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You are infected with the coronavirus. But how infected?

As Covid-19 patients flock to hospitals across the country, doctors are faced with an impossible question. Which emergency room patients are more likely to deteriorate quickly and which are most likely to fight the virus and recover?

It turns out that there may be a way to help distinguish these two groups, although it is not yet widely used. Dozens of research papers published in the past few months have found that people whose bodies were swarming with coronavirus more often became seriously ill and more likely to die, compared to those who carried much less virus and were more likely to ’emerge relatively unscathed.

Findings suggest that knowing the so-called viral load – the amount of virus in the body – could help doctors predict a patient’s progress, distinguishing those who might need oxygen monitoring. just once a day, for example, for those who need it. being watched more closely, said Dr Daniel Griffin, an infectious disease physician at Columbia University in New York.

Tracking viral loads “can actually help us stratify risk,” Dr. Griffin said. The idea is not new: managing the viral load has long been the basis of care for people with HIV, for example, and to curb the transmission of this virus.

Little effort has been made to track viral loads in patients with Covid-19. This month, however, the Food and Drug Administration said clinical labs could tell not only if a person is infected with the coronavirus, but also an estimate of how much of the virus is carried in their body.

This is not a change in policy – the labs could have reported this information from the start, according to two senior FDA officials who spoke on condition of anonymity because they were not authorized to speak publicly about the matter.

Still, the news came as a welcome surprise to some experts, who for months pushed laboratories to record this information.

“This is a very important decision by the FDA,” said Dr. Michael Mina, epidemiologist at Harvard TH Chan School of Public Health. “I think it’s a step in the right direction to get the most out of one of the only data we have for a lot of positive people.”

The FDA change follows a similar decision by the Florida Department of Health, which now requires all labs to report this information.

The omission of viral load from the test results was a missed opportunity not only to optimize the clinical resources requested, but also to better understand Covid-19, experts said. Testing the viral load soon after exposure, for example, could help determine whether people who die from Covid-19 are more likely to have a high viral load early in their illness.

And a study published in June showed that the viral load decreases as the immune response increases, “as you would expect it to be with any old virus,” said virologist Dr Alexander Greninger. at the University of Washington in Seattle, which led the study.

An increase in the average viral load in entire communities could indicate a rising epidemic. “We can get a feel for the growth or decline of the epidemic, not counting the number of cases,” said James Hay, postdoctoral researcher in Dr Mina’s lab.

Fortunately, viral load data – or at least a rough approximation of it – is readily available, incorporated into the results of PCR tests that most labs use to diagnose coronavirus infection.

A PCR test is performed in “cycles”, each doubling the amount of viral genetic material originally taken from the patient sample. The higher the initial viral load, the fewer cycles the test needs to find genetic material and produce a signal.

A positive result at a low cycle threshold, or Ct, implies a high viral load in the patient. If the test is not positive until many cycles are completed, the patient likely has a lower viral load.

Researchers at Weill Cornell Medicine in New York recorded viral loads among more than 3,000 hospitalized Covid-19 patients on the day of their admission. They found that 40% of patients with a high viral load – who tested positive at a Ct of 25 or less – died in hospital, compared with 15% of those who tested positive at higher Ct and probably at lower viral loads.

In another study, the Nevada Department of Public Health found an average Ct value of 23.4 in people who died from Covid-19, compared to 27.5 in those who survived their illness. Asymptomatic people had an average value of 29.6, suggesting that they carried significantly less virus than the other two groups.

These numbers may appear to vary very little, but they correspond to millions of virus particles. “These are not subtle differences,” Dr. Greninger said. A study from his lab showed that patients with a Ct below 22 were more than four times more likely to die within 30 days, compared to those with a lower viral load.

But using Ct values ​​to estimate viral load is cumbersome practice. Viral load measurements for HIV are very accurate because they are based on blood samples. Testing for the coronavirus relies on a swab from the nose or throat – a procedure prone to user error and with less consistent results.

The amount of coronavirus in the body changes dramatically during infection. Levels go from undetectable to positive test results in just a few hours, and the viral load continues to rise until the immune response kicks in.

Then the viral loads drop rapidly. But viral fragments can linger in the body, triggering positive test results long after the patient has ceased to be infectious and the disease is gone.

Given this variability, capturing the viral load at a given point in time may not be useful without more information on the trajectory of the disease, said Dr. Céline Gounder, an infectious disease specialist at the Bellevue Hospital Center and a member of the incoming administration coronavirus advisory group.

“When do you measure the viral load on this curve?” Asked Dr. Gounder.

The exact relationship between a Ct value and the corresponding viral load may vary between tests. Rather than validating this quantitative relationship for each machine, the FDA allowed the tests to deliver diagnostics based on a cutoff for the cycle threshold.

Most manufacturers conservatively set their machine’s diagnostic thresholds from 35 to 40, which is usually an extremely low viral load. But the exact cut-off for a positive result, or for a specific Ct to indicate infectivity, will depend on the instrument used.

“That’s why I’m very concerned about a lot of these Ct-based evaluations,” said Susan Butler-Wu, director of clinical microbiology at the University of Southern California.

“Certainly this is a value that can be useful in certain clinical circumstances,” said Dr. Butler-Wu, “but the idea that you can have a unicorn Ct value that correlates perfectly with an infectious condition versus a non-infectious condition makes me very nervous. “

Other experts recognized these limitations, but said the benefits of recording Ct values ​​outweighed concerns.

“All of these are valid when looking at the test results of an individual patient, but it doesn’t change the fact that on average, when you look at the admission test results of these Ct values, they identify really patients at high risk of decompensation. and dying, ”said Dr. Michael Satlin, infectious disease physician and principal investigator of the Weill Cornell study.

Dr Satlin said adjusting his team’s results for the duration of symptoms and several other variables did not change the high risk of death in patients with high viral loads. “No matter how you try to adjust, statistically this association is extremely strong and won’t go away,” he said.

At the population level too, Ct values ​​can be valuable during a pandemic, Dr Hay said. High viral loads in a large group of patients may indicate recent exposure to the virus, signaling an incipient surge in community transmission.

“This could be a great surveillance tool for less well-equipped settings that need to understand the trajectory of the epidemic, but lack the capacity to perform regular and random testing,” said Dr Hay .

Overall, he and others said, viral load information is too valuable a metric to be ignored or dismissed without analysis.

“One of the things that has been difficult in this pandemic is that everyone wants to be evidence-based medicine and wants to go at the appropriate speed,” Dr Greninger said. “But we should also expect some things to be true, like more viruses is usually not good.”

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