key: cord-0955047-nlgoq8xh authors: Stokes, William; Kanji, Jamil; Hu, Jia; Zelyas, Nathan; Berenger, Byron M title: Wide Variation in Cycle Threshold Values Cloud the Interpretation of COVID-19 Infectiousness date: 2021-07-29 journal: Clin Chem DOI: 10.1093/clinchem/hvab145 sha: 2b150139d30d5b44d5cae75b4a4873efbc7876ac doc_id: 955047 cord_uid: nlgoq8xh nan 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 Demand for reporting Ct values has been justified to guide the 50 administration of therapeutics, prognostication, identifying reinfection, or removing isolation 51 precautions (1). However, there are fundamental flaws when interpreting a qualitative test in a 52 quantitative manner where Ct values vary on a multitude of factors, including sample collection, 53 specimen type, reagents used, extraction/PCR platform(s), PCR targets Data recorded from 58 March to May, 2020 from the Alberta Health Services Public Health and Alberta Precision 59 Laboratory databases were linked. Symptom duration and status at the time of collection was 60 determined during case investigation by Public Health using a standardized questionnaire. Cases 61 with known symptomatology and tested with Ct values generated from Alberta Precision 62 Laboratory's laboratory-developed E gene singleplex assay were included. Based on proficiency 63 panels Oropharyngeal, nasopharyngeal and nasal specimens for SARS-CoV-2 testing were collected in 67 universal transport media 7%) were asymptomatic, 92 (1.6%) pre-74 symptomatic (symptom onset within 2 d after collection), 3,107 (54.0%) with symptom onset ≤7 75 d, and 1,770 (30.7%) with symptom onset >7 d. Excluding those tested on day 1 of symptom 76 onset, a linear positive correlation between days of symptoms and median Ct values was 77 observed Despite a linear positive correlation between days of symptom onset and median Ct value, Ct 80 values ranged widely, regardless of symptom onset or specimen type. For example Now, more than ever, it is important that the 105 laboratory continue to uphold quality standards that have, and will continue to maintain, public 106 trust in our laboratories. Reporting of Ct values to clinicians must be done cautiously and with 107 the consideration of the assay and the pre-analytic and analytic factors that are associated with Ct 108 value variability. Interpretation should be made within the clinical context by clinicians familiar 109 with these caveats or in consultation with a laboratory physician/scientist. Since qualitative rRT-110 PCR assays were designed only for the detection of SARS-CoV-2 Author Contributions: All authors confirmed they have contributed to the intellectual content of this 120 paper and have met the following 4 requirements: (a) significant contributions to the conception and 121 design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for 122 intellectual content Authors' Disclosures or Potential Conflicts of Interest: No authors declared any potential conflicts of A narrative systematic review of the clinical 140 utility of cycle threshold values in the context of COVID-19 Development 143 and validation of reserve transcriptase-PCR assays for the testing of SARS-CoV-2. 144 Real-time PCR-146 based SARS-CoV-2 detection in Canadian laboratories Predicting 148 infectious SARS-CoV-2 from diagnostic samples Performance of saliva, 150 oropharyngeal Swabs, and nasal swabs for SARS-CoV-2 molecular detection: a 151 systematic review and meta-analysis