COVID Transmissions for 2-14-2022
COVID-19 substantially increases long-term cardiovascular risks
Greetings from an undisclosed location in my apartment. Welcome to COVID Transmissions.
It has been 790 days since the first documented human case of COVID-19. In 790, the iconophile Byzantine Empress Irene was deposed by iconoclastic forces under Constantine VI. Irene is imprisoned. In a move that seems to add insult to injury, Irene’s eunuchs are exiled.
Speaking of insult and injury, today we will discuss long-term cardiovascular outcomes from the initial insult of acute infection with SARS-CoV-2. We will also discuss the FDA’s backpedaling on review of a younger-pediatric vaccine.
There is a paid “other viruses” section today, in which we’ll discuss cancer-causing viruses.
Have a great week!
Bolded terms are linked to the running newsletter glossary.
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Now, let’s talk COVID.
FDA elects to delay advisory committee meeting on vaccination of young children, preferring to take longer time to evaluate data
After asking that Pfizer prepare for an advisory committee meeting that it didn’t seek out, the FDA has now backpedaled and said they will wait for additional data on a third dose of the young-children (6 months to 5 years) pediatric vaccine formulation: https://www.nytimes.com/2022/02/11/us/politics/fda-children-pfizer-vaccine.html
I am normally very faithful in my trust in the FDA. Partly this is because they regulate my industry and I think they generally do a good job, even when I disagree with them. I have a lot of respect for the FDA. Their work is difficult and their responsibility is tremendous.
However, as a parent of a child who is nearly eligible for this product, it is hard to keep my comments on this reversal measured. To briefly review the course of events here:
Pfizer announced that their 2-dose version of this vaccine was not as immunogenic as they had hoped in children ages 2 to 5, but was immunogenic in patients 6 months to 2 years of age
The vaccine was, however, exceedingly mild in terms of safety events in both age groups
Based on this, Pfizer chose to extend their trial period and add a third dose in the older child group
The FDA requested, probably after conversations with Pfizer about these events, that Pfizer prepare a data package and have the results reviewed for potential emergency use authorization anyway, going so far as to set an Advisory Committee meeting date
The FDA then, presumably, saw the data and elected to cancel
I am not going to question the FDA on matters of scientific analysis of safety or efficacy here. I believe what Pfizer has announced and I believe the FDA has accurately come to the same conclusion that a third dose is worth attempting in the context of a clinical trial.
It appeared that, since the vaccine was safe and a third dose was expected to bolster the immune response, the FDA had decided to go forward with the authorization process so they could get the ball rolling on young childhood vaccinations. The consequences would be minimal, so they were moving forward. It seemed like a pragmatic response to a pandemic emergency. And then, for some reason, they decided to reverse course.
Where I have harsh criticism for the FDA here is in the degree to which their backpedaling was done in a public forum without a thought to the impact this would have on people. They got millions of parents’ hopes up, communicated a certain stance on vaccines, and then create a great deal of doubt by reversing course. If the pandemic has taught me anything, it is that the public generally is harshly critical of public officials who change their minds about decisions—even when those changes are justified.
As a communications professional and a pharmaceutical executive, I know how carefully interactions with the FDA are orchestrated. I also know how many confidential meetings occur between an applicant for approval and “The Agency,” as people call them. The FDA is involved in the design of Phase 3 trials. They review data periodically, talk with the trial sponsors about the conduct of the trial and unforeseen problems that may have arisen, and submit questions to those sponsors that they think it is important for the sponsors to think about before submitting data for final review.
These interactions are not generally public. In fact, they are not even generally shared with the wider team at the sponsor company. They are often kept on a strictly need-to-know basis to avoid signaling any kind of inappropriate or premature conclusion about how well an investigational drug is performing in its trial program.
So, why, I must ask, did the FDA do this particular exchange with Pfizer in public?
I cannot see a good reason for it. I am certain that if the FDA wanted to review Pfizer’s data confidentially, it could have been arranged. I am certain that a decision could have been made on whether to proceed to an Advisory Committee without requiring this very public waffling.
But that didn’t happen. And I am, unfortunately, as baffled as I am frustrated with regard to why it didn’t happen in private. From where I sit, this seems like a completely unforced public relations error on the part of the FDA. Despite my great respect for the Agency’s work in making sure Americans have access to safe and effective medicines, I am troubled at these events. It feels like they did not think about how the public nature of this could cause real emotional impacts on frustrated parents, or about how their actions could undermine public confidence in any vaccines that are ultimately authorized through this process.
It feels like a mistake, and I really hope there is a good reason it happened.
Large study of cardiovascular outcomes one year after COVID-19
A large and comprehensive study has established that for one year (at least) after COVID-19 recovery, there is a marked increase in the risk of serious cardiovascular (CV) events. This study was published in Nature Medicine: https://www.nature.com/articles/s41591-022-01689-3
The study was in the Veterans’ Administration (VA) healthcare system and used a variety of control methods to estimate the increased risk of a long list of CV events after COVID-19 recovery. One thing to keep in mind here is that the VA system has something of a selection bias for its users relative to the overall population. In other words, the people who use the VA healthcare system are not randomly selected, and this may impact how representative the results actually are. Still, with 153,760 COVID-19 cases represented in their sample, this is a lot of people.
As someone who has recovered from COVID-19, seeing this study all over the headlines for this past weekend has been really troubling. The researchers found that there is no circumstances where having had an active case of COVID-19 does not at least moderately increase your risk of negative CV outcomes.
Here is their full list:
Now, look, relative increase in risk is not the same as absolute increase in risk. I would expect that there are definitive health interventions that a person can make to improve their cardiovascular health to reduce risk of these events by a greater degree than COVID-19 generally worsens them. For many people this will be true. Certainly this is what I am thinking about when I do cardio workouts.
At the same time, these are serious increases that will have both personal effects on many people as well as systemic effects on healthcare.
What’s even more striking is that demographic features did not appear to have much impact on the increase in CV event risk. We are used to hearing a message that your risks of bad outcomes from COVID-19 are highest if you have, generally, risk factors that fall into one of two categories:
Age-related risk factors
Metabolic disorder-related risk factors
In this study, the elevated relative CV event risk did not change in subgroup analyses looking at these categories. While these categories carry an overall elevated absolute risk of CV events, in many cases, the relative increase in risk of these events after COVID-19 is agnostic to whether you carry what are normally thought of as severe COVID-19 risk factors.
A person who has COVID-19 will probably have an elevated risk of these events even if they are young and in good health. Since this is all relative, that person might have started with a lower absolute risk, but you know, I don’t love the idea of increased risk of these things, no matter how small. It doesn’t sit well with me.
Something else that strikes me here—though it is something of an aside—is the elevation of myocarditis risk. Antivaccine propagandists made a big deal out of myocarditis risks in people who got vaccinated—but often conveniently left out that COVID-19 elevates the risk of myocarditis as well. In fact, it’s substantially more likely to cause myocarditis than any vaccine. That elevated risk is very clear in the data here.
Vaccine-related myocarditis does happen, mostly in the select population of males from the teenage years to about 30, but it is still rarer than myocarditis caused by COVID-19. Also, the people who get vaccine-related myocarditis have the advantage that their bodies have not also just been weakened by the stress of fighting off a deadly virus. So their myocarditis tends to be mild—I don’t know that I can say the same of those who get it from COVID-19.
Standing up for the vaccine here brings me to another, more central point. The authors went further in their work and examined the impact of severity of acute COVID-19 on the risk increase for CV events. Here’s what they found:
These are pretty definitive findings; the worse your COVID-19, the more elevated your risk of serious CV outcomes for the next year (at least) becomes. The only standout, actually, where there is not as distinct a separation, is myocarditis—but even in these data there is obviously more risk among those who had more severe COVID-19.
Something else notable in this result is that events like cardiac arrest have a relative increase in risk for the non-hospitalized that crosses “1”; in other words, it’s possible that those who got COVID-19 and had mild cases will not have any increased risk of these outcomes at all. This applies to cardiogenic shock and myocardial infarction as well.
Now, one might say that this finding could be due to the fact that risk factors for severe COVID-19 are also often risk factors for serious CV events, except that the authors used control groups that were weighted for these demographic factors. These relative risk numbers are based on comparing populations with similar CV risk factors to one another, with the main difference being that one group had an acute COVID-19 disease with a certain severity, and the control didn’t.
In light of that, I think what we are seeing here is an estimation of actual impacts of severe COVID-19 on CV event risk, rather than just an assessment that people who tend to get severe COVID-19 also tend to be at risk of CV events. They made every effort in this work to show us what COVID-19 does, not what it is correlated with. And yet still, I would caution that correlation seen here is not necessarily causation.
That said, I think the way the work was conducted there is a good chance the increased risks were caused by COVID-19, and that more severe COVID-19 means more severe increases in CV risks.
We have a few technologies that can substantially reduce the risk of severe COVID-19. The first and foremost of these is vaccination, and indeed also boosted vaccination. Right out the gate this meaningfully reduces your risk of hospitalization, and that is connected by this work to reducing your risk of negative CV outcomes after COVID-19.
The next technologies that we have are antiviral drugs. Used early in infection, products like PAXLOVID, molnupiravir, and monoclonal antibodies can prevent a high-risk infection from become a full blown severe infection with a trip to the hospital. Which means, also potentially reducing these elevated CV event risks. For this reason, it’s really important that you not try to tough it out if you get COVID-19 and are at risk of a severe infection. If you have any symptoms of this disease, test immediately and frequently with rapid antigen tests and follow up with PCRs if you get a positive result. The reason I say this is that this method will ensure your case is identified as COVID-19 as early as possible, so that you can get these drugs when they are likely to have their greatest effect.
Vaccination keeps around 90% of the people who would otherwise be hospitalized, out of the hospital. PAXLOVID does about the same, in those who qualify for it. Using these together, I think we can keep the increases in CV risk rather small by keeping the acute COVID-19 infections as mild as they can be.
Unfortunately, not all the risk increase goes away here. It is ultimately best to avoid COVID-19 infection as much as you can for as long as you can. However, the increase in CV outcome risk can be minimized through vaccination and appropriate treatment if COVID-19 does eventually develop. The best course of action remains to prepare yourself for COVID-19 by getting vaccinated, avoid the disease to the extent that you can, and immediately seek appropriate diagnosis and treatment if that breaks down.
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.
What am I doing to cope with the pandemic? This:
Tummy time!
Letting a baby spend time on their stomach is important for building neck and shoulder strength. This is called “tummy time.”
Before I was a parent, this cute name made me think that this was somehow fun. Actually, babies hate tummy time…at least initially.
Which is why my wife and I were delighted to see, yesterday, our daughter not only not screaming her lungs out during tummy time, but actually smiling and laughing!
She then proceeded to roll over onto her back for the very first time—a milestone we’ve both been waiting for.
For length, I have left out comments from the last issue, but encourage you to go back and read the conversations on the last issue as they are often educational.
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, or if you are unable to comment due to a paywall.
If you liked today’s issue, please consider becoming a paid subscriber and/or sharing this newsletter with everyone you know.
Today’s Other Viruses section contains a small amount of COVID-19 information; all of that has been written in before the paywall, continuing with my commitment to make COVID-19 information in this newsletter free.
For those who won’t be continuing beyond that into the rest of the paywalled section below—as well as everyone who will—please know that I deeply appreciate having you as readers, and I’m very glad we’re on this journey together.
Always,
JS
Viruses that cause cancer
This one comes to us based on a paying subscriber request—one that I do not think the requester expected to have answered in so long a format, but the person asked an interesting question.
Specifically, they wanted to know if SARS-CoV-2 seemed likely to be able to cause cancers, because they have read that viruses can in some cases cause cancer. Before I insert the paywall, I’ll give my answer to that aspect: No, I don’t think it will, and I’m pretty confident in that response. I don’t think at this time there is anything to suggest that SARS-CoV-2 will directly elevate cancer risk. It has no known similarities to the handful of viruses that are known to cause cancers in humans. Like anything in life, it may have some indirect effects that can enhance cancer risk, though…but I don’t think it is likely to be a true oncogenic (cancer-causing) virus. Also, like anything with viruses, there is the potential for surprising unknowns. My expectation could be wrong. Which is another reason it’s really never a good idea to get an emerging virus on purpose.
Behind the paywall, we’ll talk about that handful of viruses and how they are able to cause cancer.