Ebola–

Only news of significance is that the FDA approved Ebanga (ansuvimab-zykl), a monoclonal antibody to Ebola which was derived from antibodies isolated from a patient who had survived an Ebola outbreak in the 1990s. Ebanga first saw use in the 2018 outbreak (the other side of the DRC from the most recent). So very similar to bamlanivimab and COVID (except bam doesn’t have its trade name yet, like Ebanga). My employer does not make Ebanga or any drugs approved for the treatment of Ebola, just for the record.

Ebanga joins Inmazeb (REGN-EB3) as the only FDA approved treatments for Ebola. Inmazeb is a cocktail of three monoclonal antibodies, each to a different part of the Ebola virus. So that strategy, at least, seems to be effective if the Ebola infection is caught early.

Coronavirus:

–Super quick update because, you know, holiday. Next week will likely be abbreviated if at all too.

–Midwest and Big Sky in the US continue to come down on numbers. Bit of a flare in the South, Tennessee in particular (for no apparent reason). California still definitely climbing a wave and Arizona still pretty frisky. In the UK, London has all but cancelled Christmas with expectation from readers on the ground there that additional restrictions on other parts of the UK are likely coming. Much of this is driven by the UK variant of coronavirus, which we will cover shortly. Elsewhere around the world, photos of raging parties without masks in Wuhan, China made the rounds this week. Again, hard to know what is real coming out of China. I don’t think we will ever get the real story of how draconian things got there. I would not put it past the CCP to stage those photos to suggest the superiority of their system–that would absolutely be in character, especially for their penchant of assuming they have a credibility around the world that I don’t think they have. They are stonewalling efforts by the WHO to investigate the original outbreak in Wuhan, so the timing of the club rave photos is especially suspicious.

On the other hand, as we have mentioned, many of China’s neighbors have, on a per capita basis at least, had a relatively smooth ride with COVID. They were likely exposed to close cousins circulating in that part of the world. As we mentioned, some have hypothesized that exposure to these “close cousins” (also known as “the kind of common cold circulating around there”) led to higher intrinsic resistance and thus more asymptomatic or less severe spread. There is no compelling reason to doubt that hypothesis. Someone can probably go back to blood samples from around there pre-COVID and see if they have T-cells that cross react to SARS-CoV-2 (should be up to 65% on the high end from previous studies done exactly like this elsewhere in the world). If they are running a 65% clip or better, pretty good evidence that the common cold of that neck of the woods was more similar to SARS-CoV-2, and helping ease their way through the pandemic.

–Again, Chinese data, but they followed 10,000 households with an asymptomatic positive index case in that household, and found only 1 probably case of spread. This argues that spread from asymptomatic patients is very rare. Hopefully there is a race to replicate these results, because that science could go a long way to convincing policy makers that post vaccination or post recovery, or hell, as long as you are asymptomatic, masks may not be required.

–It’s worth mentioning that the custom in Asia of wearing a surgical mask in public (if you recall from pictures or visiting there pre-pandemic) is not hypochonria or fashion. The people wearing the masks are not concerned about catching something themselves–they already have. All the people you saw in Asia wearing those masks pre-pandemic had mild flu or cold symptoms and were wearing the mask to protect others. That was polite society in those parts of the world. But–no symptoms, no mask. If we are truly in a “gotta wear a mask” world for the next few years post-COVID, hopefully this is the model that goes forward.

–Moderna’s vaccine got approval and started shipping. The mechanism of action is identical to Pfizer, and indeed, they are similar overall. That said, I have yet to see Moderna’s publication of their Phase 3 data. I would be more inclined to the Pfizer vaccine right now because at least we have seen the full safety profile from the Phase 3 for that one. I am sure Moderna is working furiously behind the scenes to get their publication out too.

–I have not yet got the call from the state that my number is up for vaccination, speaking of. My wife gets hers this weekend. Yes, again, she is more important than I am.

–Scare headline debunking… Only major one this week is “OMG, did you hear, thousands of people have been too sick to work or go out after getting their shot!” Technically speaking, this one is true. As part of post-approval commitment, just like every other drug on the planet, the manufacturer is required to monitor patients getting the treatment for unexpected or adverse events. In this case, there is an app that Pfizer has out that is a basic questionnaire for the known side effects of fever, muscle pain, headache, fatigue etc. and anything else unusual. Those happen between 1-3% of the time.

The data set I have seen from the government prompting this scare headline summarizes ~112,000 doses of vaccine administered thus far across the country. About ~3,000 people have responded on the app that they had some combo of fever, muscle pain, headache, fatigue etc. Or about 3% of total administered doses. Those 3,000 reported they were unable to work or participate in activities of daily living (go to the grocery store etc.)

Sounds bad, right?

But is it?

Let’s remember two things. First, those 112,000 doses have gone out primarily to healthcare workers. Second, you are in the time of COVID, where if you have a fever, or headache, muscle pain, fatigue etc. (symptoms that will be identical between COVID -or- known common side effects of the COVID vaccine), you will be asked to stay home from work AND most stores don’t want you in there either! Hospital and long term care facility screening procedures are, I would argue, among the most stringent out there, including routine temperature and symptom scans before they are cleared to come into work.

So, if you got the vaccine right now, and had one of its known common side effects, you would fail the daily “come into work screen” and automatically have a “side effect that was preventing you from work or daily activities of living.”

That the number of those matches the expected side effect frequency of the vaccine is probably not an accident. Thus far, no state or health body I am aware of has been freaked out about a large number of vaccinated people being laid up with prostrating side effects. Side effects that trip “cleared to work in the office” rules, yes, but not as severe as the articles out there make it sound. Everyone I have heard from thus far who got the vaccine has not had an issue, FWIW.

That said, there have been allergic reactions–those are being investigated, and for now you’ll be monitored for 15-30 minutes after the shot for signs of anaphylaxis. You can count the allergic reactions like that on approximately two hands thus far. Considering hundreds of thousands of shots have been given worldwide so far, these reactions, while they happen, are still pretty rare.

–Lastly, the UK variant. I actually got a hold of the exact mutations in this strain and finally got the same for the Denmark mink variant. As we mentioned before, there are mutations in the spike protein in the UK variant, and a higher number of mutations than typical for what we have seen thus far in the outbreak overall. Authorities in the UK believe the variant is sourced to a patient who was one of those “long termers” you have read about, who had low positive detection of virus for weeks after getting over COVID. That is usually prolonged clearance of dead virus particles, but in this case, was true detection of low level infection as the coronavirus managed to stay just ahead of the immune system to avoid being wiped out, at least for a couple months. As a result of that long war with the human immune system, it hit the lottery and found a mutation set that made it easier to spread to others. The reason for the concern in the news over this variant is thus two fold.

1. This is the first variant that has successfully challenged the supremacy of the D614G variant (the previous DOOOOOOOOOOOM variant that turned out to be more contagious but less severe on a case by case basis). In fact, it is outcompeting the D614G to be the dominant strain in the regions of the UK where it has been spotted. That is where the “70% more infectious” claim is coming from, although it was too early to calculate that statistic, let alone that precisely. It is probably, if not likely, a little more contagious than the D614G variant.
2. This variant has two mutations in the spike protein that, in petri dishes, resisted plasma from convalescent patients and unnamed “monoclonal antibodies” (but no one knows which antibodies were tested yet). One of these mutations is the Denmark mink variant, which got the entire mink population euthanized–all because of this “in petri dishes” resistance. No one knows for sure if these mutations will confer resistance to vaccines targeting the spike protein.

That said….

There is NO evidence that this variant is causing more severe disease or severe disease at a higher rate as a percentage of positive cases. Enough of the variant has been seen that if this was a huge phase shift in disease severity, we should know by now.

Secondly, if the two mutations in the spike protein were allowing this variant to get past the vaccine, we would expect this variant could be re-infecting patients who already caught a standard strain of COVID already. That would be confirmation that what was seen in a petri dish is also true for the real world, in terms of resistance to COVID antibodies.

And worth re-iterating, antibodies. I don’t think these variants have been tested for resistance to T-cell mediated immunity.

Regardless, so for, there are NO reports of this variant re-infecting patients who already caught and recovered from COVID, and certainly not at a rate that suggests this new variant has phase shifted and everyone is susceptible to it again. This argues that what was seen in petri dishes, as can sometimes happen, does not reflect what happens clinically “in the wild.”

Now, that could be because the immune system, when recovering from the bona fide SARS-CoV-2, makes T- and B-cell responses to MORE than just the spike protein. The vaccines will provoke T- and B-cell responses to JUST the spike protein. Because of that, Pfizer is testing their vaccine against the UK variant to see if the spike protein changes are enough to get this strain past the vaccine. Odds that these mutations will get past the vaccine are low, but they are not zero, and so this testing is a good idea.

Everything else you are reading, including new shutdowns and travel bans in other countries on those arriving from the UK, are simply abundance of caution as they continue to gauge the true risks of this new variant.

My best guess is that like D614G, it will follow the general trend of viral evolution–more contagious, but less severe disease. Odds are greater than not it still gets hammered by the vaccines.

Your chances of catching Ebola this week are equivalent to the chances that Santa won’t damn the COVID torpedoes and stays home this year.

Your chances of catching coronavirus this week are equivalent to the chances you can still hear the bells.

<Paladin>