You are going to stick *what* up my nose? [Update with TikTok links!]

These are not your grandmother’s nasal swabs.

To continue our recent discussions on disease testing, today we’re talking about swabbing and swabs. 

Perhaps you’ve been lucky enough to experience a swab test firsthand. As testing becomes more widespread, we are all likely to have a nasopharyngeal swab taken for a  COVID-19 test. When I was a child, maybe around seven, I remember going to the doctor’s office to be tested for influenza, another virus that replicates in the nasopharynx. When the nurse first pulled the slim, wire swab out of the packaging, I thought no way. No way that daunting, 5-cm long wire will fit up my nose. Sadly, I was mistaken. I won’t lie – it wasn’t the most pleasant experience. The tickling sensation lingered in my throat long after the swab had been removed. I still felt it even after my results had come back – negative, luckily for me. Just a common cold! 

This kind of swab is referred to as a nasopharyngeal swab, which I learned many years later. Nasopharyngeal swabs are used to collect samples from the back wall of the nasopharynx (hence the name), which is where the nasal passages meet the throat. Other common swab tests include nasal swabs and oropharyngeal (throat) swabs.

Nasal swabbing vs. nasopharyngeal swabbing from link.

Swabs are made out of a number of different materials. Since the nasopharynx is much farther back in the nasal passage, the swab needed to get there must be longer and somewhat bendable. The swabs used for sampling the nostrils and throat are generally stiffer and shaped like long Q-tips. The materials that comprise the tips of these swabs are different, too. If you are trying to get material out of the oral or nasal cavities for testing, you need a surface at the tip that is good at grabbing that material. It is also important to be able to wash the material off and into the testing solution when needed. Thus, regular cotton is often not suitable. 

In terms of COVID-19 testing, the swabs you’re most likely to encounter are nasopharyngeal and nasal swabs. Nasal swabs are less invasive. The swab only needs to be inserted 1 cm into the nostril and rubbed along the septum for a few seconds. Nasopharyngeal swabs, on the other hand, require a longer swab, which is inserted about 4-6 cm back into the nostrils (about half-way between the entrance to the nares and the base of the ear). The swab is then rotated inside the nasal passages and left in place for a few seconds to absorb the sample. 

Check out Dr. Klapperich demonstrating anterior nares swabbing (AN) here and here on TikTok!

Swabs made to sample the nasopharynx usually have a tip made of plastic foam, or another material with lots of surface area. These are called “flocked” swabs. Only a few factories in the world make these swabs, which is why you regularly hear about swab shortages for testing. Sadly, using a version of a regular Q-tip would not be a suitable replacement. There are a number of innovative groups around the world looking for ways around this shortage. Some of them include 3D printing swabs made from medical grade plastics. All swabs that are used to apply topical medications or collect fluid samples are considered Class I medical devices by the FDA

In studies comparing the sensitivity of nasal vs nasopharyngeal swabs for influenza, nasopharyngeal swabs were found to be slightly more sensitive (94% vs. 89% sensitivity). This means that for the flu, a nasal swab sample will lead to a false-negative test result more often than a nasopharyngeal swab. But despite their inferior sensitivity, nasal swabs are simpler and useful for “self-swabbing”- taking your own sample to send or have delivered to a testing facility. According to the most recent update to the CDC’s COVID-19 specimen collection guidelines, nasal swabs taken by a healthcare worker or via self-swabbing are acceptable if taking a nasopharyngeal swab is not possible. But these guidelines are sure to change as more information comes out about how swab type affects false-negative rates for COVID-19. Early indications are that nostril swabs are not as good as nasopharyngeal swabs for this new virus. 

The Racialized History of the Spirometer

A spirometer is a medical device often used to assess respiratory function and diagnose respiratory diseases, including asthma, chronic obstructive pulmonary disease, and asbestosis.1 To use the device, you inhale and exhale as deeply as possible into a breathing tube attached to the spirometer itself, which measures your forced vital capacity (the maximum amount of air you can breathe in) and forced expiratory volume (how much you can breathe out in 1 second).1 

Figure 1: This shows the basic set-up of a modern spirometer test. The patient wears a nose clip and breathes into a mouthpiece, and a monitor displays a graph of their inhaled and exhaled volume. (Source Wikipedia)

For each patient who is tested using a spirometer, the operator must enter information about the patient, including their age, sex, height, and race.2 Unbeknownst to many operators, selecting a patient’s race enables a “race correction” setting programmed directly into the spirometer software – typically a 10-15% lower baseline lung capacity for patients identified as Black, and 4-6% lower for patients identified as Asian.3 Despite conflicting studies contesting the validity of using racial correction factors,4 it continues to be taught in modern science. This idea that non-whites have intrinsically lower lung capacity began as a justification for slavery, and the ramifications of this notion have continued to manifest in modern-day medical devices. 

In Thomas Jefferson’s “Notes on the State of Virginia,” the former president and slaveholder described deficiencies in “the pulmonary apparatus” of Black slaves.5 Plantation physician Samuel Cartwright further elaborated on Jefferson’s sentiments with his own spirometer studies, reporting a 20% “deficiency in the negro” in regards to lung capacity.6 Cartwright promoted slavery on the grounds that forced labor was necessary for Black people’s health due to their innately lower lung capacity. He stated that “it is the red vital blood sent to the brain that liberates their mind when under the white man’s control.” 6

After the Civil War, Benjamin Apthorp Gould further expanded on Cartwright’s work by comparing the lung capacity of Black and White soldiers. Although Gould did not account for height, age, or the living conditions of recently emancipated slaves, Gould’s conclusions mirrored those who came before him: “full blacks” had lower lung capacity than “whites.” 2,5,7 Gould’s study is still cited in scientific articles today.2

Over the course of the 20th century, researchers continued to fuel the idea of innate racial differences in lung function, repeatedly failing to account for the influence of socioeconomic conditions. In a review of articles published between 1922-2008 comparing lung function between races, 94% of articles did not examine race in the context of socioeconomic status.8 Although it is often ignored in research articles, lower lung capacity has been associated with poverty in past studies, as well as other social determinants including environmental toxin exposure and healthcare inaccessibility.2,5 

In 1984, J.E. Myers published an article that questioned the body of data supporting innate racial differences in lung function. Myers conducted his own spirometer studies of Black workers in South Africa, and his calculations showed that the published South African standards considerably underestimated the lung volume of Black people.4 Myers also challenged the assumptions made in previous studies, pointing out that they neglected to account for socioeconomic factors including environmental pollutants, housing quality and nutrition quality.4 

Several years after Myers’ article, in 1999, asbestos manufacturer Owens Corning used the argument that Black people have an intrinsically lower lung capacity to evade lawsuits from Black workers with lung damage. The company tried to argue that Black workers should be held to a different standard when assessing asbestos-induced lung damage because Black people consistently score lower on pulmonary function tests.9 The motion was overruled, but the case highlighted how historic assumptions on race have infiltrated modern lung research. As in the case of Owens Corning, modified lung function standards based on race have the potential to reduce diagnosis rates for respiratory illnesses and lung damage. 

Current spirometers implement “race correction” automatically, defining race as a purely genetic difference, rather than exploring the environmental and socioeconomic factors that have been shown to influence lung function. Lundy Brahn, a Brown University professor of Africana studies and medical science, addresses these issues in her article “Race, ethnicity and lung function: A brief history,” where she provides insights on how to address lung function research in the future. 

“Research and clinical practice needs to devote more careful attention to the social nature of racial and ethnic categories and draw on more complex explanatory frameworks that incorporate disproportionate exposures to toxic environments, differential access to high-quality care and the daily insults of racism in every sphere of life that manifest biologically.” 2 

– Lundy Braun, PhD


1Spirometry: Mayo Clinic,is%20helping%20you%20breathe%20better.

2Race, ethnicity and lung function: A brief history, by Lundy Brahn

3 Breathing race into the machine: The surprising career of the spirometer from plantation to genetics, by Lundy Braun

4Different ethnic standards for lung functions, or one standard for all?, by J.E. Myers

5Science reflects history as society influences science: brief history of “race,” “race correction,” and the spirometer, by Heidi L. Lujan and Stephen E. DiCarlo

6 The Science and Politics of Racial Research, by William H. Tucker

7Investigations in the Military and Anthropological Statistics of American Soldiers, by Benjamin Apthorp Gould

8Defining race/ethnicity and explaining difference in research studies on lung function, by Lundy Braun

9Racial basis for asbestos lawsuits?; Owens Corning seeks more stringent standards for blacks, by Erin Texeira

Are pulse ox devices racist?

Black communities are already faced with substandard healthcare, so when a medical device that monitors vital signs, such as the pulse ox, is developed without Black and dark-skinned people in mind, it is much more than just a design flaw.

In our last blog post, we went into detail about pulse oximeters and their mechanism of action. As we touched on briefly, blood oxygen measurement varies greatly from person to person since it relies on light passing through tissue, which behaves differently depending on a number of biological factors. This seemingly objective method actually serves as an example of biomedical technology that fails to account for all of these factors.

We couldn’t find a single stock shot of a pulse oximeter being used on someone with dark skin at, we checked.

Low oxygen saturation levels, the type of sensor in the device, gender, and skin color have all been shown to cause errors in pulse oximetry, but the discrepancies relating to skin color may be the most glaring. Studies and extensive anecdotal evidence from clinicians have shown that any errors due to low oxygen saturation were more dramatically skewed in Black patients when compared to their white counterparts. More specifically, at oxygen saturation levels below 80%, pulse oximetry measurements are significantly overestimated in dark-skinned patients

At saturation levels below 80%, patients begin to experience oxygen deprivation to the point of organ failure (hypoxia). So, if a pulse ox reading is overestimated in a dark-skinned patient, a healthcare professional could easily miss the onset of hypoxia. This limitation of the technology is critical especially now, during the COVID-19 pandemic, which is killing Black people at a rate three times higher than that of any other racial group in America. Black communities are already faced with substandard healthcare, so when a medical device that monitors vital signs, such as the pulse ox, is developed without Black and dark-skinned people in mind, it is much more than just a design flaw. 

As engineers, we are taught that device design of any kind cannot be successful unless the product meets all necessary requirements. Just like designing a building requires every environmental condition to be taken into consideration, designing a medical device requires every kind of person to be taken into consideration.

Nevertheless, in the 1980s, when the pulse ox first underwent FDA screening, accuracy and calibration testing was conducted primarily on light-skinned people; this has not changed since then. Despite the major functional disparity, the FDA has yet to require further research and testing dedicated to developing a pulse ox that produces accurate measurements on darker skin.

To pulse ox, or not to pulse ox?

Another day, another COVID-19 discussion… 

With each passing week, we are learning more and more about how to deal with this pandemic, both individually and as a community. We are now well-versed with preventative measures like washing our hands frequently and wearing masks, but what happens if you actually start feeling sick? While the symptoms of this viral infection are varied, they usually include high body temperatures, dry cough, and shortness of breath. Most of us have a thermometer at home, with which we can easily diagnose abnormal temperatures. But, is that enough to detect the early stages of a COVID-19 infection? 

Pulse oximeters (pulse ox) are getting a lot of attention right now. If you have ever had surgery or if you have a respiratory condition like asthma, you likely know that a pulse oximeter is the little medical device that clips onto your finger and informs your doctor of your heart rate and how much oxygen is in your blood. Monitoring blood oxygen levels has been critical for COVID-19 patients because a drop in the amount of oxygen in your blood indicates the need for more aggressive interventions.  Since you can buy a pulse oximeter at the drugstore, many people are wondering if they need one at home. So why exactly do respiratory issues warrant the use of a pulse oximeter? 

When your lungs are functioning properly, around 95% – 98% of the blood in your arteries should be “oxygenated,” or carrying oxygen. Your blood carries oxygen with the help of hemoglobin, a protein that has the ability to bind to oxygen molecules. Hemoglobin is what  makes blood a great transporter of oxygen from your lungs to the other organs in your body. Without oxygen, your organs cannot function because they rely on a process called oxidative phosphorylation, which uses oxygen to produce the energy that drives all organ functions. When your lungs are compromised, like they are during a COVID-19 infection, they are unable to efficiently take oxygen in from the air and pass it into your bloodstream. As a result, your other organs don’t get enough of it to do their jobs. This condition is called hypoxia. 

The circulatory system. Red vessels are the ones that carry oxygenated blood.

Now, let’s get back to the pulse oximeters. A pulse oximeter measures the percentage of oxygen saturation in your blood by shining both a red light and an infrared light into the top of your finger. The bottom of the device has a sensor that detects the amount of light that passes all the way through your finger. You can visualize this mechanism by doing a quick little science experiment on yourself. Turn on your cell phone flashlight, put your finger on it, and see what happens. If red light shines through, your blood is probably not deprived of oxygen. Good for you! Oxygenated blood absorbs every wavelength of visible light except red, which is why the red light can go all the way through your finger. Deoxygenated blood, however, is really good at absorbing red light. Now, we can see how the pulse oximeter takes advantage of these properties of blood to give a measurement of oxygen levels. 

So, why is infrared light also necessary? Blood vessel width varies from person to person, making the volume of blood in the vessels vary as well. Only using red light would result in misleading oxygen levels because the readings would be affected by these varying blood volumes in different people. For that reason, infrared light is used alongside red light to normalize the measurement and adjust it to each user’s body. Infrared is not well-absorbed by either oxygenated or deoxygenated blood, so it is a good baseline comparison measurement. The pulse oximeter calculates the ratio of absorbed infrared light to absorbed red light to get the percentage of blood saturation. In oxygen-rich blood, the low level of infrared absorption divided by the similarly low level of red absorption results in a ratio close to 1, which is equivalent to a percentage close to 100%. As blood oxygen levels decrease, this ratio also decreases because the red light absorption (the denominator) increases while infrared absorption stays relatively constant. Readings below 92% indicate the beginning of a hypoxic state. 

How a pulse oximeter works.

The ability to detect hypoxia is what makes pulse oximeters critical for COVID-19 patients. Healthcare professionals who are currently treating these patients are finding that oxygen levels can drop well below 92% before patients have any trouble breathing. When a patient does finally go to the doctor complaining of shortness of breath, their infection and hypoxia may be very advanced. Often, symptoms like fever and fatigue can also mask early hypoxia symptoms. It is easy to get used to the mild shortness of breath or pass it off as fatigue while blood oxygen levels continue to drop. For these reasons, some doctors are suggesting that everyone should get a pulse oximeter to use at home so the onset of hypoxia can be caught early. 

A big disclaimer that many physicians are making however, is that pulse oximeters should be used at home along with thermometers and calls to your doctor. There are still many cases in which COVID patients do not present with any hypoxia, but have high fever and the telltale dry cough. So, blood oxygen level, while helpful, is not the only metric used in diagnosis.

So, should you buy a pulse oximeter? To put it plainly, it’s really up to you. If you are sick, you called the doctor, and they said you’re not sick enough to go to the hospital, it may be helpful to have one and monitor your own blood oxygen so you know if you ever do need to go in. You may want one in that situation just to keep your peace of mind. Even if you aren’t sick, and just want to be prepared, it definitely can’t hurt to get one. However, all the stories about hypoxia going unnoticed paint a scary picture. It’s important to remember that, if you can’t get your hands on a pulse oximeter right now since the demand is high, it’s not the end of the world. The vast majority of COVID patients are able to get diagnosed and get to the hospital in time if necessary just by calling a doctor. So, you really don’t need to buy that $200 pulse oximeter you found on Amazon. You can find them for about $30 at your pharmacy, but if they’re sold out, don’t panic! Just keep washing your hands, keep that 6-foot distance, and if you are sick, call your doctor. Here at the blog, however, we are device geeks – so any opportunity to have a new medical device around the house we’ll take! 

Can you really hack a ventilator?

“What did Elon Musk say this time?”: COVID-19 Edition

A few weeks ago, Elon Musk promised to purchase and send ventilators to hospitals experiencing equipment shortages. He faced backlash from the media after one of the hardest-hit hospitals in Queens, New York, tweeted a picture featuring one of the “ventilators” he sent – actually a BIPAP machine. Media outlets and Twitter users criticized him for sending these non-invasive devices rather than the life-support ventilators that hospitals desperately need. Was it a rookie mistake? Maybe. Let’s go over the differences among these medical devices that all interact with the respiratory system! 

You probably know someone who uses a CPAP (Continuous Positive Airway Pressure) or BIPAP (Bilevel Positive Airway Pressure) machine. Folks who have sleep apnea use them to sleep more safely and comfortably. When I was younger and would spend nights at my grandparents’ house, I was terrified of the CPAP mask that my grandfather wore at night, and the noises it made. Eventually, after scrutinizing the face mask and hose connected to the machine, I convinced myself that he looked like an elephant. I love elephants. CPAP machine fear: conquered.

CPAP Machine

BIPAP and CPAP machines are both non-invasive types of ventilators, not the type that are normally used in hospitals for patients that are oxygen-compromised. When we inhale, our diaphragms contract and flatten down towards our pelvis, allowing our lungs to expand and increase in volume. Throwing it back to high school physics – when the volume of a container increases, its pressure decreases. Air follows a gradient of high to low pressure, so when our lungs expand, the higher pressure air outside of our body rushes into our lungs. Ventilators generally help facilitate this process when patients need more oxygen in their systems, or their airways are compromised. CPAPs and BIPAPs deliver a constant stream of positive air pressure through the mouth and nose to keep airways open. Their main users, obstructive sleep apnea patients, need them to prevent the throat muscles from relaxing too much during sleep, so the airways can remain unobstructed. 

CPAPs can only be set to one level of pressure or slowly advance to a maximum pressure overnight, whereas BIPAP machines are a little fancier and customizable to provide support for users who need more oxygen saturation support, and higher air pressure. BIPAPs have two pressure settings – a higher one for inhaling, and a lower one for exhaling, because exhaling against a high, continuous pressure can be difficult and uncomfortable. 

Both of these assistive devices consist of a face mask covering the nose and mouth with a hose that attaches to the machine that performs all of the work. It is possible for patients with less acute cases of respiratory distress to use BIPAPs in hospitals, especially when ventilators are few and far between (more on why later), which is why Musk likely chose to send BIPAPs, rather than wait for more complex machines to be manufactured. However, CPAP and BIPAP machines can be dangerous for healthcare providers right now – leaky face masks can expose them to airborne virus particles, though it may be possible to mediate that risk by using some new innovations. 

Life-support ventilators are more invasive and complex. They have many moving parts, settings, and even customizable software, making them powerful enough to meet the demands of different conditions for patients with severely compromised lung function. Size and frequency of breaths can be monitored to manage a patient’s specific needs at all times. Slow, medium sized breaths are more beneficial for stabilizing respiratory distress than deep and slow, or rapid and shallow breaths. They also generate air pressures that are strong enough to hold open bronchioles, the small branched airways in your lungs, that can collapse under inflammation or fluid build-up – all complications of COVID-19. 

Patients who need ventilators are anesthetized while an endotracheal breathing tube is carefully inserted through the mouth and down the trachea (the windpipe), and a cuff is inflated around the breathing tube in the trachea to form a seal (like when you get your blood pressure taken). This is particularly important for COVID-19, as the cuff prevents virus particles from leaving the airway and exposing healthcare providers to the virus. Physicians must decide who gets a ventilator and who gets a CPAP or BIPAP based on the severity of a patients’ case. But, why do they even have to make that decision in the first place?


We are experiencing a global ventilator shortage due to a variety of factors, including significant disruption to global manufacturing supply chains (the resources and companies needed to manufacture products) as a result of the pandemic, and prior market demand. In 2019, before COVID-19, the entire world only needed 77,000 new ventilators a year. Now, manufacturers would need to increase their rate of production by 500-1000% percent in order to meet the demands of this public health crisis. Manufacturers have only been able to increase their production by about 30-50%. Life-support ventilators are incredibly complex and expensive machines; they require more than 700 parts that are often sourced from all over the world, and they cost about $50,000 each. Manufacturing plant size and supply chain disruptions prevent this process from accelerating to meet our needs. 

In order to combat the ventilator shortage, the FDA released new guidelines on March 22nd to allow hospitals to be more flexible with this life-saving equipment to meet the influx of cases of COVID-19 related respiratory distress. The guidelines allow small modifications in materials, software, or functionality to be made to pre-existing or newly manufactured ventilators without FDA approval. The guidelines also allow CPAP and BIPAP machines to be used for less-severe COVID-19 cases, with careful monitoring. The FDA specifies flexibility with materials for breathing tubes, which are now difficult to obtain, and ventilator motors, to increase the capability of less-powerful machines. 

Normally, these changes would need to pass through the FDA’s 510(k) pre-market approval for medical devices, a fast-tracked process that allows newly developed devices that are “substantially equivalent” to previously cleared devices to get approved quickly, without clinical trials. Now, manufacturers and hospitals have the flexibility to use modified devices without clearance for emergencies. The FDA emphasizes that the use of FDA-approved devices should be prioritized over the use of modified CPAP and BIPAP machines. In particular, they encourage the development of filters to protect healthcare providers from aerosolized virus particles when using CPAP and BIPAP machines for less severe cases, and new software to encourage remote monitoring of patients to prevent exposure. 

One example of this innovation is a group at UC Berkeley working to fit CPAP machines with endotracheal tubes and filters, eliminating the need for face masks and significantly reducing the risk of viral exposure. Ultimately, Elon Musk did the right thing here – he provided extra resources to hospitals in need. In fact, after the media backlash, Musk said that the hospitals confirmed that they had a critical need for BIPAP machines for less severe cases. Musk has also pledged to dedicate Tesla factories to manufacturing ventilators. Hopefully he and others can help refit BIPAP machines for safer use! 

Rendering of a sleep apnea device retrofitted to help COVID-19 patients. (Grace O’Connell image)

What we talk about when we talk about diagnostics.

After spending the last few weeks talking with students, journalists, neighbors and family members, I’ve decided that there might be some value in discussing some of the terminology that we use when talking about diagnostic testing.

Science communication and media relations folks always discourage “jargon” when describing scientific concepts to laypeople. However, technical terminology can be a key part of scientific discussions, especially when it’s important to be precise. Now, in the setting of a global pandemic, precision is particularly important, and I believe people can handle more complexity than the scientific community often gives them credit for. Increasing scientific literacy can empower people to better understand and digest current events. So, here are some of those definitions.

First off, is reagent. In general, a reagent is any substance that is a starting material for a chemical reaction. Do you remember finding the “limiting reagent” in high school chemistry class? That’s the chemical that runs out first; thus, limiting the amount of product that can be made by the reaction. Many outlets have reported that one of the reagents failed in the initial test that the CDC distributed for COVID-19. It is still unclear which reagent did not perform as expected, but the reagent was one of the parts of the test reaction that the CDC shipped out to labs around the country. This problem has now been fixed, and all of the CDC test components are working well. 

Negative and positive screening test cassette strips.

The next term is assay. Assay is just the word we use for “test.” Anytime you hear someone say they are running an assay or assaying for something, they are simply running a test. 

Controls and control material also come up often when discussing test design. Controls are needed to make sure that the test you are running is valid. Basically, controls are parallel experiments that you run alongside your testing to make sure that you didn’t make a mistake while running the test. We science folks are always skeptical and are always checking to make sure we didn’t make a mistake! A positive control, in the context of COVID-19 testing, is when we put some material in the reaction that we know will make the test come up positive. If that reaction does not come up positive, we know that we made a mistake someplace, or that some of our other reagents are not working properly. A negative control is when we set up a test that does not contain a sample or additional material, that we expect to come up negative. If a negative control comes up positive, then we know that we have some kind of contamination, or that something we did not expect is happening in our reaction. If this happens, we need to start over, and figure out what went wrong. In both cases, controls that do not work as expected render any test result invalid. These results are not reliable and should not be reported. 

Now, we need to cover sensitivity and specificity. These guys are a bit more complex. Sensitivity measures how little of the virus you can detect using a particular test in a particular sample. A super-sensitive test can detect very small amounts of the virus. Sensitivity goes hand in hand with the concept of a false negative. A test that is not sensitive enough might come out negative for someone who is infected with the virus, but does not have a viral load high enough to make the test read positive. It is also possible that a false negative can arise from a swab being taken improperly. 

Specificity is a measure of how well the test detects the COVID-19 virus, and not other things that might confuse the test. A very specific test is good at detecting COVID-19 and will not detect other closely related viruses. Specificity goes hand in hand with false positive rates. If a test is not very specific, it might show a positive result when someone is not infected with COVID-19, but with something else like a flu virus. 

Both false positives and false negatives make it difficult for healthcare providers to interpret test results in the context of care. Low rates of false positives and false negatives make a test more trustworthy. 

Now you know the basics of test design and metrics! We hope that this makes reading some of the science reporting a little more clear. 

Let’s Discuss Testing for COVID-19

The COVID-19 pandemic has sparked a great testing debate in this country, and you’ve likely heard a lot of terms thrown around: RNA tests, antibody tests, point of care tests, laboratory tests, etc. But what are the differences between them? When is each one useful? Not every test gives your healthcare provider the same information, and not every test is useful at every stage of an infection. 

In this post we will break down three things: the types of tests out there,  what information each test can give us, and when that information is useful. There are a lot of good explainers on this if you are interested in diving into the details, and some great resources are listed at the end of this article for more info! 

Let’s start by discussing the types of tests available. First, there are the nucleic acid tests that detect DNA and RNA. The SARS-CoV-2 virus that causes the COVID-19 disease is an RNA virus, which means that its genome is made up of RNA instead of DNA (like ours!). The RNA sequence is specific to that virus, and detecting its presence tells us if someone has been infected with the virus. This test will read as positive when the viral RNA is present, which can occur as soon as the virus is replicating in your body and until your immune system has completely cleared the virus. The amount of virus in your body is roughly proportional to the amount of viral RNA, since each viral particle contains a single RNA genome. Therefore, the amount of viral RNA in your body will change over the time that you are sick, and will go away when you are well and the virus is gone.

So, a test for the RNA, or a “nucleic acid test”, will be able to tell you when you are infected with the virus. The test will be accurate at any stage of infection as long as you have enough virus in your body. Whether you have been infected but aren’t showing symptoms, you’re feeling sick, or you’re starting to feel better, the nucleic acid test can still be positive if there is enough virus in your system. Viral load, or the amounts of virus in your body, tends to follow a pattern that starts low, peaks or levels off, and finally falls off as you get better. The amount of virus can vary from person to person at each stage of an infection. Factors like how old you are or if you are immunocompromised can alter how much virus is in your body during an infection. The variables that affect viral load for this COVID-19 disease are not yet well known. Learning more about these factors will help us get better at knowing when to test, who to test, and how to make better tests. 

The caveat about nucleic acid tests is that in most cases, they require a sophisticated laboratory set-up to perform.  This is one reason why it was difficult to ramp up COVID-19 testing in the United States. Not every lab is designed for this kind of work, which limits how many tests can be performed in a day. However, RNA tests can also be done on smaller test platforms in less sophisticated labs. These are called point-of-care tests, or POC tests. Recently, Abbott released a small scale POC RNA test for flu and other infections which interfaces with a testing system they already have in the field. The test can produce results in about 15 minutes, but only one test can be run at a time, while more sophisticated labs can run hundreds of tests or more at a time. There are about 18,000 of these instruments already in doctors offices and small labs around the country, and Abbott claims they can ship 50,000 test cartridges a day for these systems. 

Unfortunately, for a number of reasons, the United States has not invested the necessary capital and resources in POC nucleic acid testing and research. The technologies to make RNA testing portable and accessible do exist, but the cost/benefit ratio has not been favorable in the US — until now.  During a pandemic, when lots of people need tests, the economics do work. The conundrum, however, is that in normal circumstances, when a small doctor’s office is running only a few tests a day for different infections, it often does not make sense for them to have this testing on site. So, they use large lab testing companies instead. Samples from the practice are picked up like the mail by couriers and driven to central facilities for testing. The results are returned to your provider electronically. 

The COVID-19 pandemic has cast POC testing into the spotlight, making it evident just how essential it can be for disease containment. POC tests are often touted as a solution to healthcare inaccessibility in low resource settings, but the reality is that POC tests are vital to all settings. As more novel infectious agents emerge, we hope that even high resource countries will prioritize POC development.

When you first think of POC testing, what comes to mind? Many people think of urine-based pregnancy tests, which are widely available at drugstores. A pregnancy test detects a specific protein in urine called HCG, which is present in high amounts during pregnancy. If significant amounts of this protein are present, the test shows a positive result.

Pregnancy test showing positive result

For infectious diseases, these types of tests are often called “antibody tests.” When you contract a virus, your immune system will attack it, creating special proteins called antibodies in the process. These proteins bind to the virus so immune cells can locate and destroy it. The body creates unique antibodies for each pathogen it encounters, so they can be used as indicators of past or present infection. For example, if your blood contains antibodies to tuberculosis, you must have been exposed to tuberculosis at some point. These antibodies hang around in your system so that if you encounter the same disease again, your body is prepared to fight it off.

Compared to RNA tests, these kinds of antibody tests are fast and relatively simple, but they can produce false-negative results early in the disease course. For antibody tests to be effective, you need to have been sick long enough to produce the antibodies, otherwise the test will appear as a false-negative. In the setting of a pandemic, this can be particularly problematic, as false-negative results may prevent infected individuals from taking the proper isolation precautions. Furthermore, antibody tests can also give false-positive readings if you have already recovered from the infection, as the antibodies remain in your system long after symptoms resolve. Antibody tests to detect COVID-19 will likely use blood from a finger stick. The healthcare company Henry Schein has announced the availability of a new point of care antibody test that works on this principle. 

Finger with blood drop.

Nevertheless, antibody tests have a very important role to play in this pandemic. As more people recover after being sick, we will need to know who those people are because they will have developed some amount of immunity to the disease. They will likely be able to move freely through an infected population without becoming infected again. However, it is important to note that while this is true for many viral infections, it is not yet known if COVID-19 will behave exactly the same way. 

There is a second kind of antibody test that has the potential to work earlier in the course of the disease. These tests use antibodies to look for proteins on the outside of the viral envelope. We will call these viral-protein tests. For example, E25Bio, a Cambridge-based biotech company, has developed a POC test for COVID-19 that is currently being tested at Massachusetts General Hospital. The test resembles an over-the-counter pregnancy test, with one line vs two lines in the readout window. This new test, named the “Spike Dart,” can detect viral proteins in various bodily fluids, including mucus, saliva, blood and urine. The Spike Dart provides results in about 15 minutes. However, the tradeoff for quick results may be decreased sensitivity compared to the lab-based PCR assays, which is common for point-of-care tests. Nonetheless, this POC test may be a valuable tool in healthcare settings to rapidly isolate infected individuals for further testing and treatment. E25Bio has been in close contact with the FDA and hopes to attain emergency use authorization to deploy the Spike Dart in hospitals and doctors offices in the coming weeks. 

To summarize, there are three different types of tests in the news right now: RNA (nucleic acid) tests, antibody tests that look for antibodies against the virus in the blood, and viral protein-based tests that use antibodies to detect viral proteins. RNA tests are good at detecting new infections and monitoring how long a person is infected. Antibody blood tests can be more easily made portable to use in the field, but can only detect late-stage disease and past infections. Viral-protein POC tests are simple, fast, and inexpensive, but may operate at a lower sensitivity than lab-based testing.

This post was updated on 4/1/20 to include information about viral protein detection tests.

Additional Resources:

How Covid-19 Immunity Testing Can Help People Get Back to Work 

Coronavirus Testing Shouldn’t Be This Complicated

Abbott Point-of-Care Test

Current and Future Applications of Point-of-Care Testing – Centers for Disease Control

Example of Nucleic Acid Test for HIV Diagnostics – Video

Dr. Klapperich Welcomes You to the Blog

At my day job, I work on improving diagnostics for all kinds of diseases. These days that work is dominated by COVID-19. Some heroic members of my lab are still working on tests and test methods that might be helpful the next time this virus comes around.

About two years ago, I started writing a popular science book focused on medical devices and how they impact and intersect with women’s health. The work was slow, mainly because writing a book turns out to be hard.

To get my ass in gear and actually finish the book, last semester I hired three wonderful young women as research assistants. We had been meeting and chatting about this project weekly. Then COVID-19 hit us and now we are all working from home. A lot of our sci comm work has turned to the pandemic, and we decided that 280 character tweets don’t offer enough depth or permanency for the info we would like to share.

To keep this work going, Skylar, Sarita, and Lizy, and I have decided to share our (evidence based!) thoughts and some of our works in progress for the book here on the blog. You can learn a bit more about us here, but I can tell you, without exaggeration, these three women are the only reason this work can continue in this crazy time.

The scope of our writing project has expanded to include science and engineering explainers on more topics than just medical devices. I also guarantee that I will be injecting a lot of the personal into this blog. The first personal touches are the photographs. If they aren’t credited to someone else, they are my original art. -Cathie

Took this one with my Moment Macro lens at the 2017 Microfluidics GRC in Italy.