“Please hear me clearly: at this level of cases with variants spreading, we stand to completely lose the hard-earned ground we have gained. Now is not the time to relax.” Dr. Rochelle Walensky, CDC Director, CNN, March 2, 2021

      “Dr. Walensky is right, and the reason she’s right is while things are way better than they were about a month and a half ago the level of infection in the country right now is the same as at the peak of the summer surge, so we’re not in great shape. And we have variants, and variants are starting to take over, and if they become dominant and we relax restrictions I think we can absolutely see a huge spike that will really lead to a lot more suffering… We have a high level of infection, we’ve got states easing restrictions, which they should not be doing at this moment, and we’ve got the variants that are circulating that are a lot more infectious. Put all that together and I can’t help but worry about where we’re going to be for the next couple months.” Dr. Ashish Jha, epidemiologist, Dean of the School of Public Health, Brown University, CNN, March 2, 2021

      “I have to congratulate this administration for what they have done…with the vaccines… But we also have to tell the story of what is still ahead of us. And at 2.9 to 3 million doses of vaccine a day, over the next 6 to 14 weeks, when this surge is likely to happen, is not really likely to take care of the problem at all… We still have a lot of high-risk people out there, and when this surge comes, they’re going to be highly vulnerable… The other thing we see right now is that every governor wants to open schools… and as a grandfather of five children I get it. But the problem is that if you look at Europe, the challenge we’re seeing right now is a lot of transmission in schools with this new variant… So we’re going to have some tough days ahead in the older population and the younger population with this new variant virus.” Dr. Michael Osterholm, Director, Center for Infectious Disease Research and Policy, University of Minnesota, on Meet the Press, March 7, 2021

      “The pandemic still remains a very serious situation.” Dr. Rochelle Walensky, Monday, March 8, 2021, Politico.

Dear Students,

The US reportedly delivered 2.9 million vaccines into arms yesterday, far ahead of what Joe Biden initially promised and almost at the 3 million per day minimum that experts have recommended. However, the UK variant (B.1.1.1) is rapidly becoming the fastest spreading strain in the US, destined to account for at least 50 percent of new cases in Americans in the next few weeks. In Britain and Europe, this has been the threshold for new and very serious burdens on health care systems.

Right now, we Americans are feeling good. The holiday surge is over, and cases, hospitalizations, and deaths have come down an astounding 70 percent since their winter peaks. However, this is primarily the result of the mess we made by our behavior on the holidays. When we’ve been banging our head against the wall harder and harder, there is only so much credit we can take for feeling better when we stop.

But now cases and hospitalizations are plateauing at levels higher than the summer peak when the virus swept the south and west and the national surges scared the living daylights out of us. We are stabilizing at that way-high level—a convenient platform for the virus to take off in a new surge—and, right on cue, we are starting to bang our heads against the wall again, with premature openings and ending mask mandates in some states and lazy complacency in many others.

These foolhardy blunders can easily take us from the high plateau we are on into a fourth wave that will once again cause scores of thousands of needless deaths.

As the photo suggests, we are in an arms race between evolutionary changes in the spike protein—the virus’s arm for prying open our cells—and the human arms getting jabbed in the vaccination campaign. The virus is flooring its Darwinian gas pedal with new variants of concern (VoCs) in South Africa and Brazil, yes, but also New York and Oregon.

Our university is among those that have seen surges in student cases—in Emory’s case an unprecedented outbreak after a year of safe performance—due to Superbowl parties, fraternity and sorority pledging, and other activities the virus loves. So many opportunities to evolve! Now spring break is coming for many colleges, and—well, here we go again.

Good news

1. The Johnson & Johnson single-dose vaccine was given its expected Emergency Use Authorization, putting it on a par legally with the mRNA vaccines. The J&J is an adenovirus carrying viral DNA and is stable for weeks at refrigerator temperatures, a tremendous boon for rollout—as is the fact that you only need one jab. It is substantially less effective than the mRNAs at preventing cases (72 vs. ~95 percent), but, like them, close to 100 percent effective at preventing severe cases and death. Initial rollout has been slow but will ramp up fast.
2. Not vaccines, but other preventive measures (masks, social distancing, handwashing), along with the pass-through of the holiday surge, have brought cases and hospitalizations down more than 70 percent. Nursing homes, where the most vulnerable have lived and died of COVID all along, have declined even more—in their case largely due to priority vaccinations.
3. Total vaccinations, mainly with mRNA vaccines, have been deployed more and more effectively, with 450 vaccination centers and thousands of volunteers across the country. We are almost at 3 million a day, and if we can keep that up or, preferably, increase it, we have a chance of flattening the curve of the fourth wave. If we keep up masking and other preventive measures, we have a chance to avoid it altogether and by the end of the year bend the current high plateau way down—if the vaccines provide long-term immunity and the new variants can’t evade them.
4. Herd immunity through widespread vaccination—up to 85 percent is needed—can be achieved and life can return to something close to normal, with tremendous positive implications for the treatment of non-COVID illnesses, education, jobs, and mental health. Healing from this dreadful national trauma will be under way.
5. Dr. Peter Hotez has lauded the vaccine rollout in India as having the potential to save the world from the virus—even while reminding us that the US will never be safe from it until it is controlled (not necessarily eliminated) worldwide.
6. The CDC finally came out with guidelines for people who have been fully vaccinated. They can be indoors with small numbers of fully vaccinated people without masks, or with well-known low-risk people from one other household. They should not go to gatherings, eat indoors at restaurants, and the like.

Bad News

1. Variants of Concern now include the UK/B.1.1.7 (mutation N501Y), which spreads 50 percent faster and is sweeping the US but is susceptible to existing vaccines; the South Africa/B.1.351(N501Y+K417N+E484K), which spreads faster and is less susceptible to vaccines; the Brazil/P.1 (N501Y+K417T+E484K), same; the new New York variant/B.1.526 (S477N+E484K), same; and the Oregon variant/B.1.1.7 (N501Y+E484K), same.
2. Lets put this bad news in English. For each of these codes, the number in the middle represents the consecutuve position of the relevant mutation on the viral spike protein. The before and after capital letters represent the one-letter code for amino acids. Thus N501Y means the amino acid in position 501 has changed from arginine to tyrosine due to an underlying mutation (replication error) in the RNA triplet that specifies 501. Since 501 is in the binding domain of the spike protein, the mutation can and does make it easier for the virus to bind with and enter cells—thus increased transmissibility.
3. The two mutations at position 417 (K→N →or K→T) as well as the change at 477 (S→N) also affect the spike binding domain. All can enhance transmissibility and all are popping up independently in different places. Also, these Variants of Concern involve amino acid substitutions that change the shape of the folded spike protein at least a little, and are therefore able to enter our cells or resist our antibodies more easily.
4. Most concerning to scientists appears to be the E484K mutant, (glutamic acid → lysine at position 484). This mutant, present in 5 of the 6 new strains named above, makes it easier for the virus to evade our antibodies, thus undermining both natural and vaccinated immunity. Its nickname is the “Eek” mutation, and yes, it is that scary.
5. Mutations occur constantly, and some of them are adaptive, so the virus evolves. To paraphrase an old song, it’s a mighty restless bug in a mighty restless land. Scientists have a huge deal of trouble figuring out which of the many mutations are silent, and which, like the ones above, matter for humans. On top of that, the mutations operate synergistically, for better or worse, when they appear in the same strain.
6. Since we still do a woefully low amount of viral sequencing, and overall testing and tracing are low and/or declining, we are fighting the new variants in the dark without a flashlight. Our friends in vaccine manufacture and development start scrambling to invent booster shots for new variants as soon as they appear, but it’s a race against time, vaccine development vs. viral evolution.
7. There have been disappointments on the clinical side this past week. Convalescent plasma in a metaanalysis was shown to have no benefit on any standard outcome measures. Fortunately, it is being replaced with monoclonal antibodies that work better if introduced early in the illness. Dexamethasone (a steroid) increases mortality if given early in the illness but remains confirmed as effective in advanced stages. The IL-6 inhibitor tocilicumab helps if given after dexamesthasone but is harmful if given without dexamethasone. Something similar is true of other IL-6 inhibitors.
8. Standard views about children being less likely to be infected than adults may be due to testing bias, so they may be equally vulnerable. It still seems true that they don’t get as sick, but a new study finds that as high as 13 percent of children who are infected will suffer from long COVID. Dr. Daniel Griffin, who gives the clinical updates on the This Week in Virology podcast, calls this “a disaster.” Long COVID goes up by age to peak in the age period 35-49; overall it affects at least one in five people who get infected with COVID-19.

States are opening prematurely. Governor Abbott of Texas, still reeling from accusations that his negligence caused scores of death in the recent snowstorm, has decided to cause thousands more excess deaths from COVID by boldly opening Texas “100 percent.” The governors of Mississippi, Arizona, and other states are doing the same.

This failure of leadership is a step by step repeat of the mistakes that led to last summer’s and then this winter’s surge, needlessly killing hundreds of thousands of Americans, and it will have similar consequences.

Such stupidity in leadership acts synergistically, like the evolving viral mutations, with the stupidity of ordinary Americans. If you have missed it, take a look at the photo on the left. It shows the good citizens of Boise, Idaho, ceremoniously burning masks outside the state Capitol. As with all ceremonies, this one expresses deeply held beliefs, and the adults are passing their beliefs on to their children with the ceremony.

As playwright Arthur Miller said, “The paranoia of stupidity is always the worst, since its fear of destruction by intelligence is reasonable.” These neighbors of ours have bad ideas, which they probably sense cannot hold up in the face of better ones, and since they are attached to their bad ideas, the possible loss of them makes them afraid.

Yet what can we do in the face of such stupidity except continue to meet it with the best intelligence we have? Meanwhile, as always, the stupidity of our fellow citizens, including leaders, puts us all at risk. Eek.

Stay safe. It won’t be too much longer, provided we aren’t stupid enough stretch it out again.

Dr. K

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