Note: Cover -- The Coronavirus Pandemic and the Future Volume 1: Virology, Epidemiology, Translational Toxicology and Therapeutics -- Dedication -- Foreword -- Preface -- Contents -- Contents -- Chapter 1 - What We Know About the Life- threatening Novel Human Coronavirus -- 1.1 Introduction -- 1.2 The Chronology of the Outbreak -- 1.3 Initial Transmission -- 1.3.1 Worldwide Spread of the Virus -- 1.4 SARS-CoV- 2 and Its Etiology -- 1.5 Classification and Grouping -- 1.5.1 Alpha- CoVs -- 1.5.2 Beta- CoVs -- 1.5.3 Gamma- CoVs -- 1.5.4 Delta- CoVs -- 1.6 Epidemiological History of Human Coronaviruses -- 1.6.1 Severe Acute Respiratory Syndrome -- 1.6.2 Middle East Respiratory Syndrome -- 1.6.3 Detailed Documentation of SARS- CoV- 2 and COVID- 19 -- 1.7 Introductory Virology and Pathophysiology of SARS- CoV- 2 -- 1.7.1 Viral Genome -- 1.7.2 Interaction of the Spike and Receptor for Entry -- 1.7.3 Genomic Differences -- 1.7.4 Pathophysiology -- 1.8 Executive Summary and Conclusions -- List of Abbreviations -- Acknowledgements -- References -- Chapter 2 - Severe Acute Respiratory Syndrome Coronavirus- 2 (SARS-CoV- 2): Structure, Lifecycle, and Replication Machinery -- 2.1 Introduction -- 2.2 Classification of Coronaviruses -- 2.3 Genomic Structure of SARS- CoV-Ł2 -- 2.4 Life Cycle of SARS- CoV- 2 -- 2.4.1 Attachment and Entry -- 2.4.2 Replicase Protein Expression -- 2.4.3 Replication and Transcription -- 2.4.4 Assembly and Release -- 2.5 SARS- CoV- 2 RNA Replication Machinery -- References -- Chapter 3 - Accumulated Epidemiological Lessons and China's COVID- 19 Response -- 3.1 Introduction -- 3.2 Accumulated Lessons from China's Response to SARS in 2003 -- 3.3 Epidemiologicial Perspective on China's COVID- 19 Response -- 3.4 China's Control and Prevention Measures in COVID- 19 -- 3.4.1 Mask- wearing and its Comforting Effect. , 3.4.2 Epidemiological Source- tracking and Slow- down of Community Transmission -- 3.5 Comparing China's Response Against SARS and COVID- 19 -- 3.6 Concluding Remarks -- 3.7 Executive Summary -- References -- Chapter 4 - Clinical Presentation, Pathophysiology and Histopathology -- 4.1 Introduction -- 4.1 Introduction -- 4.2 The Distinct Clinical Trajectory and Disease Spectrum of COVID- 19 -- 4.3 A Novel Application of Smartphone Technology -- 4.4 COVID- 19 and Comorbidities in Severe Cases -- 4.5 ARDS and its Sequelae in COVID- 19 -- 4.5.1 ARDS in COVID- 19 -- 4.5.2 Sepsis -- 4.5.3 Septic Shock -- 4.6 Pathophysiology -- 4.6.1 Mechanism of SARS-Cov- 2 Invasion into Host Cells -- 4.7 Histopathology and Disease Manifestations: Introduction -- 4.7.1 Histopathology -- 4.7.2 Pulmonary Manifestations -- 4.7.3 Cardiovascular Manifestations -- 4.7.4 Gastrointestinal Manifestations -- 4.7.5 Renal Manifestations -- 4.7.6 Neurological Manifestations -- 4.7.7 Musculocutaneous Manifestations -- 4.7.8 Hematological Manifestations -- 4.8 Executive Summary -- Acknowledgements -- References -- Chapter 5 - Evaluation of the Disease, Sample Collection and Diagnostics -- 5.1 Introduction -- 5.1.1 Symptoms of COVID- 19 -- 5.1.2 Detection of Disease Based on Symptoms -- 5.1.3 Evaluation Criteria for COVID- 19 Based on ICMR and WHO Guidelines -- 5.2 Sample Collection -- 5.2.1 Overview of Sample Collection Guidelines from the WHO -- 5.2.1.1 Nasopharyngeal or Oropharyngeal Swabs -- 5.2.1.2 Nasal Mid- turbinate Swab -- 5.2.1.3 Anterior Nares Specimen -- 5.2.1.4 Nasopharyngeal Wash/Aspirate or Nasal Wash/Aspirate -- 5.2.1.5 Bronchoalveolar Lavage, Tracheal Aspirate, Pleural Fluid, Lung Biopsy -- 5.2.1.6 Sputum (Phlegm) -- 5.2.1.7 Saliva -- 5.2.1.8 Other -- 5.3 Recent Diagnostics -- 5.3.1 Molecular Diagnostics -- 5.3.2 Laboratory Examinations (Modified from Cascella et al.17). , 5.3.3 Imaging -- 5.3.3.1 Chest X- ray -- 5.3.3.2 Chest CT -- 5.3.3.3 Lung Ultrasound -- 5.3.3.4 Scanning Techniques -- 5.3.4 Blood Parameter Levels (Laboratory Diagnostics) -- 5.3.5 Genetic Susceptibility to COVID- 19 -- 5.3.6 Importance of Real-time RT-PCR in the Detection of COVID- 19 -- 5.3.6.1 Viral Nucleic Acid Detection -- 5.3.7 Serological Assays -- 5.3.8 Enzyme- linked Immunosorbent Assay -- 5.3.9 Magnetic Chemiluminescence Enzyme Immunoassay -- 5.3.10 Colloidal Gold Immunochromatographic Assay -- 5.3.11 Lateral Flow Immunoassay -- 5.3.12 Rapid Antigen Test -- 5.3.13 Neutralization Antibody Assay -- 5.3.14 Other Useful Diagnostics for COVID- 19 -- 5.3.15 False Negatives and Positives -- 5.4 Advantages and Disadvantages of Different Diagnostic Approaches -- 5.4.1 Detection Based on Patient History -- 5.4.2 Detection of Disease Based on Symptoms -- 5.4.3 Scanning Techniques -- 5.4.3.1 CT Scan -- 5.4.3.2 Chest X- ray -- 5.4.3.3 18F- FDG PET/CT -- 5.4.4 Laboratory Serum Diagnostics (e.g. WBC, Inflammatory Markers) -- 5.4.5 Molecular Diagnosis -- 5.4.5.1 RT- PCR -- 5.4.5.2 RT- LAMP -- 5.4.5.3 Transcription- mediated Amplification -- 5.4.6 CRISPR- based Diagnosis -- 5.4.7 Serological Assays -- 5.4.7.1 ELISA -- 5.4.7.2 GICA -- 5.4.7.3 MCLIA -- 5.4.7.4 Lateral Flow Immunoassay -- 5.4.7.5 Neutralization Bioassay -- 5.4.7.6 Rapid Antigen Test -- 5.5 Executive Summary -- Acknowledgements -- References -- Chapter 6 - Therapeutic Options Initially Available for COVID- 19 Patients and Initial Clinical Trials -- 6.1 Introduction to Therapeutic Options Initially Available for COVID- 19 Patients -- 6.1.1 General Guidelines for the Treatments Provided to COVID- 19 Patients -- 6.1.2 Common Treatment Regimens Provided to COVID- 19 Patients -- 6.1.3 Medicinal Plants as Therapy for COVID- 19 -- 6.1.4 Convalescent Plasma Therapy. , 6.1.5 Mesenchymal Stem Cell-Derived Exosomes as Therapy for COVID- 19 -- 6.1.6 Other Treatment Options -- 6.1.6.1 Corticosteroids -- 6.2 Introduction to Ongoing Clinical Trials -- 6.2.1 Ongoing Trials on Various Antiviral Agents -- 6.2.2 Immunosuppressants/Immunomodulators -- 6.2.3 Current Trials on MSCs for COVID- 19 -- 6.3 Executive Summary -- Acknowledgements -- References -- Chapter 7 - Clinical Epidemiology of Coronavirus Disease 2019: Infectivity, Clinical Spectrum and Presentation, and Population Distribution -- 7.1 Introduction -- 7.2 Infection and Tests -- 7.2.1 Viral Tests -- 7.2.2 Population- based Infection Rate -- 7.2.3 Antibody Tests -- 7.3 Clinical Spectrum of COVID- 19 -- 7.3.1 Classification by Clinical Type -- 7.3.2 Asymptomatic Cases -- 7.3.3 Severe Cases and Comorbidity -- 7.3.4 Clinical and Immunological Response -- 7.4 Regional Variation in Clinical Presentation -- 7.4.1 Clinical Manifestation -- 7.4.2 Chemosensory Dysfunction -- 7.4.3 Common Symptoms -- 7.4.3.1 Asia -- 7.4.3.2 USA -- 7.4.3.3 Europe -- 7.5 Population Distribution -- 7.5.1 Pregnancy and Pregnant Women -- 7.5.2 Infants and Pediatric Patients -- 7.5.3 Asymptomatic Cases and Clinical Severity in Children -- 7.5.4 Older Adults -- 7.5.5 Sex Differences -- 7.5.6 Occupation -- 7.6 Case- fatality Rate -- 7.7 Executive Summary and Conclusions -- References -- Chapter 8 - SARS-CoV-2 Genomics and Host Cellular Susceptibility Factors of COVID- 19 -- 8.1 Introduction -- 8.2 Coronavirus and Human Diseases -- 8.2.1 Classification of Coronaviruses -- 8.2.2 Human Coronaviruses and Diseases -- 8.2.3 The Natural Origin of HCoVs -- 8.3 Genomic Structure and Genetics -- 8.3.1 Viral Genomic Structure -- 8.3.2 The Replicase Locus and Proteins -- 8.3.2.1 Nonstructural Proteins -- 8.3.2.2 Structural Proteins -- 8.3.2.3 Accessory Proteins -- 8.3.3 Genomic Mutations. , 8.4 Viral Replication -- 8.4.1 Attachment and Cell Entry -- 8.4.2 Translation and RNA Replication -- 8.4.3 Assembly and Release of Virion -- 8.5 Host Cellular Factors -- 8.5.1 ACE2 -- 8.5.2 TMPRSS2 -- 8.5.3 Furin -- 8.5.4 DPP4 -- 8.5.5 CD147 -- 8.5.6 GRP78 -- 8.5.7 Cathepsins -- 8.5.8 Ly6E -- 8.5.9 L- SIGN and DC- SIGN -- 8.5.10 Sialic Acid -- 8.5.11 Plasmin and Other Proteases -- 8.6Executive Summary -- References -- Chapter 9 - Infection and Pathogenesis of SARS-CoV- 2: an Immunological Perspective -- 9.1 Introduction -- 9.2 SARS-CoV- 2 Virology -- 9.2.1 Structure -- 9.2.2 Genome -- 9.2.3 Proteome -- 9.2.4 Mutation -- 9.2.5 Transmission -- 9.3 Pathogenesis -- 9.3.1 Attachment to the Host Cell -- 9.3.2 Penetration of SARS-CoV- 2 Inside the Host Cell -- 9.3.3 Assembly of the RTC -- 9.3.4 Genome Replication, Transcription, and Translation -- 9.3.5 Virion Assembly and Release -- 9.3.6 Incubation Period -- 9.4 Disease Progression -- 9.5 Immunology -- 9.5.1 Innate Immune Response -- 9.5.1.1 Evasion of Innate Sensing by SARS-CoV- 2 -- 9.5.1.1.1 Evasion of PRR Sensing.Coronavirus- mediated antagonism starts with the evasion of PRR recognition. The ssRNA of coronaviruses c... -- Inhibition of Signalling Cascades. As described, TLR and RLR activation induces signalling cascades, which leads to the release ... -- Inhibition of IFN-1396983920I. Based on previous studies, various mechanisms have been adopted by coronaviruses to inhibit IFN-1... -- 9.5.1.2 Imbalanced Antiviral Defense and Pro- inflammatory Cytokine Production -- 9.5.1.3 Macrophages -- Macrophage Responses to SARS-CoV- 2 Infection.Macrophages and monocytes accumulate and trigger cytokine secretion, leading to c... -- 9.5.1.4 Alveolar type II ATII Cells in the Innate Immune Response -- 9.5.1.5 Neutrophils -- 9.5.1.6 Dendritic Cells -- 9.5.1.7 Natural Killer Cells. , 9.5.1.7.1 Modification of NK Cells Upon SARS-CoV- 2 Infection.Studies on peripheral blood samples of COVID- 19 patients have shown that i.