Respiratory viral infections and COVID

Question 1

Explain how respiratory viruses cause diseases with a range of severity

Answer 1

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

Question 2

What kind of viruses are Rhinoviruses?

Answer 2

Picornaviruses
Positive strand RNA virus

Question 3

How many serotypes of rhinovirus exist?

Answer 3

Over 150 different serotypes

Question 4

What happens when someone is infected with rhinovirus?

Answer 4

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

Question 5

Give examples of respiratory viruses beyond the common cold

Answer 5

Rhinoviruses new subtype C
Influenza viruses types A, B and C
Paramyxoviruses - RSV, hMPV, parainfluenza viruses 1-5
Adenoviruses
Coronaviruses

Question 6

Describe RSV

Answer 6

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

Question 7

Describe immunity to RSV

Answer 7

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

Question 8

Where are RSV infections restricted to?

Answer 8

Predominantly the airways
These are mucosal surfaces and are therefore protected by innate immunity and IgA

Question 9

Describe IgA memory

Answer 9

Relatively poor and recall is slow
Sufficient to prevent more severe infections later in life

Question 10

What are the problems of an immature immune system?

Answer 10

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

Question 11

Describe coronaviruses

Answer 11

Large positive single stranded RNA viruses
Common infectious agents for pigs and poultry
Very few known human coronaviruses - currently 7

Question 12

What is SARS?

Answer 12

Severe acute respiratory syndrome
A coronavirus with no existing immunity in humans

Question 13

How is SARS transmitted?

Answer 13

By droplets
From Civet cats
Civets got it from bats

Question 14

What is the main route of virus shedding for SARS?

Answer 14

Through faecal material that gets aerosolised
Symptoms show up long before virus shedding

Question 15

Describe COVID-19

Answer 15

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

Question 16

What are the varied symptoms of COVID-19?

Answer 16

Fever
Cough
Shortness of breath
Breathing difficulties
More severe cases can cause pneumonia, SARS, kidney failure and even death

Question 17

Where did SARS-CoV-2 come from?

Answer 17

Zoonotic transmission even in Wuhan market
Accidental escape of cultured stock from lab
Accidental escape of GMO virus stock from a lab

Question 18

Describe SARS-CoV-2 and the IFN system

Answer 18

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

Question 19

How is the IFN system affected in patients with COVID?

Answer 19

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

Question 20

What do mild SARS-CoV-2 infections generate?

Answer 20

Poor antibody responses

Question 21

What do more serious SARS-CoV-2 infections generate?

Answer 21

High titres of neutralising antibody

Question 22

What do human antibodies target in SARS-CoV-2?

Answer 22

Generally multiple sites on spike protein
Antibodies also raised against nucleocapsid and M protein

Question 23

What are the vaccines against SARS-CoV-2?

Answer 23

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

Question 24

What are the variants in spike protein?

Answer 24

N501Y
P681H
H69 and Y144/155 deletions

Question 25

What does the N501Y spike variant do?

Answer 25

Helps the virus latch on more tightly to human cells
The mutation is not likely to help the virus evade current vaccines

Question 26

What does the P681H spike variant do?

Answer 26

May help infected cells create new spike proteins more efficiently

Question 27

What do the H69-V70 and Y144/145 deletions do?

Answer 27

Alter the shape of the spike and may help it evade some antibodies