Repeated, widespread testing with quick results is more effective in controlling an outbreak than using a more accurate test, according to two research papers published recently that draw on a crucial way the Sars-Cov-2 behaves: people are most infectious in the first week of their illness, when the viral load in their upper respiratory tract is at its highest.
The findings hold significance for a city like Delhi where the proportion of tests turning positive has consistently been higher than the acceptable limit of 8% for weeks now, and officials are at present working on a strategy on how best to increase tests while maintaining a balance between the more reliable but slow RT-PCR test and the quick but low-sensitivity rapid antigen tests.
“At least for viruses with infection kinetics similar to SARS-CoV-2, we find that speed of reporting is much more important than sensitivity, although more sensitive tests are nevertheless somewhat more effective,” said the study that included researchers from University of Colorado and Harvard University.
Also Read | Centre to rush more expert teams for Covid management; sending teams to Himachal, UP and Punjab
The researchers make a distinction on the need to test more people when they are contagious versus those who may merely be infected. Using computational modeling of how viral load and infectiousness evolves, they determined infectiousness increased once viral load exceeded 10^6 viral copies of RNA per ml (cp/ml). RT-PCR method, they added, could detect 10^3 cp/ml in viral load while rapid antigen and LAMP tests detected concentration 10^5 cp/ml.
Using testing as a strategy to reopen cities “has placed 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, “remain expensive and as a laboratory-based assay often have sample-to-result times of 24-48 hours”.
These findings, published in Science Advances, tied in with another recent study published in The Lancet. In this, the authors analysed all scientific literature on Covid-19 till June, 2020 and found patients had the highest viral load in the first week.
“SARS-CoV-2 titres in the upper respiratory tract peak in the first week of illness. Early case finding and isolation, and public education on the spectrum of illness and period of infectiousness are key to the effective containment of SARS-CoV-2,” said the team of researchers led by Muge Cevik, an infectious disease specialist at the University of St Andrews, Scotland and an advisor to the UK government.
No study detected live virus beyond 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 too referred to this report. It added that detecting infectious people is crucial, particularly since asymptomatic and pre-symptomatic people are often aware of their infection and pass it on. “These results demonstrate that effective screening depends largely on frequency of testing and the speed of reporting, and is only marginally improved by high test sensitivity. We therefore conclude that screening should prioritize accessibility, frequency, and sample-to-answer time; analytical limits of detection should be secondary,” they said.
Experts in India agreed that testing and timely reporting is a challenge. Anecdotal feedback suggests RT-PCR tests can take up to two days in a city like Delhi. “RT-PCR tests miss 30% of infections while rapid antigen tests miss 50%. You can bring these numbers down to 5-10% by doing repeat tests but that has not been possible here,” said Dr T Jacob John, the former head of virology at Christian Medical College (CMC) Vellore.
He added that Delhi in particular faced a unique challenge because of a large population that travels to and from its satellite cities every day. “The infection risk has anyway increased because behavioural fatigue has meant that people are no longer disciplined in wearing masks or maintaining distance,” he added.
The rollout of the Feluda test, Dr John added, could address the problem of delayed results as well as low test sensitivity. “The test can return answers in one hour. I think the administration is already in talks for an immediate rollout,” he added.
The Feluda test, commercially named TataMD Check, uses a protein from a gene-editing tool known as Crispr. The test has shown high sensitivity and specificity, the two markers that indicate a diagnostic tool’s ability to detect true positives and true negatives.
For now, a temporary answer may lie in removing RT-PCR test-result bottlenecks and even ramping up the rapid antigen tests, the Science Advances study suggested after citing simulations. “Testing frequency was found to be the primary driver of population-level epidemic control, with only a small margin of improvement provided by using a more sensitive test,” they said.