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A new covid variant in a baby with high viral load puzzle researchers

Roberta DeBiazi, head of the hospital’s infectious disease, knew she could not conclude anything from a single case. But it rang alarm bells. And as researchers delve into the mystery, they find evidence that a variant with a mutation called N679S could circulate in the Mid-Atlantic region.

No one knows if the baby, which was seen in September and has since recovered, represents accident, sign of impending things or alarming changes that are already on the move as new, more transmissible options race all over the Earth.

“It could be a complete coincidence,”

; DeBazi said. “But the association is quite strong. If you see a patient who has exponentially more viruses and this is a completely different option, it is probably related. “

Jeremy Luban, a virologist at the University of Massachusetts School of Medicine, said the viral load on the baby’s nose was “in itself shocking and worth noting.” However, he was cautious, suggesting that “it may be because of the N679S or simply because it is [newborn] with an immature immune system allowing the virus to multiply out of control. “

Like The world is entering a new phase of the pandemic, where the virus is changing in significant ways, the United States is just beginning to understand its growing family tree due to the lack of coordinated national efforts to ensure consistency and monitoring options. The White House announced last week that it would invest an additional $ 200 million in genomic sequencing to help track new variants – allowing 25,000 per week to be analyzed. But experts say it will be weeks, if not months, before it can boost understanding of how the virus is changing within the United States.

Until then, findings like the one from Children’s National remain single pieces of the puzzle that may be important in determining the direction of the pandemic – or just transient scientific curiosities.

The question of the effect of the new options on children is particularly important. The National Health Authority said it was largely safe to reopen schools. Under pressure from President Biden and government officials, numerous neighborhoods that have remained entirely virtual – including DC’s public schools – are now opening for the first time this month.

Children generally do not get the coronavirus as well as adults. The rate of serious illness is low, and about 270 children have died from covid-19, a disease caused by the virus, or a related disease at sea of ​​500,000 deaths in the United States. It is not yet known why. It may be something about the biology of youth, some scientists say, or you may be more likely to be exposed to a similar pathogen lately.

There is no evidence that the N679S variant or others from the United Kingdom, South Africa and Brazil are more dangerous for children. But health officials in the UK said they were seeing an unusual influx of infections, especially among children aged 6 to 9, which was disproportionate to their share of the population. In Italy, employees are puzzled by the jump in cases in the northern city of Corzano among those in primary school and even younger.

And according to a February 9 report in the medical journal BMJ, Israel also experienced “a sharp rise in covid-19 infections among young people, with more than 50,000 children and teenagers being positive in January – more than Israel saw in each month. time of the first and second wave. “

In the United States, doctors at several major medical centers reported a spike in children’s hospitalizations, which ran parallel to what happened in adults, and a spike in MIS-C cases in January and February, a rare but potentially fatal post-viral syndrome. associated with covid-19, which occurs four to six weeks after coronavirus infection.

These increases are in line with expectations given the waves of the virus spreading across the community across the country. But at Children’s National, DeBiasi said the hospital was surprised to find that more MIS-C patients needed support at the intensive care level than last year. About 40 to 60 percent were in the intensive care unit last year, she said, and is now close to 90 percent.

However, some other institutions did not report a change in the severity of the cases. Doctors at Boston Children’s and UCLA Health said MIS-C cases were more numerous due to an increase in infections in the community, but the course of the disease looked similar to the previous one.

A doctor at Intermountain Primary Children’s Hospital in Salt Lake City also did not report a change in the severity of the cases, but said doctors had noticed that more children with MIS-C had active infections than in the past, when almost all tests were negative. virus – prompting the group to send sequencing samples in recent days.

“It’s hard to say what’s unusual, because with covid we always find something new,” said Ngan Truong, a pediatric cardiologist. “But we wondered, ‘Is this because of new strains?’ Is the virus shedding longer than previous strains? ‘”

It is not clear why hospitals in different parts of the country differ.

DeBiasi said it could be a coincidence. Maybe another virus – maybe a cold or flu – circulating in the DC area last year led to a milder disease that was confused with MIS-C, or maybe there was another regional difference unrelated to the coronavirus.

However, the team warned in an article published on February 10 that the critical location of the newly documented variant in the baby – in the area of ​​the protein spike, which researchers say gives it an advantage in binding to receptors in the body – and evidence that it infects other patients in the region. , “Emphasizes the need for increased viral sequencing to monitor the spread and emergence of variants, which may have a direct impact on recommended public health measures and vaccination strategies.”

Genomic sequencing in children

As of February 11, more than 3 million children in the United States had tested positive for the virus since the beginning of the pandemic. The biggest jump is observed since mid-November, when cases are increasing at a rate of 100,000 to 200,000 each week. But the nation’s sparse genomic sequence focuses almost exclusively on adults.

Harvard researcher Adrien Randolph, who leads an international study of children and coronavirus, said that in the early days of the pandemic, fewer children were infected, so they were not a priority for sequencing. But now that cases are rising among the youngest Americans and the virus is developing, the need to expand the sequence is urgent, she said.

“A few hospitals that say their cases are more severe in children don’t mean it’s a national problem,” Randolph said. “But we have to investigate. With the new variants, some of these children may have been infected with them. “

The variants being tracked by South Africa, Brazil and the United Kingdom have a change in their protein that affects the way it binds to cells, which scientists fear makes the variants more transmissible or possibly able to reinfect. Another in California appears to be more resistant to treatment with monoclonal antibodies.

“There are probably other types of anxiety that we’re not aware of right now,” said Neville Sanjana, a geneticist at the New York Center for Genomes and New York University who studies coronavirus mutations. “That’s the real worry.”

Sanjana, whose team was among the first to document the effect of the D614G mutation, which is worldwide today, said that as more adults get vaccinated, it becomes even more important to monitor how the mutations affect children. which will be among the last vaccinated, with clinical trials still ongoing. Experts also believe that sequencing in children may provide early warning for more infectious strains, as children appear to be more resistant to infection.

A study in Infectious Diseases at the Open Forum in June, for example, found that 95 percent of children seen in hospitals in Southern California were infected with the D614G mutation virus as early as April. At that time, only 60% of the state’s infected population had strains containing this mutation.

“If you don’t catch what is happening to young individuals, it’s short-sighted and we can’t fully understand how the virus can be different in people of different ages,” said Jennifer Dien Bard, director of the virology lab at Children’s Hospital of Los Angeles and one by the co-authors of the study.

Another major finding in the article, which examines 35 children, is the huge variety of variants that infect them – 97 unique changes from the original virus, first identified in Wuhan, China, have been sequenced – but no specific variant has emerged to correlate with the severity of the disease. This provided important evidence for researchers that something about children, their environment, or the way they were infected probably determines who gets very sick and who has a milder case.

The DeBiasi Children’s National Study included 76 patients, 27 of whom analyzed their complete genomes. The researchers found evidence similar to the study in Southern California that most options did not appear to affect the severity of the disease. Most notably, they found five children with identical viral genomic profiles, but the course of their illnesses seemed very different. On the other hand, the hospital saw two children with similar seemingly MIS-C cases, but each had very different viral genotypes.

A newborn with a high viral load is an anomaly.

The initial measurements of the amount of virus were so incredibly high that researchers put them back on another type of machine and found similar results. Genomic sequencing revealed that the virus infecting the child had a D614G mutation mutation, as well as something they had not seen before: the N679S mutation. The finding was so unusual that they redirected this analysis to another platform with the same results.

DeBiasi and other authors note that the specific change appears to be related to the way the virus enters the body.

William Hanage, an epidemiologist at the Harvard School of Public Health, speculates that “the spike mutation may have something to do with this. [viral load] was so high, but I think it’s premature to draw strong conclusions. “

Hanage called for caution in interpreting the importance of children with high viral loads: “It is likely that in order to be able to detect infection in children at all, viral loads are very high.”

At Children’s National, no other patient had the same option, but when researchers searched for an emerging international database used by scientists around the world to compare genomic sequences, they were surprised to find six more samples in Maryland and Virginia and more. two in Delaware.

Alan Begs, a Boston genomics expert for children, said that the fact that N679S appears in the database – which is a small part of the virus circulating in the world – suggests that “this variant is present in a significant percentage of the population in this area . He also said there was evidence that the eight cases had a common genetic origin, suggesting that they all “came from the same patient, initially somewhere in the region”.

There are four additional cases in Australia and Japan and one in Brazil. Medical information about them was not available in the database.

Like other researchers, Begs stressed that the article “has no evidence that this new option has anything to do with young babies.” However, he added, when so many millions of people have active infections, anything can happen in terms of mutations.

“The message at home is that as a country or a society, we are doing poorly in identifying alarming changes in the evolving virus,” he said, “and that is just more evidence that needs to change.”

Joel Achenbach contributed to this report.

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