The Testing Mess

I have not written much about testing since the early days of this crisis, because there is almost no reliable information.  The Infectious Diseases Society of America issued recommendations about testing two days ago, yet the authors admit that their advice is almost evidence-free. So, this is all I can say reliably at this time.

1.  A fabulous review article describing many aspects of SARS-1, written by scientists from Hong Kong, discusses the testing issues for SARS-1.  Sensitivity of PCR at best was 80%.  Repeat tests are necessary to demonstrate lack of infectiousness.  I highly recommend this article for concise but detailed background material on SARS-1, as no compilation like this exists yet for SARS-2, and they are extremely similar viruses.

2.  CDC decided in January it would develop a nasal swab PCR COVID test and that no one else could market COVID tests in the US.  It failed to create a usable test, so on Feb 29 FDA said others could apply to FDA for an emergency use authorization (EUA) for their tests.  But their EUA process was very cumbersome, so few applied.  Until March 16, only 4 EUAs had been issued, including the EUA for CDC's failed test.  

Still lacking testing, FDA on March 16 said that anyone could offer COVID tests in the US, and apply later for FDA approval. Between then and now, over 100 companies poured into the testing market, and FDA issued 65 emergency use approvals for both PCR and antibody tests.  These were approved on an emergency basis, and do not reflect a guarantee by FDA of test validity.  

Beginning March 31, FDA also approved tests that had been developed by 24 university and commercial labs, but only if they were performed on-site at the lab that developed them. 

On May 4, FDA issued new guidelines which will attempt to bring some order into this chaos.

3.  Antibody tests measure antibodies but do not necessarily identify immunity.  As in Lyme disease:  you may have antibodies but are still susceptible to another infection.  Or, you may have Lyme disease but are not making enough antibody to detect with existing tests, even after weeks or months.  

It is a lot more important to determine if you are immune, than to determine if you just have antibodies.  I will wait to spend my money on tests that have been shown to indicate immunity to SARS-2, as well as an antibody, if and when they become available.

4.  PCR (aka "molecular") tests look for a small portion of the virus, generally in your nasopharynx.  This is not a culture test for the virus, and does not absolutely guarantee that you have active infection and are contagious--but it is the closest we can come to diagnosing active infection in a medical lab, as a culture must be performed in a high-containment BSL-3 biosafety lab, by law.  

We don't know how sensitive nor specific each of the many available tests are, but in China the rule was to perform multiple tests before releasing people from quarantine.  We should expect false negatives, which can also result from sampling error.  Here is what the FDA says about negative results, indicating they too are concerned about false negatives:

What does it mean if the specimen tests negative for the virus that causes COVID-19? 

A negative test result for this test means that SARS CoV-2 RNA was not present in the specimen above the limit of detection. However, a negative result does not rule out COVID-19 and should not be used as the sole basis for treatment or patient management decisions. A negative result does not exclude the possibility of COVID-19. When diagnostic testing is negative, the possibility of a false negative result should be considered in the context of a patient’s recent exposures and the presence of clinical signs and symptoms consistent with COVID-19. The possibility of a false negative result should especially be considered if the patient’s recent exposures or clinical presentation indicate that COVID19 is likely, and diagnostic tests for other causes of illness (e.g., other respiratory illness) are negative. If COVID-19 is still suspected based on exposure history together with other clinical findings, re-testing should be considered by healthcare providers in consultation with public health authorities. 

Risks to a patient of a false negative include: delayed or lack of supportive treatment, lack of monitoring of infected individuals and their household or other close contacts for symptoms resulting in increased risk of spread of COVID-19 within the community, or other unintended adverse events.

5.  What concerns me as much as unreliable tests, however, is an unreliable supply of testing machines and supplies.  I want to know that FDA is identifying the best tests, and that the government is adequately stockpiling the materials needed to perform them, in the event of a massive "second wave" of illness.  Since we still lack sufficient supplies to test everyone suspected of COVID now, what plans are being put in place for a potentially much worse situation ahead?  The media should report on this.  

In Maine, state government has just announced a partnership with local animal lab testing company IDEXX to triple available COVID tests.  

It should be of interest to all that our federal government has spent roughly $100 billion dollars on pandemic and bioterrorism preparedness since 9/11, including the creation of a National Strategic Stockpile worth $7 billion, but when the emergency arrived, the federal government told the states they were on their own to obtain most of the PPE, ventilators and tests needed.  What an abject negation of responsibility!  The feds have a lot more bargaining power than individual states do, plus they have a massive contracting infrastructure that knows the suppliers and how to get things done.

Maybe when tax day comes the fat check should be going to the state, while we starve the federal infrastructure that so grossly failed us.