covid Flashcards
why did SARS-CoV-2 cause pandemic but SARS didnt
Can transmit much better through the air and through asx people
what is a coronavirus
RNA genomes - single stranded +ve sense RNA
V large genomes - ie big virus - more than 2x flu coding capacity
enveloped virons 100nm
nidovirals - nested set of mRNAs from one large genome
how many coronaviruses have infected humans
7
v are very common and cause the common cold: OC43, 229E, NL-63 and HKU-1
SARS and MERS are zoonotic
How do SARS and SARS-CoV-2 bind to cells
ACE-2
where has covid come from
horseshoe bats
bats contain lots of different coronaviruses that recombine
animals in markets/farms can act as secondary host
time course for covid infection
airborne route
most likely upper resp infection - cold and other sx
day 0 - infected
3 - virus +ve and infectious
5 - sx
At 1 wk - some people control virus and some people cant control at this point - and it diseminates - cytokine storm - problem is immune system response to the infection
factors that increased risk from covid
age
gender
chronic cardiac disease
chronic pul disease
chronic kidney disease
malignancy
obesity
dementia
dexamethasone for covid
cheap
effective in those recieving ox - or ventilated
reduced deaths in illest cohort by 1/3
Only patients that need oxygen/ventialtion benefit from dexamethasone
Because if before need ox - the immune system is still fighting virus - so by suppressing the immune system you may be doing harm
standard of care in UK now
monoclonal Ab for covid
Human monoclonal Ab
Passive immunotherapy
Not very well touched at this point because of mutations
regeneron
sotovimab
Small molecule antivirals for covid
remdesavir - nucleoside analogue - doesnt work very well against SARS cov 2 polymerase
molnupiravir - target polymerase, nucleoside analogue - terminates the RNA chain -> virus cant replicate self
for nucleoside anologues need to think about SE and specificity - every cell in body replicates nucleosides
paxlovid
* specifically designed to target sars cov 2 - targets protease - that virus uses to chop up polyprotein.
* have to give it with ritonivir. Ritonivir would interfere with metabolism of other drug - so if pt on other drugs - might not be able to give ritonivir and therefore cannot give paxlovid
vaccine for covid
mRNA vaccine encoding stabalised spike:
* means could go straight from mRNA to person without having to make the attenutation etc
* but need to modify the nucleosides - otherwise cell will recognise as PAMP
* use lipid nanoparticles to get modified mRNA into cell
need to make Ab against pre-fusion spike not post-fusion spike - otherwise risk of deleterious effect.
Engineer so spike protein never goes inot postfusion state - and only ever targets prefusion state - then you would make good ab
So stopped the sequence being able to make the transition that it normally makes
problem with covid vaccines
work
but efficacy drops off depending on how much neutralising activity the Ab that get induced have - this depends on brand of vaccine, and match between vaccine and circulating virus
covid variants of concern
omicron has displaced delta around the world
omicron less well contained by current vaccine
but associated with less severe disease
has large number of spike proteins that effect ab neutralisation - 35 mutations compared to original
long term effectiveness of covid vaccine
Great protection against severe disease and death - bvecause respond quickly and don’t pivot at day 8
But as time goes by at 2nd dose - still get sx
Short lived spike specific - so will have to give updated vaccines at least on a yearly basis
