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Does time of day influence COVID-19 test results? Ian Montgomery/EyeEm/Getty Images
  • A new study finds that the accuracy of reverse transcription-polymerase chain reaction (RT-PCR) COVID-19 tests follows a daily pattern.
  • The highest number of accurate positive results occur with midafternoon tests, while evening tests increase the number of false positives.
  • The study also suggests that midafternoon is the time of day at which both symptomatic and asymptomatic individuals are most likely to pass on the SARS-CoV-2 virus to others.

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When a COVID-19 test returns a false-positive result — meaning a person does not have a SARS-CoV-2 infection, yet the test is positive — this disrupts that person’s life unnecessarily.

However, a false negative — when someone does have an infection, but the test is negative — is more detrimental. This is because treatment is mistakenly deferred, and the individual may infect others as they continue to participate in their regular daily activities.

A new study from Vanderbilt University in Nashville, TN, suggests that the time of day at which a person takes an RT-PCR COVID-19 test may affect the likelihood of an inaccurate result.

The study found that the participants were up to twice as likely to receive an accurate positive result if they got tested in the middle of the day and not at night.

Principal investigator Dr. Carl Johnson tells Vanderbilt University Research News, “Taking a COVID-19 test at the optimal time of day improves test sensitivity and will help us to be accurate in diagnosing people who may be infected but asymptomatic.”

The study findings suggest that the human body’s daily clock — its circadian rhythm — influences the behavior of the SARS-CoV-2 virus throughout each 24-hour cycle. Other research regarding viral and bacterial infections has supported this hypothesis.

The study appears in the Journal of Biological Rhythms.

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The authors of the study analyzed a data set of 86,342 clinical tests that were administered at around 130 clinics between March and August 2020. The clinics were affiliated with a regional healthcare network in the southeastern United States. Both symptomatic and asymptomatic individuals underwent testing.

The highest number of positive results were from tests administered in midafternoon, at around 2 p.m.

This indicates that it is at this time of day that viral shedding, which is the release of infected particles into the blood and mucus, is most active.

Dr. Johnson told Medical News Today in an email, “The reason why we’re implicating shedding is that the highest amount of free viral particles in the mucus, [blood, or both] should occur right after the viral particles burst out of the host cells (i.e., are shed) and before they infect new host cells.”

During shedding, a person with a SARS-CoV-2 infection — even if they are asymptomatic — is most likely to transmit the virus when talking, exhaling, and eating near other people.

The analyzed data also indicate that an individual’s viral load becomes lower after 8 p.m. This means that a positive result from a test taken at that time of day is more likely to be a false positive.

“Because the circadian clock regulates the immune system, immunity functions better or worse at different times of day. This is a likely reason why [SARS-CoV-2] viral shedding could be rhythmic. Perhaps the virus sheds at a time of day when the immune system is least able to deal with it. But this is merely a prediction at this stage — no hard evidence on this point yet.”

– Dr. Carl Johnson

The researchers adjusted the results for age, sex, race, location of testing, month, day of the week, and other factors — “we eliminated the potential confounders that we could think of,” said Dr. Johnson.

The analysis revealed a 1.7-fold variation in the likelihood of a positive result over a 24-hour period.

The authors of the study hope that its insights will lead to more accurate test results when one considers the circadian cycle of SARS-CoV-2.

They also cite potential policy implications of their findings if additional testing confirms their insights.

First, understanding the 1.7-fold variation in tests’ sensitivity over the course of a day can help clinics “optimize test collection time, result interpretation, and patient counseling.”

Second, knowing the time of day when shedding is most active can help those who deliver care devise patient-visit schedules that will minimize the risk of spreading the virus.

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