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

Stéphane Bonacorsi; Benoit Visseaux; Donia Bouzid; Josep Pareja; Sonia N Rao; Davide Manissero; Glen Hansen; Jordi Vila

doi:10.3389/fmed.2021.711809

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

Front Med (Lausanne). 2021 Sep 23:8:711809. doi: 10.3389/fmed.2021.711809. eCollection 2021.

Authors

Stéphane Bonacorsi¹, Benoit Visseaux^{2

3}, Donia Bouzid^{2

4}, Josep Pareja⁵, Sonia N Rao⁶, Davide Manissero⁷, Glen Hansen^{8

9}, Jordi Vila¹⁰

Affiliations

¹ Department of Microbiology, Robert Debré University Hospital, AP-HP, Paris, France.
² Université de Paris, IAME, INSERM, Paris, France.
³ Université de Paris, Laboratoire de Virologie, Hôpital Bichat Claude Bernard, Assistance Publique-Hôpitaux de Paris, Paris, France.
⁴ Université de Paris, Service d'Accueil des Urgences, Hôpital Bichat Claude Bernard, Assistance Publique-Hôpitaux de Paris, Paris, France.
⁵ STAT-Dx Life, S.L. (a QIAGEN Company), Medical Affairs, Barcelona, Spain.
⁶ QIAGEN Inc., Medical Affairs, Germantown, MD, United States.
⁷ QIAGEN Manchester Ltd, Medical Affairs, Manchester, United Kingdom.
⁸ Microbiology and Molecular Diagnostics, Hennepin County Medical Center, Department of Infectious Diseases, School of Medicine, University of Minnesota, Minneapolis, MN, United States.
⁹ Department of Pathology and Laboratory Medicine, School of Medicine, University of Minnesota, Minneapolis, MN, United States.
¹⁰ Biomedical Diagnostic Centre, Department of Clinical Microbiology, Institute of Global Health, School of Medicine, Hospital Clinic, University of Barcelona, Barcelona, Spain.

Abstract

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

Keywords: clinical outcomes; cycle threshold; gastrointestinal pathogens; pathogen load; qPCR; systematic review.

Publication types

Systematic Review