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a path 3 > MICRO: ‘21st century pandemics: influenza and COVID’ > Flashcards

MICRO: ‘21st century pandemics: influenza and COVID’ Flashcards

1
Q

What are three main features of pathogens causing a pandemic?

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

List 4 viruses with pandemic potential.

A
  • Inflenza
  • Coronavirus (SARS-COV2)
  • Nipah - found in Bangladesh etc
  • Insect borne:
    • West Nile virus
    • Dengue
    • Zika
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3
Q

When have influenza viruses caused pandemics?

A
  • 1918 - Spanish
  • 1957
  • 1968
  • 2006 - Swine flu
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4
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 million

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5
Q

The natural reservoir of influenza A viruses is

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

Ducks - Aquatic birds are natural hosts to 16 antigenically distinct influenza A viruses

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6
Q

What are the characteristics of

A

8 segmented

single stranded

DNA virus

Haemagglutin (HA) and Neuraminidase (NA)

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7
Q

How must an avian influenza virus mutate to infect humans?

A

To jump from birds to humans an avian-origin influenza must mutate to:

  • Replicate efficiently in the human airway.
  • Transmit through the air between people (rather than water)
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8
Q

What is the spike protein in influenza called?

A

Haemagglutinin

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9
Q

How does an avian influenza gain the capacity to replicate in humans? What is the most common mutation?

A
  • Virus enters and buds into the cytoplasm
  • Enters nucelus
  • ANP32 proteins in nucelus are essential host cofactors that support influenza polymerase activity
  • For ANP32 to help it work the virus must adapt by a single amino acid change in PB2 E627K or PB2 627K (1918)
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10
Q

What further genetic changes are necessary for an avian influenza virus gain capacity to replicate in human cells?

A
  1. Reassortment –> antigenic shift (But this is not sufficient on its own )
  2. + Further HA mutations - must occur for it to replicate in the airway and be transmitted through air
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11
Q

How does pH in the respiratory tract affect influenza entry?

A

Influenza entry is pH dependent and HA protein is pH sensitive

  • pH is acidic in the URT - avian viruses cannot survive here and must mutate to do so
  • pH is neutral in the LRT
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12
Q

Summarise the steps of adaptation of avian influenza viruses to humans.

A
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13
Q

What measures are taken in a pandemic response?

A
  • Non pharmaceutical interventions - face mask, isolation, distancing
  • Antiviral drugs
  • Vaccines
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14
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 or false:

A

True - we do not combine influenza drugs together as they are not licensed for this

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15
Q

What is the MOA of NA inhibitors?

A

NA (AKA sialidase - sialic acid enyzume) is important in budding out to infect a new cell

NAi acts by inhibiting NA so that the virus is tethered to the cell and does not leave

Examples are oseltamivir (Tamiflu) and zanamivir (Relenza)

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16
Q

What is a new anti-influenza drug?

A

Baloxavir

Targets polymerase called PA endonuclease

17
Q

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

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

2 - grown in eggs

NB: live attenuated is used in children

18
Q

Influenza vaccine production

A
19
Q

What are the features of the inactivated influenza vaccine?

A
  • Split or subunit- HA rich
  • Given to those at risk
  • Short term strain specific immunity mediated by antibody to HA head
20
Q

What are the features of the live attenuated influenza vaccine?

A

Cold adapted virus limited to URT

Given to children - do not work in adults as they recognise it and do not get a good response

Broader more cross reactive immunity including cellular response

21
Q

How effective is the LAIV in children?

A

Cause a decrease in excess mortality when trialed in primary school children by protecting the vulnerable and elderly at home

22
Q

What is the major influenza viral antigen? What part do antibodies usually target and what are the implications for a universal influenza vaccine?

A

Haemagglutinin

Globular head domain parts are where antibodies usually attach but the probelm is that they are variable and so a universal vaccine would be difficult to make. The hope is to target the stem/stalk region.

Making a universal vaccine would let us use only one vaccine for all influenza viruses

23
Q

What does this show about SARS vs influenza?

A

SARS - transmitted usually if a person is symptomatic

Influenza - transmitted in asymptomatic and symptomatic

24
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 million

25
Q

How many coronaviruses infect humans?

A

Seven infect humans

OC43, 229E, NL-63 and HKU-1 cause 20-30% common colds

26
Q

What receptor does SARS and SARS-2 use to enter cells?

A

Bind to cells via Angiotensin Converting Enzyme 2 (ACE-2)

27
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

  • CoV with 96% similarity to SARS CoV2 has been found in pangolins.
  • CoV with 99% similarity found in bats in Laos
28
Q

Describe the course of SARS CoV2 infection.

A
  • Incubation is ~3 days
  • If virus load is well controlled, by day 8 they may be virus RNA positive but not infectious
  • If not, virus may become disseminated
29
Q
A
30
Q

A COVID patient in ITU is most likely to benefit from..?

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

Dexamethasone - by tume they reach ITU the virus may stop replicating.

31
Q

When is dexamethasone use in COVID patients helpful?

A

If using oxygen AND on ventilation

Severely ill patients only beyond the stage where virus is the biggest problem and rather it is the immune system which is causing problems

32
Q

Apart from dexamethasone, what other targeted therapies exist for COVID-19?

A

mAbs - Regeneron, Sotrovimab

Small molecule antivirals -

  • Molnupiravir: targets polymerase, nucleoside analgue
  • Paxlovid: targets protease
33
Q

What variants of SARS-CoV2 have arisen?

A
  • Alpha
  • Beta
  • Gamma
  • Delta
  • Omicron - 35 new mutations in the spike genes, less well controlled by current vaccines and do not protect from symptomatic disease; but associated with less severe disease

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