Systematic Review on the Correlation of Quantitative PCR Cycle Threshold Values of Gastrointestinal Pathogens With Patient Clinical Presentation and Outcomes

<b>Background:</b> Quantitative (q) polymerase chain reaction (PCR) cycle threshold (Ct) values represent the number of amplification cycles required for a positive PCR result and are a proxy of pathogen quantity in the tested sample. The clinical utility of Ct values remains unclear for gastrointestinal infections. <b>Objectives:</b> This systematic review assesses the global medical literature for associations between Ct values of gastrointestinal pathogens and patient presentation and clinical outcomes. <b>Data Sources:</b> MEDLINE, EMBASE, Cochrane library databases: searched January 14-17, 2020. <b>Study Eligibility Criteria:</b> Studies reporting on the presence or absence of an association between Ct values and clinical outcomes in adult and pediatric populations were included. Animal studies, reviews, meta-analyses, and non-English language studies were excluded. <b>Participants:</b> Humans infected with gastrointestinal pathogens, detected with qPCR. <b>Interventions:</b> Diagnostics assessing Ct values. Extracted data were reported narratively. <b>Results:</b> Thirty-three eligible studies were identified; the most commonly studied pathogens were <i>Clostridioides difficile</i> (<i>n</i> = 15), norovirus (<i>n</i> = 10), and rotavirus (<i>n</i> = 9). Statistically significant associations between low <i>C. difficile</i> Ct values and increased symptom severity or poor outcome were reported in 4/8 (50%) studies, and increased risk of death in 1/2 (50%) studies; no significant associations were found between Ct value and duration of symptoms or length of hospital stay. Among studies of norovirus, 5/7 (71%), mainly genogroup II, reported symptomatic cases with significantly lower median Ct values than controls. Significantly lower rotavirus Ct values were also observed in symptomatic cases vs. controls in 3/7 (43%) studies, and associated with more severe symptoms in 2/2 studies. Contradictory associations were identified for non-<i>C. difficile</i> bacterial and parasitic pathogens. <b>Conclusions:</b> In conclusion, some studies reported clinically useful associations between Ct values and patient or healthcare outcomes; additional, well-designed, large-scale trials are warranted based on these findings. <b>Systematic Review Registration:</b> [PROSPERO], identifier [CRD42020167239].