COVID Transmissions for 11-1-2021

Getting your immunity from vaccination vs getting it from infection

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

It has been 715 days since the first documented human case of COVID-19. In 715, Sulayman ibn Abd al-Malyk became the 7th Umayyad Caliph; he took the Caliphate to its greatest extent and successes.

Today’s issue focuses on the question of immunity gained from infection vs immunity gained from vaccination. There are some new data!

Bolded terms are linked to the running newsletter glossary.

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Now, let’s talk COVID.

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New information on infection-acquired vs vaccination-acquired immunity to COVID-19

A new study from the VISION Network has compared infection-acquired immunity with vaccination-acquired immunity to COVID-19: https://www.cdc.gov/mmwr/volumes/70/wr/mm7044e1.htm

This study is a real-world, observational setup in 9 US states, looking at the chances that patients hospitalized for COVID-19-like illness actually got a positive test result for COVID-19, across patients who were either vaccinated with 2 doses of an mRNA vaccine or who had been previously infected with SARS-CoV-2. People who received 1 dose of an mRNA vaccine or who received the J&J vaccine were excluded. Only people who had previous infection without any vaccination, or who had vaccination without any previous infection, were included in the two respective arms.

The main analysis examined patients who were either vaccinated or tested positive the first time between 90 and 179 days prior to the hospitalization that got them included in the trial. Choosing a consistent time window put both groups on a relatively equal playing field, but the previously infected group had significantly higher odds of being positive for SARS-CoV-2 infection on their second hospitalization, by about 5.5 times, compared with the vaccination group.

Lifting the timing window restriction had only a minor impact on this, with the relative odds falling to where previously-infected people were about 2.75 times more likely than vaccinated people to test positive during their hospitalization.

There were a number of interesting subanalyses, and I will highlight a few, but I want to note that in every sub-analysis of these data, the previously-infected group was more likely to test positive for COVID-19 during their hospitalization than the vaccinated group. There was no condition where previous infection seemed to be superior to vaccination.

The ones I want to call out are these:

• After the Delta variant rose to predominance, previously-infected people were 7.55 times more likely to test positive than vaccinated people

• People ages 18-64 were 2.57 times more likely to test positive if previously-infected rather than vaccinated

• People 65 and older were 19.57 times more likely to test positive if previously-infected vs vaccinated

This is a really interesting, if somewhat limited, study. There are specific limitations listed in the paper, but the one that jumps out at me the most is that this only considers hospitalized patients. Nonhospitalized patients may have different risk levels, so that definitely gets in the way. However, it matters if vaccines are better at keeping people from being hospitalized with COVID-19, doesn’t it?

I also am frustrated that the study has nothing to tell us about people who were both previously infected and also got vaccinated. That doesn’t take away from the results that we do have, but it does make it more limited in terms of what we can learn from this specific work.

That said, I think we do learn something meaningful here. I think it’s evident that there is an effect here, but there are other data suggesting a meaningful protective effect for prior infection in certain circumstances.

Speaking of, I also recently found a CDC-produced roundup of evidence comparing prior infection with vaccination. Let’s cover that next.

CDC review of prior infection vs vaccination

The CDC has put together a nice review of some available evidence on the question of prior infection vs vaccination that I wanted to share. A lot of it is things that I have said here before, but this resource brings in substantial citations and evidence to help support these ideas: https://www.cdc.gov/coronavirus/2019-ncov/science/science-briefs/vaccine-induced-immunity.html

The gist of this is as follows:

• We can be sure that prior infection generally reduces the risk of future infection for around 6 months, at a population level but not for any individual

• The Delta variant has reduced the effectiveness of prior infection (and of vaccination) to some degree, but only modestly

• We do not currently have tools that can tell us if a previously-infected person is protected, so vaccination is still recommended even for people who have recovered from COVID-19

What really matters about this is the information the link provides to support these claims. Everything is better when there’s supporting evidence.

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

Wedding successful!

I had a great time at the wedding I was telling you about in the last issue, and it was wonderful to see my friends finally married after having to reschedule early in the pandemic. Some of you reading this were there! It was good to see you.

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Carl had some comments on the last issue, covering a few topics:

Merck's free licensing of molnupiravir (to the Medicines Patent Pool, not WHO, by the way) will end when the pandemic is declared no longer an emergency by WHO. Considering how short patent terms are, this will probably be right at the end of its patent life anyway, of course. (I'm assuming WHO will be slow to un-declare an emergency, given that they're part of the notoriously dilatory United Nations.)

I think the weird "They're harming beagles!" freakout by some politicians is especially misguided because, as you mention, Leishmaniasis research can (and presumably will) also be used to protect dogs.

I just discovered two YouTube videos by medical researcher Susan Oliver (https://www.unsw.edu.au/staff/susan-oliver) explaining why ivermectin has not been shown to have value in treating COVID-19. Part 1 is here:

My response:

I did have "to WHO" in the headline, didn't I? My mistake. I noted Medicines Patent Pool later on. Like you I would agree that WHO will not be in any hurry to declare the pandemic over--nor do I think the pandemic will meaningfully end any time soon. Even so, Merck has a history of giving drugs away for free. Ivermectin is one of them, actually, that they've been providing free of charge or at cost to developing countries for decades; in that case, it's for use as an antiparasitic, a treatment area where the drug has strong evidence supporting its use. I suspect that if the need continues, but the pandemic ends, while molnupiravir is still on-patent, Merck will do the compassionate thing.

I like that video a lot! I think it captures a really comprehensive view of the issues surrounding ivermectin in COVID-19. I like that it covers also how the preclinical work has demonstrated the absence of a clear mechanism for any proposed effect, with prior evidence of some mechanism being dependent on the use of a cell line that doesn't reasonably model human lung cells (vero cells, which are monkey kidney cells).

You might have some questions or comments! Send them in. As several folks have figured out, you can also email me if you have a comment that you don’t want to share with the whole group.

Join the conversation, and what you say will impact what I talk about in the next issue.

Also, let me know any other thoughts you might have about the newsletter. I’d like to make sure you’re getting what you want out of this.

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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.

Correction: I wrote that the “WHO” was given rights to molnupiravir in the last issue, when I should have said the UN-backed Medicines Patent Pool was given those rights. This has been corrected in the online edition.

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

Always,

JS