Seven months into a pandemic that has claimed more than 200,000 lives and infected more than 7 million people in the United States, many people are still confused about one of the mainstays of curbing the spread of the novel coronavirus: testing.
With the Centers for Disease Control and Prevention (CDC) issuing conflicting guidance — recommending for, and then against, and then for the testing of asymptomatic individuals — it’s no wonder that even well-informed health care consumers and providers are stumped.
For instance, should you get tested right after a work colleague has tested positive? Or before visiting your grandmother in a nursing home? If those tests are negative, does that mean you’re not infected? What kind of test is best? If you’ve tested positive, do you need a negative test result before you can leave the house? Can you test positive even if you’re no longer contagious?
Megan Ranney, MD, MPH, an emergency medicine physician and director of the Brown-Lifespan Center for Digital Health at Brown University, says the confusion stems from a number of reasons — not least of which is that testing guidelines have changed throughout the pandemic due to evolving science about transmission and persistent shortages of tests and testing supplies. “This is a brand-new disease with brand-new tests, and we’re still figuring out the way that the virus gets transmitted, as well as the accuracy of these various types of tests. We’re still figuring out the best testing strategy,” she says.
“The second biggest reason we’re still confused is because instead of following the science in terms of our testing recommendations, we’re balancing insufficient numbers of tests with the science, and we’re trying to cut corners wherever we can to save the tests for those who need them the most.”
The result, says Ranney and other experts, is that despite a barrage of news about testing, many are still uncertain about how, when, and where to get tested — or even if they should.
AAMCNews talked to a handful of testing experts from Yale New Haven Hospital, the Broad Institute at Massachusetts Institute of Technology (MIT) and Harvard University, Brown University, Johns Hopkins Hospital, and the Mayo Clinic to clarify the most important information about testing — and clear up some misconceptions.
“Instead of following the science in terms of our testing recommendations, we’re balancing insufficient numbers of tests with the science, and we’re trying to cut corners wherever we can to save the tests for those who need them the most.”
Megan Ranney, MD, MPH
Emergency medicine physician and director of the Brown-Lifespan Center for Digital Health at Brown University
There are two main categories of tests for the novel coronavirus. Which one you get largely depends on where you are and why you’re being tested.
Tests fall into two primary buckets: tests for active infection and tests for prior infection, according to Bobbi Pritt, MD, chair of clinical microbiology at the Mayo Clinic in Rochester, Minnesota.
If physicians or public health officials are trying to determine whether an individual has an active infection, they will perform either a nucleic acid amplification test like a polymerase chain reaction (PCR) test or an antigen test.
PCR tests for COVID-19 look for genetic material from the virus and are sometimes referred to as the “gold standard” tests for active infection due to their high sensitivity (some say they might be too sensitive — see below for more on that). PCR tests reproduce the RNA in a person’s sample many times over using sophisticated equipment in a specialized lab, so they’re able to detect even tiny bits of virus. PCR tests tend to be expensive and take hours to produce results.
By contrast, antigen tests look for fragments of proteins from the SARS-CoV-2 virus, and while not as accurate as PCR tests, they are cheaper and faster, largely due to the way in which the sample is processed. A person provides a sample (usually through a nasal swab) and the sample is treated with a reagent and analyzed on the spot. While results are usually available in a matter of minutes, the false-negative rate for antigen tests is high — possibly as high as 50% — which means you could still be positive even though the rapid test came back negative.
Health care providers typically rely on PCR tests in the hospital setting, as they need to know with a high degree of certainty which patients are positive, Pritt says. Most clinical and public health agencies also rely on PCR testing, particularly for people with symptoms of COVID-19.
Antigen testing is most appropriate for surveillance or screening testing, like when colleges or universities are trying to determine the prevalence of the virus on campus.
“For surveillance and screening of large populations, or for rapid turnaround time results, the antigen tests make sense, but if you want clarity around a symptomatic individual, the more sensitive PCR assay is better,” says Heidi Rehm, MD, medical director of the Broad Institute of MIT and Harvard’s Clinical Research Sequencing Platform, which is conducting over 60,000 PCR tests each day.
“For surveillance and screening of large populations, or for rapid turnaround time results, the antigen tests make sense, but if you want clarity around a symptomatic individual, the more sensitive PCR assay is better.”
Heidi Rehm, MD
Medical director of the Broad Institute of MIT and Harvard’s Clinical Research Sequencing Platform
The other main bucket of tests for SARS-CoV-2 are antibody tests, which can help determine whether you’ve been infected at some point in the past. Pritt says that early hopes for a test that could clear previously infected individuals to return to work or school haven’t panned out, largely because antibodies for SARS-CoV-2 seem to disappear after a few months. Scientists aren’t yet sure whether that means immunity to the virus wanes over time or whether the antibodies themselves are just no longer present.
If a close friend or family member has tested positive, you should get tested, even if you’re asymptomatic.
In the early days of the pandemic, scientists were uncertain if those who showed no signs of illness were infectious. They have since discovered that 40% to 45% of COVID-19-positive individuals are asymptomatic — and also that those asymptomatic individuals carry just as much virus in their throats, lungs, and nasal passages as those showing symptoms.
The CDC estimates that about half of all infections are the result of transmission from an asymptomatic person, and most experts agree that testing and isolating asymptomatic COVID-19-positive individuals is key to stopping the spread of the virus.
But don’t get tested right away.
That’s because even highly sensitive PCR tests can come back negative if you’re tested right after exposure, before the virus has built up to detectable levels, according to a study co-authored by Lauren Kucirka, MD, PhD, an epidemiologist and OB-GYN resident at Johns Hopkins Hospital. “Say you had lunch with a friend who was positive. Day one is the day after you had that lunch,” Kucirka says. “What we found was that if you are tested in the days immediately after exposure, the false negative rate is anywhere from 50% to 100%.” So just because you’ve tested negative doesn’t mean you’re not harboring the virus. The average onset of symptoms is five days post-exposure, and your peak infectiousness is two days before and one day after symptom onset, according to a study published in Nature Medicine.
If you want to visit a vulnerable individual — say, your grandmother who lives in a nursing home — it’s best to get tested, but also remain vigilant.
To be perfectly safe, you should probably quarantine for 14 days before your visit. “But who can do that?” Kucirka says. A better approach might be to get tested five days after any possible exposure and then be extra cautious in the days leading up to your visit. “You want to get tested to make sure you’re not an asymptomatic carrier, and also think about whether you are in the pre-symptomatic phase,” Kucirka says.
Tests using saliva are just as accurate as tests that swab the nose or the nasopharyngeal passage.
Saliva tests are becoming more commonplace, but don’t confuse the method of sample collection with the type of test, says Heather Pierce, JD, AAMC senior director of science policy and regulatory counsel. While the early tests for COVID-19 involved swabbing the nose or the nasopharyngeal passage (NP) — and those tests are still the predominant form of sample collection — a persistent shortage of swabs has led to the development of saliva tests.
The saliva test developed by Yale University, SalivaDirect, has been widely heralded because of its accessibility and ease of use, Pierce says. While still a PCR test, it does not require a particular reagent or machine — the collected saliva can be used on PCR machines from different vendors — and it also eliminates a time-consuming step: the extraction of the RNA from the sample, says Chen Liu, MD, PhD, chair of pathology at Yale New Haven Hospital, whose federally certified lab oversaw the validation of the SalivaDirect test and is offering the test to other labs.
It may also be even more accurate than tests performed on samples taken via other methods. In April, Yale published a study on the preprint server MedRxiv that found there is more virus in saliva than in samples from a nasal swab, opening up the possibility that there will be many more saliva tests — both PCR and antigen — in the future. “While the NP swab is still the predominant method of collection, no doubt there will be more and more saliva testing,” Liu says. “We did see that the saliva test detected the virus early on, as early as two to three days.”
“What we found was that if you are tested in the days immediately after exposure, the false negative rate is anywhere from 50% to 100%.”
Lauren Kucirka, MD, PhD
Epidemiologist and OB-GYN resident at Johns Hopkins Hospital
Rapid at-home tests are in development, but they’re likely many months (if not years) in the future.
Right now, some tests allow for sample collection at home, but you still have to mail those tests in to a certified lab for processing, says Pritt. While there has been talk of a test that works much like a home pregnancy test, that type of test is likely a year or more in the future, says Ranney. “The other problem with a home test from a public health standpoint is that we can’t contact trace,” she notes.
Yes, we will still be testing for this virus in a year — and maybe longer.
That’s because even if we have a vaccine in three or six months or a year, it most likely won’t be 100% effective — and vaccine hesitancy may further limit its effectiveness, Ranney says. In mid-September, the Pew Research Institute released the results of a poll finding that about half (51%) of all U.S. adults would “definitely” or “probably” get a COVID-19 vaccine if it were available today — down from 72% in May. “In this country, a lot of people are hesitant to get vaccines. We have to make a big push, then, to get as many people tested” so we can identify outbreaks when they occur, Ranney says.
“For the same reasons, I don’t see us going into private or public situations without masks for at least a year and possibly longer,” she says. “We may even see a cultural shift, where folks start wearing masks” in public places regularly, such as when taking public transportation.
If you do test positive for the coronavirus, you’re infectious through day 10 of your illness; after that, not so much.
One area of confusion for many has been how long a person is infectious after testing positive for the virus. One study published in JAMA Internal Medicine in August found that on average, it took asymptomatic people 17 days after diagnosis to test negative, while it took symptomatic people 19 to 20 days. That doesn’t necessarily mean those individuals were still infectious.
Rehm notes that an emerging concern among pathologists has been whether the PCR test is too sensitive. “To be honest, it is so sensitive that it is turning out positive results for some people for weeks and weeks post-infection,” she says. “That’s probably due to residual RNA and is not a true sustained positive viral load.”
Adds Pritt: “You can be PCR-positive for weeks to months but you probably aren’t infectious. You’re just shedding little bits of dead RNA. The test does not distinguish live virus from dead virus.”
So, when can you feel comfortable going out in public? “You are your most infectious right about when symptoms start to develop,” Rehm says. After that, the CDC recommends waiting 10 days before venturing out. Those without symptoms can discontinue isolation 10 days after testing positive.
