17-18: SARS-CoV-2 Flashcards

1
Q

what’s very impressive about SARS-CoV-2?

A

identified and sequenced in 5 weeks because of new technologies

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2
Q

COVID hospitalisation and death by age

A

big variations by age

higher changes of death from COVID the older you are

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3
Q

COVID hospitalisation and death by race/ethniciy

A

systemic health and social inequities

less access to healthcare and issues getting access to medication

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4
Q

COVID hospitalisation and death by pre-existing conditions

A

more likely to be severely affected if you’re elderly or have co-morbidities

e.g. asthma, hypertension, obesity, diabetes, chronic kidney disease, severe obesity, etc.

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5
Q

vaccines for COVID

A

all quite efficient

e.g. pfizer, moderna, astrazeneca, covishield, J&J, sinovac, sinopharm, etc.

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6
Q

time for COVID vaccine innovation

A

speed was astounding so fear in the population about this speed
- less than a year between virus discovery and vaccine

measles which was relatively quick still took 10 years, polio took 50 and typhoid took 100

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7
Q

why did we get a COVID vaccine so quickly?

A

coronaviruses were already a concern
- SARS-CoV-1 and MERS as spillover from bats/camels making people very sick
- knew how to grow vaccines and which proteins needed to be targeted with antibodies

technology was ready

worldwide collaboration

funding for COVID research

close collaboration between pharmaceutical companies and government agencies

high infection rates so no difficult recruiting volunteers

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8
Q

variants of the virus

A

virus invading the population, people getting infected, some resistance associated with vaccination and re-infection

many waves with virus banging to find a way to re-enter or relaunch a massive infection despite variants dying out
- slightly changes don’t change how the virus infects cells but prevents antibodies from recognising the virus so better at escaping immune responses

delta 2-4x more virulent/infectious than alpha
- recognises the cells it needs to enter more efficiently
- mutations on the spike which make it better at recognising/interacting with cells

omicron generally 2.4-3.2x more transmissible than delta in vaccinated household contacts
- no difference in unvaccinated

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9
Q

what types of antibodies are produced with the vaccine?

A

need two doses

with the first dose, you don’t have that many antibodies but you do make more IgM (lower affinity antibodies that don’t improve with time) and very few IgG

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10
Q

durability of vaccine-induced antibodies against SARS-CoV-2

A

benefit of the vaccine wane, at least for antibodies and not necessarily T-cells

need for a booster, whether or not you are infected naturally
- probably never done with SARS-CoV-2 since the variant is able to escape and there is waning immunity

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11
Q

initial COVID infection

A

virus finds ACE2 receptors in the lining of the nose
- proteins recognised by the virus’ spike proteins

virus enters, makes myriad copies of itself, invades new cells
- transmission through droplets when you cough, breathe and even if you’re asymptomatic

symptoms can be absent or you develop a fever, dry cough, sore throat, loss of smell/taste, head/body aches

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12
Q

COVID infection in the lungs

A

after entering through the nose, virus goes down the windpipe to attack lungs
- this is where it can turn deadly

tiny air sacs called alveoli at the end of the lung’s respiratory tree which are lined with cells rich in ACE2 receptors
- alveoli have a lot of surface area for infection

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13
Q

what normally happens in the alveoli?

A

oxygen crosses alveoli into capillaries (tiny blood vessels beside the air sacs) and it is carried o the rest of the body

exchange of O2 and CO2

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14
Q

pneumonia associated with COVID

A

virus replicates in alveoli
- inflammation of alveoli so immune cells recruited to kill cells
- dying cells release cytokines, immune cells release cytokines and chemokines

leaves behind fluid and dead cells/pus behind
- increased fluid uptake in the lungs
- reduced ability of the blood to contain oxygen since blood comes back with fluid

underlying pathology of pneumonia with cough, fever and rapid/shallow respiration

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15
Q

acute respiratory distress syndrome (ARDS)

A

deterioration from pneumonia to develop this condition
- plummeting oxygen levels with a hard time breathing
- need ICU and artificial oxygenation

autopsies show alveoli are stuffed with fluid, white blood cells/immune cells, mucus and detritus of destroyed lung cells
- not a disease of the virus
- disease of the immune system which reacts very strong to eliminate the virus (hyper-activation)

cytokine storm
- too many cytokines which create too many immune cells and proteins
- immune system too stimulated

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16
Q

ACE2 expressed throughout the body

A

receptors for the spike

nasal - initial infection, spread and loss of smell

lungs - pneumonia, ARDS

ileum - gastrintestinal symptoms, virus shed in feces

heart - heart damage with unclear reasons

17
Q

delicate balance for SARS-CoV-2

A

initial infection without much immune response

replication, amplification and release but viral doses diminishing with time

disease ends up being a disease of the immune system and not the virus itself

18
Q

how do we target SARS-CoV-2 with this delicate balance?

A

response is to give drugs targeting the virus early on, decreasing the amount of virus so you don’t stimulate as much immune response
- when you forget about the virus, then you give drugs to target the immune response and slow it down

initially give antivirals/monoclonal antibodies which target the virus
- hopefully lowers viral dose and prevents too much immune response

then give anti-inflammatory drugs to block cytokines
- blocks recruitment of immune cells into the lungs
- better oxygenation and recovery

19
Q

SARS-CoV-2 replication

A

spike interacts with ACE2 receptors, virus is released into cells and they release mRNA genome
- genome recognised by cells which then make viral proteins

viral proteins initially one long stream of protein/polypeptide
- further degraded and cut into smaller proteins

genomes and viral proteins that are cut take mRNA and make copies
- multiple copes of mRNA recognise each other, form a new virulent virus and release to infect new cells

20
Q

drugs against SARS-CoV-2

A

different drugs given as pills for 5 days every 12 hours

molnupiravir
- act on a particular protein to make it les reliable for fewer mutations
- virus comes out highly mutated and is not viable anymore (dead end)

paxlovid
- given with ritonvir which inhibits CYP3A4
- increase half-life of drugs in the system and prevents degradation in the body