“Study predicts which kids hospitalized with RSV likely to worsen – Washington University School of Medicine in St. Louis - Washington University School of Medicine in St. Louis” plus 2 more

Study predicts which kids hospitalized with RSV likely to worsen – Washington University School of Medicine in St. Louis - Washington University School of Medicine in St. Louis
RSV is a common winter illness in children. Why did it see a summer surge in Australia this year? - The Conversation AU
Rescue of codon-pair deoptimized respiratory syncytial virus by the emergence of genomes with very large internal deletions that complemented replication - pnas.org

Study predicts which kids hospitalized with RSV likely to worsen – Washington University School of Medicine in St. Louis - Washington University School of Medicine in St. Louis

Posted: 01 Apr 2021 08:12 AM PDT

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Children with high levels of defective viral genomes likely to get even sicker

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Children hospitalized with breathing problems due to infection with respiratory syncytial virus (RSV) are likely to get sicker and remain hospitalized if they have high levels of defective copies of the virus, according to a new study by researchers at Washington University School of Medicine in St. Louis.

Children hospitalized with breathing problems due to a common viral lung infection are likely to get sicker and remain hospitalized if they have high levels of defective copies of the virus, according to a new study by researchers at Washington University School of Medicine in St. Louis.

The findings, published April 1 in Nature Microbiology, could help doctors identify those patients at high risk of severe illness due to respiratory syncytial virus (RSV), the most common cause of pneumonia and bronchiolitis (inflammation of the small airways) in children under age 5.

"Every child has been infected by RSV at least once before the age of 3," said senior author Carolina B. López, PhD, a professor of molecular microbiology and a BJC Investigator. "Some infants and small children will just develop a cold, but others end up hospitalized. We don't really know what determines whether a child will get really sick or not. So when babies are admitted to the hospital with RSV, doctors don't have a way to predict whether they will be discharged in a day or two, or end up in intensive care."

The new findings could lead to a way for doctors to triage people who arrive in the emergency room wheezing from an RSV infection, and direct the most intensive interventions to those most at risk of getting even sicker, López added.

RSV is a common respiratory virus. People get reinfected many times over the course of their lives and usually only experience cold-like symptoms. For young children and older adults, however, RSV infection can be life-threatening. Every year in the U.S., about 58,000 children under age 5 are hospitalized due to RSV infection, and from 100 to 500 die. The virus also kills about 14,000 older adults every year.

López and colleagues previously discovered that RSV, as it multiplies, makes some nonfunctional copies of its genome. These defective viral genomes are missing crucial sections, so they can't form new infectious viruses, but they do trigger a strong antiviral immune response. To find out whether the presence of defective viral genomes affects how sick people get, López collaborated with co-corresponding author Christopher Chiu, MD, PhD, of Imperial College London, Shaon Sengupta, MBBS, from the Children's Hospital of Philadelphia, and co-first authors Sébastien A. Felt, PhD, now a postdoctoral researcher at Washington University, and Yan Sun, PhD, now an assistant professor at the University of Rochester Medical Center, among others.

The researchers analyzed viral RNA in nasal washes from 122 children under age 2 who had been hospitalized with RSV. Defective viral genomes were found in 100 (82%) of the children. Those with defective viral genomes got sicker and stayed in the hospital longer than those without.

Further studies with infants who had been naturally infected with RSV but not hospitalized, and with healthy young adults who had been experimentally infected, showed that the health consequences of the defective genomes depend on when they show up in the course of illness. Those children and adults who generate detectable levels of defective genomes early in the course of an infection had shorter and milder illnesses than those whose defective viral genomes were not detected until later or those who never developed defective genomes at all.

"The defective genomes are kind of a proxy for the immune response," López said. "No matter when in the course of infection we detect defective genomes, we see a stronger immune response. But timing matters here. A strong immune response very early after infection is good because it prevents the virus from multiplying. But if the immune response comes too late, when the virus has already multiplied, it is likely very damaging and leads to more severe illness."

It is possible that a similar pattern also may be found in other respiratory viruses, López said. The researchers used a common laboratory technique known as polymerase chain reaction, or PCR, to identify the defective viral genomes in infected people. Such a technique could be adapted to other respiratory viruses.

"More and more people have been looking for defective genomes in viral infections, and every virus they've studied has turned out to have them," López said. "We have more work to do to learn whether these defective genomes really are drivers of outcomes in different viral infections. But I do think it's worth putting the energy into trying to understand what these secondary products of viruses are doing to determine the course of the infection."

RSV is a common winter illness in children. Why did it see a summer surge in Australia this year? - The Conversation AU

Posted: 09 Mar 2021 12:00 AM PST

Winter typically brings a surge in respiratory viral infections, when we see many children running around with runny noses and phlegmy coughs.

But the 2020 Australian winter was very different. Public health measures in place to control the spread of COVID-19 saw a major shift in the typical seasonal pattern of other respiratory viruses.

This has perhaps been most notable with respiratory syncytial virus (RSV), a very common cause of hospitalisation in young children over winter months in many parts of the world, including Australia.

But following an abnormal winter that saw a significant drop in rates of RSV — we found there were 98% fewer winter cases in Western Australian children — paediatric hospitals around Australia have seen unexpectedly large numbers of children presenting with RSV over summer.

So, what is RSV, and why are these changing trends important?

A winter lurgy

RSV typically circulates during winter in temperate climates, much like influenza.

It's the major cause of lung infections in children, commonly causing bronchiolitis. Symptoms of RSV include a runny nose, cough, reduced feeding and fever. Complications include wheezing and difficulty breathing, which can develop into pneumonia.

Severe cases occasionally lead to death, predominantly in very young infants.

Almost all children have had an RSV infection by age two, but infants in their first year of life are more likely to experience severe infections requiring hospitalisation, because their airways are smaller. Babies have also not built up immunity to RSV from previous years (we call this being RSV-naïve).

RSV is spread through respiratory secretions, when an infected person sneezes or coughs. In this way it's similar to COVID-19. But in contrast to the coronavirus, children are more vulnerable to RSV infection than adults. As a result, RSV is readily spread among children, especially at daycare, kindergarten and school.

How is RSV treated?

Most children will recover without needing specialist care in hospital, and children with mild infection can be treated with rest at home.

However, many children, particularly young infants, those born prematurely, and children with underlying health issues, are admitted to paediatric wards with severe RSV every year.

Treatment for RSV is focused on helping children with their breathing (for example, giving them oxygen) and feeding (for example, administering fluids through a drip).

There's no licensed vaccine for RSV, but the World Health Organization considers this a priority, and a number of vaccines are currently in development.

A doctor holds a stethoscope to a baby's chest. — Infants under one are more vulnerable to a serious case of RSV. Shutterstock

What happened to RSV in 2020?

The stay-at-home orders across Australia from late March 2020, and the implementation of quarantine for international arrivals, coincided with the start of the usual RSV and influenza season in Australia.

With these measures in place, RSV and influenza cases dropped dramatically and remained very low throughout winter.

In Western Australia, despite a relaxation of COVID-related restrictions, including schools reopening from May 2020, there was still a dramatic reduction in RSV cases through winter. This suggests border closures were important in reducing transmission from arriving overseas travellers.

RSV cases remained low until late spring, when a large surge was observed in New South Wales and WA.

The speed and magnitude of this increase was greater than the usual winter peak of RSV.

More recently, other states including Victoria and Queensland have seen a similar unseasonal rise in RSV cases.

It's likely reductions in COVID-19 restrictions have opened the door for increased RSV spread. Reduced immunity to RSV may also have contributed through both an increase in number of RSV-naïve children and possibly waning RSV immunity in older children related to the delayed season.

Studies seeking to understand exactly why we've seen a rise in RSV cases are ongoing.

Why might the Australian surge be important elsewhere?

Australia's experience may carry important lessons for Northern Hemisphere countries, including the United States and the United Kingdom, which saw similar reductions in RSV cases during their winter.

Relaxing of COVID restrictions, which is beginning in many Northern Hemisphere countries now, may provide an opportunity for rapid spread of RSV. Our experience should serve as a warning for paediatric hospitals in the Northern Hemisphere to ensure adequate staffing and available resources to meet the possible increased need.

Three young children playing with various toys. — Children mixing less as a result of COVID-19 restrictions likely contributed to the drop in RSV cases during winter. Shutterstock

Our RSV experience may also be applicable to influenza, which still remains at very low levels globally. Reduced immunity to influenza due to the skipped 2020 season may result in a very severe season when influenza returns. Seasonal influenza vaccines could be particularly important in 2021 to protect against a possible large resurgence.

Let's hold on to our good COVID habits

The COVID-19 pandemic has shown us the spread of respiratory viruses can be reduced by physical distancing and increased hygiene measures.

While we are (hopefully) unlikely to see prolonged stay-at-home orders again in Australia, ongoing basic measures including hand washing, cough etiquette and keeping snotty children at home can all help reduce the spread of RSV and influenza moving forward.

As we approach the 2021 Australian winter, by doing these simple things, as well as getting our flu vaccines, we can all help protect children, including those most vulnerable, from these important respiratory viruses.

Rescue of codon-pair deoptimized respiratory syncytial virus by the emergence of genomes with very large internal deletions that complemented replication - pnas.org

Posted: 30 Mar 2021 12:00 AM PDT

Rescue of codon-pair deoptimized respiratory syncytial virus by the emergence of genomes with very large internal deletions that complemented replication

Cyril Le Nouën, Thomas McCarty, Lijuan Yang, Michael Brown, Eckard Wimmer, Peter L. Collins, Ursula J. Buchholz

Proceedings of the National Academy of Sciences Mar 2021, 118 (13) e2020969118; DOI: 10.1073/pnas.2020969118

Severe Acute Respiratory Syndrome