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Principal Investigator: Kaitlyn Sadtler
Organization: NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING
Fiscal Year: 2021
Award: $725,967
Funding agency: National Institute of Biomedical Imaging and Bioengineering
Analysis of Undiagnosed SARS-CoV-2 Infections in the United States
Over the past year, our laboratory has led a national serologic survey effort to evaluate the number of undiagnosed SARS-CoV-2 infections. In fall 2020, we discovered almost 17 million undiagnosed infections from the first wave of infections. We have been following the same cohort of participants and sampled again in January/February 2021 followed by a year timepoint in the summer of 2021. In addition to evaluating seropositivity, we have established and added more experimental analyses to allow us to cross-differentiate between vaccine-induced and infection-inducted antibodies. We have also added assays to evaluate the polyclonality of immune response by looking at immune reactivity against a mutated form of the SARS-CoV-2 spike protein found in the immune evasive variants such as the beta variant. We expect for the results of this study to be completed in December 2021 and available by early 2022.
Evaluation of SARS-CoV-2 Antibodies in Patients with Rare Diseases & Immunocompromised individuals
In a collaborative effort led by NIAID, we are evaluating antibody prevalence in patients with rare diseases through the NCATS RDCRN network. These patients have a broad range of diseases and will help us understand the incidence of infection and the response to vaccination in these patients. As with the rare disease project our laboratory is assisting a group at NIAID that is looking at immune responses to SARS-CoV-2 vaccination in individuals with immunodeficiencies either genetic or acquired. Here, we are determining the concentration of antibody induced at different stages of vaccination and how long these antibodies persist in this population. We have begun preliminary analyses and plan to have the first data on first dose, second dose, and third doses of vaccination in these patients by the end of October 2021.
Intersection of Trauma and Infectious Diseases
We evaluated the prevalence of SARS-CoV-2 in incoming trauma patients in six trauma centers in the United States. Here, we were able to determine the incidence of respiratory disease rates in incoming trauma patients which has not previously been evaluated. There is knowledge that trauma patients have a higher likelihood of developing secondary pulmonary disease such as pneumonia in the hospital, and these data could help increasing the knowledge of what a trauma patients basal immune status to better gauge treatment options. In addition to SARS-CoV-2 prevalence, we also evaluated the systemic immune status of incoming trauma patients by utilizing a biomarker panel. We have run a preliminary study on 200 samples, and plan to expand this to almost 2000 samples for a comprehensive database of systemic immune profiles in trauma victims from multiple trauma types.
Determination of the cellular and molecular mediators of fibrosis and regeneration in trauma
Having developed a mouse model, we have completed establishment of flow cytometric panels for the analysis of immune cell infiltration and activation in biomaterial-treated muscle injury. We have detected a possible molecular mediator of fibrosis and regeneration in the context of material implants. We are currently pursuing to further understand the basic biology of this molecular mediator, and then plan to develop therapeutic modalities in the form of modified biomaterials to prevent fibrosis of materials and promote muscle regeneration.
Investigating the structure of the injury microenvironment
We have furthered our understanding of the immune microenvironment of trauma and injury through the use of cleared tissue microscopy. We have established methods and approaches to clear biomaterial-treated muscle injury and image both the biomaterial microenvironment and the injury interface. We have identified several structures within the microenvironment that are of interest to the basic biology of wound responses and healing. We are currently evaluating the geography and mapping of these structures, and evaluating the biologic mechanisms underlying the structural organization of the immune microenvironment of trauma and material implantation.
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