Testing Problems, Mutations, COVID-19 in Washington & Iran (Lecture 29)
Welcome to another MedCram covid-19 update, and I have been off for a few days from the updating because it was my turn to take the helm of the ICU. What we’re gonna be talking about is No1: 5 new deaths in Washington state yesterday. We are definitely in the growth phase here in the United States, but we can’t tell how much of a growth phase there is because we’re going to talk about testing and the lack of testing.
And we’re also going to talk about preparation; what to do before this hits now. We’ll talk about mutations. We are at a total confirmed worldwide cases here of boards of 90,000; total deaths is over 3,000; total recovered is well over 10 times, that is at 47,000. And those are the published numbers.
I’ve heard a number of people talk about the numbers in Asia, and the model to look at in some people’s opinion is going to be South Korea because it is a country that’s doing very aggressive testing, and it’s an open and democratic country. But I think the biggest thing there is the fact that they are aggressively testing, and that’s not something that we’re doing yet here in the United States for a number of reasons, which we’ll talk about.
Going over to the Worldometer website. We look at the close cases to kind of get an idea of where we’re going on the mortality because these are closed cases. You’ve either recovered, or you haven’t, and if you look at this graph, you can see that the mortality rate continues to drop. These are the people that were tested, and we’re already at about 6%; that’s going to go much lower than that once we get the full scope of the infection.
Here we have total cases worldwide. Things are starting to level off here. And I think the reason why we’re starting to accelerate again is because we’re going into the epidemic phase in a number of these other countries. And looking at latest updates for today, March 3rd, maybe a little bit behind because this is a fluid situation. By the time this gets published, there are 477 new cases and 6 deaths already today in South Korea, of course South Korea, being in the part of the world, that is the furthest ahead in time.
If we look at yesterday, we have the first case in Morocco. This was somebody from Italy. Yesterday 21 new cases and 5 new deaths here in the United States. And looking to Washington, it is going to be very important to see what’s going to work in this country and what’s not going to work. Notice that a lot of these people who are dying are in their 70s. However, there is a man in his 40s hospitalized in critical condition in Kirkland, 1 in Rhode Island, and that was a teenager contact of the previous case.
All of these people again went to the same trip to Italy. They’re saying here this is precisely why we are being so aggressive and identifying contacts and testing people who are symptomatic. There are three people in California in Santa Clara County including a couple who has recently traveled to Egypt, and there are now two in Oregon, one an adult in a county hospital in Walla Walla Washington, and the other is the contact of the first case in Oregon who is recovering at home. There are two new cases in Florida, and that is the first one in New York.
Interesting interview on CNBC. That’s also here on the Worldometer website. Dr. Mac McCarthy, who is an ER physician at new york-presbyterian. He says I’m here to tell you right now at one of the busiest hospitals in the country. I don’t have at my fingertips a rapid diagnostic tests. I still have to make my case plead to test people. This is not good. We know that there are 88 cases the United States. They’re going to be hundreds by the middle of the week. They’re going to be thousands by next week. And this is a testing issue quote “in New York state, the person who tested positive is only the 32nd test we’ve done in this state; that is a national scandal.
CNBC有趣的采访。也可以在Worldometer网站上找到。 Mac McCarthy博士是纽约长老会的急诊医师。他说我现在在这里告诉你在该国最繁忙的医院之一。我没有触手可及的快速诊断测试。我仍然必须让我的案子去测试人们。这个不好。我们知道美国有88例。到本周中旬，他们将成百上千。下周他们将成千上万。这是一个测试问题的报价：“在纽约州，测试阳性的人只是我们在该州进行的第32次测试；这是全国性的丑闻。
“They’re testing 10,000 a day in some countries, and we can’t get this off the ground,” McCarthy said, ” I’m a practitioner on the firing line, and I don’t have the tools to properly care for patients today.” And I can tell you I resonate with that as a healthcare worker. In the ICU all last week seeing patients in the emergency room. We are taking protective measures to make sure that we don’t get exposed to people coming into the hospital with covid-19, causing a lot of our health care workers to be quarantined.
So it’s really important that if anybody goes to the emergency room, to call ahead, make sure that they’re following instructions, make sure that they’re wearing a mask, especially if they have a fever, and they have symptoms, because anybody that they infect, no matter who they are, will have to be quarantined, and of course if those people that are being quarantined are our healthcare providers, well, that’s just fewer people to be able to care for other people that need it.
Now the good news there is that, as I understand it, there are going to be a lot more tests available, but they’re not going to be available until later this week. There are regulations that the FDA imposes on commercial manufacturers of these tests. They have to reach certain goals, and it’s a long and laborious procedure to get these things approved by the FDA. Those are being relaxed so we can get enough tests on the market and get labs up and running.
What you ideally want to do, and this goes back to the days of medical school when we were trained in surgery. It was always a good thing. If you took somebody occasionally to surgery for appendicitis and you pulled out a completely normal appendix. That means that you are not missing any, that means you work fighting negative test results, true negatives. So you actually need to screen widely enough so that you know you’re getting enough negative testing. What you don’t want to be doing is testing so limited that the number of tests you’re getting, you’re not catching the full magnitude of the infection.
And so I think everyone believes, and everyone’s on the same page here, that the amount of testing that needs to be done right now in this country needs to be ratcheted up by orders of magnitude over what we’re getting right now.
Here’s a story that was published in the AP a couple of days ago, and it talks about what’s going on, especially up in Washington, where the hot spots are, says here as Americans prepared, researchers at the Fred Hutchinson Cancer Research Center and the University of Washington on Sunday said that they had evidence the virus may have been circulating in the state for up to six weeks undetected.
A finding that if true could mean hundreds of undiagnosed cases in the area. They posted their research online, but it was not published in a scientific journal or reviewed by other scientists. Trevor Bedford, an associate professor who announced the preliminary findings on the virus in Washington state, said on Twitter late Saturday that genetic similarities between the state’s first case on January 20th and a case announced Friday indicate that the newer case may have descended from the earlier one.
Now, this is going to be something that we’re going to talk about when we talk about molecular biology. It is this idea about descendants. So the thing that you’ve got to understand is that the virus, when it infects your cell, it takes over the cells machinery to create more viruses, but the genes that the virus brings in is kind of sloppy, and so because of that sloppiness, there’s a lot of mutations that are made, and some of those mutations may actually end up changing amino acids. Some of those mutations won’t translate into differences in amino acids, but you can still see those mutations. And as you track those mutations in time, you can see which virus strain descended from another.
Now, those mutations can occur randomly anywhere along the genetic thread, the RNA as it turns out in this case with coronavirus, but if those mutations affect a key component, for instance, the binding protein or the spike protein on the coronavirus, that allows it to infect human cells. Well, that virus is just not going to be able to infect the next human cell, but because there are millions and millions that are made. there’s always another one right behind it that’s going to happen.
The bottom line is you rarely are going to see viruses, copies of the virus, infecting human cells that have a mutation that is critical in the binding of that protein, and therefore the binding of that site now, in this case, the binding site in the human being is the H2 receptor in the cells, in the bronchi, or the lining of the lungs. So that’s a highly conserved area.
Why is that? It’s highly conserved because those are the only viruses that are going to infect the human being. But if you look at these, just like the human race has different families, different last names, because they’re related to each other. Different coronavirus, different SAS-COV-2, different covid-19 viruses, in other words, if you were to look at the ones in Wuhan vs the ones in Washington, they are not identical to each other, they have mutated in some way, and what you can do is actually come up with a family tree, and you can see where these things came from.
They say “I believe we’re facing an already substantial outbreak in Washington state that was not detected until now due to narrow case definition requiring direct travel to China. Scientists not affiliated with the research,” said the results did not necessarily surprise them and pointed out that for many people, especially the younger healthier ones, the symptoms are not much worse than the flu or a bad cold.
He says we think that this has been a pretty high rate of mild symptoms and can be asymptomatic. The symptoms are pretty nonspecific, and testing criteria that have been pretty strict, and this is really the key here. Up to this point, you could not get testing unless you had traveled to that specific portion of China where the virus was. So these combinations of factors mean that it easily could have been circulating for bit without knowing, suggesting Lesler. So people are saying that this is high-quality work.
So what I want to do is talk a little bit more about what is going on with this mutation, and I want to introduce you to a really cool site, and that website is called Nextstrain, and this actually does real-time tracking of pathogen evolution.
If we click on the latest data and analysis here, what we’ve got here is the SARS-COV02 genome, and I think this is really cool. What you can see here, we have the initial strain over here, and we can see how through time the different mutations have occurred in different family trees. So if we play this, you can see that things started out here in Wuhan. But as things have spread across the world, there have been mutations, and we can see what the descendants are as we track it.
So interestingly the one here in California, it shows that there are nucleotide mutations from the original. There are amino acid mutations in the ORF-1-A gene; we will talk more about that. That is the gene in the virus that codes for the protein that allows it to reproduce the RNA genome of the virus.
And if we look down here, we can actually see the genome of the virus. This is the entire RNA of the coronavirus, specifically that we’re talking about here, the ORF-1-A gene and the ORF-1-b gene. For those of you who are molecular biology buffs, there’s actually an overlap in that gene right here that requires a frameshift on the ribosome to be able to translate both of these, and we’ll talk more about that in the coming sessions and updates.
What this here represents is where these mutations in the genome are occurring. We see that there are a lot of mutations occurring down here in these small genes, and not so much here. This S gene right here codes for the S protein. We can see that there are some mutations; some of these mutations may not be actually changing amino acids. However, this s protein is the spike protein on the very outside of the cell. This is the protein that is going to be binding to the ACE2 protein on the human lung cells that allows it to bind and infect them. Ostensibly, this is the portion of the RNA genome of the virus they would be injecting into your cells as a possible vaccine so that your cells could take this instruction, make the S protein inside your body, which would cause an antibody response, which would then give you the vaccine against the coronavirus.
At this point, I’d like to talk to health care providers and people who are leaders in their community, people who are members of medical groups. This is the time now to start communicating with your patients, educate them.
What are they supposed to do? If they get sick, if they develop a fever, if they develop a sore throat, if they are otherwise healthy, they don’t have shortness of breath. They’re not hypotensive, the best thing to do is to self-quarantine and stay home. Do not overburden your health care delivery system. They’re going to be plenty busy with people who are worse off. If you are going to go to the hospital, make sure you call ahead, find out what the procedures are, because they’re going to want to make sure that you’re isolated. They’re going to probably give you a mask.
Things to think about as well is to make a plan on where to go. There are hotlines. People are going to be calling in. If you have a Nurse Advice Line, make sure you double it or triple it because the volume of calls are going to increase; people are going to be very concerned. If you have the ability to do telemedicine, that’s what you should do. The coronavirus cannot infect somebody over the phone.
Next thing we need to do is plan for a surge, so that means that people who are in the hospital may be overwhelmed, and they may need to get into resources that are normally in the outpatient setting, people who are doing, for instance, Well checks.
Hospitals themselves need to start thinking about hospitals within hospitals. So, in other words, a dedicated unit for people that you suspect as having coronavirus, a place that you would need to have negative pressure rooms so that you’re not blowing out the aerosolized coronavirus into other parts of the hospital.
Something as practical as understanding that most operating rooms are under positive pressure. Some of the more modern ones can switch to negative pressure. But if you take a coronavirus patient into a positive pressure operating room, that’s not going to be a good thing. It could also be very expensive to have the ability to have coronavirus treatment all throughout the hospital, you need to have a dedicated place where contact is minimized, and the people working in that area are going to have maximal PPE (or personal protective equipment), and not have to burn through a lot of these materials because they’re going to be limited. So the time is now to start putting these procedures in place.
Now, of course, this situation is very fluid right now. Thanks for joining us.