Test Everyone
Times Of India article: Test Everyone Once A Week
We should test everyone in India once a week for COVID-19 using self-administered rapid antigen tests.
Summary
We propose that the Indian government approve the use of self-administered rapid antigen tests (Note: The Government of India has now approved at least one self-administered at-home rapid antigen test) — which are similar in mechanism and use to paper-strip pregnancy tests — by the general public without the help of a medical professional at home, at work, and in public gathering places such as shops and restaurants. These tests are fast (15-30 minutes to get a result), easy to use, and new evidence suggests that they are very accurate (80%+ sensitivity) at detecting the presence of COVID-19 in people who are actively spreading the virus (which corresponds to detectability by RT-PCR with a cycle threshold — CT value — of 30 or less).
In addition, we recommend that the Government of India deploy these tests in major metropolitan areas such as Mumbai, Delhi, Pune, Bangalore, and Ahmedabad, as well as emerging hotspots across rural India, to test every individual in those areas at least once per week. Recent evidence from Slovakia (written up in Science), Liverpool, and Nova Scotia suggests that this strategy could help reduce the incidence of new infections by as much as 70% after just a few weeks of implementation, saving potentially hundreds of thousands of lives.
The Test Everyone and Pashi teams, along with our test-manufacturing partner Oscar Medicare, stand ready to work with governments, educational institutions, and private companies to pilot, evaluate, and deploy large-scale self-administered testing immediately.
Background
The COVID-19 pandemic in India is currently surging at critical levels — as of May 1, 2021, more than 3 lakh confirmed new cases and up to thousands of confirmed deaths are being reported each day. Hospitals have been overwhelmed by the ongoing surge, and testing labs cannot cater to exponentially growing demand, routinely delivering results many days after sample collection, and even repeatedly pausing collection to get through the accumulated backlog.
Vaccination is the long-term solution to the country’s plight, but vaccine manufacturing and distribution are taking longer than expected to scale up. At the current pace, it seems likely that India will take until the middle of 2022, if not later, to achieve vaccine-derived herd immunity, even ignoring the threat of potential immunity-escaping variants. In order to make a dent in the spread of the virus without resorting to perpetual lockdowns, we must look toward public health interventions that can be applied much sooner. One such intervention is massively scaling testing so as to allow unknowing carriers of COVID-19 to find out about their status and proactively isolate themselves.
This, however, is not possible if every test must be administered by a healthcare professional or testing lab. We will use the State of Maharashtra as an illustrative example to explain why. Since the pandemic began, Maharashtra has COVID-tested slightly over 2 crore samples in total, with Mumbai accounting for close to a quarter of that number Press Information Bureau Public Tweet, 8 April 2021: https://twitter.com/PIBMumbai/status/1380178867487264775. The state has ramped up its testing count in the last few weeks, and is currently testing some 2 lakh samples per day across the state; it has also lowered the maximum cost of a COVID test to Rs. 500 or Rs. 800 (for a home visit) "Maharashtra Records 56,286 new COVID cases", New Indian Express, 9 April 2021: https://www.newindianexpress.com/nation/2021/apr/09/maharashtra-records-56286-new-covidcases-state-faces-severe-vaccine-remdesivir-shortage-2287835.html . However, the labs and testing centers that make this testing regimen possible have been unable to scale their capacity and processes fast enough to process many more tests; wait times have increased at both private and government labs, and the state government is considering a move to staff government labs 24/7 to account for the needed extra capacity.
Further, even though asymptomatic or pre-symptomatic carriers of COVID are the likely vectors of most of the current outbreak, insufficient capacity has led to deprioritizing testing on asymptomatic people. Given these problems, it is likely that many asymptomatic carriers of COVID are still going undetected, thus creating new COVID clusters and spreading the virus further in the state. In order to scale testing in Maharashtra and across the country, we must turn to self-administered rapid antigen tests.
What are self-administered rapid antigen tests?
Self-administered rapid-antigen tests are based on the same lateral flow principle as pregnancy tests; they are paper strip-based, and directly detect the proteins of the COVID-19 virus. To use them, one swabs the nose and throat with a provided cotton swab — this nasal swab can be a shallow Anterior Nares (AN) swab from the front part of the interior of the nose, as opposed to only being compatible with the deep and painful Nasopharyngeal (NP) swab that is currently standard in India. One then mixes the swab into a few drops of the provided buffer solution, and drips the mixture onto the paper strip. If one line appears after 15-30 minutes, the user is negative for COVID-19, and if two lines appear, the user is positive for COVID-19.
The UK government video below demonstrates this process step-by-step.
While rapid antigen tests from a number of manufacturers have already been approved for use in India, they are only authorized for use by testing labs, hospitals, and governmental organizations with a healthcare worker performing sample collection. They are not yet approved in India for self-collected at-home use, or for sale to the general public. (Note: The Government of India has now approved at least one self-administered at-home rapid antigen test)
Are rapid antigen tests accurate?
Rapid antigen tests are in wide use across India, but there have been concerns about too many false negatives giving COVID carriers the mistaken impression that they are not infected after taking a test. After initial testing, the false negative rate of these rapid antigen tests was thought to be as high as 40%. These concerns resulted in the Indian Council of Medical Research (ICMR) recommending in December that the use of rapid tests be capped at less than 30% of overall capacity, and that 70% of tests should still be RT-PCRSushmi Dey, “Centre to States: Limit RAT, Use RT-PCR Tests,” Economic Times, 12 December 2020: https://health.economictimes.indiatimes.com/news/industry/centre-to-states-limit-rat-use-rt-pcr-tests/79689301. It is now clear, however, that they function nearly as well as RT-PCR tests in detecting infectious individuals who are actively shedding the virus See Alex Crozier et. al., “Put to the Test: Use of Rapid Testing Technologies for COVID-19,” BMJ, Issue 8278 (February 2021): https://www.bmj.com/content/372/bmj.n208.full, and Genary Pilarowski et. al., “Performance Characteristics of a Rapid Severe Acute Respiratory Syndrome Coronavirus 2 Antigen Detection Assay at a Public Plaza Testing Site in San Francisco,” The Journal of Infectious Diseases, Vol. 223 Issue 7 (April 2021): https://academic.oup.com/jid/article/223/7/1139/6061974. A number of recent studies have shown that an individual is likely to spread the virus only if it is present in concentrations that can be detected in 30 or fewer RT-PCR cycles (i.e. CT value 30 or less) H. Laferl et. al., “An approach to lifting self-isolation for health care workers with prolonged shedding of SARS-CoV-2 RNA.” Infection, vol. 49, 2021, pp. 95–101. National Center for Biotechnology Information, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538033/., See also Bernard La Scola et al.. “Viral RNA load as determined by cell culture as a management tool for discharge of SARS-CoV-2 patients from infectious disease wards.” European Journal of Clinical Microbiology & Infectious Diseases, vol. 39, no. 6, Apr 27 2020, pp. 1059–1061. NCBI, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185831/. At those viral concentrations, reliable rapid antigen tests, for instance Abbott’s BinaxNOW test in the US and Oscar Medicare’s CAG test in India, show sensitivity greater than 80% (so a false-negative rate of under 20%). Given this newfound understanding of the accuracy of these tests and the current RT-PCR capacity crunch, ICMR has begun to encourage the scaling up of rapid antigen test capacity across the country“Indian Council of Medical Research (ICMR) issues advisory for COVID19 testing during the second wave of the pandemic”, ANI, Twitter https://twitter.com/ANI/status/1389584779369058304.
Can ordinary people administer these tests correctly?
Another prominent concern about the use of these tests revolves around self-administration at home. As of today, all samples in India are collected by healthcare workers, and there were worries that ordinary people at home would not self-collect their swabs correctly, or that oral swabs and Anterior Nares (AN) swabs from the front part of the nose would yield less accurate results than the deep and somewhat painful Nasopharyngeal (NP) swabs that are currently standard in India but can be difficult to self-collect; this could lead to false negatives through user error that would give people a mistaken impression of safety. However, studies from the UK YP Tu et al. “Patient-collected tongue, nasal, and mid-turbinate swabs for SARS-CoV-2 yield equivalent sensitivity to health care worker collected nasopharyngeal swabs.” BMJ, April 06, 2020, https://www.medrxiv.org/content/10.1101/2020.04.01.20050005v1. and Singapore Tan SY, Tey HL, Lim ETH, Toh ST, Chan YH, Tan PT, et al. (2020). “The accuracy of healthcare worker versus self collected (2-in-1) Oropharyngeal and Bilateral Mid-Turbinate (OPMT) swabs and saliva samples for SARS-CoV-2.” PLOS ONE, December 16, 2020, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244417 , among others, have shown very little to no difference between the results from professional-collected swabs and self-collected swabs. Further, studies in both Toronto, Canada Christopher E. Kandel et al. “Detection of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) in outpatients: A multicenter comparison of self-collected saline gargle, oral swab, and combined oral–anterior nasal swab to a provider collected nasopharyngeal swab.” Infect Control Hosp Epidemiol, Jan 13 2021, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870921/. and Berlin, Germany Lindner et al., “Head-to-head comparison of SARS-CoV-2 antigen-detecting rapid test with self-collected anterior nasal swab versus professional-collected nasopharyngeal swab.” European Respiratory Journal, vol. 57, no. 4, 2020. European Respiratory Journal, https://erj.ersjournals.com/content/early/2020/11/26/13993003.03961-2020. have demonstrated that self-collected oral swabs and Anterior Nasal (AN) swabs are just as accurate as the deeper Nasopharyngeal (NP) swabs.
Do other countries use these tests?
Over the past few months, self-administered at-home COVID-19 tests have become widely available across a number of countries. This includes the US, where a rapid test based on these techniques, Abbott’s BinaxNOW, has been approved by the FDA and can be bought over-the-counter at major pharmacies — studies have found the test to be a reliable alternative to RT-PCR tests in real-world settings Evaluation of Abbott BinaxNOW Rapid Antigen Test for SARS-CoV-2 Infection at Two Community-Based Testing Sites” Morbidity and Mortality Weekly Report (MMWR), January 22, 2021: https://www.cdc.gov/mmwr/volumes/70/wr/mm7003e3.htm.. Germany has approved similar tests from 7 different manufacturers that are quickly becoming available in stores “German Stores to Begin Selling COVID-19 Rapid Antigen Tests for Home Use”, 360DX, https://www.360dx.com/point-care-testing/german-stores-begin-selling-covid-19-rapid-antigen-tests-home-use.. The United Kingdom has made self-administered rapid antigen tests available for free to everyone in England via online ordering “Order coronavirus (COVID-19) rapid lateral flow tests”, Government of the United Kingdom, gov.uk, https://www.gov.uk/order-coronavirus-rapid-lateral-flow-tests..
Universal weekly testing using rapid at-home tests
Since April of 2020, a number of different epidemiologists, social scientists, and computer scientists, including the Harvard public health professor Michael Mina Michael Mina, “How We Can Stop the Spread of COVID-19 by Christmas,” TIME, 17 November 2020: https://time.com/5912705/covid-19-stop-spread-christmas/ , the Nobel-winning economist Paul Romer Paul Romer and Rajiv Shah, 'Testing Is Our Way Out,' Wall Street Journal, 2 April 2020: https://www.wsj.com/articles/testing-is-our-way-out-11585869705, and Test Everyone founder Soham Sankaran Soham Sankaran '113 Billion COVID Tests for India,' https://soh.am/writes/113_billion_covid_tests_for_india/, have suggested a strategy of universal testing using rapid tests — testing everyone in the population at least once a week. A number of independently constructed models all point to the same conclusion — testing everyone once a week could reduce the incidence of COVID-19 by more than 50% For example, see Pieter Libin et. al., “Assessing the feasibility and effectiveness of household-pooled universal testing to control COVID-19 epidemics,” PLOS Computational Biology, 9 March 2021: https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1008688 ,and Reda Cherif and Fuad Hasanov, “Universal Testing: An Overlooked COVID-19 Policy Response,” VoxEU, 15 August 2020: https://voxeu.org/article/universal-testing-overlooked-covid-19-policy-response. A simple model can be found at Paul Romer, “Simulating COVID-19,” https://paulromer.net/covid-sim-part1/ in a few testing cycles. In Mumbai, this would mean testing 2.5 million people per day. As previously discussed, this would not be possible with RT-PCR due to capacity constraints and logistical issues.
Rapid antigen tests are therefore our best shot at attempting this strategy. While we've previously discussed how these tests are quite sensitive, Paul Romer's models suggest that even a relatively inaccurate test with as much as a 40% false negative rate could significantly slow spread if deployed at massive scale. Below are three graphs from his website Paul Romer, “Even A Bad Test Can Help Guide the Decision to Isolate: Covid Simulations Part 3,” https://paulromer.net/covid-sim-part3/ comparing a baseline model (low to no testing) with testing using two different varieties of tests — one with the 20% false negative rate we've discussed for rapid antigen tests, and one with a 40% false negative rate. As you can see, even the 40% false negative test does a decent job and would likely save lives.
The evidence for the efficacy of mass testing in this manner is now quite substantial. On a small scale, data from American college campuses and the NBA bubble has shown the effectiveness of regular, frequent testing to avoid COVID spread See A. David Paltiel et. al., “COVID-19 screening strategies that permit the safe re-opening of college campuses,” medRxiv Preprint, July 2020: https://www.medrxiv.org/content/10.1101/2020.07.06.20147702v1, and Kelcie Pegher, “Coronavirus Today: The NBA’s Bubble Worked,” LA Times, 12 October 2020: https://www.latimes.com/science/newsletter/2020-10-12/coronavirus-today-nba-bubble-success-covid-lakers-coronavirus-today. On a larger scale, entire regions and even small countries have halted the spread through mass rapid testing. Most notably, the nation of Slovakia similarly tested its entire population in space of a few weeks using rapid tests last year, and by doing so reduced the national spread of COVID by 70%, as reported in a recent paper in Science Martin Pavelka et. al., “The impact of population-wide rapid antigen testing on SARS-CoV-2 prevalence in Slovakia,” Science Magazine, March 2021: https://science.sciencemag.org/content/early/2021/03/26/science.abf9648. The Canadian province of Nova Scotia has deployed pop-up booths in public and commercial spaces that offer rapid tests like the ones proposed here to avoid the larger caseload of other regions in the country Brain Platt, “Nova Scotia Embraced Rapid Testing for COVID-19 Months Ago,” National Post, 15 Jan 2021: https://nationalpost.com/news/politics/nova-scotia-embraced-rapid-testing-for-covid-19-months-ago-why-have-other-provinces-been-so-slow. The UK government has announced a policy of making twice-weekly at-home rapid tests available for free to all individuals in England on the basis of a successful trial in the city of Liverpool COVID: Tests to be Offered Twice-Weekly to All in England,” BBC, 6 April 2021: https://www.bbc.com/news/uk-56632084. See Liverpool COVID-SMART Pilot Evaluations, University of Liverpool, December-January 2021, at: https://www.liverpool.ac.uk/coronavirus/research-and-analysis/covid-smart-pilot/. These results overcame significant skepticism of the utility of mass rapid testing in the United States, as a result of which the National Institutes of Health and the Centers for Disease Control in the US have just initiated pilot programs to deploy large-scale at-home testing to curb community spread CDC and NIH bring COVID-19 self-testing to residents in two locales,” NIH Press Release, 31 March 2021: https://www.nih.gov/news-events/news-releases/cdc-nih-bring-covid-19-self-testing-residents-two-locales , as have major companies like Citibank, in cooperation with researchers at Harvard University Jennifer Surane, “Citi Debuts Rapid At-Home Covid Tests to Branch Workers, Traders,” Bloomberg, 10 March 2021: https://www.bloomberg.com/news/articles/2021-03-10/citi-debuts-rapid-at-home-covid-tests-to-branch-workers-traders. Regular, population-scale testing is fast becoming an essential component of COVID-19 containment strategy the world over.
Scaling self-administered rapid antigen tests
Testing everyone in India once a week would require the manufacture of ~200 million tests per day. While this may seem daunting, the production of these tests by companies like Pashi's partners at Oscar Medicare as well as a number of other firms making rapid antigen tests (there are over forty currently authorized by ICMR A list of currently-approved rapid antigen test kits can be found at the ICMR’s website, at https://www.icmr.gov.in/pdf/covid/kits/List_of_rapid_antigen_kits_08042021.pdf ) could feasibly scale to that number collectively from the current few million per day. As an added benefit, these tests can be manufactured entirely using indigenous materials. It would be even more straightforward to scale to the tens of millions per day required to completely cover areas with the biggest or fastest-growing outbreaks, while providing less coverage (one test per week per household, for example) to less affected areas.
Pashi’s bread and butter as a technology company is helping rapidly spin up, scale, and modify novel manufacturing processes, and we are absolutely convinced this can be done. The major bottlenecks are not in the core chemical processes used to make the paper strip itself, but rather in the manufacture of certain plastic components for and the assembly of the testing kits. There is likely enough injection molding capacity in India to serve the former, and the latter is mostly a function of available labour. If this is deemed to be of sufficient importance and funded adequately, there is a clear path to pulling this off.
How much would this cost?
It goes without saying that significantly slowing the spread of the virus would save many, many lives, the values of which are incalculable. That aside, even from a cold, purely economic standpoint, testing everyone is massively worthwhile — it pays for itself. COVID-related lockdowns have severely impacted the country’s economy; the rating agency CARE estimates that the Maharashtra lockdown alone will cost the country 40,000 crore INR every month “Maharashtra lockdown to shave off 0.3% growth”, CARE Ratings, 5 April 2021, https://www.careratings.com/uploads/newsfiles/05042021045113_Maharashtra_lockdown_to_shave_off_0.3_percent_growth.pdf . Assuming a cost of Rs. 50-100 per test, running universal weekly testing might cost on the order of a few crore INR daily across each large city. If testing much of Maharashtra weekly costs as much as 600 crore INR a month, and the state were to avoid further lockdowns as a result, the program will pay for itself more than 60 times over.
A note on vaccines
The distribution of COVID-19 vaccines in phases throughout India offers a long-term solution to the pandemic, and it is incontestable that rapidly scaling vaccination needs to be top of mind for the government and the pharmaceutical industry. Unfortunately, the ongoing surge — with its accompanying death toll and the debilitating economic impact of the resultant lockdowns — has made it clear that the virus needs to be more effectively contained until vaccination reaches sufficient levels. While those of advanced age are being given priority for vaccination, the virus is spreading quickly through not only younger adults but also children; at least 60,000 are known to have contracted the virus over the last month or two. Further, the supply of vaccines has proven greatly insufficient compared to the rate of COVID spread — it may be months before a sufficient rate of vaccination is achieved in the country’s large urban centers, and over a year before the country as a whole is sufficiently immunized India is unlikely to be vaccinated to the 70% level before the end of 2021. Some conservative models estimate that India will not reach 70% vaccination until late 2022; see “More than 85 poor countries will not have widespread access to coronavirus vaccines before 2023,” The Economist Intelligence Unit, 27 Jan 2021: https://www.eiu.com/n/85-poor-countries-will-not-have-access-to-coronavirus-vaccines/. In the meantime, hundreds of thousands more would die.
Health authorities in India and across the world have also expressed concern about the rate of mutation of the COVID-19 virus. A widespread variant in India currently classified as variant B.1.617, a twice-mutated strain of the virus, is likely to be particularly infective, and may have some resistance to the vaccines being deployed in India Jacob Koshy, “Coronavirus: Indian ‘Double Mutant’ Strain,” The Hindu, 8 April 2021: https://www.thehindu.com/news/national/indian-double-mutant-strain-named-b1617/article34274663.ece. Even if the vaccination drive accelerates in the near future, we will likely have to contend with this variant, and others, for years to come.
It is therefore clear that vaccination alone cannot be the sole mass measure taken against COVID in the short and medium term. Vaccines and testing do not represent an either-or choice, but rather must form the two major components of a combined strategy for stamping out COVID-19 in order to prevent devastation of lives and livelihoods.
The Test Everyone Plan
In light of the strong evidence collected here, we ask that Indian government approve the self-administered use of rapid-antigen tests — in particular, those with a sensitivity of 75% or greater for samples detectable with RT-PCR at a cycle threshold (CT) value of 30 or less — at home by ordinary people using self-collected Anterior Nares (AN) and oral swabs. We believe that the general public should be allowed to buy them over the counter without a prescription or referral. Furthermore, we propose that India implement free or heavily subsidized universal weekly testing as a means of containing the spread COVID-19 across the country.
We at Test Everyone are happy to help the national government, local governments, community organizations, and companies pilot and then rapidly deploy universal testing in their areas of interest. We believe that doing so could reduce the daily incidence of new COVID-19 cases in large cities like Mumbai by more than 50% in just three weeks. We intend to run at least one large-scale randomized controlled trial (RCT) of the efficacy of this approach in curbing community spread, but the existing evidence in support of immediate large-scale rollout is clear and compelling. We ask that the country not wait any longer — the time to act is now.