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Immunology > L10 Immunity to Covid-19 > Flashcards

L10 Immunity to Covid-19 Flashcards

1
Q

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

A

single stranded RNA virus

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2
Q

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

A

the spike glycoprotein

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3
Q

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

A

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

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4
Q

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

A

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

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5
Q

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

A

delta has higher levels in LRT than Omicron

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6
Q

average incubation period for omicron

A

3-5 days

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7
Q

when is an individual most infectious after infection with omicron?

A

1-2 days before the onset of symptoms

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8
Q

How do variants emerge?

A

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

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9
Q

explain natural selection for mutants of the virus

A

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

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10
Q

Which animal did Covid-19 originate in?

A

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

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11
Q

describe how covid is transmitted from person to person

A

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

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12
Q

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

A

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

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13
Q

when does virus shedding most commonly occur?

A

most often before symptom onset or a diagnosis

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14
Q

peak infectiousness from covid?

A

2 days prior to onset of symptoms

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15
Q

which age group is associated with higher viral loads?

A

over age 60 years

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16
Q

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

A

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

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17
Q

common symptoms (omicron and severe infections)

A

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

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18
Q

which variant is loss of smell/taste associated with?

A

Delta

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19
Q

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

A

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

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20
Q

which part of the respiratory tract is TMPRSS2 present most?

A

in the LRT, not as common in URT.

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

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21
Q

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

A

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

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22
Q

define hypoxemia

A

lower levels of oxygen in the blood than normal

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23
Q

what part of the virus does TLR7/TLR8 recognise?

A

ssRNA

24
Q

what part of the virus does TLR3 recognise?

A

any dsRNA intermediates.

25
Q

what activates the inflammasome?

A

viral proteins ORF3a and ORF8b

26
Q

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

A

Cytokine release: IL-1β, IL-6, TNF-α, IL-8, IL-18

Interferons: IFNα, IFNβ, Type III IFN

27
Q

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

A

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.

28
Q

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

A

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

29
Q

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

A

the interferon response.

30
Q

at what stage of disease must recombinant interferons be administered?

A

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

31
Q

What is the function of interferons in relation to viruses?

A

IFNs trigger anti-viral responses in neighbouring cells

32
Q

Do covid antibodies decay over time?

A

Yes, this makes reinfection possible.

33
Q

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

A

Up to 11 months

34
Q

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

A

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

35
Q

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

A

The Spike protein and nucleocapsid proteins

36
Q

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

A

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

37
Q

what is acute respiratory distress syndrome?

A

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.

38
Q

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

A

IL-6, IL-8, TNFα, IP10

39
Q

Which immune cells appear ‘sluggish’ in severe Covid-19?

A

Neutrophils and monocytes

40
Q

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

A

Monocytes are shown to be pro-inflammatory

41
Q

treatment for ARDS

A

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

42
Q

Laboratory tests to indicate severe Covid-19 infection

A
  • 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
43
Q

Examples of monoclonal antibodies to reduce ‘Cytokine Storm’

A

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

44
Q

Adverse effects of dexamethasone (glucocorticoid)

A

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

45
Q

Effects of glucocorticoids on NF-κβ activation

A

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.

46
Q

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

A

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

47
Q

Example of passive immunisation

A

Inject monoclonal antibodies into patient, protection wears off

48
Q

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

A

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

49
Q

What is the basis for Moderna and Pfizer vaccines?

A

mRNA from Spike gene

50
Q

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

A

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

51
Q

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

A

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)

52
Q

subunit vaccine how it works, adv and disadv

A

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

53
Q

viral vector vaccine how it works, adv, disadv

A

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

54
Q

What are the two different Spike protein conformations?

A
  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)
55
Q

nucleotide modification in mRNA vaccines

A

replacing uridine with pseudouridine, prevents mRNA degradation.

56
Q

Which method of vaccine delivery may be preferred to intramuscular?

A

Intranasal delivery

Immunology (10 decks)

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