covid: rapid test less accurate for omicron transmission

 There is increasing reliance on the rapid Covid antigen tests in determining individuals' Covid status, informing them of both their own viral status as well as the likelihood of viral transmission to others. A recent small preprint study questioned the reliability of this test, even in people with transmissible virus (see covid rapid test less accurate omicron InfectEconom2022 in dropbox, or doi.org/10.1101/2022.01.04.22268770). Thanks to Karen Henley for bringing this to my attention.

 

Details:

-- 30 individuals diagnosed with Covid-19 between December 1 and December 31, during omicron outbreaks at five workplaces in New York, Los Angeles, and San Francisco

-- all were fully vaccinated, per employer mandate, and highly boosted by patient choice

-- all subjects had daily testing at the time of diagnosis, with paired PCR and rapid antigen test results on day zero or one after the first positive specimen collection date

-- rapid antigen tests were either the Abbott BinaxNOW or the Quidel Quick Vue

-- primary outcome of interest: concordance between PCR and rapid antigen test results, and reviewing timing and Ct values corresponding to transmissibility [Ct, or cycle threshold, reflects the inverse of the SARS-CoV-2 viral load]

    -- index case was specimen collection date for the first positive PCR test with a Ct <35, as compared to the first positive rapid antigen test

    -- transmissible viral load was defined as having PCR Ct <29

 

Results:

-- 29 of the 30 cases were likely from omicron, based on S-gene dropout

    -- on days 0-1, the rapid antigen test was negative, yet the PCR Ct was <29

-- the median time between first PCR positivity to antigen positivity was 3 days

-- 5 patients had daily saliva and nasal PCR: the saliva PCR viral load peaked 1-2 days before the nasal one

-- 4 cases were confirmed to have transmitted the virus (secondary infections) between two false-negative rapid antigen tests, though the saliva PCR Ct values were between 23-28 for the N-gene (ie, a really high SARS-CoV-2 viral load)

--here are some graphs of their findings: 

graph A shows the rapid antigen test results by manufacturer, relative to the PCR Ct

graph B depicts the time from positive PCR to positive rapid antigen test

 

Commentary:

-- it is important to remember that these rapid antigen tests may vary in their sensitivity depending on the dominant SARS-CoV-2 variant of concerned (VOC), necessitating validation of these various tests with each new VOC

    -- omicron appears to be quite different from the previous VOCs, in terms of mutations (much higher numbers in the spike protein), transmissibility (higher), clinical severity (less so, in part attributable to the fact that it more efficiently infects the human bronchus leading to bronchitis symptoms, but less severe infections in the lung), and in terms of general sensitivity of the tests (viral antigens are detected more by saliva than by nasal swabs for omicron as opposed to delta variant eg see Saliva swabs are the preferred sample for Omicron detection | medRxiv)

    -- one question this raises: why is the omicron tropism different from the others? why does it not bond so aggressively to the nasal and lung tissue, which are replete with ACE-2 receptors (instead attaching to something in the saliva/throat)? and, what is it binding to in the saliva???

-- one prior concern was that these antigen tests needed a high threshold of viral particles in order to test positive, leading to their decreased sensitivity. This article however finds that not only is there delayed detection, but there are really high viral loads in the false negative tests, and cases of transmissible Covid that can therefore be missed

-- their cutpoint for the infectious PCR viral load corresponding to a Ct<29 has been found in other studies

    -- a Danish study (see https://www.medrxiv.org/content/10.1101/2021.12.27.21268278v1.full.pdf ) did find some useful information about omicron transmission:

         -- the Ct value for secondary infections from omicron did seem to decrease with Ct values >30

         -- the time to secondary infections was less in omicron vs delta

 

Several studies have assessed the sensitivity of PCR tests and have found them to be only moderately sensitive, in the 80+% range, though highly specific (eg see https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251661 , or https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240870/ ). so, PCR tests are not really a "gold standard", though it is the best we have for widespread testing.

 

Limitations:

-- a small study in 5 workplaces, limiting generalizability to other settings

-- no information on when the covid vaccines had been given (the lag between end of primary series to this assessment) nor breakdown by booster vaccination status

-- no info on who the 30 people were, what their comorbidities were, what their personal social situations were, if they used mitigation strategies to decrease viral spread, etc

-- the assumption that a Ct<29 meant viral transmissibility may not be totally accurate, though the Danish study noted above did find this was a pretty good cutoff. and this has been found in some older studies with older variants

-- no specifics on the 4 cases of transmission while antigen negative but PCR positive, so cannot assess this fully. though their PCR Ct tests were really low (18-23: ie, really, really high viral loads). and an author noted that it was by "contact tracing and epidemiology investigation": see  https://www.statnews.com/2022/01/05/study-raises-doubts-about-rapid-covid-tests-reliability-in-early-days-after-infection/?utm_source=STAT+Newsletters&utm_campaign=936e06e45e-Daily_Recap&utm_medium=email&utm_term=0_8cab1d7961-936e06e45e-149609141

--only 2 rapid test kits were tested, so results may not apply to others on the market

 

So, a few points from this small study:

-- the preferred method to diagnose omicron seems to be by salivary sampling and not nasal sampling (which seems to have a delay at least in detecting high-level viral loads). this has been shown in a couple of studies

    -- these studies were done with PCR testing. not sure they apply to the rapid antigen tests. some experts conjecture that first swabbing the throat and then the nose with the same swab may be useful. others feel that these swabs should be done as per the manufacturers' suggestions on the package insert. it seems that this is a pretty important issue and should be studied: what is most accurate way to use the rapid tests???

-- this study of almost entirely omicron-infected patients, though quite small, did find that there was a 2-3 day lag in rapid antigen testing, at a time when they probably had omicron transmissibility (which was confirmed in 4 cases, and highly likely given the high SARS-CoV-2 viral loads overall)

-- and, this means that using the rapid antigen tests as a means to detect and quarantine those with Covid may not be a particularly useful way to prevent SARS-CoV-2 transmission (at least from the omicron variant, which seems to require less time from infection to transmission: eg see above Danish study). 

    --So, using the rapid antigen tests to screen in workplaces, schools, etc is likely not to be so effective in preventing further omicron transmission. And the turn-around time for community PCR tests makes that test not useful for this purpose either

geoff

 

If you would like to be on the regular email list for upcoming blogs, please contact me at gmodest@uphams.org

to get access to all of the blogs (2 options):

1. go to http://gmodestmedblogs.blogspot.com/ to see them in reverse chronological order

2. click on 3 parallel lines top left, if you want to see blogs by category, then click on "labels" and choose a category​

3. or you can just click on the magnifying glass on top right, then  type in a name in the search box and get all the blogs with that name in them

 

or: go to https://www.bucommunitymedicine.org/ , a website from the Community Medicine section at Boston Medical Center.  This site does have a very searchable and accessible list of my blogs (though there have been a few that did not upload over the last year or two). but overall it is much easier to view blogs and displays more at a time.

 

 

please feel free to circulate this to others. also, if you send me their emails, i can add them to the list