Yesterday I made a trip (dare I say pilgrimage?) to my favorite neighborhood coffee place, a coffee roaster only open to the public on weekend mornings. It is tucked away in a small row of establishments mostly consisting of small business headquarters and tiny religious meeting places; not much going on except for the weekend coffee business. When things hit lockdown for the pandemic, the coffee started flowing again after the owner opened a window to the parking lot to make a walk up outdoor order site. I was happy to park and wait for my cappuccino and bag of beans.
I hadn't been there in a few weeks, and now the walkup window is closed. Inside, the already tiny seating area is even smaller with the counter in front of the main prep area shut down. I waited with a group of about 15 people, some masked, some not, and had a chance to catch up with Felix the owner. Looking around, I realized I was witnessing the future of the pandemic.
Tasseography
I didn't spend my wait there trying to read coffee grounds to predict the future, but as I said last week our current ability to predict the future is limited by poor data (less testing, home testing not reported, some states decreasing reporting frequency, etc). Tasseography might be as accurate as anything else. Looking to the UK once again for hints of the future, the reproductive number there is holding steady or maybe drifting down, a good sign. The variant situation is interesting, still with an overwhelming predominance of BA.2 but now with some newer recombinant lineages and even some totally new omicron sublineages (BA.4 and BA.5) detected last week. Nothing to panic about, just keep a watch.
A Befuddled FDA
Last Wednesday the FDA VRBPAC met to discuss the issue of vaccine boosters. I had a busy clinical load that day so could only attend the live meeting intermittently. Also, due to some technical problems, parts of the live meeting and the recording itself are missing audio input, including a key portion that I wanted to hear where members questioned Israeli scientists about 4th doses in older adults. The slides themselves are available though, and do provide a lot of information.
I don't think I've ever seen a group of medical experts struggle more with trying to blaze a path forward, entirely understandable because of the uncertainties of this pandemic particularly in predicting future variant emergence. What is clear, however, is that we need a new strategy available likely by the fall, when cold weather returns and people again move to more frequent indoor gatherings which will facilitate SARS-CoV-2 transmission like the Gridiron Dinner last week. Here are a few of my take-home messages from the meeting.
There isn't enough time to get clinical data on any new variant in time to decide on vaccine composition; if the past is any predictor, by the time the variant appears it's already too late for a variant-specific vaccine to be developed. This is totally different from seasonal influenza where strains seen at the end of the previous season can be reasonable guides for vaccine production for the next season. Things happen much more quickly with SARS-CoV-2. Also, at present and likely for the extended future, we don't have an antibody or other correlate of protection. Even if we did, that could change with the next variant as we've seen so clearly with omicron.
Future vaccines likely will need to bivalent or multivalent, covering more than one strain/variant, or perhaps a new approach targeting a conserved region of the virus like the nucleoprotein will be better. That latter strategy is underway but could take a longer time to develop. I doubt a vaccine targeting just the original omicron strain will cut the mustard for boosters next fall.
We've just witnessed a super spreader event in DC with some big names infected. Given current behaviors, it won't be just my favorite coffee shop that's risky. Each of us will need to weigh our own risk profiles, taking into account both individual risk factors for severe disease as well as risk factors of our close contacts. I interact with immunocompromised and unimmunized children all the time, I'll be playing it very much safe to protect them. I wear N95 masks full time when I'm around them and also when I'm in the grocery store or other indoor settings.
And yes, I wrote this post while sipping a nice cup of coffee made from Colombian beans: "medium body with hints of honey, pear, cardamom & fennel." No, I couldn't really pick out those flavors, but it tasted great.
Speaking of befuddlement :
it is possible ( ? Probable ) that those completely vaccinated ( not considering this fall booster issue ) then infected with an Omicron variant will be better protected from a fall variant than those vaccinated and not infected ....
It is also possible that any fall variant will be more severe and Paxlovid resistance
As such - can a reasonable argument be made to shed the indoor mask ( keep the N95 at work ) and figure an Omicron variant infection while fully vaccinated and Paxlovid working may be a blessing in disguise ?
If asked this - and I am being asked by my sophisticated families - what would you answer ?
Thanks for raising these issues, Michael, very important.
I'm asked some version of the "should I intentionally get infected to boost my immune response?" on about a daily basis. The short answer is no, but let me expand on that a bit. First, it goes without saying that anyone with risk factors for severe illness shouldn't take that approach - that's basically Russian roulette. Secondly, although somewhat uncommon in healthy individuals, complications from COVID-19 disease can be significant and many are still poorly understood. I'm talking mostly about cardiac, neurologic (including but not limited to long COVID or PASC), and thrombotic issues. It is still prudent to try to avoid infection, within whatever constraints on life style an individual chooses.
Antiviral resistance is a looming threat, but not something I would worry about for now. Paxlovid is a combination therapy targeting a viral protease, though it is essentially monotherapy; the ritonavir increases concentrations of the truly active agent nirmatrelvir. I mention that only because resistance is more likely to develop with monotherapy than with combination therapy. Paxlovid is the preferred treatment for outpatients with COVID-19 infection and high-risk conditions, authorized for individuals at least 12 years of age and weighing at least 40 kg. My relatively less worry about Paxlovid resistance comes mostly from the fact that so many antiviral therapies are in various testing stages now. Of course I could be wrong, but I think we'll have other options if/when Paxlovid resistance appears. I wouldn't use theoretic future antiviral resistance as motivation to have a COVID-19 party to purposely infect others. (Long ago, I think in these pages but possibly in my now defunct blog for the AAP, I mentioned my own childhood memory of serving as the vector for my older sister and her friends when I had rubella. This was before rubella vaccine and the plan was to infect all of them before they married and had children.)
Finally, this question provides a great opportunity to review Paxlovid indications and precautions, especially all the drug-drug interactions that are tough to commit to memory. Also remember that the Test to Treat program is up and running. Take this opportunity to see what locations are near you.