by Kayla Davis
figures by Jovana Andrejevic
With COVID-19 cases showing up across much of the United States, many people are increasingly curious if they have contracted the disease. Although the COVID-19 infection rate continues to rise, tests are still hard to find and nearly impossible to come by in certain areas of the country. It’s important to understand how widespread the COVID-19 infection rate is so that disease modelers and governments, as well as citizens, can make the appropriate calls on stay-in-place orders, social distancing requirements, and personal protection, as well as decisions on when to re-open cities and states. Without accurate testing throughout the population, it is impossible to know how many people have contracted the virus, understand the number of deaths attributed to COVID-19, or know how many people may have built up immunity to the disease.
Although the US currently leads the world in the number of COVID-19 tests administered, with 11 million tests as of today (May 17, 2020), only 32.39 people per every 1000 people in the US have taken a COVID-19 test compared to 65.52 in Denmark, 48.71 in Italy, and 37.57 in Germany. The 11 million tests that have been administered thus far account forabout 3% of the United States’ total population. These numbers are estimates at best, with many states reporting both testing of new patients and repeat testing of the same patients as novel COVID-19 test results. With many experts agreeing that testing is the most important thing for stopping the spread of COVID-19, why is it still so hard to get tested in many areas of the United States, and why do some states have higher testing rates than others?
Developing a test for COVID-19
Once scientists identified that COVID-19 was the result of the SARS-CoV-2 virus, they worked quickly to learn more about the virus and to develop a diagnostic test that could recognize the virus in patient samples (Figure1). On January 19th, the World Health Organization (WHO) received information from scientists on how to develop a test for COVID-19 and became one of the first groups to distribute COVID-19 test kits to countries along with a set of guidelines on how to create a test for the disease. Although the WHO had developed a test for COVID-19, it is typical for countries that have the capability to develop their own tests to do so. In the United States, rather than use the WHO test, the Center for Disease Control (CDC) mandated that they would be the only valid source for COVID-19 tests and began preparing test kits that were ready for distribution by January 28th. Note that this mandate was not uncommon, as the CDC has historically handled testing of infectious disease for the United States, such as with the hantavirus in 1993 and the Ebola virus outbreak in 2014-2016.
By late January, the CDC had developed a COVID-19 test and tested thefirst 4 COVID-19 patient samples. In the United States, any test that is developed for an infectious disease must be approved by the U.S. Food and Drug Administration (FDA). In times of crisis, the FDA can issue an Emergency Use Authorization (EUA), which gives emergency approval to otherwise unapproved life-saving medical or diagnostic products. OnFebruary 3rd, the CDC applied to the FDA for an EUA for their COVID-19 test and on February 4th the test was approved. On February 5th, nearly two weeks after the first confirmed case of COVID-19 in the United States was discovered in Washington state, the CDC sent 200 test kits to the International Reagent Resource to be distributed to more than 100 testing facilities across the United States. Each test kit had the capability of testing roughly 300 patient samples. As the first few tests started to be sent across the country, scientists noticed a problem with one of the test-kit ingredients, which made it impossible to interpret test results. This issue was attributed to a manufacturing problem, which is currently underinvestigation. By February 12th, the CDC advised all labs across the country that had begun to use the CDC-issued COVID-19 tests to halt testing with the faulty kits and went back to work making new test kits.
Regulation of COVID-19 testing in the US
When the FDA gave authorized use of the Emergency Use Authorization Act on February 4th, they also granted certain labs the ability to perform their own testing — specifically, they authorized labs that are certified to perform high-complexity testing and meet the Clinical Laboratory Improvement Amendments (CLIA) requirements. This authorization meant that labs other than the CDC could now conduct COVID-19 testing, including both government funded labs, like the Mass General Hospital’s Clinical Microbiology Laboratory and testing companies, like Quest Diagnostics. With the wait for new CDC test kits taking weeks, the validation and EUA application process for these CLIA-certified labs proved to be too slow, with only 12 labs receiving authorization for testing. On February 29th, the FDA changed the rules to allow labs that have created and validated their own tests to start testing patient samples immediately, as long as they notify the FDA of their work and submit an EUA to the FDA within 15 days. There are about 260,000 CLIA-certified labs across the US and, to date, 97 have applied and been verified for COVID-19 testing. Labs that conduct tests are required to immediately notify federal, state, and local public health agencies of all positive results. A state or territory can choose to forgo this FDA process by authorizing any lab within the state or territory to develop and perform a test through state law without interference or review from the FDA. Thus far, only a few states and testing centers have chosen to create their own tests without validation by the FDA.
Although every state could produce its own test kits, either via FDA oversight of CLIA-certified labs or direct state approval, some states still chose to wait for the CDC to distribute corrected test kits weeks after the recall of the dysfunctional ones. Even so, many states did take advantage of the FDA’s decision to expand test development and processing beyond the CDC. This effort by states and individual labs within their borders greatly increased the number of available COVID-19 tests and helped the United States begin testing patients much quicker than otherwise would have been possible.
In order to fully understand the prevalence of disease in a community, the most useful information would come from a random sample test to understand the number of people in the general population that are currently infected with COVID-19, as well as the number of people who have previously been infected with COVID-19 and built up some immunity towards the disease. The number of currently infected people can be determined using tests that directly assess the presence of the virus (Figure 1). In contrast, the number of people who were infected in the past could be identified using what scientists refer to as a serological test. Serological tests look for the presence of antibodies that have been made in a person’s body to defend them from a virus. The presence of COVID-19 antibodies in a person’s blood suggests that they have already been infected by the SARS-CoV-2 virus and built up immunity to it. Because it is known that COVID-19 can present with symptoms or without symptoms, serological testing is helpful for identifying people in the population that have been exposed to COVID-19 and become immune to it but never had any of the known symptoms associated with the disease. Ideally, this random sampling would be repeated regularly to estimate trends in infection rates. To get a clearer idea of how widespread COVID-19 transmission has been, the CDC has launched a number of small scale studies in an effort to randomly sample people for the presence of antibodies against the SARS-CoV-2 virus. Although the currently running CDC studies are a great start, wide-spread, random testing is necessary to fully understand the spread of the disease and the CDC plans to launch a broader national scale study over the summer to achieve this (Figure 2).
Despite every state and sovereign nation being approved to conduct their own COVID-19 testing, there is still a deficit in testing capability due to a limited number of CLIA-certified labs, shortages of supplies and equipment, and limits on the number of tests that can be performed in a single testing facility in a day. The recent FDA approval and promise of technological innovations in testing offers hope of rapid COVID-19 testing that could greatly expand the number of patients who could be tested in a given day, as well as increased access to testing in rural areas. However, these sorts of tests have yet to be widely deployed and tested for accuracy. Moreover, the ability of states to secure testing kits and reagents has been worsened by states having to bid against each other for essential supplies. State testing has also been largely dependent on the local urgency of testing, with states that have more patients presenting COVID-19 symptoms moving quickly to establish and expand testing (Figure 3). As of May 17th, New York currently has administered the largest number of tests at 1,338,048 but has not yet administered the largest number of tests per 1000 people at 68.8 people per 1000, surpassed by Rhode Island at 99.1 per 1000, and followed by Massachusetts at 63.2 per 1000. These states lead the nation in testing mostly because they have been the first states to be hit with high numbers of patients with COVID-19 symptoms. Four states and territories– Puerto Rico, Maine, Idaho, and Arizona– are currently testing less than 20 people per every 1000 people in the population as of May 16th, 2020.
A COVID-19 free future
As we move forward in combating COVID-19, it will be important to not only test the broad population for the current presence of SARS-CoV-2 infection but also to test individual immunity to SARS-CoV-2 infection. Testing companies are working on developing at-home testing, with 12 different research groups and companies already gaining FDA approval for a test which will likely resemble a blood sugar test with a finger-prick. The FDA has said that they will allow companies to develop and distribute serological tests, which can determine built-up immunity by testing for the presence of antibodies against SARS-CoV-2 but cannot test for a current SARS-CoV-2 infection, for at-home use. Serological testing will be incredibly useful for individuals who are trying to determine their personal risk for contracting the disease and for governments trying to determine how widespread COVID-19 infection has been.
As COVID-19 testing and serological tests continue to be developed and their use is scaled up on a state-by-state basis, it will become increasingly important for local governments to ensure that tests are being distributed fairly throughout their populations. It is crucial that testing reach both populous and rural regions within states and that they collect demographic data on tested patients, which will allow states to ensure that testing is being distributed equitably. As COVID-19 cases surge, it has become increasingly obvious that minority and immigrant populations are at particular risk for contracting and dying from COVID-19. Many factors worsen the risk in these populations, including the increased presence of comorbidities (the presence of two or more chronic medical conditions or diseases within the same patent), the increased number of essential workers within these populations, and the inability to socially distance from family members in shared housing. It will also be crucial for federal and state governments to support tribal nations, which are already facing an uphill battle as COVID-19 cases spread quickly across reservations. Lack of COVID-19 testing has not only slowed the distribution of critical medical care and equipment where it will be most needed but has also greatly hindered our understanding of how COVID-19 spreads. It will be critical for state governments to quickly scale testing in order to understand how widespread COVID-19 has become and how much of the population is at risk.
Kayla Davis is a sixth-year Biological and Biomedical Sciences student in the Graduate Schools of Arts and Sciences at Harvard University.
Jovana Andrejevic is a fourth-year Applied Physics Ph.D. student in the School of Engineering and Applied Sciences at Harvard University.
For more information:
Check out this tracker for COVID-19 testing numbers by state
Here is more on the science behind how the COVID-19 test works