Welcome to the first full day of Spring, may it bring good health on this March 20 20 20.
- Virus- a type of germ that consists solely of a bit of genetic material (DNA or RNA) wrapped in a protein coat. The coat gets the genes into the target cell where the genes force the cell to make zillions of new viruses, and on it goes.
- Coronavirus- a species name of a number of different viruses. Called corona because its protein coat is studded with spike shapes that form a crown, halo, or corona of spikes
- SARS- CoV-2- the specific name of the new coronavirus
- COVID-2019- the name of the illness that the new coronavirus is causing
- Endemic- an illness always present in a region. One could say strep throat is endemic in the US
- Epidemic- a sudden burst of an illness that comes and goes over a limited time
- Pandemic- an epidemic that bursts across the world not just one region
- Spreadability- how contagious is the disease, how many people will end up infected
- Severity- what harm does the disease cause, in terms of how sick you get and how many it will kill
Remember from earlier posts that the impact of an epidemic relies entirely on how many people will get the illness (spreadability) and to what degree and how many will be harmed (severity).
In this post we take a look at some remarkable news from Iceland and Italy and share some thoughts on the time course.
AP Televisits A Great Success!
We begin this post with noting that a number of families are taking advantage of having their child(ren) seen without having to travel to the office.
AP Televisits is our version of Facetime, Zoom, and Skype, but completely HIPPA protected and within your child’s chart. We are so pleased at how many families are now using this way to visit and be seen by their doctor. It is extremely convenient, but beyond that, during this pandemic, it is a point of medical wisdom to be using the AP Televisits for when you need to see the doctor. Keep in mind, we can always let you know if you still need to come in as we assess the situation on our Televisit.
How to do this? Easy. Just call our office at 216-591-1515, as you would to set up any appointment, but ask for it to be an AP Televisit. Our staff are able to make sure you can log in and know how to connect. I look forward to seeing you on our screen as you need to.
Iceland and the Question of the Well
One could ask, why would we be paying attention to those who are perfectly well to gain understanding about this COVID-19 epidemic? It turns out many things change if those who feel perfectly well turn out to be infected.
The data from China strongly showed that if you got this coronavirus, SARS-CoV-2, you would very, very likely get at least some symptoms, typically 3-5 days into the infection, and only very, very rarely after 14 days. Readers of Real Answers may recall that in one sample of 320,000 (!) swabs in the southern Chinese province of Guangdong, about 1600 were positive for SARS-CoV-2. And at that time there were 1500 known cases of COVID-19 in the province, all of whom were ill with symptoms. This suggested that about 94% of those infected had symptoms.
This also meant that if you felt well on any given day, and then waited 5 days, or even 14 days, and felt fine then, then you could be very confident that you were not infected on that given day.
It is this understanding that underlies all quarantining of direct contacts. After all, the assumption is that if you came into direct contact with someone with a proven COVID-19 illness, and stayed isolated for 14 days, and stayed well for those 14 days, you were not infected.
Now comes Iceland, which has tested more of its population than any nation on Earth. Not everyone in Iceland, yet, but up to over 20,000 per million. For reference, the US is now up to 7,000 per millon. Iceland plans on testing everyone. What they have found is that if you test:
- People with symptoms, about 9% are + for COVID-19
- People who are perfectly well, about 0.7% are + for COVID-19
- Iceland currently has 330 cases, 33 are people with no symptoms.
Put this all together, and it appears that about 10% of people infected with the new coronavirus in Iceland, have no symptoms. That does not mean that 10% of people who feel well have the infection. We know that number in Iceland, it is 0.7%. So if you feel well, at least in Iceland, you have a 99.3% chance of not being infected.
And, 90% of those known to be infected in Iceland, have symptoms.
[Warning, these data come from March 19. A report from Iceland on March 15 described results of testing as of that date, 10 times more tests have been done by March 19 than March 15. The March 15 report showed preliminary results that 50% of those positive were well, that ratio has not held up as the testing tested so many more people]
To my mind, that confirms the large scale testing reports from China, namely, if you feel well on any given day, and stay well for 5-14 days from that day, you have a truly excellent chance of not being infected. That chance appears to be in the range of 90-94%.
Welcome to Vo Euganeo, Italy
Welcome to Vo, a small town in Italy, about 30 miles west of Venice, home to about 3,400 people.
Vo was the first town in Italy to see one of its inhabitants die of COVID-19 and that was on February 21.
After that death, every single citizen of Vo was tested for SARS-CoV-2 infection. 89 of the 3400 people of Vo were positive, for a 3% infection rate.
After finding 3% of their town infected, the whole town was placed in lockdown, and since everyone was tested, everybody infected was put into quarantine. It is not clear at this time if infected folks were placed in quarantine in the home or in isolation out of the home.
After 14 days of lockdown of everyone, and quarantine of those infected, the number infected dropped from 89 to 6 people infected, from 3% of the town infected to 0.25%. And most remarkably, no new cases from March 13 to March 18, while the rest of the nation has seen cases soar.
I will add that of the 100 people testing positive in the town, about 50 had no symptoms. This is similar to the rate noted when the first 700 people were tested in Iceland, but as noted above, the percentage of people testing positive without symptoms in Iceland dropped from 50% to 10% when testing went from hundreds to thousands of people.
Some thoughts on the Well Amongst Us
Now, here is why it matters how many infected people feel perfectly well throughout their infection. If lots of people who are infected with SARS-CoV-2 feel fine the whole time they are infected, then:
- Testing only people who feel sick will miss all the infected people who will spread COVID-19, who feel well. That might mean less ability to stop the spread of the infection. It is very meaningful that one town shut down the epidemic in 2 weeks (!). China took 8-12 weeks.
- The mortality rate, mercifully, will fall. Say 300 people die of COVID-19 in a nation. Now let’s say about 10,000 people have the infection. That would make the mortality rate about 3%. But what if it turns out that in that nation another 10,000 people are infected but feel fine, never get tested. Now the number killed by the virus is 300 in 20,000 people infected, and the mortality rate goes down to 1.5%, which would be very good news.
- Planning on who to concentrate on isolating would have to change. Currently in the US we only test people with symptoms for COVID-19. If a lot of Americans are walking around with COVID-19, but feel fine all along, then they are circulating and spreading virus without attention to strict isolation.
At this time, it is unclear how many, or what proportion of folks who feel fine, are infected and have COVID-19. Data from huge numbers of people tested in China, a growing national testing effort in Iceland, suggest that the vast majority of infected people with COVID-19 get some symptoms of being ill, still mainly fever, cough, and sore throat, and not runny nose.
But, the data across a whole village in Italy, Vo, suggests that maybe many more than 10% of those infected are well and stay well. Time will have to tell.
How Well Will the American Strategy Work?
Once again, we simply do not know. The US has established, by our actions, that our key strategy is this: keep as many people as possible at home, literally to reduce the number of people everyone in America comes into contact with. This strategy applies to everyone who feels fine, everyone with a cold, everyone who has a mild case of COVID-19, everyone who is a contact or contact-of-a-contact of COVID-19 cases. The only people not being asked to stay at home are those so ill they need hospitalization.
Will this slow the rise in our cases? We do not know. If lockdowns and staying at home is what worked in China, some say that took 6-8 weeks to take hold and stop the epidemic. It is with this in mind that some predict the rage of this epidemic, if we stay at home, will cool down sometime in late April or early May. But that will happen only if this strategy works.
The East Asian strategy had one more element beyond the American strategy, as readers of Real Answers know well- these nations isolated known cases of COVID-19, outside the home.
Now, should strategies fail, it is anticipated that we will have surges of epidemics, like those seen in Wuhan, Iran, N Italy, and now NYC, and other hot spots. One hot spot will cool, followed by another, until we have a drug or vaccine to stop this virus.
Do We Have a Medicine to Stop SARS-CoV-2?
The complete answer is NO.
It is unfortunate that rumors are flying that we are one step away from having a drug to cure or stop this virus that causes COVID-2, the new coronavirus, SARS-CoV-2.
There are two prospects, but the field of medicine is littered with prospects, many never really prove to work. None of these are yet proven to work. I hope they do, and soon, but worry about a mad dash to give millions of people anything that even looks like it might work. We have seen this happen so many times, and the results of such an approach, if we are lucky, end in failure, but too often in tragedy.
The two prospects are chloroquine and Remdesivir.
Chloroquine is an old, very old drug tracing its roots back to the bark of the Cinchona tree of Peru, and used by the Incas for years not recorded. The Spanish enslavers learned the value of the bark and purified an active element from it quinine, which cured malaria like the bark. Quinine was used around the world since 1633, and even became a drink, quinine water. In 1934 quinine was chemically altered to a new molecule, chloroquine, but thought too toxic for people. But it worked so well to cure malaria it came into wide use in the 1940’s.
So what does the bark of a tree, and a drug that cures malaria have to do with viruses? It turns out that chloroquine, and the combination chloroquine/hyroxychloroquine, have many effects on how cells work. Keep in mind, to cure malaria, this molecule has to disrupt a full cell, the malaria parasite, so we know it changes how cells work.
In 2003, Savarino et al published a review of the effects of chloroquine on how viruses attack cells, and how cells create inflammation. It turns out that chloroquine blocks some viruses from entering cells, and for other viruses it keeps them from being copied fully in the cell. Both these actions, if complete, would stop viral infections.
The impact of chloroquine on inflammation is well-known, it is used now for people with auto-immune diseases such as lupus and rheumatoid arthritis, because it keeps cells from making substances that cause inflammation to flare. The issue of inflammation brings up a very important issue. Whenever a germ infects us, two paths to destruction open up. The first is very familiar, it is the path of the germ destroying our cells. But the other path is less well-known. This is the path of the body over-reacting to the germ and causing massive inflammation which then destroys our own cells, not just the germ.
Beyond theory, chloroquine has been tried in the therapy of AIDS and has helped, including reducing the damaging inflammation that HIV creates.
And very relevant to our hopes, in chloroquine was tested in the lab against the SARS virus in 2003 and found to slow its reproduction and lessen the creation of inflammation.
Finally, it seems relatively safe with low toxicity, even for people taking it for a few years for auto-immune disease. The one serious side effect to be concerned about is harm to the retina, which is unusual.
So, much to hope for here, but we are NOT yet able to say that use of chloroquine or chloroquine/hydroxychloroquine will stop this pandemic or save lives. We just do not know that yet.
Remdesivir is a new drug, invented in 2015 to treat Ebola virus. It works by messing up the ability of a virus to make copies of its genes, an essential step in viruses reproducing and spreading. Stop a virus from copying its genes, and you stop the infection and epidemic.
Early promise of working on Ebola led experts in the Congo to find that it simply did not work as well as some other therapies.
Remdesivir was tried in two individuals, one near Seattle, and one in Italy and both got significantly better from very severe COVID-19. The Czech Republic has approved its use to treat COVID-19. China is conducting clinical trials to see just how well it works.
Again, this drug shows promise, maybe it will really work, but it has been used in too few people to know quite yet.
- First, the AP Televisit works really, really well, and so easily. We are so pleased that families are now using it and encourage anyone who needs some help from us to consider this way to be seen by your child’s doctor. To set up an AP Televisit, just call our office at 216-591-1515 and ask for an AP Televisit, as you would any appointment, and we will be sure you are set.
- The experience of one very small town in Italy reinforces the sense that a COVID-19 epidemic can be stopped. All nations that have done so, and this village, have tested widely and isolated cases.
- We do not know how many of the total of those infected with COVID-19 will never have symptoms from their infection. The data from China, and from larger numbers in Iceland suggest that 90% or more of those of us who will be get COVID-19 will have some symptoms. Only small samples suggest otherwise.
- There are some promising drugs being seriously looked at that one day MAYBE will help us with COVID-19. The hope is twofold: 1. that it will keep seriously people alive, and 2. it will stop the epidemic. There is reason to hope that relief may come from these medications, but only to hope, as of now. Again, many, many promising drugs turn out to fail when really tried in the real world, so until any drug is proven to truly work with large numbers of people we can hope, but we cannot use.
For now, we stay home as much as any of us can. We wash our hands. We try to help those infected to isolate enough to reduce spreading the infection. And we hope to test enough people to achieve all this.
Thank all who have turned to the AP Televisits, it is a valuable tool!
To your health,