Pandemic Upheaval Offers a Huge Natural Experiment

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Send your careers story Your Work to: naturecareerseditor story @nature.com ANDREA MARSHALL ANDREA The project Our Ocean in COVID-19 launched in 2020 to track human–ocean interactions during the coronavirus pandemic. PANDEMIC UPHEAVAL OFFERS A HUGE NATURAL EXPERIMENT The disruption that the coronavirus has caused to daily life has created unique research opportunities for scientists. By Julia Rosen

oon after COVID-19 lockdowns opportunity. “If it is real and we’re seeing economic anxieties, says Kofi Amegah, an epi- began in March 2020, physicians in differences, can we use that as a natural experi- demiologist at the University of Cape Coast in certain nations noticed something ment?” says Sarah Stock, who studies maternal Ghana. “Basically, we are locked down, we are unexpected: the number of prema- and fetal medicine at the University of Edin- home, we don’t have money to feed the family, ture births seemed to plummet. Pre- burgh, UK. Researchers still don’t understand and it equals to add up to stress,” he says. Sliminary research in one region of Ireland exactly what triggers preterm birth — the lead- Amegah, Stock and more than 150 other documented a 73% decrease in very-low-birth- ing cause of infant mortality globally — or how to researchers from around the world are now weight babies1. And scientists in Denmark prevent it. But by upending daily life in disparate analysing these differences as part of the measured a roughly 90% country-wide drop ways around the world, the pandemic is offer- International Perinatal Outcomes in the Pan- in extremely premature births compared with ing scientists a chance to try to tease apart the demic (iPOP) study. The goal is to “leverage the previous five years2. In Nepal, however, role of suspected factors such as air pollution, the most disruptive and widespread ‘natural researchers reported3 that the risk of preterm hygiene, access to maternity care and stress. experiment’ of our lifetime to make rapid dis- birth — before 37 weeks of gestation — jumped In wealthier nations, for instance, pregnant coveries about preterm birth”, the team wrote by 30% during lockdown, a pandemic trend people might have enjoyed cleaner air and in a paper describing the study’s protocol5. that scientists expect to find in other eco- developed fewer infections while sequestered The effort is one of many aimed at find- nomically disadvantaged nations. In some at home than they would while commuting, for ing a small but significant silver lining to the countries, reports of increased numbers of example. In parts of Africa, however, stay-at- pandemic by using it to further scientific stillbirths further complicated the picture4. home orders might have increased exposure understanding and improve human life. By Amid this confusion, scientists saw an to smoke from cooking fires and amplified assembling and mining large data sets, asking

Work / Careers creative questions and using careful statisti- cal approaches to assess cause and effect, researchers can use the havoc wrought by the coronavirus to tackle a wide range of scientific questions (see ‘Seize the moment’). “We can’t underplay the horror of the pandemic,” Stock says. “But I think we’ve got to learn as much as we can from this.”

The sky is the limit Researchers have long relied on natural experiments to probe subjects that would be diffi- cult — or unethical — to investigate through conventional methods such as randomized controlled trials. For example, they have stud- ied the lifelong effects of stress in early life by tracking the progress of young children who 6 experienced weather disasters . YAMB LIONEL Scientists have also learnt from political Unused boats in Cameroon. Researchers are studying the effects of reduced fishing on sharks. upheavals, such as the collapse of the Soviet Union in 1991. Researchers found7 that in with asthma13,14. And that’s just the tip of the that the project is an example of how research- Russia, increased alcohol consumption iceberg, Thomson says. “The sky is really the ers in low- and middle-income countries, who probably contributed to a significant drop limit — it’s a matter of creativity.” often face funding constraints, can turn the in life expectancy between 1984 and 1994. natural experiment of the pandemic to good In Cuba, which had close ties to the Soviet Go big on data use, because it is relatively inexpensive to round Union, the fall triggered a period of food and Some studies, such as Brasseur’s, extract up and analyse existing data. “That is a golden fuel shortages that led to nationwide weight knowledge by focusing on the peak of dis- opportunity that we cannot miss,” he says. loss — and to reduced rates of diabetes and ruption. Others will unfold slowly as scientists In addition to participating in iPOP, Amegah diabetes-related deaths8. track the long-term effects of the pandemic on plans to track the effects of increased hand Now, COVID-19 has created a similar oppor- people with cancer, for instance, or on children washing on childhood mortality in Ghana. tunity, says Blake Thomson, a principal who experienced remote learning. “There’s In a September 2020 comment article in the scientist for cancer-disparity research at the clearly research to be done right now and in medical journal The Lancet Global Health, American Cancer Society in Atlanta, Georgia, the coming months and years,” Thomson says. he hypothesized that better hygiene during who wrote a 2020 article in the cardiovascu- “For decades, we’ll be wanting to revisit this.” the pandemic is likely to have reduced cases lar disease journal Circulation about learning Either way, scientists need to find or collect of common diarrhoeal diseases, which can from the pandemic9. Many people skipped data that capture the perturbations caused be fatal if untreated15. He says he will look cancer screenings during the pandemic out by the virus and related lockdown meas- for clues in the next round of data from the of fear of catching the virus, which has deeply ures. Already, researchers have capitalized Demographic and Health Surveys Program, concerned physicians. But it also presents an on mobility reports from Apple and Google which focuses on low- and middle-income opportunity “to look for areas in which, actu- to study changes in human activity during countries and is funded by the US Agency for ally, we are over-diagnosing or over-treating lockdowns. Scientists can also dig through International Development. certain people or certain conditions”, Thom- data from such sources as social media, sat- Not all researchers have had success find- son says. (Doctors cannot ask some patients ellite observations, wearable sensors and ing the data they need, so some have launched to forgo routine screening to serve as a control sales trends, Thomson says. He encourages projects to fill the gaps. When Chile entered group in clinical trials.) researchers to collect as many extra data as partial lockdown in March 2020, Eduardo Industrial shutdowns also provided a rare possible while the pandemic continues to ena- Silva-Rodríguez scrambled to set up wildlife real-world chemistry experiment for atmos- ble more future research. cameras in several major cities to investigate pheric scientists such as Guy Brasseur at For health studies, Thomson recommends reports of urban carnivore sightings. He is a the Max Planck Institute for Meteorology in databases such as the UK-based Biobank, which conservation biologist at the Austral University Hamburg, Germany. “We’re always saying, contains genetic and health information for of Chile in Valdivia and, like many researchers, to clean up the air, we need to shut down the half a million people, and the All of Us research was curious about how wildlife would respond emission sources,” he says. “Well, we’re doing programme, run by the US National Institutes to the unprecedented lull in human activity that.” So Brasseur and his colleagues tracked of Health, which launched in 2018 and includes that some have dubbed the Anthropause. changes in air pollutants around the world and a wide diversity of participants. The iPOP study Silva-Rodríguez and his colleagues man- compared them with a widely used computer has partnered with the International COVID-19 aged to get camera traps installed in Valdivia model. The results agreed “reasonably well”, Data Alliance (ICODA), a new initiative funded and Concepción. They documented several the team wrote in a study this year, validating by groups such as the Bill and Melinda Gates animals rarely seen in urban areas, including a their current understanding of atmospheric Foundation and the biomedical research small wildcat called a güiña (Leopardus guigna) chemistry and highlighting areas for further funder Wellcome, and operated by Health and the endangered southern river otter (Lon- research10. Data Research UK. ICODA compiles health data tra provocax) 16. But because the researchers Other researchers are using the pandemic from around the world to support research on weren’t studying cities before the pandemic, to study the effects of increased screen time COVID-19 and other public-health issues. they don’t know whether the animals’ behav- on physical activity in children11, of decreased Amegah and his colleagues are currently iour changed. So they will continue the study tourism on beach ecosystems12 and of reduced digitizing birth records from hospitals around as lockdowns ease to see what happens. “It’s exposure to colds and allergens on children Ghana to contribute to the database. He says not optimal,” Silva-Rodríguez admits. “We had

two options: doing nothing or doing what we University of Victoria in Canada, grappled could.” with this reality last spring. She was sitting at Silva-Rodríguez has contributed his team’s the dinner table when she grabbed one of her results to the COVID Cameratrap Comparison daughter’s crayons and a piece of cardboard Collaboration, which was first announced in Seize the and started sketching out all the ways that the a September 2020 tweet from Roland Kays, a moment pandemic might affect biodiversity — and what zoologist at North Carolina State University lessons it might contain for conservation. That in Raleigh. Many researchers are joining these The pandemic has created a natural spontaneous exercise became the basis for kinds of international partnerships in the hope experiment of unprecedented a central figure in an August 2020 paper in that similar studies conducted in different loca- proportions. Here is advice for gleaning which Bates and her co-authors exhorted their tions can offer a form of replication. But they lessons from the tragic events of the colleagues to take advantage of the “unprec- caution that scientists must always consider past year. edented concurrent confinement of nearly the circumstances surrounding each indi- two-thirds of the global population” caused vidual project. “People have to know that the Start with the obvious. See whether you by the coronavirus17. pandemic has not affected places in the world find what you expect. If so, the pandemic A follow-up study published in May syn- in the same way,” says Lionel Yamb, a marine can help to test existing hypotheses. The thesizes hundreds of reports of pandemic ecologist at Cameroon’s Institute of Agricul- pandemic also provides opportunities to impacts on wildlife and the environment col- tural Research for Development in Yaoundé. generate new hypotheses by revealing lected over the past year18. The results paint a Yamb is one of dozens of scientists partici- previously hidden mechanisms. complex picture: in some cases, species seem pating in Our Ocean in COVID-19, an effort to to have benefited from human absence, but understand human–ocean interactions during Leverage big data. Think creatively about in others, they suffered as conservation work the pandemic using eOceans, a new platform how to use existing data sources. Take ground to a halt. For example, an estimated and app that allows researchers and citizen advantage of mobility tracking, social- two million seabird chicks perished in 2020 scientists to collect, share and analyse ocean media trends, satellite observations and because people could not reach breeding col- data. Christine Ward-Paige, a marine scientist other data sources. Make use of existing onies to remove invasive rodents. based in Dartmouth, Canada, was already build- scientific databases and environmental Bates and her co-authors wrote that the ing the app when the pandemic hit and decided monitoring programmes. pandemic has highlighted the dual role of to release it early. “Maybe it could be used to humans as threats to and custodians of nature, study the impacts of COVID,” she thought. Be careful with causality. Think of all the and revealed ways to “favourably tilt this deli- Yamb isn’t sure yet how the pandemic has possible factors that could influence the cate balance” to protect biodiversity. And the affected the sharks he studies in Cameroon. outcome of interest, then try to account experiment isn’t over yet. When the crisis struck last year, the government for them. Team up with other researchers Many countries are still in the grip of the closed many fish markets, effectively ground- studying similar questions in other places. coronavirus, and others are racing to revive ing fishing boats. Fishers sometimes catch Remember that you cannot generate and their economies, creating new risks for species sharks by accident, so Yamb thinks that shark confirm hypotheses with the same data. and habitats, Bates says. “What I’m hoping is populations might have benefited from the that people will keep jumping aboard,” she break. If true, such an observation would sup- Don’t stop now. The pandemic is still says. There’s still plenty of pandemic disrup- port proposals to establish seasonal no-catch raging, and recovery could be just as tion to document — and even more to learn. zones at times when sharks reproduce. Either disruptive. Continue collecting data, even way, he says, researchers seeking to learn from if there’s no time to analyse them. The Julia Rosen is a freelance journalist in the pandemic will need to consider how these information could prove crucial for future Portland, Oregon. dynamics vary in every location. “We have to studies. think about a specific protocol that will be 1. Philip, R. K. et al. BMJ Glob. Health 5, e003075 (2020). 2. Hedermann, G. Preprint at medRxiv https://doi. carried out in each country,” Yamb says. could affect a given outcome. For instance, org/10.1101/2020.05.22.20109793 (2020). if researchers want to study the link between 3. Ashish, K. C. et al. Lancet Glob. Health 8, e1273–e1281 Pitfalls and perseverance telecommuting and worker satisfaction, they (2020). 4. Chmielewska, B. et al. Lancet Glob. Health 9, e759–e772 Natural experiments require clever have to account for many other factors that (2021). approaches to analysing data, such as compar- could influence employees’ well-being, such as 5. Stock, S. J. et al. Wellcome Open Res. 6, 21 (2021). ing what happened before and after lockdowns pandemic-related anxiety and whether other 6. Rosales-Rueda, M. J. Health Econ. 62, 13–44 (2018). 7. Leon, D. A. et al. Lancet 350, 383–388 (1997). using methods that could include interrupted family members are at home, too. 8. Franco, M. et al. BMJ 346, f1515 (2013). time series, or between a population that was If comparing locked-down versus open loca- 9. Thomson, B. Circulation 142, 14–16 (2020). 10. Gaubert, B. et al. J. Geophys. Res. Atmos. 126, subject to lockdown and another that was not, tions, researchers must consider why certain e2020JD034213 (2021). which can serve as a control. But determin- countries or regions shut down at different 11. Schmidt, S. C. E. et al. Sci. Rep. 10, 21780 (2020). ing causality can be tricky, warns Paul Ferraro, times, which might depend on political leader- 12. Soto, E. H. et al. Biol. Conserv. 255, 108972 (2021). 13. Abe, K., Miyawaki, A., Nakamura, M., Ninomiya, H. & an economist at Johns Hopkins University in ship, the presence or absence of trades unions Kobayashi, Y. J. Allergy Clin. Immunol. Pract. 9, 494–496 Baltimore, Maryland, who studies causal rela- campaigning for workers’ jobs or safety, and (2021). tionships in complex systems. “When nature myriad other factors that could bias the result 14. Kenyon, C. C., Hill, D. A., Henrickson, S. E., Bryant‑Stephens, T. C. & Zorc, J. J. J. Allergy Clin. disturbs our human or environmental system, in question, he says. And every study must Immunol. Pract. 8, 2774–2776 (2021). it does it in ways that often have multiple paths somehow account for the effects of COVID- 15. Amegah, A. K. Lancet Glob. Health 8, e1110–e1111 (2020). to the same outcome,” he says. 19 itself. Then, Ferraro says, researchers must 16. Silva-Rodríguez, E. A., Gálvez, N., Swan, G. J. F., Cusack, J. J. & Moreira-Arce, D. Sci. Total Environ. 765, Ferraro advises researchers who are try to rule out other explanations that could 142713 (2021). attempting to exploit natural experiments confound their hypothesis. In that sense, the 17. Bates, A. E., Primack, R. B., Moraga, P. & Duarte, C. M. Biol. to develop a comprehensive model, based pandemic poses a challenge because it has Conserv. 248, 108665 (2020). 18. Bates, A. E., Primack, R. B., PAN-Environment Working on mechanisms, that links not only the varia- affected so many aspects of life. Group & Duarte, C. M. Biol. Conserv. https://doi. bles of interest, but also everything else that Amanda Bates, a marine ecologist at the org/10.1016/j.biocon.2021.109175 (2021).