Infectious Disease

Pandemic Preparedness

kelseytsipis — Wed, 17 Jan 2024 15:30:50 +0000

An app-based pandemic simulation developed at the Broad Institute has become an educational tool for dozens of schools across the country.

Pandemic Preparedness

Disinformation and distrust of authorities hindered the U.S. response to the Covid-19 pandemic. Now, an app-based simulation designed by researchers at the Broad Institute is helping students prepare for future outbreaks.

Called Operation Outbreak, the app was created by the team of Pardis Sabeti, an infectious disease researcher at the Broad. Sabeti believes the app can equip students with a robust understanding of outbreaks—and how to thwart them. “Students today come to school wanting to change the world, and this is a way they can learn about the potential they can have,” she said.

To date, Operation Outbreak—generously funded by the Gordon and Betty Moore Foundation, The Rockefeller Foundation in collaboration with Dalberg Catalyst, and the Burroughs Wellcome Fund—has trained 6,000 students (ranging from sixth-grade to college) in 50 schools. Its origins date back to 2015, when Todd Brown, then a civics teacher at Sarasota Military Academy in Sarasota, Fla., wanted to nurture his seventh-grade students' interest in the Ebola virus spreading through West Africa. He emailed Sabeti and invited her to give a talk about Ebola to his students via Skype. After the talk, Brown conducted a low-tech pandemic simulation-game in which some students spread the “infection” by tagging each other with stickers.

Brown noticed how enthralled his students were by the lesson and approached Sabeti again to see what more he could do. They both agreed that the viral “infection” needed to be more realistic. At the time, Andrès Colubri—now an assistant professor at UMass Chan Medical School—who was then a postdoctoral researcher in the Sabeti Lab, was developing a Bluetooth app that would better mimic real pathogen transmission as a potential tool for combatting future outbreaks. After a few years of designing, iterating, and beta testing—with Brown leading the app’s testing in schools—the app-based program launched in 2018.

_{Avatars in the Operation Outbreak mobile app.}

All of which was before the Covid-19 pandemic. When Covid-19 struck in late 2019, the Operation Outbreak team wanted to expand Operation Outbreak’s capabilities. Enabled by the generosity of the Gordon and Betty Moore Foundation, they improved several of the app’s existing features, including parameters like “virulence” and “asymptomatic spread,” and a 15-part video series on outbreak science created in collaboration with Crash Course. “These simulations help students develop their critical thinking, teamwork, and decision-making skills,” said Tim Rogmans, founder of Sim Institute, a company that creates simulation games for education and global nonprofits.

The Operation Outbreak team also developed a visual dashboard in partnership with Fathom Information Design so students can explore their own anonymized outbreak data. In addition, the team honed the app’s proximity-sensing technology.

During the pandemic, the app was more than just a fun simulation. Two colleges—Colorado Mesa University and Brigham Young University—used it to understand how COVID-19 infections were spreading across their campuses.

_{Visualization dashboard of post-simulation data.}

Udean Williams, a staffer at Don Bosco Cristo Rey High School (DBCR) in Takoma Park, Md., used Operation Outbreak to lead a simulation this past spring, packing 300 students into the school gym. What ensued surprised her. “The government collapsed and started charging for vaccines, which were supposed to be free. So the others created a black market. It was chaos,” she recalled. “Afterwards, teachers discussed the simulation in class to help students learn how outbreaks affect society, and how they can adapt and take action.”

DBCR is part of the national Cristo Rey Network of academically rigorous private high schools that serve students from families of limited economic means. An instructional coach at DBCR, Williams helps teachers improve their lesson plans, and in Operation Outbreak, she found a tool that both students and teachers benefited from.

But she wanted to tread carefully. The DBCR student body is 85 percent Latinx and 13 percent Black—populations disproportionately affected by Covid-19. And she knew that two students had sadly lost both parents to Covid-19. Before the simulation at DBCR, Williams worked with school counselors to ensure students were comfortable participating. The Operation Outbreak team is attuned to these sensitivities and has removed the skull icon to symbolize death in the app, replacing it with a screen that displays “Sim Over”. “We want students to have a positive and empowering experience, so we’re working closely with schools to understand students’ needs and acknowledge the climate surrounding outbreaks,” said Kian Sani, Operation Outbreak’s co-head, alongside Brown, Colubri, and Sabeti.

The team is also expanding Operation Outbreak’s scope, developing an online textbook covering topics ranging from biology to epidemiology and a video series as part of a full curriculum. “We want students to deeply understand the many fields critical to overcoming outbreaks together,” said Sabeti.

—Rubina Veerakone

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Infectious Disease

From Pandemic to Vaccine-Preventable Illness

admin — Fri, 04 Jun 2021 18:23:25 +0000

An infectious disease physician and Broad scientist discusses how basic science—some of it 20 years in the making—has led to better care for Covid-19 patients.

From Pandemic to Vaccine-Preventable Illness

It has been more than one year since the World Health Organization declared the coronavirus outbreak a pandemic. More than 500,000 Americans have died of the virus, according to Johns Hopkins University, and the pandemic is still wreaking havoc across the globe, with India and Brazil facing devastating new surges in infections.

For Roby Bhattacharyya, an associated member with the Broad’s Infectious Disease and Microbiome Program and attending infectious disease physician at Massachusetts General Hospital, the past year has been an intensely emotional experience. Bhattacharyya, a 2016 awardee of the BroadIgnite program, was on the frontlines when the initial surge hit Boston-area hospitals in March 2020 and again during the second wave in January 2021. Below he reflects on the lessons he has learned—both in the clinic and lab—and what he hopes we will do better next time.

How did your experience caring for Covid-19 patients during the second wave compare to your first time on service?

There was so much more known about [the virus] that it felt completely different to be on service with almost the same number of patients as there were last March. I knew better what to expect. I knew what I could do to give a patient the best chance to survive, even if I couldn't guarantee that. We can't guarantee anything in medicine. We can just do our best. But at least I had a better sense of what our best was at that point.

For example, I didn’t give anybody the steroid dexamethasone in April [2020]. I saw enough people who died that, had I given them all dexamethasone, one of them probably would have survived had we known. But we didn’t know. And the best literature at the time suggested that it might have been harmful. I can’t beat myself up about that, but it’s certainly true that a patient I saw in January had a better chance to survive than a patient I saw last March. So that part made it easier. I lost 10 pounds in two weeks the first time I was on service from stress and not eating because I didn’t want to take my mask off. I didn’t do that the second time.

What was hard the second time was seeing people die of what I knew was a vaccine-preventable illness. I saw people who were weeks away from being eligible for a vaccine and just didn’t quite make it. So, it’s still hard. We’ve learned a lot in a year, but we’re still at its mercy to some degree.

Scientific discovery seems to be unfolding at an unprecedented pace, especially when compared to the original SARS outbreak in 2003—which we didn't know was a virus for nearly 6 months. What went “right” this time in comparison, leading to vaccines and other game-changing treatments?

For vaccines, I think we’ve built on technologies that we've been making for the last 20 years. There are a lot of unsung heroes that have come out of that—people like Katalin Karikó who worked on messenger RNA delivery when funding was hard to come by. And she and others kept working on this idea for decades and finally found a way to deliver messenger RNA in a way that was stable and wouldn’t get degraded by cells.

_{Roby Bhattacharyya}

Also, studies of SARS and MERS led to us finding the right antigen. Essentially the day after SARS-CoV-2 was sequenced, people started producing vaccine candidates because they had a delivery method in messenger RNA and knew exactly what the right antigen was because the spike protein was well-characterized from SARS and MERS.

So, I think it’s a culmination of all this detailed, careful science on diseases that were no longer threats. That’s the value of basic science and, in some ways, even curiosity-driven science.

What is a lesson that you hope will be implemented going forward?

One thing that I hope comes out of this is a more deliberate system of worldwide deployment of diagnostics and sequencing. We have the ability to both identify new pathogens and watch them develop. But we don’t really yet know how to react to that. We’re seeing that with the variants, where people are not sure how seriously to take them, and it takes a while to calibrate. But I think having the ability to gather information in a coordinated and systematic way is important. Even if this time through we don’t know exactly what to do with it, in retrospect, having the data will let us know how to react next time.

—Kelsey Tsipis

Header image credit: Lisa Ferdinando, Public domain)

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Infectious Disease

Training Teens for the Next Pandemic

admin — Thu, 15 Apr 2021 13:03:17 +0000

Operation Outbreak equips young students with hands-on experience in outbreak preparedness.

Training Teens for the Next Pandemic

In December 2019, weeks before the first Covid-19 case was reported in the U.S., a novel airborne respiratory virus hit Sarasota Military Academy (SMA), a public charter school in Sarasota, Florida. The virus spread swiftly and stealthily, causing flu-like symptoms. Healthcare workers were overwhelmed. Scientists raced to find a vaccine. The government struggled to manage the situation. And people panicked—some began hoarding food and face masks.

Fortunately, it was a simulation.

The students at SMA are part of an innovative program, called Operation Outbreak, that aims to teach users about viral pandemics and how to contain them. Developed by a faculty member at SMA and a team from the Sabeti lab at the Broad Institute, the program revolves around an app-based outbreak simulation, which assigns roles in government, public health, medicine, media, and the military to users, who then have to work together to stop a virtual pathogen spread via Bluetooth from one person’s phone to the next. Though created before the Covid-19 pandemic swept the world, it’s proving to be a valuable tool in teaching pandemic preparedness and response—critical lessons for young people facing a future at risk of more outbreaks.

“When you just sit in class and learn something, it’s hard to connect it to real life,” said Grace Wagler, a senior at SMA and participant of Operation Outbreak. “Here, I feel like I got insight into how difficult it is for different groups to work together in an outbreak.”

Thanks to the support of the Gordon and Betty Moore Foundation, Operation Outbreak has already been deployed in nearly 20 schools across the world—from Sarasota to Shanghai—with plans to launch it in at least 80 more schools by the end of 2022. The program includes not only the app but also study materials on pathogen biology, epidemiology, and public health. The team behind Operation Outbreak is also developing an open-source online textbook and a 15-part video course series on outbreak science and pandemic response.

Operation Outbreak was born out of another deadly epidemic. Back in 2015, when Ebola was ravaging countries in West Africa, a group of seventh-graders at SMA wanted to learn more about the epidemic. They posed questions almost every day to their civics teacher at the time, Todd Brown.

Brown, who is now SMA’s outreach director, leaned into his students’ curiosity, adapting their curriculum to incorporate public health and what happens during pandemics. “I integrated contemporary world news into what we were teaching about levels of government, and how things would work if something similar were to happen in the U.S.,” said Brown. “And it turned into why don't we have a simulation."

_{Students at the Sarasota Military Academy Prep participating in the school’s Operation Outbreak simulation.}

Brown reached out to Pardis Sabeti, an infectious disease expert at the Broad and Harvard, to propose the idea of running a simulation. (He had initially emailed Sabeti to request an autograph on behalf of his seven-year-old daughter, who was a fan of her research.)

Sabeti, who grew up in Florida and is a passionate educator, loved the idea. In 2016, the first official Operation Outbreak simulation using stickers to ‘infect’ participants commenced on the SMA campus. A year later, Andres Colubri, a former postdoctoral researcher in the Sabeti lab, joined the team and developed the app—bringing the experience even closer to real life.

“Our first app-based simulation worked really well, and we used an Ebola-like virtual pathogen,” said Colubri, who now leads his own group at the University of Massachusetts Medical School. “But in 2019, we switched to a SARS-like virus, incorporating elements like asymptomatic transmission. We were running this not knowing that a similar virus was spreading across Wuhan.”

While Covid-19 has made it challenging to run in-person simulations, the team has been retooling Operation Outbreak in response to the pandemic. That includes leveraging the app’s Bluetooth-based proximity-sensing to track contacts between users and assess their physical distancing efforts—a valuable capability that was used last summer at the One Summer Chicago program to train 2,000 young adults as social-distancing ambassadors.

Working with Fathom Information Design, a Boston-based group specializing in data visualization, the team has also built a dashboard that visualizes social connectivity among consented participants and tracks individual transmission patterns, including how someone got infected and spread the simulated virus, whether they were vaccinated, and did they recover.

“Our visualization dashboard really marries qualitative and quantitative analysis of post-simulation data. Both students and staff can deeply engage in and learn from this,” said Kian Sani, a co-lead for Operation Outbreak, who joined the team in 2020.

Colorado Mesa University (CMU) is already seeing the benefits of this data analysis. Last year, more than 350 CMU students participated in a four-day Operation Outbreak exercise where the app ran in the background of their phones as they mingled during their normal routines. The results were instructive. As expected, increased interactions fueled the virtual virus’ spread—but most of this simulated transmission occurred via social activities rather than in classrooms, a dynamic that could also explain Covid-19 outbreaks on campus at the time.

As part of their Covid-19 response, CMU had sorted its students into social units. But after studying the Operation Outbreak data, they decided to incorporate more student behavior into their pandemic mitigation strategies, allowing students to create their own units with both CMU and non-CMU members.

“With the visualization tools, you could see it happening in real time. We needed to engage and incorporate the student perspective in our policy making,” said John Marshall, vice president of CMU student services. The exercise is also shaping their testing strategy, which has now been expanded to include non-CMU community members.

Sabeti, who is also co-leading ambitious efforts with close collaborators in Africa to pioneer a pandemic preemption and response system, sees Operation Outbreak as an essential tool for preventing, preparing for, and coping with future epidemics. “There will be other outbreaks, and we must ensure that everyone—students, healthcare workers, public health officials—is prepared,” noted Sabeti. “That’s where Operation Outbreak can make a difference.” —Indrani Mukherjee

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Infectious Disease

Joining the Fight against COVID-19

admin — Wed, 29 Apr 2020 19:36:18 +0000

Joining the Fight against COVID-19

The Broad Institute of MIT and Harvard is contributing to the global scientific effort to overcome the COVID-19 pandemic. Our researchers quickly converted a clinical research laboratory into a viral diagnostics laboratory, becoming a state reference lab in Massachusetts and partnering with the state to conduct rapid surveillance testing in vulnerable populations, such as those in nursing homes and homeless shelters.

The Broad also announced a partnership with Partners HealthCare and Biogen to build a biobank of patient samples in order to solve some of the central mysteries of this new virus and pave the way for treatments. Broad researchers are also helping to lead a global consortium of geneticists devoted to understanding the genetic factors that put patients at risk of severe disease.

Click here to learn more the Broad’s COVID-19 research.

Eric Lander, president and founding director of the Broad Institute of MIT and Harvard and Chair of Massachusetts COVID-19 External Task Force, recently spoke to Walter Isaacson on PBS’s Amanpour & Company about the state of the pandemic—and what exactly it will take to safely reopen the U.S. Watch the video below!

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Infectious Disease

Zeroing in on Zika

admin — Fri, 23 Jun 2017 15:28:59 +0000

Donor Impact

Zeroing in on Zika

Pardis Sabeti, an infectious disease expert at the Broad Institute, knows how to put together a rapid response to outbreaks. When the Ebola virus ravaged West Africa in 2014, Sabeti and her team quickly worked with scientists and health workers on the ground to understand the epidemic. They helped their African partners diagnose the first case of the deadly disease in Nigeria—a key step towards containing it in Africa’s most populous country.

Sabeti’s team is now contending with a different scourge: Zika. Thanks in part to the philanthropic support of Marc and Lynne Benioff, they’ve assembled more than 110 Zika genomes from 10 countries and territories for the largest-to-date sequencing study of the virus, which will help guide a proactive response to future outbreaks.

Though Zika has faded from headlines, it hasn’t gone away—and the consequences of the outbreak, particularly in Brazil, have been devastating. The virus has been linked to microcephaly and other serious fetal brain defects; the World Health Organization reported that as of June 15, 2017, 2,722 Brazilian babies had Zika-related birth defects. Zika has also been connected to Guillain-Barré syndrome, which affects the nervous system and can cause temporary paralysis.

Although Zika had been known in Africa and Asia for decades—it was first identified near the Zika River in Uganda in 1947—the outbreak in the Americas caught health officials off guard. For a year after the virus was first detected in Brazil in 2015, there was very little genomic information available—even though it was essential to understanding and grappling with the virus. Sabeti’s group had shown with Ebola how valuable it could be to obtain and analyze genomes in the midst of an epidemic. “By having genomes during an outbreak, you can watch how the virus is changing and, in the process, make more sensitive and specific diagnostics,” said Hayden Metsky, a Ph.D. student in the Sabeti lab.

The first hurdle was obtaining genomes. Brazil’s laws bar medical samples leaving the country for research, and Sabeti’s personal connections mostly existed in Africa. Her lab overcame this by working with MIT’s Irene Bosch, a dengue researcher with a network of collaborators in the region, and reaching out to scientists in Brazil, elsewhere in Central and South America, in the Caribbean, and in Florida. Indeed, global teamwork epitomizes Sabeti’s MO wherever outbreaks occur. “Pardis has something not patentable—relationships with scientists in a lot of countries,” said Raffaella Squilloni, a Harvard Business School Blavatnik Fellow in Life Science Entrepreneurship working with Sabeti’s group.

But the group soon faced another hurdle. This time, it was technical: Zika is present in the body at much lower quantities than Ebola and many other viruses are, which makes it difficult to sequence. To tackle this challenge, Sabeti’s team tried three different techniques to analyze the viral genome sequence from human samples and squashed mosquitos.

_{(image credit Hayden Metsky)}

First, Metsky and fellow lab member Chris Matranga used a technique that they and their lab mates designed, which amplifies all of the genetic material in a sample, then fishes out Zika and chikungunya sequences. This approach is particularly useful for analyzing how Zika is changing inside of patients because it can detect Zika variation within samples. Plus, another team member, Mary Lynn Baniecki, was able to use the method to design Zika-specific probes as the basis for a new diagnostic for the virus.

This approach yielded 37 genomes from 66 samples. To collect even more genomes, the team supplemented their technique with a more traditional one that picks up and amplifies only Zika sequences. This more sensitive approach contributed the bulk of the 110 genomes.

Finally, the group sequenced all the viral content, in an unbiased way, in 38 samples: 30 from humans and eight from mosquitos. That allowed them to identify other viruses that were co-infecting Zika patients and mosquitos—including some that are new to science.

Together, these methods provided the single largest and most geographically diverse data set of Zika genomes available for study. Recently published in Nature, these genomes provided key insights into the outbreak: how and when Zika might have spread from country to country, and how the virus is changing over time.

Critically, the genomes revealed that Zika was lurking in Central and South America and the Caribbean for many months before it popped up on the radar. That suggests that, in the future, improved monitoring might make it possible to catch viral outbreaks early—perhaps even before viruses become outbreaks—and stop them in their tracks. In that vein, the group is developing a catch-all method to identify any virus in a sample—without necessarily knowing what you’re looking for. This pan-virus diagnostic will capture any of the approximately 300 viruses known to infect people.

The group also collaborated with other teams at the Broad to create an entirely new viral detection system for Zika and other diseases based on the genome-editing tool CRISPR. The method, known as SHERLOCK, was also partially supported by the Benioffs’ generous gift.

It’s all part of Sabeti’s vision to revolutionize the way we monitor and respond to outbreaks. “If we’ve learned anything from recent outbreaks, it’s that we need to be better prepared for the next one,” she said. “It is our hope that our work can help lay the foundation for national and global diagnostic, surveillance, and response systems that identify potential outbreaks and contain them before they spread.”

_{The Sabeti Lab Zika team}

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