Testing frequency, not precision, may be key to controlling outbreak: study
Repeat, generalized testing with rapid results is more effective at controlling an outbreak than using a more accurate test, according to two recently published research articles that draw on one crucial way Sars-Cov-2 behaves: people they are most infectious in the first week of your illness, when the viral load in your upper respiratory tract is at its highest.
The findings are significant for a city like Delhi, where the proportion of tests testing positive has been consistently higher than the acceptable limit of 8% for weeks, and officials are currently working on a strategy on how best to increase testing. keeping a balance. between the more reliable but slow RT-PCR test and the rapid but low sensitivity antigen tests.
“At least for viruses with infection kinetics similar to SARS-CoV-2, we found that the rate of notification is much more important than the sensitivity, although the more sensitive tests are nevertheless somewhat more effective,” said the study that included researchers from the University of Colorado. and Harvard University.
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Researchers make a distinction between the need to test more people when they are contagious versus those who may simply be infected. Using computational models of how viral load and infectivity evolve, they determined that infectivity increased once the viral load exceeded 10 ^ 6 viral RNA copies per ml (cp / ml). The RT-PCR method, they added, could detect 10 ^ 3 cp / ml in viral load, while rapid antigen and LAMP tests detected a concentration of 10 ^ 5 cp / ml.
Using the tests as a strategy to reopen cities “has put a microscope on the analytical sensitivity of virus assays, with a gold standard of quantitative real-time polymerase chain reaction (PCR).” But these, the report added, “are still expensive and, as lab tests, often have sample-to-result times of 24 to 48 hours.”
These findings, published in Science Advances, are related to another recent study published in The Lancet. In this, the authors analyzed all the scientific literature on Covid-19 up to June 2020 and found that patients had the highest viral load in the first week.
“SARS-CoV-2 titers in the upper respiratory tract peak in the first week of illness. Early detection and isolation of cases, and public education about the spectrum of diseases and the period of contagion are key to the effective containment of SARS-CoV-2, ”said the team of researchers led by Muge Cevik, a specialist in Infectious Diseases from the University of St Andrews, Scotland and an advisor to the UK government.
No study detected live virus after day 9 of illness, the study said, despite persistently high viral loads that were inferred from cycle threshold values in RT-PCR tests. Cycle threshold values indicate the number of times a sample was amplified before it was detected as positive for the virus.
The Science Advances study also referenced this report. He added that the detection of infectious people is essential, especially since asymptomatic and presymptomatic people are often aware of their infection and transmit it. “These results demonstrate that effective detection is highly dependent on test frequency and reporting speed, and is only marginally improved by high test sensitivity. Therefore, we conclude that screening should prioritize accessibility, frequency, and time between the sample and the response; The analytical limits of detection should be secondary, ”they said.
Experts from India agreed that testing and timely reporting is challenging. Anecdotal comments suggest that RT-PCR tests can take up to two days in a city like Delhi. “RT-PCR tests lose 30% of infections, while rapid antigen tests lose 50%. You can reduce these numbers to 5-10% by doing repeat tests, but that has not been possible here, ”said Dr. T Jacob John, former director of virology at Christian Medical College (CMC) Vellore.
He added that Delhi, in particular, faces a unique challenge due to a large population traveling to and from its satellite cities every day. “The risk of infection has increased anyway because behavioral fatigue has meant that people are no longer disciplined when wearing masks or keeping their distance,” he added.
The launch of the Feluda test, Dr. John added, could address the problem of delayed results, as well as the low sensitivity of the test. “The test can return answers in an hour. I think the administration is already in talks for an immediate deployment, “he added.
The Feluda test, commercially called the TataMD Check, uses a protein from a gene-editing tool known as Crispr. The test has demonstrated high sensitivity and specificity, the two markers that indicate the ability of a diagnostic tool to detect true positives and true negatives.
For now, a temporary answer may be to remove bottlenecks from RT-PCR test results and even increase rapid antigen testing, the Science Advances study suggested after citing simulations. “The frequency of testing was found to be the main driver of epidemic control at the population level, with only a small margin of improvement provided by using a more sensitive test,” they said.