Good antibody testing a need as country moves into next phase
Sri Lanka has fared well in tackling the COVID- 19 epidemic but it is time for a review to continue the positive measures and change the negative measures, urges Kandy National Hospital’s Consultant Clinical Microbiologist, Dr. Mahen Kothalawala.
A point brought into focus is how the testing protocol is linked to COVID-19 outbreak control, with emphasis on the need to move into quality antibody testing to get a feel of what is happening in the community.
In the early phase, many measures such as the lockdown and curfew were imposed along with intensive RT- PCR ( Reverse Transcription- Po lymerase Chain Reaction) testing to separate the infected from the non-infected and contact tracing was carried out.
Getting into technicalities, Dr. Kothalawala says that in a real time PCR assay a positive reaction is detected by the accumulation of a fluorescent signal. The Ct (cycle threshold) is defined as the number of cycles required for the fluorescent signal to cross the threshold. Ct values are inverse to the amount of viral nucleic acid which is in the sample. A low Ct valueindicates a high viral load and a high Ct value means a low viral load.
It’s usually in symptomatic patients that the viral load would be high giving a low Ct value. This would be different to those who are mildly symptomatic or asymptomatic, he says.
So the ‘ containment’ protocol followed by Sri Lanka is to hospitalize, isolate and treat the infected persons, while netting in their contacts through tracing; placing them in quarantine for 14 days and conducting RT-PCR tests on Day 7 and Day 14. If the two tests are negative, they are sent home. If they become positive they are hospitalized.
This was to ensure that there are no chances of infected people giving the disease to others, says Dr. Kothalawala, pointing out that when people are quarantined for 14 days the chance of missing someone
who is infected is 1 in 10,000. This is while in countries which quarantine people for only seven days, the chance of missing them would be 21 in 10,000.
He reiterates that this was all in the First Phase and now Sri Lanka is in the Second Phase of living with COVID- 19. There is the possibility that despite all efforts to remove positive patients from the mainstream through RT-PCR testing and contact tracing, some pre-symptomatic, mildly symptomatic or asymptomatic people fall through this testing net.
How this can occur is:
· There is a ‘ window’ when conducting RT- PCR testing if the viral threshold is low ( the RNA is inadequate), when there could be no definitive confirmation. This could occur two days before symptoms manifest or three days after mild symptoms manifest.
· The other possibilities are when a good sample is not secured by a trained person or if the person from whom the sample is being taken is uncooperative.
· The RT- PCR machine too should be optimized to meet the sensitivity of different reagents that may be used.
There is a 71-98% variation in getting the right result with a conservative estimate being 70%, he says.
This is why, Dr. Kothalawala is recommending that as Sri Lanka steps into Phase II, it should seriously think of establishing good antibody testing among the population.
“Antibody testing should not be to identify the acutely infected people but to check the spread and find out how many people have got an exposure to the virus,” he says.
Looking at the different types of antibody tests, he says that the rapid antibody test and the rapid antigen test also called the cartridge test have low sensitivity of around 40%. The ELISA test ( an enzymelinked immunosorbent assay) and the chemiluminescent test (CLT), however, are highly sensitive.
He points out that the ELISA reader is widely found in universities, hospitals as well as the Medical Research Institute ( MRI) and the need is to buy reagents under certification from the National Medicines Regulatory Authority (NMRA). Some ELISA tests have 99% sensitivity and 100% specificity.
Many countries such as Israel, China, America, France and the United Kingdom are using antibody testing as a supplementary exposure test in addition to the diagnostic RT-PCR test.
Dr. Kothalawala also refers to a 45- minute RT- PCR cartridge based nucleic acid amplification test, different to the RT-PCR test which takes 6 hours and says the first one could be used at the airport as a pointof- care test for high- risk people coming through.
“We have these machines with a tuberculosis platform in every district which can also be used as an on- demand test rather than the batch test being performed now,” he says, adding that incorporating these aspects would help smoothen out the containment phase.