Coronavirus Disease 2019 (Covid-19): A Clinical Guide

Cover
Title Page
Copyright Page
Contents
List of Contributors
Preface
Chapter 1 COVID-19: Epidemiology
	Origin
	Animal Host
	Infectivity and Incubation
	Modes of Transmission
		Overview
		Respiratory Droplets
		Aerosolization
		Direct Surface Contact and Fomites
		Fecal-Oral
		Bloodborne
		Semen and Vaginal Secretions
	Asymptomatic Transmission
	Virulence and Mortality
		Case Fatality Rate
		Serial Interval
		Reproduction Number/Reproduction Ratio
		Excess Mortality
	Demographics
		Overview
		Age
		Sex
		Race and Ethnicity
	Disease Prevention
		Vaccinations
		Personal Protective Equipment: Respirators and Masks
		Physical Distancing
		Hand and Surface Sanitation
		Adequate Ventilation of Indoor Spaces
		Use of Outdoor Spaces
	Global Impacts
		Distribution
		International Response
		Future Outbreaks
	Conclusions
	References
Chapter 2 COVID-19: Virology
	Coronaviruses
		Taxonomy
		Morphology
		Nucleic Acid
		Antigenicity
	SARS-CoV-2
		Morphology and Nucleic Acid
		Spike Protein
		Origin
		Viral Transmission
		Variants
	References
Chapter 3 COVID-19: Laboratory/Serologic Diagnostics
	Molecular Diagnostics for COVID-19
		Nucleic Acid Amplification Testing
		RT-qPCR
	RT-LAMP
	CRISPR-Based Techniques
	Sequencing Techniques
	Antigen Testing
	Viral Culture
	Antibody Testing for COVID-19
	Principles of Antibody Testing
	Antibody Assays for SARS-CoV-2
		Assay Target Selection
		Binding Assays
		Neutralization Assays
		Antibody Assay Sensitivity and Specificity
	Humoral Response to SARS-CoV-2 Infection
		Kinetics of Antibody Response
		Antibody Response and Disease Severity
		Duration of Immunity
	Current and Potential Applications of Antibody-Based Tests in SARS-CoV-2
		Management of Individual Disease and Sequelae Monitoring
		Contact Tracing
		Vaccine Efficacy
	Conclusions and Future Directions
	References
Chapter 4 COVID-19: Radiologic Diagnosis
	Current Guidelines on When to Image
		Fleischner Society
		World Health Organization
		Practical Points
	Technical Considerations to Limit Spread While Imaging
		Chest Radiography
		Cross-Sectional Imaging
		Ultrasound
	Imaging by Modality
		X-Ray
		Computed Tomography
		Ultrasound
		PET
		MRI
	Guidelines for Reporting
		RSNA
		COVID-19 Reporting and Data System
		COVID-19 Imaging Reporting and Data System
	References
Chapter 5 COVID-19: Pathology Perspective
	Gross and Histopathologic Findings in the Respiratory System
	Gross and Histopathologic Findings in the Cardiovascular System
	Histopathologic Findings in Kidney
	Histopathologic Findings in the Gastrointestinal Tract and Liver
	Histopathologic Findings in Brain
	Histopathologic Findings in Skin
	References
Chapter 6 COVID-19: Immunology
	Anatomic Progression of COVID-19
	Adaptive Immune Response in the Nasal Passages and the Lungs
	Immune Response to Immunization
	Immune Correlates of Protection from Infection
	Decline in Vaccine-Induced Immune Responses over Time
	Immune Consequences of Virologic Dissemination
	Autoantibodies Against Type I IFN
	Viral Evasion
	Immune Dysregulation
	Antibody-Dependent Cellular Cytotoxicity
	Cytokine Storm
	Conclusions
	Acknowledgments
	References
Chapter 7 COVID-19: Presentation and Symptomatology
	Pulmonary Manifestations of COVID-19
		Atypical Acute Respiratory Distress Syndrome
	Otolaryngologic Manifestations of COVID-19
		Sense of Smell
		Voice Disorders
		Hearing, Tinnitus, and Facial Nerve
	Gastrointestinal Manifestation of COVID-19
	Coronavirus and Pregnancy
		Physiologic Changes and Effect of SARS-CoV-2 Infection
		General Symptoms of COVID-19 in Obstetric Patients
		Impact of COVID-19 on Gestation: Maternal and Neonatal Outcomes
		Vertical Transmission and Possible Fetal Complications
		COVID-19 and Delivery
		Breastfeeding
		Vaccination
	Urologic Manifestations of COVID-19
		Kidneys
		Genital and Lower Urinary Tract Infection
		Disorders of Genital Organ Function
		Infertility
	References
Chapter 8 COVID-19: Risk Stratification
	Potential Biomarkers for COVID-19 Detection, Severity, and Mortality
	Host Risk Factors for COVID-19
	ABO Blood Type as an Additional Risk Factor
		ABO Blood Group and Rh Factor
		Association of Blood Group with Viral Respiratory Diseases
		Association of Blood Type with Higher Susceptibility to COVID-19 Infection and Outcomes
		Genetic Association and Underlying Molecular Mechanisms
	ML Methods for X-Ray and CT Image Classification and Prediction
	References
Chapter 9 COVID-19: Outpatient Management in Adults
	Potential Conflicts of Interest
	Initial Diagnosis
	Prognosis and Choice of Admission Versus Outpatient Management
	Home Monitoring
		Telehealth Diagnosis and Follow-up
		Pulse Oximetry Monitoring
		Post–Hospital Discharge Care
	General Management Issues
		Isolation
		Hydration and Nutrition
		Continuation of Ongoing Therapies
		Nutritional Supplements
		Anticoagulation
		Use of Home Supplemental Oxygen
	Antivirals and Anti-inflammatory Treatments
	Anti-SARS-CoV-2 mAbs
		Selection of Outpatients to Receive Anti-SARS-CoV-2 mAbs
		Bamlanivimab Plus Etesevimab
		Casirivimab Plus Imdevimab
		Sotrovimab
		Bebtelovimab
		Side Effects of Anti-SARS-CoV-2 mAbs
		Distribution of mAbs
	Oral Antivirals
		Molnupiravir
		Nirmatrelvir (PF-07321332)/Ritonavir
	Outpatient Anti-inflammatory Interventions
		Inhaled Budesonide
		Fluvoxamine
		Dexamethasone
	Drugs That Are Not Recommended for Outpatient Use
		Janus Kinase Inhibitors/Anti-IL-6 Therapies
		Chloroquine and Hydroxychloroquine
		Ivermectin
		Azithromycin
		Lopinavir/Ritonavir
		Convalescent Plasma
		Colchicine
	Summary
	References
Chapter 10 COVID-19: Inpatient Management
	Respiratory Support for Hospitalized Patients with COVID-19
		Noninvasive Respiratory Support
		Prone Positioning in Awake Patients
	Caring for the Critically Ill Patient with COVID-19
		Practical Considerations for Intubating Patients
		Mechanical Ventilation of Patients with COVID-19
		Rescue Therapies for Refractory Hypoxemia of Ventilated Patients
	Pharmacologic Therapies for Hospitalized Patients with COVID-19
		Use of Antivirals in Patients Hospitalized for COVID-19
		Anti-inflammatory Therapies for Hospitalized Patients with COVID-19
		Therapies that Have No Benefit in Hospitalized Patients with COVID-19
	Extrapulmonary Disease in Acutely Ill Patients with COVID-19
		Thromboembolic Disease
		Cardiac Complications
		Renal Complications
		Infectious Complications
	Performing Aerosol-Generating Procedures in Patients with COVID-19
		Bronchoscopy in COVID-19
		Tracheostomy in Patients with COVID-19
		Cardiopulmonary Resuscitation of the Patient with COVID-19
	Coordinating Patient Placement and Care in COVID-19 Units
		Increasing ICU Capacity
		Additional Management Considerations
	References
Chapter 11 COVID-19: ICU and Critical Care Management
	Epidemiology of Critically Ill Patients with COVID-19 Pneumonia
		Risk Factors for Severe Disease
		Mortality
	Infection Prevention and Control of COVID-19 in the ICU
		Aerosol-Generating Procedures
		Visitation
	Cardiopulmonary Resuscitation in COVID-19
	Hemodynamic Support in COVID-19
	Management of Respiratory Failure from COVID-19
		Intubation
		Ventilator Management
		Prone Positioning
	Treatment of COVID-19-Associated ARDS with Corticosteroids
	Tocilizumab for Critical COVID-19 Illness
	Extracorporeal Membrane Oxygenation for COVID-19 ARDS
	Venous Thromboembolism and Anticoagulation in COVID-19
	After the ICU: Challenges for Survivors of COVID-19 Critical Illness
	References
Chapter 12 COVID-19 in Pediatrics
	Epidemiology
		Epidemiology of Multisystem Inflammatory Syndrome in Children
		Transmission in Children
		Neonatal Transmission
		Breastfeeding
	Clinical Manifestations
		Disease Severity
		Infection in Infants (Age <1 Year)
		Cutaneous Manifestations
		COVID Toes
		Neurologic Symptoms
		Atypical Clinical Manifestations
		Imaging Findings
		MIS-C Clinical Manifestations
		Post-Acute Sequelae of SARS-CoV-2 (PASC) in Children
	Approach to Diagnosis
		Screening and Diagnosis in Symptomatic Patients
		Screening and Diagnosis in Asymptomatic Patients
		Neonatal Testing
		COVID-Recovered Patients
		Retesting of COVID-Recovered Patients
		Testing of COVID-19 Fully Vaccinated Persons
		MIS-C Diagnosis
		Hyperinflammation in COVID-19 Versus MIS-C
	Management
		Outpatient Management
		Inpatient Management
		Special Populations
		Antiviral Therapy
		Glucocorticoids
		Nonsteroidal Anti-inflammatory Drugs
		Convalescent Plasma
		Adjunctive Therapy
		Kinase Inhibitors
		Superimposed Infections
		Management of MIS-C
		Guidance for Return to Sports After SARS-CoV-2 Infection
		Vaccines
	References
Chapter 13 Pharmacologic Therapeutics for COVID-19
	Virus Life Cycle
	Drug Development for SARS-CoV-2
	Immune Responses that Contribute to COVID-19 Pathology
	Challenges to Discover and Deploy Drugs for a New Infectious Agent
	Therapeutic Classes
		Antivirals
		Camostat (Foipan)
		Nafamostat
		Upamostat
		Chloroquine and Hydroxychloroquine
	Angiotensin Receptor Blockers
		Valsartan
		Losartan
		Telmisartan
		Recombinant ACE2
		Ang(1–7)
	Viral Replication Inhibitors
		Favipiravir (Avigan)
		Molnupiravir (MK-4482or EIDD-2801)
		Remdesivir (Veklury)
		Ribavirin
		Oseltamivir
		Umifenovir
	Viral Protein Process Inhibitors
		Lopinavir/Ritonavir
		Disulfiram (Antabuse)
		Antibiotics and Antiparasitic
		Immunotherapy
	Recombinant Cytokine Therapy
		Type I IFNs
		GM-CSF
	Anticytokine Therapy
		IL-1 Receptor Antagonism
		IL-6 Receptor Antagonism
		IL-6 Antagonism
		GM-CSF Antagonism
	Neutralizing Antibody Therapy
		Recombinant Monoclonal Antibodies
		Convalescent Plasma Therapy
	Other Anti-inflammatory Therapies
		Steroids
		Cyclosporine
		Acalabrutinib
		Baricitinib
		Lenzilumab
	Experimental Therapeutics
		PAC-MAN
		Single-Domain Antibody
		Exo-CD24
		Fluvoxamine
		Clofazimine (Lamprene)
	References
Chapter 14 Co-infections and Secondary Infections in COVID-19 Pneumonia
	Bacterial Co-infections
		Streptococcus pneumoniae
		Klebsiella
		Mycoplasma pneumoniae
		Pseudomonas aeruginosa
		Legionella
	Fungal Superinfection
		Pulmonary Aspergillosis
		Mucormycosis
		Pneumocystis jirovecii Pneumonia
		Trichosporon asahii Fungemia
		Histoplasmosis
	Parasitic
		Strongyloidiasis
	Viral
		Influenza
		Dengue
		Respiratory Syncytial Virus
	Summary
	References
Chapter 15 COVID-19: Neurology Perspective
	Epidemiology and Transmission Mode
		Route to the Nervous System
		Retrograde Pathway Through Neurons
		Direct Infection Through ACE-2 Expression
	Mechanisms for CNS Complications
		Neuronal Infection
		Neuroinflammation
		Other Mechanisms
	Neurologic Manifestations
		Guillain–Barré Syndromes
		Skeletal Muscle Injury
		Encephalopathy
		Acute Myelitis
		Acute Cerebrovascular Events
	Therapeutic Strategies
	Conclusion
	References
Chapter 16 COVID-19: Cardiology Perspective
	Epidemiology
	Potential Mechanisms of Cardiovascular System Involvement in COVID-19
		Direct Viral Myocardial Injury
		Microvascular Injury
		Acute Coronary Syndrome
		Oxygen Supply and Demand Mismatch
		Systemic Hyperinflammatory Response
	Myocardial Injury in Acute COVID-19
		Acute Coronary Syndrome
		Clinical Presentation
		Diagnosis
		Management
		Thrombosis and Pulmonary Embolism
		Acute Myocarditis and Cardiogenic Shock
		Pericarditis
	Kawasaki Disease, Multisystem Inflammatory Syndrome in Children, Pediatric Multisystem Syndrome, Multisystem Inflammatory Syndrome in Adults, and Acute COVID-19 Cardiovascular Syndrome: Overlapping Post-COVID-19 Inflammatory Cardiac Syndromes
		Clinical Presentation
		Diagnosis
		Management
	Arrhythmias in Acute COVID-19
		Management
	Postural Orthostatic Tachycardia Syndrome
		Clinical Presentation
		Diagnosis
		Management
	Postacute Sequelae of SARS-COV-2 Infection
	Long-Term Management of COVID-19 Cardiovascular Disease
	Cardiovascular Effects of COVID-19 Treatments
	COVID-19 in Special Populations
		Chronic Heart Failure
		Heart Transplant Recipients
	Conclusion
	References
Chapter 17 COVID-19: Oncologic and Hematologic Considerations
	The Natural History of COVID-19 in Patients with Cancer
	Diagnosing COVID-19 in Patients with Cancer: Clinical, Serologic, and Imaging Considerations
	COVID-19 Therapeutics in Patients with Cancer
		Monoclonal Antibodies (Casirivimab/Imdevimab, Sotrovimab, and Bamlanivimab/Etesevimab)
		Remdesivir
		Glucocorticoids
		Baricitinib and Other Janus Kinase Inhibitors
		Tocilizumab and Other Interleukin-6 Inhibitors
		Convalescent Plasma
		Molnupiravir
	Practical Considerations in the Management of Patients with Cancer
	Cancer Screening and Diagnosis
	Cancer Therapy: Cytotoxic Chemotherapy
	Cancer Therapy: Immunotherapy, Targeted Agents, and Biologics
	Cancer Therapy: Radiation Therapy
	Cancer Therapy: Cellular Therapy and Hematopoietic Transplantation
	Oncologic Surgery
	Thromboembolism in Patients with Cancer and COVID-19
	Clinical Trials
	COVID-19 and Other Vaccinations
	Supportive Care
	Use and Impact of Telemedicine on Caring for Patients with Cancer
	Survivorship and Surveillance After Cancer Therapy
	Palliative Care and Advance Care Planning
	After COVID-19: The Natural History of Cancer in the Postpandemic Era
	References
Chapter 18 COVID-19: Dermatology Perspective
	Cutaneous Manifestations of COVID-19
		Exanthem Group
		Vascular Lesions
		Miscellaneous Cutaneous Manifestations
		Treatment
	Cutaneous Adverse Effects Caused by Use of Personal PMs against SARS-CoV-2
	Challenges Posed by the COVID-19 Pandemic for Dermatology: Impact on Dermatological Diseases, Dermatology Services, and Dermatology Practice
	Dermatology Registries in Response to COVID-19
	Conclusion
	References
Chapter 19 COVID-19: Ophthalmology Perspective
	Conjunctiva and Sclera
		Conjunctivitis
		Episcleritis
	Anterior Segment
		Uveitis
		Corneal Graft Rejection
	Neuro-ophthalmic Complications
		Clinical Findings and Evaluation
		Management and Prognosis
	Optic Nerve
		Active COVID-19 Infection
		Optic Nerve and Retinal Changes After COVID-19 Infection
	Retina
		Retinal Microangiopathy
		Central Retinal Vein Occlusion
		Central Retinal Artery Occlusion
	Orbit
		Orbital Cellulitis
		Orbital Inflammation
		Rhino-orbital Mucormycosis
		Orbital Emphysema
	Conclusions
	References
Chapter 20 COVID-19:  Nutrition Perspectives
	Safety Considerations for Nutrition Processes and Practice When Caring for Patients with COVID-19
	Nutrition in the Noncritically Ill Hospitalized Patient with COVID-19
		Treatment for COVID-19 and Associated Nutrition Impacts
		Steroids
		Other Treatments
		Nutrition Screening and Assessment in Noncritically Ill Patients
		Nutrition Interventions and Monitoring of Nutrition Progress
	Nutrition in the Critically Ill Patient with COVID-19
		Nutrition Screening and Assessment in Critically Ill Patients
		Guidelines
		Therapies for COVID-19 and Associated Nutrition Impacts
		Nutrition Provision, Choice of Nutrition Mode, and Monitoring
		Energy and Protein Requirements
		Estimation of Energy Expenditure
		Nonnutritional Energy
		Protein
		Micronutrients and Trace Elements
		Management of Complications
	Post-ICU Acute Care Management, Including Dysphagia and Multidisciplinary Care
		Dysphagia: Features and Recovery
		Multidisciplinary Care
	Organization and System Considerations for Nutrition Management
		Workforce and Stock/Supply Considerations
		Food Service Considerations
		Considerations in an Overwhelmed Hospital System
	Follow-up for COVID-19-Related Nutrition Issues After Hospital Discharge
	Conclusion
	References
Chapter 21 COVID-19: Nursing Perspective
	Care of the Patient in the Inpatient Setting
		Resources
		Nursing Interventions
		Prone Positioning Intubated Patients
		Modes of Oxygen Delivery: High-Flow Nasal Cannula, Bilevel Positive Airway Pressure, and Mechanical Ventilation
		Pressure-Related Injuries and Other Nursing Interventions
		Medications
		Nutritional Management
	Advance Care Planning
	Interdisciplinary Care
	Discharge Planning: Transition to Outpatient/Specialty Care
	Home Services and Transition to Home
	Humanization of Care
		Moral and Ethical Distress
	Building Resilience
	Conclusion
	References
Chapter 22 COVID-19 Vaccination: A Clinical Perspective
	Terminologies
		Storage and Handling
		Reactogenicity
		Efficacy and Immunogenicity
		Contraindication
		Precaution
	Authorized Candidate Vaccines
		BNT162b2/Comirnaty (BioNTech/Pfizer/Fosun Pharma)
		mRNA-1273 (Moderna)
		AZD1222/ChAdOx1/Covishield (University of Oxford and AstraZeneca)
		Sputnik V (Gamaleya Research Institute of Epidemiology and Microbiology, Russia)
		CoronaVac (Sinovac Research and Development co., Ltd)
		Unnamed (Sinopharm/Wuhan Institute of Biological Products co., Ltd.)
		BBIBP-CorV (Sinopharm/Beijing Institute of Biological Products)
		EpiVacCorona (State Research Center of Virology and Biotechnology VECTOR, Russia)
	Symptom Management
	Prioritization and Acceptance
	Passive Immunotherapy
		Convalescent Plasma
		Monoclonal Antibody
	Conclusion
	Acknowledgments
	References
Chapter 23 Post-COVID-19 Vaccine Imaging Findings
	Vaccines and Imaging: Past Experience
		What We Know from Previous Vaccines
		Local Reactions
		Lymphadenopathy
		Systemic Inflammation
		Neurologic Complications
	COVID-19 Vaccine: Types and Mechanisms
	Expected Findings Post-COVID-19 Vaccination
		Lymphadenopathy
	Vaccine-Related Imaging Misinterpretation
	Special Considerations for Oncologic Imaging with COVID-19 Vaccination
	Other COVID-19 Vaccine–Induced Side Effects
		Injection-Site Reaction
		Musculoskeletal Complications
		Neurologic Complications
		Thrombotic Complications
		Myocarditis
	Summary of Recommendations and Conclusion
	References
Chapter 24 COVID-19: Long-Term Pulmonary Consequences
	Long-Term Pulmonary Complications from Past Viral Pandemics
		Severe Acute Respiratory Syndrome
		Middle East Respiratory Syndrome
	Monitoring for Long-Term Pulmonary Consequences of COVID-19 Infection
		Imaging Modalities for the Diagnosis and Follow-Up of COVID-19
		Timeline of Chest CT Findings During Different Phases of COVID-19 Infection
	Long-Term Clinical Sequelae of COVID-19
		Pathophysiology
	Clinical Management
	Summary Points
	References
Chapter 25 Psychological Effects and Neuropsychiatric Sequelae in COVID-19 Patients
	Depression and Anxiety
		Cause or Consequence
		Mitigating Factors and Management Strategies
	Posttraumatic Stress Disorder
	Sleep Dysfunction
		The Bidirectional Relationship of SARS-CoV-2 Infection and Sleep Dysfunction
		Factors Associated with Sleep Dysfunction
		Management of Sleep-Associated Disorders
	Neuropsychiatric Sequelae
		Pathophysiology of Neuropsychiatric Complications Associated with COVID-19
		Cognitive Impairment Associated with COVID-19
		Long COVID Syndrome
		Management of Delirium and Long COVID Syndrome
	Conclusions
	References
Chapter 26 Mental Health Effects of the COVID-19 Pandemic on Healthcare Professionals
	Overview of Psychological Impact on Healthcare Professionals
	Impact on Healthcare Workers by Country
		China
		United States of America
		United Kingdom
		India
		Iran
		Southeast Asia
	COVID-19 Impact by Occupation and Healthcare Setting
		Frontline Healthcare Workers
		Different Medical Professionals
		Nursing Staff
		Non-frontline Healthcare Workers
		Nonclinical Healthcare Personnel
	Identifying Risk/Predisposing Factors
		Gender
		Age
		Underlying Medical Conditions
		Risk for Infection and Level of Precaution at Home
		Living Circumstances
		Infection Rate Among Peers
		Time Spent Focusing on COVID-19
		Demand for Personal Protective Equipment
	Mental Health Interventions and Strategies for HCWs
		Interventions and Strategies at the International, National, and Regional Levels
		Interventions and Strategies at the Institutional Level
		Interventions and Strategies at the Individual Level
	Conclusion
	References
Chapter 27 COVID-19: Ethical Considerations in Clinical Practice
	Crisis Standard of Care
	Resource Allocation and the Pandemic
	The Duty of Healthcare Providers
	The Problem of Pseudoscience
	Off-Label Use of Medications
	Contact Tracing
	Conclusions
	References
Chapter 28 Racial, Ethnic, and Other Disparities in the Epidemiology and Care of COVID-19
	Disparities in Risk for Exposure in the United States
		Racial and Ethnic Disparities
		Neighborhood and Environment
		Tribal and Rural Communities
		Unemployment and Occupational Risk
		The American Prison and Correctional System
		Access to Education and the American School System
	International Risk for Exposure to COVID-19
		China
		Italy
		India
		Brazil
		Iran
	Diagnostic Disparities
		Diagnostic Disparity in COVID-19 Testing
		Diagnostic Workup of COVID-19 and the Role of Imaging Utilization
	Clinical Disparities
		Hospitalizations and Inpatient Admissions
		ICU Admission
		Treatment Disparities
	Disparities in Patient Outcome
	Disparities in Vaccination
		Combating These Disparities
	Conclusion
	References
Chapter 29 Global Impact of COVID-19 on Healthcare Systems
	Healthcare Systems Before COVID-19
	International Trends and Collaboration
	Africa
		West Africa
		East Africa
		Southern Africa
		Central Africa
		Future Directions for Africa
	Asia Pacific
		East Asia
		Central Asia
		South Asia
		Southeast Asia
		Oceania/Pacific
		Future Directions for the Asia-Pacific Region
	Europe
		Future Directions for Europe
	Middle East and North Africa
		Further Directions for MENA Countries
	Americas
		North America
		Central America
		South America
		Caribbean
		Further Directions for the Americas
		Conclusion
	References
Chapter 30 COVID-19: Mass Casualty Planning
	Viral Pandemic
	The Surge
	Prehospital Planning
		Mitigation
		Emergency Medical Service Preparedness
		Field Hospitals
	Hospital Planning
		Triage and Emergency Department Capacity
		Infection Control
		Conversion of Inpatient Units
		Staff and Equipment Shortages
	Outpatient Planning
		Telemedicine
	Recovery Phase
	References
Index
EULA