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How it was found and what we know so far

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Researchers based in South Africa explain the science behind the hunt for new coronavirus variants and what we know about the latest find.

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A version of this article was originally published by The Conversation (CC BY-ND 4.0)

Since early in the Covid pandemic, the Network for Genomics Surveillance in South Africa (NGS-SA) has been monitoring changes in SARS-CoV-2. This was a valuable tool to understand better how the virus spread.

In late 2020, the network detected a new virus lineage, 501Y.V2, which later became known as the Beta variant. Now a new SARS-CoV-2 variant has been identified, known as B.1.1.529.

What’s the science behind the search?

Hunting for variants requires a concerted effort. South Africa and the UK were the first big countries to implement nationwide genomic surveillance efforts for SARS-CoV-2 as early as April 2020.

Variant hunting, as exciting as that sounds, is performed through whole genome sequencing of samples that have tested positive for the virus. This process involves checking every sequence obtained for differences compared to what we know is circulating in South Africa and the world. When we see multiple differences, this immediately raises a red flag and we investigate further to confirm what we’ve noticed.

Fortunately South Africa is well set up for this. This is thanks to a central repository of public sector laboratory results at the National Health Laboratory Service, NGS-SA, good linkages to private laboratories, the Provincial Health Data Centre of the Western Cape Province, and state-of-the-art modelling expertise.

In addition, South Africa has several laboratories that can grow and study the actual virus and discover how far antibodies, formed in response to vaccination or previous infection, are able to neutralise the new virus. This data will allow us to characterise the new virus.

The Beta variant spread much more efficiently between people compared to the ‘wild type’ or ‘ancestral’ SARS-CoV-2 and caused South Africa’s second pandemic wave. It was therefore classified as a variant of concern. During 2021, yet another variant of concern called Delta spread over much of the world, including South Africa, where it caused a third pandemic wave.

Very recently, routine sequencing by Network for Genomics Surveillance member laboratories detected a new virus lineage, called B.1.1.529, in South Africa. Seventy-seven samples collected in mid-November 2021 in Gauteng province had this virus. It has also been reported in small numbers from neighbouring Botswana and Hong Kong. The Hong Kong case is reportedly a traveller from South Africa.

Whether B.1.1.529 will be classified as a variant of interest or of concern, like Beta and Delta, has not been decided by the World Health Organization yet. We expect that it will be given a Greek name soon.

Why is South Africa presenting variants of concern?

We do not know for sure. It certainly seems to be more than just the result of concerted efforts to monitor the circulating virus. One theory is that people with highly compromised immune systems, and who experience prolonged active infection because they cannot clear the virus, may be the source of new viral variants.

The assumption is that some degree of ‘immune pressure’ (which means an immune response which is not strong enough to eliminate the virus yet exerts some degree of selective pressure, which ‘forces’ the virus to evolve) creates the conditions for new variants to emerge.

Despite an advanced antiretroviral treatment programme for people living with HIV, numerous individuals in South Africa have advanced HIV disease and are not on effective treatment. Several clinical cases have been investigated that support this hypothesis, but much remains to be learnt.

Why is this variant worrying?

The short answer is, we don’t know. The long answer is, B.1.1.529 carries certain mutations that are concerning. They have not been observed in this combination before, and the spike protein alone has over 30 mutations. This is important, because the spike protein is what makes up most of the vaccines.

We can also say that B.1.1.529 has a genetic profile very different from other circulating variants of interest and concern. It does not seem to be a ‘daughter of Delta’ or ‘grandson of Beta’, but rather represents a new lineage of SARS-CoV-2.

Some of its genetic changes are known from other variants and we know they can affect transmissibility or allow immune evasion, but many are new and have not been studied as yet. While we can make some predictions, we are still studying how far the mutations will influence its behaviour.

We want to know about transmissibility, disease severity and ability of the virus to ‘escape’ the immune response in vaccinated or recovered people. We are studying this in two ways.

Firstly, careful epidemiological studies seek to find out whether the new lineage shows changes in transmissibility, ability to infect vaccinated or previously infected individuals, and so on.

At the same time, laboratory studies examine the properties of the virus. Its viral growth characteristics are compared with those of other virus variants and it is determined how well the virus can be neutralised by antibodies found in the blood of vaccinated or recovered individuals.

In the end, the full significance of the genetic changes observed in B.1.1.529 will become apparent when the results from all these different types of studies are considered. It is a complex, demanding and expensive undertaking, which will carry on for months, but indispensable to understand the virus better and devise the best strategies to combat it.

Do early indications point to this variant causing different symptoms or more severe disease?

There is no evidence for any clinical differences yet. What is known is that cases of B.1.1.529 infection have increased rapidly in Gauteng, where South Africa’s fourth pandemic wave seems to be commencing. This suggests easy transmissibility, albeit on a background of much relaxed non-pharmaceutical interventions and low number of cases. So we cannot really tell yet whether B.1.1.529 is transmitted more efficiently than the previously prevailing variant of concern, Delta.

Covid-19 is more likely to manifest as severe, often life-threatening disease in the elderly and chronically ill individuals. But the population groups often most exposed first to a new virus are younger, mobile and usually healthy people. If B.1.1.529 spreads further, it will take a while before its effects, in terms of disease severity, can be assessed.

Fortunately, it seems that all diagnostic tests that have been checked so far are able to identify the new virus.

Even better, it appears that some widely used commercial assays show a specific pattern: two of the three target genome sequences are positive but the third one is not. It’s like the new variant consistently ticks two out of three boxes in the existing test. This may serve as a marker for B.1.1.529, meaning we can quickly estimate the proportion of positive cases due to B.1.1.529 infection per day and per area. This is very useful for monitoring the virus’s spread almost in real time.

Are current vaccines likely to protect against the new variant?

Again, we do not know. The known cases include individuals who had been vaccinated. However we have learnt that the immune protection provided by vaccination wanes over time and does not protect as much against infection but rather against severe disease and death. One of the epidemiological analyses that have commenced is looking at how many vaccinated people become infected with B.1.1.529.

The possibility that B.1.1.529 may evade the immune response is disconcerting. The hopeful expectation is that the high seroprevalence rates, people who’ve been infected already, found by several studies would provide a degree of ‘natural immunity’ for at least a period of time.

Ultimately, everything known about B.1.1.529 so far highlights that universal vaccination is still our best bet against severe Covid-19 and, together with non-pharmaceutical interventions, will go a long way towards helping healthcare systems cope.

The Conversation

By Prof Wolfgang Preiser, Cathrine Scheepers, Jinal Bhiman, Prof Marietjie Venter and Prof Tulio de Oliveira

Wolfgang Preiser is head of medical virology at Stellenbosch University. Cathrine Scheepers is senior medical scientist at the University of Witwatersrand. Jinal Bhiman is principal medical scientist at South Africa’s National Institute for Communicable Diseases. Marietjie Venter is a professor in the medical virology department at University of Pretoria. Tulio de Oliveira is a bioinformatician at the University of KwaZulu-Natal.

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VMware fixes buggy vSphere release – and Log4J, too • The Register

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VMware has restored availability of vSphere 7 Update, a release that it withdrew in late 2021 after driver dramas derailed deployments.

Paul Turner, Virtzilla’s veep for vSphere product management, told The Register that the source of the problem was Intel driver updates that arrived out of sync with VMware’s pre-release testing program. When users adopted the new drivers – one of which had been renamed – vSphere produced errors that meant virtual server fleet managers could not sustain high availability operations.

Turner said around 30,000 customers had adopted the release, of which around eight per cent encountered the issue. That collection of around 2,400 impacted users was enough for VMware to pull the release before the other 270,000 vSphere users hit trouble. That level of potential problems, Turner admitted, was considered a sufficient threshold to justify a do-over and the embarrassment of a pulled release.

VMware has since reviewed its testing program and procedures in the hope it will avoid a repeat of this error. Doing so, and repairing the release, meant a busier-than-usual holiday period for VMware developers. Turner said those who put in the extra hours will be compensated with extra time off in the future.

VMware also used the time needed to get the release ready to ensure that vSphere 7 U3 thoroughly addresses the Log4j bug. It took the opportunity to update to the latest version of the tool – which is free of the critical bug that allowed almost any code to execute without authorisation.

But VMware decided not to add anything new to vSphere while it addressed Log4j and sorted out the driver drama. Users will have to wait a few more months for another dose of VMware’s usual concoction of security updates and feature tweaks.

There’s more interesting stuff on the way, too. VMware has promised a full vSphere-as-a-Service offering is in the works, and the Project Capitola software-defined memory tech that will pool RAM across hosts. The company has also dropped hints that its plan to run its ESX hypervisor on SmartNICs is nearing release.

VMware has detailed the new/old release here and made downloads available here

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Facebook given EU go-ahead to pursue controversial Kustomer acquisition

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The EU’s antitrust chief Margrethe Vestager said she was satisfied for the company now known as Meta to pursue its Kustomer acquisition after it struck a deal for rivals.

Meta, the company formerly known as Facebook, has secured antitrust approval from the EU to pursue its acquisition of US customer services software start-up Kustomer.

The social media giant’s decision to acquire the start-up attracted EU scrutiny last April, months before its rebrand. Then known as Facebook, the company planned to integrate Kustomer’s products, including a chatbot, into its service.

Now, Meta has assured the European Commission that it will provide rivals free access to its messaging channels for 10 years.

The EU was satisfied that this addressed competition concerns which previously arose from the company’s decision to acquire Kustomer.

“Our decision today will ensure that innovative rivals and new entrants in the customer relationship management software market can effectively compete,” EU antitrust chief Margrethe Vestager said in a statement.

Last December, Vestager’s Digital Markets Act was passed by EU lawmakers as part of the body’s plans to tighten the monopoly large multinationals hold in Europe’s digital space.

Facebook had initially announced its acquisition plan in November 2020. In February 2021, the Irish Council for Civil Liberties wrote to the European Commission outlining its concerns over data that Kustomer had gathered and what might happen to that data under Facebook’s watch. The Commission also received a referral request from Austria flagging concerns over the Kustomer deal.

Other Meta acquisitions have also attracted the scrutiny of competition regulators. Last November, the UK ordered Meta to sell Giphy after its acquisition of the GIF making company was found to have breached competition rules. In the US, it is facing an antitrust suit that could force the company to sell WhatsApp and Instagram.

The EU’s decision to allow Meta to pursue the acquisition of Kustomer comes following a recent vote in the European Parliament in favour of the Digital Services Act, a companion of the Digital Markets Act. The act represents the EU’s attempt to shift the balance of power away from Big Tech in favour of ordinary people.

The long-debated act was hailed by Facebook whistleblower Frances Haugen as a “gold standard”.

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Now that I’ve finally played The Last of Us, who wants to talk about that ending? | Games

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‘OK, Dad, this is an incredible essay on the effects of grief and grey morality in a postapocalyptic society,” says the eldest child, AKA the millennial. “It’s got proper female characters, progressive takes on sexuality and tonnes of rain.”

“They’ve made a video game of The Handmaid’s Tale?”

“No, Dad. It’s The Last of Us. Don’t worry. It’s still a zombie shooter. And both games have the best ending ever.”

Now she has my interest. Video game endings fascinate me, because my generation started out with arcade games that didn’t have them. Pac-Man kept eating dots and chasing ghosts and the Space Invaders kept coming, wave after incessant wave. The first arcade game that had an actual ending was Dragon’s Lair and nobody actually saw that because it was so hard to complete.

I have a tough start with The Last of Us because I hate games where you search for stuff in every room of a house. I spend my normal life doing that with car keys and headphones. I want games where you walk into a room and all the objects get sucked into a magic pocket. But that isn’t realistic, I hear you cry. Well, neither is only being able to carry three shivs in a world where, despite the zombie apocalypse, cargo pants clearly still exist.

The Last of Us.
Jaw-dropping … The Last of Us. Photograph: Sony

I also hate any form of crafting, because that was what my generation had to do for “fun” as kids before we had video games. Whether it’s smoke bombs from sugar and explosives or a set of Action Man drawers from matchboxes, it’s all boring to me.

“Keep going,” I tell myself. “The millennial says it’s got the best ending ever.”

Throughout the first chapter of Joel and Ellie’s jaunt across a post-infected US I keep trying to guess what this great ending will be. Maybe Ellie isn’t immune to infection after all? Maybe Joel is her real father? Maybe they’re both unwitting participants in some reality TV show, I’m Infected Get Me Out of Here?

As you will all know by now – and if you’ve yet to play The Last of Us then please stop reading – the ending has Joel murder a perfectly innocent and well-intentioned doctor who wants to cut Ellie open to find a cure that will save humanity. But Joel has no truck with utilitarian philosophy, because Ellie has now become a replacement for the daughter he lost. So, he disregards mankind’s future and, by stopping the operation, effectively murders the entire human race (alongside a whole hospital’s worth of doctors).

“Why does he do that?” I asked the millennial, in one of many fantastic discussions we had about the game.

“Because he’s a white male,” came the answer, because it’s 2022 and she’s in her 20s. And maybe she’s right. Either way it is a jaw-dropping, supremely brave ending and the terrific Left Behind side-story also brought the feels.

The Last of Us Part 2
Grey morality … Ellie in The Last of Us Part 2. Photograph: Naughty Dog

So, when it came to The Last of Us Part 2, I was beyond excited. Fifty million hours later I was beyond disappointed.

Don’t get me wrong, the millennial nailed it when she said it was a great exploration of the effects of grief and grey morality. But after spending the whole game switching between two strong female characters (literally, have you seen Abby’s arms?) and contrasting factional creeds, you have the final confrontation. They fight. And … they both live. And go their separate ways. The only real damage is Ellie losing a couple of fingers, and the game portrays the worst consequence of this as not being able to play guitar any more. Seriously? That’s the biggest drawback to being fingerless in a zombie apocalypse? The first game ended with Joel murdering an entire civilisation, the second ends with Ellie murdering one song on a guitar. It’s a scene you might have found in The Secret of Monkey Island. It’s hilarious.

The Last of Us Part 2 leaves us with exactly the same non-ending as those original arcade games. Ellie and Abby will go on killing to keep their respective postapocalyptic factions going, both driven by the grief of murdered loved ones. They are both trapped, endlessly chasing ghosts. Sounds familiar…

The millennial says this shows there are no winners when it comes to revenge. I say they want both protagonists alive for The Last of Us 3. It’s a cynical cop out. But then, The Last of Us Part 2 is a game that features the most cynical scene ever, where apropos of nothing, after genuinely bravura portrayals of women, transgender and gay characters, alpha female Abby suddenly gets rogered from behind by some guy. It happens out of nowhere. The game spends umpteen hours portraying progressive sexuality, and then it’s like some marketing man decided they needed to toss the incels a piece of red meat to stop them hate-bombing all over 4chan (which didn’t work). It is easily the most gratuitous bit of nudity I have ever seen in games, and I have played The Witcher 3. The rogerer in question even has a girlfriend. Who is pregnant. Way to shit on a sister, Abby.

“It’s basically Pac-Man with gratuitous boobs,” I say to my eldest, who sighs and pours herself a large cup of coffee. This will be another long discussion.

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