1/11 Want to talk about PCR testing. Cycle threshold (Ct) means how hard did the PCR test have to work (amplification cycles) to find viral genetic material. @robertfservice @michaelmina_lab @FatEmperor https://www.sciencemag.org/news/2020/09/one-number-could-help-reveal-how-infectious-covid-19-patient-should-test-results

2/11 If Ct is low (lots of virus) then patient was shedding lots of virus & was infectious; if Ct is high (not much virus) then patient likely to be at end of infection or infected in the past and/or no longer infectious.

3/11 PCR results are quantitative and not only tell us if test is positive or negative, but also tell us HOW positive or negative. @michaelmina_lab: “We have to stop thinking of people as positive or negative, and ask how positive?” https://www.sciencemag.org/news/2020/09/one-number-could-help-reveal-how-infectious-covid-19-patient-should-test-results

4/11 Dr Bernard La Scola reported that only 3% of “cases” with Ct >35 yielded live virus when cultured. https://pubmed.ncbi.nlm.nih.gov/32342252/ 

5/11 @CillianDeGascun has been clear that in Ireland we run 35-45 amplification cycles as standard. @HSELive have also confirmed that 40-45 amplification cycles are the norm.

6/11 @JumoDr expressed shock in @nytimes that results with Ct of 40 would be considered positive and suggested that a more reasonable cut off would be 30 to 35 https://www.nytimes.com/2020/08/29/health/coronavirus-testing.html?referringSource=articleShare

7/11 @CillianDeGascun acknowledged questions about infectiousness of “cases” above this Ct range, but also warned that results in isolation could fail to distinguish between cases with viral load on the way up (very infectious) and viral load on the way down (not infectious).

8/11 @JumoDr acknowledged this & suggested non pcr repeat tests could = solution. Weak + PCR result (high Ct) should repeat test soon. If remained + then could indicate viral load going up = infectious;while a neg repeat test could indicate viral load going down - NOT INFECTIOUS

9/11 @HSELive have not invested in non PCR testing capability so that idea was never implemented. @HPSCIreland did publish proposals for “the management of weak positive (high Ct value) PCR results on 08/10/2020. http://hpsc.ie/a-z/respirator …

10/11 https://www.hpsc.ie/a-z/respiratory/coronavirus/novelcoronavirus/guidance/outbreakmanagementguidance/PCR%20weak%20results%20guidance.pdf# Proposed mgmt of specimens with Ct value >30. Step 1 advises such positive results be RETESTED. Appendix 1 of this proposal also states: “very few reports of viable SARS-CoV-2 virus being retrieved in culture from clinical specs with Ct value >34

11/11 @HSELive @DonnellyStephen @RoinnSlainte @CillianDeGascun Are @HPSCIreland proposals (08/10/2020) now implemented? Why did it take 7 months?Why no non-PCR retesting strategy for weakly + cases? Would that have allowed more accuracy with results or protected tracing system?