“The vaccine rollout has been embarrassingly slow. I’m having patients call daily, anxious, fearful that they won’t get vaccinated, and as you know we’re losing thousands of lives a day. I think what needs to happen is a better communication between the federal government and our states; we need coordination of delivery; and we need more funding to get the shots out of the refrigerator and into people’s arms.” Dr. Lucy McBride, internal medicine physician, on Bloomberg TV, January 4, 2020
“The challenge we have right now should’ve been expected. I’ve been talking about the last mile and the last inch for the better part of several months. What we did is we invested a great deal of money in the basic research and development, the licensing and approval, the actual manufacture of the vaccines, but we we forgot about what will it take to actually get this vaccine in to peoples arms… Long-term care facilities are being handled by a private pharmaceutical or pharmacy company and they were not really ready to go. Healthcare workers have been slow in getting the vaccine to because they’re also in the middle of a crisis, and so to try to do both vaccination and care for all these patients has been a challenge.” Dr. Michael Osterholm, epidemiologist, on Bloomberg TV, January 5, 2021
“Come back and look with me. I have no beds. I have nowhere to put you.” Jenna Rasnic, Methodist Medical Center Emergency Room Nurse, USA Today video, January 4, 2021
Happy New Year, sort of. If you’ve been following the news at all you know that we are in the worst phase of the American pandemic, getting worse every day. Hospitals are overwhelmed (in California, Mississippi, Georgia, etc., etc.) and the Christmas week (not to mention New Year’s Eve) surges have not even darkened their doors yet. Patients are being cared for in chapels and gift shops. Triage committees have been implemented in many hospitals so that patients can be turned away because others have a better chance of recovery. Naval hospital ships are being begged for in some cities. National guard troops have been mobilized to store the cascade of bodies needing refrigeration after death.
I won’t tell you in my own chosen words how the vaccine rollout is going, but it rhymes with “duster truck.” Also, with “muster luck.” Luck is something we have only really mustered in one domain since this time last year: the beautiful science of the vaccines. And that wasn’t luck anyway, it was earned by brilliant scientists. Apart from heroic clinical care, it’s the only thing we have done right.
If you want to understand why there are tens of millions of lifesaving vaccine doses sitting in freezers right now, why the government’s predicted number of actual vaccinations—20 million by the end of 2020—turned out to be a pathetic 2 or 3 million, all you have to do is remember the year that was: how carefully we handled containment in the early weeks, how strongly and promptly we stepped up production of personal protective equipment, how well we did testing and contact tracing throughout, how responsibly we followed the simplest public health measures, how effectively we communicated the dangers, and how cleverly we avoided and flattened the predicted and avoidable monstrosity of the fall and winter surge.
Oh wait, I forgot. We didn’t do any of those things.
Bad luck, you could say, I suppose, except it wasn’t. It was failure. Failure after failure after failure. Abject, shameful, humiliating, lazy, reckless, titanic failure. Failure on a scale and in a manner unprecedented in our nation’s history. Failure of thought. Failure of planning. Failure of ethics. Failure of patriotism. Failure of equality. Failure of caring. Failure of love.
For a while you could say we were lucky in one other way. We had a corps of nurses, doctors, and others on the front lines in ERs and ICUs who never flagged or shirked their duty even when they were crying in their cars on the way to and from work, terrified of infecting themselves and their families yet going back and back for more. They even worked out a few inventive ways of lowering our chances of death once we enter the hospital.
And how do we reward them for conspicuous bravery, compassion, brilliance, and patriotism under fire?
We reward them by grabbing them by their hospital gowns, slamming them against the ICU wall, and punching them until they fall down. We reward them by slobbering and spitting more and more virus in their beaten faces. We reward them by kicking their wounded bodies when they’re down. Those of you aiming for clinical careers take note.
And now, with the new holiday surges about to come, we will give them their ultimate reward: we will kill them with our virus. We will kick them until they are dead. And then the National Guard can come and store their bodies alongside ours in the overflow refrigerator trailers. Maybe trailer parks can double as makeshift cemeteries.
Some of you have thought that I wrote angrily before. I guess I have reached a new level of frustration, anger, and grief. To trash the beautiful hopes raised by the vaccines by having no plan to distribute them, to leave them to spoil on shelves while the hospitalizations and deaths mount and mount, is not only a last straw, not only an insult to the genius of those scientists who invented, developed, and tested them in record time and with near-perfect precision, it is an insult to humanity. Yours. Mine. Everyone’s.
Someone said that the mark of a civilized person is to be able to look at a page of numbers and weep. We are learning, more every day, to look at a graph and weep—and yet I don’t believe for one minute that we are civilized.
The Year of Colossal Failure will now be extended, not for weeks but for months. September is now an optimistic view of when we are done with this. Welcome to 2021.
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. For an up-to-date account of the clinical facts by the marvelous front-line doc Daniel Griffin, listen to TWiV episode 701, a marvelously clear step-by-step from exposure to recovery in 39 minutes.
“I feel great. I feel hopeful today, relieved — I hope this marks the beginning to the end of a very painful time in our history.”
—Sandra Lindsay, Director of Critical Care Nursing at Long Island Jewish Medical Center, after becoming the first person in New York, possibly in the U.S., to be vaccinated against COVID-19, December 14, 2020
“It was truly, truly a humbling moment to be able to do that… So, this is the light at the end of the tunnel, and we truly have to be patient in order to make this work we have to make sure that we continue on to follow the guidelines —socially distancing, wearing our mask, washing our hands, and not having large gatherings—following those guidelines along with the vaccine, we can defeat this. This is something that is giving us that huge light at the end of the tunnel. It’s still a long tunnel but again, it’s up to us to do our part to assist in stopping this pandemic. So with those things in place along with the vaccine, it’s a good prognosis for the future… Let science speak for itself.”
—Dr. Michelle Chester, DNP, director of employee health services at Northwell Health, who injected Ms. Lindsay with the vaccine, interviewed on CNN December 15, 2020
“This disease is real, it is serious and it is deadly. Wear the mask, socially distance, if not for yourself then for others who may lose a loved one to the disease.”
—Kim Miller of Carbondale, Illinois, in the obituary she wrote for her husband Scott
Two milestones for our country yesterday: the first people outside of research trials to get a COVID-19 vaccine were inoculated; and we crossed the threshhold of 300,000 deaths from the virus, by far the most of any country in the world. The vaccine will eventually be everywhere, but that death toll is only in America.
The first photo shows Sandra Lindsay (quoted above) being vaccinated by Dr. Michelle Chester (also quoted above) and the second shows Ms. Lindsay applauding as she gets her bandaid. She was one of the very first and possibly the first person in the U.S. to receive any COVID-19 vaccine outside a research trial.
People are understandably excited about the vaccine. For a few days it seemed that all I saw when I turned on the news was freezer trucks leaving Pfizer vaccine factories and distribution centers. You would think they were carrying the secret of life, and in a way they were, for those few who will be vaccinated soon. By next week at this time, trucks will be rolling out with a second very effective mRNA vaccine, from Moderna.
But I couldn’t help think of a different kind of refrigerator truck, the portable morgues that are being brought in to hospitals and coroners’ offices all over the country—and not for the first time—to store the overflow of bodies of people killed by COVID-19. Hundreds of hospitals are at full capacity for those still alive, and a third of U.S. hospitals are almost out of ICU space.
Doctors agree that death rates will go up as health care workers are overwhelmed—they, not ICU beds, are the ultimate bottleneck of care—over the next two to three months. Remember that the small number of front-line heroes being vaccinated this week will not have full immunity until the third week of January. Even according to the Trump administration, always bragging about solving the problem, projects 20 million people will be vaccinated in December, and another 20-25 million in January. That’s the first dose; 3-4 weeks later, the second dose, and then a week more for full immunity.
There are 350 million people in the U.S. We add roughly 200,000 cases and more than 2000 deaths a day, with deaths lagging by about 3 weeks. You do the math. Vaccines will have no impact on the next 60 days’ deaths (adding 120,000) and little impact in the next 60 after that. Community spread will continue up to and beyond April 1st, when deaths are projected to pass 500,000, or 600,000 with relaxation of mandates.
But you know of course what can slow the spread right now, today? Masking, social distancing, avoiding gatherings, and proper hand washing. What are the chances that enough Americans will take these simple measures during the holiday season? Close to zero, even though they would save scores of thousands.
In the past nine months, Americans have chosen the worst kind of “social Darwinism” which is contrary to Darwin’s own beliefs. We have chosen to allow the virus to kill off certain groups of people we evidently consider expendable: the old, the sick, the obese, and people whose skin is not white. And now we are cheering and celebrating the deployment of vaccines that will not make a significant dent in community spread for months, and will not stop the U.S. epidemic until we have doubled the number of deaths.
The choice is clear, as it has been all along, except now we have the worst two months of the pandemic right in front of us. We can either double down on precautions or double down on deaths. Remember that young people will be among those killed. And a much larger number of people young today will live out their lives getting reminded every day of the permanent damage the virus did to their bodies.
Celebrate the vaccines, sure, but bear in mind that they will not make a real dent for a long time. Other preventive measures will make a great difference now.
Enjoy the holidays safely, so we can truly have a blowout celebration next year. I’ll see you in January, unfortunately still on Zoom.
John Berman, interviewing Dr. Sanjay Gupta, December 3, 2020:
“But there’s every reason to think that what’s going to happen over the next three weeks isn’t just awful but I’m talking historically catastrophic I’m talking 1918 levels of pain for the next month and a half or so until the vaccine comes into play.”
“I have been tracking exactly what you said very closely John to sort of see where are we in this country as compared to what is widely considered as the worst public health disaster in the history of the world hundred years ago or at least the last few hundred years and … we have better hospitalizations, ICUs, therapeutics, and an ambulance system and despite that, if you look at the numbers, we are tracking just as badly as back then which speaks to the fact that no matter how good we get scientifically and all the wonderful things that medicine can do, despite all that, human behavior is still sabotaging us…”
“I was looking at the models again last night and the projected peak keeps moving but sometime in January —the issue really is that we may stay there and just plateau at that unacceptably high-level for a long period of time…The exponential growth is too high…90% of hospitals now are at capacity around the country. Where do you go? …if the entire country is on fire what is the escape hatch? It is becoming increasingly hard to find one”
“I don’t know where this peaks at this point I mean this is starting to defy the models even the aggressive ones in terms of how bad things could get…I don’t know if viewers have noticed but we hardly ever present those worst case models what we are presenting to you is sort of the middle of the road sort of model they could be better if we actually started to employ mask mandates and talk about those five locations restaurants, bars, cafés, hotels, houses of worship for example or it could be a lot worse as well and right now I’m not sure where we’re headed, but it’s very disheartening to hear that they’re still having this party at the White House, not just because of the White House but because then I get 100 emails from people saying hey how bad is it really? having a bunch of relatives over for the holidays will be OK right? That’s what I get all the time and I have to be the guy who says no it’s not and I hate to be the guy that says that, I enjoy a great holiday party as much as the next guy but this is not the year to do that.”
Dr. Michael Osterholm, leading epidemiologist, December 3, 2020:
“Now the actual percentage of deaths as a number of people hospitalized is going to start going up because we can’t provide the same quality of care so you’ve got that factor at the same time you’ve also got the surging number of cases overall and that’s up to us that’s on us you know. We have a lot of power over this virus if we just stop swapping air with our friends, colleagues, and unknowns and if we don’t do that we’ll see the case numbers go up while the quality of medical care will actually go down because of the inability to provide adequately trained healthcare workers that’s the perfect storm and at that point I don’t know what this number could look like. It could obviously grow substantially.”
Dr. Robert Redfield, CDC Director, December 2, 2020:
“December, January, and February are gonna be rough times. I actually believe they’re gonna be the most difficult time in the public health history of this nation, largely because of the stress that it’s gonna put on our health care system.”
It’s been almost six weeks since I’ve written an update, and the reason is I haven’t known how to approach the disaster we’re in, or to really add to what’s on the news. I have never been so proud of medical science or so ashamed of my country.
Yes, it’s been a rolling disaster since March but now it’s a quickly swelling disaster and we have failed in every possible way to do the simplest things we’ve been advised to do all along. They didn’t originate with me of course but as those of you who studied “Disease and Human Behavior” with me last spring, I have been issuing warnings about the new coronavirus since January. I have said the same things over and over again, along with others who know much more than I do about this, and all advice has been ignored.
Why repeat it yet again? Well, if a fraction of people who hear the message heed it, that is a few cases prevented and a few lives saved.
If you were in that class, you saw a version of this graph before. It was an old-fashioned looking but perfectly respectable summary of the three waves of mortality in the flu pandemic of 1918-1919, which we studied. What I’ve done here is not an exact comparison, at all. These are mortality rates of major cities around the world. I’m superimposing points and projected points in the U.S. epidemic, which as you know I believe is most accurately drawn from hospitalizations, which you can see in the second chart. What is similar is that the 1918 pandemic started with a very serious wave, or two waves depending how you look at it, followed by the real killer wave, the worldwide tsunami. In the second chart you can see how our hospitalizations nationwide came in two waves, in different parts of the country.
The second chart ends with an exponential rise that has swept past the peaks in the first two waves and is going straight up. (The chart, shown on CNN December 4th, comes from The Covid Tracking Project and is almost identical to the chart shown on the same day in the machine-learning-based model of models that integrates many sources.)
As you know if you’ve read these updates before, I like to present good news and bad news. One part of the problem right now is that the bad news is worse than ever. How do I word things when I’ve given so many warnings before? It’s not that I’ve “cried wolf”—quite the opposite, every warning I’ve issued has tragically proved true.
No, it’s that as a writer I can’t figure out how progress from bad to terrible to horrible to disastrous to catastrophic without sounding like a repetitive jerk. And how am I supposed to find words to say that the next two months will be by far the worst we have had? And that the reason will be the same as it has been all along, or at least since we went from bad to worse back in March: Not the virus, but behavior—which viruses don’t have—human behavior.
Okay, nothing new. Yes, denial has gotten worse. Heroic nurses have described people dying of COVID-19 whose last words were that COVID-19 is a hoax. Trump rallies were held throughout the summer and early fall with near-zero precautions and each one was followed by a sharp spike in cases, roughly a doubling, in the communities where they were held, with hospitalizations and deaths close behind. Failure to follow guidelines caused predictable spikes after the Memorial Day weekend, the July Fourth weekend, the Labor Day weekend, and Halloween.
Oh, did I leave out Thanksgiving? No. We don’t have the data yet. It will come soon, and it will add a big surge of cases to what is already—let’s see, are we at catastrophic yet, or only disastrous? Hmm.
I know, we’re not the only ones. Canada had its Thanksgiving on October 12th, and since Canadians also didn’t follow guidelines, they are in their Thanksgiving surge now. But they never got, and will never get, to the levels we have been brought to by American Exceptionalism. We are the worst in the world. Japan is worried right now, but they have had fewer cases in the whole pandemic than we had yesterday!
What about the good news? I’ll get to it soon, but first I have to explain why good news is bad news. The good news is mainly about vaccines, and in my opinion they are going to be wonderful. Some of you have asked me what I think of them, and my answer is that collectively they represent one of the greatest achievements in the history of science. So how can they be bad news?
They can be bad news if they add to the denial of the pandemic—if they make people think it’s basically over, right when we’re starting the worst months of it—months during which the vaccine will do little or nothing to stop it. If you are reading this, it is overwhelmingly likely that you will not be able to get a vaccine until April, May, or later.
Depending on the models, we are talking about adding between two and three hundred thousand American deaths before that time, perhaps as much as doubling the total we have today. And that doesn’t take into account an unknown but undoubtedly large minority who will refuse the vaccines, or the potential for halting vaccinations in the unlikely event of a vaccine safety disaster. By the way, if any of the three vaccines I describe below were offered to me today, I would take it.
The Good News
On November 9th the Pfizer-BioNTech collaboration on an mRNA vaccine announced completion of their Phase III trials and reported an astounding 95 percent efficacy. The FDA will make a decision on December 10th about approving it, and if they say yes, it will be deployed to the highest-priority populations starting December 15th. (An mRNA vaccine consists of messenger RNA injected with the hope that it will enter cells that read the message, assembling a spike protein of the virus, which provokes your specific immune response.) This vaccine is already approved for use in the UK.
On November 16th Moderna announced that its vaccine (also mRNA) completed Phase III trials with an efficacy of 94.5 percent. The FDA will decide on December 17th whether to approve it, and if the answer is yes it will start shipping on December 22nd.
On November 23rd, the Astrazeneca-Oxford University collaboration completed Phase III trials and announced that its vaccine had on average 70 percent efficacy, easily crossing the threshold for FDA approval (50 percent) despite falling short of the two prior announcements. However, they made a mistake in one arm of their study and only gave half the usual first dose, giving a full dose for the second injection. This arm of the study had an efficacy of 90 percent. More important, their vaccine, unlike the first two, can be stored for 30 days at ordinary refrigerator temperatures. (Their vaccine uses an adenovirus vector genetically engineered to carry the message for a coronavirus spike protein and to be unable to reproduce itself; one possible explanation for the happy dosage mistake is that some people develop immunity to the adenovirus and therefore the booster shot doesn’t work as well—unless your first shot was a half-dose. Needless to say, this is under study.)
The Bad News
Both of the marvelously efficacious mRNA vaccines have to be stored at ultra-low temperatures—the Pfizer at -70°C, the Moderna at -20—until almost ready to go into arms. Now I took a canister of liquid nitrogen (-195) with me to the Kalahari Desert to store blood samples for a study, so the temperatures themselves didn’t faze me. But I had a small number of samples and we need to store 700 million vaccine doses just to cover the US. Nothing remotely resembling the network of special freezers we’ll need exists in our country today.
Aside from the thousands of freezers, an unprecedented distribution system will have to be created almost from scratch. I heard someone from Pfizer say that 20 freezer trucks are ready now to carry the vaccine where it’s needed, but that the eventual number of truckloads would be 40,000. The vaccines have to be shipped in perfect condition, and there has to be someone at the end of each journey qualified to inject it safely.
Remember how many times we heard President Trump say that anyone who wants a COVID-19 test can get one? It wasn’t true then and it isn’t true now, in fact testing capacity is declining when it should be many times what it is today. We will have a new president, one who takes science seriously, but science can only go so far against the formidable engineering, social, and political obstacles (much authority will devolve to the states) to doubly vaccinating 350 million Americans. You have to get the first dose, then come back three or four weeks later for the second, then wait a week for your immune system to really protect you. Varying estimates say 100 million Americans will be vaccinated by anywhere from February to July.
Many, many Americans will refuse to be vaccinated, and it is uncertain whether we will ever have enough vaccine acceptance to achieve herd immunity.
Meanwhile, today is a day of milestones. There were 2,879 deaths yesterday, the highest number ever, expected to reach 3,000 a day soon. More than 100,000 people are currently hospitalized with COVID-19, and hospitals throughout the country are nearing full capacity. It isn’t the number of ICU beds or even any beds. It’s the heroes who stand next to them.
Remember when front-line health care workers left Georgia and other safe places for New York, and then later when New Yorkers returned the favor? Nobody is going to leave anywhere for anywhere because every state will need them—and many more like them—right where they are. Death rates in those hospitals will go up as they are overwhelmed.
Those of you who are pre-med or pre-nursing, remember what you see over the next two months, because it will be catastrophic, and this won’t be your last pandemic. Watch the doctors and nurses and respiratory therapists despairing, even crying every day until they collapse from exhaustion or get the virus themselves, knowing all along that this didn’t have to happen.
Because guess what: We have had since Day 1 measures as effective as many vaccines. Masking. Social distancing. Handwashing. These could have prevented most of the 277,000 deaths we’ve had so far, the untold suffering of the families of those people, and the many, many thousands who thought they had easy cases but will end up paying a physical price throughout their lives.
The same measures can save scores of thousands of lives not lost yet but standing in line for their own coffins as they go to bars, hold parties, and “celebrate” the holidays. This will be the most tragic holiday season in all of American history.
I have never been so proud of medical science or so ashamed of my country.
Mask. Social distance. Wash your hands. This is the vaccine you have had all along, and its efficacy is very very high.
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 TimesCoronavirus Resource Center (NYT). For uncannily accurate warnings, follow @Laurie_Garrett on Twitter. With thanks to Prof. Craig Hadley, I also strongly recommend this COVID-19 Forecast Hub, which aggregates the data from dozens of mathematical models, and this integrative model based on machine learning, which has outperformed most others in its projections.
“We are not anywhere near done with this and I think we have more days ahead of us than we have behind us.”
Ashish Jha, MD, Harvard School of Public Health, August 28
“The problem here is the credibility of the FDA is crumbling before our eyes. This is an agency that so many of us in the scientific world have looked up to, trusted it, we know that they have these really rigorous scientific protocols, but that’s all changed this year.”
Seema Yasmin, MD, Stanford University, September 2
“Obviously there are places around the world that have been able to control this. What I’m starting to feel is the existential threat is the human behavior. I’m discouraged and frustrated… Other countries are essentially vaccinated right now, not because they have a vaccine, but because they did these things, they are back to normal. They reduced their death rates into the dozens or hundreds, not the hundreds of thousands.”
Sanjay Gupta, MD, Emory University, September 4
You remember what TETRIS is, right?
TEsting. Contact TRacing. ISolation.
Those are the “these things” Dr. Gupta is referring to above, along with mask wearing and social distancing, that have enabled other advanced countries with large populations to have hundreds of deaths from COVID-19, while we have hundreds of thousands of deaths.
Many other countries have got this under control, and they are immediately using TETRIS to bring any new breakouts under control. Per capita hospitalizations and deaths are a tiny fraction of what they are here now, and that gap will only widen as they prevent and control their second wave—which we won’t have because never controlled the first wave, only smushed it down and smeared it, and that only a little. Our second wave will come on top of an enduring first wave.
Cases per week have gone steadily down in the U.S. for at least a month, and that is good news if real. As you know I was skeptical of case rates when they were going up because politicians were saying daily that the rise was only because of more testing. Now when we know testing is going down, because it was badmouthed by politicians and the CDC recommended doing less of it. You don’t hear politicians saying one reason for the decline in case rates is less testing. Deaths, being a lagging indicator, have gone down only slightly. Also, the southern states are doing somewhat better while the midwest is having its big first wave, and the northeast is rising but from very low levels.
Vaccine development is proceeding around the world. Phase III testing is going slowly and will be difficult to interpret because of marked underrecruitment of minority people, who are way overrepresented among the cases, hospitalizations, and illnesses.
Finally, the sum total of well-designed research has shown that steroid treatment (like dexamethasone) reduces deaths in patients severely ill with the virus. Death rate for 1,700 people across 12 countries was 32% with steroid treatment and 40% with placebo. That amounts to saving 1 in 5 very sick COVID-19 patients who would otherwise have died.
There is a lot of talk about, and even some progress in, cheap rapid testing, but the deployment of these tests has been slow due to manufacturing bottlenecks and general badmouthing of testing by politicians. Nevertheless as these tests become more available, we should make progress against our U.S. pandemic (near the world’s worst), but that would require a revival of TETRIS and a modification of behavior based on test results.
The CDC has issued a mandate against evictions until January 1, as a public health measure. But the CDC does not have a police department and it will leave enforcement to local authorities. There are many exceptions that would still allow people to be evicted, and after January 1 all those protected will owe all back rent. Perhaps there will be another Congressional stimulus package by then to soften that blow.
The latest models from IHME and Johns Hopkins agree on where we are now, and the graph shows three projections as to where we are going, depending on one of threee assumptions. The most likely scenario (dark blue line) shows where we will be on January 1 if we keep on doing what we’re doing: 300,000 deaths total, and adding about 3,000 deaths a day. If we had universal mask use, that total would be around 230,000 and the daily deaths would stay under a thousand for a while in the fall before doubling or tripling again with the cold weather (more time indoors) and the flu season giving many both viruses. If we continue to have easing of social distancing mandates, we are expected to have 600,000 total deaths and almost 12,000 cases a day by years end. You will hear some politicians say that these projections have been wrong throughout in overestimating the future damage. This is a lie. Except for the very beginning when nobody knew anything, the IHME reference scenario has been too optimistic. Testing is going down or staying at low levels in most states, contact tracing is beyond inadequate, and isolation is accordingly moot.
We’ve learned that infected people are most likely to infect others during the first week or ten days of significant viral load, which is why superspreader events attended by healthy people are the major U.S. source of viral spread right now. These are most likely to be indoor, largely unmasked, crowded events. Viruses linger in the air for hours in many such spaces. These superspreader events have included Mardi Gras, church services in Arkansas and elsewhere, funerals in Georgia and Ohio, and a Boston meeting of executives at Biogen, a large molecular technology company, among many others. The Sturgis motorcycle rally in South Dakota in early August has resulted in at least 70 cases so far (it’s difficult of course to track folks from an event like that). These are in addition to the well known virus petri dishes known as cruise ships, prisons, nursing homes, meatpacking plants, choir practices, and now colleges and universities. Luck matters, since one person can be a key superspreader, and neither you nor they know which one in the crowd they may be.
In the past month or two there has been a wave of oh-so-careful openings of colleges and universities, and now there is a national wave of even faster closings. (See my update predicting this and explaining why it was inevitable.) Despite evidence of universities acting to cover up coronavirus cases, we know that there have been outbreaks at many, and they are rapidly spreading the virus to the local communities. As of September 3, “More than 100 colleges have reported at least 100 cases over the course of the pandemic, including dozens that have seen spikes in recent weeks as dorms have reopened and classes have started. Many of the metro areas with the most cases per capita in recent days — including Auburn, Ala.; Ames, Iowa; and Statesboro, Ga. — have hundreds of cases at universities.” Thousands upon thousands of students are now being sent home, where they will bring virus to their communities. (See my update on “Bye-Bye Grannie.”)
“Sloppy coronavirus immunity” is a term that has been used to describe the handful of documented cases of people getting the virus twice (it also applies to other coronaviruses, like the common cold). At least one of the reinfected patients caught a different strain, so as you know viral evolution will play a role. It should also apply to the question of how effective any immunity from a future vaccine will be, and how long it will last. Vaccine refusal in the U.S. has been at high levels for decades, and this vaccine will be no exception, unless the rushing of it and the prior erosion of public trust swells the ranks of anti-vaxxers to unprecedented levels (especially if, as is likely, it requires two shots). Imagine a COVID-19 vaccine that gives us about the same level of protection as the seasonal flu vaccine (~50%), lasts about as long (<1 year), and is accepted by 50% of the population. So we’d have seasonal protection for a quarter of the population, have to repeat the shots every year, and we’d still have to have over a hundred million more cases and hundreds of thousands more deaths to get to herd immunity.
Harold Varmus, a Nobel Laureate and former National Institutes of Health head, and Rajiv Shah, president of the Rockefeller Foundation, published an article on August 31 called, “It Has Come to This: Ignore the CDC.” Their statement is based on the latest of a series of false, incompetent, and frankly craven pronouncements of “advice” issued or changed by the political appointee at the top of that organization, obviously in response to pressure from those who appointed him, non-doctors and non-scientists all. When Stanford’s Dr. Seema Yasmin said (above), “the credibility of the FDA is crumbling before our eyes,” she was likewise referring to the latest of multiple instances of knuckling under by the political appointee directing that organization. This would be (together with the CDC) following orders from non-doctors and non-scientists in the White House to order states to prepare for widespread distribution of a vaccine by November 1 or sooner. These non-experts say that it is purely coincidental that this is two days before our national election on November 3. The vaccine will be deployed with great fanfare on the basis of far-from-complete Phase III trials, it will put minority people at greatest risk, and there will no time to find out what damage is done by this half-baked but highly touted vaccine before people vote.
The principal advisor on the pandemic in the White House is now Scott Atlas, MD, a neuroradiologist and health policy wonk at Stanford’s right-wing Hoover Institution. Dr. Atlas has no qualifications in infectious disease, epidemiology, or virology, but he is happy to parrot the long-standing White House views playing down the virus. He has denied reports by several reliable sources that he argues openly in Task Force meetings with Dr. Fauci and Dr. Birx (the real experts) and he has more than hinted that he favors “herd immunity” as a strategy, which would entail far more American deaths than the huge numbers projected above. Like an overpopulated herd of deer, we would be culled.
I must say it surprised me to see the expression on Dr. Gupta’s face and hear him say he is “discouraged and frustrated.” I am too, and that’s why it’s been so long since my last update. Frankly, I expected more from him. He’s one of my greatest heros—a top-flight brain surgeon and medical school professor, the most inspired and gifted medical broadcast journalist who ever lived, and, I’m proud to say, our colleague at Emory.
My expectations for him were totally unfair. Unlike me, he has rubbed his nose in this stinking situation all day every day for eight months. Also unlike me, he probably has not had a dark view of human nature lasting a lifetime, based on a different branch of science—behavioral biology. So yes, he has a right to see the “existential threat” in “human behavior,” and he has more right than me to feel discouraged and frustrated, having worked his heart out 24/7 to prevent things from getting anywhere near this bad. Which it wouldn’t have if people had listened to him. It will still save many lives if people start listening now.
Mardi Gras: outbreaks. Memorial Day Weekend: big outbreaks. July 4th weekend: ditto.
So we’re in the Labor Day Weekend now.
What do I think is going to happen?
What do you think is going to happen?
PPS: 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 TimesCoronavirus Resource Center (NYT). For uncannily accurate warnings, follow @Laurie_Garrett on Twitter.
“Obviously if you do more testing you’re gonna see more cases but the increases that we’re seeing are real increasing in cases, as also reflected by increasing in hospitalization and increasing in deaths.”
Dr. Anthony Fauci, Congressional Hearing, July 31
“It’s very frustrating as an epidemiologist to see these cases at numbers continuing to rise without a national strategy, without adequate testing, without contact tracing as we need it—all of the things we’ve been talking about for months and months and these numbers are going to continue to go up until we do have these things in place.”
Dr. Ann Remoin, UCLA, August 2
“What we are seeing today is different from March and April. It’s extraordinarily widespread.”
Rep. Jamie Raskin, D-Maryland, Congressional Hearing, July 31
At this writing, a tropical storm is progressing from the Caribbean up the east coast of Florida and will proceed north from there, affecting to some extent even the northeastern U.S. This is below hurricane status but still has hurricane-speed winds and has badly flooded some Caribbean islands. Storm surges will follow after the wind and rain die down. There have been drownings. They will be very sad and perhaps to some extent avoidable.
But as you know if you’ve been following my updates, the drownings in the title above are metaphoric—the deaths are all too real, but they do not involve storm waters. Americans are drowning and dying in the flash floods of viruses, being killed partly by the accumulation of fluid in their lungs as part of the crash of lung and heart function under viral attack. And the numbers of dead are hundreds to thousands of times higher than will be caused storm drownings.
So: our metaphor likens the features of a storm in weather to the features of the resurgent viral pandemic. You know I am not impressed by a surge in cases alone, if only because our mendacious political leaders falsely claim that more testing leads to more cases. For the record, once again: it is a lie that we do more testing than any other country, and it is a lie that 99 percent of the cases detected are benign. There are simple ways to use case records to refute these lies, such as rising or falling ratios of positive tests to total tests, but I decided not to get into an argument with unscrupulous men who have the most powerful megaphones in the world. I decided to wait for a measure that has no relation at all to the amount of testing: hospitalizations.
I suggested we think of the case surges as lightning and the hospitalizations following as thunder. As we began to see a month ago, the lightning strikes across the southern half of the nation were followed a few weeks later by rolling thunder. Hospitalizations surged, hospitals overflowed, health care workers were overwhelmed, and in general the southern states that had been feeling superior to New York followed exactly in New York’s path, in a way that was as predictable as it was completely unnecessary, since New York had blazed the path—both on the way up and on the way down.
I said at that time that I was not sure that deaths would follow hospitalizations, because the average age of victims was younger, and the treatments for advanced cases were better. I said that if the cases were lightning and the hospitalizations were thunder, the next stage could, but hopefully would not be, flash floods (overwhelmed lungs and hearts) and drownings (COVID-19 deaths).
This hope was dashed, and the surge in deaths is here. That is why Dr. Fauci told Congress on Thursday that the increase in cases is real, “as also reflected by increasing in hospitalization and increasing in deaths,” contradicting the lies of his boss and the leaders of several southern states.
The huge surge in America’s cases in June, which did not occur in any “advanced” country (or even in countries like Georgia, Rwanda, and Uruguay) was not a second wave, it was a devastating extension of the first wave. All advanced countries and some developing ones completed their first wave by reducing cases to tens or hundreds per day. The lowest we ever got was 20,000 a day, and now we have 67,000, more than double the mid-April maximum of around 31,000. Every day.
These cases are not caused by increased testing, and the U.S. does not have a good testing program. Our per capita testing is behind a number of other countries, who are testing more and finding fewer cases. Also, we are doing the wrong kind of testing, taking an average of four days and often much longer to get results. These results are useless for contact tracing. As Bill Gates said months ago, what are you supposed to do, send apology notes to the people you infected before you knew your own result?
But then again, we do not have serious contact tracing, certainly not where the epidemic is worst. I and many others said months ago we would need an army of contact tracers, and we barely have any. It may be that with the numbers of cases we have now (at least 4.5 million), contact tracing is no longer a possible strategy for controlling the disease. Imagine contacting all the 67,000 new cases each day, finding all their contacts, testing them, and isolating those who (a week later) turn up positive, and then contacting their contacts, and—you get the idea.
Nationally, hospitalizations are clearly up again, the “rolling thunder” I wrote about on July 9th. This, as I showed you, was especially true in 20 states, and now it is true in more. Even averaging in the big declines in the northeast, weekly hospitalizations per hundred thousand were around 10 in mid-April, 4 in mid-June, and back up to 7 in mid-July. Multiply each of those numbers by 3,300 to get the approximate totals. Further increases are likely.
Daily deaths in the U.S., the best indicator of the progression of the pandemic, peaked in mid-April at around 2,300. They bottomed in late June at around 550. As of today they have been over 1,000 for the last few days. The increase in July was steady, large, and real. Bear in mind that these national figures average in an ongoing decline in deaths in the northeastern states, so much of the rest of the country is at an all-time high. Deaths are a lagging indicator, so they could go higher. Black, Latinx, and Native American people are affected much worse than whites. Prison inmates, nursing home residents, and workers forced into dangerous conditions in meat packing and other workplaces are most at risk.
All the above statistics were coordinated, analyzed and reported by the Centers for Disease Control, a collection of 1700 scientists ideally suited to this task. It was taken away from them two weeks ago and placed in the hands of the much less experienced and much more political Department of Health and Human Services. The only reason I can see for this change is that the people in power in Washington were not satisfied with their efforts to muzzle the CDC and distort its work, so they just admitted what they were doing and made the collation of statistics purely political.
The first vaccine to enter Phase 3 clinical trials is the one being jointly developed by the biotech company Moderna and the National Institutes of Health. This is a real-world trial in which 15,000 people will get vaccine and the same number placebo, which gives it sufficient power to see whether the vaccine protects people from community spread, and whether it is safe. It allows representation of age, sex, and minority populations. It is an mRNA vaccine of a type not approved for human use before. (For more on different vaccine types, see my update of June 20th.)
The University of Oxford/AstraZeneca vaccine, based on a chimpanzee adenovirus carrying coronavirus genetic information, is expected to start Phase 3 in August, and the Pfizer/BioNTech one, like Moderna’s an mRNA vaccine, in September. This website monitors vaccine progress. “Experts estimate that a fast-tracked vaccine development process could speed a successful candidate to market in approximately 12-18 months – if the process goes smoothly,” the website says. I think that means 12-18 months from when they started earlier this year. Roughly 150 vaccine projects are under way worldwide, the above three being among the five prioritized in Operation Warp Speed (stupidly named because it will increase anti-vaxxer rejection).
Dr. Anthony Fauci, the nation’s top infectious disease expert, did an amazing job Thursday testifying to Congress for almost four hours (with a little, actually very little help from two other officials, and a lot of speechifying from Representatives of both parties) before the House Select Subcommittee on the Coronavirus Crisis. He managed to thread the needle of telling the truth without saying anything that might get him fired, something no other government scientist or physician can do. But if you want to hear the real Dr. Fauci in a real conversation with other scientists, being himself and saying what he thinks and knows without pausing for many seconds before carefully answering, listen to the July 17th episode of This Week in Virology (TwiV-641).
Treatments are also being sought throughout the world. The ones working now are: Remdesivir, an antiviral developed for Ebola; dexamethasone, a tried and true general-purpose anti-inflammatory; and convalescent plasma (probably). On the near horizon are monoclonal antibodies derived from convalescent plasma, other anti-virals, and combinations of anti-virals. Remember that a triple antiviral therapy changed HIV/AIDS from a deadly to a chronic disease, and plays a vital role in limiting spread. (Contrary to my own hopes, since I safely took it for malaria prevention, hydroxychloroquine doesn’t work. Also, ingesting or injecting bleach or other cleaning products will kill you.)
The new recommendation of face shields or goggles along with mask wearing, social distancing, handwashing, and reversal of some of the most ill-advised state openings (bars, indoor rallies, packed houses of worship, etc.) all show promise of bending the curve downward again—cases first, then hospitalizations, then deaths—across the southern United States. Midwestern and North Central states have yet to be walloped by the two-by-four of COVID-19, and they are not learning from watching the suffering of others, so they are clearly next.
The most exciting new development that I have heard about recently is a revolution in testing proposed by Michael Mina, a virologist and clinical pathologist at the Harvard School of Public Health. Rapid, less accurate testing is the key. (Abbott’s ID Now test, which I told you about on May 12th, is only one example.) The gold standard, PCR, is very accurate, but if it takes a week or more to analyze it is almost useless. Strips of cardboard mass-printed with molecules that detect virus in swab samples have not been widely deployed yet because they are not considered accurate enough. However: They are accurate enough if used when a person has enough virus to be infectious. At $1 a day, they can be used often by everyone, with results in minutes.
I want to say something about school and college openings, which are starting now. This is a mass experiment, with the lives of students, teachers, parents, and grandparents being put at risk, with conflicting guidelines about how to do it, and with low likelihood of compliance with guidelines anyway.
Major League Baseball is failing at safe reopening, even with their vast wealth and tight organization. More than 6,600 cases have been identified on college campuses that have mostly not yet opened for the fall semester. Young children (usually) do not become very sick from this virus, but they are quite effective transmitters of it to each other and to adults. Middle and high school kids are more effective spreaders. What has happened at summer camps and in the first school openings is not reassuring.
Rebekah Jones, a scientist fired by the governor of Florida for refusing to fudge the state’s statistics the way he wanted her to, said on July 8th, “If schools are opening next month, then we’re on a third wave of this first wave of catastrophe.”
Black leaders were in the news this week. Former President Barack Obama spoke brilliantly at the funeral of civil rights giant and “Conscience of Congress” John Lewis, whose last live appearance was at a Black Lives Matter protest. He died of pancreatic cancer. Rep. James Clyburn, Democrat of South Carolina and House Majority Whip, chaired the hearing of the Subcommittee on the Coronavirus Crisis, where he and Dr. Fauci told the truth. Herman Cain, a leading black Republican and former presidential candidate, died of COVID-19, which he probably caught while proudly attending a crowded Trump rally in Tulsa, Oklahoma, on June 20th.
Stay safe, you know how.
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).
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.
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.
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.
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.
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.
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.
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.
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?
Remdesivir, an antiviral originally developed for Ebola, may or may not have significant benefits, but it’s approved for compassionate use.
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.
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.
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.
“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
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
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.
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.
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.
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.
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.)
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.”
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.
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.”
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.
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.
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!
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.