Simulation of pooled-sample analysis strategies for COVID-19 mass testing

Abstract

DISCLAIMER This paper was submitted to the Bulletin of the World Health Organization and was posted to the COVID-19 open site, according to the protocol for public health emergencies for international concern as described in Vasee Moorthy et al. (http://dx.doi.org/10.2471/BLT.20.251561). The information herein is available for unrestricted use, distribution and reproduction in any medium, provided that the original work is properly cited as indicated by the Creative Commons Attribution 3.0 Intergovernmental Organizations licence (CC BY IGO 3.0).

Group testing for SARS-CoV-2 allows for up to 10-fold efficiency increase across realistic scenarios and testing strategies

“…We study a model with two subpopulations of different prevalence, and consider prevalence values between 5% and 25% for the high-risk and between 0·1% and 5% for the low-risk group. As far as we are aware, this assumption regarding different prevalence values for two groups, so in line with the two subpopulations we mention, was first mentioned in the context of SARS-CoV-2 by Deckert and colleagues, 18 where they speak of homogeneous pools and use noninformative D2 for their analysis. However, the question of whether and how to adjust the testing procedure based on subpopulation knowledge did not arise in this work.…”

“…7 Other works over the last weeks have suggested refined approaches, typically based on examples or, from a more theoretical viewpoint, with a simplified model. [15][16][17][18][19][20][21] In this manuscript, we will demonstrate and systematically explore that even within the limitations of the initial experimental designs for COVID-19 testing, more sophisticated pooling strategies can lead to a significantly reduced number of tests. Thus connecting the recent SARS-CoV2 pool tests to the rich literature on group testing developed over the last decades may be a key ingredient for effectual national responses to the current pandemic.…”

“…A first attempt to make use of such a stratification for SARS-CoV-2 testing has recently been made with two subpopulations. 18 This paper, however, only assembles homogeneous pools within the two subpopulations and hence does not make use of the full power of informative testing. Namely, the testing efficiency can be significantly improved by smartly assembling combined pools with members of both subpopulations.…”

Large-scale implementation of pooled RNA-extraction and RT-PCR for SARS-CoV-2 detection

“…Of the 5 pools which contained one individual sample with an "indeterminate" result (in each pool), one was found to be negative suggesting potential yet negligible loss of sensitivity. 20,21,23), and 4 out of 5 pools containing a single indeterminate sample detected as indeterminate (pools 16,17,18,19,22); Pools containing 1-2 samples with low amount of SARS-CoV-2 are detected at a similar Ct (pools [9][10][11][12][13][14][15][16][17][18], showing clinical sensitivity is retained and the risk of false negatives is minimal. UD= Undetected.…”

“…While several pooling approaches for SARS-CoV-2 detection were recently suggested (e.g. [16][17][18][19]), none demonstrated adherence to current clinical standards, nor shown to work for performing RNA extraction in pools, which is typically the limiting step. Here we describe and demonstrate practical pooling solutions that save time and reagents by performing RNA extraction and RT-PCR on pooled samples.…”