–Cases across the US continue to go down. I’m sure you saw the headline this week when the number of vaccinations in one day exceeded the number of new cases for the first time. With 1.3 million vaccinations last week, even before the Federal vaccination supercenters got rolling, the Biden administration is already well on its way to one of the easy wins we mentioned earlier. Hospitalizations are going down. The effective Rt is going down.

In fact, our favorite one stop shop for Rt data has closed. If you go to Rt.live, you will now be re-directed to other sources of data as the drop has been sufficiently sustained at this point that the curators of Rt live no longer believe the metric to be as useful.

(https://epiforecasts.io/covid/posts/national/united-states/ is the best place for Rt data off that list; in fact, one of the sites they listed, the COVID Tracking Project, is also closing shop next month)

Hospital census, at least in Indiana, has fallen to the March-May peak. New admissions are plummeting. Just as a reminder, deaths are a lagging indicator. We will expect those to remain elevated, as the hospital census is still high, but falling.

–Trends are looking similar in much of the rest of the world, although vaccination rates vary locally (more on that in a second).

–So the biggest wild cards remain the new variants of concern that keep making the headlines. We have some new things to talk about on these fronts.

After last week’s update went out, Novavax, a biotech specializing in vaccines, went to press with Phase 3 results for their SARS-CoV-2 vaccine. This vaccine is a little more traditional, in that it uses an inactive virus that carries the SARS-CoV-2 spike protein. So the inactive virus gets into your cells, and just like with the mRNA vaccines, your ribosomes mistake the spike protein for something they should make. So they do. Lots of it. Causes immune reaction, leads to immunity, etc. etc.

The important part about Novavax is that they were running one part of their Phase 2b program in South Africa, right as the South African variant 20H/501Y.V2 was starting to take over. This was South Africa’s biggest peak to date, and crested around January 6th of this year. As near as Novavax can tell, apparently, 90% of the cases on their study came from this variant.

Importantly, about 30% of their patient population already had antibodies to the spike protein of SARS-CoV-2–before they ever got the vaccine. These are presumably patients who caught the virus before. Novavax further assumes (but does not know for sure, and no one does) that they caught a different variant of the vaccine in the months leading up to the trial. Their antibodies were thus part of their natural immunity after getting SARS-CoV-2.

So there are two troubling outcomes of this Phase 2b. First, the vaccine was only about half as effective in South Africa as it was in a simultaneous Phase 3 in the UK (where it was about as effective against the UK variant as the “regular” variants). Second, the seropositive patients, the ones who had caught SARS-CoV-2 before caught SARS-CoV-2 again–most of them with the new South African variant.

In fact, those in the placebo arm caught the SARS-CoV-2 variant at the exact same rate (about 2.9%) as patients who had no antibodies to SARS-CoV-2, and were thus presumably unexposed.

These would suggest that the South Africa variant is sufficiently different to get around natural immunity in a good chunk of patients AND may get around at least some vaccines (or make them less effective).

But wait…. there’s MORE!

South Africa has pre-published an in vitro study looking at the South African variant. They chucked the antibodies of 44 recovered SARS-CoV-2 patients at the South African variant, and found that for 21 patients, their antibodies were ineffective at neutralizing the virus. That would seem to fit with Novavax’s data.

But wait… there’s STILL more!

Because the picture gets a little muddled. Other researchers took 20 patients who received either the Moderna or the Pfizer vaccines and tested their vaccine-derived spike antibodies against constructs of the UK and South Africa variants. They confirmed that the pattern of antibodies formed from vaccination to the spike protein is similar to the pattern seen in natural infections. But they found there was a small, but significant decrease in neutralization, particularly against the South African variant. That finding was also replicated by a different group of researchers, also testing human or primate sera from subjects given the Moderna vaccine. Both the UK and South Africa variant reduced the effectiveness of neutralization.

However, in both of those sets of in vitro experiments, the amount of antibody present after vaccination is still far, far, far higher than the drop in neutralization effectiveness.

Basically, the individual antibodies may not work as well against the new variants in these in vitro experiments–but there are so many antibodies to SARS-CoV-2 being made that it doesn’t matter. On the whole, the patient should have at least some resistance to the variants.

–So what to make of all of this? Well, the current South Africa new case curve does not look quite like what we would expect if this new variant was raging unchecked even through previously infected people–especially with the Novavax data suggesting everyone is still equally susceptible to this strain, previously infected or not. The in vitro data suggest that the variant does reduce antibody binding, and so may be better able to re-infect patients and/or get around treatments/vaccines. Data from South Africa, on South African patients, suggest that as many 50% of people previously infected may still be susceptible to the South African variant. But the in vitro data outside of South Africa suggests that most people will have enough antibody around already, or able to be dialed up quickly, that the reduction in antibody binding should simply be overwhelmed. It’s possible there is a genetic or odd environmental component to that, as the in vitro work outside of South Africa was not done using South African patient samples.

The data suggests that at least some people may be more likely to be re-infected by the South African variant and/or that additional boosters or versions of the vaccines will be necessary to maintain immunity in the face of this variant or others like it. At least in the Novavax data, the rate of moderate to severe disease was unchanged in the placebo arm between patients who had caught SARS-CoV-2 before and those who had not, so there’s not even a severity reduction if re-infected.

–How does this change our base case? Well, the Novavax data has small numbers of people who actually caught SARS-CoV-2 on the study, but enough that it certainly suggests a reinfection possibility. Vaccination with the Novavax vaccine reduced the number of SARS-CoV-2 infections (most probably by boosting the amount of antibody available, even if it was less effective against this variant), so vaccination will still help end the pandemic. All hope is not lost there.

But, the dog is now barking at least a bit. We will have to see what happens in countries where the South Africa variant has already been detected (which is several of them, including the US). If the South African variant does not establish a foothold and start moving through that percentage of the population it can re-infect, then we are still on the base case of “pretty much over by July.” Give it a few months to gather momentum. If there is no sudden resurgence in cases, or sudden headlines of people suddenly getting sick again with COVID or sick despite vaccination by mid-April, we are still on the base case.

If we are, it will depend on what percentage of the population the South African variant is capable of re-infecting. I don’t think it is 100% based on South Africa’s new case curve over this window, but the Novavax data suggests it is not 0 either.

If our South African reader can ping the health care workers they know for how many people coming into the hospital over the last couple of months were re-infections with SARS-CoV-2, that would be useful anecdotal context….

–A good overview of the variants kicking around can be found here: https://www.the-scientist.com/news-opinion/a-guide-to-emerging-sars-cov-2-variants-68387

–Speaking of antibodies, finally got some results back on mine. There were no detectable SARS-CoV-2 spike protein IgG antibodies in my blood 7 days after the first vaccine dose. If it was a booster (because I was previously exposed), they should have been detectable. There was some evidence that recency matters though. The booster pattern was more detectable in people whose last known close exposure was in the fall versus those from the March-May peak.

Still waiting on IgM for the spike protein. If I was truly, miraculously, never exposed to an infectious dose of SARS-CoV-2, the IgM should be detectable in my “day 7 after vaccine” draw. If it is, suggests that the vaccine was the first time my immune system saw enough of SARS-CoV-2 to care about it.

My day 6 after dose 2 of the vaccine sample showed rockstar levels of IgG to SARS-CoV-2. As you would expect, when that shot really and truly IS meant to be a booster! Vaccine works…

–In other news, the UK announced a plan to mix and match the second dose of vaccines among manufacturers to ease rollout. In particular, using the AstraZeneca vaccine to follow up a first dose of the mRNA vaccines.

The AZ vaccine is a slightly different vaccine.  It uses a hollowed out adenovirus containing the spike protein sequence (in DNA this time) of SARS-CoV-2.  No, the DNA in the vaccine does not become part of your DNA. It lasts long enough to get converted to mRNA and then into spike protein as we have previously discussed. You can follow headlines about the effectiveness of the AstraZeneca vaccine, and thank you for understanding.

Since both vaccines are causing human cells to make and present the spike protein the nature of the immune response to both vaccines should be similar, and one should theoretically be an effective booster for the other.

The catch is that it is all theory, making this a courageous decision in the British sense of the adjective.  None of them have been tested in this combined manner (for safety let alone efficacy).  You are off label for both products should you do this.  This is basically a giant Phase 1/2 study that the UK will be undertaking.

My understanding is that this is still in the planning stages, and details are still being worked out. The announcement could just be a trial balloon, no pun intended, or they may roll it out as an official Phase 1/2 study in a select population first before going wide scale. We’ll try to follow, and thanks to the UK readers for their questions about it.

–Yes, I heard about China announcing anal swabs for COVID testing, and how that might be a better way to test for the virus, especially in large populations.

The jokes are just too obvious here. Make your own favorite.

For my part, I question the necessity when a (slightly) less invasive testing procedure will get you largely similar results in the same amount of time or less.

–Finally, when you have seen, you cannot unsee.

When you know, you cannot unknow.

Once you have become aware of the true danger, the real threat, you can recognize it.

Even when others might not.

So yes, thank you to the reader who sent along the following: https://nypost.com/2020/02/01/roving-band-of-herpes-ridden-monkeys-now-roaming-northeast-florida/

Yes, friends, the Army of the Bioterrorist Monkeys is back, and making a major push in Florida.

They will tell you that this is a group of escaped rhesus monkeys, who are growing as an invasive species colony around Silver Springs State Park in Florida. They will tell you that it’s only natural, as the colony grows, that it should spread through the Ocala National Forest. That it was only inevitable, since trapping and hunting of the escaped monkeys was stopped in 2012, the colony would appear out the East side of the Ocala forest and start ranging from Jacksonville through St. Augustine down to Palatka.

This only denies the truth that you know.

It is, indeed, the latest push from the Army of the Bioterrorist Monkeys. This is a shock and awe campaign. Not only demonstrating the impotence of even the mightiest hoo-man military in the face of the Army of the Bioterrorist Monkeys by seizing and controlling territory in their very heartland, it aims for utter demoralization by threatening your very hoo-man “happiest place on Earth.”

And they bring with them a weapon of terror–Herpes B virus.

And… uh… yeah, I’m kind of serious about that. Herpes B causes the kind of herpes you are thinking about in monkeys. In humans, it has a bad habit of going straight to the CNS, where untreated cases have 80% mortality. Fortunately, it responds pretty well when suspected to all the treatments you are thinking of for herpes–there have been no cases in the US when post exposure prophylaxis has started within 3 days of exposure. It can be contracted by bites or scratches from infected monkeys, and infection into the eye or mucous membranes is especially dangerous.

And yeah, just like the human herp, once you have definitively caught the monkey herp, treatment is recommended for life.

Though it seems dark now, and that the Army of the Bioterrorist Monkeys has unleashed a final master stroke, fear not…

–In a related note, concern was recently expressed about the continued territorial expansion of another invasive species of Old World primate in Florida. Similar to the rhesus monkeys, a shocking percentage have been found to be carriers of herpes virus and other maladies. Their colony size is substantially larger, and their ecological disruption has been far more profound. Indeed, the invasion of this primate, Homo sapiens, has come in waves over the past 13,000 years at least, and shows no sign of abating as they have effectively eliminated or controlled any native species that might have become a natural predator…

: )

–Recommended reading from last week. Now you know what factors may have helped unite several million to spontaneously charge at “the suits” via GameStop. What did their method unequivocally demonstrate?

Hunger Games

–If you want to follow the rabbit hole from that article, I recommend the Grant Williams conversation with Anthony Deden (put that into YouTube). And while you are at YouTube, check out 99Bitcoins’ “What is DeFi” video–and ask yourself at the end how that might impact the Citadel model.

–Your chances of catching coronavirus are equivalent to the chances that Jane will prevail, yet again…

–Life in the Time of Coronavirus:

<Paladin>