Tagged SARS-COV-2

One Marshmallow

       “These plans are so unrealistically optimistic that they border on delusional and could lead to outbreaks of Covid-19 among students, faculty and staff.”

       Laurence Steinberg, The New York Times, June 15, 2020, referring to proposed college reopenings

Dear Students,

A few weeks ago, New York Times columnist Paul Krugman (winner of the Nobel Memorial Prize in Economics) wrote a column called “America Fails the Marshmallow Test.” This is a reference to a famous 1960s psychological experiment, in which a marshmallow (or cookie, or piece of candy) is placed in front of a young child, who is told she can eat that marshmallow now, but if she waits 15 minutes, she’ll get two instead of one. Studies stemming from this experiment became a cottage industry, and among the claims made by those involved, being able to postpone gratification for greater gain was a fundamental character trait in the two-marshmallow kids that predicted much about their later success. They were said to have better “executive function,” meaning their frontal lobes were better able to suppress the impulse to get one marshmallow now in order to get two later.

Krugman understood that a 2018 study apparently failed to replicate the marshmallow study, but wanted to use the metaphor for our country’s inability to wait a little longer before lifting social distancing restrictions. Actually, the marshmallow study was not debunked by the 2018 replication, which has been criticized for controlling away some variables (like early cognitive ability) that are intrinsic to what the marshmallow test tries to measure. Also, the replication did find that the test predicted some characteristics of adolescents, just not as much as earlier studies claimed. The critics of the critics—the marshmallow defenders—called their paper “Good Things Come to Those Who Wait,” with the running head, “Delaying Gratification Matters.”

Speaking of delaying gratification, it’s not just five-year-olds who are not good at it. Adolescents are not good at it either.

I know you don’t like to think of yourselves as adolescents, but the fact is that brain development is not complete until age 25 or so, and the main part of the brain that keeps developing is precisely those frontal lobes that are involved in executive functions: planning, reasoning, analyzing, and yes, postponing gratification. This period of extended frontal cortex development has been called youth, pre-adulthood, or emerging adulthood.

Psychologist Laurence Steinberg is the world’s leading authority on brain development in adolescence and beyond, especially in relation to executive functions. He has co-authored papers in law and psychology journals with titles like “Blaming Youth,” “Young Adulthood as a Transitional Legal Category,” and “Less Guilty by Reason of Adolescence.” He has tried to protect young people from the most severe punishments for acts which they literally did not have the brainpower to control.

Now Steinberg has weighed in on a question many of you have asked me about: College reopenings in August, including ours. Steinberg, who has spent his life as a college professor researching the young, wrote an essay two weeks ago called, “Expecting Students to Play It Safe if Colleges Reopen Is a Fantasy.”

Based on his 40 years of research on young people, he writes, “Most types of risky behavior — reckless driving, criminal activity, fighting, unsafe sex and binge drinking, to name just a few — peak during the late teens and early 20s. Moreover, interventions designed to diminish risk-taking in this age group, such as attempts to squelch binge drinking on campus, have an underwhelming track record. There is little reason to think that the approaches proposed to mitigate transmission of the coronavirus among college students will fare any better.”

The evidence on the other side is very strong. Steinberg and his colleagues recently completed “a study of more than 5,000 people between the ages of 10 and 30 from 11 different countries (including both Western and non-Western ones)… Consistent with large-scale epidemiological studies, we found a peak in risk-taking somewhere between age 20 and 24 in virtually every country.” There are three straightforward reasons.

Youth (not just adolescence) is a time of 1. heightened risk taking, and 2. poor self-regulation in all cultures. These two psychological features of young adulthood are in turn explained by 3. easier activation of the brain’s reward circuits, made even worse under conditions of emotional arousal and in the presence of peers.

To Laurence Steinberg, who probably knows more about not only the psychology but the neurobiology of young people than anyone else alive, college reopenings will be a “perfect storm” for viral spread. College reopenings are also being criticized by moral philosophers, college presidents, lawyers, and, of course, some epidemiologists. Dr. Anthony Fauci, our nation’s leading expert on the pandemic, says the matter is “complicated” and will depend on what region of the country you’re talking about.

It’s not always a bad idea to take a reward now even though it may be smaller. That’s why we have the proverb, “A bird in the hand is worth two in the bush.” Young people are designed to take risks for short-term rewards because that is how they test themselves, learn about life, find mates, make friends, and generally position themselves among their peers. Up to a point you have to take risks.

But we are not talking about a torn ligament, a bad hangover, or a brush with gonorrhea. This is a situation that has never before existed in my lifetime, not even during the early years of HIV/AIDS. I have repeatedly emphasized to you that the unknowns in relation to this pandemic are greater than the knowns, and that remains true. Right now cases are on the rise in the nation, in most states, and in almost every major city in the southern half of the country from Los Angeles to Miami.

The entire state university system of California will be 100 percent online. If you were in college in a rural area of Massachusetts or New York, you would probably be safe attending live, but you are not in one of those colleges. The situation in Atlanta is uncertain, but Emory says it is taking precautions that will make reopening safe.

Last week I said that case counts are like lightning, and that I was waiting for the thunder—hospitalizations and deaths. Being no longer young, I am able to wait. Some leaders claim that the only reason we have more cases is that we have more testing. I think this is wrong, but I don’t want to argue about it because I can wait. Others say we really do have more cases but because the age of infection is on average much lower than it was a month or two ago, we will never see the hospitalizations or deaths go up by much.

Lightning is flashing all across the southern United States, and some say it is starting fires that will be impossible to control and that will in the end kill many. State after state in the south are backtracking on their openings. But the states don’t really control behavior, especially the behavior of the young.

The July 4th weekend is coming, and millions of young people will take the one marshmallow. What will you do?

Dr. K

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

“I, Corona”: My Exclusive Interview with the Little Guy Who’s Changing the World

Dear Students,

I have a special treat for you today, an exclusive interview with SARS-CoV-2, his first ever, on his life and times so far. I was able to arrange this through my special friend Charles Darwin, whom Sarsie—his preferred nickname—likes to call Uncle Charlie. Sarsie doesn’t think he’ll be confused with his older brother, SARS-CoV-1, whom he calls “pathetic,” nor does he think highly of his cousin MERS. “I mean, really, a few months in one or a few places, and then, poof! they’re pretty much gone.” He has a certain grudging admiration for cold viruses.

            But I’ll let him tell you in his own words. By the way, he insists on he/him/his, because as he puts it, “I don’t have the equipment to reproduce, so I gotta beg, borrow, or steal it from someone who does. I just put in my genes, and they do the rest. Also, let’s face it, a guy like me, who puts ambition above everything…I mean, I’m most likely gonna be male, right? Yep. My whole species, and my brothers and cousins too.”

            He asked me to call this column “I, Corona,” as an hommage to Isaac Asimov’s science fiction classic, I, Robot. “I didn’t like his three ethical laws, of course, but when he got to the part about robots that secretly run the world, I could definitely wrap my envelope around that. But why keep it a secret? Just take the world over and run it, I say.”

            What follows is a lightly edited version of our interview, with my questions removed. Not that there were many. He doesn’t let a human get a word in edgewise. So I listened and learned.

            “Yep. I’m on the move for sure. My bros and cousins were well meaning, all princes in their way—and we’ve got more princes than the Saudi Royal family—but I’m the Crown Prince (get it? Corona? Crown?) and I will be King.

            “By the way, this whole debate about am I alive? Am I alive? Are you kidding me? I’m alive and I’m eating you alive.

            “But back to the family. We’ve only been around a hundred thousand years, less than you even, but then again, we reproduce in 48 hours, you take 20 years. Do the math. Ex. Po. Nen. Shl. As Uncle Charlie would say, we can sure do some evolving.

            “The family divides up the spoils, but we’re not all equally successful. Some of the corona cousins specialized in farm critters. It’s a dirty job but somebody’s gotta do it. Let’s be honest, though, you’re not goin’ down in history for makin’ a chicken cough or givin’ a pig a belly ache. Then there’s the bunch I call the Corona Sniffles, they’ve done alright for themselves actually, they got around, they hang around, they evolve, they come back. No drama, mama, but Uncle Charlie would be proud.

            “SARS-1 did alright for himself but he just couldn’t get transmissable enough, and on top of that he only jumped from Jim to Jane, or from Zhang Wei to Mei Ling, after he gave Jim or Zhang symptoms. Jane and Mei knew to keep their distance. So my Sarsie-1 bro hit Guandong Province in China, got to Toronto somehow, and got locked in with quarantine. 8,000 cases, 800 deaths, a little economic slump, that was about it. One wave in 2003, so far done and done.

            “Cousin MERS was a killer though, too much for his own good. You kill a guy, he ain’t passin’ you on. Also Cousin MERS was never good at jumping from one of you sorry humans to the next. Probably more of you have gotten him from camels than each other. He broke out in Saudi in ’12, trickled around to 27 countries since, 2,500 cases, 800-some-odd deaths, well controlled by even your bumbling species, nothing to write home about.

            “You can see where I’m goin’ with this. I’ve done more in eight months than the rest of them put together. I’m the Crown Corona Prince by acclamation. I mean, let’s look at the facts. Okay, I was trapped in bats for I don’t know how long. I was bummed. Do you have any idea what a bat cave smells like? But I took a deep breath—the kind I make impossible for you—and channeled Uncle Charlie. He counseled patience: “Be like a Buddha Virus, bide your time, mutation and evolution will do the rest.

            “Boy, did they ever. You helped, by bulldozing forests and setting the bats I was riding free. My hosts got snared, sold, and eaten, and I was on my way. Okay: I’d evolved my way from bats to humans, but would I be like my cuz MERS, get stuck in a bat-to-human trap like he did (mostly) with his camel-to-human song-and-dance? No way. Or would I maybe take a leaf from my bro Sarsie-1’s book and only jump from Jim to Jane when Jim was already sick and Jane could avoid him like, well, the plague? Nope again.

            “I did everything by Uncle Charlie’s playbook, evolve, wait, mutate, evolve. Jump from bats to you folks (Whoopie!): Check. Jump from Zhang Wei to Mei Ling: Check. Now, jump from Zhang to Mei before Zhang gets sick—three days, a week, two weeks: Check. Now, don’t even make Zhang sick at all, ever. Or Mei Ling. True, a cough or a sneeze will spread me yards in droplets and aerosols. But if Zhang and Mei are rehearsing in the same chorus for a couple of hours, or even sitting at different tables at a restaurant with the right air circulation system, that’ll work fine for me. If they exchange looks and fall in love and do a Chinese version of French kissing, I’m golden.

            “But think about it: I can’t win big in Uncle Charlie’s sweepstakes by staying in one corner of Wuhan. So here’s where your species really starts to help me. Homo sapiens? Homo dumbellus is more like it. That young doc in Wuhan who tried to blow the whistle on me last year, right at the start? Whew, that was a close call. That could have ended me maybe, but thankfully his bosses shut him up fast. They even made him apologize for making me up! That was a great moment in my career, gave me just window I needed to zip around Wuhan.

            “He was some kind of hero. Poor guy got sick from one of the patients he tried to help, and I killed him. Wasn’t trying, you know, but there it is. He gave his life to tell the truth and save your species from mine. Not fair, but that’s how Uncle Charlie’s law swings. Or, you might say, how the fortune cookie crumbles. Sorry, couldn’t resist; but I spent enough time in China to know fortune cookies don’t crumble there, only in America.

            “Speaking of which, I was getting folks to carry me out of Wuhan to all over, even while the Chinese did a 180 and started to shut me down. They had the right government and the right science and the right culture to do it, and I was done there in a couple of more months. People cared about each other. They believed their doctors and scientists after that first blooper. They show the world how your species could win the war against mine. Or could have.

            “Some learned, some didn’t. I was rockin’ and rollin’ man. Jims and Janes, Fritzes and Gretchens, and especially Sergios and Claudias were leaving Wuhan and taking me home as a souvenir. I got a foothold on the Pacific Coast of your country in January, but that was small potatoes compared to Italy and Spain. Those folks love their grandmas, so instead of quarantining them they killed them. Okay, I killed them, but they gave me free rein.

            “Who’s they, you want to know? The young people. The ones who couldn’t sit at home. The ones who were chock full of me and I didn’t even make them sneeze. They were my ambassadors. Healthy young humans doin’ their thing, havin’ fun, hustling, moving. They’re the reason I left my Sarsie-1 bro and MERS cousin in my dust. They took me to every place on the planet. You humans talk about flyways for the flu. You mean geese and ducks. They fly south and north on two routes. They overlap a tad in the arctic. Geese? Ducks? Your species has a hundred thousand flights a day that go from everywhere to everywhere. And every one of them is carrying someone carrying me. Flu too by the way. He and I are gonna make beautiful music together. There’s gonna be some Darwinian mutual back-scratchin’ for sure.

            “Anyway, Italy mourned. Doctors and nurses were crying in the hospital halls. But I was headed for the U.K. and New York! That clown Boris thought he could pull a Sweden. I tried to help him see the light by laying him low for a while, but he squinted and bumbled again. Herd immunity? You have to be kidding me. That’s years away everywhere.

            “Treatments? Some day. Right now they’re just making a dent for the sickest, and may help me evolve resistance. I admit it’s been hard for me to reinfect someone I got to once before. I’m working on that, according to Uncle Charlie’s rules. We’ll see. The flu comes back every year in a different form. Every year a new vaccine that’s maybe half effective, and half of Homo dumbellus doesn’t even bother with it. Is that the sort of standoff I could live with long term? As they say in North Dakota (where by the way I’ll be heading soon), you betcha!

            “Meanwhile, Boris the Clown can’t hold a candle to that donkey’s rump Bolsonada in Brazil. It’s like Sweden without the modicum of leadership and with twenty times the population. Wow! Talk about a field day for me! They can’t dig graves fast enough in São Paulo. Mind you, it’s no great deal for me to be buried in a hole in the ground. But it’s the cost of doing business.

            “And then of course there’s the Clown of Clowns, the fat one with the orange face and pouffy yellow hair, the It’ll-be-gone-like-magic Gotta-open-up-our-country Whaddya-gotta-lose happy hero of every virus in Darwin’s kingdom. Sorry, it’s your country, I don’t want to hurt your feelings. But really. Open up the meat plants: Check! Don’t worry about the prisons and nursing homes or the small towns around them: Check! And then you got those folks yelling about freedom. “Don’t put your mask on me!” I love them so much I want to hug them. I do hug them.

            “And now these protests. I’m sorry, they have a right to grieve, but it doesn’t matter to a guy like me whether the crowds are righteous or not. I don’t give a flying fig whether I infect a Democrat or a Republican, as long as it’s a warm body. I am a teensy little Darwinian machine obeying Uncle Charlie’s laws to the letter. Good thing for me that guy in New York isn’t running your whole American show. I’d be beaten back into a corner for the summer and then you’d be gearing up to fight me and my buddy Flu-Boy in the fall.

            “But this is a zero-sum game, my species against yours, and I don’t think I’ll be in retreat during the summer. Maybe if you wake up in July and lock down again I’ll give you a five-minute break in September. But I’m not promising.

            “Good thing for me too that there aren’t more women running more countries. Seems like most of the countries that have kept me down or out are run by females, and the countries I win hands down are run by overgrown, overblown boys. Maybe you are actually two species: Homo sapiens, the ones with the reproductive equipment who know how to protect their own; and Homo dumbellus, the ones with DNA donation, the big shoulders, and the bluster.

            “Better believe it when I tell you you’ll be seing me around.

            “What? You think I’m ruthless the way I’m taking over the planet? How the hell do you think your species did it? You poisoned the earth, killed off half the other animals and plants, and brutalized each other beyond belief in your own species. You packed yourself into the crowds I swoon for. I can become King of the World without doing a fraction of the damage that you’ve done. It’s a miracle there were any bats left for me to evolve in.

            “But now you are really really helping me, so keep up the good work!

            “And oh, please, I’m begging you, whatever you do, please please re-elect Empty Hairdo, the Leader of the Free World who will never ever figure out how to keep it free from me.”

            Well, students, now you’ve heard it, Sarsie in his own words, uncensored, from the horse’s—or the virus’s—mouth.

            And don’t knock his hopes and dreams. He’s just following Dr. Darwin’s prescription. For him.

            Dr. D’s advice for us? Stay safe, be well, and keep in touch—from a distance.

Dr. K

100,000

Dear students,

Before I share a few post-Memorial Day thoughts about the virus and this tragic and needless milestone, I would like to mention two people who have died recently but not from the corona or any virus: George Floyd, a black man who was killed by police in Minneapolis, Minnesota, by strangulation, while handcuffed on the ground begging for his life, and Ahmaud Arbery, a black man shot and killed by vigilantes while jogging, in a modern-day lynching in Brunswick, Georgia. These tragic and needless deaths were part of the same long-standing pattern of structural racism which, as you know, accounts for the huge over-representation of African-Americans in the deaths from COVID-19.

I am frankly confused about where we are in the pandemic right now, both in our country and the world. More Americans have died of COVID-19 than in all the wars since the Korean War, and it is quite possible that before this is over we may be able to include the Korean War in that count. I see what appears to be a wholesale abandonment of the science of public health and medicine by many Americans. I can’t tell you how many, but I am pretty sure it’s enough to keep the U.S. epidemic boiling (not simmering) for months. Maybe we get a rest in September before the second wave. Or will it be the third wave?

I’ve always told you the most important thing you have to know is the limits of what you know. So I’m telling you now. I don’t know. I don’t know. I don’t know.

I don’t know about future cases, hospitalizations, or deaths because the models are shot to hell by the unpredicted and unpredictable behavior of a substantial minority of Americans. I don’t know about progress in vaccines or treatment because every announcement is not a scientific publication but a press release that hugely moves stock prices, especially of the companies involved. Remdesevir and convalescent plasma are in wide use and seem to have some effectiveness, but convincing studies have not been published. I do know something about the anti-malarial drug Whaddayagottalose-oquine. Worldwide randomized controlled trials have been stopped because more people die with it than without it. I took it for years, first to prevent malaria in Africa, then for a minor autoimmune condition. On March 25th in a private email I said that more research was needed but that I would take it if I got COVID-19. Now I wouldn’t. Lesson? Anecdotes, even from smart people, are no substitute for real studies.

This past weekend we commemorated those who gave their lives for our freedom; they died hoping we would use freedom wisely. Yesterday we flew our flags at half-mast to mourn 100,000 dead Americans. Today I want to celebrate the new warriors at the front of the coronavirus wars.

Good News

  1. Dr. Richard Levitan, 59, a leading expert on teaching intubation, left safe Northern New Hampshire to volunteer for ten days at New York’s dangerous Bellevue hospital. After his first exhausting shift he went to his brother’s apartment, where he was staying, and was kicked out by the building’s other residents. He found some kind of lodging, completed his ten days, and wrote an article teaching others throughout the world how to deal with COVID-19 pneumonia.
  2. If you click on one link in this message, make it Dr. Sharon Duclos, a Family Medicine specialist in Cedar Valley, Iowa, and watch the video, recorded on May 6th, the day before the local Tyson meatpacking plant, the source of the cases that overwhelmed Dr. Duclos and her colleagues, reopened under government orders. She appeared calm today (May 28) at a press conference with other local medical leaders; she is at around minute 14:30 in this new video. She implored people to keep taking precautions, “as we go through the little lulls and valleys, and the peaks that will occur with this, for months to come.” More on this below.
  3. Sylvia Leroy, 35, was a labor and delivery nurse at Brookdale Hospital in Brooklyn, where patients she cared for were positive for the virus. She got it. She was 28 weeks pregnant with her second child. Her own hospital did not take proper care of her. She was transferred to Mount Sinai where she got better care but went into cardiac arrest for some four to eight minutes; the doctor who called Sylvia’s sister was crying herself. They delivered her baby, Esther, by C-section. The baby needed oxygen but was “pink and healthy.” As of May 20, Sylvia was very slowly recovering from brain damage; Baby Esther was doing well. See their GoFundMe page here. Her sister once asked her why she didn’t go into private practice. “And she said to me, ‘This is an underserved community. Who is going to help them if I don’t help them?’”
  4. Dr. Ryan Padgett, 45, who played football for Northwestern in the Rose Bowl, was one of the first U.S. doctors to get the virus. It was still February, and nobody knew anything, but he was taking care of a string of patients from one nursing home in Kirkland, Washington. He was in great shape, hardly ever missed a day of work, but in March he was near death. He recovered, but still had more recovery ahead of him, when he said, “As an emergency physician, you walk into every single room and take care of whatever is there. Going back, I don’t think that will change. I hope not.”
  5. Dr. Theresa Greene, an emergency physician in Miami, temporarily lost custody of her 4-year-old daughter because she takes care of COVID-19 patients. She said, “I think it’s not fair. It’s cruel to ask me to choose between my child and the oath I took as a physician. I won’t abandon my team at work or the patients who will increasingly look to me to save their lives in the coming weeks, but it’s torture.” She and her husband have amicably shared custody since their divorce two years ago. Why is this under “Good News”? Nobody’s sick. Nobody died. However unfair it may be, mother and daughter will live to put this separation behind them.

Bad News

  1. Madhvi Aya, 61, was a doctor in India but a senior physician assistant in the U.S. She worked at a hospital in one of the poorest sections of Brooklyn; it was overflowing with coronavirus patients, and she was there until she got sick herself. At the end, in a different hospital, she was alone after texting with her husband, mother, and daughter, whom she had been very afraid of infecting. She often said, “We have to take care of our patients first.”
  2. A nurse who must keep her identity secret for her own protection was on a bus in Chicago, coming home in her scrubs from a difficult shift, coughed into the crook of her elbow, with a mask, and was punched in the face by a man who accused her of trying to give him the virus. He gave her a black eye. Attacks on coronavirus heroes in all frontline professions have been happening all over the world. “It’s not going to stop me from coming to work every single day and taking care of the people I take care of,” she said.
  3. Immigrant Celia Marcos, 61, worked as a nurse at Hollywood Presbyterian Medical Center for 16 years until her death in April from COVID-19, which she almost certainly contracted from a patient. Her family and colleagues state that she was not provided with proper PPE, which the hospital denied. Her son Donald said, “when the call of duty came, she will do the best that she could.” He also said she “coded seven times” before she died. In their last conversation he said, “when you get out of that hospital, you will retire immediately.” She barely was able to say yes. Both were crying.
  4. Jason Hargrove, 50, a bus driver in Detroit, loved his job and did it faithfully, carrying essential workers and others to their own jobs. A passenger openly coughed near him without covering her mouth, and he recorded a Facebook video about the incident. He was worried about the other passengers and himself. He said, “I feel violated.” He died of the virus 11 days later. He left home by 5am and disinfected his bus every day. He would tell his wife, “Baby, when you get off work, make sure you grab me some more Lysol… I gotta make sure that my people are protected.”
  5. Dr. Lorna Breen, 49, head of the emergency medicine department at NY Columbia-Presbyterian Hospital, contracted the virus while heroically trying to save others. She recovered, but the hospital told her to stay home. She moved from NY to her parents home in Charlottesville. There, with no history of mental illness, she took her own life. Her father said, “Make sure she’s praised as a hero.”

Under the Russian Tsars, young men were drafted into the army for 25 years. As a child I knew an old man who had chopped off the first joint of his own trigger finger to avoid that fate. And why do I mention this? Because many, maybe even most of you, have told me you want to become nurses, physician assistants, or physicians. You are signing up for roughly twice the length of service that the Tsars demanded of young people. There will be another pandemic like this in your career. You will be called on. Even medical students have been called on in this crisis. You will not say no when you are asked to put your own life, and that of your loved ones, in danger, because that is your oath. Even when you think or know that you are risking your life for stupid people who put their own lives in danger, you will serve. Know what you are signing up for.

It was very interesting for me to watch today’s press conference on local television in Black Hawk County, Iowa. This is the cutting edge of the U.S. pandemic going forward. The local Tyson meatpacking plant reopened because the governor and the president said so, and because it was in their financial interest. Three leading local physicians and county health officials spoke. They stated that they did not know what was going on at the Tyson plant and would not be getting that information. They said they could not do contact tracing of confirmed cases. A county health official laughed at the idea of testing health care workers in nursing homes, because they don’t have the resources to do it.

Don’t think about New York any more. Think about Black Hawk County. Times ten. Or maybe times 100.

Stay safe,

Dr. K

Opening Gambits: Freedom Goes Viral

            “With your talents and industry, with science, and that stedfast honesty which eternally pursues right, regardless of consequences, you may promise yourself every thing—but health, without which there is no happiness. An attention to health then should take place of every other object.” 

                        Letter from Thomas Jefferson to Thomas Mann Randolph, Jr., July 6, 1787

Dear Students,

The letter that includes the above passage was written as part of a series to a young man of great promise. Randolph was 18 on the date above, which happened to be two days after the 11th anniversary of the Declaration of Independence. The Constitutional Convention was under way in Philadelphia, but Jefferson was still posted to Paris. (The federal government, still based in Philadelphia, was suspended several times during the 1790s yellow fever pandemic.) He began the letter by apologizing for his delay; he’d been traveling in southern France and northern Italy.

There is plenty of other advice in the letters, but young Thomas had been seriously ill a couple of years earlier, and the elder Thomas was concerned. The young man did take care of himself, and when the Jeffersons returned in 1789, he courted and married Jefferson’s eldest daughter Martha. They had 13 children together; 11 survived to adulthood. They eventually became estranged because his drinking interfered with his health and their life, although she was at his bedside when he died at age 59. But first he was a colonel in the War of 1812, served two terms in Congress, and became Governor of Virginia.

His future father-in-law’s advice kept him healthy for decades, and when he stopped following it he paid the price. I wonder what Thomas Jefferson, perhaps the greatest founder of early American freedoms, would have thought of the people risking their health and that of others to protest social distancing—while crowding together and refusing to wear masks—in the name of freedom.

All 50 states and many countries are easing or marching boldly out of their lockdown phases. It’s too soon to know the results; I predict they will be fine in some places and terrible in others. However, even “terrible” is in the eye of the beholder. Sweden has twice the population of Norway but around 16 times the number of COVID-19 deaths. Swedes regret that so many elderly and vulnerable people have died, but they defend their strategy of valuing individual autonomy and freedom; they think that other countries will have to follow their lead to the elusive goal of herd immunity.

Clearly a large minority of Americans agree. New York is opening slowly and carefully, but only after rigorous measures put its severe epidemic almost completely behind it. Texas and North Carolina are opening  boldly while cases continue to rise. The US as a whole gives a false impression of decreasing cases, but that is due to the huge decline in the worst-hit state, New York; most of the country is flat or rising.

The First Amendment to the Constitution, insisted on by Jefferson and drafted by James Madison, is now being used by leading legal authorities to justify anti-lockdown protests; they don’t mention the limits on my freedom to falsely yell “Fire!” in a crowded theater, or on my freedom to drive myself home from a party where I’ve been drinking. Protests are different as long as they’re non-violent. Apparently, wilfully spreading viruses more dangerous than bullets (bullets don’t keep jumping from person to person) is non-violent.

Good News

  1. The pharmaceutical company Moderna reports that of 45 patients who received their experimental vaccine, the 8 who got two specific doses (25 and 100mg), mustered antibodies to the virus more strongly than those found in people who have recovered from the disease. This vaccine uses messenger RNA (mRNA), which the viruses uses to make its proteins; this is a new approach that could be a game-changer for other viruses.
  2. Some states are opening slowly, carefully, and systematically. California is expanding its corps of contact-tracers from 1000 to 13,000. New York is deploying both viral and antibody testing, as well as contact tracing, and is poised to reimpose any restrictions it lifts if conditions warrant that. In Germany, this sequence from lockdown to partial opening, to small outbreaks, to selectively reimposed lockdown has already cycled through. When we have broadly available testing and contact tracing, as only a few places are approaching now, we can reopen more safely.
  3. Hospital systems are no longer overwhelmed in most of the U.S., and increasing numbers of elective procedures unrelated to COVID-19 are being done. Important exceptions are small community hospitals in areas surrounding meatpacking plants, prisons, and other hot spots, which may still be headed for disaster.
  4. Stay-at-home orders have worked. A multicity ongoing study conducted by the School of Public Health at Drexel University, estimates that the successful stay-at-home patterns prevented more than 2 million hospitalizations and 230,000 deaths. There is no vaccine and no treatment that has any prospect of making this much difference in the near future.
  5. We are understanding more and more about the course of illness (look at the excellent Medscape graph below; no, really look at it), modes of transmission (very numerous), and symptoms, especially those outside the lungs, also numerous.

Bad News

  1. Just as one swallow doesn’t make a summer, 8 people responding doesn’t make a vaccine. The Moderna study is a very early Phase 1 trial. Phase 2 will involve hundreds of people, Phase 3 thousands. About a hundred other vaccine candidates are under study. I wouldn’t want to be a premature adopter of any of them. Remember that uselessness in preventing the disease is certainly not the worst possible vaccine outcome.
  2. I believe that bad blunders are being made in some reopenings. Time will tell, and it will take time because some states and localities are doing it right, some are not, and people in many places are taking more or fewer risks than their governments advise. I get that everyone is tired of being locked down. Imagine how tired we will be of death if the second wave (almost certain to come in the fall, complicated by flu season) has, like the second wave of the 1918-19 flu, far more cases and deaths than the first wave. All the carpenters in America working full tilt could not make enough coffins.
  3. The small rural hospitals that may soon be overwhelmed are far less resilient, flexible, and resourceful than the big urban hospitals that expanded their ICU, ventilator, and to a lesser extent PPE capacity, in a matter of days to weeks in April. Community hospitals, even if they could somehow get the beds, ventilators, and other equipment, do not have the expertise to use them. Perhaps an army of doctors, nurses, respiratory therapists, and others from major medical centers will fan out to the rural hotspots overnight, but those people are literally sick and tired. How much damn heroism can we expect?
  4. Lockdowns have worked, but they are ending in haphazard ways, with hopelessly inadequate testing and tracing. We just have to see what happens, and continue building up (high-quality) viral testing, antibody testing, and contact tracing. Experts keep hammering away at this advice for a very simple reason: We are not there yet. Here’s your mnemonic: TETRIS: TEsting, TRacing, and ISolation.
  5. There is so much more about COVID-19 and SARS-CoV-2 that we don’t know. First, it was “Children don’t get it,” then, “They might be carriers,” then, “They’re definitely carriers but they don’t get sick,” to “Hundreds of children are showing up with a devastating post-viral hyperinflammatory syndrome and some of them have died horrible deaths.” The number with this, Multisystem Inflammatory Syndrome in Children may or may not remain small. Also, loss of smell and taste went from “Maybe in some cases” to “Maybe in a lot of cases” to “Often the only symptom.”

Your fellow student Caroline Yoon sent me a marvelous question the other day in a message called “Your take on positive retests?” She was concerned about the apparent reinfections in South Korea and on the aircraft carrier U.S.S. Theodore Roosevelt, and asked whether there might be reactivation of a long hidden infection as with HIV. It could be reinfection or reactivation or lousy tests, no one knows. But here’s my answer:

“The evidence of possible reinfection is very concerning in the two places you mention. The South Korea cases may be attributable to testing difficulties; the negative tests they had may have missed continuing infection (false negatives; there is a lot of evidence that this can linger for weeks to months). Or, the positive retests may be due to what some call “virus litter”—fragments hanging around after the infection is over (a type of false positive). The interpretation is complicated by post-infection symptoms due to viral damage during infection that takes a long time to heal, or to overactive and prolonged immune responses. The dreadful syndrome that has been hospitalizing and in some cases killing children (fortunately still a small number) is thought to be a post-viral hyper-inflammatory syndrome, perhaps a kind of autoimmune overreaction.

“The possible reinfection cases on the Roosevelt are more concerning to me than the South Korean ones, because conditions have been so controlled. The now 13 sailors who have retested positive did so after 14 days of quarantine and two consecutive negative tests. We haven’t been told whether any of the 13 have shown symptoms. Today it was announced that the Roosevelt will leave Guam and go back to sea—presumably, one hopes, without those 13. This will be an informative, I hope not dangerous, experiment, as the ship had over 1000 cases at one time not too long ago.

“I wish I had more definitive answers. Sometimes the best we can do is admit our ignorance, while pushing science forward to alleviate it.

“Stay safe, best wishes, and thanks again for your questions, Caroline.”

“Dr. K”

Eric A. Meyerowitz, MD; Aaron G. Richterman, MD, MPH,

A Quick Summary of the COVID-19 Literature So Far – Medscape – May 18, 2020.

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

Do I Have It, Did I Have It, Am I Recovered, Am I Immune?

“A house divided against itself cannot stand.” Gov Andrew Cuomo, quoting Abraham Lincoln, quoting Matthew 12:25 and Mark 3:25

“The paranoia of stupidity is always the worst, since its fear of destruction by intelligence is reasonable.” American playwright Arthur Miller

“You can’t always get what you wa-ant. But if you try some time, you just might find, you get what you need.” The Rolling Stones, from home, yesterday

Dear Students,

A book called The Starfish and the Spider, published in 2006, was about the strength of decentralized organizations. The metaphor is not ideal, but if a spider loses its leg, it’s crippled, and if it loses its head, it’s done for. A starfish can regenerate its cut-off leg, and in some species the leg can regenerate the whole starfish. The authors argue for the strength of acephalous or headless organizations. Wikipedia and the Internet are examples. The Aztecs quickly fell to the Spanish conquerors, but the dispersed, leaderless Apache Indian tribe resisted them for centuries.

Good News

  1. The resilience of the United States as a headless organization is being tested as never before, at least since the American Revolution. How many times have we now heard, “It’s up to the governors”? Well, guess what? The governors have gotten the message! They are fighting the would-be COVID conqueror with the resilience of a headless organization. This includes Republican Governors Larry Hogan (Maryland), Mike DeWine (Ohio), and Charlie Baker (Massachusetts), and Democratic Governors Andrew Cuomo (New York), Gretchen Whitmer (Michigan), and Gavin Newsome (California). They keep asking for Federal help, and people are dying for lack of it, but they no longer expect it from the executive branch, and they are getting the job done.
  2. The Congress is another leg of the starfish. It is drafting legislation to provide funds for millions of free tests a week, both for the virus (you have the disease) and for the antibodies (you had it). New York State, which accounts for almost half the U.S. cases and deaths so far, is pretty clearly over the worst. Following Germany and other countries that understand science, New York will implement massive random antibody testing to get a snapshot of how the virus spread through its population, calculate real mortality rates, and begin finding out who may be immune.
  3. As for treatment, hydroxychloroquine has not yet worked but is still under study, as is the antiviral remdesevir, which looks much more promising. The use of convalescent plasma (from recovered patients) is also being aggressively studied. All three are in short supply, but doctors can request any of them for individual patients outside of controlled trials. Vaccines are in development in labs throughout the world.
  4. Stay-at-home measures, social distancing, obsessive handwashing, masks, and other preventive strategies have dampened the curve in many states and in the U.S. as a whole, although they have not crushed the curve anywhere. Some states will begin returning to normal life in stages recommended this week by the Coronavirus Task Force, starting as early as the first week of May. Every person who voluntarily stayed at home has been part of the headless organization defeating the virus and saving literally countless lives.
  5. Recessions and even depression do not costs lives, but contrary to intuition they save lives. This has been shown for the Great Depression, the Great Recession and other downturns. Deaths from auto and other accidents, heart disease, lung disease, and infant mortality all go down. Deaths from suicide and addiction probably go up, but overall deaths decline. Obviously if a recession coincides with a pandemic, a lot of people are going to die from the pandemic, but the idea that recession itself will cost lives in the aggregate is false.
  6. Lady Gaga and Global Citizen yesterday presented One World: Together at Home, a two-hour concert from the homes of an astounding array of huge celebrities (see highlights here). As of today they have raised $128 million for WHO, the UN, and other headless organizations fighting the virus, some abandoned by the United States.

Bad News

  1. However successful the states are on the headless starfish model, the absence of Federal funds, especially for testing, will hamper their response and cost lives. Some states are opening up too much too soon and are ignoring the fact that unknown numbers of their citizens are infected and spreading the virus without having symptoms. New research shows that sneeze droplets travel much farther than 6 feet.
  2. There is another, negative aspect to headless organization emerging: large, angry protest movements both denigrating and flaunting public health measures. This has been framed in terms of “freedom” and “liberation” and encouraged from what is left of our country’s head, but the result is massive dense crowds of people with no protection against each other. This will have an effect similar to that of Mardi Gras in Louisiana.
  3. Hydroxychloroquine trials have been disappointing so far, both because of lack of positive effect and cardiac side effects. Compassionate use of remdesivir has been more promising but it also has side effects and controlled trials must be completed before it is widely used. Ditto for convalescent plasma. Many vaccine experts doubt the timetable we have been encouraged to think about, which is 12 to 18 months.
  4. Twenty public health experts interviewed for a long article in today’s New York Times have urged us to prepare for return of the virus after the first wave, and to see this as a process that may take years. Scientists have criticized the main model that the Federal government is relying on for its normalization plan, while others have provided more plausible models that see the virus returning in multiple waves.
  5. Congress is at this writing deadlocked on major measures to provide funds for serious testing and alleviate economic suffering. Some health measures improve in recessions, but mental health measures are probably not among them, despite stress reduction for some people.
  6. The impacts of poverty, racial oppression, age, and gender are clear in this pandemic as in so many diseases. Poor people, African-Americans, and the elderly are prime targets due to preexisting untreated conditions. Women are the majority in front-line occupations, although men are more like to get sick and die. Nothing will change in the long run without changes in our society and our health care system.

“Do I have it, Did I have it, Am I recovered, Am I Immune?” These are the critical questions that we cannot yet answer. Washington says there are plenty of test kits, but the governors (both parties) say there are no swabs to do the tests and no reagents for the labs to do the analysis. Imagine that you can sit for the SAT or the MCAT, but you don’t get a pencil. Or imagine that you get a pencil and fill in the bubble sheet, but it can’t be graded.

We can’t end social distancing except as guided by widespread testing which is not yet available.

Below or attached, two graphs of the influenza pandemic of 1918-20, which we studied early in our course. The first shows overall mortality in various cities. Notice that the bumps in mortality came in three waves, the first being the smallest. The second shows the difference between the curves in Philadelphia, which had a parade of 200,000 people on Sept. 28, 1918, and waited two weeks after the first case to implement social distancing, and St. Louis, which instituted social distancing two days after the first case.

Please, be a part of the worldwide headless organization that will defeat this virus.

I know you are disappointed to be losing months of your youth, months of normal college, and for many of you the ceremonies of graduation. I am truly sorry. But I want you to have the rest of your youth and the rest of your life, and that of your parents and grandparents. We will figure out a way to make it up to you about commencement.

The “paranoia of stupidity” that Arthur Miller refers to is driving some people into the streets and into the arms of the virus. Yours is the intelligence that can subdue that paranoia.

You can’t always get what you want, but if you try some time, you just might find, you get what you need.

Stay safe, Dr. K

   

The Virus Has a Vote: Update to Students April 12, 2020

“Whatever happens over the summer, this virus is going to be back with us in the fall. And so we have to prepare for the fall as well.” Dr. Ashish Jha, Harvard School of Public Health, 4-5-20
“What we are doing is working, and therefore we need to keep doing it.” Dr. Anthony Fauci, 4-9-20
“If we are not expecting a second wave, or a mutation of this virus, then we have learned nothing.” Gov. Andrew Cuomo, 4-10-20
“The worst thing that can happen is we make a misstep and we let our emotions get ahead of our logic and facts and we go through this again in any manner shape or form.” Gov. Cuomo, 4-11-20
“Well you know I did just finish a 24 hour shift overnight so forgive me if I’m a little brutally honest, but at some point we have to accept that we open up the economy and X amount of people are going to die and the question is what is that number and what are we willing to accept. You know as we flatten the curve, if we don’t time this right there may be another spike, and this won’t be flattening the curve, it will be flattening the roller coaster. So myself, the front line health providers, we don’t want to flatten this curve, we want to crush this curve.” Dr. Sudip Bose, Emergency Physician & Iraq War hero, 4-11-20

These quotes from experts and leaders over the past week, in order of when they were said, are more eloquent in their message than I could be. The so-called first law of medicine, If it’s working, keep doing it, is operating here. But so is the first law of life: Hope for the best, but prepare for the worst.

Good News

There is a lot of good news to celebrate this Easter Sunday, and it’s more than just hope.

  1. New York, by far the worst hotspot in the U.S., has convincingly passed its peak of intubations, and that means the worst of the worst is over for New York. Daily death rates continue to be tragically high, but they are a lagging indicator and they too are plateauing. The overwhelming of hospitals has happened, but it may not get worse.
  2. Christopher Murray’s model, often cited by the Federal government task force, from the University of Washington’s Institute for Health Metrics and Evaluation (IHME), is now projecting a total of 61,545 deaths for the U.S., down from 100,000 or more projected just a few weeks ago.
  3. The West Coast states, notably Washington where the first U.S. cases were, but also Oregon and enormous California, have done an amazing job of keeping this in control from the beginning.
  4. Clinical trials of convalescent plasma, antibodies from same, hydroxychloroquine, remdesivir (an antiviral), and other potential treatments are proceeding. Some are being prescribed under the principle of “compassionate drug use” approved by the Food and Drug Administration (FDA), although their effectiveness is a long way from proven. Many promising vaccine candidates are under study.
  5. Testing is being gradually ramped up, with viral testing (to see if you have it) up to between 100,000 and 200,000 a day. Antibody testing (to see if you’ve had it) has begun in some areas.
  6. Some top Washington officials say the country may go back to normal activity on May 1. Others see a carefully planned phase-in of normal activity over the subsequent weeks to months, guided by testing, testing, testing.

Bad News

  1. Many parts of the country are behind New York on the curve. Some will succeed as the West Coast states have. Others, where social distancing has not been followed, may be disaster zones.
  2. When you read the fine print on the IHME website, you find that they are only claiming to model “the first wave” of the pandemic. They have nothing to say about future waves. (Below I discuss a more realistic conceptual model that is speculative but helps me to think about what our longer-term future may look like.)
  3. Very few states have done what the West Coast states have done from the outset, and some have done the opposite. If Los Angeles relaxes its controls too soon, it is projected to look like New York by late summer.
  4. Early results from small clinical trials have concluded that it is ethical to continue them. This means two things: a) they are not doing obvious harm to volunteers; b) they are not so dramatically effective that the trials have to be stopped so that everyone gets the treatment and no one gets a sugar pill. They could still turn out to be useful, or have bad side effects, or both. If a vaccine is available in 12 to 18 months, it will be by far the fastest vaccine development time for any novel virus.
  5. Testing remains woefully inadequate across the board, and claims to the contrary are demonstrably false. There are not enough viral tests for health workers at risk, much less for a suitable sample of Americans. If we do 200,000 tests a day, it will take half a year to test 10% of the country. Antibody tests, which if they work well enough can probably clear many people to go back to normal activity, have barely begun.
  6. The IHME models, which are the ones quoted by and guiding Federal government officials, are premised on current strict levels of social distancing continuing through May. Earlier relaxation of vigilance is projected to increase deaths, as mentioned by Dr. Sudip Bose, the emergency physician and war hero quoted above.

The model in the graph below (or attached) is a conceptual rather than precisely mathematical model, and I have problems with it, but I think it broadly shows how we should be thinking. It comes from an odd place, namely Morgan Stanley investment research (thanks to Dr. Craig Hadley for alerting me to it; the head of the unit that produced the graph is Matthew Harrison). It has errors (it assumes that children can’t pass the virus on and it is too optimistic about the timetable for a vaccine). It may have been updated today, and I will let you know if I can access it. Meanwhile, it is conceptually valuable in showing us how to think about how this will unfold. You know I consider you leaders. Use your excellent brains to navigate uncertainty, especially when so much depends on how we steer.

Note: I made a mistake in an earlier announcement about the effect of the Great Recession on life expectancy. It actually increased life expectancy and reduced mortality at all ages. The improvement was due to decreased deaths from heart disease, auto accidents, and homicides, among other causes. There were increases in opioid related deaths and suicides but these did not offset the improvements. Improved life expectancy in the Great Recession has been shown in both the U.S. and Europe. A similar paradoxical effect has been clearly shown for the Great Depression of the 1930s and is probably true of other economic downturns. I did see one study claiming to show the opposite, and that’s what I expected, but the weight of evidence goes against my expectation. That’s science for you.

Stay safe, Dr. K

 

 

Letter to my students on COVID-19, April 5, 2020

“I skate to where the puck is going to be, not where it has been.”

Wayne Gretzky, widely viewed as the greatest hockey player of all time

Volunteers
Volunteer Georgia health professionals on their way to New York

Dear Students,

This is my outlook on the COVID-19 pandemic as of Sunday, April 5, 2020. I pay close attention to many sources of information and sift or curate them as best I can. This is a constantly changing situation and you should not rely too much on me. As I’ve told you before, you are the future leaders of our country and our world and you must ultimately lead, not follow. Please let me know if you have information that is different or if you think I’ve made a mistake.

In my favor, I have been talking to you about this virus since our class began in January and I updated you every Tuesday and Thursday until Emory closed. Since then, I’ve been updating you every few days to a week. I try hard to get this right and not to scare you too much. I did try to scare you when we talked about Ebola, polio, and the flu pandemic of 1918-19, and I always said the next pandemic was a matter of when, not if. I did not know that this was it when I first mentioned it in January, but now everyone knows.

Good News

  1. The CDC has found that homemade masks or bandanas covering your mouth and nose when you leave your house will help to slow the spread. First Lady Melania Trump endorsed this, as have many other opinion influencers. It is not a substitute for social distancing, hand washing, and other measures, and it would be disastrous if people thought it was. It is an added measure on top of all those things. It is designed mainly to protect others, not you. When you breathe, talk, laugh, cough, or sneeze into the mask, the cloth will capture half or more of the moisture, and that means half the viruses if you are infected but don’t have symptoms. (You can experiment by spraying water into a glass through a cloth; only some moisture gets through.) If you do have symptoms, you must assume you have COVID-19, and self-quarantine completely until you are symptom free for three days. Call your health professional for specific instructions, and don’t dial 911 unless you are short of breath. Do not try to buy medical-grade masks; you will be taking them away from medical professionals and you may cause some of them to become sick and die. An example of how to make a mask is here.
  2. Rapid tests for the virus itself are slowly becoming more available, and antibody tests for whether you have already had the virus but recovered will become available more slowly. Widespread testing will be a game changer for control of the American epidemic, as it has been in China, South Korea, and other places.
  3. We have real leaders in this country who are regularly speaking out: Gov. Andrew Cuomo of New York, (Republican) Gov. Larry Hogan of Maryland, Speaker Nancy Pelosi, Dr. Anthony Fauci, and others. They speak honestly and to the best of their ability accurately about how to beat the virus and mitigate its economic effects. They don’t just call it a war, they act like it’s a war. Governors of many states are bypassing a mostly passive Federal government and attempting to help each other.
  4. Fortunately not all states are experiencing this wave of the pandemic simultaneously, so people and equipment are beginning to move where they are most needed. New York has by far worst crisis, so it is calling loudly for help. The state of Oregon sent 140 ventilators* to New York; this is a small fraction of what will be needed but it is a very important symbol. Twenty-two thousand health professionals from other states have gone to New York to volunteer. New York is worst now, but it will be better first, probably within a few weeks. It will then have excess ventilators and professional volunteers to send to other states as the crest of the wave moves around the country.
  5. Studies of treatments are proceeding, including convalescent plasma donated by people who have recovered from COVID-19; antibodies derived from that blood fraction; hydroxychloroquine, which has antiviral action in lab studies (and which I took for years to prevent malaria when I was in Africa, and then again for years for a skin condition); azithromycin, an antibiotic with possible antiviral actions; and specific newer antiviral drugs. I am hopeful that one or more of these will prove effective within weeks to months, much sooner than we have a vaccine. However, it is immoral to take hydroxychloroquine for prevention or self-medication at this time; it is not proven to work, and it is in short supply for people with lupus and other autoimmune diseases, who desperately need it.

Bad News

  1. We have inadequate leadership at the very top in Washington, giving out inconsistent messaging, with no national strategy for supply and logistics for COVID-19 care—ventilators, N-95 masks, shields, gowns, and other personal protective equipment (PPE), and consistent only in predicting unrealistic time frames for ending the pandemic and getting the country back to work. The government in Washington has declined to order a national lockdown for social distancing, to mobilize the armed forces to help the hospitals and the states, to order manufacturers to make desperately needed ventilators and PPE, or even to set an example for our people in things like social distancing and wearing of masks.
  2. The hospitals in New York, Detroit, and New Orleans are already overwhelmed, but the word overwhelmed will be given new meaning in those cities in the next week or two. Large numbers of health professionals, police officers, firefighters, EMTs, and other first responders are already sick and more will be. Many who are not sick are crying every day. Some, understandably, are quitting in fear of bringing this deadly virus home to their families. Similar effects will be felt in other cities throughout the country over the coming weeks. Hospitals built out in convention centers and mega-tents were ready but almost empty for days until they were allowed to take COVID-19 patients. U.S. Navy hospital ships are almost empty because they still will not take COVID-19 patients.
  3. Many people still do not take social distancing seriously. Gov. Kemp of Georgia reopened the beaches and parks in our state after closing them. In many states social distancing is not enforced and not likely to be until it is too late. According to current official government projections, the United States will see a minimum of 100,000 to 240,000 deaths if we strictly follow social distancing and other precautions. We are not yet doing that. The number of deaths in the U.S. passed 9,000 today and is doubling approximately every 3 days, which would put us over a hundred thousand in 10 days or so. If we act properly and lengthen the doubling time to 4, 5, or 6 days, it will take longer to get there. But bear in mind that the increase continues to be exponential at those longer doubling times.
  4. The Congress, especially the Senate, has offered too little too late to offset much of the disastrous economic effects of the pandemic, and as usual the poor and minorities will suffer most of the consequences, including worsening health, inadequate access to care, and premature and preventable death. Poor families have the greatest psychological vulnerability to the post-traumatic effects of this experience. Families at all socioeconomic levels have seen increases in domestic violence.
  5. Something that I have been reluctant to mention in these announcements, but which more and more authorities are considering, is the possibility that this is only the first wave. The flu pandemic of 1918-1919 had three waves. We must watch closely what happens in China, South Korea, and Japan as they declare the virus beaten and relax social restrictions. The virus is currently spreading in the Southern Hemisphere of the planet and may get worse in their winter, even as it may get better at the same time in our summer. I wish I could promise you that Emory will have live classes again in the fall.

We all need to adapt to situations that are psychologically abnormal. You can do it. Facetime or Skype with your friends and family. Have Zoom rituals, club meetings, and parties. Go outside with a homemade mask and run or walk while social distancing. Watch those movies you always wanted to see, binge-watch those hot TV series, even maybe read a book that’s not assigned for school.

Whether we have one wave or more, we will in time have treatments and a vaccine. Those who have had the virus and recovered will slowly begin normal life again. They will help restart the economy. This will end.

Your great-grandparents lived through World War I and the flu pandemic of 1918-1919. Your grandparents lived through the Great Depression and World War II. Your parents lived through the Vietnam War, 9/11, terror of terrorism, and the Great Recession. If any of your generations were in the developing world, they saw and lived through other terrible things. You can live through this. Just do what you’re supposed to do and help others as best you can. Do your homework and study. Come to class online. You are still a college student and you still have great dreams. You will live to see your dreams come true.

Dr. K

  • A note on terminology: I said in an earlier announcement that a ventilator is the same as a respirator. The Medline Plus dictionary of the U.S. National Library of Medicine says, “A ventilator is a machine that breathes for you or helps you breathe. It is also called a breathing machine or respirator.” However, other authorities use the word “respirator” to mean something entirely different, namely the top-flight hospital grade N-95 masks that screen out at least 95 percent of airborne particles not carried in oil. Because of the two meanings of “respirator,” I will avoid this word going forward. COVID-19 is the name of the disease caused by one of many coronaviruses; this coronavirus is designated SARS-COV-2. However, we all know that today “coronavirus” or even just “the virus” will pretty much get the message across.

Summary I sent my students on Wednesday, with preface/update Saturday

Photo by CDC on Unsplash

Since Wednesday the number of identified cases in the US has gone from 3,500 to 20,000, partly because of increased testing. Testing remains woefully inadequate so the real number of cases must be much higher. The US deaths have passed 200. More young people are sick and dying. Mardi Gras (Feb. 26) made New Orleans a hot spot and Carnival encouraged transmission throughout Latin America. Spring Break on Miami Beach will have a similar effect. US hospitals are begging for supplies, personal protective equipment (PPE), and ventilators (respirators),  and the government in Washington is so far not demanding that factories repurpose to produce these items. Barring drastic action, hospitals will be overwhelmed in two or three weeks, heroic health professionals will be dying at higher rates, and remaining doctors will have to decide who lives and who dies. Don’t become one of those casualties. Protect them, yourself, and those around you.

Use this source for daily future updates, interactive maps, and reliable information in days to come: https://www.nytimes.com

COVID -19 UPDATES

WEDNESDAY March 18, 2020, 8am

Here is what has changed in the past week:

  1. The WHO declared a worldwide pandemic last Wednesday
  2. Italy is probably the worst hit, with hospitals completely overwhelmed; Iran may be worse, but we have no reliable information from there.
  3. France announced a nationwide lockdown two days ago, noting a rise in severe cases in young people around the country.
  4. The U.S. President announced a national emergency & discouraged gatherings of more than 10 people.
  5. Testing became more widespread, but still lags far behind that in other countries.
  6. Testing proved that the virus is being spread by people who have no symptoms, mainly the young; the young may not know it, but they are killing the old.
  7. Stock markets crashed & economies shut down in many countries and U.S. states.

Here is where we are this morning:

  1. Many leading U.S. hospitals are seeing a dramatic rise in cases and expect to be overwhelmed soon.
  2. Many governors are calling for U.S. army and other national aid that isn’t there yet.
  3. Approximately 3,500 cases are identified in the U.S.; experts say there are 10 unidentified cases for every identified one, so the real number is around 35,000.
  4. Despite lockdown in many areas & the closing of restaurants, bars, gyms, theaters, sports events, etc. by law, experts agree social distancing is far less than needed.
  5. Hospitals are running out of supplies needed to protect health care workers.
  6. Ventilators (respirators; breathing machines) cannot be manufactured fast enough to keep up with the need; doctors will have to decide who will get treatment & who will be let go of, just like in a war zone.
  7. Doctors and nurses are getting the virus from their patients and going home; they cannot be replaced, even if machines and supplies can.
  8. The Secretary of the Treasury now warns that U.S. unemployment can go from 3 to 20 percent.
  9. Economists widely agree that we are in or are “sliding into” a recession which cannot be avoided, and which could be worse than the Great Recession of 2008.
  10. No one can tell us how long this will last or how bad it will get.
  11. Epidemics in warm countries seem to disconfirm the hypothesis that summer weather reduces the number of cases.

My advice to you right now:

  1. Stay home and urge anyone in your family who is not performing a vital service (hospital work, food and medicine deliveries, grocery stores, pharmacies) to stay home too.
  2. Maintain contact with friends and family by phone, Skype, etc.
  3. If you must leave your home, stay six feet away from any other person.
  4. If you have traveled anywhere by air, train, or bus, stay away from your grandparents & all older people for at least 14 days. Stay in touch with older people by phone & have food and medicine delivered to them if you can.
  5. Develop, & urge everyone you know to develop, skills for working, preventing isolation & sadness, & being entertained at home. If you must get out, walk in the woods or in a park where you can avoid getting within 6 feet of another person. If you have to walk the dog, use the same precautions.
  6. If you are coughing & sneezing without a fever, stay home & call your doctor. Do not just show up at a medical office or emergency room. Get a test if you can find one.
  7. If you develop a fever and feel very weak, call 911.
  8. If you are in the U.S., check the CDC web page every day:

https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/cases-in-us.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fcases-in-us.html (Links to an external site.)

  1. Wherever you are, check your national, state or provincial, and city or local health department websites every day.
  2. Wash your hands for 20 seconds many times a day; avoid touching your face as much as possible; frequently wipe down all surfaces from cell phones to kitchen counters with alcohol wipes; gloves & masks are in short supply, so use them wisely.

(Note: the photo above shows viruses in the coronavirus family, not SARS-COV-2, the causal agent of COVID-19, currently pandemic.)