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