Monday, March 23, 2020

Conditions On the Front: The Clinical Lab Test for the COVID-19 Virus


Rodney Rohde is the head of the Clinical Laboratory Sciences department at Texas State University here in San Marcos.  His department is where people go to learn how to run the horrendously complicated tests that clinical labs do, such as the CDC 2019-novel coronavirus (2019-nCoV) real-time RT-PCR diagnostic panel.  That's the official name for the CDC's test for the coronavirus.  I wouldn't know even that unless Rodney had directed me to the CDC website, where you can download the entire 48-page instruction sheet for using the test.

This is no dip-the-stick-and-look-at-the-color test.  First you have to get the reagents, which were in short supply, and according to some reports, some early sets of test kits were defective.  (Some day, when everything goes back to the new normal, whatever that is, somebody will dig around and find out exactly what went wrong.  But not right now.)  Assuming you've got a good set of reagents, and a clean-room-quality lab that has been disinfected from any kind of biological stuff that could contaminate the phenomenally sensitive test, and a 96-well cold plate at -20 C, and an Applied Biosystems 7500 Fast Dx Real-Time PCR System with SDS 1.4 software, and "molecular-grade water," whatever that is, and a bunch of gloves, gowns, pipette tips, centrifuges, and a lot of other expensive and delicate equipment, you can start doing the test—that is, if you know what you're doing, which means you have to have passed courses in Prof. Rohde's department or equivalent.  There are not that many of such trained people around.

A lot of these reagents have to be kept at -20 C or colder because the heart of the operation, the polymerase chain reaction (PCR) that doubles the number of virus-derived DNA molecules for every heating-cooling cycle, is temperature-sensitive. 

Imagine following an instruction sheet for assembling an IKEA table, directions for installing new software on your computer, and filling out your own long-form tax return all at once, while balancing a spoon on the end of your nose.  That's easy compared to running this test.  Of the 48 pages, 23 are the actual instructions of how to run the test, down to which button to press and where not to put the labels on the test vials.  Each sample produces some lines on a logarithmic graph that rise with each cycle of the doubling reaction.  A positive result is when two of the lines cross a threshold after 45 cycles.  Did I mention that each heating-cooling cycle takes several minutes and has to be controlled in temperature extremely closely, or else the whole thing screws up and you have to start over?  Once you've loaded the samples into the machine after doing a bunch of fiddly aliquot combining and dilutions and agitations, the machine runs for an hour and twenty minutes, and if you've done everything right, you get valid results.  But if one of the quality-control checks indicates contamination or some other problem, the whole set of tests has to be thrown out and you start over.

It takes a very particular type of person to do this fantastically complex yet repetitive stuff correctly day after day, week after week.  My friend Rodney is one such person, and we who are anxiously awaiting the next phase of this crisis should pause to thank every clinical lab worker who is doing this kind of job.  They are probably not pausing from work right now for anything except to eat or sleep every so often.  The amazing thing is not that the CDC sent out some defective kits early on, but that the whole complicated rigmarole ever works at all.  But it does, and many lives depend on how well, and how fast, and how many tests are done right in the coming days and weeks.

As others have said, the U. S. lost precious time in early February when the first COVID-19 cases showed up here.  The winner in this regard is South Korea, as The New Atlantis editor Ari Schulman points out in an editorial posted at that journal's website.  I can endorse his opinion, because what convinced me that the U. S. was basically flying blind in this crisis was a chart I found a week or so ago that described the number of COVID-19 tests administered per million population as of March 11.  The leader was South Korea, with I think several hundred per million.  The U. S. was about the lowest on the list, with only 23 per million population tested by then.  That meant we had no idea who had the disease, comparatively speaking.

Schulman says that the South Koreans never had to shut down their country, because they did three things early enough:  (1) They performed massive testing of both ill people and well people who thought they might have been exposed; (2) officials performed rigorous contact tracing to find the sources of the infection and tested them too; (3) infected persons were rigorously isolated until they recovered.  South Korea is now on the downhill side of their new-infection curve.  They continue to be highly vigilant, but life was never shut down there like it is being shut down here, and it looks like they won't have to do that at all.

We do, because, well, never mind why.  Recriminations are pointless.  Schulman's main point is that we need a definite criterion from our national leaders as to how we will know when we can ease up on the national shutdown.  Is it that new COVID-19 cases are decreasing?  That essentially no new cases are showing up?  Or what?  He's concerned that if the shutdown goes on indefinitely, a backlash will happen that could be worse than doing nothing.

In the meantime, you now have a wide choice of online church services to attend.  Prayer has never been more popular online. Some people are saying that this whole thing is going to be what unites us as a country again.  God has a way of doing good things with bad situations, and that would be a welcome outcome.  But first we have to get through it, and here's hoping and praying that those who are performing the critical testing can do their jobs rapidly and accurately, and that we use the test results to end the epidemic sooner rather than later.

Sources:  The official instruction sheet for the CDC test can be downloaded at https://www.cdc.gov/coronavirus/2019-ncov/lab/index.html.  Ari Schulman's editorial can be viewed at https://www.thenewatlantis.com/publications/whats-the-plan.  South Korea's downward new-case curve can be viewed at https://www.worldometers.info/coronavirus/country/south-korea/.  And I thank Rodney Rohde for replying to my query in the midst of his hurricane of a life right now. 

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