COVID Transmissions for 11-12-2021

Greetings from an undisclosed location in my apartment. Welcome to COVID Transmissions.

It has been 726 days since the first documented human case of COVID-19. In 726, Emperor Leo III (Byzantine Empire), issued several edicts about the use of sculptures and images in religious worship. This launched a period of religious strife over iconoclasm, one of the better known instances of such strife in a Christian nation.

Today, we will talk about a new vaccine that might help on a global level, and I also have a note about an NYT article that I think is misleading, about vaccine effectiveness waning.

Then we have some reader comments and questions—one about how to make decisions regarding assessing where it’s safest to travel.

Have a great weekend!

Bolded terms are linked to the running newsletter glossary.

Keep COVID Transmissions growing by sharing it! Share the newsletter, not the virus. I rely on you to help spread good information, which you can do with this button:

Now, let’s talk COVID.

---

Bharat Biotech of India releases interim Phase 3 results for another vaccine candidate, with a classical design

Bharat Biotech’s BBV-152 is a whole-virion, inactivated vaccine conjugated to an alum adjuvant. In preliminary results, published this week, it had 77.8% efficacy after two doses. The results can be read here, in The Lancet: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02000-6/fulltext

We can’t really cross-compare trials, remember. The patient populations and timing of these trials was different. Real-world studies have shown us that the efficacy of the mRNA vaccines against symptomatic disease has also dropped somewhat since the original trials. So, don’t immediately jump to the conclusion that this vaccine is “worse.” What we know is that the efficacy is in a range where this vaccine could be used for disease control, and to provide meaningful protection. That’s good.

However, since we don’t have final results, I’d like to see what comes from the trial’s completion. There are a few more questions that I’d like answers to here. For example, what about protection against the Delta variant? In this interim analysis, this vaccine candidate had numerically lower performance against the Delta variant, at 65.2%, but the 95% confidence interval overlapped with the full group efficacy and the number of Delta cases this finding is based on was comparatively low. More follow-up may increase the event numbers and get us a number that is both more accurate and more precise.

What’s most important about this vaccine, though, is how it is made and handled. This vaccine is a classical technology, and not too different from, say, cell-derived seasonal influenza vaccines (except for the adjuvant). The virus is grown in Vero cells, a cell line derived from African Green Monkeys that is particularly amenable to the tissue culture growth of viruses.¹

While the efficacy of this vaccine may not ultimately turn out to be as high as a full course of an mRNA vaccine or two doses of the Janssen/J&J vaccine, it has advantages because it is relatively easy to make, uses technologies that are already deployed for other vaccines, and can be stored at typical refrigerator temperatures.

The reality is that while we have made a large amount of progress in the last year as far as vaccinating the world, we still have a great distance to go. A vaccine like this will help us close that distance and get more people vaccinated in countries that really need it right now.

New York Times cherry-picks information on vaccine waning

There is a New York Times article making the rounds that makes a case that the vaccines in use in the US have not been waning in effectiveness to the degree that many think. While I think that the case for waning effectiveness has not been definitively made in a way that can confirm the magnitude of that waning, there is a problem with this article: it ignores a whole bunch of studies, and includes only ones where vaccine waning was modest.

Several studies have suggested more extreme vaccine waning, though it is difficult to pin down the exact magnitude. However, I think it is really inappropriate for the New York Times to selectively report the scientific data in a way that paints what may be an inaccurate picture.

The synthesis of different research results into a coherent picture is a scientific activity; I have several textbooks at home about research synthesis and a manuscript in preparation in a non-COVID disease area. Scientists like myself work hard to make sure that when we are collecting results to perform a research synthesis, the results that we take from the literature are comprehensive and unbiased. It’s painstaking work, usually requiring multiple independent researchers and pre-specified rules for inclusion of studies. Researchers who fail to do this won’t get their work past their peers on review.

The press is not bound by rules of peer review, and I think in this case that allowed the authors of the article in question to use selective reporting to misrepresent the situation as we understand it. I won’t try to speculate about some kind of motivation for this; it might just be laziness, or not knowing better. But it’s not scientific.

I won’t be linking the article, but I wanted you to know about it, in case you run across it. It’s not good science, even though it is portrayed as science reporting.

In terms of my opinion on the actual subject, I think it is clear that there has been a meaningful drop in the effectiveness of the vaccines on the market in the US. This drop only appears to impact the mildest cases of disease in a serious way, and I’m not sure how large the drop is. I think it may be prudent for booster doses to be available, but I don’t think they are necessary for everyone—it’s something to talk to your doctor about.

It will become clearer just how much the efficacy of the vaccines has declined. It will become clearer why that decline has taken place. I will keep covering this, to try to get closer to the truth.

---

What am I doing to cope with the pandemic? This:

Back at work

I’ve completed my parental leave and I’m back “at” work. Of course, I work from home still, so the big change isn’t so much where I am going as what I am doing on any given day.

There’s a lot of work to be done at my company. We’re in a critical time, with some key results coming soon and a number of ongoing activities that I’m helping to execute. At the same time, I have a daughter—my new “in-home manager”—who has to come first. Striking the right work-life balance has become more important than ever.

---

After our conversation about the potential for molnupiravir to cause mutations in patients, Carl shared with me a blog with a much more sophisticated and detailed analysis than what I provided, but that ultimately agrees with my thinking. I wanted to pass this along to all of you:

In another forum, I was pointed to this Science blog that agrees with you in much more detail:

https://www.science.org/content/blog-post/molnupiravir-mutations

Additionally, reader “Just Another Bozo On the Bus” had a question about traveling:

Hi John, Thanks as always for your careful analyses. <smile> As the pandemic seems to wane and we emerge from our bunkers, it is likely to be safer to travel to some places but not others. What is a good source of information to figure out the relative risk in various cities or countries? I would like to go to El Salvador next month (where it is warm and hope to spend time outdoors), while my wife would like to visit friends in Chicago. How can we determine the relative risk of these two (or other) destinations? THANKS!

Thanks for your kind words, and for reading. This is a good question, and hopefully folks will benefit from seeing my approach to this question:

Interesting question! For destinations within the US, I recommend using the CDC’s COVID-19 tracker: https://covid.cdc.gov/covid-data-tracker/#county-view|Illinois|Risk|community_transmission_level

That link will take you straight to the result for Illinois, which are not great-looking, particularly in and around Chicago.

Meanwhile, for International travel, the US State Department has advisories for a large number of countries, including El Salvador: https://travel.state.gov/content/travel/en/international-travel/International-Travel-Country-Information-Pages/ElSalvador.html

As you can see this currently says to “reconsider” travel to El Salvador. This is based on a CDC determination that El Salvador currently has a “high” COVID-19 transmission status: https://wwwnc.cdc.gov/travel/notices/covid-3/coronavirus-el-salvador

The scale the CDC uses for international travel is different from the one it uses for the US, which is confusing, but ultimately it takes similar incidence rates per 100,000 people to get to both ratings. Chicago and El Salvador appear to be around the same level of risk according to how I read the CDC’s assessment.

Based on that, and while I like the idea of being outdoors, I think Chicago is the marginally better choice provided these were the only two destinations possible. The reason is that Chicago has better hospitals and, for me at least (perhaps not for you) would not represent international travel. Being in a foreign country could complicate getting healthcare if one or both of you does get COVID-19.

That said, the CDC map and travel advisories suggest to me that you might want to consider going to neither of these places. There are currently several places in the US that are lower-risk than Chicago. The epidemic seems to have ebbed somewhat in Florida, for instance, which just came off of a huge peak. It might be warm enough there to be outside more, too. However, that is a state that has odd ideas about disease control, and I’d personally want to steer clear unless I knew I was going somewhere that has a high vaccination rate.

There are also several international destinations that have a “low” travel advisory for COVID-19. One of those might be a better option.

My main point in this exercise is to demonstrate my thinking:

-Check the CDC map for the US, but also consider local disease control policies

-Check the US State Department travel advisories and also CDC travel advisories for international destinations, considering also how comfortable you might be if you got COVID-19 in any given country and needed healthcare

-Assume where ever you might go, it is possible you will get COVID-19, and have a contingency plan to deal with that

-Make a decision based on what you’re most comfortable with after doing all of the above

Hope this helps!

You might have some questions or comments! Join the conversation, and what you say will impact what I talk about in the next issue. You can also email me if you have a comment that you don’t want to share with the whole group.

---

Part of science is identifying and correcting errors. If you find a mistake, please tell me about it.

Though I can’t correct the emailed version after it has been sent, I do update the online post of the newsletter every time a mistake is brought to my attention.

No corrections since last issue.

See you all next time. And don’t forget to share the newsletter if you liked it.

Always,

JS

1. Vero cells are deficient in several innate immune pathways that normally limit virus replication in tissue culture. They can serve as a convenient setting to replicate certain viruses. I maintained a Vero cell culture for many years as a graduate student, which was useful for studying virus proteins in the absence of innate immune interference.