Research in the time of a pandemic: SENTINEL- A proactive, early warning system to pre-empt future pandemics
Dr Pardis Sabeti and Dr Christian Happi from Harvard University have been collaborating for over twenty years to combat infectious diseases such as Ebola and Malaria; sequencing the first Ebola virus in Nigeria and the first SARS-CoV-2 in Africa. They have established the African Center of Excellence for Genomics of Infectious Disease, which is leading infectious disease genomics epidemiology in West Africa and has trained over 900 young African scientists who are now at the frontline of COVID-19 response. Now they have a new project on the works, building a pandemic preemption and response system to safeguard us from the possibility of future pandemics.
Dr Sabeti, how has your work on immunology and infectious diseases
changed since the onset of the pandemic?
While the direction of our work hasn’t changed, the pace has sped up tremendously. Right before the pandemic took off the US, we won a large grant from TED Audacious to build a system that detects viruses and shares that information in real-time, combining diagnostics, sequencing technology, mobile applications, and data analysis. The project was supposed to be completed over a five-year period, but we are working to do as much of it as we can now. In addition to this faster pace, we are also seeing an increase in collaborations with other research teams, government agencies, public health groups, and many other great contributors. Outbreaks focus the scientific community, and so many researchers around the world are now working on COVID-related projects, which is helping to move our work and the field as a whole forward much faster.
How has your experience with infectious diseases such as the Lassa virus, Ebola virus, Malaria informed your current work on the SARS-CoV-2 and COVID-19?
Our past experiences with infectious diseases inform our current work. Pandemics are one of the few existential threats that have largely reproducible responses. What we need to fend off Ebola, Lassa, and even standard infections that occur every year is in many ways what we need to fight COVID-19. While replication rate, transmission patterns, and other characteristics differ slightly between these threats, many of the systems that we need to build in order to combat them are the same, so we rely heavily on lessons learned from previous outbreaks to guide our current direction.
Dr Happi, during the Ebola outbreak in 2014, the first case of the Ebola virus in Nigeria was confirmed in your lab and you were able to sequence a genome of the virus and make it publicly available. You also worked towards its containment with relevant health authorities. Are there any parallels you can draw between that experience and the COVID-19 pandemic?
Yes, we diagnosed and sequenced the first Ebola virus in Nigeria, and we also sequenced the first SARS-CoV-2 in Nigeria and Africa. We are also very much involved in COVID-19 diagnosis in Nigeria and working in collaboration with health authorities for its containment. We have learnt a lot from previous outbreaks, such as Ebola, Lassa fever, Monkeypox, and Yellow fever. We have brought this experience to bear on COVID-19 pandemic response in Nigeria.
"...we diagnosed and sequenced the first Ebola virus in Nigeria, and we also sequenced the first SARS-CoV-2 in Nigeria and Africa."
Can you talk to us about the importance of leveraging existing regional networks as well as achieving cross-border and regional cooperation and integration in overcoming public health challenges in Africa?
None of this work would be possible to do alone. Over the past decade, we (Pardis and Christian) have collaborated with each other, growing our network over the years to include a cohort of scientists from our home institutions (the Broad Institute and Redeemer’s University/ACEGID), public health stakeholders across Nigeria, Senegal, Liberia, and the DRC, and leaders in sectors such as architecture, bioinformatics, and mobile app development.
Dr Happi, it was at your lab in Nigeria that the sequencing of the first COVID-19 genome in Africa took place, and you were able to deliver that within 24hrs. That is a remarkable achievement. What made such a fast response possible? And how your work is shaping Nigeria’s role as a forerunner in genetics research?
We were only able to achieve such a fast turnaround time in sequencing the first SARS-COV-2 in Africa, because we have been working in this space for over a decade and have invested a lot in terms of infrastructure, reagents, and human resources. Our work has brought a lot to the genomic landscape in Nigeria and in Africa. For instance, we have used the genomics platform that we have to show clusters of community transmission in Nigeria, as well as viral evolution. This information has been used to shape public health responses in Nigeria.
You are currently not only trying to help address this pandemic, but you are also looking to the future. Before the COVID-19 pandemic hit, you had developed a proposal for a proactive, early warning system to pre-empt pandemics, named SENTINEL. Can you tell us how the idea came about, what SENTINEL is, and if it can be put into use when a pandemic is in such an advanced stage like the one we are going through now?
Our team knows the devastating effects of a viral outbreak too well. Our team at Africa Centre of Excellence for Genomics of Infectious Diseases (ACEGID) diagnosed the first Ebola case to emerge in Sierra Leone, and if we had had a robust outbreak response system in place at that point, we could have avoided the 11,000 deaths and devastating economic toll to come. That outbreak was not an anomaly. Currently, we have no systematic way of even detecting and tracking outbreaks of many common and fatal infectious diseases, much less preventing them and saving lives.
This was the inspiration for Sentinel: a multi-pronged pandemic preemption system that will use cutting-edge diagnostics and sequencing technologies, data analysis and visualization tools, and consumer-centered mobile applications to respond to emerging pathogens in real-time.
From these experiences, we understood that the system you would put in place for pandemic preemption is the same that you would integrate for response and recovery. In understanding our current pandemic, we must build tools that can directly curb the next pandemic.
"In understanding our current pandemic, we must build tools that can directly curb the next pandemic."
How prepared were we for this pandemic?
In an assessment of health security conducted before the start of the pandemic, the Global Health Security Index warned that no country was fully prepared for epidemics or pandemics. It is clear now that many countries, including the United States, were woefully unprepared. Despite knowing about the virus early on in its trajectory, it took months to make diagnostics available and implement proper precautionary measures. Because the country was so blindsided by the severity of the outbreak, we were forced to be reactionary in our response and implement drastic measures to fight its spread. This is a stark reminder of just how important funding, support, and action is for preemption to stave off these dramatic events.
"In an assessment of health security conducted before the start of the pandemic, the Global Health Security Index warned that no country was fully prepared for epidemics or pandemics."
What should we expect in the near future as well as longer term in regards to how the pandemic develops and its effects on society?
The months ahead will continue to be challenging. New evidence suggests that the virus has mutated to become more transmissible. This evolution is similar to what we witnessed during the Ebola outbreak, where the virus appears to have picked up more mutations to become more infectious. School return is presenting many challenges and risks; we know that during the flu pandemic of 1967, reopening of schools caused the emergence of a large number of infections, and many are concerned that a similar surge will accompany the upcoming school year. We are going to continue to see strains on society, so we must stay the course.
In the longer term, there is great hope for our ability to respond to threats like COVID-19. Many vaccines are currently being put into clinical trials, and many diagnostics are being funded. We hope that these advances will better prepare us to respond to the next future viral outbreak, whenever and wherever it emerges.
"New evidence suggests that the virus has mutated to become more transmissible. This evolution is similar to what we witnessed during the Ebola outbreak, where the virus appears to have picked up more mutations to become more infectious."
How important is transparency in science and sharing data, findings? Have you seen any changes in the scientists’ working patterns and styles since the pandemic hit?
Transparency is key. One of the reasons we have been able to move so fast is because the global community has been sharing data in real time. We have also been cautious about presenting clear and well-researched data rather than rushing to publish irresponsibly. In our work sequencing COVID genomes, for example, we carefully vetted our data and thoroughly discussed the most responsible way to share these findings given some very sensitive components of the data.
I believe it is safe to call you the Batman and Robin of infectious diseases. You have been working together for over two decades. Can you talk to us about collaboration in science and how this long lasting working relationship has helped you advance research and improve humanity’s condition?
We have been working together for over 20 years and have established an incredible collaboration and strong partnership. Together, we have invested enormous resources and successfully established one of the most exciting networks of laboratories in West Africa, which has helped many governments successfully respond to many diseases, epidemics, and outbreaks. We established the African Center of Excellence for Genomics of Infectious Disease (ACEGID), Redeemer’s University, Ede, Nigeria, which is leading infectious disease genomics epidemiology in West Africa. Using the ACEGID platform, we have trained over 900 young African scientists in many aspects of genomics research, including diagnosis and outbreak response. The African scientists that we have trained are all at the frontline of COVID-19 response and helping many African countries.
"We established the African Center of Excellence for Genomics of Infectious Disease (ACEGID), Redeemer’s University, Ede, Nigeria, which is leading infectious disease genomics epidemiology in West Africa."
What will be the impact of this pandemic on policy making and future research funding? How do these affect and potentially reshape the future of research?
We believe that this pandemic will reshape global collaboration between countries, and we hope it will lead to far greater funding support for outbreak and pandemic preparedness.
Interestingly, we wrote our Sentinel proposal before the pandemic, and have seen over the years that many folks in this space understand and advocate for exactly the best way to preempt and respond to pandemics. For years, we have advocated for detecting the virus wherever it happens and enabling communities, from healthcare workers to individual citizens, to utilize that information in real time. This is only possible through robust, scalable point-of-care and high-throughput diagnostic devices, as well as mobile applications to share that information in real-time. We have pushed for these breakthroughs for years, yet there has never been sufficient political will or funding until now.
It is an unequivocal tragedy that we were not able to sufficiently prepare ourselves against COVID-19. I am hopeful that with this large wave of support and funding, we can finally enact these transformative changes on a global scale, and in anticipation of the next pandemic.
As Dr Manolis Dermitzakis said in a previous interview for this series “research has never moved faster”. What is the balance between speed and confidence in the findings shared?
There is a crucial balance between rushing to publish data and ensuring that the scientific process remains rigorous. In our work with Jeremy Luban on the D614G mutation, we were very hesitant to publish any findings before we had stringently tested our hypothesis that this mutation was associated with differences in viral transmission.
In the meantime, many other groups began publishing the same findings we already had. We thought about whether or not we should have moved faster. We still feel comfortable with our own pace, as we see how reactive the media can be, and if we were wrong, it could have created distrust in the system. That said, it did serve as a reminder that we should be moving as fast as possible while remaining as careful as possible.
What is the role of publishers during this time and where can they add the most value?
Allowing people to move quickly and allowing people to use BioRxiv or other forms of pre- peer-review sharing are critical. Specifically, it is hugely beneficial to share all of our data so that other groups can synthesize the same information and uncover new insights.
Publishers can also make sure that COVID research is open-access, so that those around the world are able to share these insights in real-time. More broadly, I am always delighted to see publishers employing creative strategies in sharing their research and insights. As research moves faster and faster in light of COVID, I think it would be hugely beneficial to incorporate peer-review in real-time and perhaps even within a public forum, while of course maintaining a high-level of rigor and accuracy.
"Publishers can also make sure that COVID research is open-access, so that those around the world are able to share these insights in real-time."
Other blogs you may find interesting:
Research in the time of a pandemic: Using supercomputers and statistical physics to inform government policies
Research in the time of a pandemic: Africa Centres for Disease Control and Prevention
Research in the time of a pandemic: The researcher's role in shaping policy and communicating with the public
All our interviews reflect the views and opinions of the interviewees.
Dr. Pardis Sabeti is a Professor at the Center for Systems Biology and Department of Organismic and Evolutionary Biology at Harvard University and the Department of Immunology and Infectious Disease at the Harvard School of Public Health. She is an Institute Member of the Broad Institute of Harvard and MIT, and a Howard Hughes Investigator. Dr. Sabeti is a computational geneticist with expertise developing algorithms to detect genetic signatures of adaption in humans and the microbial organisms that infect humans. Dr. Sabeti completed her undergraduate degree at MIT, her graduate work at Oxford University as a Rhodes Scholar, and her medical degree summa cum laude from Harvard Medical School as a Soros Fellow. Dr. Sabeti is a World Economic Forum (WEF) Young Global Leader and a National Geographic Emerging Explorer, and was named a TIME magazine ‘Person of the Year’ as one of the Ebola fighters.
Dr Christian Happi is a Professor of Molecular Biology and Genomics at Redeemer’s University, Nigeria and the Director African Center of Excellence for Genomics of Infectious Diseases (ACEGID), Redeemer’s University. He completed his PhD at the University of Ibadan, and his postdoctoral fellowship at the Harvard T. H. Chan School of Public Health. He received the Merle A. Sande Health Leadership Award in 2011; the Award of Excellence in Research from the Committee of Vice-Chancellors of Nigerian Universities in 2016; and the Human Genome Organization (HUGO) Africa Prize in 2019 for his seminal work on infectious diseases genomics in Africa, including Ebola, Lassa fever, Yellow fever, Monkeypox and Malaria.
