Table of Contents
A Guide to SARS-CoV-2 and the COVID-19 Pandemic
1
Background Information
1.1 Introduction
1.2 MolecularCharacteristics
1.2.1 Characteristics of Coronaviruses
1.2.2 Characteristics of SARS-CoV-2 Genome
1.2.3 Characteristics of SARS-CoV-2 Proteins
1.2.3.1 SARS-CoV-2 Spike (S) Protein
1.2.3.2 SARS-CoV-2 Nucleocapsid (N) Protein
1.2.3.3 SARS-CoV-2 Envelope (E) and Membrane (M)>
1.2.3.4 SARS-CoV-2 Non-structural Proteins
1.3 ACE2 Receptor
1.4 Replication Cycle
1.5 Interaction with the Immune System
1.6 Epidemiology
1.6.1 Natural Reservoirs
1.6.2 Early Human Cases
1.6.2.1 The Latham-Wilson Hypothesis
1.6.3 Climate Factors of Disease Distribution
1.6.4 Undocumented Cases
1.6.5 Superspreaders and Seeding Events
1.6.6 Mutations and Divergent Strains
1.6.6.1 Early Lineages
1.6.6.2 D614G Mutation
1.6.6.3 Mink Variants
1.6.6.4 VUI-202012/01
1.6.6.5 Other Notable Mutations
1.6.7 Infections in Non-human Species
1.7 Previous Pandemics and Waves
1.8 Viral Inactivation
1.8.1 Oxygen, Heat, pH, and Radiation
1.8.2 Soaps, Surfactants, and Detergents
1.8.3 Electrokinetic Inactivation
2 Chronology, Data, and Observations
2.1 Chronology
2.2 Current Data, Trends, and Models
2.2.1 General Definitions
2.2.2 Global Trend
2.2.2.1Universal Features
2.2.3 International Trends
2.2.3.1 Sustained Exponential Growth
2.2.4 Domestic Trends
2.2.4.1 Nationwide Data
2.2.4.2 Statewide Data
2.2.4.3 Countywide Data
2.2.5 A Modified SEIR Model
2.2.6 Bayesian Inference / Convolution Model
2.3 Symptoms of Infection
2.4 Transmission Factors
2.4.1 Incubation and Communicability Periods
2.4.2 Basic Reproduction Number
2.4.3 Contact and Droplet Transmission
2.4.3.1 Face Masks and Other Methods for Limiting Droplet Transmission
2.4.4 Evidence for Airborne and/or Fomite Transmission
2.4.5 Asymptomatic Cases and Transmission
2.5 Pathophysiology
2.5.1 Pulmonary Pathophysiology
2.5.2 Vascular Pathophysiology and Coagulopathy
2.5.3 Central Nervous System Involvement
2.5.4 Pathophysiology in Other Organs
2.6 Immunity and Reinfection
2.6.1 SARS-CoV-2 Epitope
2.6.2 The Kinetics of SARS-CoV-2 Specific Antibodies and Memory Immune Cells
2.6.3 Reinfection
2.6.4 Pre-Existing Immunity
2.7 Herd Immunity
2.7.1 Effect of Population Heterogeneity
2.8 Factors Concerning Severity
2.8.1 Age, Pre-Existing Conditions, and Clinical Course
2.8.2 Kawasaki-like Disease (MIS-C)
2.8.3 Molecular and Cellular Factors
2.8.4 Genetic Risk Factors
2.9 Fatality, Recovery, and Potential for Lasting Damage
3 Diagnosis, Treatment, and Vaccine Candidates
3.1 Diagnostic Devices and Related Techniques
3.1.1 Polymerase Chain Reaction
3.1.1.1 SalivaDirect Testing
3.1.2 Isothermal Amplification
3.1.3 Radiological Methods
3.1.4 Serological Assays
3.2 Current Clinical Treatments
3.2.1 Management of Patients with Cancer
3.2.2 Cancer, Immune Checkpoint Inhibitors (ICI), and COVID-19
3.2.3 Potential Impact of Delays in Cancer Diagnosis and Treatment on Prognosis
3.2.4 Treatment of Cancer Patients on Cancer-Related Clinical Trials
3.2.5 Management of Patients with Diabetes
3.2.6 Management of Pregnant Patients
3.3 Current and Proposed Clinical Trials
3.3.1 Adaptive COVID-19 Treatment Trial
3.3.2 RECOVERY Trial
3.3.3 Solidarity Trial
3.4 Proposed Repurposed Drugs
3.4.1 Angiotensin Receptor Blocker
3.4.1.1 Current Clinical Trials
3.4.1.2 Study Results
3.4.2 Chloroquines (with or without Azithromycin)
3.4.2.1 Current Clinical Trials
3.4.2.2 Results from Individual Trials
3.4.2.3 Meta-Analyses
3.4.3 Dexamethasone and Other Corticosteroids
3.4.3.1 Current Clinical Trials
3.4.3.2 Study Results
3.4.4 Famotidine
3.4.5 Favipiravir
3.4.6 Interleukin-6 Receptor Antagonists
3.4.7 Lopinavir and Ritonavir
3.4.8 Remdesivir
3.4.9 Other Pharmaceutical Drugs
3.5 Current Vaccine Candidates
3.5.1 RNA Vaccine Candidates
3.5.1.1 mRNA-1273
3.5.1.1.1 Phase I U.S. Trial
3.5.1.1.2 Phase II U.S. Trial
3.5.1.1.3 Phase II/III U.S. Adolescent Trial
3.5.1.1.4 Phase III U.S. Trial
3.5.1.2 BNT162
3.5.1.2.1 Phase I/II/III Global Trial
3.5.1.2.2 Phase I/II German Trial
3.5.2 DNA Vaccine Candidates
3.5.2.1 INO-4800
3.5.3 Viral Vector-Based Vaccine Candidates
3.5.3.1 Ad5-nCoV
3.5.3.1.1 Phase I Chinese Trial
3.5.3.1.2 Phase II Chinese Trial
3.5.3.1.3 Phase III Global Trial
3.5.3.2 AZD1222 (ChAdOx1 nCoV-19)
3.5.3.2.1 Pre-Clinical Trial Results
3.5.3.2.2 Phase I/II U.K. Trial
3.5.3.2.3 Phase II/III U.K. Trial
3.5.3.2.4 Phase III U.S. Trial
3.5.3.2.5 Phase III Brazil Trial
3.5.3.3 Ad26.COV2.S
3.5.3.3.1 Pre-Clinical Trial Results
3.5.3.3.2 Phase I/II U.S. and Belgium Trial
3.5.3.3.3 Phase III International Single Dose Trial
3.5.3.3.4 Phase III International Two Dose Trial
3.5.3.4 Sputnik V
3.5.3.4.1 Phase I/II Trials
3.5.3.4.2 Phase III Trial
3.5.4 Inactivated Vaccine Candidates
3.5.4.1 CoronaVac
3.5.4.1.1 Phase II Chinese Trial
3.5.4.1.2 Phase III Brazil Trial
3.5.4.1 BBIBP-CorV
3.5.4.1.1 Pre-Clinical Results
3.5.4.1.2 Phase I/II Chinese Trial
3.5.4.2 Sinopharm-Wuhan Vaccine Candidate
3.5.4.2.1 Phase I/II Chinese Trial
3.5.5 Protein-Based Vaccine Candidates
3.5.5.1 NVX-CoV2372
3.5.5.1.1 Phase II South Africa Trial
3.5.5.1.2 Phase III U.K. Trial
3.5.5.1.3 Phase III U.S. and Mexico Trial
3.5.5.2 EpiVac Corona
3.5.5.3 Other Protein-Based Vaccines
3.5.6 DIY Vaccine Efforts
3.5.7 Recommendations for Future Research
3.6 Potential Experimental Treatments and Preventatives
3.6.1 Monoclonal Antibodies
3.6.1.1 Casirivimab/Imdevimab
3.6.1.2 Bamlanivimab
3.6.1.3 Other Antibody Treatments
3.6.2 ACE2 Peptides and Recombinant ACE2
3.6.3 Other Experimental Compounds
3.6.4 Cell Therapy
3.6.5 Convalescent Plasma Transfusion
3.6.5.1 U.S. Expanded Access Trial
3.6.6 Gene Editing Therapy
3.6.7 Radiation Therapy
3.7 Potential Nutritional Supplements
4 Summary and Outlook
A Appendix
R References and Hyperlinks