Omicron Evolves and the Covidization of Scientific Publishing

Just as we thought Omicron was rolling across the US and into oblivion, a new “subvariant” has arrived and is, again, taking over. At the same time Moderna is announcing dosing of the first participant in its phase 2 study of an Omicron-specific booster. But Omicron’s evolution wasn’t unexpected – the World Health Organization’s recent update cites four lineages of Omicron, dubbed BA.1 through BA.4.

“So it goes,” to quote Kurt Vonnegut in Slaughterhouse Five. But that statement was in response to death among the Tralfamadorians – not the robust activity of a tiny virus.

It seems to me that the continual categorization of SARS-CoV-2 reflects the human urge to group, categorize, and name things to help us understand them. I think the situation is eventually going to dissolve into a continuum of genetic flux as the tango of mutation and selection continues. That’s what nucleic acids do.

Since it still new days for Omicron 2.0, here’s a snapshot:

WHAT WE KNOW 

BA.2 (newbie Omicron) is all over the world. It is most prevalent, and increasing, in southern and southeast Asia, as BA.1 (original Omicron) diminishes. In many other countries they’re already running neck-and-neck.

BA.2 is here in the USA. This time the president didn’t try to stop it by restricting visitation.

The subvariant showed up in November, first in southern Africa. It follows where there’s been an (original) Omicron spike.

BA.2 has been dubbed “stealth Omicron” because it doesn’t have a single-base deletion mutation that made BA.1 difficult to detect (the S-gene dropout phenomenon that prompted FDA to quickly retool some PCR tests and fashion a faster Omicron one in December 2021.)

The Venn diagram: BA.1 and BA.2, share 20 mutations in the spike gene, and both share a pair with Delta. Four of the mutations change the hotspot – the receptor binding domain, or RBD – that antibody treatments target.

We have a bunch of genome sequences of BA.2, but not much more. You can track them and the country-by-country distribution here.

WHAT WE DON’T KNOW

The impact of BA.2 on case counts, hospitalizations, and deaths.

Whether BA.2 is more transmissible than BA.2.

If having BA.1 protects against BA.2. When the newbie elicits its own antibody repertoire and T cell profile, it may earn its own Greek letter, countering my idea to just give up on names.

BA.2’s origins. Did BA.1 beget BA.2, or did the 20 shared mutations arise by chance? Did the Omicron siblings diverge from a shared ancestor, like humans and chimps? Did BA.2 arise in southern Africa and in parallel in southeast Asia, or jump from one to the other? (Comparing genome sequences will yield answers soon.)

The “COVIDization” of Scientific Publishing

The pandemic has had a profound effect on the ability of scientists and medical researchers to crank out articles, not to mention we science journalists. This is my 88^th COVID article – I’ve all but abandoned my regular rare genetic disease beat.

And so I was curious to notice a preprint at MedRxiv, “Massive covidization of research citations and the citation elite.” First author is John Ioannidis of Stanford, a controversial figure from his initial downplaying of COVID (in 2020 he predicted 10,000 total deaths) yet he was also the first to question the validity of Theranos’ all-in-one bogus blood test.

Ioannidis specializes in studying research, and COVID is an enticing topic. The new study consulted publisher Elsevier’s Scopus database of many thousands of citations of research papers, published through August 1, 2021. Findings were intriguing.

COVID-19 was the focus of 4% of all papers published and 20% of citations to papers published in 2020-2021.

The share rises when parsing the journals by topic, accounting for >30% of citations for science journals and 79.3% for General and Internal Medicine.

Considering only science, “98 of the 100 most-cited papers published in 2020-2021 were related to COVID-19. 110 scientists received >=10,000 citations for COVID-19 work, but none received >=10,000 citations for non-COVID-19 work published in 2020-2021.”

“For many scientists, citations to their COVID-19 work already accounted for more than half of their total career citation count.”

The paper concludes, “Overall, these data show a strong covidization of research citations across science with major impact on shaping the citation elite.” I think the quest to understand an emerging and ongoing pandemic is somewhat more than a spitting contest among researchers eager to see their names on papers, but you never know.

Covering COVID in My Textbook

I’m presently revising my human genetics textbook with McGraw-Hill for the fourteenth edition. How much COVID to include? It nestles neatly into coverage of mRNA, immunology, vaccines, cell biology, population genetics, and evolution.

The publication date is September 2023. Where will we be by then? Back to some semblance of normalcy? Still masking? Likely something in between.

Looking ahead, I can’t help but wonder when we’ll begin to see inklings of the natural selection that will act against those who refuse COVID vaccines. For they continue to perish at staggeringly higher rates than the vaxxed – yet inexplicably seem oblivious to this most obvious, stat-backed fact.

Greater knowledge of biological principles could have saved lives.