Testing, Testing…

Sometimes during a pandemic a good place to be is down a rabbit hole — like the one I went down trying to understand how testing for the virus that causes COVID-19 is done and how it’s being handled here in our province.

Let’s start with the basics, which you probably all know by now, but which are somehow reassuring to recite — like a science-based rosary.

 

SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus. Coronaviruses are a large family of viruses named for their distinctive structure — they are covered in crown-like spikes which can only be seen under a microscope. (Corona means “crown” in Latin and also in Spanish, which explains the logo of a popular brand of Mexican beer WHICH HAS NOTHING TO DO WITH THE VIRUS.)

The coronavirus family, like most families, includes some members who are relatively benign — like the common cold — and others who are more sinister. Coronaviruses can also infect animals and the more sinister members of the family start as animal viruses but end up infecting humans. These are rare, but scientists nevertheless have a word for them, “zoonotic.” Severe acute respiratory disease (SARS), which hit Toronto so hard in 2003, was a zoonotic infection (in 2017, Chinese scientists traced it to horseshoe bats and believe it passed to humans via an intermediary mammal, civets.)

As Dr. Robert Garry, a virologist at Tulane University in New Orleans, explains in this video clip, his team believes SARS-CoV-2 is a “recombinant” zoonotic virus — one created by a combination of viruses from two different animal species (possibly bats and pangolins — “scaly anteaters” native to Asia and Sub-Saharan Africa.) Garry says we don’t know how long the resulting virus has been in humans, “it could be just a few months, it could be years, it could be decades” but at some point in its journey it mutated in a way that “allowed it to spread more rapidly.”

 

Listening to Garry I realized that a calm, recitation of the facts about SARS-CoV-2 also serves a secondary purpose: displacing a lot of the nonsense. For example, Garry himself feels the need to say that this virus is naturally occurring and not a lab-generated weapon of biological warfare.

The world first became aware of SARS-CoV-2 when it caused an outbreak of an acute respiratory disease in Wuhan China in December 2019. The virus was identified by Chinese scientists and the World Health Organization (WHO) named the disease it caused COVID-19 — (CO) virus (VI) disease (D) and 19 for 2019, the year it was discovered. It does not stand for the “19th” “Chinese Virus” and if you were under the impression it did, you really need to re-evaluate your news sources. (Also, while we’re on the subject of bad COVID-19 information I just want to point out that the WHO actually felt the need to warn people that “smoking” is not an effective measure against it.)

 

Containment

WHO declared COVID-19 a pandemic on March 11.

Pandemic, it turns out, is not all that exact a term. Merriam-Webster defines it as “an outbreak of disease that occurs over a wide geographic area and affects an exceptionally high proportion of the population.”

Neither “a wide geographic area nor “an exceptionally high proportion of the population” is a particularly precise measure, but I think even were the definition more precise, what is happening with COVID-19 would meet it and the WHO was fully justified in its use of flashing light emojis:

As I write (it’s Tuesday), Nova Scotia has performed 2,525 COVID-19 tests, 51 of which have come back positive. There has yet to be any — proven — community transmission in Nova Scotia, but in a recent interview with the Halifax Examiner’s Tim Bousquet, Jason LeBlanc, director of Virology, Immunology and Molecular Microbiology at the Nova Scotia Health Authority (NSHA), said we should all behave as if there has been. We’re not going to contain or stop the virus at this point — certainly not by testing — so our only hope is to slow its progress and avoid overwhelming our health system.

This echoed something I heard on The Daily, the New York Times podcast, from one of the paper’s science and health reporters, Donald G. McNeil Jr. Asked if there were any way the US could replicate South Korea’s success in containing the virus, McNeil said:

Well, we could do that here, if we had a time machine and we could travel back in time to about January 20, because January 15 is when we know one of the first cases arrived in the United States and started spreading – that was the case in Washington. The idea that we could try to start cracking down now, when we have over 40,000 cases and 500 deaths, it’s just utterly impossible, it’s not close to anything that South Korea faced. I mean, South Korea, they were doing this kind of crackdown when they first saw cases arriving, before there was a single death.

The date for us would have been sometime shortly after January 27, when the first COVID-19 case was identified in Toronto.

So no, testing is not the answer. The answer, for those of us who do not have the virus (or have it and are asymptomatic or have it and will develop symptoms next week) is social distancing if we must be out and self-isolation as much as possible and good hygiene (wash those hands, clean those surfaces).

Now that we’ve established that testing is not going to stop the spread of the virus, I’m going back down my rabbit hole, because the testing process is interesting.

 

Up your nose

Here in Nova Scotia, according to the protocols posted on the provincial website as I write, if you have traveled outside of the province, you must self-isolate for 14 days whether you experience symptoms or not. If you develop a fever and/or new cough, you should call 811.

If you have not traveled outside of Nova Scotia and you develop what seem like COVID-19 symptoms, you should first do an on-line self-assessment and then, if it is indicated, you should call 811. (If you are so ill that you have to go to an emergency room, LeBlanc says you will be tested for COVID-19 there, but everyone should not go to an emergency room.)

Bousquet asked LeBlanc about concerns that it was impossible to get through on the 811 line and LeBlanc said it was his understanding that more staff had been brought on to handle call volumes. (In fact, on March 18, the province announced it was bringing in retired “and other” nurses to assist with 811 staffing. I don’t know if wait times have lessened since then and I cannot call to check because that would be irresponsible.)

If the 811 nurse decides you need to be tested, you will be sent to your nearest COVID-19 Assessment Centre. As I write, there are 15 listed on the NSHA website — including three on Cape Breton Island.

Bousquet also asked LeBlanc about concerns the virus could be spread at these assessment centers and LeBlanc said that these are dedicated areas and well controlled environments and while you can’t control everything, staff do all they can to limit the spread of the virus.

If you are tested, LeBlanc says there are two ways it might be done. The first is by means of a nasopharyngeal (NP) swab, which will be stuck up your nose so far it touches the back of your mouth and “given a little twist.” (You will feel some discomfort, your eyes may water, but it will be nothing you can’t handle, I know you). The swab is  then pulled out and placed in a stabilizing liquid in a “viral transport” tube.

The other alternative is a nose/throat combo swab — the same swab goes not so far up your nose but also down your throat.

You can watch a CBC reporter get her nose swabbed here, making the kind of sacrifice that reminds me why I chose print over broadcast journalism:

 

LeBlanc noted something I’ve heard from a number of sources since I started researching the COVID-19 test, which is that it should be done after the onset of illness — soon after, but after. LeBlanc said that’s because a test done too early might return a false negative and give the patient an equally false sense of security. (This is why testing everyone getting off an airplane isn’t necessarily effective.)

Okay, we can’t just stand here with our viral samples — we have to get them to the lab. LeBlanc didn’t discuss how samples taken in Yarmouth or Cape Breton are transported to Halifax, but the transportation of SARS-CoV-19 specimens is subject to the Transportation of Dangerous Goods Regulations and there are a raft of requirements for shippers transporting infectious substances.

 

Lab work

Here in Nova Scotia, the lab is the QEII Health Sciences Centre’s Microbiology Lab, which does all the testing for the province.

Initially, it could only determine negatives and was required to send positives to the National Microbiology Lab in Winnipeg for confirmation (although Public Health acted on the positives without waiting for confirmation because really, it had nothing to lose and everything to gain by doing so). The story of how the lab became certified to confirm both negative and positive tests, which it has been since March 22, is interesting — but you have to listen to Tim’s interview to hear it.

You can watch the entire testing process in this video produced by the NSHA. Be warned, the first half is entirely silent — this is not because lab workers are required to take a vow of silence, but rather, because it is “B” roll for broadcast use (in fact, I’ll bet you’ve already seen these pictures on the local news). Charles Heinstein (“Pronounced like Einstein”), technical manager of the lab, breaks the silence at the 16:30 mark, answering questions from unseen reporters.

Workers at QEII Health Sciences Microbiology Lab

Still from NSHA video

In the lab, the first step is boring and time-consuming (but vitally important) administrative work: namely, entering all the information about the patient that has arrived with the sample tube label into the hospital’s computer system. LeBlanc said this stage of the testing process was slowing them down at first, but they’ve added additional staff to handle it.

Next, some of the sample is extracted for testing.

The virus lives in the respiratory cells found in the mucus in your nose or throat (which is why you can spread it by sneezing or coughing or blowing your nose). Taking over cells and forcing them to do its bidding is a virus’ only purpose in life:

Viruses only exist to make more viruses. The virus particle attaches to the host cell before penetrating it. The virus then uses the host cell’s machinery to replicate its own genetic material. Once replication has been completed the virus particles leave the host by either budding or bursting out of the cell (lysis).

The virus particles burst out of the host cell into the extracellular space resulting in the death of the host cell. Once the virus has escaped from the host cell it is ready to enter a new cell and multiply.

Viruses basically sound like comic book villains, but like comic book villains, the SARS-CoV-2 virus has a weak spot: it can be destroyed by soap. (“Soap Man” seems like an unlikely superhero but who knows? If we make it through this, soap may finally get its due).

There’s a very good graphic feature in the New York Times showing how the SARS-CoV-2 coronavirus “hijacks” cells and it explains the power of soap this way:

 The virus is enveloped in a bubble of oily lipid molecules, which falls apart on contact with soap.

 

Amplification

But let’s assume the virus did not get destroyed by Captain Camay (okay, sorry, I’m clearly not the person who should be turning soap into a superhero). If it penetrated the cell and began replicating its own genetic material, that material will show up in the lab test done at the QEII Health Sciences Centre Microbiology Laboratory.

The researchers know what they’re looking for because Chinese scientists sequenced the virus’ genome and made it public weeks ago. (That genome is less than 30,000 genetic “letters” compared to ours, which is over 3 billion.)

The samples collected from patients contain only a very small amount of that genetic material, so it must be replicated or “amplified” to be seen. According to LeBlanc, the lab uses one instrument to extract the virus’ genetic material and then a second instrument (a thermocycler) to amplify it, basically, to cause it to replicate itself multiple times. The results can be visualized using “a special detector.” This clip from a Minnesota CBS affiliate gives a nice summary of the process — right down to the disposal of the samples after testing (they’re sterilized and thrown away):

LeBlanc says the entire process takes about half a day and the results are sent to the physician who collected the swab and, in the case of a positive result, either to infection control in the hospital or and to Public Health (which is tracking the testing on its website.)

 

Bottlenecks

Prior to the COVID-19 crisis, LeBlanc said his lab was testing about 150 specimens per week. Since testing for COVID-19 began, they have been averaging over 200 per day and on Tuesday, the province announced it was “doubling” lab capacity to “accommodate increased testing.”

Dr. Robert Strang, Nova Scotia’s chief medical officer of health, said public health can now do 400 tests per day and was looking to increase that number should it be necessary.

Public Health is now widening the scope of its testing to include people who have had close contact with confirmed COVID-19 cases and people who have been admitted to hospital with severe symptoms consistent with the virus.

As noted above, the QEII Health Sciences Centre Microbiology Lab has increased its staff to deal with the data entry aspect of the process and LeBlanc says the lab is located in a building where there are other people with “molecular skills” who are able to assist with the COVID-19 testing.

Swabs were initially a problem, he says, but they have been able to dip into the supply used for the roughly 45,000 chlamydia and gonorrhea tests done in this province each year. (TMI, I know.) Still, the companies producing the swabs the WHO has deemed the most suitable for COVID-19 testing are “straining to keep up with demand,” according to NPR and some US states are reporting shortages.

The machines themselves obviously have limitations, but it sounds like the lab has been able to purchase additional equipment, as LeBlanc told Bousquet:

To tell you the truth, money hasn’t been an issue for us. There’s been a steady stream of support from NSHA, from the province, from the Public Health Agency of Canada supporting our needs for all the reagents, all the consumables, all the instrumentation that is required to do this testing.

But watching what is happening in the rest of the country — and the world — suggests there could be other shortages on the horizon here in Nova Scotia.

Ontario, for example, is facing a medical supply shortage, and the list of items Premier Doug Ford is asking local manufacturers to help supply is alarmingly extensive: “ventilators, face masks, surgical gowns, protective eyeware, hand sanitizer, medical gloves, swabs, disinfecting wipes and lab-testing equipment.”

Many of those supplies are necessary to the testing process — as you can see from the QEII microbiology laboratory footage, researchers wear protective covering like gloves and eyeware.

Then there’s the question of reagent shortages, which are currently posing a worldwide problem as countries try to follow the World Health Organization’s exhortation to “Test, test, test.”

The Globe and Mail reported on Wednesday that a shortage of reagents is behind Ontario’s “huge” testing backlog while Manitoba’s provincial lab is “working on a solution” that may involve “manufacturing its own reagents.” Alberta’s provincial lab is getting its reagents from Agriculture Canada. (The article does not explore the situation east of Ontario which could either mean we are not facing a shortage or the Globe and Mail has once again forgotten we exist.)

But in provinces that have acknowledged shortages, the response is to prioritize testing, something Nova Scotia is clearly doing already.

LeBlanc says testing everyone is not possible in a population the size of Nova Scotia’s which is why the province is so focused on enforcing social distancing and self isolation.

We are basically being asked to assume that everyone is infected and behave accordingly — stay six feet (two meters) away from people when you undertake essential errands like grocery shopping or you are out for a walk around your block — self isolate if you have traveled, or have been in contact with someone who traveled or feel unwell.

Clean surfaces regularly.

And wash your hands. Wash them often.

Because SOAP may save the day.