Tue, 04/21/2020 - 17:47
Dear colleagues,
- What is the true sensitivity of SARS-CoV-2 RT-PCR in the diagnosis? You read a lot of widely variable figures from 50 % to 90 % and yesterday Prof Herman Goossens said on TV: very close to 100%. “There are no false negatives, but the nasopharyngeal sample is often not taken well”.
My own short answer is: “I don’t know, because I’m not sure what the gold standard is.”. And in addition… I’m not a PCR specialist (the only PCR I ever tried to do myself failed, like many other experiments), but I’m prepared to believe that the best available tests today have a very high sensitivity (and specificity), when you calibrate them in the lab. However that may not be fully relevant for the “real world”.
Just present you two papers for you contemplation:
The paper by Chan from Hongkong compares two tests targeting the RdRp (polymerase):
1) the RdRp-P2, which is specific for SARS-CoV-2, was validated on synthetic sequences, not real virus by Drosten et al and “used in > 30 European labs”
- 2) the novel RdRp-Hel (for helicase domain).
Both tests were compared on a set of 175 samples from 15 COVID patients and Table 3 clearly shows that the “Hel” test was much more sensitive as it detected the virus in 85 % of the respiratory samples, while the “P2” scored only 60 %.
The other paper by Long et al. A total of 36 patients were finally diagnosed with COVID-19 pneumonia. Thirty-five patients had abnormal CT findings at presentation, whereas one patient had a normal CT. Using rRT-PCR, 30 patients were tested positive, with 6 cases initially missed. Amongst these 6 patients, 3 became positive in the second rRT-PCR assay(after 2 days, 2 days and 3 days respectively), and the other 3 became positive only in the third round of rRT-PCR tests(after 5 days, 6 days and 8 days respectively). At presentation, CT sensitivity was therefore 97.2%, whereas the sensitivity of initial rRT-PCR was only 83.3%.
They do not describe the sampling method in detail and in the discussion they admit “This may be related to sample collection as pharyngeal oral and nasal sampling are easier collection methods, whereas lower respiratory tract sampling is relatively difficult to perform, with medical staff susceptible to get infected”
I’m inclined to believe that these people in Hongkong and China know what they are doing and that in real life, it is not always possible to take the optimal sample from the first time on one hand, but I can also imagine that a pharyngeal sample can intermittently contain few viral particles. I would be surprised that results from an “upper respiratory sample” could be as reliable as blood (for HIV testing for instance). So, what is the value of a negative test, taken under real-life “field circumstances” (e.g. an elderly home, a workplace or a school), even if trained staff is doing the best they can?
I’m really curious to know the opinion of the specialists amongst you!
- In follow-up of our previous exchanges, I add another editorial about “scientific rigor” and a nice viewpoint of our colleague Peter Van Landschoot about the role of the GI system. Peter is keen to know your opinion on his hypothesis, supported by clinical evidence, that the GI should be taken more serious as a source of virus and as an important element in pathogenesis. You can communicate with Peter through his LinkedIn. https://www.linkedin.com/pulse/why-we-should-forget-sars-cov-2-enteric-virus-well-vanlandschoot/
Best wishes,
Guido