'COVID-19 RT-PCR tests are 99.5% reliable'

Amid reports of people reporting COVID-19 symptoms yet RT-PCR tests showing they are negative, Thyrocare diagnostic chain founder A. Velumani explains why, and shares the controls in place to check against incorrect RT-PCR test results in India

COVID-19 RT-PCR tests are 99.5% reliable

Mumbai: On April 28, 2021, India reported 360,960 COVID-19 cases and 3,293 deaths. It is evident that these numbers do not reflect the true situation, and the real situation on ground is much worse and the numbers much higher. Can we get a better handle on what's really going on in India, through what our testing capability can say about the nature of and progression of the COVID-19 virus? What is India's COVID-19 testing capability today, compared to during the first wave in 2020? Are we more able to see early signals now? Besides the tools we have like vaccinations, lockdowns and other such containment measures, what can India do at the testing site to fight back against the virus?

For answers, we spoke with entrepreneur A. Velumani, managing director and founder of the Navi Mumbai-based diagnostic laboratory chain Thyrocare.

Edited excerpts:

What is the Thyrocare diagnostic laboratory chain's COVID-19 testing capacity?

As of today, we have an ability to test 25,000 COVID-19 swabs in Mumbai, 5,000 in Delhi and 5,000 in Bengaluru, i.e. a capacity of testing 35,000 swabs every day. That's the capacity of just one laboratory chain. I feel capacity is not all that a big problem in COVID-19 testing in India. The problem is the logistics of getting these 35,000 specimens from the patient's home to the laboratory during lockdown, amid panic and fears for the technicians who venture out. This has proved to be a big challenge.

In Mumbai and adjoining Navi Mumbai, where Thyrocare's headquarters are, what is the split between the number of samples or swabs that you're collecting from homes and the number being collected from people walking into your testing centres?

Walk-ins at our test centres are hardly 1% of all samples. We have a B2B (business to business) operation. Hospitals who collect COVID-19 samples from patients but don't have their own testing facility are our clients. Around 65% of the swabs we process are collected by them, and 35% we collect ourselves. Of the 65%, almost half is government business [from public healthcare centres]. Since Thyrocare is not within but outside the main city of Mumbai, our reach to homes is limited. [Home collection] would be around 30% maximum in this acute panic, pandemic environment.

How many testing centres does Thyrocare have via your partners?

That was limited in the first COVID-19 wave. In the second wave, we have created a 'Kiosk Collection Facility,' where we put up a kiosk in any hospital which has an ATM-sized space in front. This is due to one more challenge we are facing in this wave. There was a capacity in Mumbai to test 50,000 swabs per day in the first wave. But now, since about 10 days back before lockdown was announced, the need has gone up to 200,000 swabs per day, which meant four times the capacity, thus [labs] didn't have a swab collection solution. If a technician goes home to home for swab collection, he can't collect more than 10-15 samples a day. But if there's a kiosk, and patients in a 1-2 kilometre radius can walk to the kiosk, even 100 samples can be collected using just one technician. So, we have, only in the last 10 days, requested the hospitals to review this facility and requested government authorities [for permission] to operate the kiosks. This is proving to be a solution for the COVID-19 sample collection challenges that laboratories are facing.

Roughly what percentage of the Mumbai/Navi Mumbai testing capacity would Thyrocare represent in terms of total diagnostic capacity, today?

A maximum 20% of COVID-19 testing capacity in the city market, and a minimum 15%.

Do a lot of samples also come to you from outside and much further away from Mumbai?

We do have business coming from Jharkhand, Uttarakhand, Goa, but 50% of our business is from Maharashtra. We have business coming from 17 states, which is all government business. Governments collect COVID-19 samples and as their capacities are limited, they have an overflowing load, so they find a private player who has better capacity. They don't ask for a tender; they tell you a rate and ask if you can do it. If we realise that currently the testing floor has some unutilised capacity, we accept it and do the testing irrespective of the rate being too low.

You said Thyrocare's capacity is 35,000 COVID-19 tests a day. Has that number been changing or remained stable in the last six months? Suppose you get 45,000 COVID-19 swabs, how many lab technicians are required to process this?

We measure testing capacity by this many people, this much square feet, this much analyser cost per 1,000 samples. So, there is a fixed investment as well as HR [human resources] cost per 1,000 samples. By scaling up, you don't get any additional advantage, except that when you have a broad bandwidth, even when 2,000 COVID-19 specimens come to the floor, you can clear it in three hours. So, though [broad bandwidth] gives a comfort to clear big workloads, it doesn't truly offer any advantage to have two big laboratories.

I have processed a maximum 25,000 COVID-19 specimens in a day [in Mumbai], and we had around 150 technicians on the floor completing that. That is the absolute number.

When it comes to the time taken to process COVID-19 test samples, there are obviously delays being seen now. So, when you say 150 technicians and 25,000 swabs, what kind of turnaround time is that?

For turnaround time, strictly following the 'first-in, first-out' logic is very important. If you follow that, then the turnaround time is 200 minutes, or around 3.5 hours. Thus our turnaround time is around four hours for the complete process. When people say that for the last two-three days tests are not being cleared, such delay is happening with the small laboratories. Big laboratories don't have that problem. As long as your inflow to the floor is streamlined to 1,000 swabs per hour, the laboratory has an ability to clear [a result] in the fifth hour.

Mumbai's case numbers seem to have been falling in the last week. Are you getting the maximum number of samples that you can process at this particular point of time?

I must tell you that just before the lockdown was announced, there was a kind of crisis. As medical needs were growing, travel needs [of frontline and healthcare workers within the city] were growing in parallel, and the Maharashtra government said that all frontline and healthcare workers must have an RT-PCR report in hand [to travel], so that amplified [the samples needing processing] by five times. Because of which, that week, our floor also had more samples than it could process. But subsequently lockdown was announced, and the rule that frontline workers must have RT-PCR tests in hand was relaxed. Subsequently, the floor has become reasonably empty. Today, we get around 16,000-17,000 samples against our capacity of 25,000 in Mumbai.

This 16,000-17,000 samples daily demand is in Mumbai, Delhi and Bengaluru?

Around 16,000 in Mumbai alone, out of 25,000 daily capacity. Delhi is running the full 5,000 capacity and Bengaluru we recently started, so running at 50% of the 5,000 capacity.

So at this point, you're not experiencing any delays? From the point the sample arrives at the gate, you're saying it takes about 200 minutes to produce a result which could be e-mailed back to whoever sent it from anywhere in the country?

Minimum 200 (3.5 hours), maximum 300 minutes (five hours), today. Last week, we accommodated 5,000 samples from Jharkhand and 5,000 from Goa without affecting the local reporting cache.

When people complain of results coming after many days, what then could be the reason for that?

There are some reasons for such delays, even for Thyrocare. Let's take what we call 'horrible five', i.e. out of so many samples we received, which five samples went totally wrong. These are samples which were sent to us without data, without any kind of inputs for us to comply with Indian Council of Medical Research (ICMR) reporting requirements. We can't test if we don't have the KYC [know your customer information] of the patient. If the person who collected the sample had not bothered about the KYC but just sent the sample, we can't test it. These are all training challenges for the sample-collecting hospitals. ICMR today is demanding 40 different fields to be entered in the computer before you release the report. So, the testing time plus the data entry time is taking an additional almost 30 minutes per sample in a normal routine. These are the issues which probably all laboratories are facing. But if the sample comes with clean data and if there is enough capacity on the floor, I think we have reported results by the next day morning for almost 99% of samples for the last one year.

Many people, including doctors, are saying that patients are exhibiting COVID-19 symptoms and yet reports are not showing positive. One reason could be that the report might be delayed, but even if the report is timely, it sometimes shows negative whereas in all probability it's COVID-19 positive. Can you explain that from a biotechnical perspective?

Ever since I started my laboratory, this complaint has always been there. Doctors believe that the symptoms are obvious, but the laboratory is not reporting [a positive test]. We don't know what the doctors' expectations are; we only report the number the machine is producing. So, there have been negative COVID-19 results [in case of positive patients], but not very frequently.

This COVID-19 virus which hit us in March 2020 was chaotic. People with symptoms did not show positive results. People without symptoms showed positive results. So, obviously this virus produces a spectrum of symptoms from very mild to highly serious, so it's not that simple for a doctor to tell [without testing]. Having said that, the PCR [polymerase chain reaction] test is a Nobel prize-winning technology and has been seen as a gold standard in laboratories. When no other test can confirm, a PCR test can, because it looks for genetic material in the body. So, if a sample in the tube is positive, no other result can be manufactured because PCR only amplifies what is inside, so there's no false positive at all. There are some false negatives. If technicians don't collect the specimen properly, there won't be a virus inside the tube and you might be reported negative. This could be happening. But that should happen in maximum 2% of cases in an inexperienced laboratory and much less in an experienced laboratory.

So as far as you're concerned, as a diagnostic laboratory, there is no chance that even despite the mutations and changes in the SARS-CoV-2 virus which causes COVID-19, your assessment of positivity could've changed?

I think 99.5% is completely reliable; there is always a 0.5% room for error, for any laboratory test for that matter.

That 0.5% error could be because of something else, but the core technology is strong?

Technology is strong; collection procedures could be erroneous.

But, for instance, you use reagents in COVID-19 testing. You were quoted saying just a couple of days ago that you're running short of this. Is it possible that the reagents you use, or any of the other inputs required in the actual testing capability, is not keeping up with the COVID-19 virus in its current form?

The control of what testing kit should be sold in the country is with the government. If it is not listed by the government, it can't be sold in the country. That's the number one check. There are kits which look for one gene, some which look for two genes, and there are three-gene kits available in the market. There is a very slight additional cost for a three-gene kit. From the second month of the pandemic till today, we are using the three-gene kit. A three-gene kit having an error possibility is very remote, given this technology is very sturdy and very reproducible. Everyone, even ordinary laboratories, today are using a good kit. And I must remind you here every month we are required to send 10 positive and 10 negative specimens to NIV (National Institute of Virology). NIV should give a score of 10/10 for positive samples and 10/10 for negative samples. Every month we do this because this is the only confidence that we have that we are not reporting anything wrong, and this is followed by all laboratories. And I don't want anyone to suspect, in spite of this much control, that laboratories may not be producing quality [results].

So you're saying that in India, in general, laboratories like yours are using the best-in-class COVID-19 testing kits? I am seeking an assurance that when we send you samples, there is no chance of error, particularly as the virus mutates from time to time and country to country.

This is a molecule test, this is RNA, and this is the sequence which decides that it has COVID virus' signature. And if you have captured three locations in the gene, I must tell you that the chances of it going wrong is one in thousands. So, there is no room for one to suspect.

We are still in the middle of the COVID-19 pandemic. In some regions and cities, the numbers seem to be easing a little, Mumbai being a good example, while in other places, not yet. As a scientist, from a pure testing point of view, what do you feel would help us quickly understand and respond to this virus and its spread?

In the laboratories we have noticed, from April to October 2020, the percentage of positive COVID-19 tests had regularly been moving up. And then it started moving down from October 2020 to January 2021. It started at 5%, went to 40%, and came down to 5%. That means the peak was over. But in the second wave, it has gone from 5% to 40% very rapidly. Also, though in Mumbai the number of positive cases is less, the positive percentage has not come down. The testing has come down. So, if you ask me personally for the view from the laboratory floor, the percentage has not come down even in Mumbai. I still feel that Delhi is moving up.

To be very honest, no scientist, no virologist, no immunologist truly can predict what could happen. But lockdown will prevent the situation from worsening, and it might take months for us to see the numbers coming down. Numbers won't come down immediately due to the lockdown, that's too good to believe, and we need to cautiously read the numbers.

A lot of people do panic, they hear of false COVID-19 negative tests and do repeat testing. Sometimes results show no connection to what people are physiologically experiencing. So, what would your advice be to the people who are facing or getting test responses which they are not able to logically understand?

There are some metabolic disorders which, if [the diagnosis] is positive like thalassemia, this will not change lifelong. There are some illnesses like tuberculosis which take 60-90 days of treatment, then only tests are negative. Until then, tests will remain positive. You have to treat HIV a long time to see a negative result.

In the case of COVID-19, after 25 days either the virus is alive or the patient is alive. That means that this virus is a very short-lived virus. At some point of time everyone was negative, and one day some people will become positive. You can't say 'yesterday I was negative but today I am positive, how can this be'? This is one point which needs to be kept in mind. You were negative but you have become positive. You can test and find you are positive, and after three days you can test again and find you are negative. That's not some [laboratory] reporting wrong. The punchline I use to explain, even internally for our people, is, 'Every positive was negative in the previous day. Every negative was positive in the previous day'. So, technologically it can't be said that this is a laboratory error. It is the character of the virus' progress and its presence.

As you look ahead, what is it that you are anticipating or expecting in terms of desirable technological or policy inputs, policy in terms of pricing or freeing up more resources, or any other aspect which could improve the reach and quality of your testing? What is the capacity projection you have for your own laboratory?

The big challenge that the COVID-19 virus has posed to the government, hospitals and laboratories has been inconsistent demand. In September 2020, we felt that the demand would keep rising. We were willing to invest in capacity and we did invest a lot. But then, demand suddenly came down. Whether it was brought down artificially [through containment measures] or the virus truly has a wave nature [of infecting], I have no scientific explanation. Now, suddenly, I want four times more capacity than what I had in September 2020. It's going to take time to expand. So, the first difficulty is unexpected demand for tests.

Second, the government has recklessly brought down the rates for tests from Rs 4,500 to Rs 450 in some states. Now, if you don't leave anything on the table, there won't be any motivation for a laboratory to invest crores. For an additional thousand tests, I need to invest a crore. And if tomorrow that demand goes, then my crore is gone. No one is going to worry about me. These are all challenges which no one needs. The next point is, the testing cost is less, it is the sample-collecting costs that are high. Costs are 60% for sample collection and 40% for testing. Everything, the consumables, etc. to reach the customer, is costly. So, that is a challenge of how to explain every cost to the government agency so that they understand what it is.

Last but not the least, something that will help the laboratory is to have all government hospitals collect swabs, tell the laboratories to test at this rate, and laboratories will. Labs can create any capacity as long as you say, 'in the next six months, I can give this many swabs'.

Having said that, the message for the common man is: vaccine is the only way out, not lockdown. Lockdown is a paracetamol which reduces the temperature. It is not the cure. The cure is either herd immunity which should set in adequately, or before that we can add vaccination. I think expediting the vaccination should be the core focus for the government. Chasing your vaccination date should be the core focus for every citizen. I think it will take some more time. But let me tell you, it's going to be a long battle. It is not a battle of months or quarters, it is for years.

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