CNPRC Pilot Research Project Spotlight: The Impact of Age on COVID Response
In the spring of 2020, SARS-CoV-2 swept across the world, and scientists everywhere immediately jumped into action. Questions from how the virus spread, to what the infection does to the human body, to who is most at risk needed to be answered. Assistant Professor at Duke Human Vaccine Institute, Maria Blasi, wanted to learn more about the age-dependent responses of SARS-CoV-2. Specifically, she was interested in why infants and young children had lower hospitalization and fatality rates than older populations. Blasi teamed up with Assistant Professor Stephanie Langel from Case Western Reserve University School of Medicine and Sallie Permar of Weill Cornell Medical College to investigate this phenomenon.
The team used the Pilot Research Program at the California National Primate Research Center (CNPRC) to study SARS-CoV-2 pathogenesis in infant and adult rhesus macaques. The CNPRC Pilot Research Program provides investigators with unique facilities for nonhuman primate research, specialized Core services, Core Scientist expertise, and funding to conduct pilot investigations.
“We were looking for a way our expertise could contribute to this pandemic and figuring out what funding mechanisms are available,” said Langel. “We decided that the CNPRC’s Pilot Research Program would be a great way to collaborate with scientists from a variety of backgrounds to research age differences in SARS-CoV-2 response.”
Utilizing the CNPRC Pilot Research Program, Blasi, Langel, Permar, and CNPRC core scientists Lisa Miller and Koen Van Rompay teamed up to thoroughly examine SARS-CoV-2 recovery at a cellular level in two rhesus macaque infant-dam pairs. All four animals were exposed to the virus and monitored closely for two weeks, at which point samples were collected to explore how each age group responded to the exposure.
Notable Differences In Immune Response
Findings revealed noticeable differences in innate immune response in the trachea (upper respiratory tract). Langel explained, “sequencing cells in the upper respiratory tract revealed interesting signatures. We saw that infants had higher levels of interferon expression.” Interferon is a protein released by the body in response to a viral infection that can slow or even stop the virus from replicating. In addition to differences in immune response, the researchers looked for discrepancies in gene expression between the groups. They found that adult macaques displayed cellular activity that could lead to problematic overgrowth of hardening of tissues called fibrosis.
Another contrast between the age groups related to the tiny hair-like structures in the respiratory system that help clear mucus and debris from the lungs called cilia. The adult monkeys had genetic expression consistent with continued impairment of cilia function during recovery from the virus compared to the infants. The results from the current study also hinted that the infants had quicker antibody responses to the virus. Still, given the small sample size, the antibody response results are tentative, and its full extent still needs to be understood.
With the resources of the CNPRC Pilot Research Program, the authors of this study provide an animal model that can be used to investigate infant and adult response to SARS-CoV-2 infection. Between age differences in immune response and cellular activity during recovery, this research uncovered critical areas that need further exploration.
As a next step, the authors plan to expand upon their preliminary findings and increase their sample size to ensure that results are true across the population. The group would also like to explore age differences in a more immediate response to the virus since the current study focuses on the recovery period.
The CNPRC Pilot Research Program is accepting new applications until March 10, 2023. To learn more and apply visit: https://cnprc.ucdavis.edu/our-science/pilot-research-program/