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COVID-19: Biomedical research in a world under social-distancing measures

Cancelled conferences and overpriced consumables: how can biomedical research function when the lab is out of reach?

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When Wenshing Wei said bon voyage to his laboratory staff as they headed off on winter break ahead of the Chinese New Year, in mid-January, he expected to see them back in Beijing in a week or two. It’s now been two months, and, because of the ongoing outbreak of the novel coronavirus SARS-CoV-2, Wei still isn’t sure when they will return. The Peking University geneticist has been left with a skeleton crew that required special permission from government officials to reenter the lab.

Still, Wei is luckier than many. For one, he’s still able to get to his lab. Wei cancelled his 1,000-kilometer trip home to Jiangsu for the New Year at the last minute as the coronavirus continued its spread. And although his group’s work has slowed, their newer focus on computational biology has left them able to make some progress.

“The whole country is on lockdown. Although we’re severely impacted, we’re not alone,” Wei said.

Labs from across China and around the world are all struggling to cope amid the recent lockdowns, quarantines and travel restrictions due to COVID-19, the disease caused by SARS-CoV-2. Although all the scientists who spoke with Nature Medicine voiced full support of such social-distancing measures as the most important step to slow the pandemic, these measures have come at a cost. Many labs have reported shortages in vital supplies, including RNA-extraction kits (currently in high demand for SARS-CoV-2 testing), gloves, masks, gowns and other personal protective equipment (PPE). Nearly all spring biomedical conferences have been cancelled in the wake of the pandemic, as has research-related travel. Factory shutdowns and labor shortages have caused interruptions in pharma supply chains. With universities around the world shifting to online-only activities, many scientists are struggling to cope.

“I told students to prepare themselves emotionally to have to redo several months of work if there’s a shutdown,” says Jason Rasgon, a molecular geneticist at Pennsylvania State University.

With so little known about the virus’s spread and epidemiology, no one can predict precisely what will happen next. What is clear that things are likely to get worse before they get better.

Reacting to an outbreak

As reports of a novel coronavirus forced many Chinese researchers to temporarily shutter their labs in late January, virologist Linqi Zhang began ramping up his work—albeit with a much-reduced staff. Zhang, an HIV expert at Tsinghua University’s Center for Global Health and Infectious Disease, knew immediately that COVID-19 posed a major threat, so he dropped his long-term AIDS research projects and pivoted entirely toward studying the coronavirus. Together with Xinquan Wang, Zhang and his limited team wanted to solve the crystal structure of the part with sugar-decorated protein spikes that surround SARS-CoV-2, a region called the receptor-binding domain. This is the part of the virus that binds proteins on human cells, in this case angiotensin-converting enzyme 2 (ACE2), to gain entry.

Zhang and Wang were able to crystallize the domain in a week. “We did everything at lightning speed,” Zhang said. But there was only one problem: the specialized equipment that the Beijing-based crew would need to determine the crystal structure was down in Shanghai. With planes and trains halted and courier services stopped, the researchers had to hire a private driver to make the 8-hour drive. But the lab’s perseverance paid off: They managed to get a clear picture of the crystallized receptor-binding domain at a resolution of just 2.45 ångströms (for reference, the diameter of a carbon atom is 1.5 ångströms). The paper has already been accepted for publication.

Zhang’s team also used the SARS-CoV-2 spike protein to identify antibodies that could neutralize the virus in the blood of patients recovering at the Shenzhen Third People’s Hospital. They’ve also begun work on vaccine development, designing antigens to put into vaccine form, which they are now testing in animal models.

“I never imagined all those things could happen in a month or so,” Zhang said.

This progress has come at the expense of Zhang’s HIV work, and further projects are being hampered by reagents on backorder. Shipments that used to arrive overnight now take 2 weeks. Other vital items, such as gloves and masks, have been prioritized for use in caring for sick patients.

“We’ve had to wait weeks for gloves,” Zhang said.

Rasgon said that practically overnight, the price for pipette tips jumped from $150 to $950. And because of the lack of PPE, he’s had to stop all work in his biosafety level 3 lab.

Premier, a US-based firm that provides materials to hospitals and long-term-care facilities, has experienced similar shortages. They began bracing for shortages in equipment as soon as they got news of the outbreak. Most PPE used by hospitals and labs (as well as industry) is manufactured in China, and existing domestic capacity is very limited. The company’s knowledge of global supply chains made it clear that supply limitations would not be a matter of if, but when. Limitations in PPE might create further problems for pharma, according to Soumi Saha, Premier’s Senior Director of Advocacy.

“Without PPE, workers can’t create a sterile manufacturing environment, and companies may experience shutdowns,” she says.

On 4 March, India announced that it would stop exporting 26 pharmaceuticals to preserve its own drug supply, should the country be brought to a halt by the coronavirus. That followed the announcement by the US Food and Drug Administration on 27 February that a pharmaceutical manufacturer had reported shortages in at least one drug, although they declined to say which one. Precisely how COVID-19 will affect the pharmaceutical supply chain is still unclear, but Saha says that the crisis in Italy, which manufactures 12% of active pharmaceutical ingredients worldwide, is also having ripple effects.

Stuck in the middle

In North America and Europe, disruptions from COVID-19 started slowly. Although scientists including Rasgon knew that their Chinese colleagues were severely affected, the effects on their own work were minimal. But as the virus—and the official response—gained momentum, worries accelerated as well.

Once the coronavirus began striking Europe and North America, scientific societies began cancelling their spring conferences, spurred on by reports that a Boston meeting of officials at Biogen sparked more than 50 cases of coronavirus. By the second week in March, few spring conferences were left on the books. Some were cancelled with such short notice that some participants were already en route. On 8 March, Maša Davidović, a PhD student in public health at the University of Bern in Switzerland, arrived in Boston for the Conference on Retrovirology and Opportunistic Infections (CROI) only to learn that the conference had been turned into a virtual gathering while she was somewhere over the Atlantic.

She instead watched CROI lectures from a Harvard Square cafe but managed to leave the country less than 24 hours before the US European travel ban went into effect.

Other organizations, such as the Cognitive Neuroscience Society, are also investigating virtual conferences and online-learning opportunities. People such as Davidović say that they will miss the informal networking and sharing of ideas that make conferences so worthwhile, but that the current situation warrants this approach.

A viral tweet from quantitative biologist Joshua Weitz at the Georgia Institute of Technology supports these mass closures. He calculated the chances of an infected person being at events of various sizes, from a dinner party (ten people) to the final March Madness basketball game (100,000 people). Weitz’s calculations have a fair bit of uncertainty, but he said the results confirm the wisdom of cancelling conferences.

“As the virus continues to spread, the size of tolerably large gatherings is going to go down,” he said.

But the rise in online meetings and conferences, as well as demands from businesses and universities, has increased use of online meeting services such as Zoom.

In an e-mailed statement, Zoom said that “Our proven infrastructure supports over 8 billion meeting minutes a month, and we remain confident that our architecture is built to handle these growing levels of activity.”

The shift to online education around the globe has led to an upsurge in server requests to handle the extra traffic. Companies such as Dell say that all their servers are currently backordered. Njoki Mwarumba, a disaster scientist at the University of Nebraska Omaha who studies the effects of pandemics, moved her courses online as soon as she could. For Mwarumba, the COVID-19 disruptions have not only provided evidence of the importance of preparedness but also offered her students some real-life learning opportunities.

“We’re all just trying to adjust to a new normal,” she said.

Carrie Arnold

doi: 10.1038/d41591-020-00005-1

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