COVID Transmissions for 3-2-2021
Vaccine safety matters as much, if not more, than efficacy
Good morning and welcome to COVID Transmissions.
It has been 470 days since the first documented human case of COVID-19. The “470” is a sailing dinghy that is commonly used in competition sailing, including the Olympics, and is also a good “doublehanded” (2-person) teaching vessel for intermediate sailors. It’s not a beginner boat—though there is a beginner sister class, the 420, that is often a step along the way to learning the 470. The number in the name refers to the length of the vessel—470 centimeters. I’ve sailed a 470 a couple of times.
Today’s issue has some headlines, covering a global uptick in cases, but it also resurrects the “in-depth” section for a discussion on vaccine safety and how the results look for the various vaccines now on the market in the US.
As usual, bolded terms are linked to the running newsletter glossary.
Keep COVID Transmissions growing by sharing it! Share the newsletter, not the virus. I love talking about science and explaining important concepts in human health, but I rely on all of you to grow the audience for this, which you can do by using this button here:
Now, let’s talk COVID.
COVID-19 cases are rebounding globally
At a WHO briefing yesterday, Director-General Tedros Ghebreyesus noted that a global trend of increase in COVID-19 cases is emerging, reversing a 7-week trend of decreases. This is despite some countries—like Israel and Seychelles—vaccinating large percentages of their populations.
To a degree, this is not very surprising. The emergence of variants that seem to get a better foothold in humans, combined with patterns of pandemic fatigue and perhaps a false sense of security from the downward trends and available vaccines, seems to have allowed this to happen. I’m sure there are many causes contributing.
Some countries are taking this as cause to reinstate lockdowns. For those of us in the US, it would really be shocking to see the relatively small number of cases triggering these lockdowns, but it should come as a point of comparison to show us how much better things could have been with a competent response.
As a glimmer of hope, though, the first vaccines distributed by the WHO-COVAX program have arrived in Ghana and Ivory Coast, also announced at the same briefing. CIDRAP has a story on this here: https://www.cidrap.umn.edu/news-perspective/2021/03/covid-19-cases-rebound-globally-covax-immunizations-begin-africa
Another CIDRAP story focuses on how this uptick in cases is impacting the US, with a choice quote from CDC Director Rochelle Walensky, MD, MPH:
"The most recent 7-day average of cases, approximately 67,200, represents an increase of a little over 2% compared to the prior 7 days," said Walensky. "Please hear me clearly—at this level of cases with variants spreading, we stand to completely lose the hard-earned ground we have gained. These variants are a very real threat to our people and our progress."
That CIDRAP story is here, along with a kicker on vaccine hesitancy in Black Americans that is worth reading too: https://www.cidrap.umn.edu/news-perspective/2021/03/even-3-vaccines-now-cdc-head-warns-possible-4th-covid-surge
The bottom line is, in the US and around the world, we need to keep our guard up. We are near the end of the race on this and it’s more important than ever to be vigilant. We can beat this thing if we take it seriously until everyone can be vaccinated.
What am I doing to cope with the pandemic? This:
Watching: Filming of a Netflix series on my street
A Netflix show, Black Gumball (this is clearly a working title meant to obscure the actual nature of the production, but I won’t “out” them publicly) was filming on my street yesterday.
It’s always interesting when filming comes around to my neighborhood, but during the pandemic it is particularly interesting because it puts on display how the film industry is addressing COVID-19 while allowing their work to continue.
That work is, obviously, very important. I am not kidding. With so many people stuck at home, the generation of new artistic content is extremely important. So many of us have taken refuge in recorded arts during this pandemic. The existence of new artistic media content has been a real solace, and I don’t want anyone to forget it.
The film industry involves acting talent being unmasked. Black Gumball has some well-known stars in it, and they perform unmasked. They’re at great risk of infection at that time, and there’s no small risk to the crew that works on the show either. For that reason, testing of all involved is frequent in the film industry, often using rapid tests that can get results back in time to allow people to get to work. In my neighborhood today, there was a testing trailer that was set up for the purposes of this shoot.
There is an alternative world where rapid tests were made available widely during the COVID-19 pandemic, and we all got to take them each morning before going to work. In that world, we didn’t necessarily need to worry about mask discipline all the time or stay working from home for a year. Instead, we would have expected people who tested positive to stay home and get a more accurate follow-up test to confirm their diagnosis before returning to society.
This world isn’t a fantasy—it’s the world that the film industry has built for itself that has allowed it to continue operating. We could have done this for all industries, if the public health response had developed a true national testing strategy. Maybe there would still be some value in trying to set this up for everyone, even this late in the game. Dr. Michael Mina, who I greatly admire and has been calling for FDA approval of rapid antigen tests for months now, certainly thinks so.
In the meantime, I am impressed with how the film industry has made this situation work, even if it’s clearly not ideal. And I’m also grateful that this has allowed for needed entertainment content, one of the few things keeping a lot of us sane during the pandemic, to continue to be created and released.
Vaccine Safety Update
I wanted to take a minute to discuss the status of vaccine safety, because a lot of my writing focuses on vaccine efficacy, but safety is equally important. In clinical trials, we look for a favorable risk-benefit relationship, and safety studies are how we establish the risk that is paired with benefit.
By this time, most people know the common adverse effects of the mRNA vaccines. They are typically soreness, potentially mild fever, headache, fatigue, nausea, redness and pain at the injection site, and swollen lymph nodes. These were common with both mRNA vaccines, with around 94% who got the vaccine in the Moderna trial having a “solicited” (aka they asked the participants about it) adverse event (AE), vs 59.5% in the placebo group. For “unsolicited” AEs, this was 21.6% vs 19.1%.
In the Pfizer vaccine trial, for solicited AEs, numbers were reported a little differently, with injection-site and systemic AEs separated and only reported within 7 days of administration of either dose. After dose 1, systemic solicited AEs were seen in 59.1% of patients getting the vaccine after dose 1 (vs 47.0% in the placebo group) and injection-site reactions were seen in 78.6% vs 12.8%. After dose 2, systemic solicited AEs were seen in 69.9% of patients getting the vaccine after dose 1 (vs 33.8% in the placebo group) and injection-site reactions were seen in 73.1% vs 10.6%.
For both mRNA vaccines, these look to be rather high rates, but keep in mind that none of these data consider severity. Very few severe reactions were observed, and very few led to discontinuation of the regimen. There have been some rare reports of serious allergic reactions—about 2.5-5 instances in a million, depending on which you get—but these are relatively easily managed. A small number of deaths were reported in both mRNA vaccine trials (fewer than 10 in both trials), with the vaccinated arm showing either fewer deaths than the placebo arm (Pfizer trial) or an equal number (Moderna trial).
In the real-world experience, these safety profiles have largely been consistent with what has been observed, though there were some early reports of “death after vaccination” in very elderly people. I’ve covered these here before, but I want to reiterate that “death after vaccination” is very misleading as a statement. Most people who die these days die after a vaccination, because almost everyone alive today—and thus also most people who die—received some kind of vaccination as a child. Getting hit by a car 5 minutes after vaccination, and subsequently dying, counts as “death after vaccination,” too. None of the deaths that I’m aware of have been linked in any meaningful way to vaccination. The cause of death is important, and is something you should look for when being presented with new information about vaccine safety.
Now that I’ve summarized all of that, I am excited to add the results for the Johnson & Johnson vaccine. In the FDA briefing document that they submitted for consideration, solicited injection-site AEs occurred in 50.2% of patients who got the vaccine vs. 19.1% of patients who received placebo. Solicited systemic AEs occurred in 55.1% vs 35.1% of patients. Again, rates of serious adverse events and adverse events requiring medical intervention were quite low.
I have to caution against direct comparisons because there have been no head-to-head trials, but the numbers of adverse events with the Johnson & Johnson vaccine do appear to have been lower than in the trials for the mRNA vaccine trials. If it genuinely turns out that this vaccine causes fewer adverse events—with seemingly lower efficacy against any disease, but meaningfully similar efficacy against severe disease and death—it may be a viable alternative for the rare patients who have severe reactions to the mRNA vaccines that require them to stop the vaccination course. Having more options in the arsenal helps us to get this kind of flexibility.
Also, the apparently low rate of AEs in the Johnson & Johnson trial means that, perhaps, the joke in this tweet might actually be viable:
Well, not really. But it made me smile.
Ultimately, in these options, we see a set of three vaccines that have fantastic safety profiles, though all of them cause discomfort to some degree in the majority of patients. We also see that we potentially have different options that may be more viable than others for patients who cannot tolerate one vaccine or another, which is also great news. Safety monitoring in trial subjects and real-world vaccinees is continuing, and I will update here as time goes on.
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.
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.
Always,
JS
So, I speculate that tomorrow's column will deal with the Merck/J&J deal?
Do you happen to know if there are any investigations into using the J&J virus-vector vaccine as a nasal spray? The vector is a cold virus, it should readily infect the upper respiratory tract, and this might provide increased protection against infection (as opposed to symptomatic infection).