COVID Reference ENG 2021.6 (13 January 2021)

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