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Q1) Take on current testing rate of India and its situation compared to other countries.

India has come a long way from early days in the first quarter of 2020, when tests were measured in hundreds and thousands, with severe restrictions, to September when over a million tests are being done on daily basis. Expressed as tests per thousand population, this is still slightly low (about 0.8) when compared to US, UK, Western Europe (mostly above 2), but is better than other South Asian nations. An important point to note is that India has relied upon Rapid Antigen Tests (RAT) to scale testing, because of ease of use, which has limitations compared to qRTPCR.

Q2) Pros and cons of various methods to test the population.

To diagnose an infectious disease, we must either detect the pathogen or detect a specific response to the pathogen by the host. Host response, such as antibodies to the virus, occurs later in the disease and is not useful for diagnosis in a situation where the focus is on preventing spread. For early detection and diagnosis, one needs to confirm presence of pathogen. For viruses like nCOV19, the direct pathogen detection is either via nucleic acids or proteins. Nucleic acids are amplifiable and thus detectable in very small quantities in a reliable manner by quantitative Reverse Transcription & Polymerase Chain Reaction (qRT-PCR), with sensitivity around 80% and specificity near 100% when done properly on nasopharyngeal swabs. Thus, nucleic acid testing (NAT) had been the cornerstone of early diagnosis in COVID19 outbreaks, where infected cases are to be rapidly isolated from main population, bringing down R0 (The number of new people infected per case).

NAT, via qRT-PCR, requires multiple steps (RNA isolation, DNA conversion, PCR) in specialized machines, which makes it difficult to scale and takes a long time in getting the results back to the patient. This has allowed Rapid Antigen Tests (RAT) that give a visual readout i n under 30 minutes, to be introduced into the testing system. Today 2/3rd of testing is via RAT. Unfortunately, the available versions that detect antigen.

Dr. Anurag Agrawal MBBS PhD FNA FASc ATSF

proteins have low sensitivity (around 50%) and cannot detect small amounts of virus. Thus, false negatives are common. For these versions of RAT, where disease is suspected, there must be follow-up of negative RAT with a NAT. There appear to be new RAT that have higher sensitivity. This needs to be confirmed.

NAT is not restricted to qRT-PCR and can be done by next generation sequencing (NGS), isothermal loop amplification (LAMP), CRISPR based detection. These are either simpler and faster (CRISPR, LAMP) or with greater through-put (NGS such as Illumina COVID-Seq). Since none of these tests are available in India as of yet (CRISPR test FELUDA is at last stage of approval and COVID-Seq is only possible at CSIR-IGIB so far), currently the only options are classical fluorescent qRT-PCR or a simpler chip based version TrueNAT that has limited throughput.

Q3) Strategies adopted to improve the testing rates. What can be done further?

a) The most important barrier in increasing testing rate by NAT is collection of NP swabs by healthcare workers. This is put in liquid media that needs decontamination followed by RNA extraction, further slowing things. We need to switch to saliva or dry swabs and use RNA-extraction free methods. This would, in my estimate, increase our NAT throughput by two or three – fold without substantial additional investment.

b) Smart complementary use of tests is needed. While RAT have increased the testing rate and they are indeed better than not testing, it is a double edged sword if symptomatic patients found negative on RAT are not tested further. Of course, new RATs with high sensitivity would be an even better solution.

c) We need to develop and promote tests that require less infrastructure for e.g. no qPCR machine. Our lab has worked to develop such a CRISPR test called FELUDA, which has been licensed to TATA group for production. I expect it to be approved for marketing by the time this article prints. It took more time than we expected. Eventually such tests can become self-tests, but probably not yet, since there is a mental cost to testing positive and quality control may be difficult in home tests.

d) We need to discover ultra-fast tests such as breath tests which give positive or negative results in a few minutes. There is some ongoing work across the globe such as e-noses and I hope it works

Q4) Barriers to increase the testing rate?

The biggest barrier is a mindset that prevents quick testing and deployment of innovative and efficient methods. We need a faster and more effective emergency use authorization system that makes use of many minds working across the nation, as well as receptiveness to global knowledge base.

Other than this, there is a knowledge barrier. We simply do not know enough about SARS-CoV2

Q5) Special emphasis on people’s reception about getting tested. How does testing positive affect their mental status?

People are willing to be tested when there is a clear plan, in case the test comes positive and where it does not lead to chaotic degeneration of the situation. If there is clear communication and a plan, testing positive is not a problem. If people are left to imagine the worst and not given timely advice, things can be very bad. That is why I said earlier that while ideally we would develop home tests, I do not think we are ready yet.

Q6) Views about other countries. Special emphasis on China (undisclosed positive cases and testing) and New Zealand like countries having low cases. Sweden did not impose a lockdown…view on this.

No one knows the exact situation in China. Each country is different and there is no universal one size fits all strategy. Younger vs older nations, societies with elders in care facilities vs living with families, nations with prior SARS1 exposure vs unexposed nations, diverse democracies vs highly controlled nations; these are all factors determining the course of the disease and necessary intervention steps. We are all learning and each nation has different resources to work with.

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– Dr. Anurag Agrawal

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