There’s no evidence that the variant with N679S, or others from the UK, South Africa and Brazil, are more dangerous to children. But US doctors are sitting with a very unusual case.
WASHINGTON – Among the more than 2,000 youngsters treated for the coronavirus at Children’s National Hospital in the District of Columbia, one newborn was unusual.
The baby was very sick, for one. Most infected kids barely show symptoms and even the hospitalised ones tend to have mild cases.
But the real surprise came when doctors measured the infant’s viral load. It was 51,418 times the median of other paediatric patients. And when they sequenced the virus in the baby recently, they found a variant they hadn’t seen before.
Roberta De Biasi, chief of infectious disease for the hospital, knew she couldn’t conclude anything from one case. But it set off alarm bells. And as the researchers delved further into the mystery, they found evidence that a variant with a mutation called N679S may be circulating in the mid-Atlantic region.
No one knows whether the infant, who was seen in September and has since recovered, represents a chance case, a sign of things to come, or worrisome changes already in motion as new, more transmissible variants race across the Earth.
“It could be a complete coincidence,” De Biasi said. “But the association is pretty strong. If you see a patient who has exponentially more virus and it’s a completely different variant, it is probably related.”
Jeremy Luban, a virologist at the University of Massachusetts Medical School, said the viral load in the infant’s nose “in itself, is shocking and noteworthy.” However, he was cautious in speculating that it “could be because of N679S, or simply because it is a [newborn] with an immature immune system, permitting the virus to replicate out of control.”
As the world heads into a new stage of the pandemic where the virus is changing in significant ways, the United States has been so behind in tracking new variants that it’s difficult to understand the current threat, much less predict the next one.
The White House announced last week that it will invest an additional $200 million into genomic sequencing to help track new variants – making it possible to analyse 25,000 per week.
And some experts argue that some of the best bang for our limited genetic testing buck could come from focusing more on children, who could act as harbingers of more infectious strains because they are generally more resistant to the virus.
Until then, findings like the one from Children’s National remain single puzzle pieces that may be important in determining the direction of the pandemic – or merely transient scientific curiosities.
The question of the new variants’ effect on children is especially important the nation’s top health authority has declared that it is largely safe to reopen schools even as school systems in countries besieged by the United Kingdom variant have closed.
Kids in general do not get sick from the coronavirus the way adults do. The rate of severe illness is low, and about 270 children have died from Covid-19, the disease caused by the virus, or an associated illness in a sea of 500,000 US deaths.
It is still not known why. It could be something about the biology of youth, some scientists have said, or perhaps a higher likelihood of being exposed to a similar pathogen more recently.
There’s no evidence that the variant with N679S, or others from the United Kingdom, South Africa and Brazil, are more dangerous to children.
But health officials in the United Kingdom have said they are monitoring an unusual surge in infections, especially among children ages 6 to 9, that is disproportionate to their share of the population. In Italy, officials have been puzzled by a spike in cases in the northern town of Corzano among those in elementary school and even younger.
And according to a February 9 report in the medical journal the BMJ, Israel also has experienced “a sharp rise in Covid-19 infections among young people, with more than 50,000 children and teens testing positive in January – more than Israel saw in any month during the first and second waves.”
In the United States, doctors at several major medical centres reported a holiday surge in hospitalizations of children that paralleled what happened in adults, and a January and February spike in cases of MIS-C – a rare but potentially fatal post-viral syndrome associated with Covid-19 that occurs four to six weeks after a coronavirus infection.
Those increases are in line with what would be expected given the waves of community spread of the virus nationwide. But at Children’s National, De Biasi said the hospital has been surprised to find that more MIS-C patients have needed intensive care-level support than last year. About 40 to 60 percent were in the ICU last year, she said, and now it’s closer to 90 percent.
Some other institutions, however, reported no change in the severity of cases. Doctors at Boston Children’s and UCLA Health said the MIS-C cases have been more numerous because of the surge in community infections, but the course of the illness appears similar to before.
A doctor at Intermountain Primary Children’s Hospital in Salt Lake City also reported no change in the severity of cases, but said physicians have noticed that more children with MIS-C have active infections than in the past, when nearly all tested negative for the virus – prompting the group to send samples off for sequencing in recent days.
“It’s hard to say what is out of the ordinary, because with Covid, we’re always finding something new,” said Ngan Truong, a paediatric cardiologist. “But we’ve wondered, ‘Is this because of new strains? Is virus shedding longer than previous strains?’ “
Why hospitals in different parts of the country are seeing a divergence in these cases is unclear.
De Biasi said it could be pure happen stance. Perhaps another virus – maybe a cold or flu – circulating in the DC area last year resulted in a milder disease that was mistaken for MIS-C, or perhaps there was another regional difference unrelated to the coronavirus.
However, the team cautioned in a paper posted on February 10 that the critical location of the newly documented variant in the infant – in the spike protein area that researchers think gives it an advantage in attaching to receptors in bodies – as well as evidence that it is infecting other patients in the region, “underscores the need for increased viral sequencing to monitor variant prevalence and emergence, which may have a direct impact on recommended public health measures and vaccination strategies.”
Harvard researcher Adrienne Randolph, who is leading an international research effort on children and the coronavirus, said that in the early days of the pandemic, fewer children were infected, so they were not prioritised for sequencing. But now that cases are surging in the youngest Americans, and the virus is evolving, the need to expand sequencing is urgent, she said.
“A couple of hospitals saying their cases are more severe in kids doesn’t mean nationally this a problem,” Randolph said. “But we have to investigate. With new variants, it could be some of these kids were infected with them.”
Variants being closely tracked from South Africa, Brazil and the United Kingdom have a change in their spike protein that affects how it binds to cells, which scientists fear is making the variants more transmissible or possibly able to reinfect. Another in California appears to be potentially be more resistant to treatment with monoclonal antibodies.
“There are likely other variants of concern we’re not aware of right now,” said Neville Sanjana, a geneticist at the New York Genome Center and New York University who studies coronavirus mutations. “That’s the real worry.”
The newborn with the high viral load was an anomaly.
The initial measures of the amount of virus were so unbelievably high that the researchers ran them again on a different type of machine and found similar results. Genomic sequencing revealed that the virus infecting the child had the D614G spike variant mutation, as well as something they hadn’t seen before: the N679S mutation. The finding was so unusual that they reran this analysis on another platform with the same results.
De Biasi and the other authors noted that the particular change appears to be related to how the virus enters the body.
William Hanage, an epidemiologist at the Harvard School of Public Health, speculated that “the spike mutation might have something to do with why that [viral load] was so high, but I think it is premature to draw strong conclusions.”
Hanage urged caution when interpreting the significance of children with high viral loads: “It is probable that in order for infection in kids to be noticed at all, the viral loads have to be very high.”
At Children’s National, no other patients had the same variant, but when researchers queried an emerging international database used by scientists worldwide to compare genomic sequences, they were surprised to find six other samples in the Maryland and Virginia area, and two more in Delaware.
Alan Beggs, a genomics expert at Boston Children’s Hospital, said the fact that N679S appears in the database – which represents a tiny portion of the virus circulating in the world – suggests that “this variant is present in some significant percentage of the population in this area.” He also said there was evidence that the eight cases had a common genetic background, indicating that all “were originated from one patient initially somewhere in the region.”
There were four additional cases in Australia and Japan and one in Brazil. Medical information about them was not available in the database.
Like other researchers, Beggs emphasised that the paper “does not have evidence this new variant has anything to do with making little babies sicker.” However, he added, when so many millions of people have active infections, anything can happen in terms of mutations.
“The take-home message is that as a country or society, we are doing poorly in identifying worrisome changes in the evolving virus,” he said, “and this is just more evidence that needs to change.”
