Returning to Live Music and How a Tiny Mutation Sent Delta All Over the World

A few nights ago I went to my first live music show since pre-pandemic times: Ann Wilson, the vocalist from Heart. She and her new band were at The Egg, a small ovoid-shaped venue in Albany, New York. We were in the third row, very close to the stage. All of us wore masks, and should a smidge of nostril emerge, an admonishing usher materialized instantly.

“It’s great to see all of your smiling eyes!” joked Ann as she looked out at the limited-capacity audience. The performers were unmasked, Ann belting out the tunes, the guitarist next to her writhing in the throes of guitar-face, a malady in which a man playing a guitar assumes a simian visage, like Caesar in Rise of the Planet of the Apes caught deep in thought. Who knew that guitar-face would one day deter spread of a virus?

The show was amazing, full of rock classics, Heart tunes, and songs Ann wrote during lockdown. COVID restrictions just couldn’t reign in long-ingrained concert behavior. And so we all belted out Dream On and Barracuda along with Ann and her band the Amazing Dawgs, our masks undulating to the beat, as I hoped fervently that none of the oldish audience would keel over from asphyxiation.

“An Experimental Pop Concert” Simulates Viral Spread

This morning I was happy to see a new paper, “The risk of indoor sports and culture events for the transmission of COVID-19,” published in Nature Communications. Stefan Moritz and colleagues in Germany staged “an experimental pop concert” in August 2020 and found that good ventilation and “suitable hygiene measures” could limit virus-carrying aerosols and droplets.

The 1,212 attendees wore monitors to track their movements, each assigned to a “hygiene scenario:”
• no restrictions
• moderate restrictions (checkerboard seating and doubling entrances)
• strong restrictions (seating 5 feet apart and quadrupling entrances).

Each concert-goer on average contacted nine others, mostly during entry and exit. Those who had no restrictions had contacts exceeding 5 minutes throughout the event, compared to the brief and sparse encounters under the other conditions.

Based on these initial findings, the researchers developed a model of 24 infectious individuals among 4,000 attendees in an indoor space, testing two ventilation scenarios with different air exchange rates and airflows and factoring in mask-wearing. With a faster air exchange rate, each infectious person passed the virus to an average of 3.5 others. But with a slower air exchange rate, virus spewed and wafted to 25.5 people – almost a ten-fold increase. Mask-wearing cut transmission further.

“The overall burden of infections resulting from indoor mass gatherings depends largely on the quality of the ventilation system and the hygiene practices. Presuming an effective ventilation system, indoor mass gathering events with suitable hygiene practices have a very small, if any, effect on epidemic spread,” the researchers conclude.

But that was then. A year ago.

Delta Dates the German Experiment

The experimental pop concert in Germany used an overly-optimistic reproductive number (“R naught”) for the virus of one, meaning that one infected person on average passes the virus to one other. The original SARS-CoV-2 actually had an R naught of 2.3 to 2.7, the alpha variant that began in the UK of 4 to 5, and the delta variant now surging throughout the world, of 5 to 8.

Times have changed, as I wrote here 2 weeks ago in Scary Variants and Vaccine Hesitancy Set Up a Perfect Storm – for the Virus. In short, the millions in the US who haven’t been vaccinated enabled the virus to flit around enough to mutate into greater transmissibility.

But exactly how did earlier incarnations of the virus morph into delta? It turns out that the tiniest of changes lies behind faster transmission – just one RNA base swapped in for another that corresponds to a crucial part of the spike. A single, simple mutation, one of the nine that make up the delta variant, is reverberating at a global level.

How Delta Conquered the World So Fast

The viruses are festooned with spikes that latch onto our cells, like sea urchins burrowing into sand. Each spike protein has two parts: S1, which fuses the spike to the human cell, and S2, which pops the virus in. But S1 and S2 must be cut apart in order to do their jobs.

The mutation that revs up delta’s entry into our cells, called P681R, contorts the interface of S1 and S2 in a way that speeds the snipping, enabling the virus to fuse to the cell and enter much faster – a little like altering the German rock concert scenario to open the doors wider so more people can enter, faster. A team from the University of Texas Medical Branch conducted an elegant series of experiments that reveals how this all transpires, their findings available as a preprint. Viral genetic instructions then subvert the host cell to make, package, and explode with new viruses.

(Technical aside: P681R refers to swapping an arginine for a proline at position 681 in the spike protein, resulting from a single RNA base change. The spike is a chain of 1273 amino acids – hence the original name of the Moderna vaccine, mRNA-1273.)

Site 681 in the spike protein is also of interest because it’s a target for a protein-cutting enzyme called a furin. If “furin cleavage site” rings a bell, that’s because it’s central to the “lab leak” hypothesis of the virus’s origin.

The site in the spike that furin cuts, 4 amino acids long, forms a signature that algorithms can compare among species to deduce the evolution of the novel coronavirus. Because furin cleavage sites are found in certain coronaviruses that originated in rodents or bats, but not in the closest known relatives of SARS-CoV-2, the idea of a lab-nurtured bat coronavirus emerged that begat SARS-CoV-2. Or, we just haven’t identified the closest relatives yet. Science never offers “proof” and rarely amasses findings into sweeping theories. Instead, we investigate alternative hypotheses, one at a time, to build knowledge and ask new questions.

CODA

Do the findings of the experimental pop concert described in today’s Nature Communications paper, proclaiming ventilation and hygiene measures sufficient to contain viral spread at indoor mass gatherings, apply in the world of delta? How will public health measures hold up for variants yet to come? What will similar simulations reveal when audiences are parsed for vaccination status, as they couldn’t have been a year ago?

We don’t know. But one thing that we know for sure is that mutation and evolution are forces of nature that we can’t control. New mutations will arise from replication errors, combine into what we call variants, and sweep through populations on crests of positive natural selection if they benefit the virus, as the P681R mutation in the delta variant has done.

Because we can’t change the forces of nature, we must do all we can with the weapons we already have – vaccines, distancing, masks. But to stay sane, I think it’s good to experience a whiff of normalcy now and then, like I did the other night at the Ann Wilson show. Next week I’ve got James Taylor/Jackson Browne and the Dead at a large outdoor venue. I’ll be careful and wear a mask – but I can’t stop the feeling of wanting to sing along.

(Shameless plug: check out the Rose & Bolt officially licensed Grateful Dead jewelry collection, from my designer daughter Sarah.)