SNOUT: Sensitivity of PCR testing for COVID-19

If you are a research scientist like myself, you already know what SNOUT means. For non-science people, SNOUT stands for: a sensitive test that rules the disease out. What does this mean in the current pandemic of COVID-19? First, if you can recall, COVID-19 has been named scientifically SARS-CoV-2. This means that the testing for presence of the virus can be extrapolated from the evidence in the scientific literature from SARS-CoV. Again, if you are a science nerd like me, you know that there are different ways to test for viruses. It might be by presence of antigens (tiny protein particles on the organism), antibodies (the immune response in an infected individual which tells you exposure), the presence of RNA (similar to DNA, found in viruses that only have RNA for their replication), or virus isolation. Now, don’t freak out, but the test for the RNA is not a highly sensitive test. The only reason I know this is because of my scientific background (I did a Master of Science that was research based, as well as being a Doctor of Veterinary Medicine). Most people do not have this information, but they need to be aware that a negative test for COVID-19 does not rule the disease out. Check out the CDC Fact Sheet for healthcare professionals here. I was trying to explain to my husband that although he was tested, and tested negative, it does not mean he was not exposed. The medical field in Toronto was in its early stages of learning about COVID-19. They only collected a nasal swab. No sputum or blood samples were collected. The one nasal swab likely went for PCR testing to look for presence of the viral RNA of COVID-19. Now, let’s look at some of the science of PCR testing in SARS-CoV. In the first 3 days of infection, only 80% of true positive individuals tested positive. Let me re-word that: of 100 people infected with SARS-CoV, only 80 people tested positive in the first 3 days of infection (based on "a real-time quantitative RT-PCR assay with a modified RNA extraction method"). 80% That leaves 20% of infected individuals with negative tests that are free to roam about and spread the virus. Now, let's look at some of the science currently being run regarding COVID-19 (SARS-CoV-2). Let's say, like my husband's sample, you get a nasal swab performed, and this sample is sent for RT-PCR testing. Based on the science, 63% of infected individuals that had only nasal swabs collected for testing of COVID-19 tested positive. Let's re-word that so everyone can understand: of 100 people infected, 63 people test positive. That leaves 37 people who test negative who are actually true positives. 37% percent of people who are now roaming free, thinking that they are negative. The media (and some members of the public) are scrutinizing our political leaders for either not having enough tests to go around, or for not testing everyone. Let's say we did have enough tests, and everyone got tested, then all the positive tests got quarantined and all the negative tests were allowed to roam freely going about their day like usual. Now we have 37% of the infected individuals roaming freely, going about their spring break antics, spreading the disease to their vulnerable friends and family members. Do you see where I am going with this? So who do these positive tests help? The individuals who are sick and need urgent care, and the medical professionals that are caring for them. Now, however, even in the event of the lack of a positive test, the very ill folks with severe respiratory disease will be treated as if they have COVID-19. Even with newer more efficient scientific methods of RNA extraction, there will always be a limit of detection. There needs to be a minimum number of RNA strands in the sample that is collected, in order to actually detect its presence using RT-PCR. These are the reasons why not everyone needs to be tested: the limits of detection in a subclinical or non-clinical individual, and the limits of the low sensitivity of the RT-PCR test. Now back to my husband. He only had a nasal swab. No sputum and no blood sample. He tested negative. He is in quarantine. He is working from home. He's making sure that if I don't have to go to work, that I stay in the condo. But that being said, I am still working, though with restricted hours. Remember, that while veterinarians are a non-essential service, we can only safely assist you with your fur-babies if you abide by our social distancing protocols. We have a right to protect ourselves, and our staff, as well as the family we go home to, even if you feel like it is not as serious as we are making it out to be, or if you feel like you are invincible. So please listen to the public health officials who have years of experience in epidemiology. Please. Stay home. If you have to go out for groceries, keep your distance, wash your hands. If you are not feeling well, have a neighbour, friend or family member run errands for you. If you have a cold or other illness, you are vulnerable. You are at a higher risk already. Yes, this will pass, but let's try to do our part to help flatten the curve. Edit March 22, 2020: go here to understand more about samples and testing. Edit March 28, 2020: go here for information on serological testing. Edit March 30, 2020: In today's briefing, Dr. Theresa Tam, Canada's Chief Public Health Officer, mentioned that yes, Canada's RT-PCR testing has been validated, but to keep in mind that if you test too earlier, and how well you swab the person also play a role. But Ontario isn't testing a lot of people compared to other provinces. Canada is however performing one of the highest numbers of tests per capita in the world (since we have a smaller population size). Dr. Tam discussed new methods of testing that is being validated at the National Microbiology Laboratory. This may come soon. For more on validation of the RT-PCR head here.

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