hi everyone today we’re going to go over cover 19 infection and risk factors this is a special topic lecture on covid19 specifically on how it interacts with the immune system so um basically in this lesson our main question we’re going to address is what accounts for the wide range of symptoms and personal risk factors to covet 19. um we’re not going to cover a ton of new vocabulary though there will be some kind of complicated concepts that i’m going to introduce all right so just a really quick recap of viruses just reminding you all viruses have genetic material that’s dna or rna they contain proteins that might be a capsid protein that might be other helpful proteins and enzymes and in particular spike proteins depending on the virus such as covid 19’s virus which is actually its name and stars kovi too all right and the main idea for viruses is they must infect a host and use its cellular machinery to make more of themselves they cannot reproduce and make more of themselves on their own they need to get inside our cells to do so now why do we call covid19s virus stars kovi to coronaviruses well this is a massive class of viruses that basically due to the shape and presence of all their spike proteins they kind of look like all the spikes that you might find on a crown and corona is latin for crown now the distinctive feature is its many spike proteins on the surface of its envelopes so not all viruses have spiked proteins or envelopes but cova 19’s virus and basically all coronaviruses do and in particular for sorry covid19s virus um stars cov2 the spikes that it has interacts with an ace2 receptor and we’re going to go into what the ac2 receptor does today now another thing i wanted to point out is um the virus for cova 19 is what we call an ss plus rna virus it’s actually 30 000 bases long which is really unusually big for an rna virus and it’s called plus sense rna now that’s not a term i’m going to test you on hardcore but what that means is not all rna genomes and viruses are immediately usable but for this player for coronaviruses theirs are and what happens is when they dump their rna genome into our cells our cells immediately start treating that rna as though it’s ours and starts pumping out proteins that will help make more viruses immediately using our own cell machinery and the other thing about this virus in particular is its recipe um that it brings in for helping to copy its rna genome it’s called rna polymerase that’s the protein it’s going to used to copy its own genome but anyways its particular way of copying its rna genome actually introduces lots of mistakes in other words lots of mutations which is part of the reason why coronaviruses mutate so quickly as we’re seeing with covid19 so this is just kind of a recap of the process right we have our coronavirus with its spike protein for covid19 its bike protein in particular wants to find an h2 receptor on the host cell when the spike protein is think of it as a key clicks into the cell receptor think of the cell receptor as a lock it opens a lock and allows the virus to enter our cell through this whole process um it processes endocytosis or sometimes called adsorption anyways once it enters our cell it allows its um its genome to be dumped out into our cells which is then immediately read by our own cell’s machinery ribosomes and that immediately starts making the genome of the virus as well as proteins for the virus and then starts letting it assemble its virus babies which then can then exit ourselves or maybe burst out of our cells if you’re curious to learn more about viruses this is a virus explorer and this particular page has a link that you can click when you click the image and it will send you to like kind of this web interactive if you’re really curious and want to know more about viruses um same here this is a chart that kind of goes into like the history of different major important viruses that affected the world so if you’re kind of really into that stuff you can just click on this slide in particular and the graph on it and they’ll send you to a page to learn about it but you don’t have to take notes on it all right so what we do want to know and understand in our notes though is why the ace2 receptor is so important to our body and how that basically affects what covid19 will do to our bodies so the ace2 receptor is present in a lot of our epithelial cells our epithelial cells just reminding you is the cells that kind of cover the outside of our bodies and internal structures so the spike protein of stars kovi 2 engages with the ace2 receptor of our cells to enter the host i already said that before but this is just formally in your notes now this becomes an issue because our ace2 receptors happens to be present in all areas of our body that utilize what we call the renin angiotensin aldosterone system also known as ras raas now this is kind of an incredibly complicated system that it involves a lot of steps and i’m not going to go really really into it but what you need to understand is it plays a major role in regulating cardiovascular health and the kidney is super central to it so often brass issues breast dysfunction issues result in either cardiovascular which is blood vessel and heart problems or kidney problems so what it does is if your for example blood pressure lowers or if your blood pressure is too high the rast system will allow your blood pressure to regulate itself to a more acceptable homeostatic range to maintain your health of the blood flow in your body and some major hormones throughout different key organs involved in the rast system including the kidneys produce hormones that allow your body to make the correct response to correct your blood pressure all right so for example if your blood pressure is too low your kidneys will release retin and then renin will actually do a bunch of different things to increase your blood pressure all right so what you actually need to know though because it’s kind of a really complex system that we could spend a lot of time on but it’s actually more of an endocrine system and i want to focus on the immune system right now so just know it’s an endocrine system which means it uses a lot of hormones and a lot of these hormones that help affect our um blood pressure come from our liver they come from our kidney that’s run in they come from our lungs which actually produce ace and all these things can trigger the kidney to absorb more water and salt and also trigger your blood vessels to go from big and white to more narrow and this may not seem like a huge deal but it’s going to help increase your blood pressure between encouraging your kidney to take in more water and salt as well as shrinking your blood vessels it’s going to increase your blood pressure and higher blood pressure means that blood flows through your body more quickly and more easily so if you have too low blood pressure you might sometimes feel faint or fuzzy if you stand up too quickly because your blood isn’t pushing through your tissues as much as it should but very high blood pressure is also scary because if your blood pressure is too high it constantly adds tension and force and ultimately damage to your blood vessels that might be found in your heart might be found in your brain and ultimately lead to organ damage so we want our blood pressure high enough to help allow really good blood flow but not too high so it doesn’t damage our organs all right so that’s sort of the system kind of complicated but and we could learn all the individual hormones and all the organs involved but we’re not going to do that but what i do want us to understand is where ace2 falls into this map so if you look at this previous thing you’ll see there’s angiotens synogen angiotensin 1 and angiotensin ii and angiointestine too is sort of a product within the rast system that actually prevents the rast system from getting out of control prevents you from making your blood pressure too high so what it does it is it maintains that homeostasis in your blood pressure range so that it doesn’t get too whack too out of range of what’s acceptable and your ac2 proteins are really critical to this they actually work with angiotensin ii within the rast system to lower your blood pressure and help open and dilate your blood vessels and where this becomes an issue with cova-19 is because your tissues that need to be affected by ras also need to prevent rats from getting out of control which means they also have a lot of h2 receptors so any tissues involved in regulating your blood pressure and affected by blood pressure will also happen to have a lot of ace2 receptors present which means there are potential targets for stars cov2 so because it’s especially present in blood vessels and many organs involved in regulating blood pressure that’s why your liver your kidneys your heart your lung and your gi tract are all big targets for covid19 when you’re infected by it okay and this is actually related to the risk of getting very severely ill and potentially dying from coven 19. so this is a list of conditions where you have a higher risk of getting hospitalized for covid19 compared to people without these risk factors such as diabetes chronic kidney disease and we’re actually not a hundred percent sure why obesity has such a huge risk factor whether it’s just because obesity tends to be more linked to other conditions um that have damaged organs that are part of the rast system or whether there’s something some other factor we don’t quite understand that relates to more h2 receptors but we also know obesity also is a really big risk factor in addition to diabetes kidney disease hypertension hypertension just means high blood pressure and heart conditions asthma has somewhat of an increase rate though not nearly as much as being overweight for instance so um but asthma because of the lungs is part of the issue as well okay and also because ace2 and its receptors are such a huge area for covid19 to target in instances where cova-19 becomes really severe and causes really severe weird illness issues you’ll actually see that the organs where it kind of targets are related to the rast system so this possible symptoms of cobalt 19 will go into a little bit more but the kind of more severe cover 19 symptoms like pneumonia and kidney failure and death are all co are all kind of related to the rast system and also there’s some lesser known um uh symptoms of coven 19 that you may not know such as diarrhea because it’s ace2 is found in your gi tract so they’re all kind of related oh and i wanted to mention this little factor here when i talk about the kidneys is actually we don’t talk you may not have heard about it but actually kidney failure is a really big issue for people who are hospitalized with really severe covid and a lot of those people may need temporary dialysis because their kidneys stop functioning during their severe illness or they may even need potentially permanent dialysis for the rest of their life the dialysis industry that produces the machines for filtering your blood when your kidneys aren’t working they’re actually having really good stocks now because everyone’s anticipating them to have a lot of business due to covet 19 long-term symptoms for really severe cases the people who got hospitalized all right so because of the ace ii and the issues with blood pressure this actually accounts for why older people tend to have a higher risk of infection and severity for illness because ace 2 is associated with lowering your blood pressure you’re going to actually express more ace2 and contain more ace2 receptors if you are more prone to high blood pressure which is going to happen to older people compared to younger people okay another thing is because older people tend to have weaker innate immunity we’re also more likely to allow the virus to enter our bodies versus younger people in addition like i mentioned because we just typically have higher blood pressure and more health issues regarding organs in our rot system we’re also going to have a lot more ace2 activity and receptors for stars kovi 2 to enter if you’re younger you don’t nearly have as much and in fact before puberty you have a very low amount of h2 receptors at some point in your teen years after puberty you start to really express a lot of h2 receptors so actually by the time you’re a teen your infection rate is pretty much very close to those that are in their 20s young younger adults but very young kids have very low amount of ace to receptors um though they can still get covered just not as easily as older people all right in addition to that there are some medications such as medication that lowers your blood pressure and other treatments for organs related to the wrath system and some of them are actually known to increase the presence of your ace2 receptors and they discovered that during the coven 19 outbreak so so doctors are tending to try to avoid prescribing those medications to their symptoms i mean to their patients whenever possible and finally just because when you’re older you’ve had more time to damage your body and oftentimes a lot of the damage may occur in your wrath system or rat system organs like your blood vessels for example or your lungs because you’ve done stuff so just in general because cova 19 is targeting those tissues if those tissues are already weakened and damaged because of your activities in your in your life you’re going to be more likely to get ill and have a severe illness from kova 19. all right in addition to that there is a genetic factor to potentially getting a severe illness from coven 19. some people genetically just express a lot of ace2 receptors and sometimes the shape the slight variation of how you form your ace2 receptor might be just in particular really good at connecting and being vulnerable to kova 19 spike right we all have slightly different hair shapes or or tones of skin you can also have slightly different shapes of your ace2 receptor and in this case that could be very bad if it’s just particularly um one that is good at attaching to the spike protein in covet 19’s virus stars cov2 another thing you may not realize is ace2 and its receptors are actually found within neurons and glial cells in your nervous system so why is that important well for example you the because it’s an aerosol or respiratory illness the virus spreads through the air which means it is likely to come into contact with parts of your body um that breathe it in and in fact one of the first neurons it interacts with is the neurons in your no nose which is your olfactory neurons and because they have ace2 receptors they can get damaged and infected by sars cov2 which means you might get anoseemia anosmia which is the loss of smell and potentially taste because your sense of smell is connected to taste in addition it can target your brain if it gets to your brain which is actually why fatigue is a really common cobit 19 symptom and actually one of the most common covid19 symptoms that lingers even after you recover from the virus but eventually especially for smile it will come back and it’s been shown that even though fatigue can be very present and even very long lasting in people that recover or that are no longer infected by covid19s virus it’s one of the most common lingering symptoms after we you recover from illness eventually the fatigue usually lessens and fades away all right so three factors for viral infection symptoms the severity of your symptoms and this chances of you being infected one of them is just having those receptors present which has a big component due to your genetics and due to your health to an extent because your health may lead to higher expression of it or just due to the medications you take in addition to that just having the virus in your body so it can get to the tissues with ace2 receptor is really a huge factor so two things affect how much virus is in your system at any given time one is your immune system health which is the ability to block and remove the virus that’s part of the reason why cancer patients are really vulnerable to cova 19 because they have treatments that actually weaken their immune system in addition viral load is really important so meaning the more virus you take in the more likely that virus will get into your bloodstream will get into your cells will then be able to reproduce and then go on to infect more cells so actually it looks like by wearing mass you reduce the amount of virus you may take in and also reducing the scenarios and the amount of virus you may be exposed to all those things even if it doesn’t 100 percent protect you from kova 19 it looks like it has a pretty big effect on at least lowering the severity of your illness even if it doesn’t 100 protect you from getting sick it’ll lower and make it more weak more likely to be asymptomatic than something that might land you in a hospital for instance all right now in addition to that if you do get infected by a vir the virus there are a few things to watch out for all right so we have our immune system we have our levels of immunity innate immunity and acquired immunity well one part of your innate immunity in your second line of defense is your cellular defenses that’s non-specific and one of them is cytokine so cytokines if you forgot are the signals that are sent out by your white blood cells and tissues to recruit and stimulate white blood cells to the site of infection cytokines actually also have a huge role in your fever regulation because it signals and interacts with your hypothalamus to raise your body temperature which is actually interferes with ability for your bacteria and virus to replicate but one of the weird side symptoms of for some people with coven 19 is something called a cytokine storm so what happens is sometimes the cytokine effect which is supposed to help increase your immune system kind of over stimulates your immune system to a dangerous degree where it creates lots of swelling and lots of cell damage which can actually sometimes lead to death this is a very rare condition but it does have an impact on the people that happen to um die from covid19 or become hospitalized from coven 19 because for just for some reason this virus especially this virus in particular is more likely to trigger cytokine storms in patients compared to other normally normally common viruses that are found in the population like flu virus and of course we have our normal immune system response um our acquired immune system specific immune system responses and there’s nothing too special to this it’s just we have either antigen presenting cell or maybe an infected cell helping to stimulate our helper t cells which will go on to stimulate our b cells to make antibodies and our cytotoxic t cells to attack infected cells so that you are no longer sick to help get rid of the virus so this you don’t need to take notes on it’s just to remind you your acquired immune system is also really important for attacking the virus as well all right now how stars cov2 spreads in these slides we have i have a lot of videos that kind of go over how stars cov2 spreads through sneezing and things like that but um in later in our unit or within our unit we’re going to learn about a factor called r dot which is the basic reproduction rate of a virus which measures how contagious a disease is by measuring how many people an afflicted person will infect what that means is if you are sick will you infect one other person will you infect three other people will you maybe infect 12 other people that’s the r naught number the average amount a person will infect if they have that disease all right if one person is capable of infecting one or more people on average then you’re actually going to have exponential spread of a disease but if one person um it will infect less than one person meaning like it out of two people being sick they’ll go on between the two people they might infect only one under other person between the two of them then what that means is over time the disease will fade out now this is kind of hard to predict accurately because social factors are involved in this for example the are not do when in a society where no one is doing any social distancing is very different than the society where people typically wear masks very commonly even with or without a pandemic okay and also in addition to this this has a really important effect on social social health structures and considerations by epidemiologists people who study the spread of disease and make recommendations regarding the government’s response to an illness because viruses with really high r values actually need very high vaccination rates and immunity in order for that disease to be eliminated from a population so for example these are different r knots of different outbreaks and for our stars cov2 it looks like we’re kind of in the two to four range meaning one person might go on to in fact two to four people and that that number you’re going to learn means we need a fairly high rate of vaccination to permanently eradicate the disease from a population otherwise what likely what’s going to happen is it’s always going to be present they’ll hopefully weaken over time due to vaccines but we’re gonna instead of being one and done with the vaccine it is likely we’re gonna need constant boosters to the vaccine over our lifetime to address uh covenanting in the population um you kind of see this with measles measles has a really high um r naught value of 12 to 18. so in fact this is why measles was kind of the first disease to make a comeback even though we used to never think of measles before the 90s when the anti-vaxx movement happened because as soon as the numbers dropped below 95 percent measles started poking its head out and started showing up in our population just because the are not value was so high you needed a really high rate of vaccination to get rid of measles which we no longer have a really as high a rate as we need for that okay so then again for these slides there’s a bunch of videos on covid tracking and things like that if you want to read more on that but we’re going to learn more about it in our class this is a map of coven 19’s case spread and if you’re curious about looking at the stats of how it’s spread around the world you can look at john hopkins map and website on that and if you click this this map you’ll actually get connected to the link for that website on that note that concludes our lesson for the day bye
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