly low”, it is still “very hard to commit to say South Africa is over the worst” of the COVID pandemic, said Harry Moultrie, a senior epidemiologist at the National Institute for Communicable Diseases, which coordinated the modelling.

“It’s going to be a bumpy ride,” he said. “We don’t know where this virus is going to take us. We will still be seeing hospital admissions and deaths related to Covid for years to come.”

South Africa;s seven-day rolling average of new infections has fallen below 300, much reduced from a third-wave peak which hit nearly 20 000 in July.

To date, South Africa has had 2.93 million confirmed cases of COVID, with 89 504 deaths, although excess death numbers indicate the true toll may be much higher. About 34% of the nation’s 39.8 million adults have been fully vaccinated.

While some countries in the northern hemisphere such as Germany are seeing severe fourth and even fifth waves of infection driven by the spread of the delta variant, that’s not a good indicator South Africa will follow a similar path because the strain has already spread widely in the country, explained Gesine Meyer-Rath, a member of the modelling consortium.
“We have paid in a way with high deaths and a lot of destruction” during previous waves, Meyer-Rath said. “We don’t think we will have a super-fast case increase again” unless a highly transmissible new variant emerges, she said.

While the outlook for the fourth wave is brighter, the past few weeks has seen a sharp rise of influenza cases, the National Institute for Communicable Diseases (NICD) reported.

A high number of cases had been seen from the beginning of the month, including influenza-like illness and pneumonia hospitalised cases at surveillance sentinel sites.

The NICD added that there had been clusters of influenza cases reported in schools and workplaces.

The NICD’s Cheryl Cohen said: “The increase in influenza this summer, which is not the typical time for the influenza season in South Africa, is likely the result of the relaxation of non-pharmaceutical interventions to control COVID combined with other factors such as reduced immunity because flu has not circulated since 2020 and 2021.”

Sources: Eyewitness News; BusinessTech

Categories : COVID HospitalsTags :

ECG Readings Can Predict Worsening and Mortality in COVID and Influenza

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Specific and dynamic changes on electrocardiograms (ECGs) of hospitalised COVID patients with COVID or influenza can help predict a timeframe for worsening health and death, according to a new Mount Sinai study.

Published in the American Journal of Cardiology, the study shows that shrinking waveforms on these tests can be used to help better identify high-risk patients and provide them more aggressive monitoring and treatment.  

“Our study shows diminished waveforms on ECGs over the course of COVID illness can be an important tool for health care workers caring for these patients, allowing them to catch rapid clinical changes over their hospital stay and intervene more quickly. […] ECGs may be helpful for hospitals to use when caring for these patients before their condition gets dramatically worse,” said senior author Joshua Lampert, MD, Cardiac Electrophysiology fellow at The Mount Sinai Hospital. “This is particularly useful in overwhelmed systems, as there is no wait for blood work to return and this test can be performed by the majority of health care personnel. Additionally, the ECG can be done at the time of other bedside patient care, eliminating the potential exposure of another health care worker to COVID.”

Researchers did a retrospective analysis of ECGs on 140 hospitalised COVID patients across the Mount Sinai Health System in New York City, and compared them with 281 ECGs from patients with laboratory-confirmed influenza A or B admitted to The Mount Sinai Hospital.  
For each patient, the researchers compared three ECG time points: a baseline scan done within a year prior to COVID or influenza hospitalisation, a scan taken at hospital admission, and follow-up ECGs performed during hospitalisation.

They manually measured QRS waveform height on all electrocardiograms – changes in this electrical activity can indicate failing ventricles. The researchers analysed follow-up ECGs after hospital admission and analysed changes in the waveforms according to a set of criteria they designed  called LoQRS amplitude (LoQRS) to identify a reduced signal. LoQRS was defined by QRS amplitude of less than 5mm measured from the arms and legs or less than 10mm when measured on the chest wall as well as a relative reduction in waveform height in either location by at least 50%.

Fifty-two COVID patients in the study did not survive, and 74% of those had LoQRS. Their ECG QRS waveforms reduced approximately 5.3 days into their hospital admission and they died approximately two days after the first abnormal ECG was observed.

Out of the 281 influenza patients studied, LoQRS was identified in 11 percent of them. Seventeen influenza patients died, and 39% had LoQRS present. Influenza patients met LoQRS criteria a median of 55 days into their hospital admission, and the median time to death was six days from when LoQRS was identified. Overall, these results show influenza patients followed a less virulent course of illness when compared to COVID patients.

“When it comes to caring for COVID patients, our findings suggest it may be beneficial not only for health care providers to check an EKG when the patient first arrives at the hospital, but also follow-up ECGs during their hospital stay to assess for LoQRS, particularly if the patient has not made profound clinical progress. If LoQRS is present, the team may want to consider escalating medical therapy or transferring the patient to a highly monitored setting such as an intensive care unit (ICU) in anticipation of declining health,” added Dr Lampert.

Source: The Mount Sinai Hospital / Mount Sinai School of Medicine

Categories : VaccinesTags :

Attenuated Virus Confers Broader Flu Protection

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Source: Pixabay CC0

A mouse study using both attenuated and inactivated forms of influenza has helped explain why people vaccinated with the inactivated virus still occasionally end up contracting the illness. The finding should help researchers develop vaccines that offer broad protection against viruses.

Influenza is a major global health burden, with the World Health Organization estimating that it causes one billion cases annually. Each year, vaccines are developed that offer some protection against infection. But the influenza virus is a moving target that is constantly mutating, and so vaccines can lose their effectiveness as a season progresses.

Influenza vaccines commonly come in two forms: inactivated vaccines (including component vaccines) and live attenuated vaccines. Live vaccines confer broader protection against variants than inactivated vaccines, but side effects such as fevers and headaches are more common. A result they have yet to be approved in some countries. Live vaccines induce the production of broadly reactive antibodies, but until now, scientists didn’t know why.

In a recent study, Masato Kubo of the RIKEN Center for Integrative Medical Sciences and his co-workers have discovered two processes that live vaccines induce in mice that together account for their broader protection.

They found that, like the virus itself, the live vaccine virus causes the virus to replicate deep in the lungs, which in turn induces a structural change in the virus haemagglutinin, a mushroom-shaped protein on the surface of the virus involved in infecting cells. This structural change exposes previously hidden regions of antigens that the immune system can recognise.

Next, germinal cells are activated by interleukin 4 (IL-4), a cytokine heavily involved in regulating antibody production. IL-4 is derived from special T cells known as follicular helper T cells. This activation causes a minor population of B cells to proliferate and it is these B cells that are responsible for generating broadly protective antibodies.

The role of IL-4 in inducing the broad immune response came as a surprise. “Until now there had been no direct evidence to show the importance of IL-4,” says Kubo. “That was one of the surprises of this study for me.”

“We believe both processes are needed for generating broadly active antibodies: viral duplication in the lungs and expansion of the minor population of B cells,” says Kubo. “These two processes mostly likely occur when a person is infected by the influenza virus itself.”

The team now plans to see if there are similar mechanisms for other viruses such as SARS-CoV-2.

Source: RIKEN