Thread by @jeffgilchrist

COVID-19: When to use PCR, Rapid Tests, and Antibody Tests

A study looks at diagnostics for COVID-19 and their role to move from pandemic response to pandemic control ( thelancet.com/journals/lance… ). H/T: @EricTopol 🧵1/

There are 3 major methods for the detection of COVID-19 virus infection. Molecular tests (PCR) are highly sensitive and specific at detecting viral RNA and can detect it at very low levels. 2/

The PCR method of test is recommended by the WHO for confirming diagnosis of individuals who are symptomatic for activating public health measures. 3/

Rapid antigen rapid tests (RAT) detect viral proteins and although less sensitive than PCR tests, have the advantages of being easier to do, faster results, lower cost, and being able detect infection in those who are most likely at risk of transmitting the virus right now. 4/

When viral loads are high enough to be within RAT's window of detection they are very accurate (

https://twitter.com/jeffgilchrist/status/1445390396561952779

). 5/

RATs can be used as a public health tool for screening individuals at enhanced risk of infection, to protect people who are clinically vulnerable, to ensure safe travel and the resumption of schooling and social activities, and to enable economic recovery. 6/

Antibody tests detect a person's response to infection or vaccination. They can be useful surveillance tools to inform public policy but should not be used to provide proof of immunity as it remains unclear exactly what levels provide sufficient protection. 7/

Omicron may have changed this now but evidence from 113 studies in 17 countries found COVID-19 viral RNA can be detected as early as 6 days before symptom onset, concentrations peak around the time of symptom onset or a few days later. 8/

Viral RNA usually become undetectable from upper respiratory tract samples about 2 weeks after symptom onset with no substantial differences between adults and children but can be much longer. 9/

People who are vaccinated or previously infected may actually develop symptoms before the viral load is high enough to be infectious due to the rapid response from the immune system. 10/

People without any previous exposure on the other hand, their immune system takes time to recognize and mount an immune defense the first time which leads to symptoms starting closer to peak infectiousness. 11/

While viral cultures show patients can remain RNA positive for weeks after symptom onset, live virus has not been cultured from specimens collected later than 9 days after symptom onset. 12/

This suggests the mean period of infectiousness and risk of transmission could be somewhere between 2-3 days before and 8 days after symptom onset. PCR RNA positive tests could represent the detection of viral fragments rather than actively replicating viruses. 13/

You can see from the graph that the 3 types of diagnostics are useful for different purposes (

https://twitter.com/EricTopol/status/1473143057620951041

). 14/

The molecular (PCR) test has a very low limit of detection which means it can detect COVID-19 virus before, during, and after someone is infectious, sometimes for weeks afterwards. 15/

You get very high accuracy but it requires specialized skills and equipment, is more expensive, and can take days to get results depending on how busy test centers are. 16/

Antigen (rapid) tests have a much higher limit of detection but this also corresponds to around the point that people become infectious so the window of detection lets you know if someone is infected and likely infectious at the time of a positive result. 17/

Results are available in 15 minutes and can be done by people at home, they are cheaper, and can be manufactured at a large scale. 18/

RATs being less sensitive, a negative result from a rapid test could mean you are either not infected, you could be infected but the viral load is not yet high enough to detect or already past the point of infectiousness and below the level of detection again. 19/

If you are using a rapid test for screening before going to work, school, or a gathering, you should use it right before the event to see the most accurate view of your current state. 20/

Omicron replicates so quickly that even hours after your test it is possible the viral load could have increased enough for you to be infectious. Testing the night or day before does not provide you with an accurate picture of now. 21/

Antibody tests can help provide indirect evidence of an infection more than 2 weeks after symptom onset. It allows for late or retrospective diagnosis but may not be able to distinguish between immunity due to natural infection and from vaccination. 22/

Antibodies diminish over time as part of the immune system's design so waiting too long may not be able to detect a previous infection. 23/

Here is a thread on some real-world examples of how the new 5 day isolation rule may be a problem and release people from isolation who are still infectious (

https://twitter.com/jeffgilchrist/status/1476890240514146317

). 24/

There are some studies looking at the sensitivity of rapid tests with Omicron and the best place to swab now:

https://twitter.com/jeffgilchrist/status/1477282003733078016

25/