Unveiling the Untapped Potential: Discover Why Your Home Covid-19 Test Could Miss an Infection

With the rising number of Covid-19 cases nationwide, a significant number of individuals are reverting to at-home tests as a means of making informed choices regarding work attendance, school attendance for their children, and other activities.

Despite being extremely certain of their Covid-19 infection, many individuals will receive negative results from these tests. This may occur despite having a confirmed exposure or displaying unmistakable symptoms they have previously experienced.

That has led to speculation on social media that perhaps rapid tests have lost their ability to detect some of the newer coronavirus variants.

In Lynwood, California, free flu and COVID-19 vaccines were offered to members and the public in October 2022 at the LA Care and Blue Shield of California Promise Health Plans' Community Resource Center. There, syringes with vaccines were being prepared. (Photo by Mark J. Terrill/AP)

Dr. Michael Mina, an immunologist and epidemiologist who serves as the chief science officer at the telehealth company eMed, noted that every time a new variant emerges, a similar discussion arises on Twitter. Mina had advocated for the public sale of rapid lateral flow tests as a means to assist individuals in determining their contagious state.

Mina asserts that individuals who observe this phenomenon are not insane. There exist explanations as to why one may test negative for Covid despite actually being infected.

Primarily, the utilization of rapid tests has undergone changes compared to previous practices. Additionally, our immunity factors also come into play. Presently, a vast majority of us possess some form of innate immunity against the coronavirus, which ultimately influences the accuracy of the test as well.

Todd Merchak, co-leader of the RADx program at the National Institutes of Health, stated that although the tests continue to detect infections, they are still effective. The RADx program, which stands for "rapid acceleration of diagnostics," was established during the ongoing pandemic to expedite the development of coronavirus tests. Merchak emphasized that the existing COVID-19 tests have not been negatively affected by any new variants thus far.

RADx works with the US Food and Drug Administration to monitor new variants and continually assesses the performance of the Covid-19 tests sold in stores.

Tests are less vulnerable to variants

The efficacy of Covid-19 tests remains intact even when other measures like vaccines and monoclonal antibodies lose their effectiveness over time. This resilience arises from the fact that vaccines and antibodies specifically target the protruding spike proteins on the spherical viral envelope. These spikes undergo constant pressure from the environment, compelling them to undergo changes.

SAN ANSELMO, CALIFORNIA - MAY 02, 2022: In San Anselmo, California, a home Covid-19 test indicating a positive result is showcased. There has been a notable surge in Covid cases across a majority of the United States, with a projected 51% rise in cases over the preceding 14-day period. (Image credit: Photo Illustration by Justin Sullivan/Getty Images)

The demand for Covid-19 tests to be used at home is currently high, and there is no indication of any shortages occurring in the near future. Conversely, rapid tests predominantly focus on detecting the nucleocapsid proteins, also known as N-proteins, of the coronavirus. Unlike spike proteins, N-proteins exhibit less variability over time.

Researchers have prepared for any changes in the N-proteins.

In September 2022, a significant study funded by RADx and published in the journal Cell introduced a valuable tool - a comprehensive library documenting all potential variations of the N-protein over time. Using deep mutational scanning, the scientists evaluated the impact of each of these alterations on the ability of 17 antibodies employed in 11 commercially accessible rapid tests to attach to the virus. As a result, scientists can now swiftly determine if a particular test remains effective by comparing the changes in each new variant of the virus.

If the FDA suspects that a test has stopped working to detect a common variant, it conducts further analysis and may revoke authorization for the test.

When you test matters

The CDC recommends that people take a rapid test five days after a known virus exposure.

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According to an expert, when a household member tests positive for Covid-19, it is important to consider the viral kinetics. Typically, it takes about three to five days for the virus to reach a detectable level in tests.

According to him, this remains unchanged, despite the presence of new variants.

He mentioned that the new variants exhibit slightly faster replication within the body, but the time difference is a matter of hours rather than days compared to the original virus.

Now that our immune systems have become familiar with the virus, Mina believes that they initiate a quicker response, resulting in individuals experiencing symptoms at an earlier stage compared to before. This could potentially prompt individuals to undergo testing at an earlier phase of infection, even before the virus has replicated enough to be detected by a test.

"People are now opting for early testing, as early as the first or second day after exposure. However, it is important to note that the average person does not typically have a viral load that is detectable on PCR or antigen tests until day 3, 4, 5 or 6," stated Mina.

"This bias is a consequence of the convenient availability of at-home testing," he added.

To enhance accuracy, the FDA issued a safety communication urging individuals who obtain a negative result from a home test to repeat the test within 48 hours. This direction was included in the emergency use authorizations for all Covid-19 home tests in November.

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The recommendation to retest originated from a separate study funded by the government. The University of Massachusetts conducted research on over 5,000 individuals who were enlisted to evaluate the effectiveness of home Covid-19 tests in real-life scenarios. This study took place from winter 2021 to 2022.

During the study, participants administered rapid home tests to themselves every 48 hours over a period of 15 days. Additionally, they provided samples for PCR testing, a more precise method for detecting infections.

According to Dr. Nathaniel Hafer, an assistant professor of molecular medicine at UMass Chan Medical School, these tests excel in detecting even minuscule amounts of the virus, making them particularly effective in the early phase of an infection. Out of the 154 individuals involved in the study, 57 exhibited symptoms while the remaining 97 did not.

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Rapid home tests showed higher accuracy in individuals displaying symptoms. On the first day of infection, when symptoms were present, the tests detected the infection around 60% of the time. The accuracy increased to approximately 90% when the rapid test was repeated two days later.

However, rapid tests were found to be less effective in individuals without symptoms. In these cases, a single test only identified positive, asymptomatic cases around 9% of the time. Conducting a second test two days later increased the detection rate to approximately 62% for those who were positive but did not display symptoms. A third test conducted another two days later detected more than 75% of positive cases that were without symptoms.

"During the early stages of an infection, the virus level might be relatively low. Although PCR tests are capable of detecting the presence of the virus, rapid tests may not possess the required level of sensitivity," stated Hafer. "This is why it is crucial to conduct repeat testing after 48 hours."

Reason for frequent negative outcomes of rapid tests in children.

Another real-world study of rapid tests identified another reason the tests sometimes dont work well: operator error.

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A comprehensive study observed over 200 parents and 426 children attending a family clinic in Taiwan during the Covid-19 outbreak within their households. To aid in their protection, the families were provided with rapid home tests and accompanying instructions on proper usage. The average age of the participating children was 5, while the parents' average age was approximately 40. Although over 98% of the adults had received the vaccine, the majority of children had not been vaccinated due to Taiwan's previous recommendation against vaccinating children under the age of 5 at that time.

Covid-19 cases were confirmed through PCR tests, which aided in assessing the viral load in individuals.

Subsequently, researchers examined the effectiveness of rapid tests in detecting these cases. Surprisingly, even though children with more infections and symptoms than their vaccinated parents, their rapid tests frequently yielded negative results. This study revealed that negative rapid tests accurately indicated a child's good health only 38% of the time.

Researchers were perplexed by this finding. PCR tests revealed that the children who were infected had viral loads that were expected to be sufficient for yielding positive results on rapid tests. Additionally, children who tested negative often exhibited comparable high viral loads to those who tested positive, which provided researchers with a potential explanation: It seemed that, on certain occasions, the children were uncooperative when it came to providing a suitable sample, as many parents can confirm.

The study authors wrote that this discovery suggests that certain parents face challenges in collecting a reliable nasopharyngeal swab sample from their children, leading to inaccurate negative test results.

Apart from squirmy toddlers, Mina is eager for the day when it becomes normal for rapid home tests to consistently yield negative results, even after repeated testing.

"We can consider this as a triumph of our immune system, as it indicates that our immune system successfully suppressed the virus and prevented it from reaching a high enough level to trigger a positive test," he explained. "I believe this is the case for many individuals."