Why Early Afternoon Is the Best Time For Covid Testing

Covid is more frequently detected in the middle of the day due to circadian rhythm-driven fluctuations in how immune cells interact with the virus. 

This is especially important for those being given rapid tests, which are less sensitive than PCR tests. And could provide healthcare officials with better information as more of the population is vaccinated, thus helping focus on real problem areas. JL

Linda Geddes reports in The Guardian:

Covid-19 tests may be less likely to give false negative results if taken during the early afternoon, compared with other times of day. A likely explanation is increased viral shedding during the early afternoon, because of daily “circadian” fluctuations in how our immune cells interact with coronavirus. Covid-19 is more frequently detected in the middle of the day. Sample collection at these times may reduce false negative results, particularly in those who have lower viral loads. The timing of tests (is) important for rapid antigen tests, such as those being used by schoolchildren and their families, as these are more prone to giving false negative results than PCR tests.

People may shed more coronavirus in the afternoons, suggesting this may be the best time of day to take tests, while separate research indicates that school attendance has a minimal impact on serious Covid-19 infections.

The phased return of children to classrooms across the UK has prompted widespread concern that this could lead to an increase in infections. Because of this, college and secondary schoolchildren are required to take twice weekly lateral flow tests, to monitor rates of infection in the community.

However, new research, which has not yet been peer reviewed, suggests Covid-19 tests may be less likely to give false negative results if taken during the early afternoon, compared with other times of day. Candace McNaughton at Vanderbilt University Medical Center in Nashville, US, and colleagues examined the results of 30,000 PCR-based tests performed in the Nashville area between March and June last year, and found a twofold variation in the proportion that gave a positive result across the 24-hour day, with a peak at around 2pm.

Although they couldn’t entirely rule out the possibility that this could be due to different groups being tested at different times of day, a more likely explanation is increased viral shedding during the early afternoon, because of daily “circadian” fluctuations in how our immune cells interact with coronavirus, they said.

Studies of other viruses, such as influenza, have also indicated that an individual’s symptoms and viral shedding may vary across the 24-hour period.

It is also possible that other variations in our physiology, such as our nasal secretions, over the 24-hour day may interfere with the amount of virus collected on nose and throat swabs, said Dr Rachel Edgar, a virologist at Imperial College London, who was not involved in the research.

To confirm this, researchers would need to infect individuals with coronavirus and then monitor their viral loads at different times of day. Until such trials are done, McNaughton favours the precautionary principle: “If I wanted to get the most accurate test possible, I would show up for my test during the early afternoon,” she said.

The timing of tests may be particularly important for rapid antigen tests, such as those being used by schoolchildren and their families, as these are more prone to giving false negative results than highly sensitive PCR tests.

Edgar, who studies how the circadian clock affects viral infection, said: “Although understanding the reason behind the observed variation is important, the evidence presented here suggests that Covid-19 is more frequently detected in the middle of the day, and sample collection at these times may help reduce the incidence of false negative results, particularly in those who have lower viral loads.”

Meanwhile, a separate analysis has indicated that although adults who live with children experienced a small increased risk of Covid-19 infection and hospitalisation during the first part of the pandemic’s second wave, , they were no more likely to be admitted to intensive care unit or to die than adults without children.

The research, published in the British Medical Journal, was based on an analysis of anonymised medical records for 12 million British adults during wave 1 and 2 of the pandemic. It found no increased risks for adults aged 65 and under living with children of any age during the first wave, when schools were closed.

During the second wave, the increased risk was equivalent to one additional infection per 100 people for those living with primary-aged children, and two additional infections for those with secondary-aged children, compared with those living without children.

There was no increase in risk of death in either wave. In fact, people living with children aged 0-11 years were less likely to die of Covid-19 during both periods.

Liam Smeeth, professor of clinical epidemiology at the London School of Hygiene & Tropical Medicine, who was involved in the research said: “This doesn’t mean that we can be complacent, and we need to keep on monitoring and measuring what’s going on, taking all the steps to minimise spread that are being taken. But the absolute increased risks are really, really small, and they also need to be put in the context of the huge benefit to society of schools being open.”

As for why the additional risk was so small, given that children are known to become infected with and transmit the virus, their suspicion is that their caregivers catch more colds from seasonal coronaviruses, and are therefore more likely to possess antibodies that may cross-react with Sars-CoV-2. It may also be that people living with children are slightly healthier population overall, Smeeth said.