The CDC's Withdrawal of EUA for the RT-PCR Tests Does Not Mean the Test Failed Review

(AP Photo/Michael Conroy)

The CDC announced on July 21 that it would withdraw its request to the FDA for emergency use authorization (EUA) for the RT-PCR test. Many on social media are saying that the CDC is withdrawing the tests because they are inaccurate and asserting that this is proof of a “casedemic.” The notice is actually asking providers to transition to a test that returns results for COVID-19, influenza A, and influenza B (emphasis added):

In preparation for this change, CDC recommends clinical laboratories and testing sites that have been using the CDC 2019-nCoV RT-PCR assay select and begin their transition to another FDA-authorized COVID-19 test. CDC encourages laboratories to consider adoption of a multiplexed method that can facilitate detection and differentiation of SARS-CoV-2 and influenza viruses. Such assays can facilitate continued testing for both influenza and SARS-CoV-2 and can save both time and resources as we head into influenza season. Laboratories and testing sites should validate and verify their selected assay within their facility before beginning clinical testing.

The CDC’s multiplexed testing is still an RT-PCR test:

The CDC Influenza SARS-CoV-2 (Flu SC2) Multiplex Assay is a real-time reverse-transcription polymerase chain reaction (RT-PCR) test that detects and differentiates RNA from SARS-CoV-2, influenza A virus, and influenza B virus in upper or lower respiratory specimens. The assay provides a sensitive, nucleic-acid-based diagnostic tool for evaluation of specimens from patients in the acute phase of infection.

This notice is to prepare providers currently using the CDC’s RT-PCR test for when the agency voluntarily discontinues this specific test on December 31, 2021. If this were an admission that the test is fundamentally flawed, the CDC would have withdrawn it immediately. There is absolutely no indication that the decision to cancel the request for an extension of the current Emergency Use Authorization (EUA) is because the test failed a review by the FDA.

The FDA still has EUAs for other manufacturers’ RT-PCR tests. In order to receive that authorization, many of the tests were validated against the CDC’s version. RT-PCR tests in and of themselves are not the issue. Healthcare providers have been using them for everything from HIV to the flu for years. The specific problems with the COVID-19 tests are high amplification and the way they were deployed—which were not the reasons cited for the discontinuation of the EUA.

Amplification is also called the cycle threshold (Ct). Last August, the New York Times reported that many labs were using a standard of 37-40 Ct to declare a test negative. Comments from Dr. Anthony Fauci and research on positive samples indicated that very few could replicate at or above a Ct of 35. if a virus can’t replicate, it cannot cause infection or be transmitted.

Further studies showed that the time from exposure also impacted the interpretation of results, so the test results needed more context than a simple positive or negative result. Does this mean there could have been false positives? Sure, but the scope of that problem will not be known without a detailed analysis. That is not what the CDC’s notice to providers is alerting them to and the EUAs for the tests validated against the CDC version are still in place.

The deployment problem involves most people being tested outside of a medical practice. They received a positive or negative result through an app or phone call from a lab or testing site and no one ever evaluated them for symptoms, exposure, or other important factors as recommended by the World Health Organization:

WHO reminds IVD users that disease prevalence alters the predictive value of test results; as disease prevalence decreases, the risk of false positive increases (2). This means that the probability that a person who has a positive result (SARS-CoV-2 detected) is truly infected with SARS-CoV-2 decreases as prevalence decreases, irrespective of the claimed specificity.

Most PCR assays are indicated as an aid for diagnosis, therefore, health care providers must consider any result in combination with timing of sampling, specimen type, assay specifics, clinical observations, patient history, confirmed status of any contacts, and epidemiological information.

Now that the CDC is recommending RT-PCR tests for differential diagnoses between different viruses, this may improve how we conduct tests and interpret them. This change should necessitate that the tests be done in a healthcare provider’s office because symptoms and clinical history matter, as the WHO noted. The NIH also has outpatient treatment recommendations for influenza and COVID-19 approved at some level by the FDA, which the current testing sites can’t provide.

For example, most medications to treat the flu need to be given within 72 hours of symptom onset. If you went to a testing site with no clinical evaluation, you would receive the test. If it is positive for the flu, you would need to get a separate appointment with a prescribing clinician to receive appropriate treatment with an anti-viral. The elapsed time could prevent you from receiving proper treatment.

A person may also test positive for more than one virus. This situation will require clinical judgment that the current testing site setup does not provide. For example, a person may take the combination test and test positive for COVID-19 with a Ct of 38 and influenza B with a Ct of 10 within 48 hours of becoming symptomatic. They have not lost their sense of taste or smell but have a productive cough, fever, and chills. The doctor knows he has seen an uptick in influenza B in the last three weeks locally and the patient has not had known contact with someone who tested positive for COVID-19.

In this case, a clinician would most likely treat the patient for influenza B and tell him to monitor for the common symptoms of COVID-19, like loss of smell, and return if they occur. In the current testing system, the patient may have gotten a result on a phone app that said they were positive for both viruses. A treating practitioner must evaluate the details and the patient’s condition for him to receive appropriate treatment.

The CDC asking providers to transition to multiplex tests is welcome news because it should bring doctors, nurse practitioners, and physician assistants back into testing, diagnosis, and treatment. This change should also result in better care for patients and refined interpretation of test results. But reading the CDC notice as an admission of complete RT-PCR testing failure is not correct.