Epigraph Vol. 22 Issue 4, Summer 2020
Forced changes and creative solutions: The pandemic’s effects on epilepsy research
This article was researched and written in a home office, with interruptions by family members seeking help with homework, wanting to know a good place to buy a swimsuit, and asking if we were out of strawberries.
After the World Health Organization declared the COVID-19 pandemic on March 11, restrictions spread as quickly as the virus. Schools and universities closed. Research labs were shuttered, save for minimal staff to maintain cell cultures, feed animals, and check on freezers and other equipment. Clinical studies involving direct human contact—such as specimen collection or neuroimaging—were suspended. Routine patient care was shifted to the telephone or video calls, with some clinicians redeployed to COVID-19 patient care. Conferences were cancelled or postponed.
Epilepsy researchers adapted by redirecting their efforts. Those with teaching responsibilities spent time creating video lectures and alternate curricula for their students, who had been shunted to online learning. Researchers tackled projects that had been on the back burner for months, or shifted to data analysis, or drafted manuscripts and grant applications. Instead of traveling to laboratories, hospitals or conferences, people commuted to home offices to watch webinars and attend video chats.
After nearly three months, with some countries coming out of lockdown while others are still in the early phases of COVID-19’s impact, questions bubble to the surface. What will the epilepsy research landscape look like in six months, a year, five years? Will the changes imposed by the pandemic influence a systemic shift in how researchers work day to day? Has anything positive resulted from these unprecedented weeks? ILAE asked researchers across the globe to share their experiences and their thoughts about what the future might hold.
And yes, they see some silver linings.
Research shutdowns – and adaptations
Many laboratories were closed for weeks, with only occasional visits by a select few to ensure the continuity of animals and cell lines. As of mid-May, some labs are gradually reopening, but regulations limit the number of people in the lab at any given time. Also, any clinical research involving direct patient contact ceased.
In China, Dong Zhou said that because neuroimaging data requisition slowed to almost nothing, his group’s longitudinal MRI studies are at risk of information gaps.
In Iran, Ali Asadi-Pooya had just finished years of legwork to start a large research project on the genetics of seizures. He collected the first blood samples from patients in February; weeks later, the project came to a halt.
“Fortunately, I can hold onto the budget,” said Asadi-Pooya. “But the student who was trained to work on the project is graduating and I have to recruit another person.”
In Italy, Emilio Perucca and colleagues were negotiating the final version of an epilepsy clinical trial protocol. But when the pandemic began, stakeholder priorities changed, and the protocol had to be set aside. In France, Fabrice Bartolomei handled perturbations in two large projects. RHU EPINOV, which aims to improve prognosis for epilepsy surgery using large-scale computerized brain modeling, has had to stop enrolling patients. And the ERC-Galvani project, set to develop transcranial direct stimulation for epilepsy, will not begin on schedule.
Nathalie Jetté, a health services researcher, was redeployed in April as an attending physician in New York City, covering the COVID-19 internal medicine service. “That certainly affected my team and my own productivity,” she said. “Fortunately, a lot of my research involves the use of electronic medical records data or other existing data sets, so we have been able to continue that.”
In Canada, Karl Klein’s lab remained closed as of late May, and his clinical genetic study recruitment has become arduous. Before the pandemic, participants were recruited during a hospital visit—they signed forms and gave a blood sample all in one go. Now, his group calls potential participants; those who agree to enroll are sent forms and a saliva collection kit through the mail. The group had been recruiting multiple patients per week, but since the pandemic began, only 2 participants have joined. Klein said the less personal and more complicated process, along with possible fears about leaving the house to post forms, may have contributed to the dramatic drop.
Egypt’s Nirmeen Kishk was frustrated by the restrictions. Two years ago, the Cairo University Epilepsy Unit established its pre-surgical program for epilepsy. “We had just started to work as a team and perform epilepsy surgery,” she said, before the pandemic shut them down. A curfew was imposed across the country on the 15th of March, with residents required to be in their homes between 7 p.m. and 6 a.m.
In Tunisia, imports of equipment and consumables have ceased, which could delay restarting most epilepsy research once restrictions have eased. The University of Sfax’s Chahnez Triki worried that this challenge, along with the economic impact of the pandemic, could delay research results for so long that they might become obsolete.
Graduate students are in a particular pinch during the pandemic, as much of their time-sensitive research has been grounded for weeks. “One of my PhD students had to divert her attention to other aspects of her work,” said the University of Sheffield’s (UK) Markus Reuber. “She may need to redesign her project if lab testing does not become possible soon.”
Researchers have adapted. In Canada, Paolo Federico’s team is using the time to analyze data, and he’s catching up on writing papers. In Finland, Asla Pitkänen said the shutdown “left more time for data analysis. Online review of video EEGs and MRIs has worked quite well. And our lab meetings are now web conferences.”
Research goes virtual
It’s difficult to imagine how the pandemic might play out without the internet. Technology allowed researchers to replace in-person meetings with video chats, to access data online, and to attend virtual epilepsy seminars featuring speakers from around the world, all from their own homes. The online world, already a significant part of many people’s lives, became more important than ever—and it has made some aspects of research easier.
“The concept of discussing anything in Zoom meetings was not accepted in our community until COVID-19,” said Kishk. “I think it will now be very helpful to be able to send proposals by email and discuss issues by email or video conference.”
Working from home and telemedicine, both forced into practice by the pandemic, were almost universally embraced. Spurred by the rapid adoption of video conference and telepractice, Kishk and colleagues have initiated a study on the use of telemedicine for patients with neurological disorders in Cairo.
Federico and many of his colleagues have found that virtual meetings ease the stress of trying to balance work and home lives. “It’s become clear that people can work from home more often; it’s much easier than we thought,” he said. “For some people, working from home can provide benefit. For example, if I had a colleague who needed to be home at 4 p.m. every day to be with their young children, I have no problem with that. It allows for flexibility.”
“Now, many of my team members do not have to travel long distances to come to work, providing them with longer days to be productive from home,” said Jetté. “We have also become better at using telehealth for research, resulting in a lower travel burden for patients and more adherence with research visits. And video visits allow us to see our research patients in their usual environment, which can add to the experience and help us understand their living condition, surroundings and home supports.”
Online options have allowed colleagues to bond, even during social isolation, said Germany’s Katja Kobow. “Having online meetings at home with kids running around, pets entering the scene, forgetting you’re in your pajamas when you get up during the meeting to get a new coffee – that can be seen as unprofessional but I think it showed our humanity, made us laugh together, and brought us closer,” she said.
A virtual future?
Will the increased reliance on the virtual world continue after the pandemic has subsided? Some believe it will—to a degree.
“Regulated, smart working from home – that’s an important thing,” said Italy’s Marco de Curtis. “It can be much more efficient than always working on site. I hope in the future that won’t go away.”
However, said de Curtis, the loss of spontaneous face-to-face conversations between colleagues could have a dramatic negative effect. “Science is about communication,” he said. “If that is lost, then part of the research planet is lost.”
Online learning and virtual conferences have the potential to enhance international collaboration, said Reuber. “They can provide access to high-quality information to people who have effectively been excluded from it in the past,” he said. Reuber does not believe that international travel will recover to pre-pandemic levels any time soon; he notes that a decrease in such travel also could help address climate change.
Others agreed. “The current situation has given us the opportunity to reset and define priorities,” said Christos Lisgaras in New York. “If all of the ‘going virtual’ continues, it can have an important impact on the environment, with reduced travel.”
It’s unlikely that all conferences will go virtual, however, given the importance of informal conversations and face-to-face discussions that create and strengthen research collaborations.
“Digital platforms work okay, but they don’t replace in-person informal communication, and that is often when the most essential information is exchanged,” said Pitkänen.
The money question
The pandemic has led to an “unprecedented change in research practices and directions,” said Aristea Galanopoulou in New York. “Non-COVID-19-related diseases that under ‘normal conditions’ were important and devastating, such as epilepsy, seem to have disappeared into the shadows.”
What will happen to future funding for epilepsy research? Some grant funders and governments have adjusted; for example, the UK government has added 6 months to every fellowship awarded before the pandemic. Canada’s federal funding agency for health research cancelled its spring operating grant competition after more than 2,000 investigators had submitted applications; weeks later, after a high volume of negative feedback from researchers, the agency announced that the competition would resume.
Kobow assumes that COVID-19 research will reign supreme for some time. “That is money and attention that will be lost to other research areas, including epilepsy,” she said.
Others agreed. “I am concerned that the economic crisis will reduce funding opportunities for epilepsy research,” said Perucca. “I suspect that in the future, more funding will be diverted to research on infectious diseases.”
Reuber is concerned that as universities, governments and non-profits become economically strapped, they will respond with furloughs, layoffs, and decreased research funding across the board. De Curtis agreed. “I’m afraid that the poor economic conditions will affect the amount of money that local governments will feed into research in general,” he said. “This will be bad for the United States but also for Europeans, and it will be dramatic for Italy.”
Kishk has pressing concerns about her patients with epilepsy, most of whom are uninsured and receive anti-seizure medications from Cairo University’s pharmacy at no cost. “I’m really worried about the availability of medication, and I also think there will be a lag in diagnosis and proper management of people with drug-resistant epilepsy,” she said. “Thus, I suspect status epilepticus cases will increase.”
Klein has similar concerns about delays in epilepsy surgery. “There is clear data that doing epilepsy surgery reduces mortality,” he said. “In the long run, restricting treatment can cause mortality.” There’s also concern that patients will be wary of coming to the hospital, even for epilepsy surgery, due to continuing concerns about COVID-19. “I’m afraid we will not see patients in the hospital in the numbers we did before,” he said, and that lack of face-to-face contact could adversely affect not only patient care, but also research study recruitment.
Mental health concerns: Still on the back burner
Around the world, hospitals were converted to COVID-19 patient care and some epilepsy clinicians were reassigned to care for those patients, with all the uncertainty and stress that this entailed, including multiple daily deaths and elaborate processes to protect themselves and their households from infection. Other epilepsy clinicians and researchers have been homebound for weeks, where family issues cannot be escaped, and video conferences compete with domestic priorities. Some have tested positive for COVID-19 and were forced into quarantine.
During the height of the pandemic, one survey of more than 1,200 physicians and nurses in China found that 50% reported symptoms of depression, 44% of anxiety and 34% of insomnia. Pandemic aside, clinicians are already at risk for many of these conditions, yet they are also unlikely to seek help.
Perhaps tellingly, only two respondents mentioned mental health as a concern. Kobow noted that the isolation and social distancing, coupled with the rapid changes at work and home and the “feeling of a permanent yet invisible threat,” has led to emotional stress.
Galanopoulou acknowledged the significant personal toll on epilepsy researchers. “The physical distancing, the communicating through a mask, the minimization of personal interactions, the experience of human lives lost, whether in hospital or on a personal level . . . are all likely to leave a long-lasting impact. Mental health support services adapted for the needs of research and health care personnel are critical.”
Post-pandemic: What will research look like?
The pandemic has highlighted the importance of science and research, however, and that may cushion the financial impact—at least some are hopeful that it might.
Lisgaras, an early-career basic scientist, said that the pandemic makes clear yet again how important it is to translate basic science findings into clinical applications. Pitkänen agreed. “I think that the handling of the pandemic has very clearly shown the need of fact-based information and research,” she said. “I hope this will encourage governments and funding organizations to increase research and innovation budgets for bottom-up, researcher-initiated projects.”
The research world watched as institutional review boards fast-tracked COVID-19 clinical studies and a spate of COVID-19 pre-prints were shared and publicized daily as the medical community sought to understand the virus as quickly as possible. The “messiness” of science was in the spotlight; some say it may have helped people to understand how science really works, while others worried it would undermine confidence in both research and medicine.
Will these accelerations of the scientific process—seen by some as cumbersome, and others as careful—persist after the pandemic has subsided? More importantly, should they?
“For COVID-19, we needed faster ethics approvals to get clinical data, and preprints give the freshest data,” said Zhou. “But they also raise issues. I believe these changes will not be sustained after the pandemic.”
Faster science isn’t better science, said Reuber. “I am concerned that some rapid publications have been of low quality,” he said. “References to preprints could undermine trust in science if it turns out that data and interpretations with serious flaws have been published. I think spending more time on higher quality assessment processes can reduce the risk of wasting research funds and is likely to be time well-spent.”
Perucca agreed. “Peer review, while imperfect, remains the best system to prevent bad science from being widely disseminated,” he said. “Media manipulation can permit poor quality science, released as a pre-print, to gain extraordinary and harmful visibility.”
Kobow provided a different perspective. “I think preprints are a good way to publish results before entering the long and painful journey of submission, rejection, resubmission, review, re-review and so on. It also helps to protect intellectual property, so you do not see somebody else being faster in publishing, while you are still waiting for reviewer comments. And preprints allow you to receive comments from the research community that can help to improve the manuscript.”
Klein noted that pre-prints existed before COVID-19 and will continue to exist afterward, but in most cases there’s little incentive to use them. “COVID-19 has made preprints more visible because of the importance of speed in findings, but I don’t think [that process] is applicable to standard research,” he said. “If that trend happened in genetics, I would need a very high threshold for what I wanted to read, because I couldn’t read every paper and also be reviewing it at the same time.”
Crisis as opportunity
The pandemic has thrown almost all aspects of our lives into sharp relief. It’s forced sweeping changes over mere days. It’s made people rethink their life choices and helped them discover or rediscover what’s truly important to them. It’s created problems but also has provoked solutions, because if humans are anything, they are resilient.
“The greatest troubles are often the greatest stimulators of creativity and innovations,” said Pitkänen. “I am positive that this pandemic is not an exception.”
Galanopoulou sees people uniting in ways that they hadn’t before. “The creation of a united front in sharing information, data, expertise and resources, both within and across borders to enhance research and health care delivery, has exemplified the true spirit of science,” she said. “This is a starting point that would be worth building upon going forward, to carve a road to advance science and quality of life.”
ILA Communications Officer
ILAE COVID-19 and Epilepsy Research Award
To recognize research that has been undertaken during the COVID19 pandemic the ILAE will present one award to each region for the best research, published or in press. Deadline 15th December 2020.
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