Coronavirus Disease - COVID-19 (Advances in Experimental Medicine and Biology Book 1318)

In December 2019, the world witnessed the occurrence of a new coronavirus to humanity. The disease spread quickly and became known as a pandemic globally, affecting both society and the health care system, both the elderly and young groups of people, and both the men’s and women’s groups. It was a universal challenge that immediately caused a surge in scientific research. Be a part of a world rising in fighting against the pandemic, the Coronavirus Disease - COVID-19 was depicted in the early days of the pandemic, but updated by more than 200 scientists and clinicians to include many facets of this new infectious pandemic, including i, characteristics, ecology, and evolution of coronaviruses; ii, epidemiology, genetics, and pathogenesis (immune responses and oxidative stress) of the disease; iii, diagnosis, prognosis, and clinical manifestations of the disease in pediatrics, geriatrics, pregnant women, and neonates; iv, challenges of co-occurring the disease with tropical infections, cardiovascular diseases, hypertension, and cancer and to the settings of dentistry, hematology, ophthalmology, and pharmacy; v, transmission, prevention, and potential treatments, ranging from supportive ventilator support and nutrition therapy to potential virus- and host-based therapies, immune-based therapies, photobiomodulation, antiviral photodynamic therapy, and vaccines; vi, the resulting consequences on social lives, mental health, education, tourism industry and economy; and vii, multimodal approaches to solve the problem by bioinformatic methods, innovation and ingenuity, globalization, social and scientific networking, interdisciplinary approaches, and art integration. We are approaching December 2020 and the still presence of COVID-19, asking us to call it COVID (without 19). Preface Acknowledgment Contents 1: Introduction on Coronavirus Disease (COVID-19) Pandemic: The Global Challenge 1.1 Introduction 1.2 The Source of the Infection 1.3 Immunopathogenesis of COVID-19 1.3.1 Virus Entry and Spread 1.3.1.1 The Virus Binding to Its Cell Receptors 1.3.1.2 Antigen Presentation 1.3.1.3 Pathological Findings Lung Kidney Liver Heart 1.3.2 Role of the Immune System During COVID-19 1.3.2.1 Antiviral Immune Dysfunction 1.3.2.2 Cytokine Storm 1.4 Epidemiology 1.4.1 A Historical Review of SARS Pandemic 1.4.2 The Current State of COVID-19 1.4.2.1 Epidemiological Characteristics 1.4.2.2 Routes of Transmission 1.4.2.3 The Spectrum of Infection 1.4.2.4 High-Risk Population 1.5 Diagnosis and Clinical Manifestations of COVID-19 1.5.1 Diagnosis 1.5.1.1 Nucleic Acid Test 1.5.1.2 Serologic Diagnosis 1.5.1.3 Imaging 1.5.2 Clinical Manifestations 1.6 Potential Therapeutics for COVID-19 1.6.1 Interferon-Alpha and Interferon-Beta 1.6.2 Antivirals 1.6.3 Convalescent Plasma and IVIG 1.6.4 Monoclonal Antibodies 1.6.5 Corticosteroids 1.6.6 Vaccine Development 1.6.7 Nutrition 1.7 COVID19 Pandemic: Global Challenges, Prevention, and Preparedness for the Next Pandemic 1.7.1 Global Challenges of Coronavirus Pandemic (Lessons Learned from the 2003 SARS Pandemic) 1.7.1.1 Animal Source Control 1.7.1.2 Early Detection, Isolation, and Tracing Close Contacts 1.7.1.3 Rigorous Infection Control 1.7.1.4 Vaccine Development Dissemination of Information Recurrence Psychosocial Support 1.7.2 Preparing for the Next COVID-19 Pandemic 1.8 The Economy of COVID-19 1.9 Conclusion References 2: Coronaviruses: What Should We Know About the Characteristics of Viruses? 2.1 Introduction 2.2 Classification 2.3 Virion Structure and Genome Organization 2.4 Molecular Features of SARS-CoV-2 Genome and Proteins 2.4.1 Noncoding Genes 2.4.2 Nonstructural Proteins 2.5 Structural Proteins and Accessory Proteins 2.6 SARS-CoV-2 Life Cycle 2.6.1 Virus Entry and Uncoating 2.6.2 Viral Replicase Expression and RNA Synthesis 2.6.3 Virion Assembly and Release 2.7 Conclusion References 3: Ecology and Evolution of Betacoronaviruses 3.1 Introduction 3.1.1 The Emergence of an Infectious Disease 3.1.2 A Brief History of the Discovery of Human Coronaviruses 3.2 Origin and Evolution of SARS-CoV-2 and Other Betacoronaviruses 3.2.1 Genome Evolution 3.3 Ecology of Betacoronaviruses 3.3.1 Natural Hosts of Coronaviruses 3.3.2 The Environment 3.4 Conclusion References Websites 4: The Epidemiologic Aspects of COVID-19 Outbreak: Spreading Beyond Expectations 4.1 Introduction 4.2 Coronavirus-Caused Outbreaks: SARS, MERS, and COVID-19 4.3 The Characteristics of COVID-19 4.3.1 Total Affected Cases of COVID-19 4.3.2 Prevalence Rate 4.3.3 Mortality Rate 4.3.4 Case-Fatality Rate 4.3.5 COVID-19 Virulence 4.3.6 Serial Interval 4.3.7 R0 (The Reproduction Ratio or the Reproduction Number) 4.4 Relevant Reporting Sources and Predictions 4.5 COVID-19 Pandemic Details in China and Selected Countries 4.6 Bias in Estimating the Extent of COVID-19 Pandemic 4.6.1 Selective Bias or Political Bias 4.6.2 Nonselective Bias or Technical Bias 4.7 Confronting the COVID-19 Outbreak and the Impact on the Expansion of COVID-19 4.7.1 Policymaker Shortcomings 4.7.2 General Population Shortcomings 4.8 The Psychological Explanation on Determining the Extent of an Outbreak 4.8.1 Denial and Isolation 4.8.2 Anger 4.8.3 Bargaining 4.8.4 Depression 4.8.5 Acceptance 4.9 Social Impacts of the COVID-19 Pandemic 4.9.1 Social Impacts 4.9.2 Mental Impacts 4.10 The Future Outbreaks 4.10.1 Global Trades, Travels, and Transactions 4.10.2 Climate Change 4.10.3 Urbanization 4.10.4 Poverty 4.10.5 Demographic Shifts 4.10.6 Behavior Shifts 4.11 Conclusion References 5: The Incubation Period of COVID-19: Current Understanding and Modeling Technique 5.1 Introduction 5.2 The Importance of Understanding the Incubation Period 5.3 Existing Findings of the Incubation Period of COVID-19 5.4 Modeling the Distribution of the Incubation Period 5.5 Future Research Directions 5.6 Conclusion References 6: Coronavirus: Pure Infectious Disease or Genetic Predisposition 6.1 Introduction 6.2 Genetic Variants Relating to Virus Binding and Entry Receptors 6.2.1 Angiotensin-Converting Enzyme (ACE) 6.2.1.1 ACE1 6.2.1.2 ACE2 6.2.2 CD147 6.2.3 Dipeptidyl Peptidase 4 (DPP4) 6.2.4 Transmembrane Serine Protease 2 (TMPRSS2) 6.3 Genes with Immune Response-Related Functions 6.3.1 Mannose-Binding Lectin (MBL) 6.3.2 Type C Lectin 6.3.3 Human Leukocyte Antigen (HLA) 6.4 Inflammation-Related Genes 6.4.1 C-C Motif Chemokine Ligand 2 (CCL2) 6.4.2 Interleukins 6.4.3 Interferon-Gamma (IFN-γ) 6.4.4 IFN-Inducible Genes 6.4.5 RANTES 6.5 Autophagy-Related Genes 6.6 Genetic Predisposition Models for Coronavirus Infection 6.7 Conclusion References 7: Genetic Polymorphisms in the Host and COVID-19 Infection 7.1 Introduction 7.2 Methods 7.3 Results 7.3.1 Univariate Regression Analysis 7.3.2 Clustering of Genetic Polymorphisms 7.3.3 Multivariate Regression Analysis 7.4 Discussion 7.5 Conclusion References 8: How COVID-19 Has Globalized: Unknown Origin, Rapid Transmission, and the Immune System Nourishment 8.1 Introduction 8.2 When, What, and Where of COVID-19 8.2.1 The Family Coronaviridae 8.2.2 What Have Coronaviruses Brought for Human Beings? 8.2.3 SARS-CoV-2: Where Does It Come from, and How Does It Go? 8.3 Neither the Window of Viral Detection nor Viral Loads Reflect COVID-19 Severity 8.4 The Older the Age Is, the Higher the Viral Load of SARS-CoV-2 May Increase 8.5 Immune Profile of Peripheral Blood in Patients with COVID-19 8.5.1 White Blood Cell 8.5.1.1 Lymphocytes T Cells T-Cell Pattern in Relation to the Deterioration of COVID-19 T-Cell Pattern in Relation to the Severity of COVID-19 T-Cell Pattern in Relation to the Criticality of COVID-19 T Cells Become Reduced, Exhausted, and Overwhelmed in COVID-19 B Cells and Natural Killer (NK) Cells 8.5.1.2 Monocytes 8.5.1.3 Neutrophils 8.5.2 Immunoglobulins 8.5.3 Complement Factors 8.6 Cytokine Storm: A Defensive Strategy Protecting the Home Against SARS-CoV-2 or a Self-Medicated Disaster Hitting the Home by SARS-CoV-2 8.6.1 Cytokines 8.6.1.1 Baseline Levels of Cytokines in Relation to the Severity of COVID-19 8.6.1.2 Tracing Kinetics of Changes in Cytokine Levels in COVID-19 Cytokines Add Their Character to the Progression of COVID-19 The Changes of IL-6 and IL-10 Are Most Remarkable During COVID-19 8.6.1.3 IL-6: The Well-Documented Cytokine in COVID-19 IL-6 Levels in Relation to the Severity of COVID-19 IL-6 Levels in Relation to the Criticality of COVID-19 IL-6 Levels in Relation to the Viral Load of COVID-19 IL-6 Levels in Relation to the Prognosis of COVID-19 8.6.2 Inflammatory Markers 8.6.2.1 Inflammatory Markers in Relation to the Severity of COVID-19 8.6.2.2 Inflammatory Markers in Relation to the Complications of COVID-19 8.6.2.3 Inflammatory Markers in Relation to the Prognosis of COVID-19 8.6.3 Differentially Expressed Genes in Bronchoalveolar Lavage Fluid and Peripheral Blood from Patients with COVID-19 8.7 The Scenario of How the Lungs Come Down in Few Days by Macrophage Missiles in COVID-19 8.7.1 Human Studies Reveal the Kinetics of Two-Phase Lung Disease in Patients Who Died of SARS-CoV 8.7.1.1 Phase 1 (0–10 Days) 8.7.1.2 Phase 2 (After 10 Days) 8.7.2 Immunological Cells Invade the Lungs and Occupy its Nation Within 3–10 Days in Patients with COVID-19 8.7.3 Macrophage Population Properties in COVID-19 8.7.3.1 Blood Monocytes Are Larger and More Complex in Patients with COVID-19 8.7.3.2 Blood Monocytes Correlate with the Severity and Criticality of COVID-19 8.7.3.3 Blood Monocytes Express the Lower Amount of ACE2 in Patients with COVID-19 8.7.3.4 BALF Macrophages Are Different Among Patients with Severe and Mild COVID-19 8.7.3.5 SARS-CoV-2-Positive Macrophages Are Present in the Lung and Other Organs 8.7.4 Anti-COVID-19 Macrophages: Anti-inflammatory Macrophages that Induce Tolerance to Coronaviruses Resembling the Novel One in Bats 8.7.5 Pro-COVID-19 Macrophages: ACE2-Hyperactivated Macrophages 8.8 Macrophage-Mediate Cell Pyroptosis and Inflammation 8.8.1 Cell Pyroptosis: A Pro-inflammatory Programmed Cell Death 8.8.2 Cell Pyroptosis: A Double-Edged Sword 8.8.3 Cell Pyroptosis in Macrophages 8.8.3.1 Cell Pyroptosis in Macrophages During SARS-CoV Infection 8.8.3.2 Cell Pyroptosis in Macrophages During MERS-CoV Infection 8.9 Ravaged by Macrophage Missiles Under the Cytokine Storm: A Lethal Disease Model for COVID-19 8.10 Epidemiological Eye of SARS-CoV-2 Has No Exception to Any Region Worldwide 8.11 SARS-CoV-2: An International Problem Starting from Wuhan on December 11, 2019, Spreading to 199 Countries and Territories Around the World and Two International Conveyances as of March 28, 2020 8.12 Facilitators of SARS-CoV-2 Transmission 8.12.1 Stability on Surfaces 8.12.2 Multiple Shedding Routes 8.12.3 The Near-Presentation Detection of Viral RNA Gives Us No Opportunity to Recognize Asymptomatic People 8.12.4 Children Contribute Significantly to the Asymptomatic Population of COVID-19 8.12.5 The High Prevalence of SARS-CoV and MERS-CoV in Animals 8.13 Mathematical Models from Dynamics of the Primary Coming of COVID-19 to Preparedness for the Next Coming of COVID-19 8.14 National Healthcare Services Close to Kneeling During the COVID-19 Pandemic: The Need for an International Solution Rather than a Merely National Solution 8.15 Conclusion References 9: Potential Antiviral Immune Response Against COVID-19: Lessons Learned from SARS-CoV 9.1 Introduction 9.2 Innate Immune Recognition of Coronaviruses 9.2.1 TLRs 9.2.2 RLRs 9.3 Antigen Presentation Pathways 9.4 Epitope Spreading and Molecular Immune Mimicry 9.5 Antigen Epitopes and Immunodominant Epitopes 9.6 Potential Immune Evasion Mechanisms 9.7 Humoral Immune Responses 9.8 Conclusion References 10: COVID-19 and Cell Stress 10.1 Introduction 10.2 SARS-CoV-2 Cell Entry 10.3 Cell Stress 10.3.1 HSPA5 Functions in Healthy Versus Stressed Cells 10.3.2 HSPA5 over the Cell Membrane 10.3.3 HSPA5 in Cancer and Viral Infection 10.3.4 CS-HSPA5 Targeting 10.4 COVID-19 Inhibition by Targeting CS-HSPA5 and/or Spike Protein 10.5 Conclusion References 11: Clinical Manifestations of COVID-19 11.1 Introduction 11.2 Respiratory Manifestations and Constitutional Symptoms 11.3 Central Nervous System Manifestations 11.4 Gastrointestinal System Manifestations 11.5 Cardiovascular System Manifestations 11.6 Other Systems 11.7 Laboratory Findings 11.8 Imaging Findings 11.9 Disease Course and Severity Spectrum 11.10 Conclusion References 12: Pediatrics and COVID-19 12.1 Introduction 12.2 COVID-19 in Children and Adolescents 12.2.1 Pediatric COVID-19 Is Often Asymptomatic, and Severe Disease Is Rare 12.2.2 What Role Do Children Play in the Spread of SARS-CoV-2? 12.2.3 Why Is the Case Fatality Rate Low in Children? 12.2.4 The Immune Response to Viral Infections Differs Between Age Groups 12.2.5 What Are the Immune Components That Play a Role in Disease Severity During SARS-CoV-2 Infection? Moreover, How Does This Differ in Children? 12.2.6 Immaturity of the Resident Immune System of the Lung 12.2.7 ACE-2 Maturity and Abundance 12.3 Conclusion References 13: Geriatrics and COVID-19 13.1 Introduction 13.2 Elderlies: Too Frail for COVID-19 13.2.1 The Aged Immune System 13.2.2 The Increased Risk of Chronic Diseases 13.2.3 The Mature Immunity 13.2.4 The Aberrant Expression of ACE2 13.2.4.1 ACE2: A Receptor for SARS-CoV2 (2019-nCoV) Cell Entry That Is Present on Lungs, Heart, Kidney, and Testis 13.2.4.2 Dual-Function ACE2: Zinc Metalloproteinase and Microbial Collagenase 13.2.4.3 ACE2 Is Not Sensitive to ACEI 13.2.4.4 ACE2 Exists in Membrane-Bound and Soluble Forms 13.2.4.5 ACE2 Expression Decreases with Age 13.2.4.6 The Herding Behavior of COVID19 in Relation to ACE2 Under the Cytokine Storm 13.3 COVID-19 in Aged Patients 13.3.1 Clinical Features 13.3.2 Laboratory Findings 13.3.3 Imaging Findings 13.3.4 Diagnosis 13.3.5 Management 13.3.6 The Immune System, Inflammation, and Therapeutic Opportunities 13.4 Conclusion References 14: Coronavirus Diseases in Pregnant Women, the Placenta, Fetus, and Neonate 14.1 Introduction 14.2 Pregnancy, the Immune System, and Infectious Disease 14.3 Severe Acute Respiratory Syndrome (SARS) 14.4 Middle East Respiratory Syndrome (MERS) 14.5 COVID-19 in Pregnant Women 14.5.1 Studies from China 14.5.2 Studies from North America and Europe 14.5.3 Pregnancy as a Heightened Risk Factor for Women of Reproductive Age with COVID-19 14.5.4 Maternal Mortality 14.5.5 Vertical Transmission of Viruses 14.5.6 The Placenta 14.5.7 Fetal and Neonatal Infections 14.6 Conclusion References 15: COVID-19 in Patients with Hypertension 15.1 Introduction 15.1.1 Epidemiology 15.1.2 Pathogenesis 15.2 Lessons Learned from Other Types of Pneumonia 15.2.1 Hypertension 15.2.2 Renin-Angiotensin-Aldosterone System Inhibitors 15.2.3 Meta-analysis and Clinical Trials on ACEI/ARB Use and Pneumonia Outcomes 15.3 Hypertension Per Se and COVID-19 15.4 Antihypertensive Drugs and COVID-19 15.5 Guideline Recommendations 15.5.1 European Society of Cardiology: Council on Hypertension 15.5.2 European Society of Hypertension 15.5.3 The American Heart Association, American College of Cardiology, and Heart Failure Society of America 15.6 Conclusion References 16: COVID-19 and Cardiovascular Diseases 16.1 Introduction 16.2 Acute Myocardial Injury 16.2.1 Introduction 16.2.2 Definition 16.2.3 Incidence 16.2.4 Pathophysiology 16.2.5 Clinical Signs 16.2.6 Diagnostic Tests 16.2.6.1 Blood Tests 16.2.6.2 Chest X-Ray and CT Scanning 16.2.6.3 ECG 16.2.6.4 Troponin 16.2.6.5 Natriuretic Peptides 16.2.6.6 Imaging Echocardiography 16.2.6.7 Endomyocardial Biopsy 16.2.7 Diagnosis 16.2.8 Differential Diagnosis 16.2.9 Treatment 16.3 Hypertension and COVID-19 16.4 COVID-19 and CAD 16.4.1 Non-ST-Segment Elevation Acute Coronary Syndrome (NSTE-ACS) 16.4.2 STEMI 16.4.3 Chronic Coronary Syndrome (CCS) 16.5 Arrhythmias and COVID-19 16.5.1 Tachyarrhythmias 16.5.1.1 Supraventricular Arrhythmias 16.5.1.2 Atrial Fibrillation (AF) and Flutter 16.5.1.3 Ventricular Arrhythmias Treatment of Ventricular Arrhythmias 16.5.2 Bradyarrhythmias 16.6 Coagulopathy in the COVID-19 Outbreak 16.6.1 Venous Thromboembolism (VTE) 16.7 CPR 16.7.1 CPR Protocol 16.7.2 Safety Concerns 16.8 Drug-Drug Interactions Between COVID-19 and Cardiovascular Medications 16.8.1 Hypertension 16.8.1.1 ACEIs/ARBs 16.8.1.2 Diuretics 16.8.1.3 Alpha-Adrenoreceptor Antagonists 16.8.1.4 Dihydropyridine Calcium Channel Blockers 16.8.2 ACS 16.8.2.1 P2Y12 Inhibitors 16.8.2.2 Beta-Blockers 16.8.2.3 Statins 16.8.3 Heart Failure 16.8.4 VTE 16.8.4.1 Anticoagulants 16.8.5 Arrhythmias 16.8.5.1 Calcium Channel Blockers 16.9 Conclusion References 17: How Prevalent Is Cancer in Confirmed Cases with Coronaviruses and Severe Acute Respiratory Syndromes? 17.1 Introduction 17.2 Methods 17.2.1 Literature Search 17.2.2 Study Selection 17.2.3 Data Extraction 17.2.4 Quality Assessment 17.2.5 Statistical Analysis and Publication Bias 17.3 Results 17.3.1 Study Selection and Characteristics 17.3.2 Demographical Characteristics and Clinical Manifestations 17.3.3 The Prevalence of Cancer in COVD-19, SARS, and MERS Confirmed Cases 17.4 Discussion 17.5 Conclusion References 18: COVID-19 in Patients with Cancer 18.1 Introduction 18.2 Respiratory Infections in Patients with Cancer 18.3 COVID-19 in Patients with Cancer 18.3.1 Risk Factors for Severe Complications 18.3.2 Clinical Manifestations 18.4 Medical Care of Patients with Cancer During COVID-19 Pandemic: Challenges and Recommendations 18.4.1 Managing Resources 18.4.2 Cancer Centers During the Pandemic 18.4.3 Cancer Care During the Pandemic 18.4.4 Managing COVID-19-Infected Cancer Patients 18.4.5 Managing Hematological Malignancies During COVID-19 18.5 Cancer Research During the Pandemic 18.6 Conclusion References 19: COVID-19 and Tropical Infection: Complexity and Concurrence 19.1 Introduction 19.2 COVID-19 and Tropical Infection: Complexity and Concurrence 19.2.1 COVID-19 and Tropical Infection 19.2.1.1 Dengue 19.2.1.2 Chikungunya 19.2.1.3 Zika Virus Infection 19.2.1.4 Yellow Fever 19.2.1.5 Malaria 19.2.1.6 Cholera 19.2.1.7 Salmonellosis 19.2.1.8 Leptospirosis 19.2.1.9 Tuberculosis 19.2.1.10 Hepatitis B Infection 19.2.2 COVID-19 and Cancer in Tropical Countries 19.2.2.1 HBV-Related Hepatocellular Carcinoma 19.2.2.2 Cholangiocarcinoma 19.2.3 COVID-19 and Hereditary Disorders in Tropical Countries 19.2.3.1 Tropical Hemoglobin Disorder 19.2.3.2 Tropical Red Blood Cell Enzymatic Disorder 19.3 COVID-19 and Role of Primary Care Center: View on Common Pitfalls 19.3.1 Knowledge of Primary Healthcare Worker 19.3.2 The Vision of Local Primary Healthcare Center Administrator 19.3.3 Lack of Infrastructures 19.3.4 Underdiagnosis of COVID-19 19.3.5 Overdiagnosis of COVID-19 19.3.6 Poor Reporting System 19.3.7 Poor Disease Control Activity 19.4 COVID-19 in Indochina 19.4.1 Thailand 19.4.2 Lao 19.4.3 Myanmar 19.4.4 Cambodia 19.4.5 Vietnam 19.5 Conclusion References 20: Neurologic Manifestations of COVID-19 20.1 Introduction 20.2 Highway to the Brain 20.2.1 The Hematogenous Route 20.2.2 The Neural Pathway and Anosmia 20.3 Neural Invasion 20.4 The Brain-Lung Axis 20.5 Neuroinflammatory Manifestations 20.6 Neurovascular Manifestations 20.7 Conclusion References 21: Autoimmune Processes Involved in Organ System Failure Following Infection with SARS-CoV-2 21.1 Introduction 21.2 Ecology and History of SARS-CoV-2 21.3 Structure of SARS-CoV-2 21.4 Infectivity and Virulence Factors of SARS-CoV-2 21.5 Coronavirus Diagnostics and Medical Countermeasures 21.6 SARS-CoV-2 and the Human Host 21.7 Interaction Between the SARS-CoV-2 and the ACE2 Receptor-Binding Domain (RBD) 21.8 The Potential Roles that MHC Molecules Play in Infection 21.9 Cytokine Storm: Result of the Interaction of SARS-CoV-2 with ACE2 21.10 Neural Pathology of Coronaviruses: From Experimental Studies to Human Studies 21.11 Conclusion References 22: Clinical and Laboratory Predictors of Severity, Criticality, and Mortality in COVID-19: A Multisystem Disease 22.1 Introduction 22.2 Methods 22.2.1 Search Strategy 22.2.2 Study Selection 22.2.3 Data Extraction and Quality Assessment 22.2.4 Data Synthesis 22.3 Results 22.3.1 Characteristics of Selected Studies 22.3.2 Study and Patient Characteristics 22.3.3 Laboratory Findings 22.3.3.1 Severity Analysis 22.3.3.2 Survival Analysis 22.3.4 Symptoms and Vital Status 22.3.4.1 Severity Analysis 22.3.4.2 Survival Analysis 22.3.5 Comorbidities and Demographic Characteristics 22.3.5.1 Severity Analysis 22.3.5.2 Survival Analysis 22.4 Discussion 22.5 Conclusion References 23: Diagnostic Tests for COVID-19 23.1 Introduction 23.2 Specimen Collection 23.3 Viral Detection 23.4 Serological Tests 23.5 Conclusion References 24: The Role of Medical Imaging in COVID-19 24.1 Introduction 24.2 Pulmonary Imaging 24.2.1 CXR 24.2.2 CT Scan 24.2.2.1 GGO 24.2.2.2 Consolidations 24.2.2.3 Crazy-Paving Pattern 24.2.2.4 Pulmonary Vascular Enlargement (PVE) 24.2.2.5 Air Bronchograms 24.2.2.6 Reverse Halo Sign (RHS) or the Atoll Sign 24.2.2.7 Thickening of Interlobular Septa 24.2.2.8 Diffuse Pulmonary Involvement/White Lungs 24.2.2.9 Subpleural Curvilinear Lines 24.2.2.10 Pleural Effusion and Thickening 24.2.2.11 Lymphadenopathy 24.2.2.12 Lung Cavitary Lesions 24.2.2.13 Parenchymal Calcification 24.2.2.14 Centrilobular Nodules and Tree-in-Bud Nodularity 24.2.2.15 Air-Bubble Sign 24.2.2.16 Lesion Locations on Chest CT 24.2.2.17 CT Scoring 24.2.2.18 The Role of CT Scan in PCR-Negative Patients 24.2.2.19 Changes of Imaging Findings Over Time 24.2.2.20 Structured Reporting 24.2.2.21 Diagnostic Challenges in Patients with COVID-19 24.2.3 Ultrasound 24.2.4 Neuroimaging 24.2.5 Imaging Findings in Pediatrics 24.2.6 Imaging of COVID-19 in Pregnancy 24.2.7 Imaging of COVID-19 Complications 24.2.7.1 Acute Respiratory Distress Syndrome (ARDS) 24.2.7.2 Bacterial Superinfection 24.2.7.3 Pulmonary Thromboembolism (PTE) 24.2.7.4 Radiomics and Artificial Intelligence (AI) 24.3 Conclusion References 25: Therapeutic Development in COVID-19 25.1 Introduction 25.2 Antiviral Treatments for COVID-19 25.2.1 Virus-Based Drugs 25.2.1.1 3CLpro Inhibitors Lopinavir/Ritonavir (LPV/r) Darunavir/Cobicistat 25.2.1.2 RdRp Inhibitors Remdesivir (GS-5734) Favipiravir (T-705) Ribavirin 25.2.1.3 Other Antiviral Drugs Arbidol (Umifenovir) Ivermectin 25.2.2 Host-Based Drugs 25.2.2.1 Chloroquine (CQ) and Hydroxychloroquine (HCQ) 25.2.2.2 Camostat Mesilate 25.2.2.3 Bevacizumab 25.2.2.4 Recombinant Human ACE2 (APN01) 25.2.2.5 Tocilizumab 25.2.2.6 Human Immunoglobulin 25.2.3 Neutralizing Antibodies (nAbs) 25.2.4 Traditional Chinese Medicine (TCM) and Natural Products 25.2.4.1 Chinese Medicine Preparations and Prescriptions 25.2.4.2 Natural Products 25.3 Supportive Treatment for COVID-19 25.4 Precautions of COVID-19 25.5 Conclusion References 26: Immune-Based Therapy for COVID-19 26.1 Introduction 26.2 Immunopathology and Its Implications for Acute Respiratory Distress Syndrome (ARDS) Therapy 26.3 Immunopathogenesis of COVID-19 26.3.1 Innate Immune Response to SARS-COV-2 26.3.2 Adaptive Immune Response to SARS-COV-2 26.3.3 Challenges of the Immune Response Against SARS-COV-2 26.3.3.1 Immune-Compromised Patients 26.3.3.2 Cytokine Storm 26.3.3.3 Exhaustion of T Cells 26.3.3.4 Dysregulation of Type I IFN 26.3.4 Immunotherapy of COVID-19 26.3.4.1 Antibody-Based Treatments for COVID-19 Convalescent-Plasma Therapy IVIG Administration Monoclonal Antibodies (mAbs) Polyclonal Antibodies 26.3.4.2 Hemoperfusion Therapy 26.3.4.3 Immune Checkpoint Inhibitor-Based Therapies 26.3.4.4 JAK Inhibitors 26.3.4.5 Development of Decoy Receptors 26.3.4.6 Management of the Cytokine Storm Immune-Restraining Approaches Interferon-Based Immunotherapy 26.3.4.7 SARS-CoV-2 Vaccination 26.3.4.8 Cell-Based Immunotherapy Mesenchymal Stem Cells (MSCs) Natural Killer (NK) Cells T Cells and Chimeric Antigen Receptor (CAR)-T-Cell Therapy Dendritic Cells (DCs) and Engineered DCs Modulation of the Intrapulmonary Macrophage 26.3.4.9 Immunosuppressive Drugs Cytotoxic Chemotherapy Low-Dose Steroids and NSAIDs 26.4 COVID-19 Immune-Based Clinical Trials at a Glance 26.5 Conclusion References 27: Ventilatory Support in Patients with COVID-19 27.1 Introduction 27.2 Respiratory Failure and Oxygen Therapy 27.3 High-Flow Nasal Cannula Oxygen 27.4 Noninvasive Ventilation 27.5 Invasive Ventilation 27.6 Actual Guidelines and Recommendation from Scientific Societies 27.7 Pediatric Patients: A Challenge 27.8 Conclusion References 28: Nutrition and Immunity in COVID-19 28.1 Introduction 28.2 Nutritional Assessment 28.2.1 Nutritional Care in Outpatients with COVID-19 28.2.2 Hospitalized Patients with COVID-19 28.2.2.1 Nutritional Strategies for Non-ICU Patients Hospitalized for COVID-19 Energy Requirements Protein Requirements Fat and Carbohydrate Requirements 28.2.2.2 Nutritional Strategies for ICU Patients with COVID-19 Intubated and Ventilated Patients Enteral Nutrition Energy Requirements Protein Requirements Lipid Requirements Carbohydrate Requirements Parenteral Nutrition Protein Requirements Carbohydrate Requirements Fat Requirements Post-extubation Period and Dysphagia 28.3 Role of Micronutrients 28.3.1 Vitamin A 28.3.2 B Vitamins 28.3.3 Vitamin C 28.3.4 Vitamin D 28.3.5 Selenium 28.3.6 Zinc 28.3.7 Iron 28.4 Conclusion References 29: Dietary Supplements for COVID-19 29.1 Introduction 29.1.1 COVID-19: Epidemiology and Pathogenesis 29.1.2 COVID-19: Current Treatment Paradigm 29.2 Dietary Supplements Being Studied for COVID-19 29.2.1 Ascorbic Acid 29.2.2 Phytochemicals 29.2.3 Melatonin 29.2.4 Vitamin D 29.2.5 Zinc 29.3 Conclusion References 30: Photobiomodulation and Antiviral Photodynamic Therapy in COVID-19 Management 30.1 Introduction 30.2 Virology 30.2.1 Origin, Classification, and Genetical Features 30.2.2 Receptor Interactions and Cell Entry 30.3 Epidemiology 30.3.1 Source of Infection 30.3.2 Routes of Transmission 30.3.3 High-Risk Population 30.3.4 Spectrum of Infection 30.4 Diagnosis 30.4.1 Nucleic Acid Test 30.4.2 Serologic Diagnosis 30.4.3 Chest Radiography or Computed Tomography (CT) Scan 30.5 Pathogenesis 30.5.1 Virus Entry and Spread 30.5.2 Pathological Findings 30.6 Clinical Features 30.6.1 Acute Respiratory Distress Syndrome (ARDS) 30.6.2 Cytokine Storm Phenomenon 30.6.3 Cellular Immune Dysfunction 30.7 Potential Therapeutics 30.7.1 Chloroquine 30.7.2 Kaletra 30.7.3 Interferon 30.7.4 Remdesivir 30.7.5 Tocilizumab (Actemra) 30.7.6 hrsACE2 (Human Recombinant Soluble Angiotensin-Converting Enzyme 2) 30.7.7 Immunoglobulin Therapy 30.8 Photobiomodulation Therapy 30.8.1 PBM and Pro-inflammatory Cytokine 30.8.2 PBM on Macrophage Phenotype 30.8.3 Role of Photobiomodulation in COVID-19 Management 30.8.4 Photobiomodulation of the Lungs 30.8.5 Indirect Photobiomodulation 30.9 Photodynamic Therapy (PDT) 30.9.1 Mechanism of Photodynamic Therapy 30.9.2 PDT for Infectious Disease 30.9.3 Antimicrobial Photodynamic Therapy 30.9.4 Photoinactivation of Viruses 30.10 Antiviral Photodynamic Therapy in COVID-19 30.11 Conclusion References 31: The COVID-19 Vaccine Landscape 31.1 Introduction 31.1.1 Genesis of Immunization 31.1.2 Primal Vaccine Designs 31.1.3 Vaccine Strategies Beyond Whole Pathogens 31.1.4 Naked Vaccines 31.1.5 Construction Kits for Vaccines 31.1.6 Vaccines Against Emerging Pathogens 31.2 SARS-CoV-2 Vaccine Design Challenges 31.2.1 Vaccines Against Respiratory Viruses 31.2.2 The Coronaviridae Family 31.2.3 Animal Models 31.2.4 Vaccine Targets 31.2.5 Vulnerable Populations 31.3 Immunity in Covid-19 Vaccine Design 31.3.1 What Does Immune Protection Consist of: An Open Question 31.3.2 Duration of Immunity 31.3.3 Immune Interaction: Cross-Reactivity, ADE, and VAERD 31.3.4 Differences in Vaccine-Induced Immunity 31.3.5 Vaccine Development Against SARS-CoV-1 and MERS-CoV 31.4 Current Status of SARS-CoV-2 Vaccine Development 31.5 Conclusion References 32: Prevention of COVID-19: Preventive Strategies for General Population, Healthcare Setting, and Various Professions 32.1 Introduction 32.2 Transmission of SARS-CoV-2 32.2.1 Animal-to-Human Transmission 32.2.2 Human-to-Human Transmission 32.2.3 Environment-to-Human Transmission 32.2.4 Human-to-Animal Transmission 32.3 Non-pharmaceutical Preventive Interventions 32.3.1 Preventive Measures at the Individual Level 32.3.2 Surveillance, Patient Identification, and Contact Tracing 32.3.3 Population-Level Strategies 32.3.4 The Rapid Development of Diagnostic Capabilities 32.4 Pharmaceutical Prevention 32.4.1 Chemoprevention 32.4.1.1 Chloroquine and Derivatives 32.4.1.2 Remdesivir 32.4.2 Immunoprevention 32.4.2.1 Vaccine 32.4.2.2 Convalescent Plasma 32.4.2.3 Non-specific Immunoprevention 32.4.3 Traditional Medicine 32.5 Prevention in Healthcare Settings 32.5.1 Patient Assessment and Transport 32.5.2 Personnel Protective Equipment 32.5.2.1 Eye/Face Protection 32.5.2.2 Face Masks 32.5.2.3 N95 Respirators 32.5.2.4 Gowns 32.5.3 Prevention of Nosocomial Infection 32.5.3.1 Pediatric Healthcare Settings 32.5.3.2 Obstetric Healthcare Settings 32.5.3.3 Hemodialysis Settings 32.5.3.4 Laboratory Settings 32.6 Specific Guidelines for Other Professions 32.6.1 Forensic Medicine 32.6.2 Funeral Homes 32.6.3 Airline Industry 32.6.4 Border Control 32.7 Considerations in Special Groups 32.7.1 High-Risk Groups and Elderly 32.7.2 Pregnancy and Breastfeeding 32.7.3 Children 32.8 Prevention of Social Crisis 32.8.1 Education, Knowledge, and Awareness 32.8.2 Psychological Aspects 32.8.3 Economic Aspects 32.8.4 Role of International and Non-governmental Organizations 32.8.5 Regulation 32.9 Conclusion References 33: Pharmacist’s Role and Pharmaceutical Care During the COVID-19 Pandemic 33.1 Introduction 33.2 The Role of a Pharmacist During the COVID-19 Pandemic 33.2.1 Community Pharmacist Support in the COVID-19 Pandemic 33.2.1.1 Community Pharmacist in Rural and Underserved Areas 33.2.1.2 Community Pharmacist to Support Industrial Workers 33.2.2 Clinical Pharmacist’s Role in Hospital Settings During the COVID-19 Pandemic 33.3 Pharmacy Services During COVID-19 Pandemic 33.3.1 Supply of Medication and Products for COVID-19 Prevention 33.3.2 Pharmaceutical Care 33.3.2.1 Drug Dispensing 33.3.2.2 Medication Reconciliation Service 33.3.2.3 Pharmacotherapy Follow-Up (PTF) 33.3.2.4 Patient Counseling (Education, Information, and Communication About COVID-19) 33.3.2.5 Psychological Support During the Pandemic 33.3.3 PC Services in Community Pharmacies During the COVID-19 Pandemic 33.3.3.1 Drug Indication 33.3.3.2 COVID-19 Detection and Patient Referral 33.3.3.3 Testing and Immunization 33.3.3.4 Home Care 33.3.3.5 Safe Use of Infusions in Outpatient Pharmacy Services 33.3.4 PC Services in COVID-19 Hospitalized Patients 33.3.4.1 Remote Inpatient Order Review and Dispensing 33.3.4.2 Management of Drug Interactions 33.3.4.3 Monitoring and Management of Convalescent Plasma Therapy 33.3.4.4 Management of Off-Label Drug Use 33.3.5 Other Hospital Pharmacy Services During the COVID-19 Pandemic 33.3.5.1 Establish and Participate in Evidence-Based Drug Evaluation and Guidelines 33.3.5.2 Establishment of Drug Registration Research 33.4 Ensuring a Safe and Efficient Operation for Providing Pharmacy Services 33.4.1 Pharmacy Staff Training 33