Group Testing for SARS-CoV-2: Forward to the Past?
28 Apr 2020-Vol. 4, Iss: 2, pp 207-210
TL;DR: The case for whether group testing should become a key component of the strategy to combat coronavirus disease 2019 (COVID-19) is examined, as well as facilitating index case isolation and contact tracing in the early stages, and enabling frontline healthcare and other key workers to safely go to work.
Abstract: A key challenge many governments have faced in developing a response to the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been constraints in the availability of diagnostic tests. The initial focus has been on case identification [1] to facilitate index case isolation, contact tracing and quarantining—necessary measures to maximise disease suppression. Alongside this there will be an increasing need to monitor the spread of the disease in the community to understand the level of ageand geographyspecific population immunity. The challenges presented by testing for SARS-CoV-2 are as much about manufacturing capacity, economics and resource allocation as epidemiology. Here we examine the case for whether group testing should become a key component of the strategy to combat coronavirus disease 2019 (COVID-19). Even in the most developed countries, reverse transcription polymerase chain reaction (RT-PCR) testing, which involves swab testing for the virus’ genetic material and is currently the standard test, is severely constrained [2, 3]. This is due to shortages in key supplies, such as reagents, and a limit to the number of tests that can be performed per day using existing equipment [4]. Though no demonstrably effective antibody test yet exists, some governments have emphasised mass deployment of such tests as a key element of their strategy. Though still to be adequately tested, the United Kingdom (UK) government, for example, has purchased 3.5 million such tests to be used for key workers, with the hope that they will later become widely available in the community [5]. Lowand middle-income countries (LMICs) typically face even greater constraints to testing resources. A survey of preparedness across African countries indicated that in some countries testing capacity is extremely limited, leaving them ill-equipped to respond to the pandemic [6]. Low-cost, rapid diagnostic tests such as that being developed by The UK’s Department for International Development, together with the government of Senegal, may be a vital tool in many LMICs’ battle against COVID-19 [7]. Yet, even at that test’s proposed cost of just US$1 [7], the feasibility of wide-scale administration of such tests in Senegal and beyond remains unclear. Even US$1 is more than 10% of the annual public per capita health expenditure in nearly half of Sub-Saharan African countries [8], and using human immunodeficiency virus (HIV) PCR tests as a benchmark, costs of US$10 for rapid diagnostic tests for SARS-CoV-2 seem feasible [9]. There are good reasons why the World Health Organization has made “test, test, test” its mantra in the fight against COVID-19 [10]. As well as facilitating index case isolation and contact tracing in the early stages, testing for infection enables frontline healthcare and other key workers to safely go to work. Effective antibody tests could enable billions globally to safely return to work from lockdowns much sooner, with enormous economic benefits. Testing is also integral to estimating ageand geography-specific proportions of the immune compartment of the population. For example, serosurveys are crucial to predicting the future behaviour of the virus in the population. This would allow governments to understand the likelihood (and expected size) of future waves of the epidemic, and when it can be expected that sufficient herd immunity will be reached to protect the remainder of the susceptible (yet to be infected) population. Testing is also necessary to understanding the Koen B. Pouwels and Laurence S. J. Roope are joint “first author”, with order determined randomly.
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TL;DR: In this analysis, group testing was the most effective and efficient COVID-19 surveillance strategy for resource-limited LTCFs, and testing cascades were even more effective given ample testing resources.
Abstract: Long-term care facilities (LTCFs) are vulnerable to outbreaks of coronavirus disease 2019 (COVID-19). Timely epidemiological surveillance is essential for outbreak response, but is complicated by a high proportion of silent (non-symptomatic) infections and limited testing resources. We used a stochastic, individual-based model to simulate transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) along detailed inter-individual contact networks describing patient-staff interactions in a real LTCF setting. We simulated distribution of nasopharyngeal swabs and reverse transcriptase polymerase chain reaction (RT-PCR) tests using clinical and demographic indications and evaluated the efficacy and resource-efficiency of a range of surveillance strategies, including group testing (sample pooling) and testing cascades, which couple (i) testing for multiple indications (symptoms, admission) with (ii) random daily testing. In the baseline scenario, randomly introducing a silent SARS-CoV-2 infection into a 170-bed LTCF led to large outbreaks, with a cumulative 86 (95% uncertainty interval 6–224) infections after 3 weeks of unmitigated transmission. Efficacy of symptom-based screening was limited by lags to symptom onset and silent asymptomatic and pre-symptomatic transmission. Across scenarios, testing upon admission detected just 34–66% of patients infected upon LTCF entry, and also missed potential introductions from staff. Random daily testing was more effective when targeting patients than staff, but was overall an inefficient use of limited resources. At high testing capacity (> 10 tests/100 beds/day), cascades were most effective, with a 19–36% probability of detecting outbreaks prior to any nosocomial transmission, and 26–46% prior to first onset of COVID-19 symptoms. Conversely, at low capacity (< 2 tests/100 beds/day), group testing strategies detected outbreaks earliest. Pooling randomly selected patients in a daily group test was most likely to detect outbreaks prior to first symptom onset (16–27%), while pooling patients and staff expressing any COVID-like symptoms was the most efficient means to improve surveillance given resource limitations, compared to the reference requiring only 6–9 additional tests and 11–28 additional swabs to detect outbreaks 1–6 days earlier, prior to an additional 11–22 infections. COVID-19 surveillance is challenged by delayed or absent clinical symptoms and imperfect diagnostic sensitivity of standard RT-PCR tests. In our analysis, group testing was the most effective and efficient COVID-19 surveillance strategy for resource-limited LTCFs. Testing cascades were even more effective given ample testing resources. Increasing testing capacity and updating surveillance protocols accordingly could facilitate earlier detection of emerging outbreaks, informing a need for urgent intervention in settings with ongoing nosocomial transmission.
66 citations
TL;DR: An analysis and applications of sample pooling to the epidemiologic monitoring of COVID-19 with an economy of tests and a method for the measure of the prevalence in a population, based on group testing, taking into account the increased number of false negatives associated to this method.
Abstract: We propose an analysis and applications of sample pooling to the epidemiologic monitoring of COVID-19. We first introduce a model of the RT-qPCR process used to test for the presence of virus in a sample and construct a statistical model for the viral load in a typical infected individual inspired by large-scale clinical datasets. We present an application of group testing for the prevention of epidemic outbreak in closed connected communities. We then propose a method for the measure of the prevalence in a population taking into account the increased number of false negatives associated with the group testing method.
31 citations
TL;DR: The development of alternative hybrid methods, based on “in house” protocols, utilizing commercially available consumables, in combination with a reliable pooling method would provide a solution, focusing on the better exploitation of the personnel and the lab supplies, allowing for rapid screening of a population in a reasonably short time.
25 citations
TL;DR: It is found that a single positive specimen can still be detected in pools of up to 10 in the RT-PCR test to detect low viral loads of SARS-CoV-2.
15 citations
06 Aug 2020
TL;DR: Pooled testing is a useful strategy to increase SARS-CoV-2 laboratory testing capacity especially in low-income settings and came with a slight decline of test sensitivity.
Abstract: Background. International recommendations for the control of the coronavirus disease 2019 (COVID-19) pandemic emphasize the central role of laboratory testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent, at scale. The availability of testing reagents, laboratory equipment and qualified staff are important bottlenecks to achieving this. Elsewhere, pooled testing (i.e. combining multiple samples in the same reaction) has been suggested to increase testing capacities in the pandemic period. Methods. We discuss our experience with SARS-CoV-2 pooled testing using real-time reverse transcription polymerase chain reaction (RT-PCR) on the Kenyan Coast. Results. In mid-May, 2020, our RT-PCR testing capacity for SARS-CoV-2 was improved by ~100% as a result of adoption of a six-sample pooled testing strategy. This was accompanied with a concomitant saving of ~50% of SARS-CoV-2 laboratory test kits at both the RNA extraction and RT-PCR stages. However, pooled testing came with a slight decline of test sensitivity. The RT-PCR cycle threshold value (ΔCt) was ~1.59 higher for samples tested in pools compared to samples tested singly. Conclusions. Pooled testing is a useful strategy to increase SARS-CoV-2 laboratory testing capacity especially in low-income settings.
13 citations
References
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1,533 citations
TL;DR: In this paper, the authors discuss the economic impact of the Coronavirus/COVID-19 crisis across industries, and countries, and provide estimates of the potential global economic costs of COVID-2019, and the GDP growth of different countries.
Abstract: This report discusses the economic impact of the Coronavirus/COVID-19 crisis across industries, and countries. It also provides estimates of the potential global economic costs of COVID-19, and the GDP growth of different countries.
The current draft includes estimates for 30 countries, under different scenarios.
The report shows the economic effects of outbreak are currently being underestimated, due to over-reliance on historical comparisons with SARS, or the 2008/2009 financial crisis.
At the date of this report, the duration of the lockdown, as well as how the recovery will take place is still unknown. That is why several scenarios are used. In a mild scenario, GDP growth would take a hit, ranging from 3-6% depending on the country. As a result, in the sample of 30 countries covered, we would see a median decline in GDP in 2020 of -2.8%. In other scenarios, GDP can fall more than 10%, and in some countries, more than 15%.
Service-oriented economies will be particularly negatively affected, and have more jobs at risk. Countries like Greece, Portugal, and Spain that are more reliant on tourism (more than 15% of GDP) will be more affected by this crisis. This current crisis is generating spillover effects throughout supply chains. Therefore, countries highly dependent on foreign trade are more negatively affected. The results suggest that on average, each additional month of crisis costs 2.5-3% of global GDP.
1,207 citations
"Group Testing for SARS-CoV-2: Forwa..." refers background in this paper
...The capacity to undertake widespread community-level testing could help mitigate the risk that a relaxation of the current unprecedented social-distancing restrictions many governments have imposed (e.g. ceasing international passenger movements and school and workplace closures) would produce further outbreaks of SARS-CoV-2, which has been estimated to reduce global gross domestic product by up to 2.5% per month of lockdown [12] ....
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TL;DR: Defining the Epidemiology of Covid-19 Experience with MERS, pandemic influenza, and other outbreaks has shown that as an epidemic evolves, there is an urgent need to expand public health activities in response to this epidemic.
Abstract: Defining the Epidemiology of Covid-19 Experience with MERS, pandemic influenza, and other outbreaks has shown that as an epidemic evolves, we face an urgent need to expand public health activities ...
994 citations
TL;DR: The preparedness and vulnerability of African countries against their risk of importation of COVID-19 is evaluated, finding that countries with the highest importation risk have moderate to high capacity to respond to outbreaks and countries at moderate risk have variable capacity and high vulnerability.
939 citations
TL;DR: It is hoped that implementation of a pool test for COVID-19 would allow expanding current screening capacities thereby enabling the expansion of detection in the community, as well as in close organic groups, such as hospital departments, army units, or factory shifts.
Abstract: BACKGROUND: The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to a current pandemic of unprecedented scale. Although diagnostic tests are fundamental to the ability to detect and respond, overwhelmed healthcare systems are already experiencing shortages of reagents associated with this test, calling for a lean immediately applicable protocol. METHODS: RNA extracts of positive samples were tested for the presence of SARS-CoV-2 using reverse transcription quantitative polymerase chain reaction, alone or in pools of different sizes (2-, 4-, 8-, 16-, 32-, and 64-sample pools) with negative samples. Transport media of additional 3 positive samples were also tested when mixed with transport media of negative samples in pools of 8. RESULTS: A single positive sample can be detected in pools of up to 32 samples, using the standard kits and protocols, with an estimated false negative rate of 10%. Detection of positive samples diluted in even up to 64 samples may also be attainable, although this may require additional amplification cycles. Single positive samples can be detected when pooling either after or prior to RNA extraction. CONCLUSIONS: As it uses the standard protocols, reagents, and equipment, this pooling method can be applied immediately in current clinical testing laboratories. We hope that such implementation of a pool test for coronavirus disease 2019 would allow expanding current screening capacities, thereby enabling the expansion of detection in the community, as well as in close organic groups, such as hospital departments, army units, or factory shifts.
354 citations