Alina Chan Profile picture
25 Nov, 27 tweets, 7 min read
A lot of interest in the D614G mutation comes from whether it made SARS-CoV-2 significantly more challenging for other countries, including Europe and the US, to stop the spread of the virus compared to when it first emerged in China.
For instance, Malaysia's Health Ministry Director infamously said that the D614G variant is 10x more transmissible.

Even though D614G was also present in China in January. See thread:

news.cgtn.com/news/2020-08-1…
Two peer-reviewed papers were just published discussing D614G and whether more transmissible variants of SARS-CoV-2 have emerged since late 2019:
cell.com/cell/pdf/S0092…

And nature.com/articles/s4146…
The UK paper states: "Global dispersal and increasing frequency of the SARS-CoV-2 Spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of Spike D614G in the UK"
They could not conclude that D614G was being selected for - in lay terms, providing a benefit so that viruses carrying G614 would have an advantage over viruses with D614 (the original first detected in Wuhan). And said that continued study of D614G is required.
What they found in the UK: "younger patients more likely to carry 614G... 5 years older among female carriers of 614D versus 614G and 4 years older among male carriers of 614D versus 614G"

Due to how the pandemic played out, people infected with D614G were ~5 years younger.
More importantly to the public, D614G did not affect severity or mortality of covid, albeit there was a detected significant difference with D614G viral load:
The authors also commented that another variant "RdRp P323L, occurred almost concurrently with D614G... The rarity of independent occurrences of D614G and P323L make it impossible to evaluate the effects of these replacements epidemiologically"
Although "614G clusters tend to grow to a larger size than 614D clusters" this analysis only controlled for time of introduction, not age (as far as I can tell from the article), which could be an unknown confounder; younger people are in the workforce/college/active social life.
For the viral load assay, it would have also been more informative if the patient stats (including age) and time of sample collection and processing were published so that these variables can be controlled for.
The authors say so as well, but propose that "the (persistent) mean age difference of 4-5 years is unlikely to correspond to a large difference in contact rates."
Ultimately, "the estimation of the absolute size of this (D614G) effect is uncertain and much harder to predict"

The authors cannot decisively confirm whether the pandemic was "driven by D614G" or whether this mutation was "in the right place at the right time".
What about the other paper that looks at global dynamics? (Different advantages and disadvantages compared to a UK-only approach.)

"we find no evidence for significantly more transmissible lineages of SARS-CoV-2 due to recurrent mutations"
nature.com/articles/s4146…
The study expanded on the difficulties of teasing out whether D614G truly led to an increase in transmissibility, but suggested that it was "probably a demographic artefact: D614G went up in frequency as the SARS-CoV-2 population expanded, largely due to a founder effect..."
My takeaway from these papers and other papers that came before is that it is incredibly difficult to tell, 10 months after D614G emerged, whether it even slightly increases in transmissibility in humans.

In other words, it's not D614G's fault that the pandemic got this large.
Europe and the US did not get some kind of supersized SARS-CoV-2 that was unbeatable (and yet, at the same time, somehow perceived by many as a hoax).
A lot of people ask about the animal experiments, so I'll briefly revisit again. "D614G substitution does not alter SARS-CoV-2 pathogenesis in hACE2 mice." science.sciencemag.org/content/early/…
Same paper, also no difference in virus titer (quantity) in hamsters' lungs or respiratory tracts.
The one instance in which they saw a difference was when they performed an animal-to-animal transmission experiment, which suggested a possible head start for D614G, but ultimately "marginal enhancement" in hamsters.
It's unclear whether the conventional method by which these viruses were produced in monkey kidney cells could have resulted in some differences between D614 and G614 that normally wouldn't exist in real life transmission between humans.
tldr scientists have observed that the conventional way of producing SARS2 viruses (for experiments) actually selects for mutants that are not as fit in humans. Are monkey kidney (vero) cells the most appropriate producer cells for virus that will be used for infection assays?
The other hamsters vs SARS2 paper, in contrast, observed differences in virus amount but only in the nasal wash (not other part of the respiratory tract or lungs) and only at 4 days post infection (4DPI not 2 days post infection); see figure 2B and C. nature.com/articles/s4158…
Just to reinforce, one paper did not observe any changes in virus amount in respiratory tract/lungs over several days post infection, but the other paper did observe a difference only in nasal sample (not trachea or lung) and only on one of the days tested post-infection.
The latter paper also performed a competition assay where hamsters were given equal amounts of each virus. They found "respiratory tissues showed G614/D614 ratios of 1.2 to 2.6 on days 2, 4 and 7 after infection, indicating that G614 virus has a consistent advantage"
Taken together, the two hamster studies suggest a slight advantage conferred by D614G. Still, it is difficult to extrapolate this to humans, where the data interpretation is still very challenging even for top experts, and we're not spreading SARS2 from our kidneys (hopefully).
Should a country or state be more fearful if they detect D614G in their population? The answer is no.

Controlling the local spread has a ton more to do with your local public health policies than with the D614G mutation. It is not, as far as we can tell, 10x more transmissible.
One good example for this is Singapore. Many of the initially detected outbreaks were of D614G mutants (dark blue), and were quickly traced and suppressed (almost eliminated by Apr). But the non-D614G form took root in a population that was under-tracked and led to outbreaks.

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More from @Ayjchan

27 Nov
“With publication count highly valued, analysis may also be delayed as teams ‘salami slice’ the underlying results into multiple papers.” 🤣
Been in research for 12+ years and can say that the inability to reproduce a considerable amount of work published even in high IF journals has real costs - to scientists' careers, the research ecosystem, and taxpayers who are ultimately paying for the vast majority of research.
Research publishing can be compared to a game of bluff, where the biggest winners are not necessarily the most honest. But in research, there's no reward for calling someone's bluff, which can likely drag you through years of hell, stalling your own career.
Read 4 tweets
26 Nov
Great article by @sciencecohen
"Not urgently needing the vaccines at home to fight a virus it has largely quashed, (China) is playing a global game.. using the vaccine to promote the diplomacy of foreign policy objectives."
sciencemag.org/news/2020/11/g…
In-depth discussion of China vs the West's vaccine approaches: which can induce broader immunity, is easier to manufacture and distribute, has the risk of antibody-dependent enhancement of covid, and, importantly, can be readily manufactured locally in other countries...
"crucially for China’s vaccine diplomacy, many.. countries have manufacturers that have produced inactivated virus vaccines for decades.. (those) that cannot access vaccines bankrolled by Warp Speed—especially those that hosted China’s.. trials—might have a more secure vaccine.."
Read 5 tweets
24 Nov
Also people asking me about this @nytimes article about Dr. Limeng Yan, Steve Bannon & Miles Guo.

My stance has not changed. We need a way for whistleblowers to get out of China without Bannon and Guo standing in their way and damaging their credibility.
nytimes.com/2020/11/20/bus…
My original thread response when Dr. Yan released her first preprint is here: "If there is one thing that this entire saga has made clear - it is that whistleblowers (as it pertains to SARS2) have no obvious safe route of sharing their information."
For those who aren't too familiar with Dr. Yan's story, here is a quick summary:

In Jan 2020, Yan was helping her supervisor to investigate the new covid outbreak. She heard rumors about the dangerous new virus that the Chinese gov was playing down, and blew the whistle...
Read 17 tweets
24 Nov
People keep messaging me with this @NatureNews article about SARS-CoV-2-related viruses discovered in Japan and Cambodia.

What does this mean in regards to the search for the #originsofSARSCoV2 ? nature.com/articles/d4158…
First, kudos to the article: "Strong evidence suggests that SARS-CoV-2 originated in horseshoe bats, but whether it passed directly from bats.. or.. an intermediate host, remains a mystery."

Scientific consensus is that bats are the ultimate source. But how did it get to Wuhan?
The Cambodian virus from 2010: "The virus’s genome has not yet been fully sequenced — nor its discovery published — making its full significance to the pandemic hard to ascertain."
Read 12 tweets
21 Nov
USA getting close to 200,000 new daily covid cases and ~1000 covid deaths per day.

An estimated 50 million travelers this Thanksgiving. Some may have already started their trip home this weekend.

Don't need magical powers to see this will won't go well.

technologyreview.com/2020/11/14/101…
For those still on the fence, please consider alternatives to in-person Thanksgiving.

On top of the regular Zoom, Skype, Facetime, Whatsapp meetings, you can:

(1) Watch movies and Netflix with your family using Teleparty netflixparty.com
I recommend Crash Landing on You.
(2) Play super fun app/online games.

Jackbox games - I like Drawful and Trivia Murder Party. jackboxgames.com/how-to-play/

Among Us - Murder your family and friends digitally instead of at Thanksgiving dinner. cnet.com/how-to/among-u…
Read 18 tweets
20 Nov
Went from helping to co-organize the @sciencepolicy conference to being a #CSPC2020 topic.

How can scientists address questions that have been painted as conspiracy theories? And without amplifying or legitimizing misinformation related to these questions.

Thanks @Sciencish
Good tips in this graphic by @CaulfieldTim
Definitely: Always consider the body of available evidence on the topic, recognizing that science evolves.
As a scientist who has been washed out to sea on a contentious covid topic, I find it safest to talk to science journalists for news articles - professionals with some extent of scientific training, who know what to ask scientists, how to probe their reasoning and evidence.
Read 5 tweets

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