COVID-19: Update on Testing and New CDC Recommendations

The storm rages on in communities around the country. We’ve all seen that New York has been particularly hard hit. New Orleans is in the news in the wake of Mardi Gras. Here in Chicago the numbers of affected individuals keep rising. Yes, we have confirmed and unconfirmed cases in the Harper Health practice. None of our patients have come into contact with any of the providers here at Harper Health without fully donning personal protective equipment. (Dr. Meg hadn’t yet put on her head covering. Proper PPE is to have one on.)

Dr. Meg ready to get a sample

Based on some new research, the CDC released some revised recommendations on how we can prevent illness. For those who read our emails/blog posts, the recommendations won’t come as a surprise, nor should your behavior need to change much as a consequence.

What’s the new research and what are the new recommendations? Studies have recently confirmed that transmission is not uncommon between an infected person with no symptoms and a susceptible individual. This is called asymptomatic transmission. Knowing that there is asymptomatic transmission was a big driver for our recommendations for both Shelter at Home and masks.

The CDC recommendations now say that if you have been in close contact up to 48 hours before symptom onset with someone with a known diagnosis of COVID-19 or a “clinically compatible illness,” it is recommended that the exposed individual shelter at home for 14 days while maintaining social distance. You should check for symptoms, including fever, a couple of times per day. We recommend that you contact your provider if you have any symptoms that concern you. The CDC also says that everyone else is at risk of exposure, so everyone should also watch for symptoms and practice social distancing.

The two changes I have put in bold. Given the concern about asymptomatic transmission, the “48 hour before symptom onset” qualifier was added. We don’t think that there is strong data behind the 48 hour limit because it’s not clear for how long someone is infectious before symptoms come about. In fact, I hate to say it, but there are people who have disease and NEVER become symptomatic. We’ll hear more about that in the future. So, if you’ve had significant contact with someone who has been diagnosed with COVID-19, then shelter at home while keeping social distance from your family for 14 days, and please contact your provider if you develop any symptoms.

Well, what is “significant contact”? Unfortunately, that’s not entirely clear either. The CDC doesn’t help much. While they suggest the following, please contact your provider so we can help you decide whether your contact is meaningful. From the CDC:

-          Data are limited to define close contact. Factors to consider when defining close contact include proximity, the duration of exposure (e.g., longer exposure time likely increases exposure risk), whether the individual has symptoms (e.g., coughing likely increases exposure risk) and whether the individual was wearing a face mask (which can efficiently block respiratory secretions from contaminating others and the environment).

-          Data are insufficient to precisely define the duration of time that constitutes a prolonged exposure. Recommendations vary on the length of time of exposure from 10 minutes or more to 30 minutes or more. In healthcare settings, it is reasonable to define a prolonged exposure as any exposure greater than a few minutes because the contact is someone who is ill. Brief interactions are less likely to result in transmission; however, symptoms and the type of interaction (e.g., did the person cough directly into the face of the individual) remain important.

What are the practical implications of this change in recommendation? Not much. We still recommend you Shelter at Home. If you think you are out and about and going potentially to come into contact with someone who you have not given permission to be in your six foot zone of safety—i.e. those who live with you—keep your distance. And, as we recommended Monday, wear a mask. Let us know if you need help finding a mask, as a family of intrepid seamstresses is making some for the practice. Shout out to the Nibbios!

The Nibbios making masks. Team work makes the dream work!

The CDC also mentions contact with someone with a “clinically compatible illness.” This means a person who we think has disease but hasn’t yet been tested. Could this have been you or someone you know? A number of you have called the practice to talk about your symptoms with us, and we appreciate ALL of the calls; we are your partners in this. For some of you, in response to your symptoms we have said, “You almost assuredly have COVID-19. Self-isolate until you have no fever for 72 hours without medication, it’s been more than 7 days since your symptoms started, and your symptoms are pretty much gone.” For others it's been more of a challenge; the symptoms don’t quite fit the picture we have heard about. “If we could test…”

So I think it’s important we update the status of testing. Here in Chicago and in many communities, access to testing is still limited. While we have access to testing via LabCorp, the turnaround is still eight days or more (!). We're looking at Quest and other private labs for alternative solutions.  As staff members at Northwestern Memorial, we can have people tested there with a quicker turnaround, but there is a screening process that patients need to go through in order to get tested. It’s very selective.

The most common type of test that is available now in the US for SARS-CoV-2 is what’s called a reverse transcriptase PCR test (rtPCR). A sample is taken from your nose or mouth and sent to a lab. The lab then takes the sample, adds some testing liquid (reagent) and puts into a specialized (expensive!) machine that is able to extract the genetic material from the sample, multiply the copies of the genetic material and then use tags to see if SARS-CoV-2 is present. This molecular test DIRECTLY looks to see if the virus is present in your sample. If you don’t get a good sample, the test can falsely be negative even though you have disease. If you are early or late in the course of your disease and there’s not a lot of virus around, the test can likewise be falsely negative. A falsely positive test—meaning the test is abnormal but you really don’t have disease—is uncommon with rtPCR.

Early in the pandemic, the World Health Organization (WHO) developed a rtPCR test that used two tags to see if the SARS-CoV-2 was present in a sample. This is the test that is being used in South Korea and other nations starting a couple of months ago. The US chose to not use this test but develop its own. The first test from the CDC released in early February aimed to be more accurate and had three tags to identify SARS-CoV-2. Unfortunately, as you may have read, the reagents for the test were contaminated. At the same time a few private companies were developing their own tests, but the process is typically onerous, with multiple time-intensive regulatory hurdles to overcome before approval. Only after the failure of the CDC test on March 16th (!) did the FDA allow private companies to develop and release tests more rapidly. You may have heard about companies attaining Emergency Use Authorization (EUA) from the FDA to allow their test to be used to diagnose COVID-19. Access to tests has been limited by swabs, reagent and machines to run the tests. All of this is being ramped up, but it was, sadly, a lost month.

Two tests that have been in the news recently are the Cepheid Xpert Xpress diagnostic test and the Abbott ID Now test. With the Cepheid test, the sample is the same—nasal or oral swab—and a rtPCR machine is also used, here the GeneXpert system. What’s unique about the GeneXpert system is that it works much faster than many of the other rtPCR machines, so results come in just 45 minutes. The Abbott test is also an rtPCR test, also uses a machine, the Abbot ID NOW platform, and is also fast: positive results in five minutes and negative results in 15. Both of these machines are cost prohibitive for us and even if they weren’t, they aren’t available to small practices like ours.

What else? You will be hearing a lot more about immunoassay tests in the near future. Immunoassay tests look for our body’s response to the presence of the virus instead of looking for the virus itself. It’s an INDIRECT test for the presence of the virus. In this situation, the tests are measuring our immune system’s response to the virus. When we get exposed to a foreign agent such as a bacteria or virus, as part of our defense system, the immune system creates antibodies to the foreign substance. These antibodies are absolutely specific to, and seek out like a cruise missile, the infectious agent. Once attached to the virus, the antibodies act as a beacon for the rest of the immune system to work together to combat the illness. Sometimes we’re successful and sometimes we’re not.

These newer SARS-CoV-2 tests are going to look for the antibodies that our body has created in response to exposure to the virus. Early in the infection we create one type of antibody called IgM, and later we make a different type of antibody, IgG. So the presence of IgM suggests early disease, while the presence of IgG suggests you were exposed a while ago.

Some of these tests are easy to perform, requiring just a drop of blood. The test can be done in the office with no machines needed. The upside is that the test is quick and efficient and cost effective. There are downsides, though, too. It takes 5-7 days for your body to produce enough IgM to be detected, so early in the course of disease you could have a negative test, For a person who we think has COVID-19, a repeat test a few days later may be necessary to confirm illness. Secondly, the IgG test is not specific to SARS-Cov-2. Other coronaviruses you may have had in the past—remember the coronavirus is one of the usual viruses that cause the common cold—could turn the IgG test positive. So a positive test will not 100% prove that you had COVID-19.

What will prove if you had COVID-19 is a serum IgG test. With this test you take a vial of blood (not just a drop) and send it to a lab. The lab looks for the SARS-CoV-2 antibodies that may have developed in your body in response to the virus. I mentioned in a previous post that Mount Sinai hospital in NYC was working on a test. The Mayo Clinic also has developed a test and will move it to market soon. This is great news, since the Mayo Clinic is a partner to a great number of labs around the country and support complex disease testing.

We are first working to get the immunoassay molecular finger-stick tests for our practice. Again, we’re trying to be ahead of the game, so we want to be sure to get a test of good quality. We are also challenged by supply and demand. As a small practice, we can flex muscles, but they aren’t as big as those of the government. We are also deciding how best to use the finger-stick molecular tests with our patients, whether to assess current disease, to look for whether someone has had it already, or to screen our patients for asymptomatic COVID-19. Since it does require a sample of blood from the fingertip, we need to protect ourselves as we do these samples. Access to personal protective equipment will be somewhat of a stumbling block, but we’re working on this, too. Shout out to Chris!

Hope this post is useful for you to understand what you’re reading about testing. It’s been a struggle ever since this started, and maybe it’s getting a little bit better. We shall see.

More to come.

Dr. Will