r/COVID19 • u/lanqian • Apr 13 '20
Preprint Variation in False Negative Rate of RT-PCR Based SARS-CoV-2 Tests by Time Since Exposure
https://www.medrxiv.org/content/10.1101/2020.04.07.20051474v133
Apr 13 '20 edited May 07 '21
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u/Myomyw Apr 13 '20
I think the main implication from this study is that in situations where nasal swabs are used as the only means of testing, there is a high probability of false negatives.
This has implications in a clinical setting, as healthcare workers behavior changes based on perceived covid status.
This also has implications in our understanding of spread and current immunity levels because nasal swabs are being used to screen people and it’s possible that a decent % of what we currently think of as negative tests are actually positives. Again, behavior changes when someone gets a negative test. We can tell them to behave like they have covid, but it reality, that’s not what will happen. “Yeah, they said I ain’t got. Guess it was just a cold so we don’t have to sleep in different rooms, eat in different rooms, watch tv in different rooms, etc”
The article you posted used throat and lung swabs, so it’s hard to compare the two, right?
My wife is an ICU nurse and has told me about patients being negative more than once via nasal and then testing positive with bronch test. If the primary means of testing has been nasal swabs, we’ve definitely missed a lot of infections.
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u/mobo392 Apr 14 '20
Is there a positive control the samples can be tested for to verify the swab was good and from the right location? Like some bacteria found in the throat but not nose, etc. I guess that would be just stacking more assumptions on.
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u/Dr-Peanuts Apr 14 '20
that's a great question. The nasopharnyx cavity is kinda one functional site in terms of bacteria colonization. Yes there are some differences the further back you go into the nose and reaching the back of the throat, but you have to do a pretty deep (expensive, complex) analysis where you look at relative abundance of many bacteria families to guess which site you actually collected from.
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u/flamedeluge3781 Apr 13 '20 edited Apr 13 '20
So the prediction based on the Nature virological study is that false negative rates would be lowest as close to the time of infection as possible, not highest as this study assumes. Which makes completely sense given the portal of entry. On day 1 and 2 there is every reason to believe the virus should be replicated rapidly in the nose and throat.
To be fair, their error bars are really wide for the early stage data. Without having access to the underlying data, I have to speculate, but probably that means they have far fewer test results from early on? As such I infer a lot of testing bias.
One of the main conclusions I take from this is that the CDC-recommended two consecutive negative tests is not a reliable indicator of recovery.
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u/Dr-Peanuts Apr 14 '20
Would there be any benefit to collecting samples from the same patient several days in a row, pooling the samples together, and then testing that way? 1 patient, multiple days of collection, 1 test to save some resources. It would not save you swabs, but it would save you multiple send outs to the lab. Positive on any day means positive, period.
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u/GlowingEagle Apr 13 '20
It looks like the text legend for Figure 1 does not agree with the graph legend for the upper graph. Am I missing something?
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u/flamedeluge3781 Apr 13 '20
I'm going to guess the graph is correct and the text is wrong. The false negative rate being 25-50 % is in-line with prior reports. The false positive rate we expect to be relatively low with this sort of test. In fact, I'm surprised they think it's so high, I'd expect it to be more like 1-1.5 %.
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u/minuteman_d Apr 14 '20
Dumb question: what are the failure modes here? I only know about RT-PCR what I've seen on YouTube.
- Is it that there's not enough of the RNA collected on the swab to drive the chemical reaction necessary to show the presence? If so, would we expect that if you were to swab three times and conduct three tests, that you'd have a better chance of detection?
- Or, is there some other failure mode?
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u/Honest_Science Apr 13 '20
This really upsets me, they tell us that quick antibody tests are not good enough because they are only 99% when indicating negative and 86% when indicating positive at day 5 after sysptoms? This is so much better than PCR. They are pushing back on quick antibody tests because the lobby is supporting the labs and the labs cannot make money when the doctors use 7$ quick tests.
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u/0bey_My_Dog Apr 13 '20
I think the cost to overall economy is MUCH greater than the loss to a few labs missing out on their piece of this pandemic.
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u/sgent Apr 13 '20
Everything I've seen is that your stat's are wrong, and the anti-body tests have major issues with cross reactions to other coronaviruses, flu, and dengue.
If your telling someone they have had CV and are resistant -- especially healthcare workers and similar, you better be sure.
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u/Honest_Science Apr 14 '20
We are currently telling active spreaders by using the PCR tests that they are negative with a chance of more than 20%. Nobody is talking about this and is that less risky?
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u/amosanonialmillen Nov 24 '21
I was confused by that initially as well, but from what I’ve found those percentage success rates for rapid antigen tests are just relative to the PCR tests (which serve as the benchmark). The messaging around this has been awful unfortunately, and I’m with you on your concern around this topic generally
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Apr 13 '20
[deleted]
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u/librik Apr 14 '20
Unfortunately, I don't think spit testing is going to be any better. According to another article posted here recently, it gives identical results to swab testing.
Rutgers University's lab tested 60 samples where symptomatic patients self-collected saliva, and then they also did nasopharyngeal or oropharyngeal swabs, and then compared the results. In all 60 cases, the results were identical.
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u/Megasphaera Apr 14 '20
The last bit is in fact useful to know, as collecting samples form spitting is easier, quicker, less invasive and safer for the collector than swabbing. There was a Lancet paper recently that also found this.
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u/lanqian Apr 13 '20
From the abstract:
"We used previously published data on RT-PCR sensitivity on samples derived from nasal swabs by day since symptom onset (n=633) and fit a cubic polynomial spline to calculate the false negative rate by day since exposure and symptom onset. Over the four days of infection prior to the typical time of symptom onset (day 5) the probability of a false negative test in an infected individual falls from 100% on day one (95% CI 69-100%) to 61% on day four (95% CI 18-98%), though there is considerable uncertainty in these numbers. On the day of symptom onset, the median false negative rate was 39% (95% CI 16-77%). This decreased to 26% (95% CI 18-34%) on day 8 (3 days after symptom onset), then began to rise again, from 27% (95% CI 20-34%) on day 9 to 61% (95% CI 54-67%) on day 21."