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COVID-19: Sample Collection and New Testing Methods

Updated: Mar 23, 2020

It's difficult to judge from my tiny condo as to how many people are taking the lock down seriously. As my husband notes, we can see people gathering outside in groups that are larger than immediate families. The sun has been out for these past two days in Toronto, and people have been out. We lost power yesterday and drove out to get drive-thru lunch. We saw people chatting through car door windows, then the same gentlemen outside one car moved to chatting with a family in another vehicle, less than 6 feet from the window. People in Canada (and the U.S.) are so used to their freedom, that if the government tells them they should be staying home, a lot of people aren't listening.

A friend of mine is from Singapore, and she wonders why can't Canadians implement what Korea and Singapore has done. If you have a half-hour to spare, feel free to take a read of this one. The brief message is: test everyone, test positives get quarantined and traced to every individual that they came into contact with, and those people also get quarantined.

Now the rebuttal. As I already mentioned, I am speaking from personal experience through my husband's experience, there is (or was) a lack of knowledge by the medical professionals about how to even collect an appropriate sample for RT-PCR. The public health officials are great. But I am talking front-line nurses and doctors that are at your local walk-in clinic, and then the hospital my husband was referred to for collection of a sample.

It's not to say we cannot implement wide spread testing, which is what South Korea has done to reduce their R value (number of people that an infected individual passes the disease on to).

Image adapted from Our World in Data

We do however need to buy some time. We need time to train the medical professionals and recruit laboratories. Currently, RT-PCR is the standard testing practice for confirming cases of COVID-19. We have university laboratories (that we know are shut down right now) with the ability to run RT-PCR testing, as well as serology. Every university technician can be employed to do this. We need to properly train medical staff to collect appropriate samples for these tests, reducing the human error for negative results in true positives (increasing the sensitivity of the tests). There is a need of in-home point-of-care testing, which would improve self-isolation efforts.

Sample Collection for RT-PCR

First, you need to be able to collect enough viral RNA to be above the limit of detection for the RT-PCR testing to be effective. Let's say your medical staff is well trained in sample collection. As I already mentioned, one single nasal swab run for RT-PCR has a low sensitivity. Roughly 30% of true positives are missed, now free to wander, with a false sense of security, thinking they cannot infect other people.

Bronchoalveolar lavage (BAL) shows a 93% sensitivity, only 7% of true positives show a negative result. So why doesn't everyone get a BAL? If you are a veterinarian, you probably already know how to get a sample in your canine patient. The BAL requires bronchoscopy, taking an endoscopic tube with a camera into your airway, down into the bronchi, into the bronchioles and close to the alveoli, instilling a sterile saline solution to wash (lavage) the lower airway, then suctioning out this sample to use for testing. Sounds quick and easy right? At least in people, you can tell them to hold still while this is happening, but chances are it is much easier for the doctor to collect this sample while the person is sedated. Dogs are put under general anesthesia so that they don't move during the procedure. Most veterinary general practitioners do not have this expensive equipment called an endoscope. Referral veterinary practices with internal medicine specialists do. Human emergency and referral centers do, but not your local walk-in clinic or family doctor. Once that endoscopic tube goes into the airway of a person (or animal) it needs to be properly sterilized so that you do not pass any infectious organisms to the next patient. This process is time-consuming, and expensive.

Sputum samples (coughing up some mucous and spitting into a collection tube) has about a 73% sensitivity, leaving 27% of people falsely negative.

Fecal samples test positive in 29% of infected individuals. This is just another reason why you should thoroughly wash your hands after using the restroom, and before eating.

If we went with gold-standard approach to testing every person using BAL, likely the virus would have infected everyone by the time we got to testing everyone. We need another way. New laboratory testing is in the works as we type to increase the sensitivity of RT-PCR testing, increasing the detection of true positives, without increasing the costs. So, just hang in there while the scientists work on a solution for us.

Point-of-Care Testing

I introduced my mother to Google Scholar one day years ago, because I was asking her where the science was for some of the essential oils she was recommending to battle the influenza virus. We as veterinarians practice evidence-based medicine, similar to all western medical doctors. As one of my professors used to say, the plural of anecdote is not data. Some of the primary literature is hard to get because you pay for a subscription, but others are free.

A quick search online shows that research is currently being conducted to develop a point-of-care (we call them beside tests) to get results quicker, without the need of the infected individual to leave their home. Other research is occurring to not have crowds of people coming into testing centers, further spreading the disease. I guess we should all stay tuned.

Edit March 23, 2020:

In addition to developing better testing methods to identify affected individuals faster and safer, clinical trials are underway for both treatment using antiviral medications, and vaccines to amount the immune response necessary to fight the virus.

Edit at 12:30pm:

The FDA has disallowed testing from at-home collection kits for testing of COVID-19.

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