As part of getting ready to open schools, and understanding the potential that this might not apply in countries where there are limited resources for successful bid process to identify providers, this paper sets out to make the case for a critical safety measure that could allow the return to a more normal approach to schooling and allow for a degree of confidence in practices when this method is also coordinated with access and hygiene-related measures to provide a layered approach to risk reduction.
In coordination with Epixpert.pl, the American School of Warsaw engaged in a full epidemiological audit of our school facility to determine practices and assess components for a multi-layered approach to safe school opening. This work with Epixpert and Dr. Jarek Oleszczuk, MD, Ph.D., a founding partner, has been instrumental in laying the foundation for a safe and successful return to brick and mortar schooling in August.
The three goals of the audit were to 1) prevent the virus from entering the school, 2) ensure that in case the virus enters the school, it does not spread widely, and 3) keep our educational and programme delivery model as unchanged as possible. The audit provided a 14 point comprehensive set of recommendations for mitigation that will reduce the risk for our population and achieve these goals.
In addition to a comprehensive building plan and facility review, the overall audit provided to ASW included an aggressive preventative testing plan for the entire ASW population of students and staff, partnered with in-home risk assessment and facility entry control with temperature checking. The most significant of these proposals is the testing protocol and the following summary, provided by Dr. Oleszczuk, constitutes the structural backdrop to provide for the implementation of practices that being adopted in both the corporate and public service realms around the world, including, as noted below, schools at both the preparatory and post-secondary levels.
- 80% of outbreaks are caused by asymptomatic or presymptomatic carriers
- Frequent testing as a screening tool is the only approach to identify carriers
- Pooled testing has been validated both scientifically as well as in population settings as a valid approach of screening large populations while preserving resources and financial outlays, offering up to 70–80% savings
- The FDA has recently acknowledged pooled testing as a screening methodology for asymptomatic individuals
- Dr. Anthony S. Fauci has publicly announced that a US-wide strategy of pooled testing will be ready by the end of summer
- Numerous schools and universities in the US are implementing pooled testing as one of the key measures in 2020/21 academic year
- The FDA accepts nasal swab (both anterior outer nares) as an acceptable alternative to nasopharyngeal swab in SARS-CoV-2 testing
- On July 18, the Food and Drug Administration issued the first emergency use authorization for a PCR test to be used with pooled samples in the U.S.
In order to contain the spread of any pandemic (including COVID-19) before the broad availability of an effective vaccine, it is imperative to identify all carriers. An alternative is, of course, a broad lockdown that has been shown to have dramatic consequences — not only for businesses but also for schools.
In order to preserve the classroom learning, we need to employ every possible measure to identify all potential SARS-CoV-2 carriers and prevent them from entering the school.
Unfortunately, symptoms of COVID-19 appear many days after inoculation (3–12 days) so identifying ill individuals via body temperature measurements will not identify presymptomatic carriers. Moreover, over 50% of infections are asymptomatic, further confounding the identification of ill individuals. A recent study of more than 60 outbreaks in Japan demonstrated that over 80% of outbreaks have been caused by asymptomatic or presymptomatic carriers.
Thus, the only way, other than a lockdown, to identify SARS-CoV-2 carriers is frequent testing, frequent enough to occur within the window of 3–12 days.
Yet, with current lab fees around $100 per test, repeatedly administering COVID-19 tests to an entire student body will become prohibitively costly for schools. Moreover, no country has the capacity to process tests of every student.
Pooled testing is a well-established approach to track infectious disease, and has already been run successfully on coronavirus samples at labs in Stanford and Israel. In this approach, lab tests are batched in samples of several people and these batches are tested for the presence of active virus. If the test indicates at least one person in that pool is infected, repeat testing of the individuals in the infected pool can reveal the source. This follow-up step does not require a separate round of specimen collection. Rather, each person’s sample is split into two at the beginning of the process — one is subjected to pooled testing, and the other set aside in case individual follow-up testing is required. In contrast, if the pooled sample comes back negative, it could clear all members of the pool for work, at least until the next testing cycle. While there are inherent challenges in this approach, including choosing appropriate pool sizes and factoring in test-reliability concerns, estimates suggest that pooled testing could lower testing costs by up to 70–90% while the prevalence of COVID-19 remains low in the general population.
According to a recently published white paper by researchers at the University of Southern California Schaefer Center for Health Policy & Economics, this strategy can be used with polymerase chain reaction (PCR) testing. The most efficient initial pool size depends on prevalence, with rarer conditions allowing larger pools. Given the current prevalence of COVID19, even five- to 10-person pools of employees or students are likely to test negative, obviating the need for administering tests to each person. A recent study suggests that it is feasible to pool samples on this scale without significantly compromising the integrity of the PCR tests. A simple example illustrates the logic.
Consider an employer with 100 employees in a region of the country believed to suffer from a 5% prevalence of active COVID-19 infection. This employer splits up its workforce into 20 groups of five workers each. For simplicity, suppose that exactly five workers have the disease so that the employer is experiencing the same prevalence as its overall region. Under pooled testing, no more than five pools will return positive tests. The employer then tests the employees in the positive pools individually. In this case, no more than 25 individual tests are run, since there are five pools testing positive, each with five workers. Ultimately, the employer has successfully identified all five of its COVID-19+ employees, but it only needed to run 45 tests — 20 initial pooled tests and 25 individual follow-up tests. The employer saved 55 percent of the cost that would have been incurred via individualized testing.
Pooled testing works best when the employer or school system chooses pool sizes correctly. For instance, if pools are set too large, every pool might test positive. In this case, the organization gains nothing from that round of pooled tests. This issue is particularly salient in high-prevalence regions, where large pools of employees might routinely turn up at least one positive case. By contrast, employers in lower-prevalence regions can afford to use larger pools, because even large pools of employees have a good chance of testing negative in these regions. However, even relatively high-risk regions stand to gain from pooled testing. For example, pool sizes of four to seven employees could help the vast majority of organizations reap most of the gains from pooled testing, even when they are highly uncertain about the prevalence of the illness in their workforce. We estimate that pooled testing could reduce testing costs by 80 percent in low-prevalence regions, and still save 50 percent for higher prevalence (5 percent) locations. Indeed, even if prevalence climbs to 10 percent schools can save as much as 40 percent via pooled testing strategies.
The pooled sampling approach has recently been validated on a population scale during the second wave of infections in Wuhan, China, where more than 11 million inhabitants have been tested in just days.
In a recent interview, Dr. Anthony S. Fauci hailed the approach and stated that “We’re in intensive discussions about how we’re going to do it…. We hope to get this off the ground as soon as possible.”
During a recent visit of Vice President Mike Pence to the University of South Florida, Dr. Deborah Birx announced that the federal government is working to support pooled (i.e., preliminary) testing, where samples from entire families or groups can be tested in a single collection medium and sent to a lab for quick results. In the event that one person in the pooled group tests positive, then individualized testing, using medically certified testing procedures, allows for contact tracing and self-quarantines. She said that, for example, entire classrooms can be tested in this manner, as well as students in a university residence hall.
In a call with reporters on Wednesday, July 1, 2020, Adm. Brett Giroir, deputy secretary of health and human services, said he expected the program to be up and running by the end of the summer.
On June 16 the Food and Drug Administration of the United States published an important update to its EUA requirements for test manufacturers as well as laboratories who want to perform pooled sampling. In its press release, the FDA states that “Diagnostic tests are an important tool in anticipating and meeting the continuing and evolving public health needs as we combat COVID-19. Today, the FDA took a meaningful step forward in getting more tests to more Americans more quickly and making that process even easier for developers by posting template updates regarding the validation of molecular diagnostic tests for developers that intend their assay to be used for pooling patient samples or for screening asymptomatic individuals not suspected of having COVID-19.
The FDA recognizes that organizations may want to conduct screening of asymptomatic individuals as part of a broader strategy to help ensure the safety of their employees, patients, students, and others.
This method works well when there is a low prevalence of cases, meaning more negative results are expected.
Oberlin College recently announced its reopening plans and weekly testing using a pooled sampling approach is one of the key measures taken to ensure safety in the College. President Carmen Ambar recently wrote to students and detailed her plans for reopening:
Oberlin is finalizing a contract with Tempus, a private testing firm that guarantees capacity for initial and regularized diagnostic (PCR) COVID-19 testing for students, faculty, and staff who will be on campus. PCR testing provides an indication of the presence of the coronavirus by looking directly for its genetic material. Such tests can determine if someone is carrying the virus, whether or not symptoms are present. We are working with public health experts to determine the parameters and frequency of testing, but our goal is to do surveillance testing for up to 25% of our population each and every week to get a snapshot of our campus.
We are fortunate to have a local hospital almost literally on our campus, Mercy Health-Allen Hospital. We are currently in negotiations with Mercy-Allen to administer a test to our students, faculty and staff, during the move-in period and to support our weekly testing strategy. This means we will test 3,500 or more people in August and then similar numbers each month.
This won’t be easy, as it will require significant logistics and coordination, as well as a substantial financial investment. The College will be fully funding our faculty and staff, and we will be asking for some family support in the form of a testing fee for students. We did not come to this decision lightly, but public health experts say this is the best way to help ensure viral spread does not catch us by surprise.
Similar measures are being introduced by Syracuse University, which recently announced pooled testing will be used to regularly test all of its 20,000 students.
Centogene N.V., a commercial-stage diagnostics, and genetic research company, and the OESIS Network Inc., an innovation network of more than 600 schools across the U.S., have announced a partnership for COVID-19 screening of schools. The partnership will offer RT- PCR testing that can aid schools in their return to campus in the fall and continued screening to prevent a resurgence of COVID-19 over the course of the academic school year. Their approach will incorporate pooled testing, where test samples are batched — potentially reducing analytical costs.
According to the FDA, a nasopharyngeal specimen is a preferred choice for swab-based SARS-CoV-2 testing. If a nasopharyngeal specimen is not available, there are a number of alternatives.
The following specimen types can be obtained with a swab:
- Nasopharyngeal specimen collected by a healthcare professional (HCP);
- Oropharyngeal specimen collected by an HCP;
- Mid-turbinate specimen by onsite self-collection or HCP (using a flocked tapered swab); or
- Anterior nares specimen by onsite self-collection or HCP (using a round foam or spun fiber swab).
Multiple specimens from the same patient may be taken with a single swab. If a separate swab is used for collecting specimens from two different locations in the same patient, both swabs may be placed in the same vial in order to conserve collection and assay supplies. Other swab specimens (i.e., tongue swabs) may have decreased sensitivity, so caution should be exercised when interpreting negative results. More data are necessary to better understand the validity of buccal swabs, saliva specimens, or other specimen types for COVID-19 testing.
On July 18, the Food and Drug Administration issued the first emergency use authorization for a PCR test to be used with pooled samples paving the way for broader use of this approach:
This EUA for sample pooling is an important step forward in getting more COVID-19 tests to more Americans more quickly while preserving testing supplies,” said FDA Commissioner Stephen M. Hahn, M.D. “Sample pooling becomes especially important as infection rates decline and we begin testing larger portions of the population.
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