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4 Potential Research Priorities and Opportunities in Diagnostics
Pages 37-48

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From page 37...
... • Future opportunities for diagnostic tests include the measure ment of host responses, including inflammatory processes and gene regulation, metabolic changes, and epigenetic signatures. (Aucott)
From page 38...
... Stage two is where manifestations of disseminated infection are present, with approximately 15 percent of people experiencing symptoms of neurologic disease and sometimes cardiovascular involvement such as carditis. When left untreated, he said about 60 percent of people develop arthritis in the third stage of disease progression.
From page 39...
... Indirect tests pose exciting opportunities, especially for the PTLDS population, as they can potentially provide insights into the host-microbe interaction and pathogenesis mechanism. This information could help clinicians decide which treatments to use for a particular patient.
From page 40...
... is represented by a triangle in the graph; the red boxes highlight the significantly elevated levels of CCL19 in the group of study participants who developed PTLDS following pretreatment assessment; *
From page 41...
... In conclusion, Aucott called for improved diagnostics for acute Lyme disease and its infection-associated chronic illness. He shared that future opportunities for diagnostic tests include imaging approaches as well as measurement of host responses, including inflammatory processes and gene regulation, metabolic changes, and epigenetic signatures.
From page 42...
... Her lab has spent years looking at how inflammatory molecules may cause pathological blood clotting, including effects on platelets, red blood cells, and the clotting protein fibrinogen.4 They have focused on the numerous membrane receptors on platelets that can cause platelet hyperactivation when these inflammatory molecules are in circulation. In the context of COVID-19, Pretorius said, it is important to remember that platelets can form complexes with not only other platelets, but also immune cells.
From page 43...
... After the initial studies on acute COVID-19, her team also examined and found that the spike protein can trigger significant platelet hyperactivation as well as microclot formation. This finding is also supported by studies in Sweden, she noted, where researchers found that the spike protein itself is an amyloidogenic protein (Nyström and Hammarström, 2022)
From page 44...
... Pretorius and colleagues employed proteomics to try and understand what was inside the clots, but they were surprised when a basic enzymatic process was unable to digest the clots and prepare samples for proteomics analysis, Pretorius said. Eventually, they were able to conduct the analysis and found numerous inflammatory molecules trapped inside the microclot complexes.
From page 45...
... His laboratory has been working to develop clinical metagenomic sequencing as a way to diagnose acute illnesses, and potentially applying it to associated chronic illnesses. Metagenomic sequencing provides a way to comprehensively characterize the genomic material in a clinical sample by sequencing all of the DNA and RNA present, he explained.
From page 46...
... Application to Chronic Illnesses Considering the application of metagenomic sequencing in infectionassociated chronic illnesses research, Chiu revealed that most of what is sequenced is actually not the pathogen, but the patient's own DNA and RNA. This has major implications for precision medicine, as it can provide significant insights into host response, which then inform a doctor in personalizing medicine and treatment to best suit the patient.
From page 47...
... Chiu noted that advancement of this new technology will require close coordination with regulatory statues and bodies such as Clinical Laboratory Improvement Amendments and the Food and Drug Administration in order to develop useful reference standards and validation measures that could streamline the path to use in clinical practice. DISCUSSION The discussion focused mainly on the potential for future diagnostic tests and biomarker profiling.
From page 48...
... Beyond just diagnostics, metagenomic profiling could have a role as a predictive tool as well. Avindra Nath, National Institute of Neurological Disorders and Stroke, shared emerging themes that he took away from the session's presentations, beginning with the realization that there is a commonality between various types of postinfectious syndromes suggesting a shared pathophysiology though likely through different mechanisms.


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