Despite two significant coronavirus outbreaks in the last two decades that killed hundreds of people, dominated international headlines, and grabbed millions in research dollars, SARS-CoV-2 still caught researchers, national scientific advisors, pharmaceutical companies flatfooted when it emerged in late 2019. Why?
Researchers at Ben-Gurion University of the Negev (BGU) attribute our collective ignorance about coronavirus behaviors, treatments and preventions to a failure to continue research after an outbreak recedes.
In a study published in Gigascience, they discovered a disturbing pattern in coronavirus research. While the volume of research is very high during an outbreak, it drops precipitously after containment, preventing scientists from continuing to build understanding of best management and prevention practices and preventing adequate preparation for the next emerging coronavirus.
"The COVID-19 outbreak has revealed how little we know about emerging coronaviruses," said Michael Fire, a lecturer in the BGU Department of Software and Information Systems Engineering (SISE) and the founder of the Data Science for Social Good Lab. "There has been no sustained research into these types of infections, merely peaks following specific outbreaks. That pattern has left us woefully unprepared for the COVID-19 pandemic. If we want to be ready for the next pandemic, we must maintain a steady pace of research, even after the current pandemic subsides. The path to understanding is a marathon, not a sprint."
The researchers saw a similar pattern in other zoonotic infections as well. Previous studies had “discovered a pattern according to which Ebola, Zika, [pandemic] influenza, and coronavirus funding were highest after an outbreak,” co-author Dima Kagan told BioWorld. “We believe that without the appropriate budget, it is more challenging and less motivating to conduct research.”
While the number of virology papers has climbed steadily over the last 70 years, much of that research has focused on blood-borne diseases such as HIV, hepatitis B and hepatitis C. That focus has led to tremendous strides in those diseases and, in the case of hepatitis C, a cure. But it leaves the world vulnerable to other pathogens of powerful pandemic potential.
“The next pandemic will most likely involve a zoonotic respiratory virus,” said Kagan, a PhD student in Fire’s lab at BGU. “There are many hundreds of such viruses, many of which have not been fully characterized, including coronaviruses.”
The researchers analyzed a dataset of 35 million papers over nearly 20 years, which showed that studies peaked immediately after major outbreaks or epidemics then tanked within two years of containment. Even with the increased interest in coronaviruses surrounding the SARS from 2002 to 2003 and MERS in 2012, the “results demonstrate that previous coronavirus outbreaks have been understudied compared with other viruses,” the authors found.
Of the studies analyzed, nearly two million concerned virology. Viruses studied included SARS, MERS, Ebola, influenza (seasonal, avian influenza, swine flu), HIV/AIDS, hepatitis B, and hepatitis C. Just 0.4% of the virology studies involved SARS or MERS. After the first SARS outbreak, twice as many papers studied SARS than Ebola, but the trend quickly reversed. MERS never reached the level of study seen for SARS.
The researchers also noted that researchers on emerging coronaviruses published fewer papers per person than those who focused on other infectious diseases and that the studies were characterized by less international collaboration. Research on emerging coronaviruses were concentrated in just six countries.
In addition to calling for sustained research, the team urged greater sharing of code and data to “make more accurate discoveries faster by continuing knowledge from previous studies.” While researchers tended to keep critical information to themselves when studying SARS and MERS, changes in that behavior has occurred somewhat in recent years.
“Even before the COVID-19 pandemic, conducting open and reproducible research became more common,” co-author Jacob Moran-Gilad of BGU’s School of Public Health told BioWorld. “For example, there are many journals, such as Gigascience, that only publish open and reproducible studies. The COVID-19 pandemic demonstrates how important it is for the general good to openly share research findings, and not to put them behind closed paywalls.”
Data sharing may help keep research on track even once COVID-19 wanes, but a commitment to matching funding to public health priorities is still critical.
"We believe the lessons learned from the scientometrics of previous epidemics argue that regardless of the outcome of COVID-19, efforts to sustain research in this field should be made," Fire said. "More specifically, in 2017 and 2018, SARS and MERS were considered to be priority diseases in WHO's R&D Blueprint, but their research rate did not grow relative to other diseases. Therefore, the translation of international policy and public health priorities into a research agenda should be continuously monitored and enhanced."