21st Century Pandemics: Influenza and COVID Flashcards

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1
Q

What are Pandemic Ingredients?

A
  • A pandemic virus will have novel antigenicity.
  • A pandemic virus will replicate efficiently in human cells.
  • A pandemic virus will transmit efficiently between people.
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2
Q

What viral pathogens have pandemic potential?

A
  • Influenza
  • SARS-CoV-2
  • Nipah
  • West Nile Virus
  • Dengue
  • Zika
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3
Q

How many of us are infected by seasonal influenza?

A
  • 10% every winter
  • 500,000 deaths world-wide
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4
Q

What viruses pose a constant threat?

A

Avian influenza viruses

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5
Q

World War I lasted 4 years from 1914 to 1918 and resulted in 16 million deaths worldwide.
How many people died as a result of the 1918 influenza pandemic?

  1. 50,000
  2. 500,000
  3. 5 million
  4. 50 million
A

50 M

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6
Q

The natural reservoir of influenza A viruses is

  1. Pigs
  2. Chickens
  3. Ducks
  4. Tigers
A

Ducls

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7
Q

What are aquatic birds natural hosts to?

A

to 16 atnigenically distinct influenza A viruses.

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8
Q

Describe the structure of influenza virus?

A
  • 8 segmented single stranded negative sense RNA virus
  • Important proteins: Haemagglutinin and neuraminidase - spike protein
  • Haemaglutinnin - 16 flavours
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9
Q

Why don’t we catch flu from birds?

A
  • Viruses in ducks not well evolved
  • To affect humans
  • Ducks - water Borne
  • Humans - airborne
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10
Q

What ad to happen to influenza virus from birds to humans?

A
  • Mutate to
    • Replicate efficiently in human airway
    • Change spike protein to transmit airborne in humans
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11
Q

What is ANP32? How is it different in birds?

A

Protein in the human cell nucleus that is essential host cofactor - supports influenza polymerase activit.

In birds - extra 33 exon

In human - no 33 exon (virus mutates an utilises this cofactor)

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12
Q

What mutation Is responsible for the polymerase adaptation to mammals ?

A
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13
Q

What is a reasserted virus?

A
  • Human adapted virus and avian virus enter the same cell
  • Because the genetic material neatly separated in 8 segments, both viruses share this and make a reasserted virus → pandemic potential
  • Also called Antigenic Shift
  • Can occur in pigs due to close proximity
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14
Q

What else apart from antigenic shift must occur to give a virus pandemic potential?

A

The haemagglutinin must also undergo a mutation - fir in human cells and transmissible through air

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14
Q

What do viruses have to overcome in order to successfully infect human? How do some do this?

A
  • Penetrate mucus in airway
  • Human viruses - mutate to be able to bind to receptors in epithelium
  • Avian viruses can latch on to receptors in LRT
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15
Q

What is the significance of the haemagglutinin protein being pH sensitive?

A

Virus must release genetic material in endosome

pH of airborne droplets is low

Avian influenza - very sensitive to low pH - cannot be transmitted in airborne droplets

16
Q

How do we respond to pandemics?

A

• Non pharmaceutical interventions

  • Antiviral drugs
  • Vaccines
17
Q

Several antiviral drugs already exist for influenza, and are licensed for use in the clinic. However unlike HAART for HIV we don’t use them together.

True of false?

A

True - not licensed

18
Q

Describe the influenza virus replication cycle.

A
19
Q

What important process occurs in the budding out process in the viral replication cycle?

A
  • Neuraminidase - needs to cut itself away from the receptor contains silalic acid
  • If pt takes naeuraminidase inhibitor drugs (ralenza or tamiflu) → tethers virus → halts virus spread
20
Q

What does baloxavir target?

A

PA endonuclease

21
Q

The influenza vaccine given to those at greater risk of complications from flu in the UK is

  • A live attenuated virus
  • A purified fraction containing HA and NA of an inactivated virus
  • A purified HA protein expressed in insect cells
  • An immunoglobulin fraction from sera of immune patients.
A

A purified fraction containing HA and NA of an inactivated virus

22
Q

How is the influenza vaccine strain selected and produced?

A
23
Q

What influenza vaccine do we use in the UK?

A
24
Q

How could we make a universal vaccine for all flus?

A
  • target conserved stem/stalk domain in HA protein
25
Q

What part of the haemagglutinin protein do current vaccines target?

A
26
Q

500,000 people die each year from seasonal influenza. The number of deaths from COVID worldwide since January 2020 is

  1. 60 million
  2. 6 million
  3. 600,000
  4. 60,000
A

6 M

27
Q

What is a coronavirus? What is the structure?

A

RNA genomes, single stranded positive sense RNA, very large genomes… 30kb!

Enveloped virions. 100nm

Family of Nidovirales- a nested set of mRNAs from one large genome

Seven coronaviruses have infected humans:

  • OC43, 229E, NL-63 and HKU-1 cause 20-30% common colds
  • SARS and MERS are zoonotic .
28
Q

How do SARS and SARS CoV2 enter cells?

A

Bind to ACE2 - only expressed on 2% of cells in the respiratory tract also on GI tract

29
Q

The most likely origin of SARS CoV2 is:

  1. Wild waterfowl
  2. Horseshoe bats
  3. Created in a laboratory
  4. Pangolins
A

Horseshoe bats

30
Q

What is the time course of SARS CoV2 infection and COVID19?

A
31
Q

A COVID patient in ITU is most likely to benefit from

  • Kaletra, a combination of lopinavir and ritonavir usually used to treat HIV
  • Hydroxychloroquine, an antimalarial
  • Remdesivir a nucleoside analogue
  • Dexamethasone, a steroid.
A

Dexamethasone, a steroid.

32
Q

Describe the use of dexamethasone in the tx of COVID.

A

• Cheapandextensively used steroid

RECOVERY trial found Dex was effective in those receiving oxygen or ventilated.

Reduceddeathsinillest cohort by 1/3.

Now standard of care in UK.

33
Q

What monoclonal antibodies are used in COVID?

A

Regereneron

Sotrovimab - GSK antibody

Target Spike

34
Q

What are the use small molecule antivirals in Covid?

A

Molnupiravir: targets polymerase, nucleoside analgue

Paxlovid: targets protease

35
Q

What are the covid vaccines?

A
  • Inject mRNA (modified-nucleoside, purified mRNA)
    • Used perfusion spike state
  • Host makes proteins antigen
36
Q

Describe the different variants of COVID?

A
37
Q

Why is Omicron less well controlled by current vaccines?

A
  • Large number of spike mutations that affect antibody neutralisation