covid: false positive rapid antigen very rare

 

a recent large Canadian study confirmed that there were very few false positive results in rapid antigen tests for SARS-CoV-2 virus, and that the limited number of false positives were largely from manufacturing issues of the tests (see covid false pos rapid antigen rare JAMA2022 in dropbox, or doi:10.1001/jama.2021.24355)

 

Details:

-- Canada implemented their Creative Destruction Lab Rapid Screening Consortium (CDL RSC) in order to help protect against Covid transmission in workplaces

    -- this program was set up to inform the operational requirements of rapid antigen screening in workplaces

-- asymptomatic employees were screened twice weekly, on a voluntary basis

-- data collected from January 11 to October 13, 2021 during which there were two significant Delta variant waves (March to June and August to October)

-- screening results were recorded, including the place of employment, the test done, and (optionally) the lot number of the test

-- positive rapid antigen test results were referred for a confirmatory PCR within 24 hours, with a false positive antigen test being considered if the PCR was negative

-- false positive results were matched to lot number and test manufacturer, when available

-- 903,408 rapid antigen tests were conducted in 537 workplaces

 

Results:

-- antigen test: 1322 positive results (0.15% of the total done)

-- of these positive tests, two thirds were trackable and had a lot number

-- false positive results:

    -- 462 (0.05% of all screens)

        -- 278 of the false positive results (60%) occurred in two workplaces, which were 675 km apart and run by different companies

        -- all of the false positive test results from these two workplaces were from a single batch of Abbot's Panbio COVID-19 Ag Rapid Test Device

 

Commentary:

-- this study confirmed the low incidence of false positive rapid antigen testing, as defined by PCR testing within 24 hours. there was also the major finding that a lot of the false positive tests were related to a single batch of the rapid antigen tests, which suggests that the issue was in the manufacturing of these test kits. One advantage of such a systematic program as done in Canada is the potential to identify manufacturing problems early in order to be able to correct them. And, identifying such issues not only relieves individual and family/community anxiety, but would also allow workers to return to work more rapidly

-- the ability to derive these kinds of results points both to the importance of a systematic approach, with recording important specifics of tests/results (e.g., not just the results themselves, but also the actual lot numbers and types of rapid antigen tests), and to the deficiencies of the system such as ours in the US which lack systematic reporting and accumulation of data: a significant quality control issue

 

Limitations:

-- the study was not an all-inclusive assessment of rapid antigen testing. Although there were a large number of people involved and impressive data collection, allowing for more reliable Information, this was still a workplace-oriented study. And there is an inherent bias: their is the "healthy worker" effect, wherein those who work as a group are healthier than those not working, often because of medical conditions

-- there was no granular information about how the testing was done. some were done at the workplaces and some by employees at home. so, we do not know specifically if the home-based sampling (as the predominant one done in the US) was as accurate as the one done perhaps more knowledgeably and consistently by those at the workplace, limiting generalizability of these results to home-based sampling,

-- we also do not know the sensitivity of the rapid antigen testing in this study setting (would need simultaneous rapid antigen and PCR tests done)

    -- though PCR testing is the best widely-available test, it is not totally a "gold standard", with its own issues about sensitivity and smaller ones on specificity: see https://www.cap.org/member-resources/articles/how-good-are-covid-19-sars-cov-2-diagnostic-pcr-tests#:~:text=Summary,and%2098%2D99%25%20specificity ,suggesting that in the community, the sensitivity is around 80% but specificity 98-99% (ie, there may be false negative PCRs, which could distort the results above)

-- this involved the Delta variant of SARS-CoV-2 and may not apply to other variants

    -- for example, a small US study of 30 people found that during Omicron, there was less rapid concordance between rapid antigen tests and PCR results, with the median time between the first PCR positivity to antigen positivity being three days (see http://gmodestmedblogs.blogspot.com/2022/01/covid-rapid-test-less-accurate-for.html ). part of this issue is that omicron is first detected in saliva vs nasal testing. Of course, this difference in rapid antigen vs PCR would actually render fewer false positive rapid antigen tests, but it highlights some differences between testing for different variants. 

    -- unfortunately, this is the world we live in: this virus morphs so quickly that our studies will of necessity predate the most current variants, which might distort the generalizability of the studies' results to current conditions

-- the Individuals involved in the screening program were asymptomatic, and voluntary participants, leading to potential biases: would these results be the same in those who were symptomatic? and was there a significant selection bias in those who chose to be tested? were they more aggressive in other mitigation strategies? were many of the others choosing not to be tested covid-deniers (certainly a pretty large number in the US...) and more susceptible to get covid? we do not know either vaccination status of those involved, nor prior history of covid, which also might affect the results

-- these results were not entirely systematic, given that recording lot numbers was optional and there might have been confounders in how this played out. For example, did those recording lot numbers also have a more consistent/systematic approach to performing the tests?

 

so, the real messages of this study is that false positive rapid antigen testing is pretty rare, and that this may be due to manufacturing issues of the companies making these rapid antigen tests.  the results of a false positive test can be profound in terms of the individuals involved (need for quarantine, loss of work/money, and even more so in countries where there are very stringent isolation practices), as well as the community overall (witness China's approach now). and this really reinforces the importance of robust programs to test lots of people, identify the manufacturing issues of the tests and act on them quickly (or have a system whereby all with positive rapid antigen tests get a PCR test soon thereafter, though would be hard to implement consistently in the US)

 

geoff

 

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