Age-related changes in the nasopharyngeal microbiome are associated with SARS-CoV-2 infection and symptoms among children, adolescents, and young adults.

Abstract

Background

Children are less susceptible to SARS-CoV-2 infection and typically have milder illness courses than adults, but the factors underlying these age-associated differences are not well understood. The upper respiratory microbiome undergoes substantial shifts during childhood and is increasingly recognized to influence host defense against respiratory pathogens. Thus, we sought to identify upper respiratory microbiome features associated with SARS-CoV-2 infection susceptibility and illness severity.

Methods

We collected clinical data and nasopharyngeal swabs from 285 children, adolescents, and young adults (<21 years of age) with documented SARS-CoV-2 exposure. We used 16S ribosomal RNA gene sequencing to characterize the nasopharyngeal microbiome and evaluated for age-adjusted associations between microbiome characteristics and SARS-CoV-2 infection status and respiratory symptoms.

Results

Nasopharyngeal microbiome composition varied with age (PERMANOVA, p<0.001, R 2=0.06) and between SARS-CoV-2-infected individuals with and without respiratory symptoms (PERMANOVA, p=0.002, R 2=0.009). SARS-CoV-2-infected participants with Corynebacterium/Dolosigranulum-dominant microbiome profiles were less likely to have respiratory symptoms than infected participants with other nasopharyngeal microbiome profiles (odds ratio: 0.38, 95% confidence interval: 0.18-0.81). Using generalized joint attributed modeling, we identified nine bacterial taxa associated with SARS-CoV-2 infection and six taxa that were differentially abundant among SARS-CoV-2-infected participants with respiratory symptoms; the magnitude of these associations was strongly influenced by age.

Conclusions

We identified interactive relationships between age and specific nasopharyngeal microbiome features that are associated with SARS-CoV-2 infection susceptibility and symptoms in children, adolescents, and young adults. Our data suggest that the upper respiratory microbiome may be a mechanism by which age influences SARS-CoV-2 susceptibility and illness severity.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1093/cid/ciac184

Publication Info

Hurst, Jillian H, Alexander W McCumber, Jhoanna N Aquino, Javier Rodriguez, Sarah M Heston, Debra J Lugo, Alexandre T Rotta, Nicholas A Turner, et al. (2022). Age-related changes in the nasopharyngeal microbiome are associated with SARS-CoV-2 infection and symptoms among children, adolescents, and young adults. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 10.1093/cid/ciac184 Retrieved from https://hdl.handle.net/10161/24782.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.

Scholars@Duke

Hurst

Jillian Hurst

Assistant Professor in Pediatrics

Children's Health & Discovery Initiative:
The prenatal period, infancy, childhood, and adolescence, represent critical time periods of human development that include more developmental milestones than any other period of the lifespan. Conditions during these developmental windows – including biological, social, economic, health, and environmental factors – have a profound impact on lifelong health. The Children’s Health and Discovery Initiative (CHDI) was founded on the hypothesis that interventions early in life will improve population health across the lifespan. To this end, the overarching goal of the CHDI is to create a robust coalition of multidisciplinary investigators and a pipeline of infrastructure, data, and research projects focused on developing innovative approaches to identifying and modulating early life factors that impact lifelong health and well-being.

Intersections of the upper respiratory microbiome, environmental exposures, and childhood respiratory infections
Early life exposure to and colonization with microbes has a profound influence on the education of the immune system and susceptibility to viral and bacterial infections later in life. My research is focused on the influence of the upper respiratory microbiome on the development of recurrent respiratory infections, including acute otitis media (AOM), the leading cause of antibiotic prescriptions and healthcare consultations among children. Importantly, some children develop recurrent infections that are thought to be linked to dysbiosis of the nasopharyngeal microbiome. My overarching goals are to identify alterations in the upper respiratory microbiome associated with AOM and to elucidate host factors and exposures that predispose some children to the development of recurrent AOM episodes.

Heston

Sarah Mabrey Heston

Assistant Professor of Pediatrics

I am a Pediatric Transplant Infectious Diseases physician-scientist. Clinically, I diagnose and treat infections in immunocompromised children who have either undergone transplantation or who are receiving chemotherapy. My research interests are in utilizing the microbiome to improve clinical outcomes following transplantation. Specifically, I am evaluating the gut microbiomes of children undergoing hematopoietic cell transplantation (HCT) to identify actionable interventions to reduce mucosal barrier injury bloodstream infections and graft-versus-host disease, two significant contributors to post-HCT morbidity.

Rotta

Alexandre Tellechea Rotta

Professor of Pediatrics
Turner

Nicholas Turner

Assistant Professor of Medicine
Moody

Michael Anthony Moody

Professor of Pediatrics

Tony Moody, MD is a Professor in the Department of Pediatrics, Division of Infectious Diseases and Professor in the Department of Integrative Immunobiology at Duke University Medical Center. Research in the Moody lab is focused on understanding the B cell responses during infection, vaccination, and disease. The lab has become a resource for human phenotyping, flow characterization, staining and analysis at the Duke Human Vaccine Institute (DHVI). The Moody lab is currently funded to study influenza, syphilis, HIV-1, and emerging infectious diseases.

Dr. Moody is the director of the Duke CIVICs Vaccine Center (DCVC) at (DHVI) and co-director of the Centers for Research of Emerging Infectious Disease Coordinating Center (CREID-CC). Dr. Moody is co-PI of a U19 program to develop a syphilis vaccine; this program is led by Dr. Justin Radolf at the University of Connecticut. Dr. Moody is also the director of the DHVI Accessioning Unit, a biorepository that provides support for work occurring at DHVI and with its many collaborators around the world by providing processing, shipping, and inventory support for a wide array of projects.

Dr. Moody and his team are involved in many networks studying vaccine response including the Collaborative Influenza Vaccine Innovation Centers (CIVICs) and the COVID-19 Prevention Network (CoVPN).

Denny

Thomas Norton Denny

Professor in Medicine

Thomas N. Denny, MSc, M.Phil, is the Chief Operating Officer of the Duke Human Vaccine Institute (DHVI), Associate Dean for Duke Research and Discovery @RTP, and a Professor of Medicine in the Department of Medicine at Duke University Medical Center. He is also an Affiliate Member of the Duke Global Health Institute. Previously, he served on the Health Sector Advisory Council of the Duke University Fuquay School of Business. Prior to joining Duke, he was an Associate Professor of Pathology, Laboratory Medicine and Pediatrics, Associate Professor of Preventive Medicine and Community Health and Assistant Dean for Research in Health Policy at the New Jersey Medical School, Newark, New Jersey. He has served on numerous committees for the NIH over the last two decades and currently is the principal investigator of an NIH portfolio in excess of 65 million dollars. Mr. Denny was a 2002-2003 Robert Wood Johnson Foundation Health Policy Fellow at the Institute of Medicine of the National Academies (IOM). As a fellow, he served on the US Senate Health, Education, Labor and Pensions Committee with legislation/policy responsibilities in global AIDS, bioterrorism, clinical trials/human subject protection and vaccine related-issues.

As the Chief Operating Officer of the DHVI, Mr. Denny has senior oversight of the DHVI research portfolio and the units/teams that support the DHVI mission. He has extensive international experience and previously was a consultant to the U.S. Centers for Disease Control and Prevention (CDC) for the President’s Emergency Plan for AIDS Relief (PEPFAR) project to oversee the development of an HIV and Public Health Center of Excellence laboratory network in Guyana. In September 2004, the IOM appointed him as a consultant to their Board on Global Health Committee studying the options for overseas placement of U.S. health professionals and the development of an assessment plan for activities related to the 2003 PEPFAR legislative act. In the 1980s, Mr. Denny helped establish a small laboratory in the Republic of Kalmykia (former Soviet Union) to improve the care of children with HIV/AIDS and served as a Board Member of the Children of Chernobyl Relief Fund Foundation. In 2005, Mr. Denny was named a consulting medical/scientific officer to the WHO Global AIDS Program in Geneva. He has also served as program reviewers for the governments of the Netherlands and South Africa as well as an advisor to several U.S. biotech companies. He currently serves as the Chair of the Scientific Advisory Board for Grid Biosciences.

Mr. Denny has authored and co-authored more than 200 peer-reviewed papers and serves on the editorial board of Communications in Cytometry and Journal of Clinical Virology. He holds an M.Sc in Molecular and Biomedical Immunology from the University of East London and a degree in Medical Law (M.Phil) from the Institute of Law and Ethics in Medicine, School of Law, University of Glasgow. In 1991, he completed a course of study in Strategic Management at The Wharton School, University of Pennsylvania. In 1993, he completed the Program for Advanced Training in Biomedical Research Management at Harvard School of Public Health. In December 2005, he was inducted as a Fellow into the College of Physicians of Philadelphia, the oldest medical society in the US.

While living in New Jersey, Mr. Denny was active in his community, gaining additional experience from two publicly elected positions. In 2000, Mr. Denny was selected by the New Jersey League of Municipalities to Chair the New Jersey Community Mental Health Citizens’ Advisory Board and Mental Health Planning Council as a gubernatorial appointment.

Rawls

John F. Rawls

James B. Duke Distinguished Professor

We seek to understand how the intestinal microbiome contributes to vertebrate physiology and disease. To that end, we leverage complementary zebrafish and mouse models to study the integrative physiology of host-microbiome interactions. This work has identified novel and conserved mechanisms by which intestinal bacteria regulate dietary fat metabolism and systemic innate immunity. We also apply genomic approaches in these animal models to understand the transcriptional regulatory pathways utilized by the intestinal epithelium to mediate host responses to the microbiome. Using this approach, we have identified mechanisms of transcriptional and chromatin regulation that have been conserved during vertebrate evolution and also contribute to modern human diseases such as the inflammatory bowel diseases, obesity, and diabetes. To further advance our understanding of obesity pathophysiology, we developed the zebrafish as a model system for studying adipose tissues and identifying new environmental and genetic regulators of adiposity. We are also engaged in translational research in humans and animal models to define microbial and metabolic determinants of obesity and efficacy of weight loss intervention. Grounded in comparative and integrative physiology, our research program has been effective in discovering ancient mechanisms of host-microbiome interaction that are conserved across animal taxa and contribute to the etiology of modern human diseases. These insights are advancing our understanding of host-microbiome relationships in vertebrate physiology and identifying novel therapeutic targets for human diseases ranging from inflammatory bowel disease to obesity to neurological disorders.

Clark

James S. Clark

Nicholas Distinguished Professor of Environmental Science

James S. Clark is Nicholas Professor of Environment Science and Professor of Statistical Science.

Clark’s research focuses on how global change affects populations, communities, and ecosystems. Current projects explore consequences of climate, CO2, and disturbance on dynamics of forests. His lab is using long-term experiments and monitoring studies to determine disturbance and climate controls on the dynamics of 20th century forests in combination with extensive modeling to forecast ecosystem change. Clark has authored over 150 refereed scientific articles and published four books, including Models for Ecological Data (Princeton, 2007), Models for Ecological Data in R (Princeton, 2007), Hierarchical Models of the Environment (Oxford, 2006), and Sediment Records of Biomass Burning and Global Change (Springer, 1997). Full publication list. Clark received a BS from the North Carolina State University in Entomology (1979), a MS from the University of Massachusetts in Forestry and Wildlife (1984), and a PhD from the University of Minnesota in Ecology (1988). Between his MS and PhD, he studied one year at the University of Göttingen under a Fulbright-DAAD fellowship. At Duke University, Clark teaches Biodiversity Science and Applications and Ecological Models & Data. He has served as Director for the Center on Global Change, and Director of Graduate Studies for the University Program in Ecology. He currently serves on the University Program of Ecology Executive Committee and chairs the Nicholas School of the Environment committees on Life Sciences and Distinguished Professorships. Clark is recipient of ESA’s William Skinner Cooper Award, for his research on barrier beach dynamics, and George Mercer Award, for studies of climate change and fire. For excellence in teaching and research, he was one of 15 scientists recognized by President Clinton with the National Science Foundation s five-yr Presidential Faculty Fellow Award. He was named an Aldo Leopold Leadership Fellow, on behalf of the Ecological Society of America. He is a Distinguished Alumnus from Natural Resources Conservation, University of Massachusetts. In 2005, he was elected to the American Academy of Arts and Sciences. Clark has testified before congress on behalf of the Ecological Society of America and the NSF budget. He served on editorial boards for Ecology and Ecological Monographs (1996 -1999), Annual Reviews of Ecology and Systematics (1998 – 2003), Global Change Biology (1994 – 2002), Ecosystems (2003 – 2007), Trends in Ecology and Evolution (2006-), and the Journal for Agricultural, Biological, and Environmental Statistics (2010 – ) and on NSF Advisory panels for Ecology (1992 – 1997), Earth System History (1994), LTER (2000), and Ecology and Evolution of Infectious Disease (2009). He chaired ESA’s Mercer Award Committee and was Vice President for Science (1999 – 2004). He was a founding member of the Science Advisory Board of the National Center for Ecological Analysis and Synthesis.

Woods

Christopher Wildrick Woods

Wolfgang Joklik Distinguished Professor of Global Health

1. Emerging Infections
2. Global Health
3. Epidemiology of infectious diseases
4. Clinical microbiology and diagnostics
5. Bioterrorism Preparedness
6. Surveillance for communicable diseases
7. Antimicrobial resistance

Kelly

Matthew Kelly

Associate Professor of Pediatrics

My research is broadly focused on elucidating the complex interactions that exist between the host microbiome and exogenous pathogens that cause infections in children. We have several ongoing projects evaluating: 1) the impact of the upper respiratory microbiome on the risk of colonization and invasion by bacterial respiratory pathogens among infants in Botswana; 2) associations between the gut microbiome of pediatric stem cell transplant recipients and the risk of infections (bloodstream infection, C. difficile infection) and graft-versus-host disease; and 3) the role of the gut and respiratory microbiomes in mediating COVID-19 infection susceptibility and disease severity in children. Ultimately, I aim to develop strategies that use targeted modification of the microbiome for the prevention of infections in children.


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