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A new analysis reveals that the course of SARS-CoV-2 infection and the immune response it causes is completely different in adults and children.
Researchers found that children and adults produce different types and amounts of antibodies in response to SARS-CoV-2 infection, suggesting that the course of infection and the immune response are completely different in these two age groups.
“Our study provides a thorough examination of SARS-CoV-2 antibodies in children, revealing a stark contrast to adults,” said Dr. Donna Farber, immunologist at Columbia University Vagelos College of Physicians and Surgeons, the George H. Humphreys II Professor of Surgery Sciences in the Department of Surgery, who led the study with Dr. Matteo Porotto, associate professor of viral molecular pathogenesis in the Columbia Department of Pediatrics.
Children are less affected by SARS-CoV-2 infections
According to the team, one of the surprising manifestations of the COVID-19 pandemic is that most children fight the infection with very few problems, while older people struggle. Infection with SARS-CoV-2, the virus that causes COVID-19, causes adults to develop respiratory symptoms that can become severe and lead to acute respiratory distress syndrome (ARDS). Children, on the other hand, are largely spared from respiratory diseases, but they can develop the life-threatening multisystem inflammatory syndrome (MIS-C).
“This is a new infection for everyone, but children are uniquely adapted to seeing pathogens for the first time. This is what their immune system is designed for. Children have many naive T cells that are able to recognize all kinds of new pathogens, while older people are more dependent on their immunological memories. We are not so able to respond to a new pathogen … “Faber said.
Children produce fewer neutralizing antibodies
In their paper, the researchers studied 47 children – 16 treated for MIS-C and the other 31 with confirmed COVID-19 but not MIS-C – and 32 adults with symptoms ranging from milder disease (patients able to recover to home) to those hospitalized. with severe COVID-19. According to the team, half of the children without MIS-C had no COVID-19 symptoms.
In their analysis, children with or without MIS-C produced the same antibody profile, but this profile was different from that found in adults.
The children had fewer antibodies directed against the SARS-CoV-2 Spike (S) protein that the virus uses to infect human cells. The children’s antibodies also had the least neutralizing activity, while all the adults produced neutralizing antibodies. The antibodies found in the sickest adults had the most neutralizing activity.
Farber said that the sickest individuals who have the most neutralizing antibodies likely reflect the amount of time the virus is present in the sickest patients: “There is a connection between the extent of your immune response and the extent of the ‘infection: the more severe the infection, the more robust the immune response, because more immune cells and immune reactions are needed to eliminate a higher dose of a pathogen. ”
Farber also said that the fact that children produce very few antibodies targeting the protein S suggests that the infection does not spread much or damages many of their cells. Porotto added: “Because babies clear the natural virus quickly, they don’t have a widespread infection and don’t need a strong antibody response.”
The team suggests that this reduced course of infection in children may indicate that they are infectious for a shorter period of time than adults, and therefore less likely to spread the virus, although the researchers did not measure viral loads in children.
“Current studies in other countries indicate that school-age children are not vectors for the novel coronavirus, so our data are consistent with those results,” Farber said.
Children should still respond well to SARS-CoV-2 vaccines
The researchers said that despite producing fewer antibodies in response to SARS-CoV-2 infection, children shouldn’t have a weaker response to a future vaccine, as developing vaccines do not mimic the normal route of infection. .
“Although infants do not produce neutralizing antibodies in response to a natural infection with SARS-CoV-2, vaccines are designed to generate a protective immune response in the absence of an infection,” Farber explained. “Children respond very well to vaccines and I think they will develop good neutralizing antibody responses to a SARS-CoV-2 vaccine, they will probably be better protected than adults.
Focus on the future: what is missing from the adult immune system?
Although the study suggests that the course of the infection is different for adults and children, why this is the case is still unclear. Columbia researchers now want to understand why children shed SARS-CoV-2 more easily and what might be missing in the adult immune system, preventing them from doing the same.
Farber, Porotto and their colleagues are currently looking for differences in the response of T lymphocytes, specifically the T lymphocytes that reside in the lung. Previous research from Farber’s lab has shown that these tissue-populating T cells are more important in fighting lung infections than the T cells that circulate through the bloodstream.
The team suggests that children can generate a stronger immune response to SARS-CoV-2 infections by distributing interferon and macrophages to indiscriminately attack pathogen-infected cells. While other studies have indicated that the innate immune response may be delayed in SARS-CoV-2 infected adults. Farber commented: “If the innate response is really strong, this can reduce the viral load in the lungs and the adaptive response antibodies and T cells have less to clear up.”
The team said it may also be possible that SARS-CoV-2 is less able to infect children’s cells, likely because they express fewer proteins required by the virus to infect human cells.
Columbia researchers are now testing these possibilities with cells from children versus adults.
The article was published in Nature Immunology.
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