All About Testing

There are 3 kinds of tests for SARS-CoV-2 under the FDA’s Emergency Use Authorization (EUA): Molecular, Antibody, and Antigen testing.

Molecular test — RT-PCR (Reverse transcription polymerase chain reaction): This is a molecular in vitro diagnostic test that identifies the presence of virus in the body through collection of nasopharyngeal, oropharyngeal, or other respiratory specimens by swabbing.

A false-negative result may occur if:

    • a specimen is improperly collected, transported or handled
    • inhibitors are present in the specimen
    • there are too few virus particles present in the specimen.

Detecting the presence of the virus doesn’t indicate whether or not someone is infectious.

A single negative result does not mean you can skip social distancing or stop wearing a mask.

A negative test result only means that you didn’t have COVID-19 at the time of testing. It’s possible your sample was collected too early in your infection.

You could also be exposed to COVID-19 after the test and then get infected and spread the virus to others.

If you develop symptoms later, you may need another test to determine if you are infected with the virus that causes COVID-19.

Antibody Test — Serology: Blood test with a turn-around time of typically same day, but sometimes can take a couple days. Serology is especially important because it may detect previous infections in people who had few or no symptoms.

Antibodies are proteins made by the immune system in response to a foreign substance (called an antigen). Each antibody recognizes a small portion of a single antigen (antibody specificity) so an antibody that recognizes the virus that causes chickenpox will not recognize the virus that causes measles.

There are 5 different types, or classes, of antibody: IgG, IgM, IgA, IgE, and IgD. Most rapid novel coronavirus tests look for IgG and IgM. After an infection, your body starts to produce IgM antibodies first, which can be detected after about a week and hang around for a couple weeks after your symptoms start. IgG antibodies are part of your immune system’s long-term arsenal, detected after 2 weeks from the start of symptoms, peaking around 30 days, and hang out for months or even years after you recover.

IgM antibodies: Produced first, detected ~ 1 week after start of symptoms. Because it is only detectable for a couple weeks, it is used to determine recent infection.

IgG antibodies: Produced later, detected ~ 2 weeks after start of symptoms. Because it can be detected for months or years after infection recovery , it is used to determine past infection.

cov-2-immune-response-timeline.001

In general, there are two kinds of antibody test methods: binding antibody or neutralizing antibody tests.

Binding antibody tests: These tests use purified proteins of SARS-CoV-2, not live virus, and can be performed in lower biosafety level laboratories (e.g., BSL-2).

Point-of-care (POC) tests usually use lateral flow to detect IgG, IgG and IgM, or total antibody in whole blood, serum, plasma, and/or saliva. A common example of a lateral flow device is a home pregnancy test. Some point-of-care tests can be performed on blood collected from a fingerstick rather than a blood draw.

Laboratory tests typically use ELISA (enzyme-linked immunosorbent assay) or CIA (chemiluminescent immunoassay) to detect IgG, IgM, and IgA antibodies, either individually or as total antibody.

Neutralizing antibody tests: As of July 2020, the FDA has not authorized the use of neutralization tests for SARS-CoV-2 yet.  In this test, a serum or plasma sample is infected with live virus in a test tube to determine if the antibodies are functionally capable of preventing infection.  Because this method involves the live virus, it requires a higher biosafety level (BSL-3 or BSL-2 laboratory).

Virus neutralization tests (VNT): Here, the SARS-CoV-2 virus comes from a clinical isolate or is modified for the assay. This testing must be done in a BSL-3 laboratory and can take up to 5 days.

Pseudovirus neutralization tests (pVNT): This test uses a non-SARS-CoV-2 modified virus (e.g. vesicular stomatitis virus, VSV) that has a piece of protein from SARS-CoV-2 attached to it. This testing can be performed in a BSL-2 laboratory, depending on the particular strain.

Unfortunately, just because we can detect them doesn’t automatically mean that they can provide immunity/protection from reinfection.

Antibody testing results shouldn’t be used to decide if someone can return to work. It also shouldn’t be used to group people together in settings such as schools, dormitories, and correctional facilities that increase the risk of transmission.

Antigen test — Rapid: Rapid diagnostic test with a turn-around time of less than one hour. Antigen tests look for specific proteins on the surface of the virus and can diagnose an active infection.

Unlike antibody tests that detect your immune system’s response to the virus, antigen tests detect viral proteins directly. The two major antigenic targets of of the SARS-CoV-2 virus are the spike glycoprotein (S) and the nucleocapsid phosphoprotein (N).

Depending on the complexity of the method, these tests can be performed in <30 minutes or may take a couple of hours. 


Have general questions? Comments?

Email asktheoptimisticscientist@gmail.com or comment below!

Resources/Further Reading

Interim Guidelines for COVID-19 Antibody Testing (CDC, updated 8/1/2020)

Great Video Explanation of Antibodies & Serology Tests (Beckman Coulter, 5/22/2020)

Incubation vs Infectious Period

Incubation Period: The time from when someone is infected to when symptoms develop. Based on existing evidence-based research, the incubation period of SARS-CoV-2 and other coronaviruses (e.g. MERS-CoV, SARS-CoV) ranges from 2–14 days. 50% of people will become ill 5 days after infection.

Infectious Period: The time when an infected person, who may not be showing symptoms, can transmit the virus to others. While it varies from person to person, it is typically ~ 7 days.

Begins: 

2 days before the start of signs/symptoms

Ends:

  1. 10+ days after illness onset and
  2. symptoms are improving and
  3. there has been no fever within the past 24 hours (without anti-pyretic medications).

Some immunocompromised individuals or those with severe COVID-19 may shed the virus for 20 days.

For asymptomatic individuals, it is more difficult to define their infectious period.

Updated CDC Isolation Guidelines

Yesterday, the CDC updated their recommendations regarding when someone can end their isolation. The following changes have been made to the guidance with regards to the duration that a person should be fever-free before they may leave isolation:

Prior guidance:

An infected person must isolate for at least 10 days after onset of symptoms, and may be released from isolation if their symptoms have improved AND they have had no fever, without the use of medicines, for at least 3 days

New guidance:

An infected person must isolate for at least 10 days after onset of symptoms, and may be released from isolation if their symptoms have improved AND they have had no fever, without the use of medicines for at least 24 hours. 

Surface Survival of SARS-CoV-2

Seriously, how long can this thing survive on surfaces?

In an earlier post, I referenced some preliminary research suggesting that SARS-CoV-2, the virus that causes COVID-19, can live in the air and on surfaces between several hours and several days. This work, originally released as a pre-print and recently finalized and published in the New England Journal of Medicine, found the virus is viable for up to 4 hours on copper, 24 hours on cardboard, 48 hours on stainless steel, 72 hours on plastics, and is also detectable in the air for 3 hours. 

A lot of posts present this information out of context and headlines can make it sound frightening, “SARS-CoV-2 Lives on Plastic for 72 Hours!!!” However, what’s more important is the amount of virus that’s still alive. It’s <0.1% of what the investigators started with. So, infection is theoretically possible but extremely unlikely at the levels they saw after a few days. 

Another important thing to mention lies in the experimental design of the aerosol component of the study. It has some caveats. They found that the virus can be detected in the air for 3 hours in the lab. However, in nature, respiratory droplets fall to the ground at a faster speed than the aerosols generated in their experiments. This is because the lab-generated aerosols are smaller (<5 μm) than what is produced from a cough or sneeze, so they remain in the air at face-height longer than the natural, heavier particles. It’s not a perfect comparison (though science rarely is, we just do our best). The size of these particles can affect how they move through the air and how they impact a surface. 

So, at the end of the day you’re more likely to become infected through the air if you’re next to an infected person versus a contaminated surface. Make sure you clean surfaces with disinfectant or soap – they work because they disturb the oily external layer of the virus keeping it from infecting your cells. 

The Optimistic Scientist

“Writing organizes and clarifies our thoughts. Writing is how we think our way into a subject and make it our own. Writing enables us to find out what we know—and what we don’t know—about whatever we’re trying to learn.”
William Zinsser, Writing to Learn: How to Write–And Think–Clearly about Any Subject at All

Thanks for joining me!

The Optimistic Scientist was born out of a desire to apply my favorite aspects of being a bench scientist – pursuing new information to be applied to today’s therapies with an OCD level of attention to detail – to my thirst for creativity, writing, and education. I needed a place where I could respond to today’s headlines and comment on the technical design of an experiment and its claims, in a way that current media is sorely lacking.

I’ve always cast a wide net when it comes to what areas of science interest me. My passion isn’t limited to a single scope, although the combination of skills and techniques I’ve acquired over the years in research has somewhat eloquently led me to cancer immunotherapy. At the end of the day, I just really like learning. I love reading articles and finding textbooks on topics I know nothing about, and I like following those rabbit holes of “Why?” , “How?” and “What if?” from something I’ve read online or see on television. If you ask my friends, I’m frequently responding to our lives with, “That’s not how that works” when a sci-fi movie tries to haphazardly toss in a fancy gene name to explain some mystical phenomenon. My best friend will say I am impossible to watch medical dramas with. (If I see one more doctor wheel their patient to the MRI suite and then run the MRI, I’m going to throw something at the TV). I like to learn more (have I mentioned I like learning?) about what I don’t know, and I’m not a fan of seeing science or medicine misrepresented in films, television or news sources.

Beyond what you see in films or television, social media has drastically changed the way we communicate and receive news. We’re bombarded with information that requires us to determine its validity. I want to help non-scientists navigate new findings and help encourage people to look at every outrageous headline with a healthy dose of skepticism. Too much skepticism though isn’t great either, so that’s where the optimism comes in. We need to be critical about what information we trust and who we’re trusting to teach us what we don’t know. Everyone benefits when we remain open-minded and skeptical by not blindly sharing every new “article” published that claims the exact opposite health benefits of what you were told last month. However, we can lose sight of the good in the world if we let ourselves drown in all the crap that’s out there. Climate change is real folks, but I’m optimistic we’ll figure something out. Our current political landscape is a nightmare, but I remain optimistic that it won’t be like this forever.

So I invite you to walk with me, ask me all the science questions you’ve ever had but never found answers to, send me an article you want explained, whatever and I’ll do my best to critique and clarify what’s presented. We can all learn a bit more together about the world around us.

Friendly reminder in the form of a comic – alternative facts are not welcome. This is a place for science not anecdotal evidence presented as law. I welcome your input about what to investigate and I welcome intelligent discourse, but just like all those yard signs, hate has no home here. So please keep that in mind before you hit enter.

six nine opinions

So! With that in mind, what is something you’ve seen in the news that you want some answers about? Shoot me an email at asktheoptimisticscientist@gmail.com!

Making lemonade out of lemons since the late 1980’s,

The Optimistic Scientist