Tagged disease

Les Jeux Son Faits: COVID-19 Update to Students

“If some areas, cities, states, or what have you…prematurely open up…my concern is that we will start to see little spikes that might turn into outbreaks.” Dr. Anthony Fauci, answering Sen. Patty Murray, May 12, 2020

“When the outbreak started, sir, we had an aggressive contact tracing program, but unfortunately as the cases rose, it went beyond the capacity…so we lost the containment edge.” CDC Director Dr. Robert Redfield, answering Sen. Tim Kaine, May 12, 2020

“The purpose of science is not to open the door to infinite wisdom but to set some limit on infinite error.” Bertold Brecht, Life of Galileo

Dear Students,

Les jeux son faits. Or in English, the die is cast. Or in plain American, the dice have been rolled. Think of a slow motion video with a close-up of a hand releasing the small dotted cubes. We watch them seem to float through the air, then one, then the other touch the table surface ever so gently, then they bounce and float again, and then…

Never have I hoped so much that I would lose a roll of the dice, because I (among others) have hypothesized disaster. I want to come up “snake eyes” and slink away from the game. I want the majority of states opening up to come up with sevens and elevens. I want the American people to win this great gamble. We know so little about this virus that there’s a chance for an unlikely outcome, on either side.

No matter now though. Les jeux son faits. The video is so slow that it may take two weeks for the rolling dice to come to rest.

I am not going to repeat what I said in my previous updates about patience and precautions. My news this week is about what in our course we always called “Nuts & Bolts.” The slogging may be a little heavy in places. After all, I’m the professor. Knowledge is news. Knowing what you know is good news.

Good (Science) News

  1. We have known the sequence of this virus, SARS-CoV-2—causing the illness COVID-19—since early January. It is a single strand of RNA of a strain new to humans, with a wide adaptability, causing disease in many mammals. There is a bat coronavirus that is 93% identical to it, but other human SARS-CoVs are only 80% identical. It has a large genome for an RNA virus, with multiple “hot spots” for mutations, although it mutates slowly compared to flu.
  2. Corona, meaning crown, refers to the club-shaped surface proteins (aka “spikes”) that cover the surface created by the RNA with the help of human cells’ machinery. It has to get into our cells, and we have known since March that it does that because the spikes recognize an enzyme on cell surfaces called ACE2, normally part of a complex sequence controlling blood flow and blood pressure. Spike proteins use ACE2 to (sort of) pry open the cell. Once in, the RNA replicates itself and makes spike and other proteins protecting it and countering our immune system. It can do this (I’m estimating) a gazillion times.
  3. The first and still most accurate test for active cases of the virus uses a version of PCR (the polymerase chain reaction) to amplify the virus’s RNA enough to measure it accurately. Last month a device from Abbott called ID Now that amplifies viral RNA much more rapidly was approved for emergency use. Last Friday (5/8) the FDA approved for emergency use a first-in-class test for viral antigens, meaning fragments of viral proteins. It is also possible to infer the presence of the virus indirectly from very high levels of IgG antibodies (Abs, pronounced “ay-bees”). At-home testing is partly approved; DIY sample collection, send in the sample.
  4. With regard to establishing who has had the virus and recovered (or never showed symptoms), there are up to 12 approved antibody tests and 200 more in development. Most of these are qualitative, especially the rapid-diagnostic ones (RDT; 10-30 min) using finger pricks, saliva, or nasal swabs. They tell you you either do or don’t have IgG or IgM antibodies to the virus. ELISA assays (2-5 hr), showing how your antibodies combine with viral proteins in a dish, can be quantitative. Neutralization assays (3-5 days) put your cells and Abs in a dish with the virus and quantify the amount of Abs needed to block the virus from entering the cell.
  5. Treatments under study include antivirals (Remdesivir and others developed for older viruses), immunotherapies (which, like interferon beta, strengthen the immune system), convalescent plasma (from recovered patients), immune globulins (Abs purified from same), monoclonal antibodies (Abs specific to viral proteins, mass-produced from cloned cells), and others. Remdesivir shortens hospital stays in very sick COVID-19 patients from 15 to 11 days. (For true nerds, Remdesivir mimics the RNA base adenine; it slips into adenine’s place in viral RNA replication, dashing the virus’s reproductive dreams, partly.)
  6. Roughly 100 labs around the world are developing COVID-19 vaccines by varying methods to increase the chances of success. This includes DNA and RNA vaccines matching part of the viral genome, proteins mimicking part of the spike, and other strategies. The first clinical trials were begun 62 days after the virus sequence was published, by far the fastest time ever, around 10 more were added by late April, and more will begin soon. Dr. Fauci said today that, “this is a virus that induces an immune response, that people recover, the overwhelming majority of people recover from this virus… The very fact that the body is capable of spontaneously clearing the virus tells me that, at least from a conceptual standpoint, we can stimulate the body with a vaccine that would induce a similar response.” So he considers it “much more likely than not that somewhere within that time frame [12-18 months] we will get a vaccine.”

Bad News

  1. The supply chain is not robust for any of the above, and will not be for many months. Remdesivir, the only proven (in an unpublished study), partially effective treatment is being rationed to states and hospitals, forcing doctors to play God. There is not yet a serious plan to ramp up new pharma factory building to meet the coming demand for treatments or vaccines, if and when they are proven.
  2. We continue to have a poor grasp of the nature of this virus. It behaves differently in different countries, perhaps more so than be explained by the varying quality of social hygiene. No one knows how many asymptomatic cases there have been, why there is so much variation in the length of presymptomatic infectiousness (~2-14 days, average around 5), why young adults have mild or no illness, why children are usually asymptomatic carriers but (rarely) develop a just-discovered life-threatening illness (viral? post-viral?), why it attacks the lungs in most patients but in some attacks the heart or other organs while sparing the lungs. One thing we do know: it is very contagious. In evolutionary terms, it’s very clever: “I’ll infect the active young without (usually) killing them, because they’ll carry me around the globe.”
  3. Testing for active infection is currently around 250,000 a day nationally. Even the Federal government says we will probably need to get to 1.5 million a day, and other public health authorities and economists say will need 20 million a day or more to safely get the economy, including education, back up to speed. Our government brags that we have more testing per capita than South Korea. Yes. Now. After that country has beaten down the first wave of the pandemic because it had scores or hundreds of times more testing than we did in February and March. Contact tracing is practically non-existent so far, and hundreds of thousands of tracers may ultimately be needed. See what other countries have done here.
  4. Testing is less sensitive (does it pick up everyone who has the virus?) and specific (does it identify accurately those who don’t) as it becomes more rapid. Antibody testing is far behind active virus testing, which is far behind that in other countries. Ab testing is also less accurate. Regulation of antibody (serological, post-illness) testing is chaotic; companies governed by profit motive abound.
  5. Only one treatment (Remdesivir) is proven effective in COVID-19 illness, and Dr. Fauci (who almost leapt out of his seat with excitement when he first announced it) today called the effect “modest.” There are no meaningful treatments yet. Remdesivir helps (we think) but as mentioned is being rationed to a fraction of the patients who need it. This rationing will be repeated with any future proven treatments. The treatment ultimately will likely be a cocktail of different drugs, as with HIV, but that took years to develop. A smart friend of mine, Cynthia Fox (author of Cell of Cells) says her motto is CCC—Cocktails, Cocktails, Cocktails!
  6. The bottleneck for vaccine deployment has nothing to do with lab science, it has to do with three phases of clinical trials. That’s what will take 10 to 16 of the 12 to 18 months (minimum) needed. Why? because some vaccines have triggered devastating immune responses, sometimes deadly. I remember 1977, when the swine flu vaccine caused hundreds of cases of a nervous system disease, and the 1990s, when early rotavirus vaccines caused very serious intestinal complications requiring surgery. I want you to trust vaccines, but only vaccines that have been properly studied for safety and efficacy. Unlike the lab development phase, that can’t be rushed.

Also in today’s Senate hearing, Dr. Fauci said, “The idea of having treatments available, or a vaccine, to facilitate the reentry of students into the fall term, would be something that would be a bit of a bridge too far.” I hope he is being too pessimistic, but hope doesn’t make things happen. Sometimes, if we’re lucky, science does. And science needs patience.

Stay safe, Dr. K

Opening to What?

            “I think right now, because there’s been good news really, that the opening up is starting to happen faster than we expected, appears to be doing so safely, then there is a chance that we won’t really need a Phase Four [Congressional support package].” White House economist Kevin Hassett, Fox News, Saturday

            “Is this guy serious?” Mayor Bill DeBlasio, later that day

            “It’s devastatingly worrisome to me personally because if they go home and infect their grandmother or their grandfather who has a co-morbid condition and they have a serious or a very — or an unfortunate outcome, they will feel guilty for the rest of our lives,” Dr. Deborah Birx, Sunday.

            “This is definitely government overreach.” Lockdown protester on social distancing

Dear Students,

Given our studies of evolution in disease (Darwinian medicine), you won’t be surprised to learn that the pandemic coronavirus is mutating and adapting, although fortunately more slowly than seasonal flu. Nor will you be surprised to see natural selection operating at different levels. We are not sure that a bat was the origin, but if bats have it you know they’ll be evolving too. And so will we. Here is how the city planning commissioner of Antioch, California put it in a Facebook post:

The shelter in place needs to end, we as a species need to move forward with our place on Earth…This virus is like a human version of a forest fire, a forest fire will burn through and burn off all the dead trees, old trees…The strong trees survive and the forest replenishes itself and flourishes once again… If we look at our population as the forest you will see many similarities. We have our old, we have our weak and we have our drains on our resources. This virus is targeting those sectors of our population. If we were to live our lives, let nature run its course, yes we will all feel hardship, we will all feel loss. I am sure everyone of us would lose a person who we hold dear. But as species, for our Nation and as a Planet we would we would strengthen when this is all settled. We would have significant loss of life, we would lose many elderly, that would reduce burdens in our defunct Social Security System, health care cost…make jobs available for others and it would also free up housing… We would lose a large portion of the people with immune and other health complications… But that would once again reduce our impact on medical, jobs and housing. Then we have our other sectors such as our homeless and other people who just defile themselves by either choice or mental issues. This would run rampant through them and yes I am sorry but this would fix what is a significant burden on our Society… Of course we would lose many of the “Healthy” maybe even myself but that is the way of the World!

I am sure you see the logic in this as clearly as you see its inhumanity. This is so-called Social Darwinism at its worst, and the end result is a Nazi-like culling of the “unfit” from our populations. Nazis carried out mass murders as “euthanasia,” and one of the ways they did it was to crowd Jews into ghettos where typhus and other deadly microbes were brewing and then (see above) “let Nature take its course.” A friend of mine, Tosia Szechter Schneider (now 92) lost her mother and other family members to typhus in one of those Nazi-encouraged experiments in letting Nature take its course. You may remember what Darwin said about this in The Descent of Man:

The aid which we feel impelled to give to the helpless is mainly an incidental result of the instinct of sympathy, which was originally acquired as part of the social instincts, but subsequently rendered…more tender and more widely diffused. Nor could we check our sympathy, if so urged by hard reason, without deterioration in the noblest part of our nature… If we were intentionally to neglect the weak and helpless, it could only be for a contingent benefit, with a certain and great present evil.

In other words, Darwin rejected the moral lapses that some people argued should derive from his own theory. He understood that being human gives us choices that other animals don’t have, and he wanted us to use those choices to protect the weak, not “let Nature take its course.”

            But you might decide Darwin is wrong and the Antioch commissioner is right. I hear some young people have suggested COVID-19 parties where you can infect each other, get a (probably) mild illness, and get it over with! I suggest the following song after you’ve had a few beers. (It’s sung to the tune of the title song in the ‘60s musical Bye Bye Birdie.):

Bye bye Grannie,

We’re gonna miss you so!

Sorry, Grannie,

But ya gotta go!

If you’re curious about this tune click the link now, because after Nature takes its course, no one left alive will remember it, and you’ll never hear of it again.

[Important disclaimer! I don’t really advise you to have a COVID-19 party!]

Good News

  1. “Good to be with you,” said Gov. Cuomo Sunday to one of the four governors joining him virtually and pragmatically in a new consortium. New York, the tip of a severed starfish point, has regenerated much more of the point by bonding with Connecticut, New Jersey, Pennsylvania, and Delaware to coordinate rules and to bulk-buy protective and testing equipment at better prices.
  2. Remdesivir, an antiviral that was developed for Ebola, has reportedly shown its ability to reduce ICU stays from 15 to 11 days in very sick patients. This, if it holds up, is great news. The drug will not be withheld in new trials (now unethical), but will be added to other study drugs in continued research. Bill Gates’s foundation and others are working aggressively (“The Therapeutics Accelerator”) on a treatment that would use monoclonal antibody technology to derive drugs from convalescent plasma, among other treatments.
  3. Testing of two main types (for current virus and for antibodies raised by past virus) is ramping up, although not nearly fast enough. Home self-tests (like the ones we have for pregnancy) should soon be more widely available. Contact tracing, far behind testing, is slowly improving. Random-sample testing in a few places is beginning to clarify how the virus has spread and who (by age, location, ethnicity, and gender) is affected most.
  4. New cases in South Korea that appeared to be reinfections of people who already had it (i.e. they lost their protection in weeks to months) now appear to have been head fakes (false positives), caused by what one expert calls “viral litter”—non-dangerous fragments of viral RNA lingering from the infection.
  5. As many as a hundred labs worldwide are working as hard and fast as they can on vaccine candidates. 95 percent of these could fail in clinical trials (the hard part) and we would still have a few to use. Factories are being built and adapted long in advance of this to produce up to billions of doses that will eventually be needed. Up to 14 vaccines have already entered Phase 1 clinical trials, much sooner than most experts expected.
  6. The modelers at the University of Washington (IHME, led by Chris Murray) have detected a heat effect that is much less than it is with some other viruses but greater than previously thought for this one. Therefore a hot summer will work to a modest extent against the social factors making things worse.

Bad news

  1. Rules are being relaxed by states in an uncoordinated way, without a flicker of national leadership, except in the direction of greater risk. Few if any of the states reopening have met the national standard, put forth recently, of having declining cases for two weeks; most still have rising cases. The Federal government has ordered meatpacking plants, essentially petri dishes for the virus (like cruise ships and prisons), to reopen and stay open, and these are and will be places from which many American communities will become disaster areas.
  2. As Bill Gates remarked on CNN Friday, the so-far modest impact of remdesivir is not going to make us say, “Let’s go to the movies.” Experts note that a smaller study (but a good one, and large enough to show a substantial effect if there were any) in The Lancet found no effect of the same drug. The larger study praised by Dr. Fauci has not been published or peer-reviewed, and all we have so far is a press release and his word.
  3. Testing and contract tracing, the life blood of safe reopening (and therefore of economic recovery) is primitive in our country. We have around 200,000 tests a day nationally, done for the sick and a few others (like health care workers) in most places, but otherwise haphazardly. Expert opinion on how many tests we need range from 5 million a week to 20 million a day. Given that we are most infectious in the first few days of symptoms, or even before, tests that take days to get results are of limited value in controlling the pandemic. “What’s the point?” Bill Gates asked the other evening. “Do you just send apology notes to the people you infected in those 3 or 4 days?” The Gates foundation is supporting the scale-up of rapid testing.
  4. Perhaps the biggest unanswered question is what is the extent of our immunity after having had the virus and how long it will last. Could it be like chickenpox, one and done for life? Or more like flu, protection for a season? The same questions apply to vaccines; this year’s flu vaccine was 50 percent effective.
  5. Speaking of vaccines, the 12-18 month time-frame often mentioned for getting to distribution of a safe and effective vaccine would be by far the shortest in history. Animal models have limits; Dr. Sanjay Gupta reminded us the other day of an old doctors’ saying: Rats lie, monkeys exaggerate. Perhaps the brute force of a hundred labs parallel-processing various methods will accelerate the time to large human trials, but those trials take time. Many will fail and some may fail dangerously.
  6. Internal Trump administration memos revealed today project 3,000 cases per day in June, about double what we have today and higher than the highest peak so far (~2500 in mid-April). These new projections may to be what led President Trump to say yesterday that total deaths could go to 100,000. Given how optimistic he has been in the past, this could be interpreted as meaning that he is deliberately choosing economic activity over preventing mortality, and we should be prepared for more.

Almost half the country is officially open to some extent as of today. “Government overreach”—for your protection—is (temporarily) ending in many states. Watch the states, as well as other nations (with much better testing) that are opening and see what happens. It’s interesting that Dr. Birx (quote up top) misspoke slightly in expressing her worries about the people who don’t do social distancing in protests: “they will feel guilty for the rest of our lives”—the line between “their” and “our” indeed blurs.

Nationally, we’ve been stuck on a fairly stubborn plateau of cases and deaths as states with increases replace those with declines. Projected cases, hospitalizations, and deaths that two weeks ago gave me hope of a more normal summer before a possible fall wave were based on the assumption of serious social distancing through May. That hasn’t held, and all models are projecting more deaths. The latest today (May 4) from IHME projects 134,000 deaths by August, almost double the number projected 6 days ago. I wish I could tell you that college will be live in the fall. As Gov. Cuomo said today, “Know what you don’t know.”

I don’t know for sure, and I’m sorry to have to say it, but it seems to me we have chosen mobility over sheltering and death over life.

The weather’s great, go out (seriously), enjoy a walk or a run alone or with someone you trust. Wear a mask (as Cuomo says, it’s a sign of love and respect for others, because it protects them from you), stay at least six feet (two meters) away from anyone not part of your household, go home as soon as you can, and wash your hands obsessively. While you’re out, observe the crowds who aren’t doing the above, and if you’re religious say a prayer for them, because in a couple of weeks they are going to need it.

As for you, please to take to heart what Tim Cook, head of Apple, said to the new Ohio State grads in his online commencement address: “I hope you wear these uncommon circumstances as a badge of honor.” This is my hope for you in your own futures. Do the right thing now, and live to brag for the rest of your lives about how you made it through COVID-19. As you have heard me say many times, you are lucky to have great gifts, and the world has a right to expect leadership from you.

Dr. K

Note: Please don’t just rely on me. I recommend the following good sources: The Bill & Melinda Gates Foundation COVID-19 Update, aka The Optimist; This Week in Virology (TwiV) podcast; IHME (U. of Washington) model website; COVID-19 UpToDate for medical professionals; and for all readers: Why the Coronavirus is So Confusing. Dr. Ashish Jha of the Harvard School of Public Health said on Thursday, “I grew up as a public health person loving and admiring the CDC, arguing and believing that it is the best public health agency in the world… But in this entire pandemic, it’s been one fiasco after another. And it’s either possible that all of the scientists all of a sudden forgot their science, or there’s something at the leadership level that’s really hindering them.” 

 

 

 

 

 

 

 

 

 

 

 

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