Preface
Preface to the First Edition
Contributing Authors
COVID Reference International
Content
0. Top 10
1. Epidemiology
Hotspots of SARS-CoV-2 Transmission
Hospitals
Long-term care facilities
Homes
Leisure venues (bars, clubs, choirs, karaokes, discos, etc.)
Workplaces
Schools and nurseries
Universities
Family meetings
Mass gatherings
Sports events
Religious gatherings
Closed and densely populated spaces
Prisons
Homeless shelters
Cruise ships, aircraft carriers, etc.
Special Aspects of the Pandemic
First outbreak (China)
Preparedness (Taiwan, Vietnam, Japan)
Surprise or unpreparedness (Italy)
Unwillingness to prepare, or simple denial (UK, Iran, USA, Brazil)
Partial preparedness (France)
Good virologists, huge lab network, family doctors (Germany)
Christmas
Herd immunity? Not yet! (Sweden)
Deferred beginning, then major impact (South America)
Splendid isolation (New Zealand, Australia)
Africa: The unknown outcome
The SARS-CoV-2 pandemic: Past and Future
Natural course of a pandemic
The 2020 Lockdowns
Curfews
The “second wave”
Herd immunity: Not yet!
Vaccines: In sight, finally! But be patient!
‘Variolation’ – Finding of the year?
Outlook
References
2. Transmission
Summary
Introduction
The Virus
SARS-CoV-2 and its kin
Ecology of SARS-CoV-2
Person-to-person transmission
Routes of Transmission
Respiratory transmission
Fomites
Mother-to-child
Cats and dogs et al.
Hypothetical modes of transmission
Stool, urine
Sweat
Blood products
Organ donation
Sexual transmission
Human corpses
Transmission Event
Virus
Transmittor
Transmittee
Transmission setting
Indoor environments
Temperature and climate
End of Quarantine
Prevention
Outlook
References
3. Prevention
Introduction
Prevention at the personal level
Good respiratory hygiene/cough etiquette.
Face masks
Hand Hygiene
Physical/Social distancing and avoiding crowded conditions
Chemoprophylaxis (not there yet!)
Prevention at the community/societal levels
Tracking apps
Travel bans/border closures
Vaccinate for seasonal influenza and (almost there) for COVID-19
Containment or mitigation of COVID-19?
Conclusion
References
Prevention at the personal level
Good respiratory hygiene/cough etiquette.
Face masks
Hand Hygiene
Physical/Social distancing and avoiding crowded conditions
Household hygiene
Prevention at the community/societal levels
Widespread testing, quarantine and intensive contact tracing
Quarantine and isolation of suspected or confirmed cases
Test. Treat. Track.
Tracking apps
Mandatory face masks
Ban on mass gatherings
Localized and nationwide Lockdowns
Travel bans/border closures
Vaccinate for seasonal influenza and for COVID-19 (not yet available)
Environmental hygiene and disinfection
Hospitals and other health care settings
Nursing facilities
Long-term Care Institutions
Workplaces
Schools
Prisons
Homeless shelters
4. Virology
Introduction
References
Taxonomy
Genomic variation
Origin and hosts
Stability and transmission of the virus
Cell tropism, ACE expression
Spike protein
Binding to ACE
Cell entry
RNA-dependent RNA polymerase (RdRp)
Animals and animal models
Vaccine (see also Immunology)
Pathogenesis
Other key papers
5. Vaccines
Summary
Approved SARS-CoV-2 vaccines – An overview
Dosing schedule
Distribution
Impact on the Pandemic
Mutations and vaccine efficacy
Prices
Questions
Vaccines
Tozinameran
mRNA-1273
ChAdOx1 nCoV-19
Vaccine platforms
mRNA vaccines
Replication-incompetent vectors
Other vaccine platforms
Vaccine candidates in Phase III Trials
BBIBP-CorV (China)
CoronaVac (China)
Covaxin (India)
Sputnik V (Russia)
Wuhan Institute vaccine (China)
Convidecia (China)
CvnCoV (Germany)
Ad26.COV2.S (Belgium/US)
NVX-CoV2373 (US)
CoVLP (Canada)
ZF2001 (China)
SCB-2019 (China)
Immunization fundamentals
Passive immunization against SARS-CoV-2
Convalescent plasma
Monoclonal antibodies
Issues to address during vaccine development
Immunization with recombinant SARS-CoV spike (S) -coding modified vaccinia virus Ankara (rMVA) causes hepatitis in ferrets.
Type 2 immunopathology in the lungs of immunized mice
Type 2 immunopathology in the lungs of immunized primates
Questions for the Future
Correlates of Protection
Longevity of the immunological memory against SARS-CoV-2
Pre-existing immune responses against SARS-CoV-2
Outlook
References
6. Diagnostic Tests and Procedures
Diagnosis
Specimen collection
Nasopharyngeal swabs – practical issues
Fecal shedding
Specimens other than respiratory and gastrointestinal: blood, urine, breast milk
PCR
Qualitative PCR
Quantification of viral load
Cycle threshold (Ct) values
Test systems other than conventional RT-PCR
Access to rapid diagnosis is key to the control of the SARS-CoV-2 pandemic. In the future, point-of-care testing could relieve pressure on centralized laboratories and increase overall testing capacity. Besides PCR, additional potentially valuable amp...
Point-of-care tests
Diagnosis in the setting of a shortage of PCR test kits
Serology (antibody testing)
Tests
Indication in clinical practice
The kinetics of antibodies
Radiology
Chest computed tomography
Ultrasound, PET and other techniques
References
7. Clinical Presentation
Incubation period
Asymptomatic cases
Symptoms
Fever, cough, shortness of breath
Musculoskeletal symptoms
Gastrointestinal symptoms
Otolaryngeal symptoms (including anosmia)
Cardiovascular symptoms and issues
Thrombosis, embolism
Neurologic symptoms
Dermatological symptoms
Kidneys
Liver
Ocular and atypical manifestations
Laboratory findings
Inflammation
Hematological: Lymphocytes, platelets, RDW
Cardiac: Troponin
Coagulation: D-dimer, aPTT
Lab findings as risk factor
Clinical classification
Outcome
Case fatality rates (CFR)
CFR among health care workers, well-defined populations
CFR compared to influenza
Older Age
Sex and ethnicity
Obesity
Co-morbidities
Predisposition
Overburdened health care systems
Reactivations, reinfections
Long-term sequelae/Long COVID-19
Outlook
References
8. Treatment
Addendum 22 November
Addendum 20 November
Addendum 15 November
1. Inhibitors of the viral RNA synthesis
RdRp inhibitors
Remdesivir (Veklury®)
Favipiravir
Other RdRp inhibitors: sofosbuvir, galidesivir
Protease inhibitors (PIs)
Lopinavir
Other PIs
2. Various antiviral agents
Human recombinant soluble ACE2 (APN01)
Camostat (Foipan®)
Umifenovir
Oseltamivir
Hydroxychloroquine (HCQ) and chloroquine (CQ)
3. Monoclonal Antibodies and Convalescent Plasma
REGN-COV2
Other mAbs, some key papers:
Convalescent plasma (passive immunization)
4. Immunomodulators
Corticosteroids
Interferons
JAK inhibitors
Cytokine blockers and anticomplement therapies
Other treatments for COVID-19 (with unknown or unproven mechanisms of action)
Acalabrutinib and ibrutinib
Colchicine
Famotidine
G-CSF
Iloprost
Other treatments with no effects
Azithromycin
Leflunomide
N-acetylcysteine
Outlook and Recommendations
Outpatient, mild to moderate (no risk factors)
Outpatient, mild to moderate (with risk factors)
Hospital, severe
References
9. Severe COVID-19
Definition and classification
Features, course and outcome
Spotlight: The situation in a German COVID-19 hospital
Management and mechanical ventilation
Special situations in severe COVID-19
Prone positioning
Extracorporal Membrane Oxygenation (ECMO)
Tracheostomy
Lung Transplantation
References
10. Comorbidities
Hypertension and cardiovascular comorbidities
Treatment of hypertension during the pandemic
Treatment of coronary heart disease during the pandemic
References
Diabetes mellitus
References
COPD and smoking
References
HIV infection
References
Immunosuppression (other than HIV)
References
Cancer
References
Transplantation
References
Other comorbidities
Dialysis
Neuropsychiatric
Various
11. Pediatrics
SARS-CoV-2 infection in children
Common coronaviruses in children: tropism, incubation period and spreading
Epidemiology of COVID-19 in children
Natural course and risk factors for complications
Pathophysiology and immunopathology
Transmission
Vertical transmission
Horizontal transmission
Diagnosis and classification
Laboratory and radiology findings
Symptoms and signs: Acute infection
Children and adolescents
Neonates and infants
Pediatric inflammatory multisystem syndrome temporarily associated with SARS-CoV-2 (PIMS-TS) (or synonym Multisystem Inflammatory Syndrome in Children (MIS-C) or Kawasaki-like Disease
Management
Infection control in the medical setting
Infection control outside the medical setting
Supportive treatment (respiratory support, bronchodilatation therapy, fever, superinfection, psychosocial support)
Treatment of respiratory failure
COVID-19-specific drug treatment
When to treat with drugs
Inhibitors of viral RNA synthesis
Inhibitors of viral entry
Immunomodulatory drug treatment
Immunotherapy
PIMS / MIS-C
References
12. The First Eight Months
Dezember - March
Sunday, 1 December
Thursday, 12 December
Monday, 30 December 2019
Tuesday, 31 December 2019
Thursday, 1 January
Friday, 3 January
Sunday, 5 January
Tuesday, 7 January
Friday, 10 January
Sunday, 12 January
Monday, 13 January
Tuesday, 14 January
Saturday, 18 January
Monday, 20 January
Wednesday, 22 January 2020
Thursday, 23 January
Friday, 24 January
Saturday, 25 January
Monday, 27 January
Tuesday, 28 January
Thursday, 30 January
Friday, 31 January
Sunday, 2 February
Thursday, 6 February
Friday, 7 February
Saturday, 8 February
Monday, 10 February
Tuesday, 11 February
Wednesday, 12 February
Thursday, 13 February
Wednesday, 19 February
Thursday, 20 February
Saturday, 22 February
Sunday, 23 February
Monday, 24 February
Tuesday, 25 February
Wednesday, 26 February
Friday, 28 February
Saturday, 7 March
Sunday, 8 March
Monday, 9 March
Tuesday, 10 March
Wednesday, 11 March
Thursday, 12 March
Friday, 13 March
Saturday, 14 March
Sunday, 15 March
Monday, 16 March
Tuesday, 17 March
Thursday, 19 March
Friday, 20 March
Sunday, 22 March
Monday, 23 March
Tuesday, 24 March
Wednesday, 25 March
Thursday, 26 March
Friday, 27 March
Sunday, 29 March
Monday, 30 March
April
Wednesday, 1 April
Thursday, 2 April
Friday, 3 April
Saturday, 4 April
Sunday, 5 April
Tuesday, 7 April
Wednesday, 8 April
Thursday, 9 April
Friday, 10 April
Saturday, 11 April
Sunday, 12 April
Monday, 13 April
Tuesday, 14 April
Wednesday, 15 April
Friday, 17 April
Saturday, 18 April
Sunday, 19 April
Monday, 20 April
Tuesday, 21 April
Thursday, 23 April
Sunday, 26 April
Monday, 27 April
May
Friday, 1 May
Sunday 3 May
Monday, 4 May
Tuesday, 5 May
Wednesday, 6 May
Thursday, 7 May
Friday, 8 May 2020
Sunday, 10 May
Monday, 11 May
Tuesday, 12 May
Wednesday, 13 May
Friday, 15 May
Saturday, 16 May
Monday, 18 May
Wednesday, 20 May
Thursday, 21 May
Friday, 22 May
Saturday, 23 May
Wednesday, 27 May
Sunday, 31 May
June
Wednesday, 3 June
Tuesday, 4 June
Friday, 5 June
Saturday, 6 June
Sunday, 7 June
Monday, 8 June
Tuesday, 9 June
Wednesday,V 10 June
Thursday, 11 June
Friday, 12 June
Saturday, 13 June
Sunday, 14 June
Monday, 15 June
Tuesday, 16 June
Wednesday, 17 June
Thursday, 18 June
Friday, 19 June
Sunday, 20 June
Week 26
Sunday, 21 June
Monday, 22 June
Wednesday, 24 June
Thursday, 25 June
Friday, 26 June
Saturday, 27 June
Week 27
Sunday, 28 June
Monday, 29 June
Tuesday, 30 June
July
Wednesday, 1 July
Thursday, 2 July
Friday, 3 July
Saturday, 4 July
Week 28
Sunday, 5 July
Monday, 6 July
Tuesday, 7 July
Wednesday, 8 July
Thursday, 9 July
Friday, 10 July
Saturday, 11 July
Week 29
Sunday, 12 July
Monday, 13 July
Tuesday, 14 July
Wednesday, 15 July
Thursday, 16 July
Friday, 17 July
Saturday, 18 July
Week 30
Monday, 20 July
Tuesday, 21 July
Wednesday, 22 July
Thursday, 23 July
Friday, 24 July
Saturday, 25 July
Sunday, 26 July
Monday, 27 July
