L10 Immunity to Covid-19

Question 1

is covid-19 double or single stranded? DNA or RNA?

Answer 1

single stranded RNA virus

Question 2

which part of the virus structure is responsible for variants of this virus

Answer 2

the spike glycoprotein

Question 3

name the domain of the spike protein where the most changes are seen in variants of SARS-CoV2

Answer 3

the RBD domain, receptor binding domain which binds to ACE2.

Question 4

where does omicron have a higher affinity for replication within the respiratory system?

Answer 4

omicron has been shown to replicate 70 times faster in cultured bronchi tissue. much less efficient at replicating in the lung epithelia.

Question 5

which variant(s) of SARS-CoV2 has shown higher levels of replication in the lower respiratory tract?

Answer 5

delta has higher levels in LRT than Omicron

Question 6

average incubation period for omicron

Answer 6

3-5 days

Question 7

when is an individual most infectious after infection with omicron?

Answer 7

1-2 days before the onset of symptoms

Question 8

How do variants emerge?

Answer 8

The more people that are infected, the greater the chance of mutations arising. These mutations/variants give the virus an evolutionary advantage.

Question 9

explain natural selection for mutants of the virus

Answer 9

natural selection for mutants allows the virus to propagate more efficiently and become the predominant strain of the virus.

Question 10

Which animal did Covid-19 originate in?

Answer 10

bats, COVID-19 most similar (96%) to Bat coronavirus RaTG13

Question 11

describe how covid is transmitted from person to person

Answer 11

spread via respiratory droplets which can be either inhaled or deposited on muscosal surfaces.
respiratory droplets released via talking and coughing.

Question 12

why do children and adolescents have a lower susceptibility to infection than adults?

Answer 12

this is because kids and teens have underlying protection as they were likely infected with coronaviruses as an infant, more recently than adults

Question 13

when does virus shedding most commonly occur?

Answer 13

most often before symptom onset or a diagnosis

Question 14

peak infectiousness from covid?

Answer 14

2 days prior to onset of symptoms

Question 15

which age group is associated with higher viral loads?

Answer 15

over age 60 years

Question 16

What are the risk factors for severe disease (COVID-19 infection)?

Answer 16

Age (life-threatening disease increases sharply over age 65)
Male patients more likely to suffer severe Covid-19 infection
Diabetes
Hypertension
Obesity
COPD
Chronic Kidney Disease

Question 17

common symptoms (omicron and severe infections)

Answer 17

omicron: cough, stuffy/runny nose, fatigue, sore throat, headache, fever.
severe cases: pneumonia with fever, dry cough, dyspnea, pulmonary infiltrates.

Question 18

which variant is loss of smell/taste associated with?

Answer 18

Delta

Question 19

name the protein which helps the virus gain access to the host cell

Answer 19

Transmembrane protease serine-2 (TMPRSS2) is critical for the fusion of the virus with the host cell membrane and its subsequent entry into the cell

Question 20

which part of the respiratory tract is TMPRSS2 present most?

Answer 20

in the LRT, not as common in URT.

omicron does not bind very well to TMPRSS2 hence, less pathogenicity.

Question 21

name another protease which also is involved in covid-19 infections

Answer 21

FURIN. can cleave a unique amino acid sequence (PRRA) located between S1 and S2 domains of the spike protein.

Question 22

define hypoxemia

Answer 22

lower levels of oxygen in the blood than normal

Question 23

what part of the virus does TLR7/TLR8 recognise?

Answer 23

ssRNA

Question 24

what part of the virus does TLR3 recognise?

Answer 24

any dsRNA intermediates.

Question 25

what activates the inflammasome?

Answer 25

viral proteins ORF3a and ORF8b

Question 26

What results from triggering NF-κβ and IRF transcription factors? Which cytokines and interferons?

Answer 26

Cytokine release: IL-1β, IL-6, TNF-α, IL-8, IL-18 | Interferons: IFNα, IFNβ, Type III IFN

Question 27

Is there lower or higher production of interferons in the lungs in Covid compared to other respiratory viruses?

Answer 27

There is lower IFN production in the early stages of the Covid infection than other respiratory infections. This is a way that Covid evades the innate immune system.

Question 28

is late stage disease and prolonged IFN production associated with better or worse outcomes?

Answer 28

worse outcomes, possibly due to chemokine and inflammatory cell infiltration of the lung

Question 29

severe covid infection is associated with impaired response of which component of the immune system?

Answer 29

the interferon response.

Question 30

at what stage of disease must recombinant interferons be administered?

Answer 30

must admin early in disease as late admin can actually worsen condition.

Question 31

What is the function of interferons in relation to viruses?

Answer 31

IFNs trigger anti-viral responses in neighbouring cells

Question 32

Do covid antibodies decay over time?

Answer 32

Yes, this makes reinfection possible.

Question 33

How long have long-life plasma B cells (LLPCs) been shown to survive in the bone marrow?

Answer 33

Up to 11 months

Question 34

What is associated with somatic mutation in VH genes in germinal centres?

Answer 34

This mutation is associated with the production of non-neutralising antibodies.

Question 35

Which components of the COVID-19 virus is the antibody response tailored to?

Answer 35

The Spike protein and nucleocapsid proteins

Question 36

Describe the T cell response to Spike proteins in Omicron variant of COVID-19

Answer 36

Spike protein mutations in Omicron are still recognised by T cells due to the presence of conserved peptides on the Spike (glyco)protein

Question 37

what is acute respiratory distress syndrome?

Answer 37

ARDS is characterised by difficulty breathing and low blood oxygen levels due to fluid build-up in the lungs. the fluid build-up prevents proper transfer of oxygen from the air into the the body and removing carbon dioxide.

Question 38

Disease severity and death is associated with drastically increased serum levels of which inflammatory mediators?

Answer 38

IL-6, IL-8, TNFα, IP10

Question 39

Which immune cells appear 'sluggish' in severe Covid-19?

Answer 39

Neutrophils and monocytes

Question 40

Which cell type has an opposite to normal function in severe Covid?

Answer 40

Monocytes are shown to be pro-inflammatory

Question 41

treatment for ARDS

Answer 41

extra oxygen via breathing machine, needs quick onset (within a few days) due to potential risk of scarring and permanent reduced function in alveoli.

Question 42

Laboratory tests to indicate severe Covid-19 infection

Answer 42

- Elevated C-reactive protein (CRP) - produced in liver in response to infection - Elevated D-dimer: fibrin degradation product present in blood after a clot - Elevated neutrophils: of an immature phenotype - Decreased levels of T and B lymphocytes

Question 43

Examples of monoclonal antibodies to reduce 'Cytokine Storm'

Answer 43

IL-6 inhibitor Siltuximab, or IL-6 receptor inhibitor Tocilizumab.

Question 44

Adverse effects of dexamethasone (glucocorticoid)

Answer 44

It is potent so it has many side effects. It can inhibit host response to pathogens, leading to immunosuppression

Question 45

Effects of glucocorticoids on NF-κβ activation

Answer 45

Activation of NF-κβ by cytokines is blocked by glucocorticoids. Glucocorticoid-receptor complexes bind to the p65 subunit of NF-κβ. This prevents NF-κβ activation of inflammatory genes.

Question 46

antivirals for covid-19, indications, risk reduction, what stage of disease

Answer 46

emergency use in mild/moderate cases, 50% risk reduction for hospitalization and death, 5 days after symptoms

Question 47

Example of passive immunisation

Answer 47

Inject monoclonal antibodies into patient, protection wears off

Question 48

How do DNA and RNA vaccines work? List the advantages and disadvantages

Answer 48

Use DNA/RNA molecules to teach the immune system how to target key viral proteins. Adv: easy and quick to design Disadv: never been done before, none in use currently

Question 49

What is the basis for Moderna and Pfizer vaccines?

Answer 49

mRNA from Spike gene

Question 50

How do live attenuated vaccines work? What are the adv & disadv

Answer 50

Weakened version of virus Adv: stimulates robust immune response without causing serious disease Disadv: may not be suitable for immunocompromised Example: MMR vaccine

Question 51

How does an inactivated vaccine work? List the adv & disadv

Answer 51

Inactivated vaccine uses the whole virus but it is killed first by chemicals or heat. Adv: safe Disadv: not as effective as a live virus Example: Polio, Sinovax (Chinese Covid-19 vaccine)

Question 52

subunit vaccine how it works, adv and disadv

Answer 52

Uses a piece of virus surface to focus immune system on a single target Adv: focuses on single target, cannot cause infection Disadv: may not induce strong response Example: Hepatitis B, pertussis, HPV

Question 53

viral vector vaccine how it works, adv, disadv

Answer 53

Uses harmless virus to deliver viral genes to induce immunity Adv: stronger response Disadv: careful selection of safe virus, immune response to vector can reduce efficacy Example: Astrazeneca, Janssen

Question 54

What are the two different Spike protein conformations?

Answer 54

1. Pre-fusion: 'standing up' conformation (Moderna mRNA, Pfizer, J&J) 2. Post-fusion: flat, 'lying down' conformation (Spike changes when it fuses with ACE receptor)

Question 55

nucleotide modification in mRNA vaccines

Answer 55

replacing uridine with pseudouridine, prevents mRNA degradation.

Question 56

Which method of vaccine delivery may be preferred to intramuscular?

Answer 56

Intranasal delivery