December 11, 2023

At the onset of the Covid-19 pandemic, the fight against the disease was described by heads of government and public health bosses on primetime television.

Countries would receive daily updates collated from data that had been analysed by the world-leading virologists and academics.

But three years later, the pandemic’s trajectory is becoming more difficult to predict – and decision-makers are increasingly reliant on the warnings of a diverse bunch of independent researchers.

This week, Ryan Hisner, a teacher from Indiana, US, was listed alongside various academic co-authors on a paper in Nature, describing how the antiviral drug molnupiravir used to treat patients with Covid-19 may be fuelling the evolution of new variants by creating a specific set of mutations.

The first of these mutated variants was identified by another amateur virus hunter – Nick Rose, 27, a software engineer from Wisconsin. While it is not clear whether such mutations help the virus to tolerate the drug, the findings could have implications for how antivirals are deployed, scientists say.

In common with other self-taught Covid sleuths, Hisner has no formal education in virology – just a knack for spotting patterns and the motivation to wade through reams of genetic data each day. Now with several years of experience under their belts, experts argue that such individuals have become a crucial component of global virus surveillance.

And their work has become ever more important, thanks to a drop in the number of genetic sequences being shared by many countries and a narrow focus on sequences from hospital patients.

With at least 1,700 versions of Omicron co-circulating and continuing to evolve, the worry is that some of them may recombine to create a hybrid virus with unpredictable consequences.

An electron microscope image of the virus that causes Covid-19.
An electron microscope image of the virus that causes Covid-19. Photograph: AP

As such, these dedicated amateurs stress now is not the time to let our guard down. And the experts say we should listen to these dogged researchers.

Prof T Ryan Gregory, an evolutionary biologist at the University of Guelph in Canada, said: “Most of the discovery of new variants, informing the world about them, and characterising them is increasingly being done by a fairly small handful of people who do not necessarily have a formal training in biology but are now some of the world experts as far as I’m concerned.

“The amount of information we have that’s due to their efforts is remarkable. And I would argue their role is becoming increasingly important as [official Covid surveillance] falls back.”

Dr Shay Fleishon, the head researcher for variants and pathogen evolution at Israel’s Ministry of Health, said: “The work of these independent scientists is not just beneficial, it is really crucial. No pathogen, or indeed organism, has ever been sequenced to the extent that this virus has, but to mine this knowledge and craft policies in real time is a huge responsibility. It is very hard to do without their help.”

A health worker inoculates a student with a Covid vaccine at a school in Bangalore.
A health worker inoculates a student with a Covid vaccine at a school in Bangalore. Photograph: Manjunath Kiran/AFP/Getty

In many countries, a proportion of samples from people who test positive for Covid-19 will be sent for genome sequencing to identify the precise mutations their virus contains, with the results uploaded to the international Gisaid database. By studying these sequences, scientists can keep track of the spread of variants and identify new ones.

During the early days of the pandemic, such work was the preserve of experienced scientists with the biological knowledge and technical skills to make sense of the tens of thousands of genetic sequences being uploaded each day.

But as the pandemic has rolled on, they have been joined by people from all walks of life with the interest and motivation to learn these skills, aided by the interactions they have had with these experts on Twitter, now rebranded as X.

Josette Schoenmakers’s interest in viral genetics sprang from frustration about the lack of information about new variants being communicated by government officials in the Netherlands. Alongside a natural love for figuring things out.

“I love to do Sudokus and logic puzzles, and while this is more sophisticated and complicated, you still have to puzzle and find things out,” Schoenmakers said.

With the physiotherapy practice she works for as an administrator closed because of Covid restrictions, Schoenmakers, 51, began compiling her own lists of which variants had been detected and where, and sharing this information on social media.

Gradually, her tweets attracted the attention of international scientists, and her graphs started being reproduced by newspapers – including this one. In January 2022, when all eyes were focused on the rise of the newly detected Omicron variant, it was Schoenmakers who spotted the emergence of a sublineage called BA.2, which eventually took over. “She was the one who raised the alarm, when we were all still focused on BA.1,” Fleishon said.

Pedestrians walk past an electronic billboard promoting the NHS’s Covid vaccine booster programme, in central London, in December 2021.
Pedestrians walk past an electronic billboard promoting the NHS’s Covid vaccine booster programme, in central London, in December 2021. Photograph: Tolga Akmen/AFP/Getty

Similarly, it was Federico Gueli, a dog educator from Italy, who identified the BQ.1 “Cerberus” variant that drove further waves of infection during late 2022 and early 2023, while Hitoshi Sakaguchi, a retiree from Japan , has become the “frontrunner” when it comes to recombinant variants – those containing genes from several variants, such as Deltacron, a hybrid of Delta and Omicron.

Scientists are also using this network of self-taught experts as an informal peer-review system for their own discoveries. In early August, Fleishon identified a viral sequence containing an unusually high number of mutations drawn from a patient in Israel. While such viruses are occasionally detected in immunocompromised patients and do not spread any further, this patient appeared to have caught it from someone else – suggesting a new and highly mutated variant may be circulating more broadly.

Wary of publicly announcing this without further proof, Fleishon shared this information with the close-knit community of virus hunters that Schoenmakers, Sakaguchi and Gueli are part of.

The next day, Hisner announced that he had identified two matching sequences that had been uploaded in Denmark, confirming Fleishon’s fears. This was the BA.2.86 Pirola variant, which has now been detected in at least nine countries and has been linked to a recent care home outbreak in Norfolk, UK.

Such collaboration is a common feature of the virus-hunter community. Dr Thomas Peacock, a virologist at Imperial College London who co-authored the Nature paper with Hisner, said: “Although a lot of countries have some sort of variant surveillance programme set up within their public health systems, the variant hunters are really good at bridging the streams of data coming from different countries and linking stuff up.

“A lot of the public health-affiliated variant tracking groups work very closely with the variant hunter community, and they work very closely with many academics. Without them, we would understand a lot less about what’s going on, or would be spotting stuff a lot later.”

They are also behind the informal naming system that has come up with the likes of Kraken and Arcturus to describe the XBB.1.5 and XBB.1.6 variants, as well as more recent nicknames such as Pirola.

A doctor shows a sample of the Pirola variant of coronavirus.
Amateur sleuths are behind some of the informal names of coronavirus variants, including BA.2.86, nicknamed Pirola. Photograph: Cristian Storto/Alamy

Similar to how virus hunters are helping to bridge gaps left by national Covid surveillance programmes winding down, these DIY nicknaming efforts are motivated by a desire to keep the public informed about how the virus is evolving. Gregory, who acts as the spokesperson for these efforts, said: “The standard criteria for a nickname is ‘are people going to need to talk about it’.”

Because no additional Greek letters have been assigned since Omicron emerged in November 2021, “we’re missing a whole level of communication,” said Gregory. “What the nicknames have done is tried to fill that gap.”

Deciding them involves “a lot of discussion within the group about whether something needs a name, what to name it, when it’s time to name,” Gregory added. “I’ll even say, ‘are we good to put this name out now?’, recognising that they tend to get picked up pretty quickly when we do.”

The efforts of these individuals are all the more remarkable, considering the amount of time they spend doing the work for no pay.

Hisner still works as a teacher but spends “every spare minute that I have outside school doing this work, until I go to bed”.

Such is the expertise he has developed that he was recently approached by a bioinformatician at the University of Cape Town in South Africa about formalising his research as part of a master’s degree in viral evolution – something Hisner hopes to do alongside his teaching work.

Predicting what will happen next is further complicated by the number of variants that are co-circulating. One concern is that some of these viruses may recombine inside an individual host – a situation that becomes more likely when infection rates are high.

If it does, the good news is that this dedicated network of Covid sleuths will be watching and ready to sound the alert.

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