As Covid-19 patients flood hospitals nationwide, doctors face an impossible question. Which patients in the ER are likely to deteriorate rapidly and what is the greatest chance of fighting and recovering the virus?
There seems to be a way to distinguish these two groups, although it is not yet widely used. Dozens of research articles published in the last few months have found that people whose bodies were infested with the coronavirus were more likely to become seriously ill and more likely to die, compared to those who carried far fewer viruses and were more likely to to arrive unharmed.
The results suggest that knowledge of the so-called viral load – the amount of virus in the body – can help doctors predict the course of a patient, and distinguish those who need oxygen only once a day, for example, from those who need it. is. more closely monitored, said Dr. Daniel Griffin, a doctor of infectious diseases at Columbia University in New York.
Tracking viral loads “can actually help us stratify the risk,” said Dr. Griffin said. The idea is not new: viral load management has long been the basis for caring for people living with HIV, for example, and stopping the transmission of the virus.
Little effort has been made to detect viral loads in Covid-19 patients. This month, however, the Food and Drug Administration said clinical laboratories can not only report whether someone is infected with the coronavirus, but also an estimate of how many viruses have been carried in their body.
According to two senior FDA officials who spoke on condition of anonymity, laboratories could have reported this information throughout because they were not authorized to speak publicly about the matter.
The news was nevertheless a welcome surprise to some experts who have been forcing laboratories to record this information for months.
“This is a very important step by the FDA,” said Dr. Michael Mina, an epidemiologist at the Harvard TH Chan School of Public Health, said. “I think it’s a step in the right direction to make optimal use of one of the only information we have for many positive individuals.”
The FDA change follows a similar step by the Florida Department of Health, which now requires all laboratories to report this information.
The omission of viral load from test results was a missed opportunity to not only optimize strained clinical resources, but also to better understand Covid-19, experts said. For example, analysis of viral load shortly after exposure may help to indicate whether people dying from Covid-19 are more likely to have high viral load at the onset of their disease.
And a study published in June showed that the virus load decreases as the immune response increases, “just as you would expect it to be for any old virus,” says Dr. Alexander Greninger, a virologist at the University of Washington in Seattle, who led the study.
An increase in the average virus load in entire communities may indicate an increase in epidemic. “We can get an idea of whether the epidemic is growing or declining, without relying on the number of cases,” said James Hay, a postdoctoral researcher in Dr. Mina’s lab, said.
Fortunately, viral load data – or at least a rough approach to it – is readily available, built into the results of the PCR tests 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 deliver a signal.
A positive result at a low cycle threshold, or Ct, implies a high viral load on the patient. If the test is not positive until many cycles are completed, the patient is likely to have a lower viral load.
Researchers at Weill Cornell Medicine in New York on the day of their survey recorded viral loads among more than 3,000 Covid-19 patients admitted to the hospital. They found that 40 percent of patients with a high virus burden – whose tests were positive at a Ct of 25 or lower – died in hospital, compared with 15 percent of those with positive tests at higher Cts and presumably 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 illnesses. People who were asymptomatic had a mean value of 29.6, indicating that they carry far fewer viruses than the other two groups.
These numbers seem to vary very little, but they correspond to millions of viral particles. “These are not subtle differences,” said Dr. Greninger said. A study by his laboratory showed that patients with a Ct of less than 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 an experience. Viral load measurements for HIV are very accurate because they are based on blood samples. Tests for the coronavirus depend on the nose or throat imprint – a procedure subject to user errors and the results of which are less consistent.
The amount of coronavirus in the body changes drastically during the infection. Levels rise from undetectable to positive test results within hours, and viral loads increase until the immune response begins.
Then viral loads decrease rapidly. But viral fragments can linger in the body, causing positive test results long after the patient has stopped being contagious and resolved the disease.
Given this volatility, recording viral load at one point may not be helpful without more information about the trajectory of disease, says Dr. Celine Gounder, a specialist in infectious diseases at Bellevue Hospital and a member of the coronavirus. advisory group of the incoming administration.
“When do you measure the virus load on that curve?” Ask dr. Gounder.
The exact relationship between a Ct value and the corresponding viral load can vary between tests. Instead of validating this quantitative ratio for each machine, the FDA authorized the tests to make diagnoses based on a cut-off for the cycle threshold.
Most manufacturers set the machining thresholds for diagnosis from 35 to 40 conservatively, values that usually correspond to an extremely low virus load. But the exact threshold for a positive result, or for a specific Ct to indicate contagion, depends on the tool used.
“That’s why I’m very concerned about many of these assessments based on Ct values,” said Susan Butler-Wu, director of clinical microbiology at the University of Southern California.
“It is definitely a value that can be useful in certain clinical circumstances,” said Dr. Butler-Wu said, “but the idea that you can have a unicorn Ct value that correlates perfectly with an infectious versus non-infectious condition makes me very nervous.”
Other experts acknowledged these limitations, but said the benefit of registering Ct values outweighed the concerns.
‘All of these are valid points when we look at the test results of an individual patient, but that does not change the fact that when they look at the test results of these Ct values, they really identify patients at high risk of compensating. and die, ”said dr. Michael Satlin, an infectious disease physician and lead researcher in the Weill Cornell study, said.
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 virus load. “No matter how you try to adapt, statistically, this association is very strong and will not go away,” he said.
Also at the population level, Ct values can be valuable during a pandemic, said dr. Hay said. High virus burden in a large group of patients may indicate recent exposure to the virus, indicating an emerging upsurge in community transmission.
“It can be an excellent oversight tool for institutions with fewer resources that need to understand the epidemic orbit but do not have the ability to test it regularly, at random,” said Dr. Hay said.
He and others have generally said that information about viral loads is too valuable a measure to be ignored or discarded without analysis.
“One of the things that was difficult in this pandemic is that everyone wants to do evidence-based medicine and go at the right speed,” said Dr. Greninger said. “But we should also expect certain things to be true, because more viruses are usually not good.”