Caveats of Reporting Cycle Threshold Values from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Qualitative Polymerase Chain Reaction Assays: A Molecular Diagnostic Laboratory Perspective

Poon, Kok-Siong; Tee, Nancy Wen Sim

doi:10.1093/cid/ciaa1399

Cited by 11 publications

(10 citation statements)

References 3 publications

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“…Applied to our health system’s patients, this approach increased the estimated COVID-19 recurrence incidence by nearly an order of magnitude. This discrepancy simultaneously highlights the limitations of recurrence definitions based solely on Ct values (given Ct variation across the COVID-19 disease course [ 2 ] and between assays, laboratories, and specimen collection methods [ 18 – 20 ]), and, on the other hand, the importance of comprehensive clinical evaluation when incorporating symptoms and exposure as criteria for COVID-19 recurrence.…”

Section: Discussionmentioning

confidence: 99%

“…However, the CDC protocol simultaneously suggests prioritizing investigation of potential recurrence occurring ≥90 days from the initial positive test, and the relatively low frequency of probable or possible recurrence in the 60–89 day versus ≥90 day window suggests few probable or possible recurrences would have been identified in the 45–59 day window. Finally, while the sensitivity analyses that used normalized Ct values and restricted evaluation to patients tested serially on the same platform are reassuring, between-platform variation in gene targets, Ct ranges, and other assay parameters may have influenced the apparent Ct trajectories among patients whose recurrent test took place on a different platform than the original test [ 18 – 20 ].…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of potential COVID-19 recurrence in patients with late repeat positive SARS-CoV-2 testing

et al. 2021

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Background SARS-CoV-2 reinfection and reactivation has mostly been described in case reports. We therefore investigated the epidemiology of recurrent COVID-19 SARS-CoV-2. Methods Among patients testing positive for SARS-CoV-2 between March 11 and July 31, 2020 within an integrated healthcare system, we identified patients with a recurrent positive SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) assay ≥60 days after an initial positive test. To assign an overall likelihood of COVID-19 recurrence, we combined quantitative data from initial and recurrent positive RT-PCR cycle thresholds—a value inversely correlated with viral RNA burden— with a clinical recurrence likelihood assigned based on independent, standardized case review by two physicians. “Probable” or “possible” recurrence by clinical assessment was confirmed as the final recurrence likelihood only if a cycle threshold value obtained ≥60 days after initial testing was lower than its preceding cycle threshold or if the patient had an interval negative RT-PCR. Results Among 23,176 patients testing positive for SARS-CoV-2, 1,301 (5.6%) had at least one additional SARS-CoV-2 RT-PCRs assay ≥60 days later. Of 122 testing positive, 114 had sufficient data for evaluation. The median interval to the recurrent positive RT-PCR was 85.5 (IQR 74–107) days. After combining clinical and RT-PCR cycle threshold data, four patients (3.5%) met criteria for probable COVID-19 recurrence. All four exhibited symptoms at recurrence and three required a higher level of medical care compared to their initial diagnosis. After including six additional patients (5.3%) with possible recurrence, recurrence incidence was 4.3 (95% CI 2.1–7.9) cases per 10,000 COVID-19 patients. Conclusions Only 0.04% of all COVID-19 patients in our health system experienced probable or possible recurrence; 90% of repeat positive SARS-CoV-2 RT-PCRs were not consistent with true recurrence. Our pragmatic approach combining clinical and quantitative RT-PCR data could aid assessment of COVID-19 reinfection or reactivation by clinicians and public health personnel.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Evaluation of potential COVID-19 recurrence in patients with late repeat positive SARS-CoV-2 testing

et al. 2021

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“…These and other predictors should be further studied using larger sample sizes to assess their ability to predict COVID-19 status 13 (Supplementary material). As a semi-quantitative proxy of viral loads, RT-PCR Ct values have been used for evaluating clinical outcomes and transmissibility for acute respiratory tract infections, influenza, and the Middle-East Respiratory Syndrome (MERS), the latter caused by another coronavirus [19][20][21] Despite the evidence supporting the role of RT-PCR Ct values on point of care evaluations, 13,22 variability among different RT-PCR diagnostic kits, and local viral load interpretability, [23][24][25] supports its application in tandem with other cues for COVID-19 diagnosis or management.…”

Section: Discussionmentioning

confidence: 99%

Cycle Threshold Values in the Context of Multiple RT-PCR Testing for SARS-CoV-2

Romero-Álvarez¹,

Garzon-Chavez²,

Espinosa³

et al. 2021

RMHP

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Discharge or follow up of confirmed coronavirus disease 2019 (COVID-19) cases depend on accurate interpretation of RT-PCR. Currently, positive/negative interpretations are based on amplification instead of quantification of cycle threshold (Ct) values, which could be used as proxies of patient infectiousness. Here, we measured Ct values in hospitalized confirmed COVID-19 patients at different times and its implications in diagnosis and follow up.Patients and Methods: Observational study between March 17th-May 12th, 2020 using multiple RT-PCR testing. A cohort of 118 Hispanic hospitalized patients with confirmed COVID-19 diagnosis in a reference hospital in Quito, Ecuador. Multiple RT-PCR tests were performed using deep nasal swab samples and the assessment of SARS-CoV-2 genes N, RdRP, and E. Results: Patients' median age was of 49 years (range: 24-91) with a male majority (62.7%). We found increasing levels of Ct values in time, with a mean Ct value of 29.13 (n = 61, standard deviation (sd) = 5.55) for the first test and 34.38 (n = 60, sd = 4), 35.52 (n = 20, sd = 2.85), and 36.12 (n = 6, sd = 3.28), for the second, third, and fourth tests, respectively. Time to RT-PCR lack of amplification for all tests was of 34 days while time to RT-PCR Ct values >33 was of 30 days. Conclusion:Cycle thresholds can potentially be used to improve diagnosis, management and control. We found that turnover time for negativity can be large for hospitalized patients and that 11% cases persisted with infectious Ct values for more time than the current isolation recommendations.

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“…every patient had complete data for infectiousness evaluation. Also, Ct values can vary enormously between different samples and laboratories 36 . Despite these limitations, our experience of estimating admitted asymptomatic patients' infectiousness and exposure events via Ct values targeting three genes may be helpful to other health centers.…”

Section: Discussionmentioning

confidence: 99%

Coronavirus disease 2019 (COVID-19) admission screening and assessment of infectiousness at an academic medical center in Iowa, 2020

Alsuhaibani

Kobayashi

Trannel

et al. 2021

Infect. Control Hosp. Epidemiol.

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Objective: Patients admitted to the hospital may unknowingly carry SARS-CoV-2 and hospitals have implemented SARS-CoV-2 admission screening. However, because SARS-CoV-2 RT-PCR may remain positive for months after infection, positive results may represent active or past infection. We determined the prevalence and infectiousness of patients who were admitted for reasons unrelated to COVID-19 but tested positive on admission screening. Methods: We conducted an observational study at the University of Iowa Hospitals & Clinics from July 7 to October 25, 2020. All patients admitted without suspicion of COVID-19 infection were included and medical records of those with a positive admission screening test were reviewed. Infectiousness was determined using patient history, PCR cycle threshold (Ct) value, and serology. Results: A total of 5,913 patients were screened and admitted for reasons unrelated to COVID-19. Of these, 101 had positive admission RT-PCR results. Thirty-six patient were excluded because they had respiratory signs/symptoms on admission on chart review. Sixty-five patients (1.1%) did not have respiratory symptoms. A total of 55 patients had Ct values available and were included in this analysis. The median age was 56 years, and (51%) were male. Our assessment revealed that 23 patients (42%) were likely infectious. The median duration of in-hospital isolation was five days for those likely infectious and two days for those deemed non-infectious. Conclusions: COVID-19 infection was infrequent among patients admitted for reasons unrelated to COVID-19. An assessment of the likelihood of infectiousness using clinical history, RT-PCR Ct values, and serology may help discontinue isolation and conserve resources.

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Caveats of Reporting Cycle Threshold Values from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Qualitative Polymerase Chain Reaction Assays: A Molecular Diagnostic Laboratory Perspective

Cited by 11 publications

References 3 publications

Evaluation of potential COVID-19 recurrence in patients with late repeat positive SARS-CoV-2 testing

Evaluation of potential COVID-19 recurrence in patients with late repeat positive SARS-CoV-2 testing

Cycle Threshold Values in the Context of Multiple RT-PCR Testing for SARS-CoV-2

Coronavirus disease 2019 (COVID-19) admission screening and assessment of infectiousness at an academic medical center in Iowa, 2020

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