Respiratory viral infections and COVID Flashcards
Explain how respiratory viruses cause diseases with a range of severity
They can make you feel unwell
They can make you ill enough to go to the GP
They can hospitalise you
They can kill you
What kind of viruses are Rhinoviruses?
Picornaviruses
Positive strand RNA virus
How many serotypes of rhinovirus exist?
Over 150 different serotypes
What happens when someone is infected with rhinovirus?
Does not spread to the lower respiratory tract because they replicate best at a few degrees below normal body temp
Mainly confined to the nose
Rarely cause fever
Give examples of respiratory viruses beyond the common cold
Rhinoviruses new subtype C
Influenza viruses types A, B and C
Paramyxoviruses - RSV, hMPV, parainfluenza viruses 1-5
Adenoviruses
Coronaviruses
Describe RSV
Main cause of infant hospitalisation and severe bronchiolitis
Life-long reinfection is common
Can hospitalise of even kill the old
Associated with wheezing or asthma in later life
Describe immunity to RSV
Some protective Ig are inherited by placental transfer and can be acquired from breastfeeding
Protective Ig are made in response to RSV but this is a poor response in neonates
Despite repeated reinfection our Ig response declines with age
Where are RSV infections restricted to?
Predominantly the airways
These are mucosal surfaces and are therefore protected by innate immunity and IgA
Describe IgA memory
Relatively poor and recall is slow
Sufficient to prevent more severe infections later in life
What are the problems of an immature immune system?
RSV infections show unbalanced Th1/Th2 responses
This depresses inflammatory cytokine production, CD8+ responses and IgG production meaning clearance is slow and development of memory is poor
This enhances IgE production, leading to allergy/asthma
Describe coronaviruses
Large positive single stranded RNA viruses
Common infectious agents for pigs and poultry
Very few known human coronaviruses - currently 7
What is SARS?
Severe acute respiratory syndrome
A coronavirus with no existing immunity in humans
How is SARS transmitted?
By droplets
From Civet cats
Civets got it from bats
What is the main route of virus shedding for SARS?
Through faecal material that gets aerosolised
Symptoms show up long before virus shedding
Describe COVID-19
First cases describes DEC 2019 in Wuhan
Wuhan suffered 80,000 cases and 4,000 deaths
Wuhan fish and live animal wholesale market case cluster suggested transmission from animals
A coronavirus but not SARS-CoV
What are the varied symptoms of COVID-19?
Fever
Cough
Shortness of breath
Breathing difficulties
More severe cases can cause pneumonia, SARS, kidney failure and even death
Where did SARS-CoV-2 come from?
Zoonotic transmission even in Wuhan market
Accidental escape of cultured stock from lab
Accidental escape of GMO virus stock from a lab
Describe SARS-CoV-2 and the IFN system
SARS-CoV-2 is extremely sensitive to IFN in vitro - omicron especially
SARS-CoV-2 grows much better in cells that cannot respond to IFN
SARS-CoV-2 encodes multiple antagonists of the IFN system
How is the IFN system affected in patients with COVID?
13.7% of patients with life threatening COVID have autoantibodies against type 1 IFN
3.5% of patients with life-threatening COVID have genetic defects in their IFN signalling pathways
What do mild SARS-CoV-2 infections generate?
Poor antibody responses
What do more serious SARS-CoV-2 infections generate?
High titres of neutralising antibody
What do human antibodies target in SARS-CoV-2?
Generally multiple sites on spike protein
Antibodies also raised against nucleocapsid and M protein
What are the vaccines against SARS-CoV-2?
mRNA - Pfizer-Biontech, Moderna
Subunit - Novavax
Viral vectors - ChAsOx, Sputnik, J & J - all give some neutralising Abs and seem to give good protection but not good at limiting spreading
These vaccines are against the original Wuhan strain
What are the variants in spike protein?
N501Y
P681H
H69 and Y144/155 deletions
What does the N501Y spike variant do?
Helps the virus latch on more tightly to human cells
The mutation is not likely to help the virus evade current vaccines
What does the P681H spike variant do?
May help infected cells create new spike proteins more efficiently
What do the H69-V70 and Y144/145 deletions do?
Alter the shape of the spike and may help it evade some antibodies
