Table Of ContentCOVID-19
COVID-19
Origin, Detection and Impact Analysis Using
Artificial Intelligence Computational Techniques
Parag Verma
Ankur Dumka
Alaknanda Ashok
Amit Dumka
Anuj Bhardwaj
First Edition published 2022
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This work is specially dedicated to our mentor
Late Shri. Girdhari Lal Kak (Former, USF
Convener-Dehradun Chapter) who had always
encouraged us to move forward with a positive
mindset. He is not with us today due to the
COVID-19 pandemic, but his blessings
and his guidance always inspire us to
move forward. You (Kak Sir) will always
live with us in our golden memories.
We would like to thank Monica Dumka,
Mudita Bharadwaj, Naina, Siddhi, and our
parents for all the support and time they
have given to complete this project.
Contents
Authors ............................................................................................................................xvii
Part I Origin and Background of COVID-19
Chapter 1 Introduction to Emerging Respiratory Viruses
with Coronavirus Disease (COVID-19) ...........................................................3
Introduction .....................................................................................................3
New and Newly Recognized Respiratory Viruses ..........................................4
Influenza Viruses ........................................................................................4
H1N1 Influenza ...........................................................................................5
H2N2 Influenza ...........................................................................................5
Avian Influenza (AI) ...................................................................................5
A(H7N9) Virus .......................................................................................6
A(H5N1) Virus .......................................................................................6
Other AI Viruses ....................................................................................6
Hantavirus ...................................................................................................8
Human Metapneumovirus (HMPV) ...........................................................8
Bocavirus ....................................................................................................9
Coronavirus .................................................................................................9
HCoV-229E and HCoV-OC43 ...............................................................10
Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) .........10
Middle East Respiratory Syndrome Coronavirus (MERS-CoV)..........11
SARS-CoV-2 .........................................................................................11
Timeline of the Emerging Viruses ................................................................11
SARS-CoV-2 .................................................................................................14
Current Worldwide Scenario of SARS-CoV-2 ..........................................14
Time Line of the Outbreak........................................................................16
Emergence of Coronavirus (SARS-CoV-2) ...............................................19
Compression of Coronaviruses in Humans—SARS-CoV,
MERS-CoV, and COVID-19 .........................................................................22
Prevention, Control, and Management Strategies from
SARS-CoV-2 .................................................................................................25
Containment Strategies for SARS-CoV-2: Isolation, Quarantine .............25
Principles of Modern Quarantine .............................................................26
Computational Technique of Analysis Effect of Containment
Strategies ...................................................................................................28
SIR Model for Pandemics .....................................................................28
SIQR Model ..........................................................................................31
SEIR Model ..........................................................................................33
SEIRS Model ........................................................................................35
vii
viii Contents
Additional Preventions Tips for Community ............................................36
Case and Contact Management .................................................................37
Community Containment ..........................................................................37
Notes ..............................................................................................................38
References .....................................................................................................39
Chapter 2 The Origin Molecular Structure, Function, and Evolution
Insights of COVID-19: Morphogenesis and Spike Proteins ..........................47
Introduction ...................................................................................................47
Emergence of SARS-CoV and SARS-CoV-2 ................................................49
Classification of Coronaviruses .....................................................................51
Key Features and Entry Mechanism of Human Coronaviruses ....................53
Morphology, Genomic Structure, and Its Variation
of SARS-CoV-2 .............................................................................................55
Genome Sequencing .................................................................................55
Genome Structure .....................................................................................55
Accessory Proteins ....................................................................................57
Structural Proteins of Viral .......................................................................58
S Protein ...............................................................................................58
E Protein ...............................................................................................60
M Protein ..............................................................................................60
N Protein ...............................................................................................61
Structure, Function, Antigenicity, and ACE2 Recognition
by the SARS- CoV-2 Spike Glycoprotein ......................................................62
SARS-CoV-2 S Protein CTD Interactions with Human
ACE2 Receptor .........................................................................................63
Correlation of the SARS-CoV-2-RBD and SARS-CoV-RBD
Interaction with Human ACE2 Receptor ..................................................63
Exhibits Distinct Epitope Features of SARS-CoV-2 on
the RBD from SARS-CoV .......................................................................64
Computation Approach .................................................................................66
Q-UEL Methods .......................................................................................66
Theory Behind the General Strategy ....................................................66
Fundamental Principles of Epitope Prediction for
Design of Synthetic Immunizations .....................................................66
Q-UEL: A Knowledge Representation Toolkit .........................................67
Sources Data and Material ...................................................................67
Important Notation ...............................................................................68
Results ..................................................................................................69
Machine Learning Clustering Technique .................................................95
Genome Sequence Analysis..................................................................95
K-Means Cluster Algorithm..................................................................97
Dataset ..................................................................................................99
Results ..................................................................................................99
Notes ............................................................................................................101
References ...................................................................................................101
Contents ix
Part II COVID-19 Screening, testing and Detection
Systems: Different Paths to the Same
Destination
Chapter 3 Real Time-Polymerase Chain Reaction (RT-PCR)
and Antibody Test .......................................................................................111
Introduction .................................................................................................111
Real Time RT-PCR .....................................................................................112
RT-PCR Method in Testing .....................................................................113
Principle Behind RT-PCR Testing ..........................................................114
How Does RT-PCR Work in Coronavirus Case? ....................................115
Nucleic Acid Testing ...............................................................................115
Nucleic Acid Testing for SARS-CoV-2 ...............................................117
Integrating Nucleic Acid Detection with Clinical
Management .......................................................................................118
Device Description and Test Principle ....................................................118
Description of Pooling ............................................................................119
Computational Technique of RT-PCR Test Diagnostic
Sensitivity and Specificity Reconstruction for COVID-19 ..........................121
Data and Methods ...................................................................................122
Data.....................................................................................................122
Statistical Analysis .............................................................................123
Results .....................................................................................................125
Digital Polymerase Chain Reaction ............................................................129
Statistical Foundations of dPCR .............................................................130
Binomial Probability and Poisson Approximation .............................130
Quantification Accuracy .....................................................................131
Most Probable Number (MPN) ..........................................................131
Copy Number Variant (CNV) Applications .......................................132
Absolute Limit of Quantification Due to Specimen Sampling ...........133
Hypothesis and Technological Implications .......................................133
Conclusion of the Statistical Foundations of dPCR ............................134
Performance Metrics ...............................................................................134
Sensitivity of Detection ......................................................................134
Dynamic Range of Detection .............................................................135
Practical Considerations in the Reliability of dPCR
Measurements-False-Negative/Positive Signals .................................135
Miniaturization and Hyper-Compartmentalization ................................136
Chamber Formats ...............................................................................137
Computational Technique of ddPCR Test for Sensitivity
Assessment of COVID-19 ...........................................................................144
Materials and Methods ...........................................................................145
Specimens Collection, Storage, and Pooling ..........................................145
Preparation of Groups of 16 and 32 Individuals .....................................146
Detection of SARS-CoV-2 by Grouped DPCR Testing ......................146
