A short history of scientific debate (beware, Groundhog Day vibes)

A: How do we know it originated at the market?
B: Because it's not engineered
A: It could be natural and come via a lab collection right?
B: Well we have proven it's not from a lab in any way
A: How? B: Read the paper. It's in a prestigious journal by expert scientists. If you were a scientist you wouldn't question the point.
A: I've read the paper, and I am a scientist, and you only said it's not engineered, but a natural virus could still come through lab collection right?

Peer review is becoming anachronistic due to increasing peer competition. Recently it appears more likely to handicap a good paper than improve a bad one. If you have a good paper and submit to a competitive journal, it's hard to avoid a reviewer who is competing against you and motivated to slow you down.

If you have a bad paper, you just submit to a less competitive journal happy to collect your publication fees.

Out today in @jama: Paxlovid reduces relative risk of post-coronavirus condition (PCC, a.k.a. PASC and "long COVID"☹️) by 26%. Absolute risk reduces from 17.5% to 13%.

First study showing protease inhibitor treatment reduces long-term sequelae.

jamanetwork.com/journals/jamai… Some details: Patient is VA population, so 86% male, and mostly older (age 62y ± 15y SD), and had ≥1 risk factor for progression to severe disease (hence could get Paxlovid). Paxlovid patients were then matched with similar patients in the VA database for comparison.

NYTimes writers with no training in quantitative fields have managed to weave a complex story out of a few non-specific facts. Now statisticians and professors who used to be @nytimes heroes are being branded literally as "liars" here for pointing out we don't actually know. Those writers who think they were doing some service to society, or had the Dunning-Kruger confidence that they could understand the words so could accept and amplify the theories read to them, really need to pause and look at what they have actually done.

Read this and wonder, if Messonnier was so clearly correct and honest (and she was), and Redfield so incapable and politically subservient (and he was), then why did the WH replace Redfield with the equally incapable and politically subservient Walensky?

nytimes.com/2023/03/21/hea… The article above is about how CDC staffers recognized asymptomatic spread even as Redfield refused to warn let alone acknowledge it. A year later we have Walensky refusing to recognize that vaccinated people could get and transmit variant strains

https://twitter.com/michaelzlin/status/1485507481744789506

"In some cases, the amount of animal genetic material was greater than ... human genetic material, consistent with the presence of SARS-CoV-2 in these samples being due to animal infections."

Also consistent with animals, not humans, living in the cages😉
zenodo.org/record/7754299… Useful to note that the “samples” with SARSCoV2 RNA and animal DNA aren’t blood/saliva/mucus. They are surface and water samples. This was not mentioned by @nytimes in their recent articles, but that would have avoided misconceptions from juxtaposing "samples" and "animal".

This month, news outlets publicized the assertion that SARSCoV2 transport to Wuhan was via the wildlife trade, based on most early COVID19 cases being at/near the Huanan market (where live animals did indeed leave DNA 🙄)

The stories also repeat claims of no contrary evidence. The claims of no contrary evidence are insistently made by the authors of two market-origin papers who claim those are the only "expert" ones

However, true experts would know of two studies by more distinguished authors that suggest the earliest cases may have started elsewhere

This may be a shock to some on Twitter, but trying to guess someone's political leanings based simply on whether they agree or disagree with an extremist view of one party is highly unreliable. Say belief A is unpopular in both parties, but marginally more popular among Republicans. It's very possible for someone to disagree with that belief and still be a Republican.

The same holds true for Democrats.

Okay finally found the cough medicine I was looking for: Same active components as Mucinex or Robitussin, but no dyes, sugar, or thickeners. Robitussin and Mucinex are very viscous, making it hard to drink all the dispensed liquid from the measuring cup. I've always wondered if it was because the thickener was required for drug solubility. It's not. The guanifesin and dextromethorpan are fine in a watery formulation.

Today's breathless @nytimes story: animal cages previously known to have SARSCoV2 DNA on them now known to have animal DNA on them. Using DNA loosely to mean genetic sequence. Am aware SARSCoV2 is an RNA virus

Really no need to resort to personal insults.

It's just as IQ-challenged to insist that 2 lineages in marketgoers means it was in non-human animals first. The "lineages" were just a few mutations apart; they could have arisen anytime in the human population going to the market Two bases to be exact. Which can occur in a single person easily. (Mean evolution rate is 1 nt per transmission, but actually viruses in each person have more than 1 nt mutation, but most mutants break the virus)

Below is the complete "thought" process
virological.org/t/early-appear…

Scientists can get gaslit too. If you want to see an example, read the below from a PNAS essay trying to convince us that a lab researcher picking up SARSCoV2 while collecting bat samples isn't a lab leak scenario. Blue-highlighted text: sliding in a flimsy argument as proof via reference, without saying what that is. If it were so logical, just present it here.

What it was: that a 2-nt difference seen in human samples from the start "proved" the virus evolved in a non-human animal.

Some news today on one of the more interesting and controversial COVID19 topics, the Novavax vaccine

In a sense a recombinant protein vaccine should be one of the least controversial things ever, but the fast and new RNA vax have been soaking up all the $ and attention The relative lack of data on Novavax, and the slow speed of its approval, have become their own controversies.

Anyway, Novavax revealed at today's VRBPAC meeting that they need 6mo lead time to prepare boosters for new strains. This is new useful info:

reuters.com/business/healt…

Today we're worried by XBB.1.5 which reached 40% of US cases. David Ho's paper called its immunoevasiveness "alarming"

XBB.1.5 is a BA.2 derivative. I had said as early as June that FDA should request a BA.2+BA.5 booster. Instead FDA went Wuhan+BA.5.

XBB.1.5 is another FDA fail It doesn't require either a FDA position or a PhD to know that it's better to cover both extant strains in a 2022 booster. It was obvious that derivatives can arise from either BA.2 or BA.5. Maybe *more* likely from the earlier-peaking BA2 as there was more recent immunity to BA5

NEJM: remdesivir analog VV16 similar to Paxlovid in Chinese trial. Main issue is there was no placebo, only Paxlovid comparison, so unclear how much the patients benefited vs no treatment. Minor issue: non-blinded patients self-reported symptoms used to assess clinical score. Sustained clinical recovery was symptoms dropping to mildest level for 2d.

Most were vaccinated. Median 4d from symptom onset to 1st dose. Adding 3d incubation period → 7d from infection. This is similar to the Paxlovid trial, so expect low rebound rate

nejm.org/doi/full/10.10…

This will be my COVID-19 metathread for 2023. It will index my tweets on SARSCoV2. As the virus and our immune systems evolve, so will our responses in terms of prevention, therapy, and policy. First, a link to the COVID-19 metathread of 2020-2021

https://twitter.com/michaelzlin/status/1476327912194265094

Sorry, have been busy with holiday obligations, which in academia means writing papers.

But before the year ends I'd like to wish everyone a healthy 2023.

We can also see how my prediction for 2022 did. 1 year ago I suggested 2022 would be the year COVID19 becomes "like the flu". I was right in one way and wrong in another.

https://twitter.com/michaelzlin/status/1476987713223946240

Yesterday UK's MHRA approved GSK/Sanofi's protein-based COVID-19 vaccine (EU approved last month)

The novel aspect of this vaccine is it uses Beta rather than original SARSCoV2 spike

Interestingly, works better on all tested variants, including original

gsk.com/en-gb/media/pr… The history of this vaccine is quite convoluted. In 2021, they tested 5mcg original spike and found it insufficient in older people. They then upped to 10mcg.

https://twitter.com/michaelzlin/status/1455230212757614593

There are many tragedies of COVID-19. One of the more ironic ones is that despite COVID-19 vaccines having saved the lives of >3M Americans, anti-vaccine sentiment is higher than ever.
washingtonpost.com/politics/2022/… We're used to the psychology of no good deed going unpunished, and people resisting coercion to do things that are good for them.

But vaccines have a special hurdle: vax benefits are delayed and invisible, so they can only be trusted if data and decision-making are trusted

Yes
theatlantic.com/science/archiv… What Pfizer says about "real scientists" vs what real scientists say

We need to improve quality of clinical research and peer review

These researchers ask what's the rebound rate of Paxlovid or molnupiravir.

But only hospitalized patients are studied. That means they had severe symptoms and big immune response

Of course they will rebound less Sure enough, rebound rates were low in the hospitalized population.

But the abstract is misleading in not mentioning the hosptialization, implying the conclusion is for anybody in general.

The broad policy recommendation at the end is especially not justified.