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30. COVID-19: Why a negative test doesn't clear you to see Grandma, Vax updates


We review the false negative rates of different COVID testing, the known knowns and known unknowns of the Moderna vaccine.


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We discuss:


Why the lack of a legitimate gold standard is a challenge when comparing different tests for COVID-19 [01:45];

  • A gold standard is a test that is recognised as so good that all other tests can be compared to it.

  • Reverse transcriptase PCR (RT-PCR) is used as a gold standard for COVID-19 because it is the best widely available test. But we’ll see it’s far from perfect.


RT-PCR: why we shouldn't be reassured by a negative test result [03:45];

  • This test looks for viral genes. It’s “the slow test”.

  • A positive RT-PCR for covid-19 has more weight than a negative test because of the test’s high specificity (≅90-100%) but only moderate sensitivity.

  • An Annals of Internal Medicine study showed that the false negative RT-PCR rate for patients who ended up developing COVID from time of exposure was 100% on day 1, 67% on day 4, 38% on day 5, and 20% on day 8. After day 8, the false negative rate steadily increased.

  • The RT-PCR test’s high specificity (90-100%) means that if it’s positive, you can be pretty sure that the patient has COVID.


“A single negative covid-19 test should not be used as a rule-out in patients with strongly suggestive symptoms.”

How your pretest probability of disease affects your interpretation of test results [07:00];

  • If there is a high pretest probability (or suspicion) of COVID and a negative test result, the chances are higher that the test is a false negative result than for someone with a low pretest probability.

  • BMJ link: Interpreting a COVID-19 test result (in consideration of the pretest probability)


The COVID antigen test: faster and more widely available, but less accurate [08:10];

  • Tests for viral proteins. Can get results within hours.

  • Has a higher false negative rate (lower sensitivity) compared to RT-PCR. CDC reports a sensitivity of 84-98% compared to RT-PCR.

  • Antigen levels in specimens collected beyond 5-7 days of the onset of symptoms may drop below the limit of detection of the test. This could result in a falsely negative test result (while the PCR test would likely be positive).

  • Rapid antigen tests are only approved by the FDA for use on symptomatic people within the first 5-12 days from symptom onset. It has not been approved for asymptomatic screening.


A NYT report of a rapid antigen test study showing suboptimal test sensitivity when applied to asymptomatic people [10:15];

  • For symptomatic people, rapid testing was 80% sensitive compared with PCR, meaning that it picked up 80% of the cases that were positive by PCR.

  • For asymptomatic people, the rapid test was only 32% sensitive (again, using PCR as the gold standard).

  • For people with a high viral load in the swabbed area (symptomatic or not), the test picked up 85% of PCR cases.

  • At the moment, the viral load (or “cycle threshold”) cannot be used to predict how contagious one might be. You can still be contagious with a negative test.


Why you can’t rely on a negative test to make your decision to travel or spend time with family/friends for the holidays [12:05];

  • The CDC estimates that approximately 40% of those infected with COVID are asymptomatic and ½ of transmission happens before symptom onset.

  • Even if you quarantine and self-isolate before and after your test, there’s still a chance the test could be a false negative result (especially if you’re asymptomatic).

Whether you need to quarantine if you’ve been in close contact with someone who themselves was exposed to a known COVID patient [13:30];

  • The CDC currently does not recommend quarantining in this scenario unless the person you were exposed to developz symptoms (or tests positive)


The Moderna vaccine which has a reported efficacy of 94.5% [14:00];

  • 30,000 people are included in the Moderna study, and 37% of trial volunteers are from racial and ethnic minorities. The study has been going on since July and will last for 2 years.

  • Injections were given 28 days apart, with ½ receiving the vaccine and ½ a placebo.

  • The first interim analysis showed 95 cases of COVID with 90 of those in the placebo group and 5 in the vaccine group. COVID defined as having at least 2 symptoms and a positive test

  • Of the 11 severe COVID cases, all were in the placebo group.

And more.


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Shownotes by Melissa Orman, MD


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