AUTHOR=Bonacorsi Stéphane , Visseaux Benoit , Bouzid Donia , Pareja Josep , Rao Sonia N. , Manissero Davide , Hansen Glen , Vila Jordi 

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

JOURNAL=Frontiers in Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.711809

DOI=10.3389/fmed.2021.711809

ISSN=2296-858X

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Objectives:</bold> This systematic review assesses the global medical literature for associations between Ct values of gastrointestinal pathogens and patient presentation and clinical outcomes.</p><p><bold>Data Sources:</bold> MEDLINE, EMBASE, Cochrane library databases: searched January 14–17, 2020.</p><p><bold>Study Eligibility Criteria:</bold> 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.</p><p><bold>Participants:</bold> Humans infected with gastrointestinal pathogens, detected with qPCR.</p><p><bold>Interventions:</bold> Diagnostics assessing Ct values. Extracted data were reported narratively.</p><p><bold>Results:</bold> Thirty-three eligible studies were identified; the most commonly studied pathogens were <italic>Clostridioides difficile</italic> (<italic>n</italic> = 15), norovirus (<italic>n</italic> = 10), and rotavirus (<italic>n</italic> = 9). Statistically significant associations between low <italic>C. difficile</italic> 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-<italic>C. difficile</italic> bacterial and parasitic pathogens.</p><p><bold>Conclusions:</bold> 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.</p><p><bold>Systematic Review Registration:</bold> [PROSPERO], identifier [CRD42020167239].</p>