XE and why we may want Omicron to mutate

 XE— a new sister lineage of Omicron— has peppered the headlines this week. And while it’s important for scientists to track every change of the virus, I don’t think the public needs to be anxiety-ridden every time this virus changes. This is what viruses do to survive, and we should anticipate this. In fact, Omicron mutating may be good news for us.

XE (And XG, XR, Xl, etc., etc.,)

XE is not a new variant of concern. Instead it’s a recombinant or a combination of BA.2 and BA.1. As like what happened with “Deltacron,” XE was likely created when someone was infected with two different viruses at the same time. We are seeing more and more recombinations now because distinct viruses are circulating (Delta, BA.1, BA.2) at the same time.

Because someone can be infected with two viruses at the same time, the two sublineages can enter a person’s cell at one time. Then, when the virus tries to replicate inside the cell (to further spread to other cells), the genetic material can be mixed up. This is different from a mutation from a single infection, as depicted from the figure below.

(Figure from The Conversation. Original source here)

XE has BA.2’s spike protein copied and pasted onto the 5' part of BA.1. We have documented BA.1 and BA.2 mixing in other ways, too, which has resulted in other sublineage names like XR, XN, XP, XQ, etc., etc. Virologist Tom Peacock made the fantastic figure below displaying the phenomenon.

(Tom Peacock)

XE was first detected in England in mid-January and has caused more than 600 cases in England (which is <1% of cases). As of March 22, 763 XE cases had been identified in the greater U.K. It’s also been identified in India, China, and Thailand.

Since March 25, XE has shown modest growth advantage over BA.2. Latest estimates from the U.K. are showing a 10% increase of transmissibility over BA.2 (and BA.2 has a 40% increased transmissibility over BA.1, or the original Omicron). This means XE is slightly more contagious than the other sublineages.

The good news is that because the spike protein determines immune invasion, infection-induced defenses that people acquired against Omicron and/or our vaccinations should still work against this new recombinant.

The WHO said they won’t give XE a Greek letter name and will still consider it Omicron until “significant differences in transmission and disease characteristics, including severity, may be reported.” These differences haven’t been found so far. At the end of the day, XE is still considered Omicron.

Omicron mutating could be good news

While it would be wonderful if this virus just disappeared, this isn’t going to happen. It’s going to continue to mutate, especially given the high transmission levels across the globe.

Unfortunately, two years into this pandemic, this virus hasn’t provided any hints about where it’s going. Like I’ve written before, coronaviruses typically evolve in a ladder-like pattern. The flu does this, too. In other words, there is one major lineage, and every few years, a new variant sweeps and the others go extinct. (See Panel A in the figure below for a depiction).

But we haven’t seen this pattern with SARS-CoV-2. The next big variant hasn’t been coming from the last: Omicron didn’t come from Delta, and Delta didn’t come from Alpha. Instead, SARS-CoV-2 evolution looks like Panel B in the figure above. And this is incredibly puzzling.

(Next Strain)

But this may be because we just haven’t given it enough time. It’s only been two years, and other evolutionary trees, like the common cold, also had two-year time frames in which there were no ladder-like changes.

If SARS-CoV-2 starts evolving in a ladder-like pattern (something we would eventually expect) from Omicron then it will have more “flu-like” drift in evolution. This means that SARS-CoV-2 will inch towards more immune escape and higher transmissibility. This, coupled with seasonality, will determine attack rates. But it won’t be huge, unpredictable jumps like we saw with Delta → Omicron. And if we have more “flu-like” drift with SARS-CoV-2, this would be good news for two reasons:

1. We won’t have sweeping attack rates for a while. That’s because ~50% of Americans were infected by Omicron in 10 weeks. (Which is completely mindboggling. We’ve never seen a virus burn through a population at this rate. As a comparison, the flu infects 10-20% of a population in a span of 20ish weeks.) Large infection-induced immunity coupled with vaccine coverage will no doubt help build an immunity wall.

2. If SARS-CoV-2’s future becomes more predictable, then we’ll be able to anticipate mutations and prepare. For example, we could then plan to develop, roll out, and distribute updated vaccines like we do with the flu every year. There was an 8-hour discussion about this very topic at the FDA this week.

The virus is changing incredibly quickly, but a huge event in the next 12 months isn’t likely

We just don’t know what will happen next, though. Dr. Trevor Bedford, evolutionary virologist, made two big points during his presentation to the FDA this week.

First, he made it clear that the virus is mutating incredibly quickly. It’s changing about four times faster than the flu. In his figure below, you can see the SARS-CoV-2 graph is far more steep than the other three graphs depicting the rate of influenza mutations. This means that in just two years, SARS-CoV-2 has accomplished the same level of evolution compared to five years of H3N2 (flu virus). We hope that once we finally get transmission under control, the rate will eventually be slower than the flu.

(Trevor Bedford)

Second, while we expect with high certainty a “flu-like drift” of SARS-CoV-2, an “Omicron-like event” or a huge evolutionary jump can take place again, too. Unfortunately (or fortunately) we only have one data point over two years (i.e. Omicron), so our guesstimates have a high level of uncertainty. Dr. Bedford estimated that an “Omicron-like” event will happen every 1.5 to 10.5 years. We don’t know if this is a rare occurrence or a more common event. But, in the next year, Dr. Bedford estimates there’s a 70% chance we will not have another Omicron-like event.

(Trevor Bedford)

For the next “Omicron-like event,” according to Dr. John Beigal at the NIH, there are really only two antigenic spaces or areas of vulnerability this could happen: a virus that is closer to Beta, or a virus that is closer to Delta. Both very far from Omicron, which perhaps makes an Omicron-specific booster not a slam dunk decision.

Bottom line

We know that the virus is going to combine and mutate. XE is just another example. If Omicron continues to mutate, it may be a silver lining, because then we may finally be able to better predict where this virus is going and how to proactively prepare for it. In the meantime, we need to try and keep transmission down as best as possible so this virus doesn’t have the opportunity for another “Omicron-like event.”

"Your Local Epidemiologist (YLE)” is written by Dr. Katelyn Jetelina, MPH PhD—an epidemiologist, biostatistician, professor, researcher, wife, and mom of two little girls. During the day she has a research lab and teaches graduate-level courses, but at night she writes this newsletter. Her main goal is to “translate” the ever-evolving public health science so that people will be well equipped to make evidence-based decisions.

https://yourlocalepidemiologist.substack.com/p/xe-and-why-we-may-want-omicron-to

CDC Documents Early Covid Reinfections, Questions Natural Immunity Against New Variants

 New research from the Centers for Disease Control and Prevention documented 10 cases of early coronavirus reinfection from the omicron variant shortly after infection from the delta variant, raising questions about the lasting power of natural immunity against new variants.

The agency found 10 patients across four states who fell sick with the omicron variant within three months of a previous infection from the delta variant between October 2021 and January. The timing intervals between infections ranged from as few as 23 days to up to 87 days.

The report documented a small pool of reinfected individuals who were relatively young, so its findings “might not be generalizable to the U.S. population,” researchers stated. The median age of the group at first infection was 11 years old.

“Nonetheless, this study highlights potential limits of infection-induced immunity against novel variants,” they continued.

Nine of the patients were symptomatic during their first infection. Of the data available for eight of the patients during their second infection, six were symptomatic during reinfection.

The report concluded that “although the epidemiology of COVID-19 might change as new variants emerge, vaccination remains the safest strategy for preventing future SARS-CoV-2 infections.”

Reinfections became especially more common during the surge of the omicron variant, which sent coronavirus cases and hospitalizations to record levels. However, early reinfections have not been well studied and not much is known about their occurrence.

A small Danish study published in February suggested that the omicron subvariant BA.2, or “stealth omicron,” can reinfect people shortly after they recover from the more common lineage of omicron, though the occurrence is “rare” and is seen “mostly in young unvaccinated individuals with mild disease not resulting in hospitalization or death.”

Due to rapid tests taken at home and limited capacity for strain testing in general, “most early reinfections are likely not identified,” the CDC report stated.

https://www.usnews.com/news/health-news/articles/2022-04-07/cdc-study-documents-early-coronavirus-reinfections-raises-questions-about-natural-immunity-against-new-variants

Shanghai residents risk punishment in lockdown, sneak out at night to barter for food

 Each night under the cover of darkness, Shanghai resident Zhang Hongyan and her neighbours conduct barter transactions to get essentials which are in short supply due to the city’s coronavirus lockdown.

The residents conduct their bartering at night to avoid being caught outside their homes by authorities who enforce strict penalties for anyone caught breaking lockdown. On Thursday night, Zhang, who lives in the Baoshan district of the city, offered 10 eggs for barter in a WeChat group chat in the hope of receiving some fruit in return. On this occasion she was lucky, one of her neighbours agreed to give her a few apples in exchange.

“It’s not convenient during the day. I’ll leave the eggs at your building gate now and you go get them quickly,” she told the neighbour, named Anan, at 10 minutes to midnight.

“OK I’ll fetch it and leave the apples there. Non-face-to-face transaction to reduce the risk of infection,” Anan replied.

Shanghai residents have gone back to a cashless barter economy; trading for food and essentials as the megacity of 25 million people remains under lockdown since nearly two weeks ago.

Things being swapped range from garlic to sanitary towels after residents were ordered to stay at home to curb the city’s worst Covid-19 outbreak to date — driven by the highly transmissible Omicron variant of the virus.

While most households have received some supplies from the government after most of the city went into lockdown from Monday last week, the ancient way of trading has regained popularity within resident compounds as people find supplies running low and delivery services unable to keep up with demand.

On Thursday Shanghai recorded over 21,000 new infections, of which 824 were symptomatic, pushing the total number of cases since March 1 to a new high of 131,000. There is no word from the municipal government yet when it will lift the citywide lockdown.

Shanghai started a de facto citywide lockdown on April 5 when the municipal government reversed its earlier plan of ending a two-phase shutdown of Pudong and Puxi, the eastern and western sides of Huangpu River. Over the past week, nearly all of the city’s 25 million residents were confined to their homes, while supply chain issues have caused severe delays to the delivery of food and basic essentials for many in the city.

Vice-Mayor Chen Tong admitted on Thursday that some residents’ daily lives had been affected by the delivery delays and claimed that officials would fight “on the front line” to supply adequate food and necessities to people.

Cici Chen, a local woman living in a large residential compound in Songjiang district, said bartering had become an important part of her daily life and for residents in her building trying to help each other.

“At first some people offered certain stuff for free if they had adequate stock, but those who took it would volunteer to give something in return to express their gratitude. So gradually more people joined and it’s become our new way of surviving,” she said.

As the mother of a two-year-old child, Chen said she received baby milk formula powder and diapers from neighbours and in return she is trying to find them eggs and milk.

“Shanghainese are quite cold when it comes to relationships with neighbours, but this situation has brought our hearts together,” she said.

The practice is a little harder when the two sides live in different buildings, as the Shanghai government has stressed that the lockdown means people have to stay at home until restrictions are lifted. As a result people are unable to collect deliveries from the gates of their community or even dispose of their rubbish.

Designated volunteers or the community’s security guards have been enlisted to carry out these jobs instead.

But despite the risks of being caught breaching the lockdown by leaving one’s building, many are doing just that in order to trade for basic supplies while the authorities struggle to contain the virus.

https://www.scmp.com/news/people-culture/article/3173658/china-coronavirus-shanghai-residents-risk-punishment-breaching

Elon Musk Builds a Machine to Download Our Brain and Personalities

 It's a bit of fiction meeting reality. 

Billionaire Elon Musk has ambitions for the future of humanity. 

And the whimsical and visionary CEO of Tesla  (TSLA) - Get Tesla Inc Report seems in a hurry to realize this vision. 

What the wealthiest man in the world has in the boxes is likely to raise the hair of more than one of his detractors. Above all, it risks raising ethical questions. The billionaire says it will soon be possible to upload your brain abilities into humanoid robots.

"Could you imagine that one day we would be able to download our human brain capacity into an Optimus?", Mathias Döpfner, the CEO of Business Insider's parent company, Axel Springer, asked Musk in a recent interview.

Optimus is a robot Tesla introduced in 2021.

"I think it is possible," Musk responded.

"Which would be a different way of eternal life, because we would download our personalities into a bot," Döpfner continued.

Musk agreed, and then added:

"Yes, we could download the things that we believe make ourselves so unique. Now, of course, if you're not in that body anymore, that is definitely going to be a difference, but as far as preserving our memories, our personality, I think we could do that."

Will You Be Able to Transfer Your Brain Soon?

When asked if it's imminent, Musk doesn't say no.

"I'm not sure if there is a very sharp boundary. I think it is much smoother," he developed. "There is already so much compute that we outsource. Our memories are stored in our phones and computers with pictures and video. Computers and phones amplify our ability to communicate, enabling us to do things that would have been considered magical."

"We've already amplified our human brains massively with computers," he said.

The first Tesla robot, namely "Tesla Bot", was introduced in August 2021. It was 5 feet and 8 inches tall and also weighed 125 pounds. In January, Musk called it "the most important product development we're doing this year."

Musk indicated in January, during the fourth quarter earnings' call, that the next big product Tesla is working on in 2022 is Optimus, a human in a robot suit the company unveiled in August 2021. The Tesla Bot, as it was dubbed, would use the same artificial-intelligence systems that helped power Tesla vehicles, Musk said.

"I think actually the most important product development we're doing this year is actually the Optimus humanoid robot. This, I think, has the potential to be more significant than the vehicle business over time," he told analysts. "If you think about the economy, it is -- the foundation of the economy is labor. Capital equipment is distilled labor. So what happens if you don't actually have a labor shortage? I'm not sure what an economy even means at that point. That's what Optimus is about, so very important."

Humanoid Robots Are Here

In the interview, Musk ensured that the humanoid robots are almost there.

"I certainly don't want to have anything that could potentially be harmful to humanity. But humanoid robots are happening," he said. "The rate of advancement of AI is very rapid."

Besides their use in Tesla factories where they will perform repetitive tasks, Musk sees other uses for these robots.

"Optimus is a general purpose, sort of worker-droid. The initial role must be in work that is repetitive, boring, or dangerous. Basically, work that people don't want to do," the billionaire explained.

He also believes that Optimus will play a role in our daily lives: Optimus is "a general focused humanoid."

A prototype Optimus will be ready by the end of the year and Tesla plans to market it from 2023, says Musk.

"I think we will have something pretty good at the prototype level this year, and it might be ready for at least a moderate volume production towards the end of next year," Musk promised.

However, Musk admitted in 2018, too much automation is a "mistake".

"Yes, excessive automation at Tesla was a mistake. To be precise, my mistake. Humans are underrated," he wrote.

https://www.thestreet.com/technology/elon-musk-builds-a-machine-to-download-our-brain-and-personalities

Gottlieb: Omicron BA.2 subvariant unlikely to cause ‘national wave’ in U.S. now

 Dr. Scott Gottlieb told CNBC on Tuesday that he believes the U.S. this spring will avoid a “national wave” of infection related to the more contagious omicron BA.2 subvariant.

However, the former Food and Drug Administration commissioner said on “Squawk Box” that he thinks cases are being “dramatically” underreported in some parts of the country. Given the reliance on at-home testing now, he estimated that in the Northeast, as few as one in seven or one in eight infections are actually showing up in official case counts.

“I think we’re further into this than we perceive,” Gottlieb said, pointing to Germany and the U.K., where cases have started to decline quickly from their recent, BA.2-related peak.

In the U.S., BA.2 is the dominant version of Covid, according to the Centers for Disease Control and Prevention. Some expect that within two weeks, it may displace the earlier version of omicron, which caused a surge in cases and hospitalizations late last year and into 2022.

Both Covid infections and hospitalizations have retreated more than 90% since their January highs during the omicron wave.

“It’s probably not going to be a national wave of infection” from BA.2, predicted Gottlieb, who led the FDA from 2017 to 2019 in the Trump administration and now serves on the board of Covid vaccine maker Pfizer. “It’s probably going to be centered in the Northeast, maybe Florida. I think by the time it starts to spread nationally, we’ll already be deep into the summer, and that’ll provide a seasonal backstop.”

The picture may change once fall rolls around for a few reasons, Gottlieb said. “We’ll have to contend with this in the fall,” he said. “If [BA.2] is still the dominant variant in places in the country that it really didn’t get in right now, it’ll start to spread in the fall as people’s immunity starts to wane, they get further out from their vaccination and their prior infection from omicron.”

https://www.cnbc.com/2022/04/05/dr-scott-gottlieb-believes-omicron-bapoint2-subvariant-unlikely-to-cause-national-wave-in-us.html