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.
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.
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Shownotes by Melissa Orman, MD