–Alright, let’s do this…

–Stateside, similarly to Thanksgiving, the New Year’s Eve pop in new cases has dropped in most states. Nationally, the hospital admissions and census continue to drop. They are still considerably higher than the Great Memorial Day Experiment/Riots peak in the summer, and in fact are only now back to the March-May peak.

That said, an extremely optimistic sign. In specific states to watch, New York may be in the early stages of turning the corner on its winter peak. That is notable because multiple cases of the UK strain have been identified in New York. New York is also testing very intensively right now, so the recent decrease, if sustained is real.

Similarly, in Indiana, CDC surveillance picked up a case of UK strain this past week. Yet, new cases are down and the New Year’s Eve bump did nothing to halt the decline in the hospital admissions rate or census.

Colorado was the first state to identify a patient with UK strain. New Year’s was a slight pop off of what is otherwise straight declining cases in Colorado. Like New York and Indiana, new cases have again resumed their decline.

In fact, on rt.live about 1/3rd of the states are in the green–an Rt < 1.0 consistent with steady declines in new cases.

–There was much consternation after we went to press last week, and through this week, about the explosion of cases in Ireland, where the Rt jumped dramatically. This coincides with the identification of the UK strain there just after Christmas. The UK strain was also identified in France and Japan around the same time. Both France and Japan saw slight increases in the rate of new cases in the following weeks, consistent with the suggestion that this new strain is more contagious. However, both France and Japan are both down off their peaks this week, much like New York, Colorado and Indiana. Indiana and Colorado are in the green on Rt live (although the error bars are above 1.0), and New York is hovering just above 1.0 (with error bars below 1.0). Contrast this with Ireland’s sharply rising cases and estimated Rt of 3 and some change, and Ireland looks more like an outlier instead of a bellweather as far as spread of the UK variant.

Indeed, Ireland may simply finally be getting its big wave, as all of other states and nations mentioned were either already well into the throes of another big wave or just behind it when the new UK variant was identified.

–Thus, the dog that is STILL not barking: You are NOT hearing about large numbers of reinfection with ANY of these newly identified “scary COVID strain of the week” cases.

But we would be if that were happening in any significant numbers.

So while it is true that we do not yet know for sure if they have mutated the spike protein enough to evade the vaccine and current spike protein targeted treatments, these more contagious variants should be spreading through people who already got the vaccine or got over COVID before. At least, they should if they were able to.

So at least for the vaccine, the absence of reinfection reports argues strongly that none of the new variants du jour are getting around the vaccine. Same for natural immunity from those who caught, and recovered from, SARS-CoV-2.

–Yes, the state and nation data we just covered also argues that. If the new variant was both more contagious AND able to evade existing immunity by a radically new spike protein, we would expect several, if not all of those locations where the variant has been identified, to look more like Ireland. A sustained and rapid explosion of new cases. Haven’t seen it yet. We’ll watch for a few more weeks to be sure, but all are looking good right now.

–Ohio State announced the identification of Ohio Strain SARS-CoV-2 yesterday. This has the N501Y mutation in the spike protein that has also been found in the UK variant. However, it has two completely different mutations and appears to have arisen independently. The N501Y seems to be a recurrent emergence around the globe right now. My guess is that this is a popular new mutation for SARS-CoV-2 in places that have had sustained transmission for awhile because 1) it’s easy for the virus to do and 2) is an evolutionary advantage for the strain with it because the virus is struggling to find susceptible hosts–a kick up in contagiousness is keeping it alive. Similar to other new strains with N501Y, the Ohio variant became the dominant strain in Columbus around Christmas and into the first week of January.

In the interests of promoting unity at this fragile time in the nation’s psyche, I will refrain from asking again if anything good ever comes from Columbus.

In case you are wondering, Ohio’s Rt is hovering at 1.02, with error bars below 1.0 right now on Rt.live Similar to much of the rest of the nation, new cases are declining in Ohio this week.

–ANOTHER KEY POINT: There is NO evidence (and we should expected to have heard about some by now) that any of these new variants are causing more severe disease or severe disease more frequently. More contagious (perhaps) but at most only as severe, and possibly even less as again, hospital admissions and census are declining even in many places where these new variants are circulating.

–ANOTHER KEY POINT: SARS-CoV-2 does not have infinite degrees of freedom to mutate the spike protein. It needs the spike protein to invade human cells via the ACE receptor. That receptor has a certain shape, that the spike protein must be able to recognize and grasp. Thus, there are a finite number of ways that SARS-CoV-2 can change its spike protein and still grab the ACE receptor with it. Some of those would require too many changes in its RNA at once and are thus wildly improbable. Others will still bind the ACE receptor, but less strongly, and that virus strain won’t survive. Equally improbable is that the virus changes the spike protein to grab some other receptor by accident instead of ACE, and still be able to effectively invade human cells. As the virus runs into more and more people who have either caught it already (and are now immune) or been vaccinated, there will be a strong pressure on the virus to mutate or die. That is why you are seeing more variant detection (coupled with just doing more sequencing of virus isolates), and many of them clustering on similar patterns of mutations. These are the subset that are both 1) “easy” mutations to occur, 2) still bind the ACE receptor and 3) give the virus some other edge to get around higher and higher levels of population resistance.

This isn’t the virus taking a scary new turn. That turn is possible, yes, but far less likely than not.

Instead, this is soft biological evidence that we are at the beginning of the end, at least from a medical standpoint.

–That is being hastened by wider vaccine adoption. Many states are now rolling out to high risk populations, and you should check with your local health authorities for who is now eligible. I am still experiencing no noticeable side effects. Most if not all of the floor here at work has now had the first shot. The only side effects were varying degrees of shoulder soreness where the vaccine went in. I have heard of one reader who got the second shot already, and had a couple chills, but nothing debilitating.

–Speaking of vaccines and the floor here at work, no update on my antibodies. We’re collecting more than just my sample on the floor, and thus a few samples are catching up.

–In other news, reader questions this week about how infectious the asymptomatic are. Turns out there is a recent publication that addresses this! You can find it here.

The short version is that Singapore, being a small island, followed 628 cases of COVID earlier this fall. Those positives were a mixture of symptomatic and asymptomatic, and they also tested antibodies on them. From those 628 COVID positives, they identified and followed 3,790 close social contacts. Of those 3,790 close contacts, exactly 89 (2%) caught COVID during the follow up from one of those known positives. That fits with the “about 1-2% of the population” incidence per week we calculated back of the envelope off the UFC testing some months ago when asking when we might see sufficient herd immunity.

So of those who have wondered how even close contacts, or family members, can test positive and others never did or seem to, now you have a peer reviewed publication about it! It’s contagious, but simply being a high risk contact does not guarantee you will get exposed to an infectious dose. It just makes it more possible than before.

Of those 89, a little under half got their COVID from among the asymptomatics of the 628 positive index cases. BUT, most of those 628 were asymptomatic cases. So you were 3.85 times more likely to catch COVID from someone with symptoms than someone who did not have symptoms.

Stop the medical presses and make ready the Nobel Prize, I know.

But this does prove that 1) asymptomatic carriers CAN spread COVID but 2) they are not nearly as good at it as symptomatic cases, and 3) close contact exposure to COVID is necessary but sufficient to guarantee you will catch the disease. You might get the gold star for hand washing around the ill, even the asymptomatic ill, and dodge the bullet.

Now, some limitations to this study are that it’s not clear when the asymptomatics were detected in the stage of infection. If they were early, and thus lots of live virus particles may have been present, that may explain why “asymptomatic” carriers were still able to spread COVID. If they were late in the infectious period when it was caught (and it could only have happened via screening, and there are no symptoms to “time” the infection), that may explain why close contacts of these “positive” dodged the proverbial bullet.

Other potential confounding variables are that although they restricted the 3,790 close contacts of the index cases with quarantine, there is no way to know if those who went on to develop SARS-CoV-2 were exposed to another positive not on the study who gave it to them instead of the index case. For example, you might have gotten on this study as a close contact of an asymptomatic positive. But three days ago you were unknowingly close to someone with symptoms. You test positive for COVID on this study and it’s attributed to the asymptomatic case. Meanwhile, your real exposure was that dude with a sniffle he thought was allergies passing you in the grocery store.

But it’s at least some data towards these questions.

–We also mentioned forever and a day ago that IL-6, a signal for the immune system that also tends to go up in aging, was associated with higher risk for severe disease from SARS-CoV-2. Since older people tend to have both higher IL-6 and higher risk of severe COVID, it was not clear how causative IL-6 might be for severe COVID. It’s possible, for example, that measuring IL-6 was merely identifying old people, who, through other co-morbidities, were more at risk for severe COVID. IL-6 inhibitors got a boost this past week when trials in the UK showed a significant reduction in mortality and ICU stay for patients in the ICU with severe COVID. This comes after a failed study in a randomized trial in Italy for the same drugs though, and mixed from a similar trial in France. So Roche is continuing clinical trials for its IL-6 inhibitor in a large international Phase 3 study that is estimated to finish sometime this quarter per Clinicaltrials.gov.

–So a popular question this week has been “what comes next?”

Look, if I was that good at predicting the future, you would be reading headlines about “Doctor Wins $500 Million Dollar Powerball and MegaMillions Drawings on Consecutive Days” then waiting for your invite to party on my new Caribbean island.

I don’t know what comes next, particularly those of you reading this stateside. I can tell you from a medical perspective, CDC already estimates at least 30% of the US has immunity to SARS-CoV-2 now. That’s in the ballpark of our UFC envelope numbers. Anecdotally, I’m not only running into more people who have already had the virus (with a positive test), but more of them are now remarking to me how the majority of the people they know and run into frequently have either been positive or got the vaccine. That is consistent with rising herd immunity. Between the vaccine and the old fashioned way, we do appear to be on pace for the long end of our UFC estimate. That means significant herd immunity by Q2 of this year.

Does that stop the lockdowns? I don’t know. And your local mileage will vary on that. Again, those are political decisions. I see fear mongering that the reports of all these new strains are the “excuse for new restrictive lockdowns” and I roll my eyes. They were in some places like the UK, sure. But other states and nations have not immediately thrown a higher level of restrictions up yet. I can see the new US administration going either way honestly–but much of the US response in terms of lockdown conditions and durations has been state dependent and likely will continue to be. Your extremes will run from California to Florida. And lockdowns may still happen even if the current positive trends in new cases, hospitalizations, treatments and vaccine rollouts continue. Why? If for no other reason than it is tough to come back from the war sometimes. Your local situation will unquestionably vary and in ways I cannot predict.

I will say that historically, pandemics have marked inflection points. We mentioned the dichotomy of outcomes out of the Black Death before. Even the 1918 Spanish Flu saw monarchies swept away, a push towards a new co-operation of nations, the rise of Communism and economic changes that precipitated first the Roaring 20s (with inflation in the US and Germany) followed by the Great Depression. Yes, I agree that World War I had more to do with a lot of that, but considering how many more civilian deaths were due to the Spanish Flu, that pandemic didn’t help. Institutions already pressure and suffering crises of confidence seem to have a high morbidity and mortality rate in pandemics, no matter the causative microbe.

I don’t know how it all resolves.

But I know that giving into fear never solves anything.

I have yet to see a social media post solve anything either ; )

I think it is advisable, probably regardless of where you live, to make yourself as anti-fragile as possible. That supply of canned food you got way back when should not have expired yet. Certainly keep that around. Diversify your investments and your income, if you at all can. Again, the lesson of history is that coming out of pandemics tends to be a very bumpy time. 2021 might not be quite as unusual as 2020, but I would still anticipate a very odd year.

–There is a good podcast out there with possible solutions to “The Social Dilemma”. If you are interested, hit me up, and I will point you to it. It’s a very packed hour.

–Your chances of catching coronavirus are equivalent to the chances the reason the checkout clerk knows you are old enough to buy the wine with a millisecond’s glance at your license is because your birth year starts with a “1”.

<Paladin>