HIV and ID Observations

John Keats, portrait by Joseph Severn

Wow, that was quite the depressing post-holiday week in ID Land.

For that, we can thank the new villainous variant, Omicron, which arrived ironically just as most of us here in the United States sat down to celebrate something approaching a “normal” Thanksgiving for the first time in two years.

Oh yes indeed, thank you very much for joining us, Omicron. How do you like your cranberry sauce?

Talk about an unwelcome guest at the party.

Here in Boston, like many parts of the northern U.S. and Europe, the arrival of Omicron joins a very active pandemic still dominated by Delta. It’s not like we needed this new highly transmissible, immune-evasive version of SARS-CoV-2 to jolt our holiday season. The current version (Delta) of the world’s least-favorite virus remains quite capable of straining hospital resources; disrupting school, work, and travel; and putting us all on edge.

Sigh.

Meanwhile, everyone wants to know what happens next. I totally get it — the pandemic has been with us for what feels like an eternity, and an accurate prediction would be highly valuable for all. Since the news broke about Omicron — has it really been less than 2 weeks? — these predictions have come in two vastly different flavors.

First the doom and gloom:

It’s highly transmissible … and very vaccine evasive … lots of reinfections … so many mutations … case rates skyrocketing in South Africa, fastest increase ever … super-spreader events among fully vaccinated … kids getting hospitalized … already it’s on all continents … some monoclonal antibodies won’t work … spike gene target failure, whatever that means … >30% test positivity in some parts of South Africa … transmission with minimal contact in Hong Kong … how do you even pronounce this stupid word …

Or alternatively, maybe it’s not so bad after all:

Cases are mostly mild … hospitalization rate is lower than with Delta … our cellular immunity (from vaccines or prior infection) will save us from severe disease … Omicron may have genetic material from common cold coronaviruses, and we live with those, don’t we? … maybe the mutations will make it less virulent … the vaccine manufacturers are tweaking the vaccines to respond … our PCRs and rapid antigen tests still work … some monoclonals (sotrovimab, AZD7442) should still be effective … antivirals are coming soon … this will be how the pandemic finally plays out, a mild disease leading to broad immunity …

So which one is it? Are we headed back to square one, and soon will be decontaminating our groceries and packages again? Or are we close to the pandemic endgame, optimistically predicted before, but this time we really mean it?

The reality is undoubtedly somewhere between these two extremes. We can’t possibly be going back to square one; we know so much about this virus by now:

I absolutely hate this title in ⁦@TheAtlantic⁩

To say we know nothing completely neglects the research, learnings and experience of past 2 yrs.

We know SO much about Omicron. 

Relative to ALL we DO KNOW, the things we don’t know are minor

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https://t.co/a3eFjCgOBq

— Michael Mina (@michaelmina_lab) December 4, 2021

On the other hand, Omicron could very well pose quite the challenge, as it appears to have qualities similar to Delta and has so many spike protein mutations that vaccine scientists gasped when they first saw the structure. In other words, beware overly optimistic predictions about Omicron just as much as doomsday scenarios.

Where does that leave us? At times of great uncertainty, I try to channel the teaching from a memorable college English literature course on Romantic poetry. (I know, pretentious — but stay with me on this one.) The great poet John Keats, writing to a friend, cited an ideal state of mind for the creative process, one he called “negative capability.”

Despite the word negative, he meant it in a quite positive way, as it describes a person “capable of being in uncertainties, mysteries, doubts, without any irritable reaching after fact and reason.”

Not surprisingly, I’m not the first person, and not even the first doctor, to think of this important quality while trying to navigate unknowns while living through a pandemic. Indiana University’s Dr. Richard Gunderman (who has way more titles than I) wrote earlier this year a highly pertinent essay:

Rather than coming to an immediate conclusion about an event, idea or person, Keats advises resting in doubt and continuing to pay attention and probe in order to understand it more completely … Negative capability also testifies to the importance of humility, which Keats described as a “capability of submission.” As Socrates indicates in Plato’s “Apology,” the people least likely to learn anything new are the ones who think they already know it all.

I’ve tried this negative capability approach this past week with the deluge of questions sent my way by worried colleagues, friends, and family.

Here’s a brief personal example, posted with permission:

Maybe it’s a copout, but for questions like this, there is no 100% correct, data-driven, or accurate answer. What would you say?

And how are you doing, folks?