Study Suggests Day 4 of Symptoms Best for Accurate COVID-19 Tests

Testing for COVID-19 on the first day of having symptoms is common for those who suspect an infection. However, a study published in Clinical Infectious Diseases suggests that for individuals using at-home rapid tests, the optimal time for testing may be on the fourth day of experiencing symptoms.
Researchers analyzed data from 348 adults who were newly diagnosed with COVID-19 based on PCR testing. These tests are considered the gold standard for accuracy because they are very sensitive and can detect even small amounts of coronavirus. This is the type of COVID test you’d typically get at a doctor’s office and requires a lab analysis to get results.
All of the participants in the study shared information regarding when their symptoms started and any recent COVID-19 testing they had done. The researchers then performed an analysis to determine—hypothetically—when rapid tests would be most sensitive among this group of people, in part by using something called a single molecule array test to look at antigen concentrations.
The findings suggest rapid test results would be most likely to match PCR test results when conducted four days after symptoms began. According to the study, this is when the amount of virus in the body, known as the viral load, typically reaches its highest point.
“This means that the sensitivity of home COVID tests is expected to be highest around the fourth day of symptoms, even though many symptomatic people with SARS-CoV-2 infection might test positive on home tests before that,” senior study author Nira Pollock, MD, PhD, associate medical director of the infectious diseases diagnostic laboratory at Boston Children’s Hospital.
The accuracy of a test depends on its sensitivity, specificity, and the detectable amount of the disease, like the COVID viral load, said Charles Bailey, MD, medical director for infection prevention at Providence St. Joseph Hospital and Providence Mission Hospital in Orange County, California.
This may be because the researchers were testing a highly immune adult population; 91% had a history of vaccination, natural infection, or both.
Sensitivity refers to the test’s ability to accurately detect infections, while specificity refers to the test’s ability to rule out an infection in someone who is not COVID-positive, Heba Mostafa, PhD, MBBCh, associate professor of pathology at the Johns Hopkins University School of Medicine and director of the Molecular Virology Laboratory at the Johns Hopkins Hospital. Tests with low specificity are more likely to show a false positive.
“Based on the publication, the sensitivity is expected to increase at day four, and the specificity is high regardless of the day the test is performed,” Mostafa said. “But based on all of the information we have collected so far, the sensitivity of the [rapid] antigen tests is lower than a molecular [PCR] test. Symptomatic people with a negative antigen test should be tested with a second test 48 hours after the first test—this approach is expected to increase sensitivity.”
The researchers say you shouldn’t change your testing habits based on this small study alone. People should stick to the current guidelines recommended by the Centers for Disease Control and Prevention (CDC) if they have any COVID-19 symptoms. This means testing immediately.
Those who test negative for COVID-19 on a rapid test should repeat the test 48 hours later.
Pollock said that even though her study found certain peak times for testing, it doesn’t necessitate delaying testing when experiencing symptoms such as headaches, sore throat, coughing, stuffy nose, fever, or chills. The sooner you test positive, the sooner you can make decisions about isolation and treatment to keep yourself and others safe.
“The key is that people need to know that one test is not enough. If they test negative on that first test, they need to test again 48 hours later, as recommended by the FDA and CDC,” said Pollock. “Our study suggests that if that second test is negative, another test on the fourth or even fifth day of symptoms might be needed.”
According to Bailey, established policies and guidelines are generally not changed based on a single study. Plus, the current study had a relatively small sample size and used PCR cycle threshold data to estimate hypothetical results of rapid antigen tests, which he said wouldn’t typically lead to policy changes.
“A larger sample with adequate representation of all relevant patient cohorts (e.g., age, gender, vaccine status, immune competency, etc.) and inclusion/performance of antigen tests would be needed to drive a guidance change, in my opinion,” said Bailey.
Still, he said research like this is a step in the direction towards updated guidelines in the future if necessary—especially as the study comes from the “CDC’s backyard in Atlanta.”
CDC spokesperson Jason McDonald told that the CDC updates its guidance when needed to align with ongoing and up-to-date monitoring of data.
“Agency officials and scientists are actively reviewing COVID-19 guidance to ensure that it continues to reflect the current state of the virus and data,” McDonald said.
If you were exposed to someone with COVID-19 and don’t have any symptoms, wait at least 5 full days after your exposure before taking a test, said McDonald.
He reiterated that if you test negative using an at-home rapid test, you should test again in 48 hours. If both tests are negative, consider retesting after another 48 hours for a total of three tests. Free at-home tests are available to order at COVIDTest.gov.