Frontiers of COVID-19 : Scientific and Clinical Aspects of the Novel Coronavirus 2019

This book aims to serve the critical interests of the global community by supplying the most current knowledge and understanding of Covid-19 epidemiology, treatment, and prognoses. There was much uncertain and contradictory information published in the first year of the novel coronavirus. The dynamics of COVID-19 have now been realized, including the type of antibodies produced in infected patients and their limited lasting endurance. This book will set the record straight on the concept of “herd immunity” and explore the current vaccine trials taking place in different countries. This comprehensive book will illuminate recent advances regarding COVID-19 and offer a possible roadmap on how to move forward. Frontiers of COVID-19: A Pathophysiology and Epidemiology Roadmap of Novel Coronavirus Disease will be a vital and forward-looking guide for infectious disease clinicians, scientists and researchers, and students at the graduate level. Introduction Part I: History, Epidemiologic Background and Pathogenesis of Coronavirus Main Topics History of Coronaviruses Epidemiology and Demographics of COVID-19 Pathogenesis of COVID-19 Chapters Included Chapter 1: Surfaces as a Source for SARS-CoV-2 Transmission Chapter 2: Humoral Immune Response in SARS-CoV-2 Infection and Its Therapeutic Relevance Chapter 3: SARS-CoV-2 Invasion and Pathogenesis of COVID-19: A Perspective of Viral Receptors, Bradykinin and Purinergic System Chapter 4: Genetics and Biological Characteristics of SARS-CoV-2 Chapter 5: COVID-19 Impact on Host at Pathophysiological and Cellular Level Chapter 6: Identification of the COVID-19 Droplet Deposition Path and Its Effects on the Human Respiratory Tract Before and After the Disease: A Scoping Novel Respiratory Mask Design Chapter 7: SARS-CoV-2 Variants: Impact of Spike Mutations on Vaccine and Therapeutic Strategies Chapter 8: Global Biologic Characteristics of Variants of Concern and Variants of Interest of SARS-CoV-2 Chapter 9: Emergence of COVID-19 Variants and Its Global Impact Part II: Clinical Observations Main Topics Respiratory Symptoms Cardiovascular Complications Neurological Complications Gastrointestinal Symptoms Psychological and Sociological Issues Chapters Included Chapter 10: Psychological Impacts of the COVID-19 Pandemic Chapter 11: Spatial Epidemiology of COVID-19: Disease Risk, Prognosis, and Complications Chapter 12: Eye Disorders and Neuro-ophthalmic Manifestations Chapter 13: Evaluation and Management of Dysphagia During the COVID-19 Pandemic Chapter 14: Gastrointestinal Manifestations of COVID-19 and Inflammatory Bowel Disease in the COVID-19 Era: Clinical Overview and Updated Guidelines Chapter 15: Post COVID-19 Conditions: The New Challenge to Mankind Chapter 16: Association of Alpha 1 Antitrypsin Deficiency with COVID-19 Mortality Rate Chapter 17: Social Cognition Approaches to Understanding and Changing COVID-19 Preventive Behaviors Chapter 18: Neurological Complications of COVID-19 Chapter 19: The Impact of Covid-19 on Surgical Disease Part III: Interventions and Treatments Main Topics Diagnosis of SARS-CoV-2 Infection Current Treatments Chapters Included Chapter 20: Pre-hospital Management of COVID-19: Looking for a Future Perspective Chapter 21: Biotechnological Strategies in the Intervention and Treatment of COVID-19 Chapter 22: Vitamin D: A Potential Prophylactic and Therapeutic Agent Against COVID-19 Part IV: Current Trends and Future Directions Main Topics Ongoing Clinical Trials for Treatment and Vaccination Future Directions for COVID-19 Management in Clinical Practice and Research Post-COVID-19 or Long COVID Chapters Included Chapter 23: Rational Repurposing of Drugs, Clinical Trial Candidates, and Natural Products for SARS-Cov-2 Therapy Chapter 24: In Silico Drug Repositioning for COVID-19: Progress and Challenges Chapter 25: Computationally Repurposed Natural Products Targeting SARS-CoV-2 Chapter 26: Different Platforms, Immune Response Modulators, and Challenges in SARS-CoV-2 Vaccination Chapter 27: SARS-CoV-2 Vaccine Against Virus: Mission (Im)possible Chapter 28: COVID-19 Vaccines Authorized by Stringent Regulatory Authorities and Vaccine Chapter 29: The Global Evolution of a Pandemic on Clinical Practice Chapter 30: Anticipated Long-Term Neurobehavioral Outcomes Following COVID-19 Chapter 31: The Road Ahead References Contents Part I: History, Epidemiologic Background and Pathogenesis of Coronavirus Chapter 1: Surfaces as a Source for SARS-CoV-2 Transmission Introduction Persistence of Infectious SARS-CoV-2 on Surfaces Detection of Viral RNA on Surfaces Surrounding of Confirmed COVID-19 Patients in Health-Care Settings Surrounding of COVID-19 Patients in Non-Health-Care Settings Public Surfaces Detection of Infectious SARS-CoV-2 on Surfaces Probability of Surfaces to Be the Source for SARS-CoV-2 Transmission References Chapter 2: Humoral Immune Response in SARS-CoV-2 Infection and Its Therapeutic Relevance Introduction Pathogens and Antibodies Evolve Together Antibody Kinetics After SARS-CoV-2 Infection The Role of Antibodies in COVID-19 Antibody Titers Antibodies Functionality Antibodies and Reinfection Antibody Production Modulated by Cytokines Maternal Antibodies Conclusion References Chapter 3: SARS-CoV-2 Invasion and Pathogenesis of COVID-19: A Perspective of Viral Receptors, Bradykinin, and Purinergic System Introduction Human Cell Invasion by SARS-CoV-2 ACE-2 and SARS-CoV-2, The Supposed Main Mechanism CD147 and CD209, Additional Mechanisms of Infection Bradykinin and Kinin–Kallikrein System Functional Relation Between Angiotensin-Converting Enzyme-2 (ACE2) and Kallikrein–Kinin System: Implications in COVID-19 Bradykinin Storm Purinergic System as Target in the Modulation of Immune System Triggered by SARS-CoV-2 Purinergic Signalling Involvement of Purinergic Signalling on the Modulation of Inflammatory Process Generated by SARS-CoV-2 Infection Pharmacological Approaches References Chapter 4: Genetics and Biological Characteristics of SARS-CoV-2 Introduction SARS-CoV-2 Genome and Replication Genomic Structure Viral Replication Key Structural Proteins Spike (S) Envelope (E) Membrane (M) Nucleocapsid (N) Genetic Diversity of SARS-CoV-2 SARS-CoV-2 Classification Evidence of Genetic Recombination Genetic Mutations of SARS-CoV-2 Concluding Remarks References Chapter 5: COVID-19 Impact on Host at Pathophysiological and Cellular Level Introduction Cardiovascular Diseases Hypertension Diabetes Obesity Obesity-Related Complications and COVID-19: Immune Dysfunction and Adipose Inflammation Thrombosis in Obese COVID-19 Patients COVID-19 and the Obesity Paradox Neurological Modalities Cancer Immunocompromised Status Oral and Maxillofacial Manifestations Oral Mucosal Lesions Associated with COVID-19 Effect of Poor Oral Hygiene and Periodontal Diseases on COVID-19 Effect of Nasal Irrigation and Antimicrobial Oral Rinses on COVID-19 Disease Outcome COVID-19–Associated Mucormycosis Kidney Injury Molecular Pathways Involved in the Development of COVID-19 Pathology NFκB Signaling The p38 MAPK Signaling JNK Pathway IRF Involved Signaling JAK-STAT Pathway Conclusion References Chapter 6: Identification of the COVID-19 Droplet Deposition Path and Its Effects on the Human Respiratory Tract Before and After the Disease: A Scoping Novel Respiratory Mask Design Introduction Methods Computational Model Governing Equations Numerical Solution and Method Verification Results The Flow Enters from the Nose with the Closed Mouth—Group A Simulated Airflow and Droplet Transport and Deposition Simulated Solid Domain Deformation The Flow Enters from the Mouth with Closed Nose—Group B Simulated Airflow with Droplet Transport and Deposition Simulated Solid Domain Deformation Discussion Conclusion References Chapter 7: SARS-CoV-2 Variants: Impact of Spike Mutations on Vaccine and Therapeutic Strategies Introduction Variants of Concern (VOC) The B.1.1.7 Lineage (Alpha Variant) Origin Genetic Alterations, Impact on Protein Structure and Antigenicity Effect on Convalescent and Vaccine Sera Effect on Vaccine Efficacy Effect on Antibody Therapy The B.1.351 Lineage (Beta Variant) Origin Genetic Alterations and Impact on Protein Structure and Antigenicity Effect on Convalescent and Vaccine Sera Effect on Vaccine Efficacy Effect on Antibody Therapy P.1 Variant (Gamma Variant) Origin Genetic Alterations and Impact on Protein Structure and Antigenicity Effect on Convalescent and Vaccine Sera Effect on Vaccine Efficacy Effect on Antibody Therapy The B.1.617.2 (Delta Variant) Origin Genetic Alterations and Impact on Protein Structure and Antigenicity Effect on Convalescent and Vaccine Sera Effect on Vaccine Efficacy Effect on Antibody Therapy Variants of Interest (VOI) Epsilon (B.1.427 and B.1.429) Variants Zeta (P.2) Variant Eta (B.1.525) and Iota (B.1.526) Variants Theta (P.3) Variant Kappa (B.1.617.1) Lambda (C.37) Variant Uganda Variant (A.23.1) Conclusion References Chapter 8: Global Biologic Characteristics of Variants of Concern and Variants of Interest of SARS-CoV-2 Background SARS-CoV-2 Variants of Concerns and Their Characteristics SARS-CoV-2 Alpha Variant SARS-CoV-2 Beta Variant SARS-CoV-2 Gamma Variant SARS-CoV-2 Delta Variant SARS-CoV-2 Variants of Interest (VOI) and Their Characteristics Long-Term Manifestations of COVID-19 Conclusions References Chapter 9: Emergence of COVID-19 Variants and Its Global Impact Introduction Reasons for Emergence of SARS CoV-2 Variants Nomenclature of the SARS CoV-2 Variants Major COVID-19 Variants Variants of Concern B.1.1.7 or the Alpha Variant B.1.351 or the Beta Variant P.1 or the Gamma Variant B.1.617.2 or the Delta Variant Variants of Interest Other Notable Variants Impact of Viral Variants Impact on Disease Spread, Virulence, and Therapeutics Impact on Diagnostic Tests Strategies to Prevent Emergence of Newer Variants Conclusion References Part II: Clinical Observations Chapter 10: Psychological Impacts of the COVID-19 Pandemic Introduction Psychological and Psychiatric Impacts of the COVID-19 Pandemic General Population-Based Estimates of COVID-19-Related Psychiatric Symptoms and Psychological Distress Distress and Psychiatric Symptoms Among Specific Sociodemographic Groups Children and Adolescents Students and Young Adults Frontline Healthcare Workers Other Essential Workers Parents Pregnant Individuals Members of Racial and Ethnic Minority Groups Suicidality Heterogeneity and Temporal Variability of Adverse Psychiatric Effects Associated with the COVID-19 Pandemic Risk and Protective Factors for Psychological Distress and Psychiatric Illness During the COVID-19 Pandemic Potential Risk Factors for Increased Distress and Psychopathology in the COVID-19 Pandemic Younger Age Female Sex/Gender Pre-existing Psychiatric Conditions Socioeconomic Disadvantage Racism Possible Protective Factors Against Psychopathology During the COVID-19 Pandemic Increased Age Healthcare Knowledge and Adoption of Precautionary Measures Psychological Traits and Behaviors Psychiatric Manifestations of COVID-19 and Its Aftermath Neuropsychiatric Manifestations of COVID-19 and Putative Pathophysiologic Mechanisms “Long COVID-19,” Its Neuropsychiatric Symptoms, and Potential Mechanisms Psychiatric Sequelae of COVID-19 Psychological and Behavior Adaptation Strategies Conclusion Further Readings Chapter 11: Spatial Epidemiology of COVID-19 Pandemic: Disease Risk, Prognosis, and Complications Introduction Global Variation in COVID-19 Case Incidence and Mortality: Impact of Vaccination and New Variants of Concern Spatial Variation of Risk Factors for SARS-CoV-2 Transmission and Mortality Pre-existing Comorbidities and the Risk of COVID-19 Mortality Spatial Variation of Genetic Predictors of SARS-CoV-2 Meteorological and Environmental Predictors of COVID-19 Transmission and Mortality Mental Health and Psychological Stress Consequences of COVID-19 Pandemic Conclusion References Chapter 12: Eye Disorders and Neuro-ophthalmic Manifestations of COVID-19 Introduction Pathophysiological Mechanisms Eye Disorders Conjunctivitis and Keratitis Retinal Disorders and Choroiditis Neuro-ophthalmic Manifestations Optic Neuritis Ocular Motor Nerves Palsy Miller Fisher Syndrome Looking to the Future References Chapter 13: Evaluation and Management of Dysphagia During the COVID-19 Pandemic Introduction Mode of Transmission of SARS-CoV-2 Infection The Characteristics of Dysphagia in Patients After Recovery from COVID-19 Videofluoroscopic Swallowing Study Findings After Severe COVID-19 Clinic Setup and Precautions Necessary When Assessing Patients with Dysphagia During the COVID-19 Pandemic The Selection of Patients with Dysphagia and the Selection of Their Assessment During the COVID-19 Pandemic Management of Dysphagia in Head and Neck Cancer Patients During the COVID-19 Pandemic: A Practical Strategy Implementation of Rehabilitation of Swallowing During the COVID-19 Pandemic: From the Acute Hospital to the Old Age Home Telemedicine and the Evaluation and Management of Patients with Dysphagia Management of Dysphagia in the COVID-19 Era: A Multidisciplinary Approach Conclusions References Chapter 14: Gastrointestinal Manifestations of COVID-19 and Inflammatory Bowel Disease in the COVID-19 Era: Clinical Overview and Updated Guidelines Gastrointestinal Manifestations Clinical Background and Pathogenesis of Gastrointestinal Manifestations in COVID-19 Gastrointestinal and Hepatic Presentations of COVID-19 Diagnosis and Treatment of GIT and Hepatic Manifestations of COVID-19 Protection of the Health Care Workers Inflammatory Bowel Disease (IBD) in the COVID-19 Era Clinical Background of the Condition Effect of COVID-19 on IBD Effect of IBD on COVID-19 Guidelines for IBD Treatment and Follow-Up, Dilemmas, and Differences Guidelines for Vaccination Future Research Points Conclusions References Chapter 15: Post COVID-19 Conditions: The New Challenge to Mankind The Post COVID-19 Syndrome Cardiovascular Involvement in COVID-19 Cardiovascular Complications in COVID-19 Life After COVID-19: Results of the First National Campaign in Bulgaria Imaging Methods of Choice in COVID-Related Cardiovascular Complications Acute Coronary Syndrome as Part of the Post COVID-19 Conditions Pulmonary Embolism in COVID-19 Patients Conclusion References Chapter 16: Association of Alpha 1 Antitrypsin Deficiency with COVID-19 Mortality: Basis for Clinical Trials Introduction Host Genetics of COVID-19 Targeting TMPRSS2 to Treat COVID-19 Correlation of COVID-19 Case Fatality Rate with A1AT Deficiency Mechanism of the Protective Effect of A1AT Clinical Trials of A1AT in COVID-19 Conclusion References Chapter 17: Social Cognition Approaches to Understanding and Changing COVID-19 Preventive Behaviors Introduction Social Cognition Theories Used to Explain and Change Behavior Social Cognition Determinants of COVID-19 Preventive Behaviors An Application of Theory- and Evidence-Based Strategies to Promote a COVID-19 Preventive Behavior Key Challenges and Future Directions Conclusion References Chapter 18: Neurological Complications of COVID-19 Introduction Neurological Manifestations and Neuropathophysiology of Respiratory Viruses Classification of COVID-19 Neurological Complications Anosmia and Ageusia Encephalopathies CNS Inflammatory Syndromes Encephalitis Encephalomyelitis and Myelitis PNS and Neuromuscular Alterations Guillain-Barré Syndrome Spectrum Other Neuropathies and Neuromuscular Disorders Cerebrovascular Disorders Ischemic Stroke Intracranial Hemorrhage Cerebral Venous Sinus Thrombosis Cerebral Vasculopathy Neuro-Covid Imaging Moving Forward References Chapter 19: The Impact of COVID-19 on Surgical Disease COVID-19-Induced Hypercoagulability COVID-19-Induced Gastrointestinal Pathology Tracheostomy in the COVID-19 Era Impact on Elective and Non-Urgent Surgery Impact on Trauma/Acute Care Surgery Delays in Care Due to COVID-19 Perioperative Effects of COVID-19 Future Considerations References Part III: Interventions and Treatments Chapter 20: Pre-hospital Management of COVID-19: Looking for a Future Perspective Introduction SARS-CoV-2 Diagnosis Home Setting Multidimensional Assessment Early Clinical Symptoms Laboratory Biomarkers Imaging and Instrumental Tools Pharmacological Interventions Monoclonal Antibodies Antiviral Agents Corticosteroids Other Drugs Respiratory Support Oxygen Therapy Prone Positioning and Pulmonary Rehabilitation Future Perspectives References Chapter 21: Biotechnological Strategies in the Intervention and Treatment of COVID-19 Introduction Repurposing of Known Drugs Against COVID-19 First COVID-19 Vaccines: Efficacy and Clinical Symptoms After Application Vaccines from Modified Viral mRNA Vaccines Developed from a Viral Vector Inactivated Virus Vaccines Anaphylactic Reactions and Thrombotic Events Variants Neutralizing Monoclonal Antibodies for COVID-19 Treatment and Prophylaxis Natural Products in the Treatment Against COVID-19 Bioactive Substances and Vitamins in the Treatment of COVID-19 Propolis: A New Alternative Against COVID-19—Cases of Reports The Use of Propolis: Clinical Cases Concluding Remarks References Chapter 22: Vitamin D: A Potential Prophylactic and Therapeutic Agent against COVID-19 Introduction SARS-CoV-2 and COVID-19 Vitamin D, Its Various Forms, and Functions The Role of Vitamin D in Respiratory Infections and COVID-19: A Case for Its Prophylactic Effect Can Vitamin D Deficiency Increase the Susceptibility to COVID-19? Immunophenotype of COVID-19 and Vitamin D Deficiency Management of Vitamin D Deficiency for a Therapeutic Effect Regulation of Thrombotic Complications by Vitamin D—A Therapeutic Model? Vitamin D and the Inflammatory Response The Positive Role of Vitamin D in COVID-19 Complications Conclusions and Future Perspectives References Part IV: Current Trends and Future Directions Chapter 23: Rational Repurposing of Drugs, Clinical Trial Candidates, and Natural Products for SARS-CoV-2 Therapy The COVID-19 Pandemic and the Urgent Need for Effective Drug Treatments Rationale for, and Examples of, Successful Drug Repurposing Computational Repurposing of Drugs SARS-CoV-2 Molecular Targets Used for Repurposing Spike NSP3 (Papain-Like Protease) and NSP5 (3C-like Protease) NSP7, NSP8 and NSP12 (RNA-Dependent RNA Polymerase, RdRp) NSP13 Helicase NSP14 (3′ to 5′ Endonuclease, N7-Methyltransferase) NSP15 (endoRNAse) NSP16 (2′-O-Ribose-Methyltransferase) Computational Methods for Virtual Screening Protein Structure Preparation and Grid Preparation Drug and Clinical Trials Databases for Screening Molecular Docking Molecular Dynamics Simulation and Binding Free Energy Estimation Examples of Virtual Screening—Results, Validation, Leads Main Protease (Mpro) RNA-Dependent RNA Polymerase (RdRp) Helicase Summary and Perspective References Chapter 24: In Silico Drug Repositioning for COVID-19: Progress and Challenges Introduction Drug Repurposing In Silico Drug Repurposing Methods Knowledge Mining and Integration Strategies Genetic Analysis Methods Connectivity Map Strategy Network Analysis Methods Computer-Aided Drug Design In Silico Drug Repurposing for COVID-19 Chloroquine Hydroxychloroquine Lopinavir–Ritonavir Remdesivir Favipiravir Oseltamivir Ribavirin Ivermectin Corticosteroid Tocilizumab Opportunities and Challenges Conclusion References Chapter 25: Computationally Repurposed Natural Products Targeting SARS-CoV-2 Attachment and Entry Mechanisms Introduction Structural Features of SARS-CoV-2 Spike Protein Inhibitors of SARS-CoV-2 Receptor Binding Domain (RBD) for Angiotensin-Converting Enzyme 2 (ACE2) Alkaloids Sterols Peptides Polyphenols Curcuminoid Stilbenols and Stilbenoid Flavonoids Anthraquinone Tannin Terpenoids Organic Sulfides and Other Organosulfur Compounds Phenolic Acids Miscellaneous Natural Products Inhibitors of SARS-CoV-2 Receptor Binding Domain for GRP78 Alkaloids Polyphenols Peptides Terpenoids Inhibitors of SARS-CoV-2 Receptor Binding Domain for NRP-1 Binding Region Inhibitors of Host Cell TMPRSS2 Alkaloids Peptides Polyphenols Flavonol and Flavone Chalcone Hydrolysable Tannin Proanthocyanidins Anthraquinone Xanthone Phenolic Acids Terpenoids Prospects References Chapter 26: Different Platforms, Immune Response Modulators and Challenges in SARS-CoV-2 Vaccination What Influences a Vaccine’s Response? SARS-CoV-2 Vaccines: Development Scenario, Platforms Used, and Their Particularities Vaccine Platforms Whole-Pathogen Vaccine Adenovirus-Vectored Vaccine Protein Subunit Vaccine Nucleic Acid Vaccine Immune Response Modulators Immunization Routes Adjuvants and Delivery Systems The Use of Mucosa Vaccines for SARS-CoV-2 Potentially Modified Response to Vaccination Disease-Modifying Therapies and Immunocompromised Patients Childhood Pregnancy SARS-CoV-2 Variants Booster Doses and Heterologous Prime-Booster Schemes Conclusion References Chapter 27: SARS-CoV-2 Vaccine Against Virus: Mission Accomplished!? A Virus with Potential Mutations in the Viral Spike Protein and Beyond The Pressure is on References Chapter 28: COVID-19 Vaccines Authorized by Stringent Regulatory Authorities and Vaccine Candidates Expecting Approval in 2021 Introduction Vaccine Development and Production Timeline How Were COVID-19 Vaccines Developed in Less Than a Year Vaccine Trials Were Done in Parallel Instead of Sequential Rolling Submission of Regulatory Dossier Scientific Data from Other Coronaviruses Global Collaboration and Data Sharing Funding for COVID-19 Vaccine Research Coalition for Epidemic Preparedness Innovations (CEPI) Advancements in Science and Technology COVID-19 Community Transmission in Many Countries Different Types of Vaccines for COVID-19 CoronaVac (SinoVac Biotech) BBIBP-CorV (Sinopharm) Covaxin (Bharat Biotech) NVX-CoV2373 (Novavax) ChAdOx1/AZD1222 (Oxford University/Astra-Zeneca) Sputnik V (Gamaleya Institute) Ad26.COV2.S (Johnson & Johnson) Comirnaty mRNA Vaccine (Pfizer, BioNTech, Fosun) SpikeVax (mRNA-1273) (Moderna, National Institutes of Health) Zy-CoV-D COVID-19 DNA vaccine (Zydus Cadila) Current Knowledge Gaps References Chapter 29: The Global Evolution of Clinical Practice During a Pandemic Regional Variations in the Evolution of COVID-19 Potential Advanced-Stage Pathology of Disease Processes Managing Surgical Backlog Ambulatory Care and the Outpatient Setting Employee Screening Protocols Personal Protective Equipment Bed Allocation Reliance Upon Communication and Social Media for Clinical Updates The Influx of Case Reports and Preliminary Data in Journals Novel Collaborations for Large-Scale Data Conclusion References Chapter 30: Anticipated Long-Term Neurobehavioral Outcomes Following COVID-19 Physiological Mechanisms of Long-Term Cognitive Change Hypoxia and Hypoxemia Stroke Post-Intensive Care Syndrome Chronic Metabolic Dysfunction Neurodegenerative Risk Psychiatric Conditions That Impact Cognition Depression Anxiety Posttraumatic Stress Disorder Additional Clinical Considerations The Neuropsychological Evaluation Patient, Caregiver, and Community Factors Chapter Summary References Chapter 31: The Road Ahead (Editors) The Known Knowns Prevention Risk Stratification Diagnosis Treatments Vaccines The Known Unknowns New Drugs Variants Long COVID Main Topics of Concern The Unknown Knowns The Unknown Unknowns References Index