Clinical Significance of Quantitative Viral Load in Patients Positive for SARS-CoV-2.

Cycle threshold (CT) refers to the number of cycles in a reverse transcriptase polymerase chain reaction (RT-PCR) assay needed to amplify viral RNA and can be used to indicate viral load. CT is inversely related to viral load, where lower CT values indicate higher viral levels. Data suggest lower CT scores are associated with worse outcomes in COVID; however, quantitative CT scores are not typically reported to patients. This retrospective analysis examined the use of CT scores in patient counseling for positive COVID results and suggests that higher viral loads were associated with greater need for prescription drug therapy in the outpatient setting. Patient perception of CT score was found to influence masking and quarantine behavior. We hypothesize that a quantitative threshold for viral load such as CT can be useful in patient counseling, estimating need for drug therapy, and influencing behavior toward public health concerns.

Circulating Extracellular Vesicles Containing Xenobiotic Metabolizing CYP Enzymes and Their Potential Roles in Extrahepatic Cells Via Cell-Cell Interactions.

The cytochrome P450 (CYP) family of enzymes is known to metabolize the majority of xenobiotics. Hepatocytes, powerhouses of CYP enzymes, are where most drugs are metabolized into non-toxic metabolites. Additional tissues/cells such as gut, kidneys, lungs, blood, and brain cells express selective CYP enzymes. Extrahepatic CYP enzymes, especially in kidneys, also metabolize drugs into excretable forms. However, extrahepatic cells express a much lower level of CYPs than hepatocytes. It is possible that the liver secretes CYP enzymes, which circulate via plasma and are eventually delivered to extrahepatic cells (e.g., brain cells). CYP circulation likely occurs via extracellular vesicles (EVs), which carry important biomolecules for delivery to distant cells. Recent studies have revealed an abundance of several CYPs in plasma EVs and other cell-derived EVs, and have demonstrated the role of CYP-containing EVs in xenobiotic-induced toxicity via cell-cell interactions. Thus, it is important to study the mechanism for packaging CYP into EVs, their circulation via plasma, and their role in extrahepatic cells. Future studies could help to find novel EV biomarkers and help to utilize EVs in novel interventions via CYP-containing EV drug delivery. This review mainly covers the abundance of CYPs in plasma EVs and EVs derived from CYP-expressing cells, as well as the potential role of EV CYPs in cell-cell communication and their application with respect to novel biomarkers and therapeutic interventions.