Microbiology 19 - Influenza and Covid-19 Flashcards

1
Q

What drives zoonosis of influenza viruses from wild water fowl?

A

Antigenic drift

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2
Q

What must a mutation change to produce a pandemic-producing virus ?

A

Transmissibility between humans
Antigenic novelty

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3
Q

What is the mechanism of action of amantidine, and what is it used for?

A

Targets M2 ion channel
Used to treat strains types of influenza virus

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4
Q

3 drug classes against influenza

A
  1. Amantidine
  2. Neuraminidase inhibitor
  3. Polymerase inhibitor
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5
Q

What class of drug is oseltamivir?

A

Neuraminidase inhibitor

Neuraminidase is the enzyme (spike protein) that cleaves sialic acid to allow virus to exit the cell and infect other cells

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6
Q

What influenza vaccines are used in the UK?

A
  1. Inactivated vaccine
    - Haemaglutinnin and neuraminidase proteins
    - used in adults
  2. Live attenuated (used as a nasal spray)
    - used in children ONLY

not effective in adults because they’ve encountered the viral flu antigen before

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7
Q

What is the most important reason why SARS 2003 was so much easier to contain than SARS Covid 19?

A

Patients had easily-identifiable symptoms that developed quickly and so could be isolated - covid-19 is much more insidious!

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8
Q

Most likely origin of COVID-19

What is a likely secondary host?

A

Horseshoe bats

Likely secondary host: pangolins

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9
Q

Describe the genome of SARS-Cov2

A

Huge single-stranded RNA genome

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10
Q

How does covid bind to cells to gain entry?

A

They use their spike protein to bind to ACE2 receptor in the host

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11
Q

How long after infection is covid infectious?

A

3 days

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12
Q

From which day is COVID-19 symptomatic?

A

Day 5

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13
Q

What is the time course of covid-19 infection?

A
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14
Q

What is the predominant variant of COVID?

A

Omicron - current vaccine is less effective against it, but also causes less severe infection

Omicron has a large number of Spike mutations that affect antibody neutralization

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15
Q

Recall 2 important factors that will be at elevated serum levels in covid infection, and can be useful clinically?

A

IL-6
D-dimer

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16
Q

What benefit is remdesivir shown to have in coronavirus?

A

Shortens time to recovery

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17
Q

In which patients is dexamethosone effective at reducing coronavirus death?

A

In those who are receiving oxygen

*dexatheasone is used in ITU setting

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18
Q

Monocloncal antibodies and small molecule inhibitors for covid

A

Monoclonal: Regeneron, Sotrovimab

Small molecules:

1) Molnupiravir: targets polymerase, nucleoside analgue
2) Paxlovid: targets protease

19
Q

Natural reservoir of influenza A virus

A
  • wild birds like ducks, geese and **migratory waterfowl (mostly)**
  • From this reservoir, the virus can cross over to other animals
  • It can also end up in mammals including humans
20
Q

How does influenza enter the human cell and spread?

A
  • The virus is particularly vulnerable during the transmission phase when it is going in between people
  • They attach to cells via sialic acid receptors
  • They enter through endosomes
  • The acidity of the endosome triggers a fusion event by which it releases its genome into the cell
  • The genome then travels to the nucleus and takes over host factors to drive transcription and translation
  • New viral products are produced (proteins and genome)
  • They will assemble at the surface of the cell and bud off to produce hundreds of copies of the virus
21
Q

2 possible outcomes when avian influenza A crosses over into humans:

A

1) Sometimes they can just cause a zoonoses which is a dead end:
- can cause a severe disease but does not transmit on to other human
- People exposed to the animal can get the virus
- but not as much of a Public Health issue, as it will not cause a large outbreak
2) However, if the virus undergoes various MUTATIONS it can transform from avian to human virus:
- leading to pandemic influenza
- Pandemic influenza transforms into seasonal influenza

→ undergoes antigenic drift and human adaptation

→ changing a little bit year on year (hence vaccine is updated each year)

-Therefore, all current human influenza was originally a pandemic flu

which was originally a bird virus

-It has undergone mutations to go from a virus in birds to now infecting humans

22
Q

Why does influenza B, C and D not cause pandemics?

A

Not in animal reservoirs

Do not exist in antigenically different form to human variants

→ humans can recognise and act against them

24
Q

Can you use influenza drugs in combination?

A

No- but this is worrying as this risks viruses developing mutations against one antiviral

25
26
27
What famiy is influenza virus from?
Orthomyxoviridiae
28
Structure of influenza virus?
* enveloped virus * filamentous morphology * negative sense segmented RNA genome (8 **segments**)
29
3 key properties of a pandemic virus
1. novel antigenicity 2. can replicate well in the human airway 3. can spread rapidly between people
30
what are the different antigenic flues that affect humans each year?
1. **Influenza A H1**: peaks beginning of January 2. **Influenza A (H1N1)**- peaks end of December 3**. Influenza B** (peaks March)
31
What does the influenza vaccine given to high risk groups contain? What about the one given to children?
Purified fraction with HA and NA of inactivated virus Children: live attenuated vaccine
32
What is the natural reservoir of influenza virus?
Ducks
33
Why is human-human transmission of bird flu difficult?
Bird flue - H5N1 difficult as the virus can't replicate in the cold temperatures of the upper airway
34
What are the two main receptors on influenza and what are they used for?
**Haemaggglutinin**: binds sialic acid receptors to allow entry of the virus. Virus envelope fuses with the endosome--\>release of virus **Neuraminidase**: i.e. sialidase, cleaves residues allowing exit of virions from host cell; disrupts mucin barrier
35
What does H5N1 actually mean?
h= haemagglutinin n= neuraminidase
36
What is antigenic drift?
Accumulation of point mutations changes the nature of the antigen over time eg thsi is what happens between the different strains of influenza
37
What is antigenic shift?
Recombination of genomic segments during assembly and egress of two co-infecting flu strains --\> rapid potentially whole antigenic change for a viral strain --\>potentially allows for exchange of RNA segments between human and animal strains
38
39
What are the two steps required for an animal virus--\> human pandemic
1. acquire the abilty to INFECT human cells either by: a) acquire mutation in pOLYMERASE protein or b) recombination of gene segments (when another virus that's capable of infecting human cells also infects at the same time) and: 2. Acquire the ability to transmit between humans
40
What was unusula about the swine flu pandemic?
elderly people were relatively spared
41
How does amantadine work? why is there resistance?
targets m2 ion channel ## Footnote single amino acid mutation in M2 (S31N) makes virus resistant \*NB: only works for influenza A (not influenza B)
42
Give an example of a neuraminidase inhibitor. what is its MOA ?
Oseltamivir - tamiflu Zanamivir- relenza \*\*need to use them \<48 hours after infection for them to be effective Neuraminidase inhibitors- prevent viruses from spreading through the respiratory tract (i.e. target spread rather than entry)
43
44
What type of vaccine is SARS COV2 vaccine?
mRNA vaccines encoding stabilized spike