New Research Finds Key Differences Between Children & Adults With COVID-19

Recent findings shed light on why younger children exhibit fewer severe COVID-19First identified in 2019 in Wuhan, China, COVID-19, or Coronavirus disease 2019, (which was originally called "2019 novel coronavirus" or 2019-nCoV) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has spread globally, resulting in the 2019–22 coronavirus pandemic.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>COVID-19 symptoms compared to adults. The study observed that infants and young children who contracted SARS-CoV-2Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the official name of the virus strain that causes coronavirus disease (COVID-19). Previous to this name being adopted, it was commonly referred to as the 2019 novel coronavirus (2019-nCoV), the Wuhan coronavirus, or the Wuhan virus.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>SARS-CoV-2 had a strong, sustained antibody response to the virusA virus is a tiny infectious agent that is not considered a living organism. It consists of genetic material, either DNA or RNA, that is surrounded by a protein coat called a capsid. Some viruses also have an outer envelope made up of lipids that surrounds the capsid. Viruses can infect a wide range of organisms, including humans, animals, plants, and even bacteria. They rely on host cells to replicate and multiply, hijacking the cell's machinery to make copies of themselves. This process can cause damage to the host cell and lead to various diseases, ranging from mild to severe. Common viral infections include the flu, colds, HIV, and COVID-19. Vaccines and antiviral medications can help prevent and treat viral infections.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>virus and high levels of inflammatory proteins in the nose but not in the blood. This immune response contrasts with that typically seen in adults with SARS-CoV-2 infection. Co-funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of HealthThe National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. Founded in 1887, it is a part of the U.S. Department of Health and Human Services. The NIH conducts its own scientific research through its Intramural Research Program (IRP) and provides major biomedical research funding to non-NIH research facilities through its Extramural Research Program. With 27 different institutes and centers under its umbrella, the NIH covers a broad spectrum of health-related research, including specific diseases, population health, clinical research, and fundamental biological processes. Its mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>National Institutes of Health, the research appears in the journal Cell.  

Study Methodology and Participants

The investigation involved 81 full-term infants and young children whose mothers enrolled in a NIAID-supported cohort study at Cincinnati Children’s during their third trimester of pregnancy. The study team trained mothers to collect weekly nasal swabs from their infants starting when the babies were 2 weeks old. The team also drew blood from the babies regularly, starting at age 6 weeks, as well as when the children became infected with SARS-CoV-2 and during subsequent weeks and months.

These samples enabled the scientists to study the children’s immune responses before, during, and after they were exposed to the virus for the first time. Fifty-four of the children became infected and had mild COVID-19, while 27 who tested negative through the study period served as matched controls. At the time of infection, the children were 1 month to nearly 4 years old, and half were 9 months or younger. The study also included weekly nasal swabs from 19 mothers with COVID-19 and 19 healthy mothers as controls, as well as blood samples from 89 adults with COVID-19 and 13 healthy controls.

Key Findings: Child vs. Adult Immune Response

The researchers examined many aspects of the babies’ and adults’ immune responses to the virus through an approach called systems immunology. The study revealed that young children’s antibody response to SARS-CoV-2 differs from that of adults. Typically, adults produce antibodies to the virus at levels that spike for a few weeks, then decline. In contrast, the infants and young children in the study produced protective antibodies at levels that spiked and remained high for up to the full 300-day observation period. 

The scientists also found that the blood of adults with SARS-CoV-2 infection typically had high levels of proteins called inflammatory cytokines, which are associated with severe COVID-19 and death, while the blood of babies and children did not. However, the children’s noses had high levels of inflammatory cytokines and a potent antiviral cytokine.

Implications and Recommendations

According to the researchers, these findings suggest that cytokines snuffed out SARS-CoV-2 infection right at the site where the virus entered the children’s bodies, potentially explaining the mildness of their COVID-19 disease. The findings also suggest it may be possible to devise vaccine adjuvants that mimic the immune responses observed in young children by stimulating persistently high antibody levels without causing dangerous excess inflammation in the blood.   

Children aged 6 months to 4 years who got COVID-19 vaccines before September 12, 2023, should get one or two doses of updated COVID-19 vaccine, depending on which vaccine and how many doses they previously received. Children aged 6 months to 4 years who have not been vaccinated should get two or three doses of the updated COVID-19 vaccine, depending on which vaccine they receive. 

Reference: “Multi-omics analysis of mucosal and systemic immunity to SARS-CoV-2 after birth” by Florian Wimmers, Allison R. Burrell, Yupeng Feng, Hong Zheng, Prabhu S. Arunachalam, Mengyun Hu, Sara Spranger, Lindsay E. Nyhoff, Devyani Joshi, Meera Trisal, Mayanka Awasthi, Lorenza Bellusci, Usama Ashraf, Sangeeta Kowli, Katherine C. Konvinse, Emily Yang, Michael Blanco, Kathryn Pellegrini, Gregory Tharp, Thomas Hagan, R. Sharon Chinthrajah, Tran T. Nguyen, Alba Grifoni, Alessandro Sette, Kari C. Nadeau, David B. Haslam, Steven E. Bosinger, Jens Wrammert, Holden T. Maecker, Paul J. Utz, Taia T. Wang, Surender Khurana, Purvesh Khatri, Mary A. Staat and Bali Pulendran, 29 September 2023, Cell.
DOI: 10.1016/j.cell.2023.08.044

Bali Pulendran, Ph.D., and Mary Allen Staat, M.D., M.P.H., led the study. Dr. Pulendran is the Violetta L. Horton Professor and co-director of the Institute for Immunology, Transplantation and Infection at Stanford University in California. Dr. Staat is the Kulkarni Endowed Chair in Infectious Diseases and a professor of pediatric infectious diseases at Cincinnati Children’s.