Objectives: We aimed to assess the association between rapid antigen detection tests and real-time reverse transcription-polymerase chain reaction assay for severe acute respiratory syndrome coronavirus 2. Methods: We searched PubMed, Cochrane Library, EMBASE, and the Web of Science from their inception to 31 May 2023. A random-effects meta-analysis was used to estimate false positives in the RADTs group, relative to those in the RT-PCR group, and subgroup analyses were conducted based on the different Ct value cut-offs (<40 or ≥40). We performed this study in accordance with the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Results: Fifty-one studies were included and considered to be of moderate quality. We found a satisfactory overall false positive rate (0.01, 95% CI: 0.00-0.01) for the RADTs compared to RT-PCR. In the stratified analysis, we also found that the false positive rates of the RADTs did not increase when Ct values of RT-PCR (Ct < 40, 0.01, 95% CI: 0.00-0.01; Ct ≥ 40, 0.01, 95% CI: 0.00-0.01). Conclusion: In conclusion, the best available evidence supports an association between RADTs and RT-PCR. When Ct-values were analyzed using cut-off <40 or ≥40, this resulted in an estimated false positive rate of only 1%.

Testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using reverse transcriptase polymerase chain reaction (RT-PCR) may generate indeterminate results (with a cycle threshold ≥30), requiring further investigation to determine the clinical significance. Patient variables which could predict a definitive result (\'Detected\'/\'Not detected\') post indeterminate result would aid in optimization of bed management and utilization of limited resources. A retrospective observational study of indeterminate SARS-CoV-2 results in an Irish tertiary hospital from March 2020 to March 2022 was performed to determine whether demographics, comorbidities and immunosuppression were associated with a definitive result upon subsequent investigation. Data was obtained from patient and laboratory records. Analysis of association was explored using Fisher\'s exact test, and predictability was tested using logistic regression. Of 411 patients with an initial indeterminate test, investigation showed that 299 (72.2%) patients had a subsequent definitive result; 29 were Detected and 270 were Not detected. In the Detected group, a prior diagnosis of COVID-19 was associated with a reduced risk of becoming Detected (crude odds ratio (COR) = 0.10, 95% CI 0.03-0.35). In the Not detected group, vaccinated patients were less likely to have a Not detected result on subsequent testing (adjusted odds ratio (AOR) = 0.57, 95% CI 0.34-0.94). Patients with previous COVID-19 infection were less likely to have a Detected result and vaccinated patients were less likely to have a Not detected result upon investigation of an indeterminate result. This study emphasizes the need for a good clinical and medical history in the management of SARS-CoV-2.

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].

Cycle threshold (CT) values are correlated with the amount of viral nucleic acid in a sample and may be obtained from some qualitative real-time polymerase chain reaction tests used for diagnosis of most patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, CT values cannot be directly compared across assays, and they must be interpreted with caution as they are influenced by sample type, timing of sample collection, and assay design. Presently, the correlation between CT values and clinical outcomes is not well understood. We conducted a systematic review and meta-analysis of published studies through April 19, 2021, that reported an association between CT values and hospitalization, disease severity, and mortality in patients ≥18 years old with SARS-CoV-2. A meta-analysis of 7 studies showed no significant difference in mean CT values between hospitalized and nonhospitalized patients. Among hospitalized patients, those with CT values <25 had a high risk of more severe disease and mortality than patients with CT values >30 (odds ratio [OR], 2.31; 95% CI, 1.70 to 3.13; and OR, 2.95; 95% CI, 2.19 to 3.96; respectively). The odds of increased disease severity and mortality were less pronounced in patients with CT values of 25-30 compared with >30.

The ability to predict likely prognosis and infectiousness for patients with COVID-19 would aid patient management decisions. Diagnosis is usually via real-time PCR, and it is unclear whether the semi-quantitative capability of this method, determining viral load through cycle threshold (Ct) values, can be leveraged.
We aim to review available knowledge on correlations between SARS-COV-2 Ct values and patient- or healthcare-related outcomes to determine whether Ct values provide useful clinical information.
A PubMed search was conducted on 1 June 2020 based on a search strategy of (Ct value OR viral load) AND SARS-CoV-2. Data were extracted from studies reporting on the presence or absence of an association between Ct values, or viral loads determined via Ct value, and clinical outcomes.
Data from 18 studies were relevant for inclusion. One study reported on the correlation between Ct values and mortality and one study reported on the correlation between Ct values and progression to severe disease; both reported a significant association (p < 0.001 and p = 0.008, respectively). Fourteen studies reported on the correlation between Ct value or viral loads determined via Ct value and disease severity, and an association was observed in eight (57%) studies. Studies reporting on the correlation of viral load with biochemical and haematological markers showed an association with at least one marker, including increased lactate dehydrogenase (n = 4), decreased lymphocytes (n = 3) and increased high-sensitivity troponin I (n = 2). Two studies reporting on the correlation with infectivity showed that lower Ct values were associated with higher viral culture positivity.
Data suggest that lower Ct values may be associated with worse outcomes and that Ct values may be useful in predicting the clinical course and prognosis of patients with COVID-19; however, further studies are warranted to confirm clinical value.