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MB4030 > L10: COVID-19 > Flashcards

L10: COVID-19 Flashcards

1
Q

What are the 4 common coronaviruses circulating in the human population?

A
  • OC43
  • HKU1
  • 229E
  • NL63
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2
Q

What type of virus is SARS-CoV-2?

A

positive-sense ssRNA enveloped virus with a lipid bilayer

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3
Q

What 2 large genes does the SARS-CoV-2 genome encode?

A

ORF1a and ORF1b

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4
Q

How do variants emerge?

A
  • Survival of the fittest
  • Natural selection for mutants
  • Production of escape mutations from immunocompromised patients with persistent infection
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5
Q

Which COVID-19 protein is the most immunogenic?

A

the Spike protein

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6
Q

What does the Spike protein bind to?

A

ACE-2 receptor

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7
Q

What protease is critical for the fusion of the virus with the host cell membrane and its subsequent entry into the cell?

A

TMPRSS2 (transmembrane protease serine-2)

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8
Q

ARDS is characterised by?

A

dyspnoea and hypoxemia

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9
Q

What is characteristic of severe COVID?

A

Cytokine storm - increased concentrations of cytokines IL-6, IL-8 & TNFα, and chemokine IP-10 in serum

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10
Q

Where in the body is there a high abundance of inflammatory macrophages in a patient with severe COVID?

A

lungs

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11
Q

What happens the interferon response in severe COVID?

A

it becomes dysregulated

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12
Q

Which cells appear to be functionally sluggish in severe COVID?

A

myeloid cells like neutrophils and monocytes
(high numbers made but are dysfunctional)

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13
Q

What can be seen in the blood of patients with severe COVID-19 during an acute infection?

A
  • neutrophilia
  • monocytosis
  • fever
  • functionally exhausted NK cells
  • exhausted DCs, leading to low IFN levels in blood
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14
Q

What do NETs do?

A
  • promote spread of virus
  • cause thrombosis & organ damage
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15
Q

3 most common symptoms of long COVID?

A
  • shortness of breath
  • cognitive dysfunction (‘brain fog’)
  • fatigue
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16
Q

Where do the majority of mutations in the Omicron variant take place?

A

in the RBD of the Spike protein

17
Q

What are new COVID-19 variants of concern?

A
  • BA.2.75.2
  • BQ.1.1
18
Q

What strain of COVID-19 have we been vaccinated with?

A

the original Wuhan wild-type (WT)

19
Q

Severe COVID-19 markers

A
  • increased levels of IL-6, IL-8, TNFα & IP-10
  • elevated CRP
  • elevated D-dimer
  • elevated neutrophils (appear to be of an immature phenotype)
  • decreased lymphocytes (lymphopenia)
  • serum bicarbonate
  • thrombocytopenia
20
Q

Innate sensing of COVID-19

A
  • TLR7/TLR8 senses virus ssRNA (mainly by pDCs)
  • TLR3 senses dsRNA intermediates
  • RIG-1/MDA5 senses cytoplasmic viral RNA
  • TLR4 senses Spike protein
  • TLR2 senses envelope protein
21
Q

What does innate sensing trigger in COVID-19?

A

NF-κβ and IRF activation, leading to the production of cytokines (IL-1β, IL-6, TNFα, IL-8, IL-18) and IFN-α, -β, & -λ

22
Q

Prolonged __ production in late stage disease correlates with a worse outcome.

A

IFN

23
Q

COVID-19 patients have vast quantities of __ __.

A

antibody-secreting plasmablasts

24
Q

What are lost in the lymph nodes and spleen of severe COVID patients?

A

germinal centres (Bcl6+ GC B cells and Bcl6+ Tfh cells are also markedly reduced)

25
Q

In severe COVID, abundant __ cells and aberrant __ production are seen in lymph nodes.

A

abundant Th1 cells
aberrant TNFα

26
Q

Why is the loss of germinal centres in severe COVID-19 significant?

A

This loss does not give rise to long-lived B cell memory or high affinity B cells

27
Q

What immune responses are not substantially affected by COVID-19 variants?

A

CD4+ and CD8+ T cell immune responses

28
Q

Why is a robust T cell memory important in COVID?

A

because CD4+ and CD8+ T cell responses play an important role in resolving infection and moderating disease severity

29
Q

What is another name for the BioNTech/Pfizer COVID-19 vaccine?

A

BNT162b2

30
Q

What is another name for ‘adapted vaccines’, and what do they contain?

A

updated boosters - contain mRNA of the original WT strain and mRNA in common between the Omicron BA.4/BA.5 lineages

31
Q

2 examples of COVID-19 antivirals

A
  • Molnupiravir (RNA-dependent RNA polymerase inhibitor)
  • Paxlovid (PF-07321332/Ritonavir) - SARS-CoV-2 protease inhibitor
32
Q

What is the benefit of the inhibitors as COVID-19 antivirals?

A

they tend to be quite resistant to variants

33
Q

Examples of mAbs to COVID-19 Spike protein

A
  • Regeneron: REGEN-COV (Casirivimab + Imdevimab): not very effective against Omicron
  • Eli Lilly: Bamlanivimab + Etesevimab
  • Bebtelovimab: active against Omicron variant

MB4030 (10 decks)

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