Defining Key Terms

• PCR Test: The standard global coronavirus test, known for its accuracy in detecting even minimal viral presence. However, it is not easily scalable due to shortages of both tests and testing facilities in the U.S.
• Antigen Test: A type of rapid test that provides results in as little as 15 minutes. It is cost-effective and easy to administer, but lacks the accuracy of PCR tests.
• FDA: The agency responsible for evaluating new tests, ensuring their accuracy is comparable to that of PCR tests for approval.
• Dr. Michael Mina: An epidemiologist advocating for antigen tests and critical of the FDA's stringent accuracy requirements.
• Quick Fixes: Solutions that seem straightforward and promise transformative results, but often fail to deliver.
• Federal Officials: Under scrutiny for their pandemic response, they are on the lookout for simple yet effective solutions.
• You: Frustrated and skeptical about the national pandemic response, hoping for innovative solutions that are quick and efficient.
• The U.S.: A nation on the brink of a significant election.

Current State of COVID-19 Testing

Back in March, I discussed the myriad technical, logistical, and regulatory challenges affecting coronavirus testing in the U.S. While other nations established robust testing and contact tracing systems, the U.S. was only beginning to confront a pandemic for which it had no clear plan. States and localities scrambled to manage outbreaks, resulting in a disorganized testing environment characterized by under-resourced public health labs, universities, and private companies struggling to meet overwhelming demand for PCR tests. Months later, long testing lines, significant backlogs at labs, and a lack of national coordination for contact tracing are still prevalent. It's evident that the current state of affairs is inadequate; change is necessary.

Recently, a wave of optimism has surrounded antigen tests, a rapid testing option that yields results in as little as 15 minutes and can be conducted outside of lab settings. This sparks visions of a future where children are tested upon entering schools, adults at their workplaces, gyms, and grocery stores. Those who test positive would be sent home, while others could return to a more typical lifestyle. This vision is so appealing that XPrize is offering $5 million to anyone who can develop such a test.

However, existing antigen tests are not yet capable of fulfilling this vision. The tests that are quick and user-friendly still lack the required accuracy for widespread use, leading to both false positives and negatives at concerning rates. Experts warn that the public might misinterpret unreliable test results; those who receive false positives could mistakenly believe they are contagious, while those who test negative may assume they are safe and neglect necessary precautions such as distancing and mask-wearing.

Yet, if one believes in this vision despite the tests' imperfections, as Dr. Mina does, another hurdle arises: the FDA. For a test to gain federal approval, it must meet specific sensitivity and specificity standards relative to PCR, the gold standard in virus detection. While a test does not need to be as sensitive as PCR, it must achieve a minimum threshold that current antigen tests have not yet reached.

Consequently, those advocating for immediate implementation of this vision may need to persuade the FDA to modify its approval criteria. One strategy could involve questioning the sensitivity of PCR testing itself.

Is PCR Too Sensitive?

Is PCR a sensitive test? Yes, it can detect very small amounts of the virus.

Is this a positive aspect? Generally, yes. Early detection reduces the chance of transmission. PCR can identify the virus from nasal samples, even in cases of poor collection technique, and can detect viral presence in saliva, even when the quantity is low. It can also identify virus in samples that have partially degraded over time, as well as those transported in various media.

Occasionally, PCR may detect residual genetic material from a past infection — remnants that do not pose a risk of contagion.

Ah. You read this over your morning coffee, and the article implies that most people testing positive might fall into this post-infection category.

But is this assertion accurate? Likely not.

Let’s clarify.

You carry minimal amounts of the virus at two key moments during infection: the onset and the recovery phase. The latter period generally lasts longer than the initial phase, leading the article to conclude that those with little viral load are likely past their peak contagiousness. By examining PCR data from multiple labs, they infer that numerous samples indeed show low viral loads.

But can we reliably gauge how much virus an individual carries based solely on PCR results? This remains a contentious point, even among scientists accustomed to well-controlled experiments as opposed to variable clinical samples.

PCR test results are not merely positive or negative; they produce numerical values. Lower numbers correlate with higher viral loads, while very high numbers indicate no viral presence — a negative result. The middle range, however, can lead to confusion. A high value might suggest a low viral load, but could also stem from various clinical factors such as timing between sampling and processing, collection techniques, and sample consistency. In general, PCR's numerical output isn’t a reliable indicator of an individual's viral load.

Despite this, the article relies on these numbers, establishing a cutoff above which it concludes "insignificant amounts of virus" are present. It fails to specify the cutoff or the rationale behind it, hindering comparisons with data from other labs. If other facilities do not observe similar high PCR results, discrepancies might arise from specific laboratory conditions or geographical factors, including equipment differences, sampling methods, transport and storage protocols, and the timeliness of testing requests. Lengthy wait times could bias results toward late-stage infections.

In summary, we cannot accurately infer "contagiousness rates" based on PCR numerical data, nor can we generalize findings nationwide. The claim that 90% of individuals are non-contagious likely encompasses all stages of infection, and suggesting they need not isolate could have severe ramifications.

The Risks of Simplistic Solutions

Straightforward solutions are appealing. Amid a global pandemic and a critical election, the allure of an easy fix can be dangerously misleading.

Dr. Mina advocates for a policy shift that would impose stringent caps on the PCR values linked to positive results. While this change could significantly lower reported infection rates in the short term, it would create a false sense of pandemic control. In the long run, this could lead to an increase in viral transmission, as individuals who receive a "clear" result may ignore isolation and contact tracing protocols.

Despite the lack of data connecting these values to the transmissibility of the virus, and a warning from the College of American Pathologists, CDC officials are considering this proposal for future policy decisions.

Simple solutions are appealing.

Citing Dr. Mina, various media outlets have framed the widespread adoption of antigen tests as an obvious choice. They describe rapid tests fit for daily at-home use as "the wand that will accomplish this feat," claiming there’s "no technical hurdle…only a lack of political will." Dr. Mina further asserts that these strip tests could be "mass-produced in weeks and freely distributed by the government to everyone in the country."

However, numerous experts caution that current antigen tests aren't suitable for the extensive surveillance testing that Dr. Mina envisions. One study indicated that testing all elementary school students three times a week would yield nearly 800,000 false positives weekly. If millions are tested daily, positive results may become meaningless as people disregard what they see as unnecessary isolation. Negative results are also questionable, with the CDC recommending that anyone exhibiting symptoms or with known exposure should "confirm negative antigen test results with an RT-PCR test." Moreover, supply chain challenges that plague PCR testing are likely to arise if testing is scaled to Dr. Mina's proposed levels. Although the concept of universal rapid testing is compelling, we currently lack the tests necessary to turn it into reality.

Despite ongoing issues with Abbott's antigen tests, which were recently linked to outbreaks at the White House, the government has procured 150 million rapid tests from the company, promoting this initiative as "President Trump's all-of-America approach to bolstering our world-leading COVID-19 testing capacity," and "fully leveraging America's industrial and innovative capabilities." In July, rapid point-of-care tests were distributed to nursing homes, only to be discontinued due to accuracy issues.

Simple solutions appeal not only to federal officials but to us as well. With the election approaching, the current administration is incentivized to invest in quick fixes presented to the public as cure-alls — and we have little time to witness their shortcomings.

Fast, frequent, and widespread testing could indeed be transformative, as Dr. Mina ardently asserts. It’s a valuable goal to strive for, even if we never fully achieve it. However, attempting to reach this goal by undermining public confidence in the only reliable test we currently have is shortsighted. Misleading messaging aimed at uniting the public around an unproven alternative will only deepen public apathy over time.

Simple solutions are enticing.

However, they divert our attention from the need for a comprehensive and coordinated response appropriate to the complexity of the crisis. The true solution requires as much emphasis on public trust as it does on technological fixes. It necessitates the use of multiple testing modalities, taking into account the balance between sensitivity, frequency, and the crucial role of public confidence. It should prioritize contact tracing and promote consistent, scientifically-backed messaging around mask usage and social distancing, while keeping the public informed about new treatments and vaccines without fostering false hopes.

But simple solutions continue to attract attention.

And so do simplistic narratives.

The first video discusses the availability of free at-home COVID-19 tests later this fall and provides guidance on how to order them.

The second video explains how to properly conduct an at-home COVID-19 rapid antigen test, ensuring accurate results.