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COVID-19 diagnostics: Testing times

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Experts discuss the dilemma presented by COVID-19 self-tests, weighing the benefits with the risks

As we embark on the third year of the COVID-19 pandemic, governments across the world have tried to match steps with the various variants. A large part of the COVID-19 strategy has been modifying and implementing testing protocols. The latest advisory from the Indian Council of Medical Research (ICMR) on January 10 this year was the seventh version, and was in response to the sweep of the Omicorn variant, leading to the third wave.

Unlike in the previous two waves, this time, in addition to the gold standard molecular tests – rRT-PCR, TrueNat, CBNAAT, CRISPR, RT-LAMP, Rapid Molecular Testing Systems, as well as newer SARS-CoV-2 Omicron or variant detection rRTPCR assays – India also had a fair number of Point-of-Care (POC) Tests, which were home or self-test / Rapid Antigen Tests (RAT).

The latest INSACOG weekly bulletin dated this January 10 finally admits that Omicorn is being spread within the community rather than just from travellers. Hence RAT tests would seem to be the answer to the change in strategy required as the COVID-19 pandemic enters a new phase.

The surge in COVID-19 testing has swelled the market outlook for the diagnostics sector (See story: COVID19 diagnostics: Market watch) But while RAT tests were flying off chemists’ shelves and online pharmacies, due to the sheer convenience, these advantages also created a problem for governments. As patients tested themselves in the privacy of their homes, not all were following the dictate to upload/report the test results, positive or negative, on the ICMR portal at: https://cvstatus.icmr.gov.in.

Saurabh Gupta, Head –Strategy, Mylab Discovery Solutions explains why he feels that the benefits of self-test kits far outweigh the risks (see box: Benefit to risk ratio for self-test kits)

Speaking about the Mylab’s COVID self-testing kit, Dr Shirshendu Mukherjee, Mission Director, Grand Challenges India, Biotechnology Industry Research Assistance Council (BIRAC), Dept of Biotechnology points out how the home diagnostic kit from BIRAC supported Mylab has been able to reduce the load on regular pathology labs, saving cost of running and rerunning RT-PCR analysis in strained healthcare laboratories.

But one major disadvantage is that RAT kits have lower accuracy than the gold standard RT-PCR tests. Alluding to the drawbacks of the testing technology itself, Gupta rationalises, “Self-test kits are based on lateral flow antigen test principle and are roughly 70-80 per cent accurate. The good thing is that false positives are negligible which is very important when the positivity rate is so high. RT-PCR is the gold standard but because of the limited supply – we have to choose between testing and testing with an 80 per cent accurate kit.”

But as Sunil Mehra, General Manager for Abbott’s Rapid Diagnostics Business in India explains,As with any rapid diagnostics, negative results must be combined with clinical observations, patient history and epidemiological information. Negative results do not preclude COVID-19 infection and cannot be used as the sole basis for treatment or other management decisions.”

Mehra too stresses that rapid antigen tests have been indispensable in helping people make critical decisions about their health by quickly identifying infectious individuals to reduce further virus spread. Referring to Abbott’s test kits, according to him, during clinical evaluations of asymptomatic individuals, no false positives were identified with Panbio COVID-19 Antigen Self-Test.

An important advantage of self-test kits is that they “have empowered patients to move ahead with greater confidence in regards to their health,” points out Dr Sandeep Sewlikar, Head-Medical and Scientific Affairs, Roche Diagnostics. Roche’s newly launched At-Home Self-Test is the latest addition to the India marketplace and Dr Sewlikar is confident that while they may seem to be a late entrant in the market, “we are ensuring a streamlined supply chain system to foster uninterrupted supply of kits.”

Dr Sewlikar also homes in on the timeframe when RAT kits work best, that is, when people show symptoms and have high viral loads. Hence, he reasons that they work best when people are tested immediately after onset of symptoms. However, he too agrees with his peers that there is a likelihood of getting a false negative result if there is an error in sampling, testing or when a person has low viral load. Hence, in case of a negative result with a RAT kit in a symptomatic person, further testing by RT-PCR is recommended.

But there are already examples of next-generation ‘smart’ diagnostic devices like the systems developed by Zurich-based Bloom Diagnostics which address some of these short-comings. As Dr Angelica Kohlmann, chairperson and co-founder, Bloom Diagnostics explains, “Bloom Diagnostics, beyond having developed digital, connected self-tests, also built extensive software around the product, which allows to increase sensitivity and with it, also specificity.” Patients using Bloom are guided step-by-step via the Bloom App, minimising sources of error. Extensive usability testing was performed with this purpose, indicates Dr Kohlmann.

Highlighting the need for quick decision, Bhupendra Chaudhary, President – Sales & Marketing, Transasia Bio-Medicals adds, “SARS-CoV-2 continues to baffle medical experts with its presentations. It is crucial for clinicians to identify early, those who are at risk. This will aid them in recognising the future need for admission to ICU, improve allocation of patients for specific therapies and initiation of preventive strategies.”

Which is why Chaudhary feels that self-tests are the need of the hour as they provide an added layer of information. Home tests cannot be reported currently, but he points out that RT-PCR labs take more than 12 hours to provide a user with a report, and the patient’s symptoms could increase in severity during this long wait for results if proper treatment is not started.

Chaudhary therefore suggests that even if a patient has symptoms and gets an RT-PCR done, the patient should also conduct a RAT or a RAT home test to quickly assess the condition. This can help in taking precautionary measures and also help healthcare workers to provide appropriate prophylaxis to the patient and avoid any serious developments of COVID-19. “RT-PCR is the gold standard for COVID-19 testing but RAT or home tests are a quicker and easier way to ensure the self-care and ensuring safety of their loved ones,” reiterates Chaudhary.

Globally, RAT tests for COVID-19 diagnosis already outnumber the RT-PCR tests, points out Thomas John, MD, Agappe Diagnostics, even as COVID-19 Antigen Test, currently the nucleic acid-based polymerase chain reaction, is used as the standard for COVID-19 diagnosis.

Adding to this argument, John analyses,Worldwide 60 per cent of the COVID-19 disease diagnosis is dependent on RAT and the remaining 40 per cent stake is held by RT-PCR. ICMR has given permission for COVID-19 self-test by May 2021 in order to increase the testing rate in rural areas. Benefits are ready to use COVID-19 antigen test card, a patient can perform the test without any external help, required only nasal sample, easy sample collection, prefilled lysis buffer with dropper head for direct sample addition to the cassette, result within 15 minutes and the result can be synchronised with ICMR website also through the mobile app.”

Amit Chopra, MD, India and South Asia, Thermo Fisher Scientific agrees that while the self-test kits have the potential to be game changers, there are several challenges that need to be addressed. Apart from safe disposal of the self-test kits, lack of a mechanism to report positive cases significantly impacts the testing and tracking strategy of SARS-CoV-2 virus.

Different variants, different kits?

But how effective are these test kits at detecting variants of the original SARS-CoV-2 strain that display a high number of mutations, like Omicron? From time to time, we hear reports of variants from across the world that public health authorities are tracking closely, like the IHU variant from France.

Abbott’s Mehra reasons that as the pandemic evolves, so must testing strategies. As he explains, “To ensure we stay a step ahead, through Abbott’s Pandemic Defence Coalition, we have a network of research, academic and public health collaborators strategically placed around the world that are actively sequencing viruses to look for the next viral threat including COVID variants. Having this established network allows for quick sharing of new information and the ability to provide samples faster – within days rather than the typical weeks or months – so we can verify our tests perform against the latest mutations.”

Mehra cites that a thorough assessment was conducted with both the Omicron and Delta variants, concluding that Abbott’s tests can effectively detect the virus. Most recently, Abbott reportedly completed extensive testing on Omicron virus laboratory culture samples as well as unique clinical specimens obtained from patients infected with the Omicron, a total of 74 clinical specimens tested to date.  “In all cases, our studies confirm that our rapid antigen tests continue to detect the Omicron variant at comparable viral load levels as all other variants and the original SARS-CoV-2 strain,” he emphasises.

Mylab’s Gupta too reassures that all their products detect all major Coronavirus variants including Omicron, because “we target a different genetic area than the one which has mutation. Also, a recent study conducted by researchers at the Columbia University, US shows that CoviSelf successfully detects the Omicron variant. This adds to confidence in India’s ability to detect the infections early and isolate fast with home test kits.”

Dr Sewlikar of Roche Diagnostics too confirms that their At-Home Self-Test can detect the Omicron variant while Thermo Fisher Scientific’s Chopra points out that Omicron’s underlying biology has put Thermo Fisher’s TaqPath assay, an RT-PCR test, in the spotlight as it targets multiple regions of the viral genome and was recommended by the World Health Organization (WHO) as the best-positioned diagnostic kit for screening potential cases of Omicron. And on the RAT side, Thermo Fisher’s Accula system, a rapid test that uses PCR technology provides accurate results in 30 minutes helps meet the continuing demands for rapid and reliable COVID-19 testing, especially in the point of care format.

Balancing the risks with the benefits

John is aware of the risks of depending too much on self-testing in a country like India. India has still not yet thought of declaring the pandemic as endemic flu unlike many European countries, he points out. He agrees that self-testing is not an ideal solution in India primarily because people are not trained, and they will not take the sample with proper insertion. Hence, false negatives will be more due to deviation in protocols and Government will have no control over the positivity extent, depending on the outlook of Indians at large.

Patients in India are not the only ones not reporting their results. As Gupta of Mylab says, “Be it India or in the US, this has been the case that self-test reporting is not 100 per cent. What this does is that it makes the case count look smaller than what it is and epidemiologists do not have all the information that they need. This is true and this data is very helpful. However, if we look at it pragmatically, the world reality on the issue has changed with the third wave and case count may not be relevant anymore.”

Dr Sewlikar too defends RAT kits saying, “Not reporting results to authorities and not following isolation or quarantine guidelines are behavioural issues rather than a specific drawback of home tests.”

Dr Kohlmann is of the opinion that knowing is better than not knowing and a number of people are responsible and will avoid infecting others.

                                                Source:Saurabh Gupta, Head –Strategy, Mylab Discovery Solutions

Track hospitalisations, not case numbers

To support the case that case numbers are not really that important anymore, Gupta points out that the US’ CDC has dropped mandatory reporting of self-tests from its guidelines and indicates that people should isolate, tell close contacts and get in touch with healthcare workers if there are severe symptoms.

Indeed, experts in India too seem to think that at least in the Omicron-driven third wave, hospitalisation count could be a more relevant metric than case count. To quote top US expert Dr Anthony Fauci who has recommended that a better number to look at is hospitalisations rather than case count because many infections have few or no symptoms, “it is much more relevant to focus on the hospitalisations as opposed to the total number of cases.”

The same concerns have been voiced in the US, but the US government knows that self-test is the key instrument in their fight against COVID-19 and hence the US government continues to promote self-testing – even reportedly giving out free kits.

As Gupta of Mylab puts it, “Saving lives by quick isolation is more (of a) priority than counting numbers.” According to a healthcare consulting firm’s study in December, US took roughly 40 million COVID tests per week. Of those, 12 million are PCR tests and roughly 28 million are antigen tests. Among the antigen tests, the vast majority are taken at home and never reported to public health agencies. Inspite of this reality, the US government announced a plan for 500 million self-tests, which indicates that the priority is saving lives, reiterates Gupta.

Awareness is key

Even though case numbers are not as important, the data would be useful, both for healthcare policy makes as well as citizens. Gupta points out that the government in the US is running public interest campaigns to tell citizens that they should report results in either case. For example, if people report a positive test, they can get quick hospitalisation in case of emergency. Secondly, they can get their insurance claim for the expenses done if they test positive.

Hence, we need more awareness to be created that reporting is beneficial to people. Mylab’s Gupta suggests that the Indian government should also start an awareness campaign, for example as a ringtone message, as was done for the COVID-19 vaccination campaign.

Dr Sewlikar explains how Roche Diagnostics has incorporated mechanisms into their test kits that enable people to report their results. “Our test kits come with an instruction guide that encourages people to download the ‘My Covid-M’ app using the QR code which will help them read and interpret the test results and also update the results to the ICMR database (as mandated by ICMR). Moreover, after obtaining the results, a person is expected to follow the isolation and care guidelines recommended by ICMR and MoH&FW.”

Individual right vs public good: the Novak Djokovic moment

Self-tests are definitely an important part of the future of healthcare. Besides the COVID-19/Omicron scenario, where the benefit to risk ratio for a self-test kit is highly in favour of self-test kits, as detection is better than not detecting it at all, there are numerous other diseases where the same scenario is playing out.

And companies like Bloom Diagnostics are already tapping into this medical and healthcare consumer need. Dr Kohlmann informs the Bloom has an extensive pipeline and the goal is to one day be able to cover many diseases via home-tests, with real-time results and guidance, which is “the most important factor.” This she says, “will dramatically change healthcare systems for the better, and lower costs significantly.”

As an example, she points out that to date, Bloom already helped many people find that they have iron deficiency, for example, which they didn’t know. “Some felt very tired or exhausted, and with the support of Bloom they were able to track ferritin, and to get back to normal levels with the help of the right nutrition and supplements.

Another example Dr Kohlmann mentions is hypothyroidism, a thyroid insufficiency, where the Bloom teams of scientists, medical doctors and software engineers developed the algorithms together to detect people who had this condition.

While smart diagnostics like Bloom’s tests might still be out of reach of the majority of India’s population for now, the promise and potential of rapid diagnosis self-tests will have to be balanced by concerns on accuracy. There is also the larger question of an individual’s right to privacy to not disclose medical information, when weighed against the greater common good of containing a pandemic. A classic example is tennis star Novak Djokovic’s refusal to disclose his COVID status and subsequent deportation from Australia.

Since the diagnostics market is moving towards self-tests and point-of-care diagnostics, public health policy makers are sure to confront this basic dilemma more often, not just with COVID-19 but other disease conditions like AIDS/HIV, etc. As always, there are no easy solutions.

Viveka Roychowdhury

[email protected]

[email protected]

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