COVID-19: Elucidating the role of the microbiome in COVID-19 induced hyperinflammation
EMSL Project ID
60070
Abstract
Efforts to manage the global pandemic caused by SARS-CoV-2 have been hampered by our poor understanding of critical factors that determine the short-term and long-term health effects of COVID-19. Over 200 nations have been affected by COVID-19, yet the impact, fatality rate, and severity of the disease differ substantially not only among countries, but also among geographic locations within a country and among different demographic groups. Approximately 20% of SARS-CoV-2 infections lead to acute respiratory distress syndrome (ARDS), a severe form of COVID-19 that is thought to be caused by the harmful actions of various inflammatory mediators, including IL-6 and IL-17. The gut microbiome plays a central role in modulating immune responses, and quantitative differences in microbiome composition among COVID-19 patients experiencing differences in disease severity have been reported. Patients with severe COVID-19 are often afflicted with GI symptoms during the course of their disease. Collectively, these observations point to links between severe COVID-19, and gut microbiome composition and function. However, the molecular basis of how these factors are interrelated is poorly understood. Thus, there is a critical need to solve this problem in order to determine whether microbiota-targeting options are viable strategies to treat COVID-19 or manage severe disease risk.Early in the outbreak, we envisioned the need for this research addressing the microbiome’s role in regulating and modulating the immune response to COVID-19. To pursue this agenda, we initiated a close collaboration with IU Health Arnett Hospital (IUHAH) in Lafayette, IN. Following IRB approval, we began collecting specimens from individuals admitted to IUHAH. These patients, COVID-tested upon admission, are assigned to three subgroups depending on the test results and infection’s resolution (non-COVID, mild/severe, critical). Since August, we have obtained samples from ~120 patients (the collection is still ongoing). All the collected blood and fecal samples have been de-identified and pre-processed by the IUHAH clinical lab. They are currently stored in a secure biobank at Purdue, following the approved biosafety protocol. We also secured patients’ consent for accessing their electronic health records (EHR).
The long-term goal of our research is to define mechanisms underlying susceptibility to severe forms of COVID-19 in order to stimulate the development of new therapeutic strategies. Our objective in this proposal is to define relationships between the gut microbiome and the risk of severe COVID-19 leading to hyperinflammation.
Our central hypothesis is that abnormal microbiome compositional and functional profiles coincide with severe COVID-19-induced hyperinflammation. Relationships between the gut microbiome and COVID-19 severity are likely modulated by the patients’ age, genome, and medications. We have formulated this hypothesis based on evidence that microbiome perturbations can lead to elevated basal levels of systemic inflammation and microbiome disturbances are linked to hyperinflammation in mouse viral infection models18. These, in turn, could increase the risk of severe forms of COVID-19, often leading to death. Our rationale for this study is that its successful completion would provide a strong evidence-based foundation to justify developing treatments targeting gut microbiota and molecular effectors (e.g., inflammatory effectors) found to mediate susceptibility to severe COVID-19. To test our central hypothesis, we propose the following specific objective: Identify the relationship between patients’ microbiome composition and function, host response, and COVID-19 severity.
We will use multi-view analysis to integrate the 'omics data and infer causation from microbiome and metabolome parameters.
Project Details
Project type
Limited Scope
Start Date
2021-07-06
End Date
2022-09-30
Status
Closed
Released Data Link
Team
Principal Investigator