1 2 3 ... 5
mtn (Forum Supporter)
mtn (Forum Supporter) MegaDork
4/16/20 5:39 p.m.

For further updates, go to page 2 of this thread.

 

Warning: Wall of text. I will be updating this first post in the thread every time I get a new update. Each update, I will put “X Y Z” without the spaces before the new post, and “Z Y X” at the end (and remove it from the prior post) so you can CTRL+F it and won’t have to scroll for 6 hours to get to the end.

These are updates that a retired MD (internist) who is a friend of the family has been posting. Note that I am just putting this here as I found them extremely educational and I suspect they are more accurate than anything we're hearing from any news outlet.

I have reformatted it the best that I can, but these were originally made on facebook, I copied and pasted into an email from my phone, and edited on my computer, so please excuse any annoying formatting quirks with the post.

Additionally, I have redacted personal identification information just because I do not personally know him (Good chance I met him at some point but I don't recall him) and felt it to be "safer". I have not changed anything of substance - I have only reformatted it to make it easier to read, and taken out possible identifiers. 

 

March 19

 

I just finished reading an article published in the annals of internal medicine on March 10th. It confirms a 5 day incubation period for SARS-CoV-2. 99% of infected will have symptoms by 14 days. Infected will test negative for from 2-9 days post exposure. Looks like patients who are quarantined post exposure should be retested 9 days post exposure, Of those who follow 14 day isolation, 1% will go out into the world and develop symptoms and become contagious.

 

Be smart, isolate yourself as much as possible.

 

 

 

 

March 21

 

On the bright side, Moderna will begin to safety test their vaccine on Monday though Kaiser in Seattle. They are starting with 45 healthy volunteers.

Inovio will start safety testing their vaccine next month. They will be featured on Sixty minutes tomorrow.

 

There is a long road between safety testing and making a viable vaccine available to the public. Maybe "the Donald" can actually help by cutting the red tape and fast tracking the process.

 

Great Britain is trying to create herd immunity by allowing their population to become ill. They are trying to protect the at risk, but are allowing the young and healthy to become ill right up to the tipping point of their healthcare system. They are making a huge bet that the ill will develop immunity. Only time will tell. Has all the earmarks of a great tragedy.

 

To date none of the combos of either HIV or antiviral drugs have shown any efficacy.

 

As too mortality rates, we flat don't know the denominator of the equation. The real numbers will be more accurate as testing becomes more widely available. Our country has failed there, despite the rhetoric from Pence.

 

The best efforts to re-frame this has come from using the website put up by Johns Hopkins, coronavirus.jhu.edu

Using their data, South Korea, 1%, Germany .28%, U.S. 1.4%. I think these numbers will look worse in two weeks, as they do in Italy, but much better when we are testing those with only mild symptoms and no fever.

 

On the bright side some good news on testing.

  • South Korea is testing 20,000 people a day. Part of the reason their mortality numbers look so good.
  • As of last Wednesday CDC reported only 32,000 tests done at its facilities and other public health labs!
  • The FDA has put up a great many obstacles to rapid expansion. These appear to be in the past.
  • There is still a supply problem to ramp up the CDC's methodology, but other methodologies are being allowed to ramp up. One of those, from is Thermo-Fisher Scientific, they say they have 1.5 million tests ready to ship. Hopefully within two weeks we can test all the sick and exposed.

 

FEMA says they have started shipping masks and other equipment from the stock piles. They say the have started shipping today, but have only been involved for 48 hours? Shades of Katrina.

 

Keep safe and isolated.

 

 

 

 

March 23

 

On the bright side, no great surprises on 60 minutes last night. Inovio and Moderna are safety testing their vaccines. Best case, a year before ready. Gilead and Regeneron are testing anti-virals, shouldn't take long to see if they are efficacious.

Oxford is working on an at home test, which if it is accurate, would cost about 25 dollars.

 

Imagine what could happen if everyone took this problem seriously and self isolated. The numbers would drop like a rock..

 

 

 

 

March 24

 

On the bright side, the FDA has announced it will allow private manufacturers to market test kits without their review. That should fix the testing problem fairly quickly. Hopefully buyers will look closely at the quality control data before buying them.

 

Sick docs in NYC are being asked to stay at work and to wear a mask. Sounds like a really bad idea.

 

The UK has changed its mind. They now have a strict lock down, enforced by the police. That prior decision is going to kill a lot of people.

 

Amazon is looking to add 100,000 employees to deal with the demand!

 

The first vaccine trial patient was indeed injected yesterday in Seattle.

 

Keep safe, 100 people died in New York yesterday.

 

 

 

 

March 25

 

I read an article today by my favorite medical Author, Atul Gawande. An Amazing man, look for him on YouTube. He has written some wonderful books. The article was published 3/21/2020. even my friend, Gerry Kern, the former editor of the Chicago Trib would be impressed with his delivery. He writes about how Singapore and Hong Kong avoided the spread of the disease in Healthcare workers. The blueprint should be adopted by all healthcare systems. I have already passed it on to management at [Local hospital].

 

It is certainly a message of hope.

 

Stay safe, isolate.

 

 

 

 

March 26

 

The amount of data and information seems to multiply faster than the virus.

 

UK is manufacturing 3.5 million antibody tests so they can tell who is immune and can safely return to work.

VIR a California biotec, has identified two antibody drugs which neutralize the virus, human trials to begin soon.

Italy reported decreasing numbers of new cases despite nearly 700 deaths yesterday. More than 1,000. have died in the U.S.

 

The March 26 issue of The New England Journal of Medicine had multiple articles regarding the pandemic.

" the case mortality may be considerably less than 1%" we are getting a better handle on the denominator as testing becomes more widely available.

  • Normal seasonal influenza .1% mortality
  • Pandemic flu in 57 and 68 9%
  • Sars-1 10%
  • MERS 36%

So, the problems continue to be the total number of cases, the lack of immunity, the lack of effective therapies, the lack of a vaccine.

 

My bet literally is on regeneron pharmaceuticals to be the first one in with a marketable antibody treatment, hopefully by the end of summer. They are big enough to mass produce it.

 

Be safe, isolate.

 

 

 

 

March 27

 

It is amazing how much data and new findings are coming out every day. My friend sent me a link to MT. Sinai in NYC. They have developed an antibody test using the ELISA method. They say it is both sensitive and specific, both very important things for tests. They didn't give hard numbers. This can be used to see who is immune already. They confirm that we have no natural immunity to SARS-CoV-2. They say there is no evidence that people who have already been ill can lose their immunity and become re-infected (not yet anyhow). They will begin later this week to do plasmaphoresis on people with antibodies, concentrate it and give it to the very ill. The hope is that it will stop the virus in its tracks. This would be huge, if it pans out. Shouldn't take long to find out.

 

For those of you who eat Pangolins, you'll have to look that one up, Nature has found that they harbor two different lineages of corona viruses, one 97% similar to SARS-CoV-2.

 

Lancet, a British medical publication has demonstrated that social distancing cuts the spread rate from 2.64 p-er infected person to 1.84. The so called R naught.

 

That's all for today, stay safe.

 

 

 

 

March 29

 

I'm sure you all have heard the warnings about taking ibuprophen with CoVid-19, The WHO has rescinded its position as there is no evidence this is true. I'd stick with Tylenol anyway, but if you take Advil you don't have to stop. It is not gasoline on the fire.

 

Abbott is to begin marketing a rapid test next week, positives in 5 minutes, negatives in 13. They will ramp up production to 50,000 per day. Could be a game changer, Abbott has a history of being very reliable. Under the current rules no FDA approval is necessary.

 

A company named CytoDyn has begun testing its drug leronlimab, in critically ill patients. Seven have been dosed thus far, two were able to be taken off the ventilator. This is a monoclonal antibody the blocks the CCR5 receptor to prevent the damage caused by our own immune systems, the so called cytokine storm. If it is that dramatic, it won't take long to find out. The drug was developed for other problems, The company is holding all of its doses for the current crisis.

 

Stanford published a bit of data, They tested 562 people, only 49 were positive, thus far, for the virus. 11 of those 49 also tested positive for another virus as well. That is not good news.

 

Stay safe.

 

 

 

 

March 30

 

On the brighter side, drive in movies are making a comeback, some report a 90% increase. Some states won't allow them to be open.

 

Dr. Fauci has suggested we may see up to 200,000 deaths in the U.S. from the virus. I think he may be trying to balance out the approach of Trump. University of Washington thinks 81,000 in the next 4 months. Estimates from credible sources vary from a low of 38,000 to 162,000.

 

In my opinion, due to the lack of available testing, we are underestimating how many people have been exposed, were mildly ill or asymptomatic, and are now immune.. If we all follow the rules, and new therapies emerge,I hope we will come in under the UW prediction. Please remember, even if you are immune, you can still transfer virus to others, keep washing those hands and avoid contact.

 

Battelle, a tech development company, has developed a way to sterilize previously used N-95 face masks. They are vaporizing hydrogen peroxide. They claim they can treat 80,000 masks a day, the FDA is only allowing them to do 10,000. What's up with that?

 

We are now being told that elevated temp is not the rule, and may not be the best way to screen for who should be tested. If you are sick and coughing, don't assume you don't have the virus just because you don't have a fever.

 

Stay safe, isolate..

 

 

 

 

March 31

 

Well sports fans, was up early today to read about what's new. I must admit, it's a bit overwhelming. I felt like I was in high school making notes for a term paper. I will try to be concise. Everything today is good news.

  • There may be a leveling off of admissions in both SF and NYC, China reported only 5 deaths yesterday.
  • I listened to the outgoing and incoming CEOs of Abbott last night. They are working 24/7 to crank out their rapid test, goal is to get to 100,000 per day from the current 50,000. This test requires instrumentation, they are working on one that does not. They are trying to prioritize who gets what, initial goal to provide testing for those on the front line. They have 2 million going out!
  • Inovio is going to start clinical trial of its vaccine in April, China is starting clinical trials of its vaccine also in April. J+J has received a huge federal grant for its vaccine, Seems a little weird as they are not a vaccine company. I counted 22 companies working on a vaccine in the Clinical Trials Arena.
  • China is testing 30 drugs for efficacy, they have approved Favilavir for clinical use. Gileads anti viral Remdesivir is being studied in Wuhan. They are looking at 761 patients in a randomized, placebo controlled trial ( the best kind of study ) They should have data within a few weeks. The WHO has noted that this drug has demonstrated efficacy, whatever that means, pretty vague.
  • My favorite company still is Regeneron, They are testing two monoclonal antibodies both of which have been shown in mice to clear the virus. They are also testing their drug Kevzara, an IL-6 inhibitor, to try and block the cytokine bomb that is going off in the very ill.
  • Takeda pharmaceuticals. is gearing up to test their version of a hyperimmune globulin, made from plasma of patients who have recovered from the virus. This is the same approach that the Mt. Sinai group is looking at. Takeda is capable of mass production.
  • I like the big companies best as they can gear up production of their drugs if they are shown to be effective. The little guys will have to find a partner.
  • Next up, hydroxychloroquin, with and without the drug in a z-pack. France is looking at 80 in an uncontrolled study using both drugs, they reported shortening of time of viral shedding and " clinical improvement" 3 were admitted to ICUs and one died. 93 percent had no viral shedding by day 8. Many trials are in place, especially in China, I've read that Novartis, a pharma giant is going to study this. That will be a big help. I give it 50/50. In the studies already going, it is clearly not a miracle or a game changer.
  • The CDC is considering whether to change its stance on all of us wearing masks. I won't leave home without one. Neither should you. Bandannas are Ok, a fitting mask is better. Make your own.

 

Isolate and be safe. .

 

 

 

 

April 1

 

It is becoming clear that I could read data 24 hours a day at this point. I'm going to read until 10 a.m. and then post what seems most relevant. I'll limit today to mortality, serology, transmission, and vaccines.

 

I have almost 50 years experience critically reading studies from peer reviewed journals. Making sense of non-peer reviewed studies, published and unpublished is quite difficult, even for me.

 

  • Mortality rates out of China show 1.38% mortality. If you add in the people without symptoms, it's about 0.66. That is 6 to 10 times as much as regular seasonal influenza.
  • In the U.S., mortality is 0.9% in the otherwise healthy, 10% in those with heart disease. Those aged 70-79 have an 8% mortality (me ). 3.6% in the 60 to 69 range (Patti). From the MMWR, those 20 to 54 < 1%, < 19 zero.
  • The older you are, the more health problems you have, the more careful you need to be.
  • The results on serology (blood testing for antibodies) are a bit disappointing. Using combined IgG and IgM testing only 40% are positive at seven days or less, while almost 100% are positive at 15 days. Useful to see who has really been infected. Lots of people who think they had it early on, probably did not. The flu and other respiratory illnesses being more likely.
  • The Johns Hopkins website pretty much pans both chloroquine and hydroxychloroquine as therapies. Available data doesn't show much.
  • I looked hard today at transmission. The WHO and the CDC disagree. The WHO feels direct airborne transmission is minimal, and has to be less than 3 feet from someone coughing or sneezing. This is the old aerosol vs. droplet effect.
  • There are no great studies. That debate continues even for influenza. Looking at Meta studies from SARS, MERS, and Flu, masks may be beneficial, possibly helpful.
  • Epidemiologists can't tell the difference between droplet and aerosol spread.
  • Dr. Donald Millen at the University of Maryland thinks the WHOs position is not well thought out and dangerous.
  • Clearly hand to mouth is the biggest risk, masks probably cut down the risk of you giving it to others. The CDC is considering changing the recommendation about all of us wearing masks.
  • The data below on vaccines was from a podcast by Dr. Greg Poland, a vaccine researcher from Mayo with 30 years of experience. He also made some comments about therapies.
    • The immunity/vaccine arena is very complex. Most of the current vaccines being developed and evaluated are monoclonal, only against the S protein of Sars-CoV-2. Polyclonal vaccines have a much better chance of being effective, using 4 proteins from the virus instead of one.
    • The reason it takes so long to develop is to insure the vaccines are both safe and effective. It took 6 years for the Ebola vaccine. They are trying to speed this one up. They are testing non-human primates and humans at the same time instead of in sequence. They are pulling reviewers as quickly as they can. There have been monoclonal vaccines in the past which actually made people worse.
    • There are multiple researchers developing monoclonal antibody therapies. Once developed, they can be rapidly mass produced. This seems the most likely avenue for short term help.
    • The problem with plasma based therapies from those with antibodies is that they require one donor to treat one to two patients. These are polyclonal antibodies.

 

stay safe

 

 

 

 

April 2

 

New day, same problems, so much info, so little time. What we do today manifests in 14 days. What we did 14 days ago we will see today. It is time for a national stay at home policy! Behind the curve yet again on a national level. The single biggest question out there, in my mind, is how long will people who have been infected remain immune. MERS patients have long lasting immunity. SARS-1 patients have short lived immunity. Only time will tell. I pray for the 1-3 year variety, lasting long enough for us to have a workable vaccine.

 

  • Duke has confirmed the use of vaporized hydrogen peroxide to sterilize masks without compromising their integrity. Great news.
  • I read a statement from the WHO on aerosol spread. It can and does happen in hospital care of sick patients. This is mostly when intubated patients are given treatments or when their tubes are placed or removed, and when they are given CPR.
  • They speak of droplet transmission, as opposed to aerosol transmission. If you are within 3 feet of a person who has the virus and they cough or sneeze, these droplets in contact with your mouth or nose or eyes can make you ill.
  • A editorial in the New England Journal of Medicine (NEJM) yesterday did an experiment showing aerosolized virus in the air for three hours. The WHO's response was this was created by a powerful machine which is much different than a person coughing. This same article showed viable virus gone from cardboard in 24 hours, drastic reduction in viral counts on steel in 48 hours, and plastic in 72 hours. The take home message: spray or wipe down everything you bring into your home.
  • There was a great article in the Lancet today, the British version of the NEJM. It looked at stats from China. They examined 3665 cases of PCR confirmed cases. In the sickest patients, deaths occurred at 17.8 days in, hospital discharge was at 24.7 days, This helps explain why the health systems are being overwhelmed. The mortality rate for these people was 1.38%. It was 0.32% under 60 and 6.4% over 60. It was a whooping 13.4% over 80! They then estimated the overall mortality of the virus, which includes those ill but not PCR confirmed, at 0.66%. Hospitalization rates increased with age.
  • Transmission by people who are ill but not yet symptomatic is being confirmed by multiple sources: Nature, a great journal, and Morbidity and Mortality Weekly Report (MMWR).
  • It is estimated that of 157 new cases in Singapore, 10 were from contact with people with no symptoms... not such good news.
  • Testing is indeed ramping up. More than one million tests have been done. There is a huge backlog at the biggest private labs. Quest is the worst one. This has hugely affected California which lags behind in testing severely. Quest over- promised and continues to under-deliver. It is criminal..

 

Last topic for the day, once again vaccines.

One of my closest friends in medicine, [redacted] started out as a Harvard MBA, then went to med school and just recently retired as a full professor of Pediatrics at the U.of W, this despite the fact that he worked in Spokane. He was involved in vaccine research for a good part of his career. He is one of the smartest docs I know. When he went to conferences with the big boys in vaccine research, he would always tell me about being in awe of how bright these guys are. They are working hard to give us a viable vaccine.

 

Among the many issues involved with developing a vaccine, the biggest one, in my mind, is that of vaccine immune enhancement. This is pretty complicated. One part of this is antibody induced enhancement (ADE). The targeted virus is able to leverage antibodies to aid infection. The other part of this is Th2 immunopathology. This is like an allergic reaction, where there is a faulty T cell response, which can make you sick or even kill you. The classic example is from the 60's...

an attempt to create a vaccine for RSV killed two toddlers, and derailed the research for a generation. We have a vaccine now that saves a ton of lives, and prevents countless hospitalizations. It had its costs.

The WHO has formed a special committee to look at the enhancement issue for COVID-19 vaccine, so we should have a summary report in a few months.

 

 

stay safe.

 

Many thanks to my wife, who reviews and helps me make sure it''s in English, not my forte. I will wait to post until she has reviewed it from here on.

 

 

 

 

April 3

 

I was going to try to keep things simple today. As usual, there are too many important topics out there to do so. I just want to reiterate, it is perfectly fine to share the material, that is why I am making it " public".

 

The first topic of the day is once again testing. As I posted previously, the FDA deregulated testing. This means that they have allowed marketing of testing they have not reviewed. This is a two-edged sword. Not all tests are created equal. It is a good idea to ask, as testing explodes, where the methodology came from when you have a test. There are many kinds of tests out there. Testing for antibodies, IgG/IgM , is one you will see more and more. IgM goes up first, then IgG after you have the virus. This is a useful test if you want to know if you have already had the virus. Only 40% of people who have had the virus will be positive at 7 days or less! That number is close to 100% at 15 days. If you are positive, you may assume you are now immune, at least for the short term. We don't know how long it will last. Even if immune, you can still transfer the virus to others. You could be ill enough to be in an ICU and have a negative antibody test.

 

Becker's Hospital Revue published numbers projected by a modeler from the University of Washington. It projects when the virus will peak and when it will be controlled by state. It will be control for most hospitals by mid April, NYC by April 9, Washington state by April 11, Ill by April 20, April 26 for Idaho and Cal, May 5 for Oregon. These are just projections based on available data. Hope they are close. The virus will peak and resolve.

There will be, most certainly a second and third wave. I expect we will see a bump when social distancing is relaxed. We will likely see a third wave next December. If this bug behaves like seasonal flu, which it likely will, the southern hemisphere will get walloped this summer. Hopefully they will have learned from our experience and mistakes.

 

For those of us who reside in [Local Idaho County], we have the most per capita cases of anywhere in the country. This means that random physical contact with a single individual is more likely to be a source of infection than anywhere else in the USA. Be very careful. Isolate and protect yourself.

 

New observations suggest that up to 25% of infected people may never have symptoms. Most people with the virus will be without symptoms for 48 hours. Data from Singapore and China showed lags from infection to symptoms of 2.5 and 2.89 days respectively. What this means to you is that people who feel completely well can give you the virus.

 

You will see more and more mentions of masks in public. The CDC is going to change its recommendation, it is just a matter of time. The National Academy of Science believes that bioaerosols are generated by exhalation. They believe the virus can be spread by close breathing or talking! Sixty singers in Washington state went to choir practice. Forty of those sixty people later became positive for the virus. Wearing masks when out in public should cut down transmission from those who are infected, but without symptoms to all of the rest of us. Start now. The life you save may be your grandmothers.

 

Read an article in the NY Times yesterday. They talked about DNA testing for the virus. It just goes to show that not everyone who is writing knows what they are talking about. SARS-CoV-2 is a single strand RNA virus. It does not have DNA. You have to read critically. Just because it's in writing, on the internet, or coming out of a politicians mouth does not mean it's true.

 

Stay safe, isolate, wear a mask in public.

 

 

 

 

April 4th update:

Good morning everyone. Hope you are all staying safe.

The CDC, as predicted, has suggested we all wear masks when out in public. There are now many many sites and postings that instruct how to make you own. Some of these are a riot. The funniest I have seen was a woman using her thong as a mask. It seems to make a difference in Asia, nothing to lose. The UK is considering an immunity passport, which will allow those who have antibody to return to work. I think this is a great idea. I hope we will see this soon.

It seems to be a slow science day. I will write again about testing to help you understand a little better what is going on. It is very important that all understand that testing is just a tool. A negative test does not mean you don't necessarily have SARS-CoV-2 which I will refer to as the virus from here on out. A positive test does not necessarily mean you have the virus. Bear with me and I will explain. [Harvard MBA/Pediatric Professor friend who worked on vaccines] my friend and colleague, had suggested I write about this today. It was already in the pipeline. This is the second time he has suggested I write about a topic I was already working on. This time Steve also wrote a piece on the subject and sent it to me. I have asked that he post it. If he does, I will re-post it for all to see. As Steve is a researcher and a full professor of pediatrics, his piece is in medical. I'll try to put mine in English.

  • First, from the March 31st issue of the NEJM, the premier journal in our country if not the world, here is some new info on testing. First I'll report the results, then explain what the terms mean.
  • The article compared the IgM serology, blood test for antibody using ELISA, with PCR, the swab test looking for the RNA of the virus. As you may recall from prior postings, IgM is the immunoglobulin that goes up first when a person's immune system battles the virus. PCR (polymerase chain reaction) takes the viral RNA and amplifies the particles so they can be measured.
  • During the first 7 days, PCR beat serology, 66.7% sensitivity for PCR, 38.3% for antibody. During the second 7 days, 54% for PCR, 89.6% for antibody. Others have reported that by day 15 virtually 100% of antibody tests are positive if you look at IgG and IgM. By day 5.5 antibody was better than PCR. More importantly, by day 5.5, if you did both, the sensitivity was 98.6%. By day 5.5 single PCR had dropped off to 51.9%.
  • This same group looked at a family cluster. The family members of the sick patient were negative for swab and positive for antibody.
  • Li and his group (the people that published this data) have developed a lateral flow immunoassay, which can be done at the point of care. It requires a drop of blood, no equipment, and takes 15 minutes to get a result. It looks at IgM and IgG. Their sensitivity was 88.7%, and specificity was 90.6%.

 

First I will explain what this means to you, then for those who care, explain sensitivity and specificity.

  • If you first became infected within a week, the swab test will miss that you are actually infected 1/3 of the time. If you first became infected two weeks ago the swab will miss that you are infected 1/2 of the time. If you first became infected 15 days ago the blood test will be right nearly 100% of the time. By then the swab will be nearly worthless. The obvious conclusion is that we should be doing both tests, when we screen people who are either ill or have been exposed.
  • Sensitivity means, how often a test on an infected patient will show they have the virus. Specificity shows how often a positive will be correct. Even using both tests, PCR and blood, a small number of people will test negative, who are infected (false negative). A positive test will be incorrect nearly 10% of the time (false positive). I will call attention to this with both the county and the hospital.
  • Looking at this data, we are clearly underestimating the number of people who are infected. Many, many with a negative swab are infected.
  • Is totally reasonable to ask, when your being tested, about the sensitivity and specificity of the test you are being given.

 

Stay safe, isolate.

 

 

 

 

April 5

 

One would think that on a Sunday there wouldn't be too much to write about. Wrong! For those readers who don't know me, I am a retired internist in [Local Idaho County] - the nations per capita leader in cases of the virus - with 41 years of practice experience. Once again, feel free to share this. I made it public with that in mind.

 

As availability of testing increases, the number of reported new cases is going to be deceiving. The number of deaths will be deceiving as well as the length of time between admission to the hospital and death is long . The number of admissions to the hospital would be useful, but I don't see anyone tracking that. Hang in there as the numbers seem to increase.

 

  • The AMA (American Medical Association) sent a letter to the governors of all 50 states, encouraging closing non-essential businesses and limiting non-essential gatherings.
  • A joint letter from the AMA, the American Hospital Association, and the American Nurses Association stated, "Physicians, nurses and healthcare workers are staying at work for you"... "please stay at home for us."
  • The CDC website looks more and more useful to me. The links include, 'self checker', 'what to do if your sick', 'how to protect yourself', and 'take extra precautions'.
  • The good news is that ER visits and hospital admissions for seasonal flu are dropping as we near the end of influenza season. That should make things easier for hospitals and ERs in many ways.
  • One of the many problems facing healthcare is end of life decisions. Making these decisions over the phone with families of unconscious patients is extremely difficult. If you don't have one, download and execute a living will. Better yet, have a durable power of attorney for health care and make sure your designee understands what you want.
  • I have seen one statistician write that the number of people in Washington State infected by one sick person has dropped from 2.7 at the start to 1.4 now. Social distancing and hand washing is helping.
  • There was an article published in The Lancet yesterday regarding testing. This is the UK's most prestigious medical journal. It reiterates the current position of the FDA. They have told testing manufacturers, " You can start sending it (tests) right away and then send us your data. If we don't like it you have to take your product back." An obvious two-edged sword.
  • I looked at data from several manufacturers yesterday. In my mind, at least one had skewed their results to look better than everyone else. We will have to be careful.
  • The article further stated, the total number of people who have been infected is purely an estimate. We need hard data. (Only mass testing will give us that.)
  • One researcher, Hibberd, argues that once people develop immunity to a specific corona virus, they should probably have immunity for life. This seems doubtful to me based on available data, but wouldn't that be nice. The article further discusses the issues regarding creating sensitive and specific antibody testing (see yesterday's post.)
  • Part of the issue is some of the current tests will be positive for the antibody from other corona virus infections. One of this family of viruses caused SARS-1, three others cause the common cold. The search is on for a surface protein that is completely unique for SARS-CoV-2. When found, it will be the key to avoiding false positives, which going forward will be a huge issue in telling who is truly immune. Would hate to send people back to work who think they are immune, but are not.
  • The chief of surgery at Columbia University, Dr. Craig Smith, is writing daily e-mails from the front line. They have apparently gone viral. Might be worth a look.

 

That's all for today.

 

Stay safe, isolate.

 

 

 

 

April 6

Corona virus update # 17

 

For any first time readers, if you like what I post, you might consider at least skimming these posts in sequence. It will help with terms and the progress we are making.

 

  • A group of researchers from Yale have done a statistical analysis of data from Asia and feel that if we all wear masks when out in public, we could decrease the death rate by 10%. Again, the life you save might be your grandma's. Aerosol research done with non-SARS coronavirus patients, the common cold, has shown that at 6 feet, viral RNA can be recovered, 40% from aerosols, 30% from respiratory droplets. When the patients wore masks, both went to zero. The presence of viral RNA does not necessarily mean there is enough virus to cause infection.
  • The number of deaths in NYC dropped from 630 on Saturday to 594 on Sunday. Lets hope this is the beginning of a trend. California and Washington State are showing signs of improvement according to Medscape. Spain and Italy appear to be leveling off. South Korea's numbers are plunging, and only one death reported in China. U.S. deaths over the weekend, Fri 1169, Sat 1344, and Sun 1137. It's a bit early, but hopefully leveling off to down trending. We will see. It is hard to understand those that think this is all a conspiracy to control us, when in this country alone this many are dying.
  • On the negative side, the number of new cases in Singapore spiked. The first cases have been found in the slums of Mumbai. This could be a new raging hot spot.
  • The governors of 8 states are still resisting lock down. In my mind they will all be guilty of manslaughter when this is finally over.
  • The Chinese lock down is being relaxed, vacation areas are being opened. I fear they will see a second wave... time will tell, and hopefully we will learn from their experience. Austria will begin to open businesses on April 14th.
  • CVS, Walgreen's, Walmart, and Target on a deal with the government, will begin opening testing centers. A government spokesman tells us that all hospitalized patients, healthcare workers, and sick elderly will be able to be tested during the coming week. If they are speaking of PCR, it will not help much those who have been sick for more than a week.
  • With regard to the chloroquine question, it is not a cure but could be helpful. That much is certain. The good news is that a study is being set up out of Henry Ford Hospital in Detroit. Hopefully it will be designed well and will give us definitive answers as to how useful it may be.
  • On the bright side, the FDA is working to enable access to convalescent plasma. (See prior posts.) The agency expects to "be able to move thousands of units of of plasma to patients who need them in the coming weeks." This will of course, require thousands of donors. This will also require hundreds of techs, and a pipeline. We will see.
  • A second treatment, hyperimmune globulin, is also under development. It is more complex.

 

Stay safe, isolate, wear a mask when out in public

 

By the way, for those over 70.5, the Required Minimum Distribution has been waved for 2020.

 

 

 

 

April 7

SARS-CoV-2 Update Number 18

 

Most importantly, it's National Beer Day!

 

Today I'll post about three things... 1st- ventilators, 2nd-statistical bias, and 3rd- today's stats.

 

Vents:

  • There is a lot out there on ventilators. Over my career of 44 years, I intubated patients and managed them on ventilators.
  • I took care of many patients with ARDS (acute respiratory distress syndrome.) JAMA published data on ventilator care and mortality. In one region of Italy they reported on their experience. The average ventilator patient required 14 cm. of PEEP (positive end expiratory pressure), to maintain oxygenation. That is pressure in the system at the end of exhalation, when the pressure is usually zero... 15 cm. was the absolute limit I used. We know that high pressure damages lungs proportionately to the amount of time you have to use it.
  • The death rates for patients on ventilators is all over the map... 34% in the UK, 50% in Washington State, and 30 of 37 in one case report from China. These are horrible numbers. Physicians are using the normal protocols for ARDS. It has been suggested that the disease behaves more like high altitude pulmonary edema than ARDS. The suggestion is that we use as little pressure as possible, rather than as much PEEP as the patient can tolerate. One report offered that this approach had a zero mortality rate... a little hard to believe. I expect we will see more and more ventilator experts trying this approach. It needs to be formally studied.

 

 

Statistical Bias:

  • All those who read medical literature know you have to read statistics with caution. They are easy to manipulate, and can give a false impression of what is really happening.
  • In the case of the virus, the interventions we introduce take at least two weeks to manifest... social distancing, wearing masks, etc. Death rates have an even longer lag time. The number of new cases is skewed by the lack of testing capability. As testing ramps up there will be a skew toward increased numbers of new cases. Probably the best numbers to follow, will be number of admission to both the hospital and the ICU, although in places like NYC, people are being sent home who would have been admitted two weeks ago. From my perspective, if we see a drop in new cases reported, despite more tests being done, that is much more improvement than you would assume.
  • It would appear that African Americans are more likely to be effected severely by this disease. They compose 72% of the deaths in Chicago, and 70% of the deaths in Louisiana.

 

Today’s Stats:

  • China reported 0 deaths yesterday, and only 32 new cases. They are allowing limited travel, and some of their vacation spots are showing up to twenty thousand people in relatively close quarters. I expect this to be catastrophic, but we will see over the next 2 to 4 weeks.
  • In Italy the number of new cases dropped for the first time in three weeks. In South Korea, the number of new cases was less than 50 for the second day in a row.
  • In NYC, the number of deaths increased to 731, and France had its highest number of deaths at 613. Remember the lag in deaths as discussed above.
  • Both Idaho and Washington State appear to be showing a head and shoulder pattern with regard to new recorded cases. That is a very good thing if it holds. The number of new cases in Washington State is dropping dramatically.
  • The new case numbers in India are doubling every 4 days. They have a national lock down. The problems there will be horrific.
  • South Carolina joins the lock down states. Only 8 states are without it. Dr. Fauci seems to feel the remainder of states have a functional lock down. My Professor Friend (whom I will refer to as the professor from this point on) met Dr. Fauci once. Steve said he is the smartest guy he ever met. He further said Fauci has trained half the virologists on the planet... an exaggeration I am sure. You might want to listen to what Fauci says. The professor posted about vaccines today and you should read that as well.

 

That's it for today, stay safe, isolate, wear a mask in public.

 

P.S.

 

Bank of America has opened a portal for government loans to small businesses. They've had 175,000 responses thus far!

 

 

 

 

April 8

SARS-CoV-2 Update #19

 

On the bright side, some good news...

  • Data from China published in 'Proceedings of the National Academy of Science' showed great promise for plasma infusion.Ten patients with severe disease were given a 200 ml. infusion of inactivated convalescent plasma from recovered donors. All symptoms in all patients "disappeared or largely improved" within 1-3 days. There were no serious side effects. Viral load was undetectable in seven viremic patients in 7 days. (Viremia means there is recoverable virus actually in the bloodstream. This is a bad thing.)
  • At this point, if I were ill, that is what I would want. Pence promised a few days ago, that plasma would be available quickly. I hope he was correct.
  • I was sent an article from China yesterday by my friend [redacted], M.D. I couldn't tell where it had been published. It was not yet peer reviewed. That being said, it was elegant, well-written with beautiful models, which had been computer generated. To fully understand the science, one would have to have a PhD in molecular biology. The basics were that they believe this is an ancient virus. They conclude that the viruses non-structural proteins bind to porphyrin. This is a substance that is contained in our hemoglobin. This binding then makes the hemoglobin less able to carry oxygen. This renders affected individuals, effectively anemic, and oxygen starved, but not from their lung disease. They further postulated that chloroquine and an antiviral Favpiravir work by both preventing this binding, and by preventing cell destruction. We will have to see if this theory gains traction outside of China. I will keep you posted, if I see it confirmed.
  • Sick people coughing while wearing a mask do not completely block virus. Three patients doing so 8 inches from a petri dish showed growth of the virus. Keep your distance.
  • Dr. Fauci is optimistic that schools will be open by fall.
  • California says they are procuring 200 million masks a month. Further, the number of people going to the hospital and the ICU has eased.
  • Many are reporting a ramp up of ventilator production. As I read their plans, the new ventilators will be for export, or to replenish and beef up our stockpile, as we will be way past the peak need by then.
  • As the death numbers mount, you may want to reread yesterdays post about lag and skew of data. It is not unexpected, and doesn't really mean much.
  • The owners of [local lab] plan to begin to do antibody testing within the next week or two. They plan to gather data in a way that might be used for research. It will not cost $100.00
  • In anticipation of this I will devote tomorrow to revisiting testing, so you all know what to do, and what the tests mean.
  • Looking at new cases in [Local Idaho County], Idaho, which has been the worst per capita county in the U.S. is very encouraging. We will become the most immune county in the U.S. on a per capita basis. April 1st- 64 new cases, April 2nd- 95 new, 3rd- 54 new, 4th- 5 new, 6th- 13 new, and 7th- 3 new. Looks like we have peaked and are dropping like a rock!

 

That's all for today, stay safe, isolate, wear a mask when out in public. Make it a dense one.

 

 

 

 

April 9

COVID-19 Update #20

 

After a few days, when I had to dig to find material worth commenting on, we are back to so much out there I could read all day and not come close. I watched the [County in Idaho where he lives] town hall meeting last night. Since that has local implications only, I'll save it for last. It is, however, very important for [County in Idaho where he lives] residents. There are some things that need to be clarified, I will do that privately before discussing them publicly.

 

As promised, I am going to revisit testing today. It is important that you understand what you are getting, and what to ask for. My sources for today's briefing include, The NEJM (New England Journal of Medicine) article from March 31st, the Lancet article from April 4th, (I have re-posted), and a JAMA (Journal of the American Medical Association) article published online April 6th. Just as a reminder, these briefing are meant to be read in order, so I will not spell out abbreviations over and over. There are two main kinds of tests, RNA testing, done with a swab, this is what all testing has been to date. Then there is serology (blood test) which is just ramping up. They are very different, and have very different uses.

  • First, RNA testing. This is the test which is being done for people who are acutely ill. I felt fine yesterday, today I have a fever, I'm coughing, and I feel short of breath... this is the test you need. This test is dependent on where it comes from in the body, and the technique of the collector. During the first week of illness it is positive in only 66.7% of patients. It deteriorates in its utility from there on. During the second week it drops to 54%. What this means to you is that if you are acutely ill, this test will be negative in 1/3 of patients who have the virus and it is less and less accurate over time. If you are negative, it does not mean you do not have SARS-CoV-2! You need to self isolate. The JAMA article stated,"it is important to emphasize that...a negative RT-PCR result does not exclude COVID-19." The turn around time for this test has been 12-14 days or more. The reference labs over-promised and under-delivered. From this point on,at least here in [County in Idaho where he lives], if you are severely ill, we will have the test back in 15 minutes, a positive can be as fast as 3 minutes. The rest of the testing should have a 24 hour turn around time, within the next week. The [local] system will be able to do 100 RNA tests at a time and theoretically 1000 a day, according to [Local doc]. Thank you [local hospital]
  • Second, serology testing. This is done with a drop of blood, or a standard blood draw. This measures antibody to the virus, There are multiple kinds of antibody, for the most part, we are assaying IgM, and IgG, usually in combination. The majority of the kits going out are a simple yes/no answer, they are very fast, like doing a pregnancy test. It is possible to quantitate one or both; that takes longer and is done only in the bigger labs. The New England Journal article used an ELISA assay for IgM. By 5.5 days it was more accurate than the RNA test. During the first 7 days it was positive, on average, only 38.3% of the time. During the second week of the illness, it jumped to an average of 89.6%, and by day 15 it was virtually 100%. At day 5.5 (and this is very important), using both tests detected the infection 98.3% of the time.
  • What this means to you is, if you have a negative swab test and you are sick, you should have an antibody test. If both are negative and you are still sick you should have them repeated in a few days. If the hospital can't or won't do the serological test, you should have it done privately.
  • If you were sick two weeks ago, the swab test is worthless, but the serology test should be very accurate.
  • Now for the disclaimers. These are my opinion. I did spend more than a decade as medical director for a laboratory. I think I understand better than most the pitfalls and limitations of testing. As mentioned in previous posts, the FDA waved approval for serology. They said, sell your kits, then send us your data, if we don't like it, you will have to recall your kits... a clear two- edged sword. All these tests will have false positives and false negatives. Hopefully under 10 % in each direction. The verification process should be done against known PCR positive cases for positives, and pre-epidemic blood for the negatives, many are using serum from Sept. 2019. I've seen several who are testing their kits against reagent control only. I really don't like that at all.
  • There will be some patients told they are negative, who are not. There will be some told they are positive who are not. If we equate positive antibody testing to immunity, and we are wrong, that is a bad thing. We have to find a unique protein on this virus, so serology will never say yes and be wrong. The problem is that could take months and months, and it might not even exist. We will have some positives that reflect antibodies to other coronaviruses, we are going to have to live with that for the time being.
  • [Local] Apothecary should be up and running by a week from today with a test kit for antibody. [Redacted] Urgent Care may or may not be continuing to test. The [local city] is launching a cooperative study on antibody with other partners. (see their press release)

 

 

 

I am now 4 hours into today's project. I am going to post this and write a second piece later with the news of the day and excerpts from the [County in Idaho where he lives] town hall meeting last night.

 

 

Be safe, isolate, wear a mask in public.

 

 

 

 

April 9 part 2

COVID-19 update # 20-B

 

Now for part two, first the world, then [County in Idaho where he lives].

  • South Korean CDC has noted 51 cases where people were sick, became negative times 2 (their definition of recovery), and were then positive again. Hard to know what that means. Keep you posted. They have the world's most expansive testing program.
  • The Feds are ending support for testing sites on Friday. Some will close without that support. Colorado Springs and one outside of Philly will be gone. The later has done 5,000 tests to date.
  • The Institute for Health Metrics has posted new projections. These are based on full social distancing continuing. U.S. deaths 60,415 by August 4, 2020. They see the peak death rate for the country coming on April 12, NYC to peak today, Cal to peak on April 15, Idaho April 16. Hope they are correct, or even close.
  • India used to have 14/20 of the most polluted cities on the planet. It has dropped to 1/20 since their lock down. New Dehli residents are seeing blue sky for the first time in their lives. L.A. now has the cleanest air of any major city in the world!
  • [Local updates redacted]
  • I was happy to learn that people from outside our valley are asked to self isolate for 14 days on arrival.

 

 

 

Stay safe, isolate, wear a mask in public

 

 

 

 

April 9/10

COVID-19 Update #21

 

Funny, it doesn't seem like three weeks. In some ways it seems like three years.

  • In NYC, the number of new admissions to the hospital is dropping.
  • The State of Washington is sending ventilators back to the Fed stockpile. They also announced the Army field hospital by Century Link Field would be removed.
  • California is loaning its excess ventilators to other states.
  • Health and Human Services rolled back its plan to withdraw help from testing sites... thank goodness... now Donald needs to stop threatening the WHO.
  • The CDC is beginning its own testing programs, and doing this to begin to collect solid data. They are beginning by testing in hot spots. I wonder if they know about [Local Idaho County]. Stanford is doing research as well. They have, in three Bay Area locations, set up testing for 3,200 people; the data should be forthcoming. In [Local Idaho County], data gathering for participation in a study should begin soon. I am not completely sure who we will be partnering with. The press release stated Fred Hutchinson in Seattle, and Dr. O'Connor mentioned the Virology Dept. at UW. The Albany College of Pharmacy and Health Sciences was mentioned by both. I pulled up the latter online. You should too.
  • Many debates continue to rage regarding the virus and its behavior. One of those areas is: Will it be seasonal like the flu and other respiratory viruses? I hope so, as it will give us a chance to work on therapies and a vaccine before next winter. The WHO believes it will not. Dr. Iwasaki, a professor of immunobiology at Yale thinks it will. He believes the dryness of winter is what drives this. Droplets become aerosol if the fluids evaporate quickly. Dr. Lowen, an associate professor of microbiology and immunology at Emory, points out that H1N1 influenza back in 2009 didn't start out like seasonal flu, but became that way later. It began in April and May of that year.
  • China had only 5 new cases last week. Most of those were imported. The experience there will inform us going forward. Sweden has decided not to lock down. I pray their experiment won't go the way that it did in the U.K.
  • I strongly suggest you take your information from people who know what they are talking about, like Dr. Fauci. There is a lot of fake news out there, coming from both sides of the aisle. Let's stick with the facts and informed opinions and not with politics.
  • Melinda Gates has spoken about how bad this problem is going to be in the developing world. Lack of testing, lack of clean water and basic sanitation, and inability to isolate, will all come into play. I am trying to follow the numbers from the slums in Mumbai and others. The Lyari slum in Karachi, Pakistan holds 2/3 of that city's 16 million people. The last thing I saw was 3 deaths and 22 cases in Mumbai. I look for this to double every three to four days. It will be vastly under reported due to lack of testing. I expect many will die in place.
  • If you ever had any doubts, we are all in this together. Problems anywhere in the world are our problems as well. Find a way to help, be it locally, nationally, or globally. As Ram Dass would have said, if he were still alive, "Compassion In Action " is the key. Local food banks are in real trouble. More demand, less food due to restaurant closures. You can start there.
  • Read a report on takeout food. FDA feels no problem with the food itself. How its handled is another matter. My advice, only use restaurants you know and trust.

 

 

The engineers out there will get a kick out of this: New Jersey is looking for COBOL users to help with their unemployment claims. Kind of like if the IRS announced they needed experts in hieroglyphics to help with tax returns. It is pretty clear what the problem is. Time to brush up on FORTRAN another 50 year old computer language.

 

 

Be safe, isolate, wear a mask in public.

 

 

 

 

April 11

COVID-19 Update #22

 

From this point on I will rely on all of you sharing these posts on your timelines and request that you do so. I will not be accepting friend requests from people I do not know.

 

I read a very interesting discussion in the NY Times magazine yesterday, about when will we get back to normal. It is an interesting read, although full of speculation and projections. I expect they are correct in saying concerts, conferences, and sporting events with crowds of people will be more than a year away. They stated that mortality rates from less pollution and fewer auto accidents will be significant. I think the increase in suicides will offset this. We will see. One point they make is that at some point we will have to make an ethical decision about re-opening society and the deaths we will create by doing so. One quote offered said the presence of disease kills people, the lack of a livelihood kills people as well.

On the brighter side... the data.

 

My problem, how to reduce 4 pages of notes into something useful.

  • From the NEJM April 9-10, Gilead's anti-viral Remdesivir had a compassionate use trial from 1/25 through 3/27/2020. All patients were severely ill. Follow up was 18 days. 68% had a lowering in class of oxygen support, 17/30 on ventilators were able to come off (extubation), and 47% were well enough to be discharged.
  • O.K., now I want plasma and Remdesivir. Let's hope they (Gilead and the FDA) crank this up. Gilead has given up its orphan drug status so it could be manufactured generically sooner. Thank you Gilead, for making the ethical decision as always.
  • From the Lancet dated April 11th. on chloroquine and hydroxy chloroquine: The WHO and the European version of the FDA feel there is not enough evidence to support their use. The U.S. FDA and the French are permitting it. The FDA's chief gave it a maybe as she announced the EUA (emergency use authorization). She cited no references to studies.
  • Michael Ackerman, a Mayo clinic genetic cardiologist, states 1% of those taking the drugs are at risk for long QT, which predisposes one to sudden death. If we give it to millions, thousands will die. The efficacy is questionable, the side effects are known. If I gave it to 400 of my well patients and it killed one of them I would be very upset. There is a phase three trial underway, I would wait for results. I am assuming this is the Novartis trial, the drug's manufacturer.
  • At the very least, a baseline EKG followed by an EKG on the drug, should be given to any planning on taking the drugs.
  • Speaking of clinical trials, I read through the updated list on 4/10/2020. There are more than 100 outside the U.S. and 57 inside the US. Hooray for science. 55% of the U.S.trials are treatment trials, 3.6% are vaccine trials. The CDC has a guide to current treatment options.
  • The WHO has weighed in on point of care rapid testing. They feel at this point it is for research only. The FDA, obviously, does not agree. I think the FDA is correct on this. If you have it done, do it through a professional who is also gathering useful data for analysis. It is on the FDA to review the tests, and pull the ones that don't measure up.
  • From Becker's Hospital Review: The UW has published new projections for peak hospital stress:
    • The Nation- today!
    • Vermont-April 1
    • Washington State- April 2
    • California-April 13
    • Idaho- April 14
    • Oregon- April 22.
  • An unrelated article in 'Becker's' stated 354 rural hospitals are at risk for closing. That's 25% of the remaining 1,430. Idaho is at risk for 4, which is 19%. This is a bad thing for rural states.
  • Yet another small study report for China published in the NEJM: Five patients critically ill on ventilators were given two plasma infusions from recovered patients. Over the next two to nine days 3/5 came off the ventilators, 4/5 lowered 3/3 inflammatory markers, the fifth lowered 2/3 markers. Virus in the blood stream (viremia) cleared in all 5 by day 12, and as early as day 1.

 

OK Pence, where is the plasma from recovered patients? Every critically ill patient in the U.S. should be getting this.

 

That's all folks

 

Stay safe, isolate, wear a mask in public

 

 

 

 

April 12

COVID 19 Update #23

 

Happy Easter everyone. I hope you are all staying safe and well.

 

Having a slow news day today. I'll share what I've found and then shift to my opinions, which may or may not have value.

  • First and foremost, Remdesivir, Gilead's antiviral drug, is both being disseminated and rigorously tested (see yesterdays post). The NIH is doing a double blind, placebo controlled study of this drug. This is the best kind of science and data gathering. Given the behavior of this virus, I expect an early answer. The norm is to have a panel that reviews the results in an ongoing manner. If there is a clear advantage which is statistically significant, they will halt the study and publish results. I am hoping for an answer quickly.
  • In the meantime, Gilead has 1.5 million doses of the drug on hand. Each treatment takes 10 doses intravenously, so they have enough for 150,000 patients. The drug was tried extensively for Ebola, they already have substantial safety data. They are actively manufacturing 500,000 treatment courses, that's 5 million doses. Their goal is to complete this goal by October. My hope is that places like NYC will apply for compassionate use doses to Gilead. I'm sure this is being looked into.
  • Data from NYC shows the deaths in NYC continue to escalate (see prior posts on lag and skew). The more important statistic shows the number of hospitalizations is dropping. Very good news.
  • The tech world is really helping in the fight against this disease. Both AI (artificial Intelligence) and 5-G are making a huge difference. One example, a small early stage biotech, had as their mission, screening blood samples for antibodies that would help people fight off COVID 19. They screened 5 million immune cells and identified 500 antibodies. It took them 11 days.
  • The FDA is warning about antibody testing. Many companies are coming out with tests. The FDA has only reviewed one so far. All will be vetted over time. Many will be forced to withdraw. Stick with people you trust.
  • Locally, the folks at the [Local lab] have obtained funding and will do antibody testing at no charge. They have as a goal, testing the entire population of the valley. They are in the process of testing 100 known PCR positive patients to see how sensitive their assay is before proceeding. Look for further updates soon. Nice work!
  • As I review what's in the news, I see more and more blaming going on. This has no value, as Dr Fauci says, we are where we are. We should be fixing the problems, not fixing the blame.
  • The largest problems I see going forward, are the decisions to try to re-open the economy. It should be a rolling gradual process. Doing this too soon will risk a second wave of cases, We should monitor places like China and South Korea to see what happens as they do this ahead of us.

 

Stay safe, isolate, wear a mask in public.

 

 

 

 

 

 

POST FROM HIS PROFESSOR FRIEND April 12

 

Treatment Options

Everybody wants a cure. A magic bullet. There will be effective treatments. Too many talented professionals are working on it. When effective therapies emerge we still must remember that control of any viral pandemic is prompt implementation of public health measures. This is not as scientifically “sexy” as the magic bullets but infinitely more important.

The first modality of care is supportive care. It attempts to reduce morbidity and mortality by treating serious symptoms and making the patient comfortable while the illness takes it course. It may range from simple outpatient care with fever reduction and pain relief to hospitalization. Admission to the hospital involves metabolic support with fluid and nutritional therapy. Vital signs are monitored with oxygen therapy moving to ICU therapy involving ventilator support as necessary. Medications may be utilized on compassionate off-label basis or as part of controlled clinical trials. It is labor intensive and with Covid-19 often intense and prolonged!

Antiviral therapy goals involve eliminating the virus from the body or even prevention of infection. Clearing the virus from the blood stream prevents further invasion of target cells preventing ongoing cell death and dysfunction. The reduced viral load would decrease potentially harmful continued immune stimulation. By elimination of virus further contagion would be eliminated preventing further transmission to others.

Viruses are a curious form of life. They have no mechanisms for metabolism or replication. They cannot move. They are a collection of structural proteins which form the body – in the case of coronaviruses a sphere – surrounding a core of genetic material, RNA or DNA, which can code for replication. The virus requires attachment to and invasion of a susceptible host cell – often species specific – with insertion of its genetic code into the host cell where it hijacks the host metabolic capability to replicate its proteins and reassemble into a complete infective form. These are then released back into the host to infect more cells. It often has specific recognition proteins on its surface to initiate and facilitate this process – the infamous spikes of a Corona virus.

The life cycle of a virus offers several avenues of approach:

1: Attachment and inactivation of the virus before invasion

2: Interference with the attachment of the virus to the host cell

3: Prevention of viral replication within the host cell

4: Prevention of release of the completed virions.

Prior to appearance of HIV disease in the early 1980’s there was little success or interest in developing antiviral drugs. Coincidentally with the epidemic was an emerging bioscience permitting development of successful antiviral treatment. It was as if the disease emerged as the technology to defeat it was developing! This technology has exploded over the past thirty years permitting isolation of potentially effective agents. Antivirals specific for HIV, Influenza, Herpes, Ebola and Hepatitis C are now commonly utilized and intense interest is now focused on Corona viruses. This had been built on research into SARS and MERS corona viruses. Unfortunately interest, direction and funding flagged with the rapid containment of those outbreaks. Current antivirals will build on this early research and will all require completion of the multi-phase FDA approval process with double blind clinical trials before general release into the physician’s armamentarium.

The first proposed therapy is the use of convalescent serum. This is isolated from the blood of patients who have survived the virus and have developed protective antibodies. These antibodies will identify and inactivate the virus prior to infection of further host cells. They must be administered intravenously (IV). This has historically been used back even to the pre-antibiotic era to treat both bacterial and viral infections. It is labor intensive and requires identification of potential donors and their participation. Early results are promising.

A more recently developed approach would be to identify to the critical antibodies and with genetic engineering produce specific – monoclonal – antibodies. They could be manufacture relatively easily and in significant quantities. They may be administered intramuscularly (IM) or IV. This has been utilized with Palivizumab (Synagis) for prevention of RSV infections in severely premature infants with success. Compassionate use with plasma infusion of convalescent serum and controlled trials are emerging. Keyzera (Sanofi/Regeneron) a neutralizing monoclonal antibody is entering trials.

There is a myriad of proposed antivirals in development in many countries sponsored by government agencies, university research teams, and private pharmaceutical houses. A few approaches warrant discussion. Several HIV drugs and combinations are being have been considered and are currently being evaluated. Remdesivir (Gilead) was developed for MERS and may work by preventing replication. The New England Journal reported a compassionate use trial which reported improvement in 68% percent of the patients. It was not clear whether med reduced viremia and mild to moderate side effects were noted. It is not clear whether observed side effects were from the med or the underlying illness. Remdisivir is administered IV and relatively difficult to make. Gilead has relinquished rights to permit multiple sourcing! Multiple trials are underway.

Galdisivir (Biocryst) has shown broad-spectrum activity against Ebola, Zika, Marburg and Yellow Fever as well as corona virus. It inhibits replication and trials are underway. Avigen (Fuji) is an oral antiviral developed for Influenza which works by prevention of replication. Current anti-influenza medications (Tamiflu) prevent release of drug and are not effective with coronavirus Avigen had promising trials in China and is now being actively investigated both as a therapeutic agent and a prophylactic. A medication which may be used for prevention or early intervention in preferable to medication used for subsequent severely ill patients.

The last medication discussed today will be chloroquine/hydroxychloroquine highly touted by the current administration. These drugs have around a long time for treatment of malaria. They have acknowledged widespread antiviral action interfering with both attachment and replication. There have been observational studies with mixed results in several different countries including China. With well recognized significant cardiac and ocular side-effects classic double-blind clinical trials are a necessity before recommendation for routine use. These trials are underway.

Clearing the virus is the first step. Discussion of the hyper-immune response and resultant cytokine storm contributing to the morbidity and mortality of Covid-19 is required and will be the subject of our next discussion.

 

 

 

 

April 13

COVID-19 Update #24

 

If indeed you find this information useful, please post it and any priors on your homepage, as I have stopped accepting friend requests from those I do not know.

It's a slow medical news day. Just a few comments from around the world, then a more indepth look at Remdesivir.

  • [Local Idaho County] looks to have reported only 8 new cases over the past three days, but 44 over the past week. Perhaps a skew from Easter weekend, we will have to see over the next few days.
  • China reported 100 new cases as they relax isolation. Their government is stepping in to censor scientific articles. Therefore, from this point on, data from China will have little value. Too bad, their data would have been so useful.
  • Spain is rolling back its restrictions. This will be ugly. I would expect a second wave by May 1.
  • While Italy reported 431 deaths, their admissions to ICUs dropped for the ninth day in a row. As you may recall from prior posts, hospital and ICU admissions reflect current state of the virus, deaths reflect what happened 16 days ago.
  • Austria will begin opening small shops this week.
  • Denmark is sending its children back to school on Wednesday.

 

Now for Gilead's experimental drug Remdesivir.

I previously reported on their compassionate use study, published in the New England Journal. It was very encouraging, but lacked any control arm, and it was a small number of patients. The drug is available for compassionate use in three California hospitals including California Pacific Medical Center (CPMC), and in four New York hospitals including Mt. Sinai. The drug has been used many times worldwide in this capacity.

The good news... their are seven clinical trials ongoing with this drug. Gilead itself is running two open label trials. The National Institute of Health (NIH) is running a double blind, placebo controlled study. The WHO is running a massive study.

Gilead's trial on moderately ill patients was just expanded from 600 patients to 1600 patients. They expect preliminary results by the end of May. Their trial on severely ill patients was just expanded from 400 to 2,400 patients. Preliminary results should be available by the end of April. One of the goals will be to see if a five day course works as well as the 10 day course. If it does, they could treat twice as many patients with the drugs available.

The trial being run by the NIH includes patients with mixed severity, but won't report until late May.

The trial being run by the WHO also includes patients with mixed severity. The number being enrolled is to be 10,000. They won't report until the end of June.

The greater the number of patients you look at, the sicker they are, the more dramatic the results, the sooner you are likely to see a statistically significant result. If this drug is as good as I think it might be, we may be giving it to a lot of people within a month or so. If it keeps people who are moderately ill from getting sicker and being transferred to ICU or being intubated and placed on a ventilator, that would truly be a gift from God.

As I stated yesterday, the normal in placebo controlled double blind studies is to have an oversight panel. These panels have two jobs. As they review the ongoing data, if a new drug is clearly hurting people, they pull the plug and end the study. If the drug is clearly making a significant difference, they pull the plug and offer the real drug to those in the placebo arm. I am hoping for early ends to the double blind placebo controlled studies... we will see.

 

 

The NIH is actively recruiting people for a study to determine how many people are antibody-positive, who have never been clinically ill. If you want to participate, you can go to their website and volunteer. Our friends at the [Local lab] will be way out in front of this. We live in a very high prevalence area, 431 known positive out of roughly 22,000 people. Hopefully, if their goal of testing the whole county comes to pass, we will have data the whole world will be eager to see.

 

That's all for today, stay safe, isolate, wear a mask when out in public.

 

 

 

April 14

COVID-19 Update #25

Lots of interesting things to report today.

  • Ridgeback Bio, a small biotech firm has begun early stage testing of an oral antiviral. They tout it is active against ten different CoVs including SARS-CoV-2. The first human dose was on Monday, as they work through safety and dosing. They have a very aggressive plan. If they find it effective, they will have to find a way to scale it.
  • From the preprint server, medRxiv: A Chinese study testing antibody at discharge from the hospital in patients who were mildly ill, looked at 175 patients. Those who tested negative were retested at two weeks. They report that 30% had low antibody levels, and ten of seventy five had no measurable antibodies... raises a lot of questions including, how does one recover without antibodies? This study will be repeated many times going forward; we will have to see if it is validated.
  • There were multiple posts in Becker's Hospital review. The highlights follow.
    • Robert Redfield M.D., the director of the CDC, stated on 4/13/2020, "We are near the peak right now."
    • Dr. Fauci stated on 4/10/2020, that within a week or so we should have early data from the NIH antibody study of healthy volunteers. This is going to be very important.
    • The White House task force is considering certification of immunity for those with known prior infections. I think this would be a good idea.
    • There are now 70 vaccine candidates worldwide. I count four in human trials, two from China in phase 2, and Moderna and Inovio's in phase 1. The latter are U.S. based.
    • The last item from Becker's was a summary from the CDC on seasonal flu . I'll save that one for last.
  • Apparently Google and Apple have put together a case tracker which is private, meaning the gov won't be able to invade your privacy. If offered, you should participate.
  • Cases are beginning to spike in Russia, This has resulted in many cases of Chinese citizens returning home, positive for the virus. They are being isolated.
  • The FDA has finally approved vaporized hydrogen peroxide for treating masks that have been used. It is now in use at 6,000 hospitals nationwide.
  • Rutgers has developed a saliva test for viral RNA, I don't have any details yet. I expect it won't be as sensitive as others, but would require no techs to collect the specimen. I will try to find out more about this for tomorrow.
  • South Korea is sending us 750,000 test kits.
  • Abbott's point of care RNA test is 95% sensitive down to 100 virus copies per ml. This is incredibly good. It also shows zero cross reactivity with other viruses. That is a game changer. We have this system at our hospital, but with only 500 tests, just being used for staff on the frontline and critically ill patients. Abbott is working 24/7 to make more tests, trying to crank it up from 50,000 per day to 100,000 per day. Many thanks to [colleague] for sending me the package insert.
  • Multiple countries are now beginning to restart their economies.
  • I listened to the CEO of Levi Straus last evening. They have 500 stores in China, all but one have reopened. Their biggest store in China, and their newest was in, you guessed it, Wuhan
  • At least three areas are trying to open up a bit at too great a risk to their populations, in my opinion:
    • Spain and Italy, two of the worst places in the world for the virus, are giving it a go. We will see what happens in a few weeks. Hopefully they have some restrictions in place.
    • The third is [redacted], my hometown. [Hometown] has decided to allow an ordinance to expire, and without an emergency meeting of the city council, allow landscaping and construction to resume on a limited basis. [Hometown] mayor says we will be 'the canary in the coal mine'!
  • In [County in Idaho where he lives]... [Towns in the county] and the county itself are waiting another week to see what happens with new cases. [Town in county] is allowing limited resumption. They are isolated with, at least as far as I can tell, no cases.
  • [Redacted], one of our county commissioners, was kind enough to send me the 18 point standards and limitations for resuming work. It is well thought out.
  • The mayors and governors are trying to work together, and are, for the most part, listening to experts. Dr. Fauci's ability to remain calm, collected and patient in order to get the message out in spite of adversity, has been impressive to say the least.
  • Lastly, the CDC has gathered data on seasonal influenza. This is very complicated this year. In normal years, they track those who test positive and those with FLI (flu like illness). Hard to tell the difference between SARS-CoV-2 and the flu without testing. They reported the numbers in a range, and I am giving the low end numbers. Thank goodness the seasonal flu is waning. It will help to take some burden off hospitals. Unfortunately, NYC remains one of the areas that is still hot.
  • For the 2019-2020 flu season they report a minimum of 24,000 deaths, 410,000 hospitalizations, and 39 million illnesses. Thank goodness we have a vaccine, which only half of us take, and antivirals that work.

 

Stay safe, isolate, wear a mask in public, and look for testing if you are ill.

 

 

 

 

April 14 part 2

COVID-19 Update # 25B

From this point forward I will forego political commentary and stick with the facts, and my opinions about the facts.

  • As I am typing, here is a brief update on chloroquine, and hydroxychloroquine. During the 44 years I was in practice, I had occasion to use both drugs. In the old days there were many countries in which the strains of malaria were still sensitive to chloroquine. The drugs for chloroquine resistant strains were not very well tolerated. Chloroquine made a lot of people feel unwell, it was hard to maintain compliance. I used hydroxychloroquine in a few patients over the years, mainly for Lupus. Had to watch for visual toxicity. Neither drugs were easy to use, but did their jobs.
  • Novartis is doing a study on its utility for COVID-19. They are the manufacturer. There are people out there who truly believe these drugs have helped them. This is the reason we do placebo controlled double blind studies. You would be amazed at how many people have either side effects, or benefits from taking blanks.
  • The few non-controlled reports I've seen are mixed to slightly beneficial. One Latin American study was trying a higher dose to see if that would be more efficacious. They aborted the study as patients were having heart rhythm issues. Better answers should be forthcoming. In the meantime your physicians are free to prescribe it at their discretion.

 

See you tomorrow, stay safe, don't be fooled by dropping case numbers. This isn't over... yet. Already a lot to report on tomorrow.

 

 

 

 

April 15

COVID-19 Update #26

 

It's 10:50 a.m. and I am so done reading. Put in two hours last night, and three hours this morning. I am not cut out for sitting in front of a computer for six hours a day.

  • Two of the world's largest vaccine manufactures, GlaxoSmithKline (GSK) and Sanofi, have announced they will collaborate on a vaccine. I have been wondering where these guys have been. If found to be safe and effective, it won't be ready until the second half of next year.
  • Johnson & Johnson has announced it will ramp up production of its vaccine, even as it spends the next year and more, testing and developing.
  • Funding of the WHO is big news today. If interested, pull up Bill Gates' comments.
  • I have written many times about the FDA waiver and antibody testing. I have suggested that you use good judgement about whose testing you use. The FDA has stepped back from the waiver as the market has become flooded with faulty low quality tests. In my opinion, those who use this crisis as a way to scam the public, should be locked up and have the key thrown away.
  • Speaking of scams: the FDA and the FTC are sending out letters and warnings to those peddling cures for SARS-CoV-2.
  • I counted eight companies that have been warned about making false claims on their products. When an effective therapy is found, it won't be a secret. The sheer number of cases being reported for stem cell companies and drugs for other diseases being used for Covid-19, is becoming staggering. These single use case reports have no value other than prompting further studies. Wait for the science.
  • Speaking of waiting for the science, a study from France, just published and the most definitive so far, looked at 180 patients admitted to multiple hospitals. These patients were begun on hydroxychloroquine on day one. They found that the death rate and ICU admissions at seven days were actually worse for those taking the med, although that difference was not statistically significant. They also found that 10% had to stop the med for side effects by day four. They concluded the drug had no benefit at all.
  • The Pasteur Institute in Paris is working on its own idea for a vaccine. They plan on using the measles vaccine as a trojan horse, when combined with a single protein from SARS-CoV-2 to induce antibody production... interesting idea, also 18 months away.
  • While I'm thinking about it, "60 Minutes" had a wonderful show this past Sunday. It featured an NYC ER doc/trauma surgeon, who made an impassioned plea regarding staying isolated... well worth watching. The NY Times had some wonderful pictures this morning of the field hospital that has been erected in Central Park. You should take a peek. Hard to imagine being gravely ill, on a ventilator, in Central Park, in a tent, in the mud. Shades of MASH.
  • I continued to be stunned at the disconnect between the IMF's prediction of the worst recession since the great depression, and the optimistic rally in our own stock market.
  • Ecuador is becoming a new hotspot in South America, with mass graves appearing virtually overnight.
  • Singapore is experiencing a second wave of the virus. Cases in Russia are surging.
  • The CDC and FEMA are drafting a plan for the reopening of the U.S. Hope they look at Singapore as they do this.
  • A study from the Harvard School of Public Health warns that we may have to practice periods of social distancing until 2022, unless a vaccine becomes available sooner.

 

Back in the good old days, when I had to look up journal references by hand (meaning find them in a book the size of an Oxford dictionary, called the Indicus Medicus, published one year at a time, write down the citings on a piece of paper, and pull the actual journal from the stacks), there was a recurrent phenomena, that was more striking back then. I would open a copy of a journal which had just arrived by mail, and there would be an article on the very subject I was getting ready to research. When that happened, it would save me hours. Last night, right after posting #25B, there were only two new journals in my inbox. One was an article on retinopathy (eye damage) caused by chloroquine, the second was an online copy of the April 14th NEJM. It contained an article under the heading "Perspective" entitled, "Drug Evaluation During the Covid-19 Pandemic". It was written by some Harvard docs out of 'the Brigham". This article spoke about the process in general and the drugs chloroquine and hydroxychloroquine specifically. I have always felt that there were no coincidences. The article reiterated the points I made in #25B. It's always nice to have validation of one's views, especially one minute later in a major journal. It went on to point out, the EUA (emergency use authorization) issued by the FDA on the above mentioned drugs, was only the second time in its history that the FDA has done this for a drug for unapproved indications. It also commented on how the drug approval process will be measured in weeks for this crisis, where it normally takes years. Once again, a two edged sword.

I have more notes, but that's it for today.

Stay safe, isolate, wear a mask in public, get tested if you are sick.

 

 

 

 

April 16

COVID-19 Update #27 for 4/16/20

 

Two quick reminders: I don't accept friend requests from those I don't know, and I am relying on you to repost the updates, if you find them useful.

  • Abbott labs, the same company who brought us the 5 minute, instrumented, RNA test being used for frontline workers and critically ill in hospitals (including ours), is rolling out 1 million antibody tests today, and will be shipping 4 million total by the end of the month, and then scaling up to 20 million a month in May. A very reliable company, this will help immensely. They have a home version in development.
  • The FDA has now officially approved three antibody tests: Cellex, Chembio, and Ortho. I expect Abbott's will be following soon.
  • Hair dye is the new toilet paper.
  • A 99 year old WW II vet set out to raise $1,250.00 (actually probably pounds) for Britain's National Health Service, by walking in his garden. As of Wednesday evening, the number was up to more than 12 million dollars.
  • [County in Idaho where he lives] has reported only 17 cases over the past 6 days. The county total is now 463. Another 8 days of these kind of numbers, and it will be time to start making decisions. Governor Little has extended the shelter at home order until April 30 in our state.
  • The bane of vaccines is mutation of the target organism.
  • We see this every year for influenza... different strains in different years. It is one of the reasons we don't have an HIV vaccine. There is chatter out there about new strains of CoV-2... no hard evidence yet. I went looking for the facts at bioRxiv, a preprint server for biology. Between it and a sister site for medicine, there were 1,633 articles on SARS-CoV-2 posted. These are not yet published and not peer reviewed. I won't be reading all of these.
  • "Becker's" published a list of aid to states by the government. It was on a per case basis.
    • Idaho- $100,000 per case
    • Nebraska- $379,000 per case
    • New York- $12,000 per case.
    • Doesn't seem right, does it?
  • Dr. Fauci has been active the past few days and fully expects back to school in September, but it will be different.... social distancing until we have a vaccine. Much hinges on widespread testing, identification of new cases, isolation of new cases and contact tracing for isolation and testing. Enter Google and Apple. He stated, "I think we are going to be in good shape."
  • Many children rely on their meals at school to be their main source of nutrition. Some communities will feed kids-in-need breakfast. In our county we send kids-in-need home with backpacks full of food for the weekend. With schools closed, I see this as a huge issue. I don't know about you, but It brings tears to my eyes to think about these kids going to bed hungry. Call your local foodbank and see what they need, help if you can. I am going to pull up our local food banks website, The Hunger Coalition, and send them money. Those over 70.5 can send money directly from an IRA and avoid taxes on the donated amount. Ask how. NYC is spending 170 million on emergency meals.
  • Another way to help, if your more than 15 days out from a SARS-CoV-2 infection, is to donate plasma. Call your local hospital or visit their website. Call the Red Cross. They would probably like your blood as well.
  • The FDA has approved the saliva test for RNA developed by Rutgers. It will roll out in New Jersey (imagine that). I hope they can find a way to scale it.
  • Fisher Island, Florida. has arranged to test every resident. I hope we will be next.
  • N.Y. is set to require a mask when 6 feet of separation is not possible.
  • California was one of the first states in with regard to virus exposure and isolation measures, it may be the first state out. Governor Newsom says they will use facts, science, evidence and the advice of public health experts in making decisions. Nice to hear.
  • There was an article published yesterday in the NEJM. It profiled the experience out of Stony Brook University, New York, in the ER. Seventy percent of their patients were able to go home, 30% had to be admitted. Ten percent required ICU admission or ventilation right away, and another 15% required this within 2 days. They also explained how they retrofitted their hospital to deal with the high flow of sick patients.
  • Temple is launching a new multi center clinical trial (BREATH) for Gimsilumab. This is a fully human monoclonal antibody against GM-CSF, that is to say, granulocyte macrophage colony stimulating factor for those who care. This substance is felt to be a key driver of lung hyperinflammation, and is upregulated in SARS-CoV-2. I mention this only because it is representative of the many trials being launched to evaluate treatments.

 

Be safe, isolate, wear a mask when out in public.

 

 

 

 

 

April 17

COVID 19  Update #28

 

I wrote most of this after midnight last night.  I was feeling a bit down about most of the news.  That was until this morning, when I read some new information on Remdesivir.  Those that read my daily posts know I have been talking about this drug and the clinical trials for some time.  The severely ill limb of the trial is due to report before the end of the month.  It enrolled 2,400 patients being treated at 152 different sites.  Part of the trial is to determine if 5 days of therapy will work as well as the standard 10 days.

  • The University of Chicago has had 125 of the severe cases in the trial.  An internal video was leaked.  In it they reported only two deaths.  Most of these patients had been discharged by 6 days.  Guess that means they don't need 10 days of therapy.
  • Until reported with the control arm, and the side effect profile, this data is still anecdotal.  Speaking of anecdotes, a 57 year old factory worker was admitted to the University of Chicago on April 3.  His fever was to 104F, he was struggling to breathe, and he was placed on oxygen.  On April 4th, he had his first dose of Remdesivir.  His fever dropped, he immediately felt better, and by the fourth dose he was discharged.
  • I will be looking for hard data by the end of next week.  Stay tuned.  I am hoping this will be a game changer for those sick enough to be in the hospital.  If this holds up, they may have to break the code on the moderately ill arm, and the FDA will need to push approval.
  • This is, without question, the best news I have heard since the pandemic began. 

 

As we pass the peak, we are going to venture into uncharted waters.  Our decisions will have to be educated guesses, followed by close evaluations of outcomes.  Our leaders at every level understand that being overly aggressive will have a cost in both illness and lives lost.  Being overly conservative will crash the economy worldwide, cost people their homes, cause their businesses to go bankrupt, force people into unemployment, to sink below the poverty level, and to put their kids to bed hungry.

  • There may be no balance point.  There may be no right decisions.
  • The answers are not going to be the same for every state. They won't even be the same for different regions within states.  Our own state of Idaho is a perfect example:
    • The urban areas are in pretty good shape. 
    • The isolated mountain area that is Blaine County has been a hot spot, at one point the worst per capita county in the U.S. 
    • Some counties haven't had a single case yet.
  • My observations scare me.  I went to the small grocery store in [Small Idaho town] 30 minutes before closing to avoid any kind of crowd.  What I saw, was only half the people there wearing face coverings, and only one of two cashiers wearing a mask.
  • I wear a mask in public to protect you from me, not the other way around.  It may be that I also get some modicum of benefit as well.  When I see people not wearing masks when in close contact, especially in this county, it tells me they don't care about me or my health.  I'd like those who don't wear masks to remember this.
  • I saw the unprotected crowds at the capital in Michigan protesting social isolation.  In the picture I saw, two out of 20 were covering their faces.  The people looked more like a crowd on a Florida beach during spring break, than a group of people scared about being out of work.
  • Do your part, do your best, help others if you can.

 

Now on to the other news of the day...

  • 'Practical Cardiology' posted a video where the Chief Science and Medical Officer of the American Heart Association warned about the dangers of taking the combination of azithromycin and hydroxychloroquine.  The cardiac complications of the two together are additive.
  • The American Medical Association has issued a plea to the president to reverse his decision to defund the WHO.
  • Many are asking why we are shut down now, when we didn't for Ebola, SARS-1, MERS, or H1N1. 
    • Ebola, SARS-1, and MERS never became pandemics, thank goodness, due to the efforts of many organizations including the WHO. 
    • H1N1 was bad, but we had a vaccine (which half of us didn't bother to take), and antivirals which were effective if taken early on.
  • There have been a minimum of 9,282 health care workers infected with SARS-CoV-2, according to 'Becker's'.
  • Some experts feel we shouldn't reopen until we have testing enough for all who have symptoms.  That would be 750,000 per week, excluding hot zones.
  • Quest, who was an early underperformer has now done 800,000 tests, and has geared up to perform 45,000 a day.
  • I have always liked the idea of certification of immunity to be able to return to work in the early stages of recovery.  One question I saw today regarding this was, what do we do if people intentionally then try to get infected so they can go back to work?  That puts a big hole in that idea.
  • Beaumont Health based out of Royal Oaks, Michigan, stated on April 14th, that it is starting the countries largest serology testing.  It will test all 38,000 of its employees.  This should produce some very useful data, especially for hospital systems.
  • The WHO is sending 1.5 million tests to 120 countries.  Its director general, whom I will refer to as 'Dr.T' stated, "You cannot fight a fire blindfolded".  He further stated, "We cannot stop this pandemic, if we don't know who is infected."... testing testing testing!
  • The FDA is actively encouraging plasma donation and has approved its use in those seriously ill with the virus.
  • China, the worlds second largest economy, shrunk during the first three months of the year... duh.  The second and third quarters will tell us a lot more.
  • NYC will require face masks be worn when social distancing can not be accomplished.  This goes into effect on Friday at 8 pm.
  • France is extending lockdown into May, and Great Britain at least another three weeks.  Thank goodness, I thought Great Britain was about to make another tragic error.
  • I read about what is on the list for phase one of the re-opening.  With physical distancing provisions, the list included: restaurants, movie theaters, sporting venues, places of worship. gyms, and the resumption of elective surgeries. My own elective back surgery was cancelled, I have no intention of being admitted to the hospital until September, and maybe not even then.  The rest of the list seems way premature.  I'm sure we will hear many others weigh in on this shortly.

 

Until tomorrow, stay safe, isolate, wear a mask in public.

 

 

 

 

 

COVID-19 update #28B

April17

 

I just went to Gilead's web site to further look at the trial. It is indeed an " open label " trial. This means there is no control arm, everyone is getting the drug, and everyone knows it. Sorry for the confusion. The NIH trial of Remdesivir is the double blinded controlled one. More tomorrow.

 

 

 

 

COVID-19  Update #29 

April 18, 2020

 

Big news on the vaccine front... Sarah Gilbert, a professor of Vaccinology at the University of Oxford, did an interview with Bloomberg.  They have a vaccine in human trials.  They are one of 4... CanSino Bio (China), and Moderna and Inovio in the US are the others.  There are 70 total in some stage of development. The difference is, Prof. Gilbert says they would love to start giving vaccinations as early as September. There are a lot of 'ifs' involved in this.  They are however, beginning to manufacture their vaccine in anticipation of it all going well.  They will require tens of millions of pounds ($) to ramp this up.

 

  • They have begun a 500 person clinical trial.  Participants are from 18 to 55 years old, and have been divided into 5 groups.  One group will have a second vaccination at 4 weeks. 
  • It is a randomized, controlled study.  They will evaluate safety and efficacy at 6 months with an option to look again at one year.
  • The trial is expected to expand to older adults, and to expand to 5,000 people.  They see the biggest difficulty in trying to evaluate efficacy, is that rates of transmission are going up and down in different areas.
  • Oxford's candidate vaccine has the catchy name... 'ChAdOx1nCoV-19'.  Hopefully it will have an easier name soon.  It is a recombinant viral vector vaccine.  What this means is that they take a harmless virus and modify it to have the same spike protein as SARS-CoV-2.  They have created multiple vaccines with this tech already.

 

I look for the Professor to weigh in on this.

 

Other things:

 

  • The NIH announced on Friday they are going into partnership with 16 drug companies, the program is named ACTIV.  They hope to standardize methods and models that researchers are using, make sure they have adequate equipment, and form one joint control arm.  It's about time.
  • The FDA has approved a broader range of swabs for testing. This should relieve one of the big bottlenecks for RNA testing.
  • You all have been reading about the Theodore Roosevelt and its captain. They have tested 94% of its 4,800 crew.  Of the 600 who tested positive, 60% were asymptomatic.  If my calculations are correct, that means the 240 had symptoms, and 360 did not.  That means for us, that there are a lot more people out there with the virus than we know.  Most of them are infected without having any symptoms.  The data on all of this will be exploding soon.
  • Most of the projections that are being used are coming out of the U of W.  The group, referred to as the IHME, is coming under fire as it uses, as some are asserting, antiquated tools for modeling.  They seem to change their numbers frequently. They seem to be using different tech than most other epidemiologists.  This kind of modeling is perfect for AI and 5-G.
  • The Journal of Infectious Disease demonstrated that four out of the seven coronaviruses that affect humans are seasonal. They run from December to April or May and disappear.  We can only hope that this virus might behave the same way. Also worth noting SARS-1 just disappeared.  MERS recurs only in small clusters. Most likely the virus will just persist and create a chronic problem.

 

I have two more pages of notes, but I'll leave those until tomorrow.

 

Stay safe, isolate, wear a mask in public.

 

 

 

 

COVID-19  Update #30 

4/19/2020

 

I'll start with a little review, just in case you are reading a re-post.  I was licensed to practice for 44 years before I retired. I was a specialist in Internal Medicine. I have two colleagues who post regularly, when they do, you should read what they write. mtn note: I am posting any time I see one of these updates, but I am reliant on someone else to share them for me to see them.

 

  • The first is The Professor. He was a pediatrician, who practiced here in Idaho, and then in Spokane.  He set up, participated in, and supervised vaccine trials for many years.  He retired as a full professor of pediatrics from the University of Washington. 
  • The second is, Dr. A.G.  She was trained as a pediatrician as well, at John's Hopkins.  She has spent most of her career as an integrative medicine specialist.  She co-wrote a book for Mosby on the evidence base for integrative therapies.
    • mtn note: Think of Mosby as the Chiltons manuals of the medical world, but don’t look too far into that analogy. They’re an academic publisher of textbooks and academic journals. Their parent company produces The Lancet.
  • Yesterday, I asked The Professor to weigh in on the Oxford vaccine trial.  My greatest worry was that 6 months of safety and efficacy testing before release, was too little.

 

The professor responded, in a comment, that Professor Sarah Gilbert and her group will be using antibody titers to determine efficacy, and not disease prevention.  He went on to say this was not uncommon in vaccine trials.  This group has prior experience with the same carrier virus in the MERS effort, to bolster their safety data.  The tech has moved forward rapidly. Six months is inconceivably short, but this is an emergency. Some of this is directly quoted, some is paraphrased. Yay science, looks like September is possible, if their vaccine is safe and effective.  They are moving into production ahead of approval.  They will never be able to scale this on their own. They would need to produce 3 billion doses to give one to everyone who wants one.  We will find out if we are "all in this together".

 

  • As of April 17th, the US has tested 3,423,034 people, 686,991 were positive.  Remember, the RNA test is very specific for this virus, but it misses 1/3 on its best day.  I expect that the real number of those infected is somewhere between 10 to 20 times that number.  We are about to find out.  My best estimate is that 10 million have had the disease.
  • Becker's Hospital Review posted an extraordinary timeline on testing in the US.  I did copy it down, but it is way too long to rewrite it here.  If you are interested, you can go to the site. mtn note: I could not find this, anyone who can, let me know…
  • The Infectious Disease Society of America has published a statement about therapy.  Their opinion is no drugs should be taken for SARS-CoV-2 outside of a clinical trial. It is just human nature for clinicians to want to do something. The hardest thing to do is nothing at all.  In a vacuum, the snake oil salesmen come out of the woodwork. The IDSA goes on to point out that, chloroquine, hydroxychloroquine, the combo of azithromycin and hydroxychloroquine, toclizumab, corticosteroids for ARDS, the combo of lopinovir plus ritinovir, are all approved by the FDA for other problems, yet none are proven to work for Covid-19. They went on to say, "The road is littered with drugs that have in-vitro activity (in a lab, in a non-human test), for respiratory tract infections, and yet do nothing when given to people."
  • That being said, Rutgers is doing a clinical trial on the combo of azithromycin plus hydroxychloroquine. They have enrolled 160 patients. and started on April 3rd, stay tuned.
  • Johns Hopkins is tracking cases per state, among many other things.  On Friday I saw new case numbers on the states that have not made a stay at home order.  In the past week...
    • Oklahoma increased 53%
    • Arkansas increased 60%
    • Nebraska increased 74%
    • Iowa increased 82%
    • and the winner...South Dakota increased 205%
    • North Dakota, Utah, Wyoming all increased at a rate comparable with the stay at home states.
  • I also read in Becker's, a list of criteria on resuming elective surgery.  Quite an interesting list.  I will write about reopening tomorrow.
  • As we discussed yesterday, the guiding metrics seem to be wrong yet again.  Many places are spending much more time at peak than was predicted.  My guess is, human behavior. People hear we are over the hump and relax isolation standards.
  • So, here comes the negative part, with a positive suggestion. Feel free to skip.
    • The U.N. is reporting thousands of children are dying, and millions are becoming impoverished.
    • We can do something about this, just choose:  local, statewide, nationally, internationally, you can make an impact. To quote Nike, "Just do it."

 

Another famous quote, "All that it takes for evil to triumph is for good men to do nothing."   It's close and you'll have to figure out who said it.

 

Stay safe, isolate, wear a mask in public.

 

 

 

 

COVID-19  Update #31 

4/20/2020

 

So, first some comments on scattered subjects and then a look at reopening.

  • The more successful we are at isolation the more people will say its not real and was never necessary.
  • As the pandemic progresses, the disparities are becoming more obvious.  I'll give two examples. 
    • In South Sudan, there are 4 ventilators and 24 ICU beds for 12 million people. 
    • In Venezuela, there are 84 ICU beds for 32 million residents.
    • What will happen when these countries are hit?  Hopefully, the world steps up.  Hopefully, the WHO and our country will lead the effort.  I'm trying to picture the 5 boroughs of the greater New York area with 4 ventilators.  It could be a humanitarian crisis of epic proportions.
  • In Africa, the AIDS crisis will make this much, much worse.
  • The FDA has been under constant fire regarding testing.  In my opinion it is well-deserved. 
    • The first error was declining the WHO-approved testing early on. 
    • The second, while under fire for a lack of testing, allowing any manufacturer to market their test, and seek approval later.  There are now 90 allowed, but only 4 have been formally vetted.  The only thing worse than a lack of testing, is bad tests with inaccurate results.
    • It is now on the FDA to vet these tests as quickly as possible, and demand the withdrawal of the bad ones.  They need to do this ASAP.  They appear to be moving at a snail's pace.
  • The best country for looking at reopening would be China.  As their government has begun to censor their scientific literature, it can no longer be trusted.  There was a piece a few days ago in the Times that talked about recovery in Wuhan City... the factories going 24/7, taking everyone's temp before they enter a building, and closing a business for weeks, if an employee is sick with the virus.  The restaurants are empty, take out is brisk.
  • Singapore's initial response to the virus was iconic.  They had widespread testing, tracking and isolation.  They reopened, and then came the second wave.  Since March 17th, the number of cases jumped from 266 to 5,900.  What is postulated, was they didn't test and track their migrant workers in dorms.
  • Japan focused early on containment and not on testing, and now the countries health system is struggling to cope.
  • Hong Kong relaxed social distancing last month and have now had to re-tighten.
  • Jacksonville Fla. is reopening its beaches.
  • Most expert opinions, that I have read so far, seem to agree.  If we want to reopen the economy without a huge second wave that sends us back to square one, we will have to be able to test, isolate, and track contacts.  How many tests does that mean?  The estimated are all over the board . My guess is a million per day.
  • A working viable vaccine would be a great help.  Knowing who is immune would be huge.  Knowing how long immunity lasts would be very important.  Having treatment that prevented patients from getting sicker would be huge.  I think we are weeks away from this last one.
  • Trying to reopen without testing, tracking and ability to enforce isolation is, in my opinion, foolish.  We have to be patient.

 

The next paragraphs are political regarding Blaine County, Idaho.  Feel free to just skip them, if you hate politics.

 

[Local county and local towns/cities] have joined the [local town] in allowing their ordinances to expire, and therefore allowing construction and landscaping to resume.  They have decided we, as a county, should lead the way.  In my opinion, if they wanted to take risks and be at the forefront, they should have waited another week, two would have been prudent.  To do it now is beyond understanding.  We were per capita, the worst county in the USA, just a few weeks ago.

The eighteen-point guidelines they have drawn up are excellent.  If they could be enforced, it might just be alright. The second day of [local town’s] decision, I saw a violation in my backyard.  No one riding, walking or running on the bike path or on the road by my house has been wearing a mask. This despite the fact that some were panting, blowing, and exercising hard. Only one third of shoppers are wearing masks, only half the checkers.  This observation was only 15 minutes one day last week. You need to protect yourself despite these decisions.  Do not let our dropping numbers fool you.  A second wave into the summer months will be catastrophic for the local economy.

 

Stay safe, isolate, wear a mask in public

 

 

COVID-19  Update #32 

April 21, 2020

 

I start out every day thinking there won't be enough to write about today.  I end up every day trying to decide what to include and what to drop because there is way too much. I think that today we will do statistics and reopening, but first just a bit about plasma therapy.

 

I have been waiting for big news on this front ever since Pence promised 100,000 units would be available, it seems like, more than a week ago.  I went out looking for it today. Mt. Sinai in NYC, was the first to put out data so I went there. I was born in Manhattan, and raised on Long Island. There are actually 4 locations for Mt. Sinai. I found they have an assay for quantitating antibodies, that the FDA is allowing them to use for research.  One of its many uses should be to tell us who has high titers of antibody in their blood.  These should be, theoretically, the best plasma donors.  The New York Blood Center has set up a convalescent plasma bank.  Those hospitals with a Mayo Clinic IND (investigational new drug) clearance will be allowed to use it.  I hope to see an unpublished but completed paper soon.

  • There is now a National COVID-19 Convalescent Plasma Project.  It includes 40 top health institutions over 22 states.
  • [Local Idaho County] has added only 13 new confirmed cases over the past seven days and one each day for the past two days for a total of 471.  Our population is 23,000.
    • Looking over the past two weeks, it means we have achieved suppression.  That is when each infected person is infecting less than one new person.
  • I then went looking for the Stanford data.  As you may recall, they went out and did serological testing in multiple sites in Santa Clara county, last week.  They tested more than 3,000. The statistics folks are up in arms about all the flaws and biases in the study.  My opinion is that you have to start somewhere. 
    • They postulate that between 48,000 and 81,000 in their county have already been infected.  Those numbers are 50 to 85 times the number of known positives.  That is really bad news.  I'll give you a new term today... seroprevalence.  That is the percent of a population that is positive for antibody.  You will be seeing this term more and more.
    • Their conclusions:  95% of their population is still vulnerable. There are a lot of asymptomatic people out there spreading the disease.
    • In my opinion, they should study [Local Idaho county, was at one point the highest per capita of cases in the country].  They should test everyone who is willing.  That would produce numbers free from bias.
  • UC Berkley is going to test 5,000 in the East Bay, hopefully with less bias than the Stanford study.
  • We are now at 170,000 deaths worldwide, 42,000 of those in the US.  Looking at the big map, the southern hemisphere has hardly been affected, yet.  Europe and the US look like they were hit by a bomb.
  • Singapore is now up to 8,000 cases.
  • A prison in Marion, Ohio is the hotspot.  Of 1,828 inmates, almost 3/4 are positive, as well as 103 employees.

 

I think we should be talking about prevention of a second wave, rather than how do we reopen.

  • First, there has to be hospital capacity to deal with an increase in cases. 
  • Second, you need to be able to test all who have symptoms.  This means the swab or spit test RNA by PCR.In my opinion, it also means serology testing those who are PCR negative, as a single PCR swab will miss one third.
  • Third, the ability to contact trace and isolate. 
  • Fourth, in the absence of a vaccine, be able to treat those who are hospitalized.

 

Despite these needs, several states are getting ready to open up on a limited basis.  Texas starts with retail to go... an excellent idea.  Georgia... the list is a tough one for me... Gov. Kemp is talking about opening gyms, hair salons, and tattoo parlors.  He further wants to open movie theatres and restaurants on April 27. While I hope for the best, this seems like wishful thinking, rather than a plan.

 

My sister is a front line nurse at Grady in Atlanta. I think they will be very busy in two to three weeks. I hope I am wrong.

 

Be safe, isolate, wear a mask in public

 

 

 

Update from “The Professor”... This was actually prior to the update on April 12, still trying to find the original Part 1 of this... Sorry, but I'm getting this stuff piecemeal, for some reason Facebook isn't showing all posts for me in order, or even at all... For instance, I just saw a post from 10 hours ago despite refreshing the page multiple times. 

 

Vaccines Part 2

 

I began these posts inspired by those of Dr. [mtn’s friend of a friend]. He was my best friend in the [Local Idaho] medical community and has remained so to this day. We have shared wine tasting trips, rock & roll concerts, bike rides and frequent dinners. He is the consummate Internist; “old school” with incredible clinical judgment. He has been providing frequent posts recording and reviewing current events in the era of Covid-19. My posts are discussions of the basic science behind clinical events are meant to compliment his posts! Don’t miss them. He will be referred to as the clinician.

 

[Clinician] and I became friends during the days when HIV/AIDS came to [Local Idaho Community]! That was the time when Dr. Fauci learned and developed an approach to combatting emerging viruses and resultant disease. He freely admits missteps and mistakes and has learned from them. He is our rock during these trying times.

 

I recently retired from active practice. When I left Idaho, I began the practice of consultative and developmental pediatrics in Spokane, Washington.  I became  involved with the University of Washington Medical School teaching medical students and residents. I was fortunate to serve as Principal Investigator with numerous clinicals trials. Many of them involved vaccinations and antiviral compounds.

 

Covid-19 virus is a single strand RNA virus subject to change or mutation. Random mutations are usually fatal to the virus but infrequently may change the structure just enough to permit the virus to avoid detection by the immune system. This is the case with Influenza virus requiring yearly adjusted vaccines. It would be desirable to find a target protein involved in replication of the virus rather than identification (spike) proteins. Replication proteins cannot change without fatal consequence to the virus. They must be conserved. Vaccines are now under study for both Influenza and all Corona viruses which target these proteins. This would prevent the need for yearly adjusted vaccines.

 

Covid-19 virus appears to have many sites of action which lead to the observed morbidity and mortality. There is direct action of the virus which causes host cell death. The more serious pulmonary symptoms are caused by a viral pneumonia accompanied a hyper-aggressive immune response which causes a picture similar to Acute Respiratory Distress Syndrome (ARDS) or shock lung. We know that many signs and symptoms of many common infections are actually caused by the immune response to the illness. ARDS is the product of an exaggerated hyperimmune reaction. The cytokine (immunomodulators) storm results in the pulmonary damage leading to respiratory distress, intubation and artificial ventilation. If we produce a hyper-immune response by vaccination we may contribute to the mortality of the infection. This is exceedingly rare but has happened in the past Respiratory Syndrome Virus (RSV) is an RNA virus which causes mild to severe respiratory distress in susceptible infants. The initials RSV are familiar to many parents of young infants. The infants begin to cough, wheeze and the resulting illness is the most common admission to children’s hospitals in the United States. With 150,000 admissions per year and no direct treatment, vaccine development has been a priority for pediatric infectious disease specialists for 40 years. Unfortunately, the first clinical trial had to be cancelled when vaccine recipients had increased mortality when infected during annual community spread after vaccination. The vaccine exaggerated the immune response. There is ongoing research but no successful vaccine has been brought to market. mtn note: For those of you who aren’t aware, my wife and I lost our daughter in 2018 two weeks after she was born. While we’re not sure exactly what happened, we’re about 99% sure that virus had attacked her heart (no, not Covid – this was 2018, we don’t know what virus it was). One of the things that we learned during our two weeks of living in a NICU/PSHU (Pediatric Surgical Heart Unit, within an ICU) was that pediatric medications aren’t really a thing. Almost every medication that is used is old, accepted from a time before we did clinical trials. Why? Because it is almost impossible to do trials on pediatric patients. And it is easy to see why – would you, as a parent, agree to sign your child up for a clinical trial in which they may not even get a drug (control group), knowing that they may die from it? Science is hard when it is done in real life. Just an interesting thing that I learned… now back to the actual medical professionals:

 

We don’t know if this is an isolated event or if it may occur with a Covid-19 virus vaccine. Clinical trials will sort this out. The rotavirus vaccine that has virtually eliminated forty thousand pediatric admission for episodic winter vomiting/diarrheal disease required several trials with up to 80,000 subjects before eliminating potential side effects. It took several years. This is why infectious disease specialists demand appropriate clinical trials before recommending utilization of any potential vaccine or therapy. A personal “hunch” is no substitute for good science. Hopefully good science will prevail in this environment.

 

As daunting as vaccine development seems it pales in contrast to implementing a successful candidate. We have a reservoir of talented, innovative scientists dedicated to developing appropriate tools to combat the virus. Implementation of a comprehensive vaccination program will require a nationally directed and coordinated program with intense social consequence. Questions of mass vaccination – mandatory? – to provide herd immunity or selective allocation to vulnerable populations will need to be discussed and answered. What percentage of immune population will be necessary to prevent circulation of the virus? No virus can circulate without a body of susceptible individuals.  Administrative experience and dedicated political leadership will be required. No matter how successfully production ramps up a relative scarcity of the vaccine will be present as it deploys. Questions of allocation both within the United States and outside our borders need to be answered. Establishing an effective distribution system will be paramount.

 

There will be the loud and disruptive anti-vaccination protest to be sure. Influenza circulates yearly causing forty to seventy thousand excess deaths each year. Vaccines are available tailored to all age groups which either prevents infection or reduces severity. Roughly 60% of children receive the vaccine, and only 45% of adults! Virtually all the children dying from the flu this year were not vaccinated. Covid-19 appears to be more lethal than influenza by a factor of ten. Will the populace be required to vaccinate to prevent another wave of infection? Questions to ponder.

 

 

Later this week I will discuss approaches to treatment.

 

 

 

 

Numerous updates from “The Professor”

 

 

Treatment – Part II

Errata: I failed to mention the lipid (fats and sugars) part of the surface viral structure.

The numbers of young, healthy people perishing in the 1917 flu epidemic was unprecedented in modern times. For many years it was thought to be secondary bacterial pneumonia causing the mortality. From a modern perspective the time from infection to death was astonishingly short for bacterial infection to cause the deaths. Another mechanism was implied Acute Respiratory Syndrome (ARDS) was first described in the British Medical Journal Lancet in 1967. The article described patients who had a sudden deterioration in lung function in a variety of clinical settings – burns, trauma, bacterial infection. The course was rapid. It became identified frequently in the Vietnam War associated with a variety of battlefield trauma.

 

As our understanding of innate human immune systems progressed, numerous factors were identified which controlled, amplified or inhibited innate immune reactions. They carry the names interleukins, interferons, tumor necrosis factors, chemokines, lymphokines. They are small proteins - peptides - which came to be named cytokines.  Many medications advertised on television for control of autoimmune diseases – Rheumatoid Arthritis, Crohn’s Disease, Multiple Sclerosis act by blocking cytokine action and reducing inflammation. They can also inhibit the action of proliferative disease – Psoriasis and Cancers. They can support the body by stimulating red cell growth, immune system function during chemotherapy. While they can be medically exceedingly useful cytokines can act as a two-edged sword. They are generally impressively expensive.

 

Covid-19 virus infection starts its course by attaching to the ACE-2 receptor on human cells initiating viral replication. In the upper respiratory tract, it is commonly controlled by the host immune system with no or minimal symptoms and the patient recovers with little or no knowledge they had been ill. They were contagious during this time however. If infection progresses to the lower respiratory tract where there more dense receptors the disease can be more severe. If the immune reaction goes into overdrive with massive release of immune modulators – the cytokine storm – the immune system becomes the major source of further morbidity and mortality. The lungs become stiff, fibrotic and fell with cellular debris and fluid. Shortness of breath is perceived by the patient and they become critically ill.

 

This is highly likely the cause of the 1917 Influenza death rate, the cause of ARDS, and the source of the rapidly declining respiratory function in Covid-19 leading to hospitalization, ICU status, ventilation and unfortunately death. It also provides for an opportunity to interfere with process and favorably affect the course.

 

Comprehensive care of Covid-19 patients will evolve into a two-pronged approach. There will be clearance of the virus by antiviral agents. Medications will then be directed at reducing the inflammation caused by a potential or existing cytokine storm. Clinical trials are currently underway with numerous existing or developing immune modulators. These trials will determine efficacy, safety, route of administration, and guide us to the best timing of use for maximal individual and community benefit. Unfortunately, there are few short cuts with this process. The medications will be most likely be expensive with early shortages and questions of priority and distribution will have to be addressed. There over 60 and counting candidates either entering early animal or human trials or under further development around the world. Compassionate use has become more common and may provide direction for further development.

 

Apeiron Biologics has an approach to flood the body with false ACE-2 receptors confusing the virus. Alnylam Pharmaceuticals and Vir Biotechnology are trying to block attachment with proposed pharmaceuticals. The ACE-2 receptor is intimately associated with blood pressure regulation side effects will be carefully monitored.

 

There are ten cytokine Anti-Tumor Necrosis Factor Medications licensed for use in the United States. They are advertised frequently on television. Infliximab (Remicaid-Janssen) and Adalimumab (Humira-Abbvie) have been well studied for other indications with good safety profiles. They will be looked at for Covid-19. Il-6 receptor antibody Tocilizumab (Actemra-Genetech) has been studied in France with promising results.

 

I have highlighted a small representative sample of potential therapeutic agents. These compounds will be reducing the hyperimmune response. They also may also impair the needed immune reaction to clear the virus. These are questions to be answered in a properly constructed clinical investigations. There is no place for hunches in this process.

 

 

Immunology 101!

Understanding the immune system permits us to describe the natural course of Covid-19 or any infectious disease. It helps us understand the interaction between host and infectious agent. This understanding will determine means to control a budding epidemic before it progresses into a pandemic. A sophisticated immune system is essential for life. Without it any organism would rapidly succumb to infection. Witness the “Bubble Boy” an inherited genetic lack of immune function or HIV/Aids an acquired immunodeficiency.

 

Immune systems developed very early in evolution and have been refined over the ages. Virtually all jawed vertebrates share the same basic mechanisms. The systems are layered from basic barriers to specific reaction to specific organisms. Functions of the immune system include protecting the host from pathogenic organisms – parasites, bacteria and viruses - and identifying and eliminating budding cancers. It also serves to clear the body of dead cells and internal debris and maintain surveillance of its environment. There are complex signaling systems between components and active short and long term memory function.

  • The first component is the barrier of intact skin or integument. While some parasites my pierce intact skin, viruses and bacteria require a portal of entry to infect. A burn, laceration, puncture or presentation to susceptible mucous membranes is required. Thus the importance of shielding the nasopharynx or eyes from possible contamination.
  • The second layer is non-specific immunity which actively identifies and removes unwanted invaders. Early in development the body develops a sense of self with tags specific to the individual. The immune system learns to ignore cells with the “self” markers. When this system goes awry, we have autoimmune disease (rheumatoid arthritis, lupus). The body literally attacks itself.

 

Antigens are the presenting part of an organism which provokes the immune response. They may be proteins, sugars or nucleic acids (the components of genes-RNA, DNA) Nonspecific immunity begins with inflammation. This is the warning signal. There is increased blood flow, capillaries become leaky permitting immune cells to leave the blood stream to attack an invader and immunocompetent cells flood to the area. Specific identification of the invader is not required; just the recognition of non self. It is the most immediate reaction and critical to health of the host. Cells involved are neutrophils – white blood cells which can engulf and destroy bacteria and viruses. Their number typically rises in blood counts with acute infection particularly bacteria. Natural killer cells can attack cancers and macrophages typically clean up the area. Signals are sent to the more sophisticated adaptive immune system.

 

Dendritic cells engulf the invader and serve to present the invader to lymphocytes. This serves to sensitize and activate the immune system to the specific threatening organism. This occurs in lymph nodes. The first presentation is to T-cells (remember HIV and the destruction of T-cells!) They are a type of lymphocyte white blood cell. This reaction is amplified with cytokine signaling. Memory T-cells process the identifying antigen and store this memory to mount a reaction if the same invader presents itself months, years or a lifetime in the future. Cytotoxic T-cells may attack and eliminate infected cells or potential cancer cells. Helper T-cells work with B-cells – another classification of lymphocyte – to promote antibody production specific to the invading organism.

 

B-cells are the engines which produce antibodies. When stimulated the B-cell lymphocyte transforms to a plasma cell which turns out vast quantities of specific antibodies. The antibodies are structured to bind to a foreign antigen. This binding permits neutrophils and other killer cells to engulf and destroy the infecting agent. Cytokines are also released to amplify the response. B-cells can act independently or at the direction of memory T-cells.

 

There are four major classes of antibody. IGM is secreted first and rapidly cleared. Its presence signals recent infection. IGG is the most important protective class and may take several weeks to be present. It will remain in the bloodstream for several years to lifetime. Its presence signals an infection in the past. Hopefully it signals ongoing immunity. These are the antibodies most proposed tests will measure. There is also IGA present in entry portals – the GI tract, saliva mucous membranes. IGE evolved to protect against parasites and is involved in allergic phenomena.

 

When one is vaccinated there is a primary T and B cell response which typically takes two weeks to mature and may provide short or long term protection. With a live virus vaccine an actual infection occurs which provokes memory T-cell responses such that protection may last years or a lifetime. This memory processing takes several months. When challenged months or years later there is a rapid response within four days. Thus the advantage of live virus vaccines! Currently developing DNA vaccines may also provide continuous protection. There are serious questions when evaluating vaccine trials. We need to know what level of antibody provides immunity. We need to know length of protection.

 

When looking at personal antibody testing we also need to know accuracy. One needs to know the false positive and false negative rates. There are over 60 test platforms currently in trial and use in the United States. Very few have been tested and only four validated by the FDA. Remember the only thing worse than no information is bad information!

 

I know this topic is complicated and what I presented is an overt simplification. I hope the knowledge presented permits readers to evaluate and comprehend the mass of articles and data available in the media and on the web!

 

 

Hunches Versus Science

The Veterans Administration just completed an analysis of the use of hydroxychloroquine (Plaquenil) for Covid-19 infection. The results have been submitted to the New England Journal but have yet been subject to peer review. The study was funded by National Institutes of Health (NIH) and the University of Virginia.

  • Researchers analyzed records of 386 male veterans hospitalized with confirmed corona virus Covid-19 infection at VA medical centers. 28% of those receiving hydroxychloroquine plus usual care died. 22% of those receiving azithromycin plus hydroxychloroquine passed. The group that had the same usual care without the medication had 11% deaths. The use of hydroxychloroquine made no difference in ventilator use.
  • There was not difference in the groups which would suggest another reason for the outcome. There was a suggestion of increased organ damage in the medication group.
  • This was admittingly a retrospective study but the largest group looked at so far. Prospective double-blind studies are underway under the direction of NIH.
  • Scientists in Brazil stopped part of a hydroxychloroquine study when one fourth of the higher dose group had heart rhythm problems.
  •  

Science not anecdotal observations, hunches or gut feelings needs to drive eradication of this pandemic. Dr Fauci has consistently given solid unbiased advice about management of Covid-19. He is a distinguished brilliant virologist who speaks from experience and always with the truth as his moral compass.

 

Corona Viruses

  • Corona viruses were identified as animal pathogens in the 1930s. They are enveloped single strand RNA viruses of the Nidovirales order. They are named for the spike like surface proteins visualized with electron microscopy.
  • Several species were identified as human pathogens in the 1960s. They are most frequently associated with routine upper respiratory infection illness with rhinorrhea, (runny nose!) nasal congestion, sneezing, sore throat and cough associated with low grade temperature. Symptoms are self-limited and peak in 3-4 days. It is often described as a bad cold with increased frequency in winter. Occasionally it is associated viral (walking) pneumonia and could trigger bronchiolitis and croup in infants. Immunity after infection is short-lived resulting in annual recurrences.
  • SARS-CoV emerged in 2002-2003 as a serious problem. It was associated with severe symptoms although asymptomatic and mild cases were described. It originated in the “wet markets” of China from horseshoe bats through civet cats. It propagated to Taiwan, Vietnam, Hong Kong and Singapore. The major western center was Toronto, Canada. It occurred primarily in adults associate with high fever, chills, myalgias (muscle pain) with nonproductive cause and dyspnea (difficulty breathing) 25% developed watery diarrhea. Twenty percent required intubation and ventilation. The overall death rate was 10%! Case fatality rate in those over 60 was 50%! Adolescents had clinical picture of adults while young children had mild courses.
  • The SARS outbreak lasted 9 months with 8096 cases and 774 deaths. Treatment was supportive with no specific therapy available. There have been no identified cases since 2004. The lethality of the disease led to aggressive public health measures as identification, contact tracing and quarantine and this was successful in containing the outbreak. The seriousness of the infection ed to early research into appropriate testing procedures and early antiviral therapy but rapid decrease in infection terminated much of the effort.
  • SARS stimulated early concern for possible pandemic viral infections with unknown or newly discovered (novel) agents. Pandemic monitoring and response planning was initiated under President Bush and continued with President Obama. The offices and their function was eliminated by President Trump. The Gates foundation committed significant funding for ongoing research and Bill Gates made his memorable speech describing a viral pandemic more a threat to mankind than nuclear war.
  • MERS-CoV was identified as the causative agent of Middle East Respiratory Syndrome in 2012. It emerged in Saudi Arabia and Qatar with bats as the carrier with propagation through dromedary camels. While it has been identified in 27 countries 80% have been recorded in Saudi Arabia. Its distribution is closely associated with camels. It is associated with older males and with symptoms of fever, chills, shortness of breath, nonproductive cause and severe myalgias. There have been greater than 1900 cases with 858 deaths. The case mortality rate was estimated at 36%! Once again aggressive public measures help control the epidemic but a single traveler from the middle east to South Korea led to a cluster of 186 cases and 36 deaths.
  • The seriousness of this original presentation led to renewed research into vaccines and antiviral therapy. There were better bioscience tools available in 2012-15 than ten years before and significant progress was made but with the waning of the epidemic funding diminished.
  • SARS and MERS were the prototype novel corona virus infections. We hear the terms frequently as the basis for further research into Covid-19. However there is very different epidemiology at work here. The very lethality of MERS and SARS helped control the infection. The virus needs a continuous supply of live hosts and susceptible targets to propagate. It also needs a prolonged period where the virus can transmit to subsequent host with facilitated person to person transmission. These were not present with these syndromes. They conditions are present with Covid-19. The presence of long periods of contagiousness without knowledge of infection makes Covid-19 the perfect agent for pandemic.

 

I will try to bring some light to the concept of epidemiology later this week. Please continue to follow  the clinician (the posts mtn is sharing) for up to date developments.

 

 

 

 

 

COVID-19  Update #33 

April 22, 2020

 

Right up front, many thanks to my darlin' wife who reviews the post every morning.  She is a perfectionist, and makes the post more readable.

 

News for today:

  • Hong Kong reported zero new cases yesterday.  This is their second wave.  They appear to have achieved containment a second time.  They have learned and are extending closures and distancing another two weeks.  Georgia and others should pay attention.
  • In Beijing, they had opened gyms with tight restrictions, and movie theatres as well.  The government has closed both back down.
  • Russia is escalating, with 5,642 new cases Monday.  (Probably many multiples of this.)
  • Sweden's deaths are off the charts at 1,200 and climbing.
  • Singapore continues to escalate in its second wave... 1,111 new cases.  They state only 20 are citizens. (so what?)
  • New York, after being stuck in the 590-700 deaths per day range for awhile, looks to be declining... only 478 on Monday. The better indicator, admissions and ICU admissions, continue to drop, but still 2,000 per day.  They are testing a sample of 3,000 New Yorkers out of 20 grocery stores, to get an idea of what percentage have been infected statewide.  They will have the same bias and problems that the Stanford study had.
  • Remdesivir had a bit more news. 
    • A clinician at Montefiore hospital in the Bronx has stated he thinks it's helping, no numbers from him. 
    • There was an interesting piece posted on Reuters, on its mechanism of action.  It is highly complex, in the simplest terms, it binds to a section of an SARS-CoV-2 enzyme, RNA dependent RNA polymerase, which in turn inhibits viral replication.
    • The data we will be seeing early on in both Remdesivir and convalescent plasma will be in the most severe patients.  I think where it will work the best is earlier on, before all the damage is done, which is just my opinion.  That data will be a bit longer in coming.
  • In the largest study to date, run out of the VA hospital system, 368 patients were studied comparing hydroxychloroquine with standard care.  The paper has been submitted to the NEJM for publication.  There was no difference in who had to be ventilated.  With hydroxy- 28% died, with hydroxy and azithromycin- 22% died, and on standard care- 11% died.
  • The hydroxychloroquine numbers were statistically significant. The conclusion was, it was of no benefit and more people died while on it.
  • The New York Times is displaying a lot of new graphing techniques, which I think are very helpful in seeing how things are going.  Take a look, it is free.
  • I read that the So. Carolina beaches are reopening.
  • It looks like none of the states that are reopening have had a 14 day decline in new cases.
  • Idaho is talking about the first of May to reopen, Governor Little says, unless something in the data precludes it.
  • These decisions need to be data driven, they affect us all.
  • The pandemic is going to end up closing a lot of rural hospitals.  As anyone who works in a hospital system knows, elective surgeries are what pay the bills.  When patients are in ICUs or on ventilators, the hospital gets killed financially.  It is absolutely backwards, but it is what it is.  It will be a great blow to many small isolated communities.
  • I read a post which referred to the catastrophic second wave during the 1918 H1N1 pandemic. This was not due to people's behavior, the virus went through a mutation which was much more lethal than the original.

 

 

 

 

COVID-19  Update #34 

April 23,2020

 

  • Be careful of statistics, they can be either very informative or very misleading.  I'll give you an example:  Over the past five days the numbers of new cases in my county have been, 0,1,1,2,4. I could say the number of new cases here is doubling every day and that would be correct.  In reality it means nothing unless we see a clear trend over the next few days.
  • The FDA has become a major disappointment.  Taken as a whole, their efforts have done more damage than good.  I view them the way we all viewed FEMA during the first crucial days after Katrina.  I am hoping they will do better as new drugs and treatments come forward.  They are used to plodding along.  New drugs can take up to 7 years to be approved.
  • The NIH has issued new guidelines.  They state no drugs should be given pre or post infection, if they are not involved in a clinical trial.  While I understand this position and the need for evidence-based recommendations, I think compassionate use should be wide-open while we wait.  I think the patients and their docs should decide the best course of action.  I'd want 200cc of high antibody plasma on admission and again 3 days later if I was still in the hospital.  If I was clearly getting worse, I'd want 5 days of Remdesivir.  Benefits, by far, outweigh the risks.
  • The British Medical Journal published data on persistence of viral load.  The median for stool was 22 days, the median for respiratory secretions was 18 days, the median for serum was 16 days.  The presence of detectable virus and contagion are not the same thing.
  • Our friends at the FDA have issued another EUA (emergency use authorization) for Lab Corp's home version of the swab test for RNA by PCR.  You do the swab at home, and then mail it to LabCorp and they send you the results.  I think the false negatives will be overwhelming.  I'm not sure how I feel about sending live corona virus through the mail.
  • Cases have arrived in Haiti, likely from the Dominican Republic.  The DR already has a significant problem.  In 2010, 820,000 in Haiti were infected with cholera.  Slums, crowding, malnutrition, lack of clean water (much less soap), and low income all contributed.  Its poverty may have protected it until now, but no longer.  Half of Haiti's population earns less than $2.41 per day.  Urban slums and refugee camps all over the world are at great risk
  • Based on deaths in Santa Clara county Feb 6 and Feb 17 proven from SARS-CoV-2, we probably had the virus in this country in late January.
  • In New York, the single day death toll is under 500 for the third day in a row.  Imagine that only 500 a day dying from a virus in New York, is a cause for celebration!  How much the world has changed.  New York, with the financial aid of Mike Bloomberg, is going to hire a tracing army, to help those who are positive to isolate, and hopefully their contacts.
  • Mexico is now over 10,000 cases, with 970 dead.  They had more than 1,000 new cases yesterday, clearly on the steep side of the curve.
  • I will be looking for prelim results on Gilead's clinical trial on severe cases being treated with Remdesivir today and tomorrow.  I'll keep you posted.  This could be huge.
  • The MMWR (morbidity mortality weekly report) published data on homeless shelters.  They looked at 19 shelters in four major cities.  They tested 1,200 residents and 300 staff from the end of March until early April.
  • First, in shelters with two or more known cases:
    • 17% of residents and 17% of staff were positive in Seattle
    • 36% of residents and 30% of staff were positive in Boston
    • 66% of residents and 16% of staff were positive in San Francisco
    • 18% of residents and 21% of staff were positive in three different shelters in Washington State.
    • In shelters with only one or zero cases the prevalence dropped off to 1 to 5%.
  • Vaccine updates:
    • Germany's Bio N Tech began human trials on 200 healthy volunteers, ages 18 to 55, for their vaccine candidate.
    • Oxford's team began human trials on April 22nd.  They estimate an 80% chance of success.  Remember, this is the group that is manufacturing as they test. Their goal is September for a viable vaccine available to the public.

 

 

Stay safe, isolate, wear a mask in public, be part of the solution

 

 

 

 

COVID-19  Update #35 

April 24,2020

 

The amount of disinformation out there is becoming staggering. Just because it is in writing or posted on the internet, does not mean it's correct.  If something seems wrong, including what I write here, look for verification elsewhere.

 

Some of the non-medical sites are being written by folks that just don't have the background to really understand what they are writing about.  It's a bit like when I watch some medical drama on TV. The actors make statements or diagnoses, the x-rays are up sideways and are of the wrong body part.  While that drives me crazy, this (disinformation on COVID-19) is flat out dangerous. One site, that I just subscribed to, published last night. It was as if it was written by a spin doctor.

 

  • First, it condemned antibody testing because someone with antibodies gave the virus to others. A person with an antibody response may still be contagious, and that same person can transfer the virus from their hands to another persons skin. This is no surprise.
  • Second, and I have seen this on several sites, they implied that the FDA had given EUA (emergency use authorization) to only four antibody test producers. This is incorrect, the FDA said anyone could sell their product and that the FDA would review their data later, and pull any products that didn't pass muster. They later changed this, as too many tests were very inaccurate. They have reviewed the data and approved 4 companies products. They need to review the other 86 ASAP.
  • Third, they implied that anyone with positive antibodies was immune. We flat out don't know.
  • Fourth, they said that Gilead's drug was a "bust" based on a study out of China. (See below)

After reading these postings I blocked the site.

 

I will post what I hope will be a useful review of testing Monday morning.  I am getting a lot of questions as antibody testing roles out. More on antibodies:

  • New York has posted it's survey of 3,000 grocery shoppers. The results were much better than the Stanford study. In NYC, 21% of those shoppers were positive for antibody. Statewide the number fell off to 14%. In Santa Clara county, only 5% had antibody.
  • Chile has rolled out its version of immunity certification. This plan might just work in NYC. While any certification of immunity program will have its problems, it will be far superior to the Georgia approach. Those with false positive antibody testing will be at risk. Those with true positive antibody testing may not be immune.
  • My view is that anyone with antibodies, if indeed they have a second infection with SARS-CoV-2, will have a much milder case. The documented second infections worldwide is very small. I am not even certain it is a real phenomena.

 

Other bullets:

  • The WHO posted a study from China on Remdesivir. They immediately took it down. The study had been terminated for lack of enrollment. In my view, since the government of China has taken over what is published, and how it is reported, any data from China is now tainted, and must be verified.
  • The mayor of Las Vegas wants to re-open casinos.
  • As of today one can go out and have a massage, a tattoo, or your hair done, in Georgia, as long as you practice social distancing while doing it. WHAT?
  • Please do not inhale or ingest disinfectants.
  • Ecuador has reported 537 deaths. The New York Times stated they think the number is 15 times that.
  • Many decisions are being made based on modeling. These models come from a variety of reputable sources. In a section of the Times called "Upshot", they reviewed 5 different models. The plots of disease and deaths from the virus are so divergent that only one conclusion seems valid: The "modelers have underestimated how little they know."
  • There are a lot of inaccurate antibody tests out there. Make sure you understand whose test you are taking. It is up to the FDA, who allowed this to happen, to pull the products that are not reliable.
  • By the end of this week, more people will have died from the virus in the United States than died in the 10 years of the Vietnam war.

 

Stay safe, isolate, wear a mask in public, don't believe everything you read. My wife has not yet reviewed this, but it's getting late. I will repost this later.

 

 

 

 

 

 

COVID-19  Update #36 

April 25, 2020

 

The best sources of reliable information (for me) have been the NEJM, the New York Times, JAMA, Doximity, and the Lancet. Today I'll focus on the 4/24/2020 issue of the NEJM and three of the articles published there.  If you know me well enough to have my e-mail, and request it, I can try to send you a link to this issue.  Do not use my e-mail for questions please.

 

  • One article talked about rates of transmission in a skilled nursing facility.  It was very sobering. Twenty three days after the first positive test in a resident, 64% of the residents were positive.  Fifty-six percent were asymptomatic.  As of April 3rd, of the 57 patients with the virus, 11 had been hospitalized (three in the ICU), and 15 had died.  This means that many had died in place. There are three main conclusions drawn from this study and editorial comment that followed. 
    • First, infection control focused solely on patients with symptoms was inadequate to prevent transmission, once the virus was in the facility. 
    • Second, we must test asymptomatic people in prioritized settings, such as jails and nursing homes.
    • Third, wear facemasks in public; just because you are infected without symptoms does not mean that the people you infect will be as well.
    • mtn provided link: https://www.nejm.org/doi/full/10.1056/NEJMoa2008457
  • The second article was under the heading 'Clinical Practice' entitled, "Mild Or Moderate Covid-19".   It is the single best review article I have seen, thus far in the medical literature. This, you would have to read yourself.  It is mostly in English, and not medical.
  • The third article was a beautifully written piece on how the virus has affected the Navajo Nation.  It is moving, and paints a wonderful picture of their culture.  A must read as well.
  • Nineteen states will be resuming limited elective surgeries between now and the end of May.  Our hospitals are taking a huge financial beating.  This will help them stay afloat.  If healthcare is one of your philanthropic interests, now is the time to step up. (emphasis by mtn)
  • From the NYT... the mosques in Pakistan, and I'm sure in many other countries, are crowded for Ramadan.  Social distancing is not really possible.  This could be a very bad thing.
  • I see several of the pundits in the financial world trying to manipulate the data in favor of reopening the economy.  One was saying that the mortality percentage is much lower than we thought. This is a true statement, and not anything new. The suggestion is that it's safer than we thought. The other way to look at this is, the total number of deaths is unchanged.  The total number of deaths is underestimated, even in the U.S., world wide it is vastly underestimated.  If by the end of this pandemic, one in three Americans have been infected, and the mortality rate is 0.5% (a pretty good estimate), 500,000 will die in the U.S. alone.  It is our job to hold these percentages down.  We can do this if we work together.
  • There has been concern that two classes of medication primarily for hypertension, ACEs and ARBs, might be a problem if a person taking them were infected.  This was a worry, as the virus uses the ACE 2 receptor to gain access to our bodies.  Two well written articles have refuted that concern, and show it might actually be of some benefit to be on them in those that remain hypertensive after admission.

 

This feels like it's getting a bit long.  I'll leave you with a recent quote, it is not grammatically correct but makes a point.  "If you see anyone on TV try to give you medical advice, turn it off.  Call an actual doctor.  Your doctor.  And talk to them about your situation."

 

Stay safe, isolate, wear a mask in public, be part of the solution

 

 

XYZ

 

COVID-19  Update #37 

April 26,2020

 

I meant to lead off yesterday with an update on Captain Moore.   It was the best thing I had read in a week.   As you may recall from a prior post, this is the 99 year old WWII vet, who set out to raise money for Britain's National Health Service by walking in his garden.  His initial goal, as far as I can recall, was 1,250 pounds.  There was a lovely picture of him walking in his garden, using his walker. Well, Captain Moore has gone and set two world records, according to Guinness.  He has now raised 35 million dollars. This is a record for an individual on a charity walk.  He also recorded a single of "You'll Never Walk Alone"... this also to raise money.   It hit the top of Britain's singles chart, with 82,000 combined chart sales.  He is now the oldest person to ever hold that position.

 

  • It has become clear that this virus has hit minorities and people from disadvantaged groups.   In the U.S., it has been especially lethal to African Americans.  Their are some who believe that Georgia's policies are a direct attack on people of color.
  • The European Union, pressured by China, has backed down on its criticism of China's global disinformation campaign. This, in my mind is not a time to play politics.  It's a time to put aside our differences and work together.
  • JAMA published an article describing the California experience, within the Kaiser network, during the month of March, 2020.  No patients were lost to follow up.  They tested 16,201 people. The surprises for me in this data was the lack of other viral infections, and the age of those admitted.
    • 1,299 were positive for SARS-CoV-2 (8%).  
    • Of those testing positive, 377 were admitted to the hospital (29%), 113 were admitted to the ICU (8.7%), and 110 were placed on mechanical ventilators.
    • The group aged 60 to 69 was the most common hospitalized  and admitted to the ICU.  I was surprised that 45% of those hospitalized were less than or equal to 59.
    • Forty-four percent of those admitted were tested for Influenza A and B, and RSV.  None were positive.
    • At the end of the study period they looked at those with "discharge dispositions" (meaning no longer in the hospital). Sixteen had died, of the 68 ICU patients with discharge dispositions, 34 (50%) had died.
  • The New York City area was also reported on.  They looked at 5,700 patients from the greater NYC area, from 3/1/2020 until 4/4/2020.
    • They reported only 2% were found to have other viral infections.  This again, a surprise to me.
    • Among those who were discharged or died during the study period (2,634), 14.2% were treated in the ICU, 12.2% on ventilators, and 21% had died.  The percentage of patients in the ICU or on ventilators was greater in the 18 to 65 group, than the over 65 group.  This again, was a surprise for me.
  • There was a review of available literature on pediatric illness with the virus.  This was also in JAMA.   There was a surprising lack of hard numbers, but they confirmed that those ill recovered quickly and only one became severely ill, but recovered.  That is the only good thing about this virus as opposed to the flu.   I wonder, as I'm sure many others have as well, what is it that protects the very young from this virus?

 

I'm back to work on tomorrow's post on testing, in the meanwhile, stay safe, isolate, wear a mask in public.

 

 

 

ZYX

 

For further updates, go to page 2 of this thread. 

mtn (Forum Supporter)
mtn (Forum Supporter) MegaDork
4/17/20 11:48 a.m.

Updated 4/17

Aaron_King
Aaron_King PowerDork
4/17/20 12:05 p.m.

Thanks for the updates, I have sent this to a couple of people.

engiekev
engiekev Reader
4/17/20 1:50 p.m.

Great updates!

Pedantic correction:  it's Royal Oak, MI "Beaumont Health based out of Royal Oaks, Michigan, stated on April 14th, that it is starting the countries largest serology testing.  It will test all 38,000 of its employees.  This should produce some very useful data, especially for hospital systems."  

Things have been pretty crazy in Michigan after the recent "protests" (if you can call them that), honestly its showing who understands the situation and who does not. MI is 3rd in the country for cases and deaths, and we're not dropping down the list anytime soon thanks to the campaign rally that was held at the capital.  Unfortunately many of those who attended live in rural areas and small cities, where the virus had not been widespread in Michigan yet.  Those rural areas are now likely to see a spike in cases and deaths within the next couple weeks, and may result in prolonging the stay at home orders.

mtn (Forum Supporter)
mtn (Forum Supporter) MegaDork
4/17/20 9:03 p.m.

Another (very small, but significant) update for 4/17.

trigun7469
trigun7469 SuperDork
4/18/20 5:05 a.m.

Thank you for the updates. He/She been following herd immunity in Sweden?

mtn (Forum Supporter)
mtn (Forum Supporter) MegaDork
4/19/20 2:13 p.m.

Updated from my phone, will reformat later from my desktop.  

trigun7469 said:

Thank you for the updates. He/She been following herd immunity in Sweden?

I’m not sure if he has but will send him a question to opine on it. I’m not going to post the graphs I’ve seen on it, as I have not been able to verify their accuracy, but I’d expect him to have a pretty negative view on it based on his prior posts and the fact that in my opinions it’s pretty obviously a bad idea IF the charts are accurate. 

bluej (Forum Supporter)
bluej (Forum Supporter) UberDork
4/19/20 2:27 p.m.

Thanks so much for sharing these here, it's nice to get some genuine health professional perspective with less, um, media packaging.

EastCoastMojo (Forum Supporter)
EastCoastMojo (Forum Supporter) Mod Squad
4/19/20 6:04 p.m.

Agreed, these posts have been extremely insightful and calming, thank you for sharing them. Science!

mtn (Forum Supporter)
mtn (Forum Supporter) MegaDork
4/19/20 9:59 p.m.

Updated for post on 4/19

Javelin (Forum Supporter)
Javelin (Forum Supporter) MegaDork
4/19/20 10:43 p.m.

Thank you for sharing this.

mtn (Forum Supporter)
mtn (Forum Supporter) MegaDork
4/20/20 3:08 p.m.

Updated for 4/20, and sadly, no jokes for 4/20. I am disappoint. 

 

mtn (Forum Supporter)
mtn (Forum Supporter) MegaDork
4/21/20 1:18 p.m.

Updated for 4/21, along with a post from his Professor friend. The professor's post should have come prior to his post on April 12, but either I did not notice it or Facebook hid it from me until today when the internist, the guy posting all of these, shared it. 

mtn (Forum Supporter)
mtn (Forum Supporter) MegaDork
4/22/20 1:19 p.m.

Updated 4/22, along with a bunch of updates from "The Professor". This was a large textdump today due to that, and I apologize for that. I think we are caught up with The Professors updates now. 

 

Even though those are long and more "medical language" than the clinicians updates, I really recommend reading them as they were extremely enlightening. 

MadScientistMatt
MadScientistMatt PowerDork
4/22/20 2:31 p.m.
trigun7469 said:

Thank you for the updates. He/She been following herd immunity in Sweden?

Sweden is about the same size as Georgia, has a slightly lower number of diagnosed cases, but about double the number of deaths. Doesn't exactly sound like their approach is working out very well.

wheelsmithy (Joe-with-an-L)
wheelsmithy (Joe-with-an-L) UltraDork
4/22/20 3:14 p.m.

MTN: Thank You. This is, I feel, the best news source available. Be Well.

 

aircooled
aircooled MegaDork
4/22/20 3:55 p.m.
MadScientistMatt said:
trigun7469 said:

Thank you for the updates. He/She been following herd immunity in Sweden?

Sweden is about the same size as Georgia, has a slightly lower number of diagnosed cases, but about double the number of deaths. Doesn't exactly sound like their approach is working out very well.

Sweden is theoretically way farther down the "curve" then we are.  They "should" be getting all their deaths done with early, while ours will be spread out for a much longer time.  A direct comparison is not terribly appropriate.

One downside to their approach (even if it works exactly as planned) is they will not be taking advantage of any new developments in treatments that might save people from dying.  They will also not have anywhere near the economic, or social effects of full lockdown (which will certain take some lives or at least livelihoods).

Both will still have to figure out what to do with the vulnerable populations.  Theoretically, if Sweden reaches heard immunity, the vulnerables will be safe.  Of course... they will need to keep anyone not from Sweden or not verified clean out of Sweden, or at least away from the vulnerable population somehow.

mtn (Forum Supporter)
mtn (Forum Supporter) MegaDork
4/23/20 12:48 p.m.

Updated 4/23

 

I think he is talking about New York State in the bullet today, not just New York City. Out of curiosity, I wanted to see how this compared to a “normal” day. Using their health department data, NYS had an average of:

  • 425 deaths per day in 2017
  • 420 in 2016 (leap year)
  • 421 in 2015
  • 408 in 2014
  • 418.6 deaths per day average from 2014 to 2017

500 deaths per day would represent an increase of between 18% on the low end and 22% on the high end, with the overall average increase being about 19%. That is even if the 500 deaths was for ALL deaths, not just COVID. So even if all other deaths have stopped, and the only reason people in NYS are dying right now is COVID, we are still seeing a 19% increase in fatality for the state.

One possible problem with this data is that it is evenly weighted over a whole year, so in theory this could mean nothing if, in a normal year, deaths go significantly up in March and April compared to the rest of the year. I couldn’t find this data for New York State, but the CDC states that January, February, and December are the months with the highest average daily number of deaths. My own guestimation is that March and April are pretty close to average for the year, May-Sep is the low point, and Oct-Nov are pretty close to the average, with Dec-Feb being the high points. But this is just a guess. 

aircooled
aircooled MegaDork
4/23/20 1:48 p.m.

mtn:  Please thank you wife for us.  The format is indeed very readable!  yes

Javelin (Forum Supporter)
Javelin (Forum Supporter) MegaDork
4/23/20 1:55 p.m.

Mailing coronavirus?!? surprise

mtn (Forum Supporter)
mtn (Forum Supporter) MegaDork
4/23/20 2:24 p.m.
aircooled said:

mtn:  Please thank you wife for us.  The format is indeed very readable!  yes

 


You need to thank the Dr.'s wife, not mine! She is the one formatting it and editing it. But I should thank my wife anyways, she's awesome.

 

I need to ask him if he's ok with me sharing his name and localities. In any case, I am only formatting it from a facebook status into something that you can read on a webpage. Technology is a weird thing, when I read his posts on the Facebook app they are perfect. When you paste into a forum or word doc, they're not at all... That is where I come in bulleting things. I don't change ANYTHING other than adding bullet points and redacting personal information. 

mtn (Forum Supporter)
mtn (Forum Supporter) MegaDork
4/24/20 3:19 p.m.

Updated for 4/24. He does not recommend inhaling or ingesting disinfectants.

Shadeux (Forum Supporter)
Shadeux (Forum Supporter) Dork
4/24/20 4:15 p.m.

In reply to mtn (Forum Supporter) :

mtn, thanks so much for doing this! I look forward to each one.  yes

mtn (Forum Supporter)
mtn (Forum Supporter) MegaDork
4/25/20 3:39 p.m.

Updated 4/25

mtn (Forum Supporter)
mtn (Forum Supporter) MegaDork
4/27/20 8:37 a.m.

I just updated with his 4/26 update. Hopefully another one is coming today. 

 

1 2 3 ... 5
Our Preferred Partners
F7IgJq14ECnX67YZ9kWanivAvIoaqEhNrIvGSHevyKY9wnh8vAxgDvayYBYVpPC9