The Next (Predicable) Test SNAFU

Testing is key and it is expanding in the US and our community — finally! However, I believe that we need to integrate a “suspect” or clinical case definition as part of Influenza-like Illness (ILI) and COVID-19 surveillance. We want to track and trace all possible cases. (https://onesalud.com/2020/04/07/make-sure-everyone-counts-change-the-way-we-define-covid-19/). Until we are responding to clinical COVID-19 and testing all contacts we will be hobbled in epidemic control and, importantly, we invalidate the experiences of people in the community. The clinical diagnosis of a suspect COVID-19 case allows public health interventions to be initiated and to be systematic.

Testing is key however, regrettably, the test used for diagnosis of the virus (RT-PCR that picks up viral nucleic acid) is not as good as we wish. Based on data from China, Italy, and the US it appears that 30% of persons with COVID-19 are “false negatives”.  Every laboratory test has problems with “sensitivity” and this particular test is a bit worse than some other tests in that regard. Thus, it is estimated that the test picks up 70% of people with COVID-19 and misses at least 30%. These misses may be because collecting the specimens is difficult and sometimes the swab will miss the virus.  In addition, if the test is done early in the disease or late in the course of illness there may be fewer viruses in the naso-pharynx (way back in the nose and throat). (See photo at top) These realities mean that a person may have COVID-19 but test negative. In fact you can have a person test negative then on re-test have a positive result. This uncertainty is frustrating but it is not uncommon. It does not mean that someone is re-infected. These tests are picking up bits of viral RNA and often those traces of virus are detectable for a while and sometimes may simply mean specimen contamination.  It does not absolutely mean that a person is contagious still however, more work is needed.

In the Journal of the American Medical Association published May 6, 2020 there is a valuable contribution about testing that provides a useful timeline of diagnostic markers for detection of COVID-19 (Figure above)
https://jamanetwork.com/journals/jama/fullarticle/2765837

In a quote from the article “In a study of 205 patients with confirmed COVID-19 infection, RT-PCR positivity was highest in bronchoalveolar lavage specimens (93%), followed by sputum (72%), nasal swab (63%), and pharyngeal swab (32%).5 False-negative results mainly occurred due to inappropriate timing of sample collection in relation to illness onset and deficiency in sampling technique, especially of nasopharyngeal swabs. Specificity of most of the RT-PCR tests is 100% because the primer design is specific to the genome sequence of SARS-CoV-2. Occasional false positive results may occur due to technical errors and reagent contamination.”

Testing is key. It is another storm on our horizon as we try to discern who actually needs to be isolated and quarantined and when those periods can end. There are many decisions that need support from reliable and valid testing. What will happen as we are trying to stringently control the flares of COVID-19 in the community is that the test performance will bedevil us. This is an area where technological innovation will be welcome!

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