41. Viral Disease Outbreak Flashcards
Overview of coronavirus
- recongised in a range of animal species, widespread among mammals and birds
- can cross species barriers to infect new animal species
- has 4 groups - alpha, beta, gamma, delta - based on antigenic relationships of spike, membrane and nucleocapsid proteins
- has a proof reading mechanism to reduce mutation
Morphology and structure of coronavirus
- pleomorphic and enveloped
- club-shaped surface projections - trimers of spike protein - classic crown appearance (distinctive arrangement of spikes from surfaces)
- non-segmented single-stranded RNA genome of around 30kb - largest known RNA virus
- helical nucleocapsid
Replication of coronavirus
- attach to receptors on host cells via S protein
- tissue tropism mainly determined by the S1 part of S protein and by the type and distribution of receptors on host cells
- viruses replicate in host cell cytoplasm with a growth cycle of 10-12 hrs
Types of coronavirus and immunity in humans
- four seasonal human coronaviruses - common cold
- immunity to this is short
Transmission of human covid
- respiratory droplets
- direct or indirect contact
Virus genetics of covid-2
- enveloped single-stranded RNA virus
- beta-coronovirus
- 79% nucelotide similar to SARS virus
- 96.2% same to bat covid RaTG13
- most closely related to virus from horseshoe bat
SARS 2003 overview
- severe acute respiratory syndrome
- first occurred in china 2002
- SARS-CoV animal virus in origin, natural reservoir (crossed species barrier to humans)
- transmission in droplets, direct/indirect contact, excreted in faeces, on smooth surfaces
- spectrum of illness of severe respiratory disease to milder presentations - fever
- inflammatory damage - increased levels of proinflammatory cytokines associated with pulmonary inflammation and severe lung damage
Impacts of SARS
- social and economic disruption
- impact on travel internationally
- impact on health services
Explain MERS 2012
- middle eastern respiratory syndrome
- reported in saudi arabia - spread to other countries
- MERS-CoV, a coronavirus
- MERS-CoV endemic in dromedary camels and causes outbreaks of zoonotic origin in Arabian peninsula
What is MERS like?
- 2-14 day incubation
- severe acute respiratory illness - fever, cough, shortness of breath
- more severe in older, weakened immune system, chronic disease like cancer, renal disease, diabetes
- transmission from infected patient secretions, close contact
Mutation rate of SARS-CoV2
- relatively low - around 2.5 mutations per genome per month
- similar to other covids
- ongoing genome sequencing is critical to understadning diversity of virus and vaccine development
Virus structure of SARS-CoV-2
- viral envelope coated by spike glycoprotein, envelope and membrane proteins
- host cell binding and entry mediated by spike proteins
Viral entry and interaction of SARS-CoV-2 in humans
- enters human host cell by binding to human angiotensin-converting enzyme 2 (ACE2) receptor with viral spike protein
- distribution of ACE2 receptors explains sites of infections and symptoms
- receptors found on epithelium of other organs like intestine/endothelial cells in kidney and blood vessels
- higher infectivity and rates or transmission than related viruses like SARS and MERS
How infectious is SARS-CoV-2?
- highly
- R0 to be around 2.5 to 3.51 which is higher than SARS/MERS
What is the basic reproduction number?
- R0
- average number of secondary infections produced by typical case of infection in a population where everyone is susceptible
- used to measure transmission potential
Why is SARS-CoV-2 so infectious?
- infects upper respiratory tract as oppose to lower tract in SARS/MERS
- viral particles have less distance to travel in airway to reach target cells (easy transmission)
- also structural differences in surface proteins and viral load kinetics of SARS-CoV-2
Route of transmission for SARS-CoV-2
- infected respiratory droplets
- aerosols
- direct/indirect contact with nasal, conjunctival, oral mucosa
- respiratory particles inhaled or deposited on mucus membranes
- fomites
- still viable on smooth surfaces at lower temp and humidity for many days like air-conditioned stainless steel
Both SARS 1 and 2 are readily inactivated by …
commonly used disinfectants
Duration of infection of SARS-CoV-2
- peak load is observed at time of symptom onset or in first week of illness
- highest infectiousness potential just before or in first 5 days of symptoms
Disease severity of SARS-CoV-2
- rages from asymptomatic to lethal
- dysregulated immune responses can contribute to severe disease
- excessive immune response to SARS-CoV-2 reported, high levels of cytokine release and ‘cytokine storm’
Systemic impact of SARS-CoV-2
- in severe cases, triggers aberrant host immune response
- overproduction of pro-inflammatory cytokines
- cytokine storm
- acute respiraotry distress syndrome
- septic shock/multi-organ dysfunction
It is suggested that SARS-CoV-2 isn’t limited to airway cells but …
Explain
- cardiac, gut and immune cells can be targeted too
- secondary results on inflammation and blood clotting suspectedly
- affect multiple organ systems in body
- chronic symptoms caused like long lasting fatigue, shortness of breath
SARS-CoV-2 has 2 types of variant. Name them
- variant of interest
- variant of concern
Explain SARS-CoV-2 variant of interest
- has mutations that are suspected or known to cause significant changes and circulating widely
Explain SARS-CoV-2 variant of concern
- known to spread easily, cause more severe disease, escape body’s immune response and change clinical presentation
Explain SARS-CoV-2 Omicron variant
- most heavily mutated variant to emerge so far and carry those similar to previous variants of concern
- associated with enhanced transmissibility and partial resistance to vaccine induced immunity
- unusually large number of genetic changes - particularly in spike protein