The RSV virus, which kills 60,000 infants and young children every year, ushers in the world's first "defense weapon" designed for all infants

With the arrival of autumn and winter, the pediatrics of major hospitals are crowded with children
with "cold and fever".
Respiratory infections have caused a lot of trouble to families with children, and many parents have spread the saying
that "in winter, nine out of ten babies cough".

In addition to the common common cold and flu, Professor Shen Kunling, consultant of the National Clinical Research Center for Respiratory Diseases, reminds that there is a more dangerous respiratory virus, which is more transmissible than influenza, severe and fatal, and is the number one cause of infant hospitalization in the world - it is respiratory syncytial virus (RSV).

In the United States, children's RSV is spreading at unusually high levels, overwhelming children's hospitals
, CNN reported.
Several hospitals said they had been "overwhelmed
" by children with RSV.

RSV is a hidden and difficult to prevent, making it a major health threat to infants and young children worldwide and a huge disease burden
worldwide.
The good news lately, though, is that it can be prevented with a single shot
, just like the flu.
But instead of a traditional vaccine, it is a preventive monoclonal antibody
that has just been approved in the European Union.

RSV, a "nuclear bomb" hidden behind a "cold and fever"

Many people have never heard of respiratory syncytial virus (RSV).

But in fact, almost every adult has been infected with RSV unknowingly at one time or another, and it is likely that it has been infected many times
.

This is because RSV infection is generally an upper respiratory tract infection at the beginning, with symptoms similar to the common cold, and it is easy to hide in many viral and bacterial infections that cause cold-like symptoms.

According to statistics, 95% of infants and young children under the age of 2 have been infected with RSV ^[1].

Infants under one year of age are particularly at risk, with RSV infection accounting for more than 80 percent of acute respiratory infections in infants at the peak of the acute respiratory virus epidemic ^[2].

。

However, because the symptoms of RSV infection in the early stage are easily confused with colds, its harm has not been really taken seriously
for a long time.
Severe RSV infections mostly affect people with weaker bodies and weaker immune systems, such as children and the elderly
.
For infants and young children, RSV is like a "nuclear bomb" hidden in the respiratory system, and is the leading cause of infant hospitalization ^{worldwide [3].}

Infants and young children infected with RSV are often accompanied by wheezing or dyspnea, such as open nostrils during breathing, rapid or short breathing, grunting sounds, chest sinking with breathing, and signs that the skin turns blue or purple due to lack of oxygen ^[4].

We cannot predict which babies will become seriously ill and end up in the hospital: 15~50% of children will affect the lower respiratory tract due to RSV infection, which may cause bronchiolitis, throat tracheobronchitis and even viral pneumonia
.
1~3% of infants and young children need to be hospitalized after RSV infection, and 5~10% of infants and young children who are hospitalized It can be severe enough to require admission to an intensive care unit (ICU/PICU) ^[5].

For infants and young children, RSV infection is like a devil's lottery: the bomb does not explode, and it is safe; As soon as the bomb explodes, it may take away the lives
of young people.

Studies estimate that in 2015 alone, 33.
1 million RSV lower respiratory infections occurred in infants and young children under 5 years of age worldwide, resulting in 320 10,000 people were hospitalized and nearly 60,000 died – equivalent to a child dying of RSV infection
every ten minutes.
Of these, 1.
4 million were hospitalized and more than 27,000 died among infants less than six months of age ^[6].

China is considered to have one of the highest numbers of
lower respiratory tract infections (LRTIs) in children due to RSV infection in the world.
According to WHO statistics, about 35 million children under 5 years of age were infected with RSV in 2020, including children in China 3 million ^{people [7].}

A study shows that the number of hospitalizations for acute lower respiratory tract infections caused by RSV in children under 5 years of age in China accounts for 18~27% of the global total; On average, 2,500 young children are hospitalized with RSV infection every day, and up to 7,400 young children die a year ^[8].

。

RSV infection can also persist into adulthood: severe RSV infection in infancy and early childhood significantly increases the risk of asthma ^{later in life [9].}

Controlling RSV infection and reducing hospitalization and death in infants and young children have become common goals
of the medical community.

Antibody "defensive weapons" show their skills to help babies defend against RSV infestation

In 1957, scientists first identified RSV in childhood respiratory infections and, through antibody analysis, found that the viral infection was extremely common in infants and young children ^[10].

For more than 60 years, a large number of related studies have opened a window
for human understanding of viruses and infection control.

Unfortunately, RSV infection is difficult to prevent and treat
.
For many years, neither targeted treatments nor good preventive measures have emerged, and the associated disease burden has not improved
in the long term.
But in recent years, this status quo is being upended
by advances in technology.

In terms of vaccines, with the blessing of new technologies, RSV vaccines, which were originally considered extremely difficult to develop, have become an arena
for dozens of international "players".
Several vaccines to prevent RSV have entered phase III clinical trials, none of which are currently on the market
.

On the other hand, the WHO recommends prioritizing the use of long-acting monoclonal antibodies to help prevent RSV infection in infants and young children ^[11].

Recently, there has been a major breakthrough
in monoclonal antibody technology.
Just this November, Beyfortus (nirsevimab), a long-acting prophylactic monoclonal antibody, was approved for the first time in the European Union, making it possible for monoclonal antibodies to help prevent RSV infection in a wide range of infants and young children.

Beyfortus was jointly developed
by Sanofi and AstraZeneca.

Humans have discovered in the last century that antibodies can play a vaccine-like role to prevent RSV infection
.
In 1998, palivizumab, the first specifically for RSV prevention, was approved for marketing in the United States, and although the effect was obvious, it took up to 5 months RSV is injected once a month during
peak season.
Therefore, countries such as Europe, the United States, Japan and other countries have limited palivizumab to infants with the highest risk of severe RSV
.

Therefore, we need a monoclonal antibody
with stronger neutralizing ability, longer half-life, and no need for multiple injections.
Clinical trial results show that nirsevimab can accurately neutralize the places with the strongest binding ability on RSV virus, so it has higher neutralization efficiency ^[12].

In vitro experiments, nirsevimab was more than 50 times more capable of neutralizing RSV virus than palivizumab, and in rat pneumonia models of RSV, it was also stronger than palivizumab 9 times ^[13].

[Pictured.
Nirsevimab binds to the prefusion RSV virus F protein in prefusion conformation, which is the most common for RSV viruses A moment of "vulnerability" (Image source: CDC ACIP, June 2022).

In addition to being more combative, Beyfortus has also achieved "one needle to the end"
.
It introduces YTE mutations in the Fc domain of the antibody, allowing the average half-life of the antibody in the human body to reach about 60-70 days ^[13], which is common The average half-life of IgG antibodies is about 3 times ^that of a single injection to provide sustained protection for infants and young children throughout the RSV epidemic season
。

In terms of clinical trials, two key clinical studies at Beyfortus have demonstrated its effectiveness
.
A phase II clinical trial in preterm infants at less than 35 weeks' gestation ^[15], and a Melody phase III trial in healthy term infants or late preterm infants, demonstrated that its effects are no longer limited to high-risk infants.
It can help protect a wide range of infants and young children against RSV ^[16].

Does the risk of lower respiratory tract infections from RSV infection be significantly reduced after one injection of Beyfortus? The results are positive – and more than
seventy percent lower.

Clinical trials have shown that in preterm infants, Beyfortus reduced the risk of lower respiratory tract infections caused by RSV by 70.
1%; In late preterm and term infants, published results from the first group of participants showed a 74.
5%
reduction in risk.
The results of both trials were published in the New England Journal of Medicine [^13][14].

In 2021, Melody Clinical Trial was named by Nature Medicine as one of 11 clinical trials that will change the future of drugs in 2022 ^[17]
。

[Pictured.
] Stand-alone injection of Beyfortus maintained good RSV protection for 150 days (Credit: Citation 16).

In addition to providing efficient protection, Beyfortus is also highly
secure.
As a preventive agent for RSV designed for all infants and young children, Beyfortus has had a similar incidence of adverse effects to saline in multiple clinical trials [^16][17].

In November 2022, Beyfortus was approved by the European Commission as the world's first and only product that can be widely used in the prevention of RSV disease in infants and young children, and is expected to wear one for more babies.
" body armor"
.
In China, Beyfortus was also awarded by the Center for Drug Evaluation (CDE) of the National Medical Products Administration of China in January 2021 The "breakthrough therapy drug procedure" is expected to accelerate the approval of marketing
.

Is it worth it to cover all infants and toddlers? Settle accounts for RSV

If Beyfortus can extend its target population to all infants and young children, as vaccines do, another concern from a public health policymaking perspective is the "cost-effectiveness"
of prevention.

In fact, antibodies to prevent RSV are really "worthy"
.
In terms of public health, Beyfortus can not only help protect infants and young children from the risk of RSV during an epidemic season, but also be "economical" and efficient from a public health perspective
。 During periods of surge in RSV infections, severe illness in large numbers of infants and young children can lead to strained
hospital beds.
Taking 2019 as an example, more than 600,000 children under the age of 5 were hospitalized with RSV infection ^{in China [8].}
, while the number of pediatric hospital beds is only 359,000 ^[18].

Beyfortus significantly reduces the risk of medical visits and hospitalizations after infection in infants and young children, and also plays a public health role
in preventing medical runs.

At the same time as the advancement of science and technology, the spread law of the RSV virus is also quietly changing
.
In the past, RSV was generally popular in the winter and spring from November to March, but in recent years, perhaps due to the new crown epidemic, RSV has shown an anti-seasonal trend, and the peak of the epidemic is more severe than in previous years
。

In August 2021, there was already an unusual peak of RSV infection in the northern hemisphere, and in Australia in the southern hemisphere, RSV infection also rarely appeared in the summer of January February
.
Since October this year, the number of RSV infections in many regions of the United States has continued to rise, and the United States is facing a serious pediatric medical run, with more than 70% of pediatric hospital beds in
the country.
Public health experts say the United States will face RSV, the new crown and the flu "Tripledemic"
at the same time this fall and winter.
Positive RSV detection rates in other parts of the world are also much higher than in the same period in a normal year ^[19].

[Pictured.
] RSV cases in the United States have seen an unusual summer peak, with the number of cases rising significantly since September 2022 (Credit: CDC).

In this case, compared with the vaccine that can only take effect 1~2 weeks after vaccination, Beyfortus, a passive immune agent with flexible use time and immediate effect, will have more significant
advantages.

From the results of the Melody trial, it was estimated that using Beyfortus in just 11 infants and young children reduced one lower respiratory tract infection, and for every 57 infants and young children, one respiratory infection due to hospitalization was avoided
。 This protective efficiency is no different from many childhood vaccines ^[16].

The approval of Beyfortus will give all infants and young children the opportunity to live the first winter
of their lives safely without RSV infection.

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