Tag: influenza

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

Attenuated Virus Confers Broader Flu Protection

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

Double Threat of Flu and S. Pneumoniae Unravelled

Streptococcus pneumoniae bacteria. Image by CDC on Unsplash

Researchers have found a further reason for why flu and Streptococcus pneumonia are such a deadly combination, by a surface protein causing it to stick to dead or dying lung cells. The finding by University of Alabama at Birmingham (UAB) follows thirty years after the discovery of the surface protein, called pneumococcal surface protein A, or PspA.

This new mechanism had been overlooked because it facilitates bacterial adherence only to dead or dying lung epithelial cells, not to living cells. Previously, researchers typically used healthy lung cell monolayers to search for bacterial adhesins that aid infection. In flu, the virus killing off lung cells was found to set the stage for S. pneumonia attachment to the airway, thereby worsening disease and pneumonia.

Study leaders Carlos Orihuela, PhD, and David Briles, PhD, professor at UAB, said their findings provide further explanation for how an infection by influenza A flu virus — followed by S. pneumoniae superinfection — causes severe pneumonia and a high death rate. Understanding of this mechanism could also lead to improvements for disease treatment and vaccination.

A historical example of the deadly synergy of flu infection followed by S. pneumoniae superinfection is found in banked lung samples from the 1918 Spanish influenza pandemic that killed 40 million to 50 million people — the vast majority of these samples showed co-infection or secondary infection with S. pneumonia.

The UAB research on PspA began with puzzling results from experimental lung infections of mice with influenza A, followed by either wild-type S. pneumonia that has the intact PspA gene, or a mutant S. pneumoniae that lacks PspA. Lung homogenates from mice infected with the wild-type had much higher numbers of S. pneumonia bacteria than lungs infected with the mutant. However, when researchers washed the interiors of the lungs and collected that bronchoalveolar lavage fluid, they counted similar numbers of the wild-type S. pneumonia and the mutant.

“This unexpected result was interpreted to mean that wild-type S. pneumoniae were more resistant to dislodgement than S. pneumonia with a pspA gene deletion, and it served as rationale for further experimentation,” Dr Orihuela said.

From this, the researchers were then able to show that PspA functions as an adhesin to dying host cells, as well as its previously established virulence mechanisms. The researchers also detailed the molecular mechanism of this bacterial adherence.

Both influenza A infection and release of the S. pneumoniae toxin pneumolysin cause death of lung epithelial cells. As they are dying, cells’ phosphatidylserine residues wind up on the outer cell membrane, where they bind the host enzyme glyceraldehyde-3-phosphate dehydrogenase, or GAPDH. In turn, the S. pneumoniae PspA on the bacteria surface binds to the GAPDH. PspA-GAPDH-mediated binding to lung cells increased S. pneumoniae localisation in the lower airway, and this was enhanced by pneumolysin exposure or co-infection with influenza A virus.

One of the fragments of protein responsible for the binding was introduced into the lungs of influenza-infected mice and reduced the disease severity of S. pneumoniae superinfection, presumably through binding competition.

“Our findings support the targeting of regions of PspA for therapeutic and vaccine development against influenza A/Streptococcus pneumoniae superinfections,” Dr Orihuela said. “Importantly, and despite more than 30 years since its discovery, PspA was not previously shown to function as an adhesin. Thus, our finding of PspA’s role in adherence substantially advances our knowledge on the interactions of S. pneumoniae with its host.”

Source: University of Alabama at Birmingham

Journal information: Sang-Sang Park et al, Streptococcus pneumoniae binds to host GAPDH on dying lung epithelial cells worsening secondary infection following influenza, Cell Reports (2021). DOI: 10.1016/j.celrep.2021.109267

SA Study Finds That Influenza is Widely Spread by Asymptomatic Cases

Image by Arek Socha from Pixabay

A new study investigated the prevalence and transmission of influenza in rural and urban South Africa communities.

The study was conducted by the National Institute for Communicable Diseases (NICD), Perinatal HIV Research Unit (PHRU), WITS Agincourt HDSS in partnership with the US Centers for Disease Control and Prevention (CDC), who also funded the study. 

Influenza, a communicable viral disease caused by a spectrum of influenza viruses, affects the upper respiratory tract, including upper and lower respiratory passages. The virus can be transmitted in droplets from coughing, talking or sneezing, and through touching contaminated surfaces.

Researchers enrolled 100 rural and urban households in South Africaeach year and observed them for 10 months. Systematic twice-weekly nasopharyngeal sampling of all household members were conducted, with samples tested by polymerase chain reaction (PCR) for influenza. A total of 81 430 samples were collected from 1116 participants in 225 households, out of which 917 (1%) tested positive for influenza and 79% of households (178/225) had ≥1 influenza-positive individual.

The burden of was high in a rural and an urban African setting, the study revealed, with over three-quarters of households and more than one in three individuals experiencing at least one flu infection each year. It is important to note that the flu incidence risk was similar between the rural and urban areas who participated in the study. The study also showed that recurring flu infections in the same annual flu epidemic, particularly in children, were a common occurrence, accounting for 15% of those infected. Young children also experienced the highest burden of flu infection and symptomatic illness — and compared to other age groups, they were more likely to spread the flu to others in their household.

In addition, the study also revealed that slightly over half of the flu infections were symptomatic. Asymptomatic individuals were also able to spread flu, transmitting the flu to approximately 6% of household contacts. For this reason, authors of the study believe asymptomatic infections to be an important driver of flu transmission.

Medically attended influenza-associated influenza like illness (ILI), defined as a fever and cough as captured by the World Health Organization-recommended flu surveillance programs, suggests the prevalence of flu within communities may be much higher than observed at healthcare facilities. Understanding the community burden and transmission of seasonal influenza is crucial for vaccination programmes and non-pharmaceutical interventions, as well as pandemic preparedness.

In conclusion, the study provides important data on the community burden of flu and transmission thereof in an African setting, a topic that hasn’t been adequately explored. It also contributes important findings relating to symptomatic and asymptomatic flu transmissions, and has implications for the use of non-pharmaceutical interventions and vaccination strategies that target children.

A similar study to examine the burden and transmission of SARS-CoV-2 in the same communities including the role of asymptomatic infections in the spread of SARS-CoV-2 was initiated in July 2020 and results of this study are expected in the coming months.

Source: National Institute for Communicable Diseases