While Covid-19 patients flood hospitals across the country, doctors face an impossible question. Which patients in the emergency room are more likely to deteriorate quickly and which are more 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 found that people whose bodies teemed with the coronavirus more often became seriously ill and were more likely to die, compared to those who carried much less virus and were more likely to come out relatively unscathed.
The results suggest that knowing the so-called viral load – the amount of viruses in the body – could help doctors predict a patient’s course, distinguishing those who may need an oxygen test only once a day, for example, from those who need to be. monitored more closely, said Dr. Daniel Griffin, an infectious disease physician at Columbia University in New York.
Tracking viral loads “can really help us stratify risk,” said Dr. Griffin. The idea is not new: viral load management has long been the basis of care for people with HIV, for example, and to prevent 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 laboratories can report not only whether a person has been infected with the coronavirus, but an estimate of how much virus has been carried in his body.
This is not a policy change – labs could have reported this information all the time, 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 put pressure on laboratories to record this information.
“This is a very important move by the FDA,” said Dr. Michael Mina, an epidemiologist at the Harvard School of Public Health TH Chan. “I think it is a step in the right direction to get the most out of one of the only pieces of data that we have for many positive individuals.”
The FDA move followed a similar move by the Florida Department of Health, which now requires all laboratories to report this information.
The omission of viral load in the test results was a missed opportunity not only to optimize depleted clinical resources, but also to better understand Covid-19, experts said. Analyzing viral load shortly after exposure, for example, can help reveal whether people who die from Covid-19 are more likely to have high viral loads early in their illness.
And a study published in June showed that viral load decreases as the immune response increases, “just as you would expect it to be for any old virus,” said Dr. Alexander Greninger, a virologist at the University of Washington in Seattle, who led the study.
An increase in the average viral load in entire communities may indicate an increase in the epidemic. “We can get an idea of whether the epidemic is growing or waning, not counting the case count,” said James Hay, a postdoctoral researcher in Mina’s laboratory.
Fortunately, data on viral load – or at least a rough estimate of it – is readily available, incorporated into the results of the PCR tests that most laboratories use to diagnose a coronavirus infection.
A PCR test is performed in “cycles”, each doubling the amount of viral genetic material originally extracted from the patient’s 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 limit, or Ct, implies a high viral load in the patient. If the test is not positive until many cycles have been completed, the patient probably has a lower viral load.
Researchers at Weill Cornell Medicine in New York recorded viral loads among more than 3,000 patients hospitalized with Covid-19 on the day of their admission. They found that 40 percent of patients with high viral loads – whose tests were positive at a Ct of 25 or less – died while in the hospital, compared with 15 percent of those who tested positive at higher Ct and presumably more viral loads. low.
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 with 27.5 in those who survived the illnesses. People who were asymptomatic had an average value of 29.6, suggesting that they carried much less virus than the other two groups.
These numbers may seem to vary very little, but they correspond to millions of viral particles. “These differences are not subtle,” said Greninger. A study from his laboratory showed that patients with Ct less than 22 had more than four times the chance of dying in 30 days, compared with those with a lower viral load.
But using Ct values to estimate viral load is a complicated practice. HIV viral load measurements are highly accurate because they are based on blood samples. Tests for coronavirus depend on rubbing the nose or throat – a procedure that is subject to user error and whose results are less consistent.
The amount of coronavirus in the body changes dramatically during the course of the infection. Levels increase from undetectable to produce positive test results in just a few hours, and viral loads continue to increase until the immune response is activated.
Then, viral loads decrease rapidly. But viral fragments can remain in the body, triggering positive test results long after the patient is no longer infectious and the disease has been cured.
Given this variability, capturing viral load at one point in time may not be useful without more information about the path of the disease, said Dr. Celine Gounder, an infectious disease specialist at Bellevue Hospital Center and a member of the new coronavirus advisory group. administration.
“When on this curve are you measuring your viral load?” Asked Dr. Gounder.
The exact relationship between a Ct value and the corresponding viral load may vary between tests. Instead of validating this quantitative relationship for each machine, the FDA authorized the tests to provide diagnostics based on a cut to the cycle limit.
Most manufacturers conservatively define the limits of their diagnostic machines from 35 to 40, values that generally correspond to an extremely low viral load. But the exact limit for a positive result, or for a specific Ct to indicate infectivity, will depend on the instrument used.
“That’s why I look forward to many of these assessments based on Ct values,” said Susan Butler-Wu, director of clinical microbiology at the University of Southern California.
“It is certainly 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 versus non-infectious state me makes you very nervous. “
Other experts acknowledged these limitations, but said the benefit of recording Ct values outweighed concerns.
“All of these are valid points when looking at an individual patient’s test results, but that doesn’t change the fact that, on average, when you look at the admission test results for these Ct values, they really identify the patients at high risk of decompensation and dying, ”said Dr. Michael Satlin, an infectious disease physician and lead researcher in the Weill Cornell study.
Dr. Satlin said that adjusting his team’s results to the duration of symptoms and several other variables did not alter the high risk of death in patients with high viral loads. “No matter how hard you try to adjust, statistically, this association is extremely strong and will not go away,” he said.
Also at the population level, Ct values can be valuable during a pandemic, said Dr. Hay. High viral loads in a large group of patients can indicate recent exposure to the virus, signaling a sudden increase in transmission in the community.
“This could be a great surveillance tool for environments with fewer resources that need to understand the path of the epidemic, but do not have the capacity to conduct regular and random tests,” said Dr. Hay.
Above all, he and others said, viral load information is too valuable a metric to be ignored or discarded without analysis.
“One of the things that has been difficult in this pandemic is that everyone wants to do evidence-based medicine and wants to go at the appropriate speed,” said Greninger. “But we should also expect certain things to be true, as more viruses are generally not good.”