Tagged evolutionary medicine

“Baby, There’s COVID Outside”

            “Dr Chris Murray from the IHME told Anderson this earlier tonight, they’re expecting over 100,000 additional deaths between now and June … they don’t think that the US will reach herd immunity before next winter. I mean that’s a pretty scary proposition—what do you think?” 

            “I think that Dr. Murray and his colleagues are probably right… It’s going to take us quite some time to get…enough supply. Hopefully we’ll reach that by by mid-summer but…we really need the vast majority of adult Americans to take the vaccine, and I’m afraid that because of the pandemic of disinformation, it’s going to be really difficult to do that, and so I’m hopeful that we can do this by winter and have a normal Christmas and New Year’s, but it’s going to take a lot of hard work for us to get there, and the variants can really throw a wrench into the works… I really do worry about the variants, because if you have something that’s a lot more transmissible then it’s not just a matter of linear spread; so something that’s 50% more transmissible, you’re not going to get 50% more infections, you’ll get many many many times more infections… I also worry about variants that potentially could be less effective with the vaccines that we have and we may always be happy to play catch-up so we vaccinate everyone, but then there are variants, and then we have to get boosters to target those variants. So we could always be trying to play catch-up here, and that is a big problem.” Dr Leana Wen, with Don Lemon, CNN, 2-19-21

            “The virus and the pandemic as we know it is not the virus and the pandemic that we face right now… This virus is changing and it is changing rapidly. There about 4000 different variants… To find a variant you have to genetically sequence, it requires skill, immense computing power, and frankly not many countries are doing that… Those three main strains [UK, South Africa, Brazil/Japan] are out there and they are improvements from the original virus, because that’s the way evolution works. When there is even a tiny advantage that advantage is pushed along through natural selection at an enormously rapid rate because evolution in viruses happens very very quickly… I’ve been following the story of one particular intensive care nurse who was quite optimistic because she had gotten her vaccine and then her COVID ward suddenly changed when these mutant strains arrived:”

            “We’ve seen patients now with absolutely no past medical history, not overweight, runners, people who go to the gym, people in their 40s, and these patients are dying.”

            “What would you say to Americans who might not have woken up yet to the fact that this is coming?” 

            “If you love your family, if you love the people you know, wear a mask, stay indoors, wash your hands, be careful, just realize that this will kill.” Richard Engel with a UK intensive care nurse, MSNBC, 2-21-21

Dear Students:

This is much my favorite of several parodies of the old song, “Baby It’s Cold Outside,” making the cloud rounds since Christmas. I know, it’s cold outside too. Colder than it has ever been in, for instance, Texas, where due to the incompetence of state leadership, at least 32 people have died from the winter storm—of at least 69 nationally—as of yesterday.

My heart goes out to the victims, their families, and the millions of others who suffered from no heat in freezing cold—some made fires from their furniture—and no water due to ice-burst pipes. But consider.

The 7-day moving average of daily deaths in Texas from COVID-19 was 119 on Saturday. So, despite the lowest death rates since November, during the week of the storm the virus killed over 800 people, or around 25 times as many as the cold did. But the storm news thoroughly dominated the air waves all week, with virus stories and analyses relegated to short segments late in the hour.

Nationwide we are under 2,000 deaths a day, down from 4,000 in mid-January (see the chart). This is terrifically good news. But we are still far above the summer peak and only around the immensely disturbing first peak of last spring. That’s with all the advances in treatment and two months of vaccine roll-outs.

Hospitalizations have dropped similarly, a tremendous boon to our frontline healthcare heroes, and cases have dropped even more. But all are still at or above previous peaks. We just crossed the nauseating milestone of half a million deaths.

Baby, it’s COVID outside.

Good News

  1. New cases in the US have dropped 70 percent from the winter peak, hospitalizations and deaths have been halved. This is most likely due overwhelmingly to the pass-through of the holiday-period recklessness and the resulting unprecedented surge. Improved behavior, partial immunity due to prior infection and (to a very small extent) vaccination have probably helped.
  2. The vaccine roll-out continues with great fanfare but at a slow pace. We have reached over 60 million vaccinations, mostly first dose, and that is increasing at 1.6 million a day. So far this is overwhelmingly the Pfizer and Moderna mRNA vaccines, but the Johnson & Johnson single-dose one is on the verge of Emergency Use Approval, with more to come.
  3. A study in Israel, where vaccination rates beat the world, shows that a first dose of Pfizer vaccine affords 85 percent protection between 15 and 28 days out. This is far better than anyone expected. Another Israeli study showed that a double dose prevents transmission as well as disease, at a rate of 89 percent; this was a big question mark until now.
  4. Treatment advances continue, including monoclonal antibodies for early-stage patients to keep them out of the hospital, and late stage tocilizumab, an interleukin-6 (IL-6) inhibitor, given after or with the steroid dexamethasone. Immune system interventions like these, science fiction a few decades ago, are working. Early anticoagulant (blood thinner) treatments and vitamin D supplements also make a difference.
  5. The new administration in Washington has set a new tone. Masks are cool and people from the top down are modeling their use. Social distancing, handwashing, and other preventive measures are mentioned frequently. The stupid culture wars over prevention are not done, but the federal government is on the side of science.

Bad News

  1. SARS-CoV-2 is evolving fast. The 4,000 variants mentioned above are of uncertain importance, but some could change the game, and not enough people in government or news outlets are talking about them. The UK variant spread like wildfire there and doubled hospitalizations almost overnight. Cases of it are doubling every 10 days here and it will be the dominant US strain by March. Cases of the South African and Brazil/Japan strains are here. The first is resistant to some vaccines and the second is implicated in a new epidemic that engulfed Manaus, an Amazonian city of 2 million.
  2. Dr. Peter Hotez, probably the nation’s leading expert on vaccine development, says we need 3 million doses in arms per day, almost twice what we have now, and there are no plans announced to get to that number. Dr. Michael Osterholm gave up his own second dose because he believes triage requires that we (like the UK) choose to vaccinate twice as many people once before we give second doses (see #3 above).
  3. President Biden has promised to “level” with us, and, like FDR, to give it to us “straight from the shoulder.” But if he did that, he would not talk about 600 million doses by mid-summer as if it were adequate. He would apologize and pledge more. And he would certainly not, as I have heard him, blame his predecessor, which is uncomfortably reminiscent of what his predecessor did.
  4. Israel, the UK, and even the United Arab Emirates show that vaccinations can move much faster than they are moving here now. The UK has been on lockdown for many weeks and will reopen only slowly as conditions allow in March. Bhutan, Rwanda, and Senegal have done far better than we have in controlling this pandemic. Are we still too proud to learn the lessons all those countries and more have to teach us?
  5. The issue of school reopenings has been handled by the new CDC Director, Dr. Rochelle Walensky, almost as bumblingly as by her predecessor. On Sunday the 14th CNN’s Jake Tapper asked her to defend her new guidelines. She tripped all over herself. She said (for example) that community transmission has to be controlled where the school is. Tapper pointed out that 99 percent of US schoolkids live in red zones. No answer. This was without noting that thousands of schools would go bankrupt if they met the guidelines for cleaning, ventilation, and so on. Biden’s White House did not back her up. Of course kids need school, but the new CDC is still being disingenuous. Vaccinate the teachers, janitors, and food workers.

Speaking of kids, I reached the two-week anniversary of my second Pfizer dose on Friday, and on Saturday I snuggled with my grandkids while reading to them for the first time in almost a year. We were outside and I was still masked, but it was a great feeling. One of the new studies mentioned above told me I would be unlikely to carry it asymptomatically to them

As I said to some of you yesterday, I wish I could tell you to party. You have as much right to party as I have to hug my grandchildren. But if you do it now, you will join the ranks of the foolish who infect themselves and others.

This is not over. Not all 4,000 viral mutants are “variants of concern,” most are biologically silent, but some make the disease more likely to transmit, more deadly, or more resistant to vaccines and our own immunity. I was happy to hear cable news talk about natural selection, but I am not happy with the results of that selection. And we are underestimating it because we do so pathetically little viral genome sequencing.

Dr. Michael Osterholm said Friday on PBS that we are in the calm before the storm, and that a new surge caused by the UK variant (B.1.1.7, which current vaccines do prevent) is inevitable. Based on the UK’s own experience, we could see 195,000 hospitalizations a day, compared to the 130,000 a day that overwhelmed our hospitals in January—the surge that among other things required a fleet of refrigerated trucks to store the bodies.

Dr. Fauci said yesterday we may still be wearing masks in 2022—some degree of normality by the end of ’21, but not without masks and other precautions between now and then. Today he said, “This is a common enemy. We’ve all got to pitch in. We’re in some good shape now with the vaccines, but it’s going to be a race against the infections that keep coming.”

Dr. Tom Gillespie, of Emory’s Environmental Sciences Department, was quoted in yesterday’s New York Times (“And Then the Gorillas Started Coughing”), commenting on two San Diego Zoo gorillas that contracted SARS-CoV-2—which they could only have gotten from humans—warning that apes and other infectable species could become a reservoir that preserves the virus after the pandemic and circulates it back to us. Viruses of many kinds are a long-term threat.

Mohamed El-Arian, financial advisor and president of Queen’s College, Cambridge, said today we were in a two-horse race, vaccines against the virus, but that now it’s a three-horse race, with the third horse being the new variants, and if that horse comes up fast, we could be in bad trouble again. We only beat the third horse with the precautionary measures we have been advised to take all along.

As you know, Emory itself, which has done very well all along, has had an unprecedented burst of cases among students in just the past week, for unknown reasons.

Parts of the country are in the deep freeze, but baby it’s covid outside. Stay safe,

Dr. K

PS: Please don’t rely just on me. The best resource on what is happening specifically in the state of Georgia is Dr. Amber Schmidtke’s Daily Digest. More generally, I recommend the following: The Bill & Melinda Gates Foundation COVID-19 Update, aka The Optimist; for the science of viruses, especially the new coronavirus, This Week in Virology (TWiV) podcast; Dr. Sanjay Gupta’s podcast, Coronavirus: Fact vs. Fiction; COVID-19 UpToDate for medical professionals; and for the current numbers: Johns Hopkins University (JHU); Institute for Health Metrics and Evaluation (IHME); Our World in Data (OWiD); The New York Times Coronavirus Resource Center (NYT). For uncannily accurate warnings, follow @Laurie_Garrett on Twitter. I also recommend this COVID-19 Forecast Hub, which aggregates the data from dozens of mathematical models, and this integrative model based on machine learning. For an antidote to my gloom, check out the updates of Dr. Lucy McBride, who doesn’t see different facts but accentuates the positive.

Between the Lightning and the Thunder

Dear Students,

As you know, when you see the sky light up because of a bolt of lightning, it takes a few seconds before you hear the thunder, because of the difference between the speed of light and the speed of sound. The lag varies, and the loudness of the thunder varies.

That’s my metaphor for today, the day after the sacred American holiday of Juneteenth, the day the last large group of African-Americans were freed from slavery in 1865. It’s also the day that 19,000 people are converging on an indoor space in Tulsa, Oklahoma, currently experiencing a rise of COVID-19 cases. About 90 percent of them will not be wearing masks, and almost none of them will be six feet away from the nearest person. One million people competed for the privilege of being one of those 19,000. Interviews show that as they enter the arena they are not worried. At this hour (5pm Saturday) the arena is already packed with early arrivals.

If you can’t guess my hypothesis about their level of risk, you haven’t been paying attention to anything I’ve said since January.

But, it’s a hypothesis. When I see lightning, I listen for thunder, but I don’t always hear it. Sometimes it’s too faint. Also, my hearing is not that great any more.

So the lightning might be crowds—including crowds of left-wing protesters—and the thunder might be cases of viral illness. You might recall that there was a huge difference in the size of the 1918 flu epidemic in Philadelphia compared to St. Louis. The difference was directly attributable to a big parade in Philadelphia at the wrong moment, while there was no such parade in St. Louis. Parade: lightning; huge spike in cases only in Philadelphia: thunder.

But you might also remember that the count of cases does not impress me as the right outcome measure. That is because the number of tests strongly influences the number of cases. There are ways of correcting for that, but major state and national leaders continue to say that the rise in cases in some states is due to better testing, period.

Consequently, I am not going to write today about the number of cases; instead, I am going to wait for a much better measure: the number of hospitalizations, and then, the number of deaths. So I am going to use the metaphor differently: spike in cases: lightning; spike in hospitalizations and deaths: thunder.

I don’t know for sure that today’s party in Tulsa will even result in lightning; it will take a couple of weeks to see a spike in cases there, and leaders in Oklahoma and Washington will say that it’s because so many people at the party got tested. So that would for me just be the lightning. A spike in hospitalizations and deaths two to four weeks after that would be the thunder. We would be in August.

There is my kind of lightning—rapidly rising cases—in Arizona, Texas, and Florida. In two weeks we might see my kind of thunder begin to roll. We will see. Science takes patience. I am not wanting to be insensitive. I am recognizing that half the country and half its leadership do not expect that thunder.

You might also remember that in 1918, Philadelphia carpenters could not make coffins fast enough. Maybe St. Louis sent some carpenters there.

So while we wait to see if Tulsa needs carpenters, I’ll make this update about nuts and bolts: 5 vaccines, 5 treatments. Most are good news.

5 Vaccines

There are at least 130 to 140 vaccines in development around the world. The 5 I’m going to mention are the ones already chosen by Operation Warp Speed, a Federal government program to fast-track development and prepare for mass production (hundreds of millions of doses; the world will need up to 7 billion) if one or more  of these works. It is not clear what criteria were used to choose those 5, but it is likely that the name “Warp Speed” will increase the number of vaccine refusers. Fast and good don’t always go together.

Two of the 5 are messenger RNA vaccines, which deliver coronavirus mRNA into our cells, where they make surface spike proteins that can raise a specific immune response to the viral envelope. No mRNA vaccine has been approved for use in any disease, although some are in clinical trials for other diseases. Three of the 5 are viral vector vaccines, which use a partly disabled different virus to deliver coronavirus genes into cells, to make the surface proteins that provoke the immune response. This principle has yielded an effective vaccine for Ebola and an ineffective one for HIV.

Interestingly, none of the 5 Warp-Speed candidates is a weakened or killed whole-virus vaccine (polio, chickenpox, measles, mumps, etc.); a protein-based vaccine (HPV/cervical cancer); a recombinant vaccine, such as genetically engineered yeast that produces viral proteins in our bodies (shingles, hepatitis B); or a DNA vaccine, in which coronavirus genes are introduced into our cells (none such approved for human use).

In other words, three proven principles were not chosen for Operation Warp Speed.

  1. Moderna (mRNA): Press release said it worked in 8 people, stock price skyrocketed, then crashed on expert skepticism. Phase III (large) clinical trials to begin in July if all’s well. No similar vaccine approved for anything in humans.
  2. BioNTech/Pfizer/Fosun (mRNA): Clinical trials under way; perhaps a few million doses available for emergency use in the fall if all’s well. No similar vaccine approved for anything in humans.
  3. AstraZeneca/U. of Oxford (viral vector is a chimp adenovirus): Phase II/III testing starting in England and Brazil. Could have emergency doses by October; has the manufacturing capacity to produce 2 billion doses eventually. The general principle has worked in Ebola.
  4. Johnson&Johnson/Beth Israel-Harvard (vector is a monkey adenovirus): Phase I/II safety trials begin late July. The general principle has worked in Ebola.
  5. Merck/IAVI (vector is a stomatitis virus): Merck actually used this method to make their successful Ebola vaccine. Clinical studies on corona expected to start this year.

Bad news: No knowledgeable person thinks it’s likely we will have a vaccine widely deployed before 2021 at the soonest, although a few think it’s possible.

Good news: Never before in human history has so much money, effort, and scientific talent been thrown at developing a vaccine for one disease.

5 Treatments

  1. This past week, the tried and true (and cheap) anti-inflammatory drug dexamethasone was announced in a press release to reduce COVID-19 death rate in very sick patients. No peer-reviewed publication, no data available for other scientists to examine. But, as doctors joke, dexamethasone works for everything (it’s sort of cortisol x 20), so why not this?
  2. Remdesivir, an antiviral originally developed for Ebola, may or may not have significant benefits, but it’s approved for compassionate use.
  3. Convalescent plasma, which contains anti-COVID-19 antibodies from people who fought off the virus, has been proved safe in a Mayo Clinic study of 20,000 hospitalized patients, and may be effective in reducing mortality, perhaps especially if given earlier rather than later.
  4. In a very disappointing, even scandalous outcome, peer-reviewed papers published in two top medical journals proved flawed and had to be retracted. Not only can’t we rely on press releases, we may not be able to rely on top journals. Also, maybe, hydroxychloroquine isn’t dangerous in this disease, just (probably) ineffective.
  5. Triple antiviral therapy combined with immune-boosting interferon beta was more effective than the same with one of the antivirals omitted, suggesting that as with HIV we will more likely succeed with combination therapy than one magic bullet. None of the three was remdesivir. Boy, do we have a lot to learn.

Experts are more optimistic about an effective combination therapy sooner than a vaccine. But don’t forget, Sarsie-2 is consulting his Uncle Charlie Darwin every few hours about how  best to evolve and adapt.

As I write, at 7pm Saturday, a crowd of unmasked thousands packed into an arena in Tulsa is waiting for their President to deliver a campaign speech. Fortunately for those people, the arena is not full.

You may know that the President was persuaded to move his rally there from Juneteenth to June 20th in response to outrage from Americans of all ethnic groups who understand the symbolic meaning of Juneteenth. You may or may not know that the rally is being held a stone’s throw from the place in Tulsa where the greatest mass murder, an attempted genocide really, against African-Americans, just 99 years ago.

Remember, if your country refuses to stay safe, you can still protect yourself and your loved ones. Use your mind. Use your brain.

Dr. K

Darwinian News, Hot Off the Press

In the Darwin bicentennial, new insights into fossils, genes, birdsong, and cancer.

google-logo-fossil1The latest issue of Nature to land in my mailbox-the May 28th one-was not a tribute to Darwin in honor of his 200th birthday and the 150th of The Origin of Species; Nature has been there, done that. But it might as well have been another celebration for him, Read more