A comprehensive strategy to lower number of COVID-19 tests

*
Assif Assada, Muzafar Ahmad Wanib, Kusum Deepc
a
Islamic University of Science and Technology Awantipora, India,192122
b
National Institute of Technology Srinagar, India,190006
c
Indian Institute of Technology Roorkee, India, 247667
*
Corresponding Author Email assifassad@gmail.com

Abstract

In this paper a strategy is proposed for accelerating COVID 19 testing, recently few
models particularly based on the concept of pooling samples from multiple patients in a single
test tube and then perform bulk testing have been proposed. However the efficiency of these
models depends on percentage of positive COVID 19 patients which is completely missing in
these studies and hence limits their practical applicability.

In this paper two already proposed models for COVID 19 testing are thoroughly analyzed
using simulated data, and efficient strategies are proposed based on percentage of positive
COVID-19 tests. Further insight about the pool size to be taken is also provided.

This study will help practitioners to adopt testing strategies dynamically and save
millions of tests worldwide. Thus makes it possible for the implementation of expanded testing
in larger population to identify asymptomatic patients and curb the spread of pandemic.

1) Introduction:

Corona Virus (COVID-19) a type of virus that infects humans, typically respiratory
system, leading to an upper respiratory infection. Corona virus has Virions (Virus Particles) that
measure 120 nm (1 nm= 10-9) in diameter. The first case of the novel corona virus was detected
in Wuhan city in "late December 2019", spreading the whole globe with in the span of three
months, victimizing about 2 million people, the pandemic is still spreading like wild fire.

There are mainly two techniques for testing of the Corona virus namely Molecular Tests and
Serological Tests.

Molecular Tests: These tests look for the signs of an active infection. In this test the
sample is taken from the back of the throat with a cotton swab that is then sent off for testing.
This test actually undergoes a polymerase chain reaction (PCR). A PCR test can confirm a
diagnosis of COVID-19 if it identifies two specific SARS-CoV-2 genes. The PCR tests are
currently used worldwide to identify the patients and are particularly useful for detecting cases of
infection with mild or no symptoms. Millions of PCR tests have been performed worldwide to
identify COVID-19 patients.
Serological Tests: These tests detect antibodies that the body produces to fight the virus.
These antibodies are present in anyone who has recovered from COVID-19. These antibodies
exist in blood and tissues throughout the body. This test mainly requires a blood sample. The
samples would be taken at least 21 days after symptoms first developed.

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 Due to COVID-19 pandemic whole world is facing the challenge in the form of testing,
as it is the only way to identify the patients particularly asymptomatic that can be identified and
isolated so as to break the chain of spread. However conducing mass tests is not only financially
challenging but time consuming also. Thus optimizing the testing process can play a great roll in
curbing the spread of this pandemic.

2) Pooling Method (PM) for PCR Testing

On March 19, 2020 researchers from two Israeli institutes (Technion-Israel Institute of
Technology and Rambam Health Care Campus) introduced a novel strategy to test more than 60
patients simultaneously for COVID-19 [1-4]. Researchers from Germany have also successfully
used pooling strategy for testing COVID-19 patients [5]. The method simply pools multiple
samples in a single test tube. They are screened using the normal PCR testing procedure. Even
when joint examination of 64 samples is conducted in which only one is positive carrier the
system identified that the sample is positive. Only in those rear cases, where the joint sample is
found positive, individual test for each specific samples is performed. The strategy will help to
screen asymptomatic carriers and many researchers have referred this innovation as a significant
milestone in fight against COVID-19. This strategy of combining samples is referred as Pooling
Method (PM).

The Pooling Method (PM) seems promising however the effectiveness of the proposed strategy
is dependent on percentage of positive cases. The questions like following need to be addressed
before adopting the model:

1. How effective is this strategy if 1% of the tests turnout to be positive.

2. Is it really necessary to create larger pool of samples involving cumbersome logistics or we

can achieve comparatively good efficiency using smaller sample.

In order to answer such questions we analyzed the model by carrying out simulations on a
computer, taking 6400 persons divided in 100 pools, each pool containing 64 samples (referred
as Pool Size), further it is assumed positive cases are uniformly distributed across pools. Each
simulation is repeated 20 times and the results are averaged.

Table I shows the simulation results with respect to percentage of positive cases. As expected the
proposed method works fine when the percentage of positive cases is extremely small (say less
than 0.1% i.e. one positive test in thousand tests). However what is surprising the strategy hardly
shows any benefit when the number of positive samples is moderately small (say for example
around 1%). As an example when the number of positive cases is just 5% (320 out of 6400) we
end of performing 98% (6257) tests. The reason for this somewhat surprising behavior is since
there are 5% (i.e. 320 out of 6257) positive persons, they are enough to contaminate all the 100
pools, and thus we end up examining almost every single sample. Similarly when there are just
1% positive cases (64 out of 6400), 3200 tests need to be performed as 64 positive samples can
easily contaminate 50 Pools. Thus at 1% of positive case even though number of tests gets
reduces to half (compared to brute force approach requiring 6400 tests) but the benefit is much
less than expected. If the number of positive case is 10%, we need to perform more tests than

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number of persons to be tested, as testing pools just adds redundancy rather than serving any
purpose.

Another important parameter in the PM model is Pool Size. There is a tradeoff between pool size
and performance. Clearly small pools involve less logistics and hence are easy to create than
large pools, on the other hand large pools have the potential to reduce number of tests.

In order to reflect this tradeoff simulations were carried out for different Pool sizes, Table II
summarizes the results, these results can be utilized by the practitioner to determine optimal pool
size. As an example if the positive cases are around 1%, 8 rather than 64 is the optimal pool size.
Further at 0.1 % even though optimal pool size it 32, the practitioner may choose pool size of 16
as it will reduce the complexity of creating pools on the cost of increasing few tests.

Table I: Percentage of Tests Required

Percentage of Number of Tests Percentage of tests required
positive Cases Required
(for 6400 Persons)
50% 101.56%
6500
40% 101.56%
6500
30% 101.56%
6500
25% 101.56%
6500
20% 101.56%
6500
15% 101.56%
6500
10% 101.36%
6487
5% 97.76%
6257
4% 93.36%
5975
3% 86.76%
5553
2% 73.36%
4695
1% 50.46%
3229
.5% 30.96%
1981
.1% 9.26%
593
.05% 5.56%
356
0.01% 2.26%
145
0.001% 1.76%
113
0.0001% 1.76%
113

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 Table II: Percentage Tests Required as per Pool Size

Percentage Pool Size

of positive 64 32 16 8 4 2
samples
30% 101% 103% 106% 106% 100% 101%
20% 103% 103% 102% 94% 84% 88%
10% 101% 99.5% 87% 70% 59% 70%
5% 97% 85% 61% 44% 43% 60%
1% 50% 32% 22% 23% 29% 53%
0.5% 30% 20% 14% 17% 28% 52%
0.1% 9.2% 7.2% 7.7% 12.9% 25% 50%
0.05% 5.5% 5.0% 6.9% 12.5% 25% 50%
0.01% 2.2% 3.2% 6.25% 12.5% 25% 50%
0.001% 1.76% 3.2% 6.25% 12.5% 25% 50%
0.0001% 1.76% 3.2% 6.25% 12.5% 25% 50%

3) Binary Elimination Algorithm (BEA) for COVID-19 testing:

Researchers from India extended the pooling strategy of [6], and proposed an algorithm which
they call Merkle and Binary trees for accelerated COVID-19 testing, since the algorithm
eliminates half of the samples at each stage (like Binary Search) we call the algorithm as Binary
Elimination Algorithm (BEA) in this study. Like Pooling Method samples from individual
persons are pooled together, if the Pooled sample tests negative then all the patients in the pool
are negative, however if the Pool tests positive in BEA the patients are divided into two mutually
exclusive groups and each group is tested separately, the same process is repeated for subgroups.
Figure 1(reproduced from [6]) explains BEA, suppose 16 persons are to be tested, the samples of
two persons are mixed as shown at Stage I of Figure 1, then samples produced at Stage I are
again mixed resulting in Stage II samples, the process continues till final pool sample (at Root of
tree) is produces. The red dot in Figure 1 shows positive patient and the green dots show
negative persons. The pool sample tests positive, so both the samples at Stage III are tested. The
sample on right hand side (Stage III) is negative, thus all these 8 patients are negative and need
not to be tested further, however the left hand sample (Stage III) is positive they are further
divided into two groups and the process continues. Thus only 9 tests rather than 16 are required
using BEA.

However the algorithm shows worst case behavior if all the patients in the sample are positive, as
an example if all persons in sample of 16 and are positive the algorithm needs to perform 31
tests, a sample size of 64 with all positive patients requires 127 tests. In general if the pool

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 sample size is N, BEA requires 2N-1 tests in the worst case. It won't be out of place to mention
the authors of the proposed algorithm have shown the worst case complexity as N+3 [6] which is
wrong.

Mixed Samples (Root)

Mixed Samples (Stage III)

Mixed Samples (Stage II)

Mixed Samples (Stage I)

Persons 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

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Since in the worst cases number of tests required by BEA is approximately twice the number of
persons to be tested, the question is will it serve any useful purpose when applied for COVID 19
testing. In order to answer the question detailed analysis on simulated data was performed. The
sampling strategy used for BEA is exactly the same as used for PM in previous section, the
comparative analysis of PM and BEA is summarized in Table III.

When the number of positive cases is high (more than 20%), BEA performs very poor, the
number of tests required is more than number of persons to be tested. However as the percentage
of positive cases start decreasing, performance of BEA algorithm shows improvement. At 10%
positive cases for 6400 persons, Pooling Method (PM) requires 6487 tests whereas BEA method
requires only 4563 test. At 1% positive cases PM requires 3229 tests compared to BEA
requiring only 824 tests. As evident from Table III BEA performs consistently better than PM
method when the positive cases are less than 10%. Figure 2 shows graphical comparison of the
two algorithms, it is evident from the graph BEA performs consistently better then PM when the
number of positive cases is less than 18%.

Table III: Comparative Analysis

Percentage of tests Number of tests Percentage of tests Number of tests
Percentage of required required required required
positive Cases by Pooling Method (PM) by PM by BEA by BEA
(Pool Size of 64) (for 6400 persons) (Pool Size of 64) (for 6400 persons)
50% 101.56% 169%
6500 10816
40% 101.56% 155%
6500 9920
30% 101.56% 136%
6500 8704
25% 101.56% 123%
6500 7872
20% 101.56% 109%
6500 6976
15% 101.56% 92%
6500 5888
10% 101.36% 71.3%
6487 4563
5% 97.76% 43.76%
6257 2801
4% 93.36% 37.03%
5975 2370
3% 86.76% 30.06%
5553 1924
2% 73.36% 21.89%
4695 1401
1% 50.46% 12.87%
3229 824
.5% 30.96% 7.71%
1981 493
.1% 9.26% 3.02%
593 193
.05% 5.56% 2.31%
356 148
0.01% 2.26% 1.69%
145 108
0.001% 1.76% 1.6%
113 102
0.0001% 1.76% 1.6%
113 102

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 Comparison of Methods
8000
No. of tests required for 6400 persons
7000

6000

5000

4000

3000 PM

2000 BEA

1000

0
0% 3% 6% 9% 12% 15% 18% 21% 24%
Percentage of positive cases

Figure 1

Another important parameter for Binary Elimination Algorithm (BEA) is Pool Size, increasing
Pool size may increase the efficiency of the algorithm on the cost of increasing the logistics for
testing. In order to determine optimal pool size with respect to percentage of positive cases
simulation were carried for different Pool sizes and the results are summarized in Table IV. The
simulation parameters are same as used previously. At 5% of positive cases the optimal pool size
is 8 and at 1% it is 64. Further at 1 % even though optimal pool size it 64, the practitioner may
choose pool size of 16 as it will reduce the complexity of creating the pool on the cost of
increasing few tests.

4) Conclusion:

This study focused on two recently proposed strategies (PM and BEA) for testing COVID-19
patients. It was found that Pooling Method won't serve any purpose if the number of positive
cases is more than 10%, further Binary Elimination Algorithms (though increases some logistics
in sample collection) performs consistently better than PM algorithm when the number of
positive cases is low.

The performance of both strategies (PM and BEA) can be tremendously enhanced if utilized for
asymptomatic patients only having very less chance of testing positive.

This study provides a comprehensive strategy for COVID-19 testing and can be utilized by
practitioners to dynamically change the test strategy with respect to percentage of positive cases
and logistics involved in taking large pools. We believed that the insights provided in this paper
have the potential of saving millions of tests.

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 Table IV: Percentage Tests Required as per Pool Size (BEA)
Percentage Pool Size
of positive 64 32 16 8 4 2
Cases
30% 136% 134% 131% 125% 113% 101%
20% 109% 107% 103% 98% 90% 88%
10% 71.34% 70.7% 67.36% 63.2% 61.8% 70.8%
5% 43.56% 42.6% 40.83% 38.67% 43.34% 60%
1% 12.87% 13.31% 14.46% 19.5% 30% 53.2%
0.5% 7.7% 8.7% 10.56% 16.25% 28% 52.2%
0.1% 3.02% 4.4% 7% 12.8% 25% 50%
0.05% 2.31% 3.71% 6.6% 12.57% 25% 50%
0.01% 1.69% 3.18% 6.25% 12.5% 25% 50%
0.001% 1.6% 3.15% 6.25% 12.5% 25% 50%
0.0001% 1.6% 3.15% 6.25% 12.5% 25% 50%

5) References

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Available: https://www.israel21c.org/israelis-introduce-method-for-accelerated-covid-19-testing/

[2] “Israeli researchers announce new, faster testing method for covid-19.” accessed: 16-04-
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announcenew-faster-testing-method-for-covid-19/

[3] “Israelis introduce method for accelerated covid-19 testing,” accessed: 16-04-2020. [Online].
Available: https://www.tabletmag.com/sections/science/articles/pooling-covid-19-israel
[4] “Israeli researchers introduce pooling method for covid-19 testing of over 60 patients
simultaneously,” accessed: 09-04-2020. [Online]. Available:
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pooling-method-for-covid-19-testing-of-over-60-patientssimultaneously.html
[5] Pool testing of SARS-CoV-02 samples increases worldwide test capacities many times over"
accessed: 16-04-2020. [Online]. Available: https://aktuelles.uni-frankfurt.de/englisch/pool-
testing-of-sars-cov-02-samples-increases-worldwide-test-capacities-many-times-over/
[6] A.B Dar, M.A Wani, A.H Lone, R Naaz,"Merkle and Binary Tree Inspired Method for
Accelerated COVID-19 Testing: A Concept" DOI: 10.13140/RG.2.2.26116.88969

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