The first section of Part III will cover the most immediate healthcare response - which is to test and diagnose patients for COVID-19, to get a clear picture on the extent of the spread of infection. It also covers the current technologies used in diagnostics: RT-PCR, LAMP, Lateral Flow and ELISA. It would also highlight key companies and comparison of the technologies involved.

1. Overview of Current Testing Technologies Compared
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Coronavirus Pandemic
Part III (A): Diagnostic Technologies

2. Coronavirus Pandemic Series
Part III (A): Diagnostic Technologies
• Key challenges in detecting
COVID-19 in populations
• Critical sectors in R&D
• Stages in testing
• Diagnostic methods
• Diagnostic highlights
• Technologies compared
• The need for effective
diagnostic tools
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3. Part II Recap: Public Policies & Impact
There is currently no vaccine or
specific treatment for COVID-19.
The consensus now is to flatten the
curve & reduce community spread.
Key points:
• >3.5 million cases (May 4th, 2020)
• Countries are enforcing lockdowns,
mandatory curfews – offices, malls &
schools are closed
• The global GDP is expected to shrink by
almost 1% in 2020, key industries such as
aviation, oil & gas, hospitality, leisure,
etc. are severely impacted
Source: Worldometers.info, UN, Medium.com
The United States
Most Affected
>1.18m cases
>68k deaths
Spain, Italy,
France, Germany
& UK
Epicenters of
pandemic in Europe
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4. Key R&D Sectors To Address COVID-19
Source: WHO R&D
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A:Diagnostics
• IDENTIFICATION
• It’s critical that
local healthcare
systems can
diagnose
patients quickly &
effectively
• Asymptomatic
patients
represent a
considerable
portion of cases
B:Therapeutics
• TREATMENT
• With almost 1.7
million active
cases worldwide
(and rising),
healthcare
providers are in
desperate need
of effective
treatment
options
C:Vaccines
• PREVENTION
• Development,
production &
coverage of
vaccines is
crucial to prevent
future outbreaks
of COVID-19

5. Diagnostics: Identifying Positive cases is key
Source: https://www.medrxiv.org/content/10.1101/2020.02.03.20020271v1 & Nordic Life Science
Patients who tested positive
can be isolated & quarantined
to prevent/slow the spread of
the virus.
Testing helps to pinpoint "hot spots"
where community-wide measures
can be implemented (such as
social distancing, movement
restrictions, curfew, etc.).
A broader, global scale of testing
may be necessary.
No Country Tested
>14% of Population
To date, most
countries lack data
on prevalence
Need to Test,
Isolate & Treat 80%
of Patients
As symptoms onset
(24h) to control the
spread in 1 year
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6. Key Challenges: Detecting COVID-2019
Source: GAO Science & Tech Spotlight: Coronaviruses
High infection rate & global spread
Virus has long incubation periods (up to 14 days)
Widespread cases of asymptomatic (patients
without any signs or symptoms)
The need for rapid, accurate, cost-effective point-
of-care diagnostic kits for large scale testing
Outbreak detection requires cooperation among
nations, potential political bottlenecks
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7. STAGE I: DIAGNOSTIC TESTING
• For patients with acute symptoms.
• Determine if symptoms due to
COVID-19 or something else.
• RT-PCR, LAMP testing of
nasopharyngeal swab, sputum or
stool sample
STAGE II: EXPOSURE TESTING
• Determine if person is exposed to
SARS-CoV-2 and developed an
immune response.
• Immunology assay (antibody test)
of blood sample
Stages in testing: Diagnostics & Exposure
Source: https://www.labtestsonline.org.au/learning/index-of-conditions/covid-19/what-s-ahead-for-covid-19-testing
Quarantine & Isolation Treatment/Intensive Care
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8. COVID-19 Diagnostics
Known Methods, Highlights & Random Testing
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9. RT-PCR technology is the
most established and
documented method
used in most medical
research & diagnostics.
Current Diagnostic Technology Platforms
Source: CEBM Oxford, John Hopkins Center for Health Security
2. Isothermal
Amplification
(LAMP)
3. Lateral
Flow Assay
1. RT-PCR
4.
Immunology
Assay (ELISA)
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10. Source: https://www.cebm.net/covid-19/what-tests-could-potentially-be-used-for-the-screening-
diagnosis-and-monitoring-of-covid-19-and-what-are-their-advantages-and-disadvantages/
Short for Reverse Transcription-
Polymerase Chain Reaction,
RT-PCR is used to detect the
SARS-CoV-2 virus that's causing
COVID-19.
RT-PCR tests are fairly quick,
sensitive and reliable, producing
results in 3-4 hours. It’s highly
accurate and widely used in research
and medicine, the technology is
already in place to test for COVID-19.
Diagnostic Method: RT-PCR
RT-PCR captures and amplify regions of the
virus' genetic material, fluorescent markers
are used to detect the virus.
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11. Understanding the RT-PCR Diagnostic Process
Step 1:
Bio sample is
collected (tissue
swab or sputum)
Step 2:
Bio sample is
broken down
Step 3:
Genetic material
is isolated
Step 4:
Test kit enzymes
applied; mixture
prepared
Step 4:
Enzymes copy RNA
to DNA, fluorescent
marker binds to
target sequence
Step 5:
Strands
undergoes
‘amplification’
POSITIVE:
Target DNA has
been amplified,
virus is present
NEGATIVE:
Target DNA not
amplified, virus
absent
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12. Diagnostics Highlight: cobas® 6800/8800 by Roche
Source: https://www.dialog.roche.com/pk/en_us/products_and_solutions/molecular-lab/cobas-6800-8800-systems.html
The cobas® 6800/8800 systems
automate preparation & testing
using RT-PCR technology to
detect the SARS-CoV-2 virus.
Fully integrated, automated, and has
a modular design that can expand as
capacity requirements increases.
Received FDA Emergency Use
Authorization on March 13, 2020.
Widely used in test labs globally. The high-volume cobas 6800/8800 can
significantly increase testing capacity.
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13. Source: https://www.biospace.com/article/releases/bgi-s-real-time-sars-
cov-2-test-to-detect-novel-coronavirus-receives-fda-emergency-use-
BGI's highly sensitive test can
return results within 3 hours.
It can detect the SARS-CoV-2
virus in bronchoalveolar
lavage fluid (BALF) and
throat swabs.
The company has performed over
500,000 SARS-CoV-2 tests in its
own central laboratories in China.
Diagnostics Highlight: BGI Genomics RT-PCR
BGI is distributing detection kits to more than
70 countries & regions. They've also donated
over 130,000 tests since the beginning of the
outbreak.
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14. Diagnostic Method: LAMP
Source: https://www.cebm.net/covid-19/what-tests-could-potentially-be-used-for-the-screening-
diagnosis-and-monitoring-of-covid-19-and-what-are-their-advantages-and-disadvantages/
Loop-mediated Isothermal
Amplification (LAMP) is
similar in process to RT-PCR.
While RT-PCR uses a series of
temperature changes to produce
copies of the viral DNA, LAMP is
conducted at a constant
temperature of 60-65°C.
The amount of DNA produced in
LAMP is much higher than in RT-
PCR and a positive test result can
be read by eye.
Newer, simpler, and cheaper, LAMP can be
done within hospital laboratories, reducing
the time between sampling and diagnostic.
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15. Large scale testing requires a
point-of-care rapid diagnostic
kit that doesn't depend on
specialized equipment or labs.
Abbott's ID NOW™ platform is a
portable instrument that can be
deployed where testing is
needed most.
To date, cross-validation is still
required to prevent false
negatives & ensure accuracy.
Diagnostics Highlight: Abbott ID NOW™ COVID-19
While the standard LAMP takes 2-3 hours, ID
NOW™ can give results within 5-13 minutes.
Source: https://abbott.mediaroom.com/2020-03-27-Abbott-Launches-Molecular-
Point-of-Care-Test-to-Detect-Novel-Coronavirus-in-as-Little-as-Five-Minutes
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16. Diagnostics: RT-PCR vs LAMP
RT-PCR
• Reverse transcription-
polymerase chain reaction
• Quantitative, technical
readout
• Requires cycling between
different temperatures
• Often requires a laboratory,
time needed to send samples
• Gold standard in DNA testing
LAMP
• Loop-mediated isothermal
(nucleic acid) amplification
• Much higher amplification
• Qualitative results can be read
by eye
• Doesn't require thermal
cycling, require less energy
• Portable, easier to operate
• Relatively new
Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263587/
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17. Diagnostic Method: Lateral Flow Assays
Source: https://www.cebm.net/covid-19/what-tests-could-potentially-be-used-for-the-screening-
diagnosis-and-monitoring-of-covid-19-and-what-are-their-advantages-and-disadvantages/
Lateral Flow/Colloidal Gold
Immunochromatography is
currently used to detect
antibodies of the disease in a
patient’s blood.
Using the same technology
commonly used for pregnancy tests,
it detects the patient’s immune
antibody response to the virus rather
than detecting the virus itself. Results can be obtained in 15 minutes. The
appearance of lines for IgG or IgM, or both
indicate a positive test.
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18. Diagnostic Method: Lateral Flow Assays
Source: https://www.cebm.net/covid-19/what-tests-could-potentially-be-used-for-the-screening-
diagnosis-and-monitoring-of-covid-19-and-what-are-their-advantages-and-disadvantages/
A small blood sample (collected from a vein or finger-prick) is dropped onto a spongey pad
within the test device. A few drops of diluting liquid or 'buffer' are added to help the blood
sample flow across the device. Lateral flow immunoassays for SARS-CoV-2 detect two types
of protective antibodies: IgM and IgG.
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19. Enzyme-Linked Immunosorbent
Assays detect antibodies
produced in the patient’s blood
due to infection.
The test can be performed in
one tube or well and involves
mixing patient samples,
antibodies, antigens, and
enzymes with a color-changing
molecule (qualitative).
Diagnostic Method: ELISA
Simple & cheap, ELISA is well established
and documented. Testing can be completed
on multiple samples at once, and results can
be produced within 1-3 hours.
Source: https://www.cebm.net/covid-19/what-tests-could-potentially-be-used-for-the-screening-
diagnosis-and-monitoring-of-covid-19-and-what-are-their-advantages-and-disadvantages/
19

20. Diagnostic Method: ELISA
Source: https://www.cebm.net/covid-19/what-tests-could-potentially-be-used-for-the-screening-
diagnosis-and-monitoring-of-covid-19-and-what-are-their-advantages-and-disadvantages/
Credit: CEBM
1:
Blood sample
added to a well
with specific
SARS-CoV-2
antigens
2:
Patient’s
antibodies will
attach to virus
proteins, excess
washed off
3:
Other antibodies
& enzymes
added as 2nd
layer, excess
washed off
4 & 5:
Colorless
molecules added
into well to react
with 2nd layer
enzymes
6 OR 7
Color change
indicates patient
is tested positive
for COVID-19
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21. Diagnostic Technologies Compared
Technology
Molecule
tested
Laboratory or
Point of Care
Time to
Results
Sampling Site
No. of Samples per
Batch
RT-PCR Viral RNA Laboratory
3-4 hours or
more
Nasopharyngeal swab,
sputum, stool
Up to 96 samples
LAMP Viral RNA
Laboratory or
Point of Care
2-3 hours
Nasopharyngeal swab,
sputum, stool
Up to 96 samples (lab) or
1-4 (point of care)
Lateral Flow
Antibody
(less commonly
antigen)
Point of Care 15-20 minutes Blood for antibody testing 1 patient sample
ELISA
Antibody
(less commonly
antigen)
Laboratory 1-3 hours Blood for antibody testing Up to 96 samples
Source: https://www.cebm.net/covid-19/what-tests-could-potentially-be-used-for-the-screening-
diagnosis-and-monitoring-of-covid-19-and-what-are-their-advantages-and-disadvantages/
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22. Diagnostic Technologies Compared
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RT-PCR LAMP Lateral Flow ELISA
*Standard of Accuracy ++ + ± +
Speed of testing ± + + +
Platform portability - + ++ -
Qualitative results - + ++ +
Quantitative results ++ + - ±
Cost of technology & maintenance - + ++ +
Ease of use/training - ± + ±
*Accuracy is the most critical aspect in identifying whether a person is infected with COVID-19 or not.

23. The need for Effective Diagnostics
Finding The Right Fit
To date, there is no single
diagnostics solution that is
cost-effective, rapidly
deployable, accurate, and
fast.
Further R&D is required,
given the need to conduct
random testing quickly,
accurately, and at a much
larger scale.
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24. Ongoing R&D Projects
Source: Various Online Research as of Mid-April 2020
Diagnostics, 112
Therapeutics, 117
Vaccines, 61
Diagnostic
Technologies
To date, about 38% of
ongoing R&D projects are
focused on developing
diagnostic technologies to
accurately & effectively test
patients for COVID-19.
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25. • Identifying COVID-19 is key to quarantine, isolate & treat patients.
It provides a clearer picture of the extent of spread.
• RT-PCR is currently the most widely used method of diagnosing
patients for COVID-19, given the accuracy, high capacity &
robustness. It also provides a quantitative readout.
• Qualitative diagnostics includes LAMP, Lateral Flow Assays &
ELISA, where results can be read by eye.
• Further R&D is required for diagnostics, given the need to conduct
random testing quickly, accurately, and at a much larger scale; as
current methods still have room for improvement.
• While new technologies are already in use, cross-validation is still
needed to ensure the accuracy & sensitivity of tests, avoiding false
negatives (preventing the unnecessary spread of infection).
Conclusion
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