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THREAD: Why is PCR Cycle Threshold so important?
RT PCR tests are capable of detecting trace amounts of RNA, which can be present for up to 12 weeks after infection (Source: CDC). The tests amplify (multiply) the RNA samples by cycling.
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RT PCR tests are capable of detecting trace amounts of RNA, which can be present for up to 12 weeks after infection (Source: CDC). The tests amplify (multiply) the RNA samples by cycling.
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The higher the Cycle Threshold (Ct Value) means it took more multiplication to detect the RNA, and the likelihood of infectious virus decreases.
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"A positive PCR result reflects only the detection of viral RNA and does not necessarily indicate the presence of viable virus"
https://jamanetwork.com/journals/jama/fullarticle/2765837?utm_source=instagram&utm_medium=social_jama&utm_term=3323932512&utm_campaign=content_marketing&linkId=88059733
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https://jamanetwork.com/journals/jama/fullarticle/2765837?utm_source=instagram&utm_medium=social_jama&utm_term=3323932512&utm_campaign=content_marketing&linkId=88059733
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For most cases, the virus is only infectious for 10 days (longer in only severe cases), yet virus is detectable well beyond that time period. Higher Cycle thresholds pick up “older” infections that are less likely to be contagious.
https://www.cebm.net/covid-19/infectious-positive-pcr-test-result-covid-19/
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https://www.cebm.net/covid-19/infectious-positive-pcr-test-result-covid-19/
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The public receives a test result of simple binary "Positive/Negative" or "Detected/Not Detected" - and as far as we have found, the results provided give no supporting information about what Cycle Threshold where the positive detection occurred.
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The FDA, with their Emergency Use Authorizations, have issued Molecular Diagnostic Templates for PCR test manufacturers that referenced 40 Ct, but stated in an email to New York Times that they "do not specify" the threshold setting.
http://www.fda.gov/media/135900/download
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http://www.fda.gov/media/135900/download
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We have found that many labs and manufacturers are using Cycle Threshold Settings of 37-40 Ct or even more.
Example product sheet from " Xpert Xpress SARS-CoV-2 test"- found it reaches a predetermined threshold of45 Cycles (see page 16)
https://www.fda.gov/media/136314/download
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Example product sheet from " Xpert Xpress SARS-CoV-2 test"- found it reaches a predetermined threshold of45 Cycles (see page 16)
https://www.fda.gov/media/136314/download
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Recent scientific evidence is showing that a Higher Cycle Threshold value is strongly related to non-infectious virus:
"A cut-off RT-PCR Ct > 30 was associated with non-infectious samples."
Source: Center for Evidence base Medicine.
https://www.medrxiv.org/content/10.1101/2020.08.04.20167932v3
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"A cut-off RT-PCR Ct > 30 was associated with non-infectious samples."
Source: Center for Evidence base Medicine.
https://www.medrxiv.org/content/10.1101/2020.08.04.20167932v3
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"A binary Yes/No approach to the interpretation RT-PCR unvalidated against viral culture will result in false positives with segregation of large numbers of people who are no longer infectious and hence not a threat to public health."
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“RT-PCR cycle threshold (Ct) values correlate strongly with cultivable virus. Probability of culturing virus declines to 8% in samples with Ct > 35 and to 6% 10 days after onset.”
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How big is this problem? According to the report in the NYT, between 43 and 63% of Tests would no longer qualify as positives under accurate cycle threshold guidelines. https://www.nytimes.com/2020/08/29/health/coronavirus-testing.html
