Recent Study Highlights Distinctive Immune Responses to COVID-19 Among Children and Adults

A color-enhanced scanning electron image shows a cell (depicted in purple) infected with the Omicron variant of the SARS-CoV-2 virus (shown in green), taken from a human subject. This image was obtained at the Integrated Research Facility of the National Institute of Allergy and Infectious Diseases (NIAID) in Fort Detrick, Maryland. Image Credit: NIAID

Newly published research illuminates why younger children tend to experience milder COVID-19 symptoms compared to adults. The study found that young children and infants infected with SARS-CoV-2 generated a robust and enduring antibody response. These children also exhibited high concentrations of inflammatory proteins in the nasal passages, but not in the circulatory system, contrasting with the typical adult immune response to SARS-CoV-2 infection. Supported in part by the National Institute of Allergy and Infectious Diseases (NIAID), a division of the National Institutes of Health, the study has been published in the scientific journal, Cell.

Research Methodology and Sample Population

The study included 81 neonates and young children whose mothers participated in a NIAID-funded cohort study at Cincinnati Children’s Hospital during their final trimester of pregnancy. Researchers trained these mothers to collect nasal samples from their infants starting at two weeks of age. Blood samples from the children were also taken regularly, beginning when they were six weeks old and continuing when they contracted SARS-CoV-2, as well as in the weeks and months that followed.

By analyzing these samples, researchers were able to investigate the children’s immune responses prior to, during, and post-exposure to the virus. Among the study participants, 54 children became infected and showed mild symptoms of COVID-19, whereas 27 who remained uninfected served as the control group. The children were between the ages of one month and nearly four years at the time of infection; half were nine months old or younger. The study also included nasal samples from 19 mothers diagnosed with COVID-19 and 19 healthy mothers as control subjects, along with blood samples from 89 infected adults and 13 healthy adult controls.

Primary Findings: Differences in Immune Responses Between Children and Adults

Researchers employed a systems immunology approach to study various facets of the immune responses in both children and adults. Unlike adults, who usually produce antibodies that peak and then wane over a few weeks, the infants and young children in this study showed elevated antibody levels that were sustained throughout the entire 300-day observation period.

The blood of infected adults was generally found to contain elevated levels of inflammatory cytokines, which are linked to severe disease outcomes and fatalities. In contrast, the children’s blood samples did not exhibit such high levels. However, elevated levels of these inflammatory cytokines, along with a potent antiviral cytokine, were found in the children’s nasal passages.

Implications and Advisory Guidelines

The findings imply that in children, cytokines may neutralize the SARS-CoV-2 virus directly at the point of entry, which could account for their milder symptoms. The study further suggests the potential for creating vaccine adjuvants that simulate the immune responses seen in young children, aiming to sustain high antibody levels without inducing excessive inflammation in the bloodstream.

For children aged between six months and four years who were vaccinated prior to September 12, 2023, it is recommended to receive one or two booster doses of the updated COVID-19 vaccine, depending on the type and number of doses initially administered. Unvaccinated children in the same age range should receive either two or three doses of the new vaccine, depending on the specific vaccine they will be administered.

Source Citation

The research was led by Bali Pulendran, Ph.D., and Mary Allen Staat, M.D., M.P.H. Dr. Pulendran serves as the Violetta L. Horton Professor and co-director of the Institute for Immunology, Transplantation and Infection at Stanford University in California. Dr. Staat holds the Kulkarni Endowed Chair in Infectious Diseases and is a professor of pediatric infectious diseases at Cincinnati Children’s Hospital. The study was published on September 29, 2023, in the journal Cell, with the DOI: 10.1016/j.cell.2023.08.044.

Frequently Asked Questions (FAQs) about COVID-19 immune responses in children and adults

More about COVID-19 immune responses in children and adults

• Cell Journal Article
• National Institute of Allergy and Infectious Diseases (NIAID)
• Cincinnati Children’s Hospital
• Systems Immunology Approach
• Vaccine Adjuvants
• Stanford Institute for Immunology, Transplantation and Infection
• Overview of Cytokines