Study Finds Kids Develop Different Antibodies When They Get COVID-19

Study Finds Kids Develop Different Antibodies When They Get COVID-19
  • A new study published Nov. 5 in the journal Nature Immunology adds to our understanding of the differences between how children and adults respond to the new coronavirus, SARS-CoV-2.
  • Children have a distinct immune response to the new coronavirus compared to adults.
  • Researchers saw that children who had contracted SARS-CoV-2 produced lower levels of neutralizing antibodies and fewer types of antibodies.

One of the striking things about COVID-19 is that children who have contracted the new coronavirus rarely develop the kinds of severe respiratory and other symptoms seen in adults.

In addition, most children who develop COVID-19 have mild or no symptoms.

This doesn’t mean children are immune to the new coronavirus.

A small number of children with COVID-19 can develop a serious condition called multisystem inflammatory syndrome in children (MIS-C). Scientists aren’t certain, though, why some children get very sick and others don’t.

A new study published Nov. 5 in the journal Nature Immunology adds to our understanding of the differences between how children and adults respond to SARS-CoV-2.

Researchers from Columbia University and other institutions found that children’s immune response to SARS-CoV-2 is distinct from that of adults. This was true even in children who developed MISC-C.

Shane Crotty, PhD, a virologist at the La Jolla Institute for Immunology, said this finding wasn’t a given.

“Children definitely have a different disease outcome from adults,” he said, “but that could be for a lot of different reasons.”

Distinct immune response in children with COVID-19

After analyzing blood samples taken from adults and children, researchers saw that children who had contracted the new coronavirus produced lower levels of neutralizing antibodies and fewer types of antibodies.

The immune system can produce many different antibodies specific to a virus. Neutralizing antibodies bind in a way that blocks infection.

The results of the study don’t mean that children’s immune response was weaker, because that implies that “more is better,” said Dr. Ravi Jhaveri, associate division head of infectious disease and professor of pediatrics (infectious diseases) at the Ann & Robert H. Lurie Children’s Hospital of Chicago.

“The adult patients with the worst symptoms of ARDS [acute respiratory distress syndrome] had the highest levels of antibody,” Jhaveri said, “while children with varying levels of symptoms, mostly milder, had lower responses.”

Even among adults, those with severe symptoms had higher levels of neutralizing antibodies compared to adults with mild symptoms.

Again, the higher levels of neutralizing antibodies didn’t correlate with better disease outcomes.

“People tend to oversimplify that neutralization is all we should care about, but this may not be the whole story,” Jhaveri said. “Sometimes the best antibodies are the ones that help the immune cells find and destroy a virus.”

Researchers didn’t look at this kind of immune activity.

Sean Diehl, PhD, an associate professor of microbiology and molecular genetics at the University of Vermont, said another interesting finding of the study is that the adults produced antibodies that bound to more parts of the virus.

“Adults are targeting both the outer spike protein, as well as the nucleocapsid that binds to and protects the genome of the virus,” he said. “But kids are only making antibodies against the spike protein.”

This could have implications for coronavirus testing. Some antibody tests, including those made by Abbott and Roche, look only for antibodies that bind to the nucleocapsid. These tests may miss children who currently have the new coronavirus or who had an infection in the past.

Diehl said adults may be producing more types of antibodies because they have a higher viral load than children. The researchers didn’t measure how much virus people had in their body, so this connection isn’t clear.

However, the fact that both children and adults produced neutralizing antibodies against the spike protein bodes well for COVID-19 vaccines, Diehl said.

Many vaccine candidates currently being studied target the spike protein. Preliminary data from some phase 3 trials suggest that these vaccines are effective in adults. This suggests they may also work in children, who haven’t been included in many of the ongoing trials.

In the new study, researchers analyzed antibodies from a single point in time from 79 participants in four groups:

  • convalescent plasma donors who had recovered from COVID-19 without being hospitalized
  • adults hospitalized with severe COVID-19 ARDS
  • children hospitalized with MIS-C
  • children who had a coronavirus infection but didn’t develop severe illness

The study was too small to show whether children’s antibody levels differed with age. The blood samples also came from one hospital in one region of the country, so the results may not apply to everyone.

Antibodies just one part of immune response

Alessandro Sette, Dr. Biol.Sci., an immunologist at the La Jolla Institute for Immunology in California, said the results reinforce the idea that it’s not just antibodies that determine how sick someone gets from COVID-19, but many factors are involved.

We already know that people with other medical conditions, such as obesity, cardiovascular disease, and diabetes, are more at risk for severe disease.

In addition, Diehl said that in certain adults with severe COVID-19, some of the damage is caused by an overreaction of the immune system rather than the virus itself.

“In these people, the immune system is acting quite strongly and causing a lot of collateral damage,” Diehl said.

It’s not clear, though, why some children have more severe disease than others. The researchers offered several possible reasons.

The lower levels of neutralizing antibodies in children may predispose them to persistent infection in other parts of the body, leading to MISC-C.

Or the presence of non-neutralizing antibodies could lead to a condition known as antibody-dependent enhancement (ADE), which is known to occur in other viral infections.

More research in this area is needed.

While the new study looked at antibodies — proteins that bind to the virus to prevent infection — the immune system also has a cellular component.

This includes killer T cells that attack cells invaded by the virus, and helper T cells that help coordinate the immune response.

“Some data show that adults who have a more benign outcome have good T-cell responses — both helper and killer T cells — and also antibody responses,” Sette said.

A person’s T-cell response may be a better indicator of how sick a person gets with COVID-19, according to Sette. In the new study, the researchers didn’t measure people’s cellular immune response.

Jhaveri also sees a possible role for T cells in determining the severity of illness.

“It may be that a child’s cellular response is really strong and the antibodies have to do less work,” Jhaveri said, “and the opposite is true for adults.”

Some researchers have proposed that T cells from people who have recovered from COVID-19 could be used to treat other people, similar to how convalescent plasma therapy is thought to work.

Although the new study shows a difference in antibody response between children and adults, Jhaveri said the data don’t indicate whether children are more likely to transmit or contract the new coronavirus.

Crotty said results from other studies on this topic have been mixed.

“I’ve seen data that seem to indicate that kids get infected just as much [as adults] but don’t get sick,” he said. “And I’ve seen other data that indicate that kids don’t get infected as much.”

More research is needed to fully understand how children’s immune systems respond to the coronavirus, but this can be challenging simply because children with COVID-19 don’t get as sick.

“You don’t have access to as many cases in children to study,” Sette said, “because many may go undetected.”

“That is one of the things that is very important about this study,” he added. “It is one of the first studies to really have a very careful, quantitative analysis of the antibody response in kids with and without MISC-C syndrome.”

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