The CDC has awarded Vanderbilt University Medical Center a two-year, $3.7 million contract to determine genetic and bacterial factors that may increase the risk for severe illness and death from COVID-19. The multiomic investigation will specifically focus on how the severity of COVID-19 disease may be affected by the bacteria in the respiratory microbiome.
Vanderbilt is uniquely positioned to do this kind of investigation because of the depth of its resources in genomics, virology and infectious disease, said Suman Das, Ph.D., an associate professor of medicine at Vanderbilt. In a paper published in the Journal of Allergy and Clinical Immunology, Das and colleagues reported that SARS-CoV-2 interacts with respiratory bacteria in ways that potentially worsen symptoms.
Das and Jonathan Schmitz, M.D., medical director of the Molecular Infectious Diseases Laboratory at Vanderbilt, are the project’s co-principal investigators. Co-investigators include Simon Mallal, M.B.B.S., scientific director of the VANTAGE (Vanderbilt Technologies for Advanced Genomics) and IMGSCT (Immunogenomics, Microbial Genetics and Single Cell Technologies) cores, and Julie Bastarache, M.D., associate professor of medicine at Vanderbilt.
Exploring Interacting Factors
Little is known about the relationship between SARS-CoV-2 and the upper respiratory tract (URT) microbiome. In their recent publication, Das and colleagues sought to address this knowledge gap by 1) comparing the URT microbiome between SARS-CoV-2-infected and -uninfected adults and 2) examining the association of SARS-CoV-2 viral load (an independent predictor of disease severity) with the URT microbiome during COVID-19.
The URT microbiome was characterized using 16S ribosomal RNA sequencing in 59 adults (38 with confirmed, symptomatic, mild to moderate COVID-19 and 21 asymptomatic, uninfected controls).
The abundance of 21 taxa were significantly different between adults with and without SARS-CoV-2 infection, with 13 taxa being more abundant (including Brevundimonas, Corynebacterium, Granilucatella, Anaerococcus, and Peptoniphilus) and 8 being less abundant (including Corynebacterium_1, Prevotella, Staphylococcus, Anaerostipes, and Neisseria) in SARS-CoV-2-infected versus -uninfected adults.
Likewise, among adults with COVID-19, 21 taxa were significantly different between those with and without high viral load, with 9 being more abundant (including Neisseriaceae, Anaerococcus, Peptoniphilus, Campylobacter, and Enterococcus taxa) and 12 being less abundant (including Corynebacterium_1, Staphylococcus, Granulicatella, Neisseria, and Prevotella taxa) in those with high viral load when compared with those with low viral load.
“Future studies with larger sample sizes and serial sample collection will be needed to examine how SARS-CoV-2 interacts with the URT microbiome and how these viral-bacterial interactions can impact the clinical progression, severity and recovery of COVID-19,” the authors wrote.
The Early-life Respiratory Microbiome
Das and colleagues, including Christian Rosas-Salazar, M.D., first author on the paper and an assistant professor of pediatrics at Vanderbilt, have studied interactions between respiratory viruses and the microbiome for several years. They have previously reported that infants who have higher amounts of the bacterium Lactobacillus present in their nose or upper throat during an acute respiratory syncytial virus infection are less likely to develop childhood wheezing illness.
“We know very little of the risk factors for outcomes in COVID-19, so understanding these viral-bacterial interactions may be key to predicting severity.”
“Bacteria in the respiratory tract may be important in modulating how you respond to an invading virus,” Rosas-Salazar said. “We know very little of the risk factors for outcomes in COVID-19, so understanding these viral-bacterial interactions may be key to predicting severity.”
The researchers hope that by understanding these interacting factors, they will be able to predict disease severity from SARS-CoV-2 and determine which patients may or may not respond to antiviral treatments including antibody therapy.
Key resources include BioVU, Vanderbilt’s massive biobank of more than 400,000 individual samples of DNA and other biological materials, and MicroVU, which includes bio-banked specimens containing more than 200 different species of bacteria linked to the Vanderbilt research data warehouse. Co-directed by Schmitz and Maria Hadjifrangiskou, Ph.D., associate director of the Vanderbilt Institute for Infection, Immunology and Inflammation, the resource includes respiratory specimens from COVID-19 patients.
“Overall, this study will define the epidemiology of SARS-CoV-2 genotype evolution and emergence of new genotype diversity across a continuum of disease severity, help improve decision-making by physicians caring for SARS-CoV-2 -positive patients in both the hospital and outpatient settings, and guide public health policy for the control of SARS-CoV-2 disease burden,” Das said.