A recent study has shed light on how to enhance the effectiveness of a new wave of rapid tests, which includes tests for COVID, flu, RSV, and all-in-one tests.
In households across the United States, there are numerous unused COVID-19 tests.
When individuals experience symptoms, they often have questions: When is the best time to get tested? How reliable are the results? And what steps should be taken if the test is positive?
In a paper released on June 14 in the journal Science Advances, researchers from CU Boulder introduce a new mathematical model to swiftly address these questions, not just for COVID but also for emerging rapid tests for respiratory syncytial virus (RSV), the flu, and other infectious diseases.
One crucial finding: Recommendations can vary significantly depending on the specific virus.
“For COVID, we discovered that it is advisable to wait two days after symptoms appear before using a test because the virus may not be detectable until then,” explained first author Casey Middleton, a doctoral student in the Computer Science department and the IQ Bio program. “For flu and RSV, it is best to take the rapid test as soon as symptoms surface.”
A novel generation of all-in-one tests
Middleton and senior author Daniel Larremore, a computer science professor at the BioFrontiers Institute, developed this model to tackle various challenges that have arisen with the widespread availability of rapid tests post-pandemic.
In recent times, companies have introduced “all-in-one” tests that can simultaneously detect SARS-CoV-2 (the virus causing COVID-19), influenza A and B, and RSV, with some doctor’s offices and pharmacies offering a combined testing option on the spot.
At-home COVID testing has become routine, with individuals frequently performing nasal swab tests to safeguard their loved ones.
“If you’re deciding whether to attend a book club or visit grandparents for Bingo night, testing is a wise choice,” stated Larremore, whose laboratory integrates computer science, mathematics, epidemiology, and biology to address public health issues. “However, COVID has evolved, with each variant behaving differently, impacting how they interact with tests.”
When Middleton and Larremore input data on Omicron variants, patient behavior, and other factors into their computational model, they discovered that if a person with COVID uses a rapid test immediately upon experiencing symptoms, the test may produce a false negative result up to 92% of the time. Waiting two days after symptoms onset reduces this rate to 70%. Individuals who can afford a second test on the third day experience a lower false negative rate, with the tests detecting about a third of infections.
This is due to the fact that most people have previously been exposed, causing their immune systems to respond upon encountering COVID again, resulting in symptoms. Moreover, new variants in individuals with some immunity spread slightly slower than the original strain.
“Although symptoms appear sooner, it takes longer for the virus to reach detectable levels in your system,” Middleton added.
On the other hand, RSV and flu viruses multiply rapidly, so by the time symptoms manifest, there is already sufficient virus present to yield a positive test result.
“This is the dilemma,” Larremore remarked. “If you rush in and test for all three immediately, you can gain valuable insights from flu and RSV tests, but you may have tested too soon for COVID. Waiting a few days may be more opportune for detecting COVID, but may be too late for flu and RSV.”
While a 66% false negative rate might seem high for a COVID test, Larremore emphasized that the tests are designed to identify individuals with a high viral load who are most likely to infect others.
“Identifying only a third of infections can significantly reduce transmission if we identify those most likely to infect others,” he noted.
Rethinking isolation strategies
Given sufficient at-home tests, the study also proposes a “test to exit” approach, in which individuals test themselves again before deciding whether to resume work and social activities, offering a more efficient way to prevent additional COVID infections than the five-day isolation regimen recommended by the Centers for Disease Control until March.
“In most cases, the five-day isolation guideline led people to isolate for too long,” Middleton pointed out. “The test-to-exit strategy effectively releases individuals who are unlikely to transmit the virus early but retains those with high viral loads.”
Larremore’s earlier research played a crucial role in influencing the distribution of COVID-19 vaccines during the initial stages of the pandemic and in persuading policymakers to prioritize rapid testing.
Both Larremore and Middleton anticipate that their new model will assist companies in developing more effective tests, guide healthcare providers in offering better recommendations, and enable policymakers to provide prompt, data-driven guidance on testing in the event of another pandemic.
