It is difficult to measure how long a person with COVID-19 will remain infectious.Credit: Agustin Marcarian/Reuters/Alamy
When the US Centers for Disease Control and Prevention (CDC) cut the recommended isolation time for people with COVID-19 in half to five days in December, they said the change was motivated by science. . Specifically, the CDC said that most SARS-CoV-2 transmissions occur early in the course of illness, one to two days before the onset of symptoms and for two to three days afterward.
Many scientists questioned that decision then and continue to do so. Such dissent is reinforced by a series of studies confirming that many people with COVID-19 remain infectious well into the second week after first experiencing symptoms. Reductions in the length of the recommended isolation period, now common around the world, are driven by politics, they say, rather than reassuring new data.
“The facts of how long people are infectious really haven’t changed,” says Amy Barczak, an infectious disease specialist at Massachusetts General Hospital in Boston. “There is no data to support five days or anything shorter than ten days [of isolation].” Barczak’s own research, published on the preprint server medRxiv, suggests that a quarter of people who have contracted the Omicron variant of SARS-CoV-2 could still be infectious after eight days1.
a numbers game
Although the question is simple: how long is someone with COVID-19 contagious? Experts warn that the answer is complicated. “We always think of it as black and white … whether someone is infectious or not, but really, it’s a numbers game and probability,” says Benjamin Meyer, a virologist at the University of Geneva in Switzerland.
And that numbers game has changing rules and baselines. Emerging variants, vaccination, and different levels of natural immunity brought on by previous infection can influence how quickly someone can clear the virus from their system, Meyer says, and this ultimately determines when they stop being infectious. Behavioral factors also matter. People who feel unwell tend to mingle less with others, she adds, so the severity of a person’s symptoms may influence how likely they are to infect others.
One thing most scientists are confident of is that PCR tests can return a positive result even after someone is no longer infectious. This probably occurs when the tests, which detect viral RNA, detect non-infectious remnants left behind after removing most of the live virus.
In contrast, lateral flow (or ‘rapid antigen’) tests offer a better guide to infectivity, because they detect proteins produced by actively replicating viruses.
“There are still all these things that we’re not exactly sure about, but if I had to boil it down to one very concise message, it would be that if you’re antigen positive, you shouldn’t go out and interact closely. with people you don’t want to get infected,” says Emily Bruce, a microbiologist and molecular geneticist at the University of Vermont in Burlington.
What about someone who has been negative on a lateral flow test for a few days but still has a fever and dry cough? Bruce says it’s important to remember that while persistent symptoms may look and sound serious, they don’t indicate ongoing infectiousness.
“You can definitely have symptoms longer than you test positive for lateral flow,” she says. “And I think that’s because a lot of the symptoms are caused by the immune system and not directly by the virus itself.”
transmission tests
In countries such as the UK, the relaxation of isolation guidelines coincided with the withdrawal of free lateral flow testing. So assuming that many of the people following the new recommendations will stop isolating after five days, without being tested, scientists have been investigating in particular how many people with COVID-19 are likely to remain infectious after this point.
It’s not practical to track direct transmission of the virus from large numbers of people and measure how it declines over time, so the researchers rely on proxy measurements to determine the point at which they would expect people to stop being contagious.
Researchers with access to a high-security biosafety level 3 laboratory, such as Barczak, can do this by running experiments to test whether live SARS-CoV-2 can be cultured from samples taken from patients over several consecutive days.
“If you’re still shedding the virus that we can get out of your nose by culture, at least there’s a good chance you’re still infectious to other people,” she says. As different variants emerged and various research groups performed these experiments, Barczak says, a consensus emerged that it is highly unusual for people to shed cultivable viruses after ten days. “So it’s very unusual for people to remain infectious after ten days,” she says.
Other studies take a step further from the real world and use viral RNA levels measured by PCR tests to infer whether someone is infectious. This makes it easy to work with large samples. For example, a project run by the Crick Institute and University College Hospital, both in London, may be based on PCR tests carried out on more than 700 participants, obtained from the time symptoms developed.
A study based on this group suggests that a significant number of people retain viral loads high enough to trigger onward transmission between days seven and ten, regardless of the type of variant or how many doses of vaccines people have received. The study was published on the medRxiv preprint server on July 102.
“We’re not measuring live virus, but there’s a lot of work in the literature now that provides a pretty good mapping of what constitutes a viral load that is likely to produce infectious virus,” says David LV Bauer, a virologist at Crick. Institute who is a co-investigator on that study. “So while it’s not a perfect image, it’s reasonable.”
‘rebound phenomenon’
Yonatan Grad, an infectious disease specialist at the Harvard T.H. Chan School of Public Health in Boston, Massachusetts, who has worked on similar PCR-based studies of infectiousness, agrees that ten days is a useful rule of thumb for when people should no longer be contagious. But he cautions that a small number of people could still be infectious beyond that point.
Some of these cases in the United States have been linked to the common antiviral drug Paxlovid (nirmatrelvir-ritonavir), he says. “There is a rebound phenomenon where people will see their symptoms appear to resolve and may even come back negative on a rapid test, but then a few days later the symptoms and the virus come back.”
Barczak says that this is one of the key questions that researchers are studying now. “Antivirals change the dynamics of symptoms, they change the dynamics of the immune response, and they change the dynamics of how it’s cleared,” she says. “I think this is really important, because people are out in the world thinking that they are not infectious after ten days. But, if they have the Paxlovid bounce, they could be.”
Source: www.nature.com