The Pandemic Prevention Institute Partnership Helps Uncover Breakthrough Infections

These “Regional Accelerators” look different in each part of the country—tackling local challenges with ingenuity and cross-sectoral collaboration, while improving representativeness of sampling, access to underserved communities and incorporating new technologies for surveillance, including wastewater and air sampling.

Provincetown Outbreak Provides Crucial Lessons

In Massachusetts, the Regional Accelerator team at the Broad Institute of MIT and Harvard swung into action in response to the major outbreak in Provincetown, Massachusetts, last summer. Vaccination rates in the state were relatively high and Provincetown hadn’t suffered a single confirmed coronavirus case for a month. Following CDC guidance of no indoor mask mandate for vaccinated people, many felt a pandemic corner had been turned.

However, just days after the July 4th weekend, cases in Provincetown started to increase. Public health officials realized they had an outbreak on their hands among a largely vaccinated population—the first such large scale outbreak recorded in the United States. This contributed to the CDC’s decision to reintroduce indoor mask guidance for vaccinated people.

Well before this outbreak, the Broad team had been sequencing SARS-CoV-2 viruses from cases across the state, directly aiding the Massachusetts Department of Public Health (MADPH)’s genomic surveillance efforts. The surge in a highly vaccinated population (in Barnstable Country, MA, approximately 84% of eligible individuals had one dose administered by late July 2021) raised important questions about the ability of the new Delta variant to infect and spread between vaccinated individuals.

The Broad Institute knew the need to link genomic tracking to key meta-data like vaccination status as part of the pandemic response and, with support from the PPI, they were ready to respond.

The team, led by Drs. Pardis Sabeti and MacInnis, worked with colleagues at the MADPH to sequence SARS-CoV-2 viruses from the outbreak, link sequencing data to vaccination status, identify the variants involved, and determine whether the virus was spreading from vaccinated people. What the team found turned the Covid-19 response on its head: vaccinated individuals were being infected and transmitting to other individuals.

The Challenges of Data Gathering

Uncovering this information wasn’t a given and wasn’t easy. Linking vaccination status of an individual case to the genetic sequence of the virus from their infection isn’t automated in most  health information systems tracking Covid-19 test results.

To tackle the challenge, the Broad Institute sequenced the genomes of the viral samples and passed the information back to the state, which then re-connected the sequence information to private patient health to capture each person’s vaccination status. With that information included officials eliminated any of the patient’s personally identifiable information before passing the dataset back to the Broad to analyze.

“It was a lot of manual work and Excel spreadsheets,” MacInnis said. “So, in this era of big data and advanced information systems, we returned to a 1980s approach.”

The team rapidly communicated their findings via a pre-print, later published in a peer-reviewed journal, which synthesized genomic and epidemiological data from 467 individuals, including 40% of known outbreak-associated cases. The Delta variant accounted for 99% of sequenced infections, and the outbreak included viruses originating from more than 40 sources. One source led to approximately 83% of the cases in the outbreak. From this, the team showed extensive spread of the virus from and between fully vaccinated people, the first large scale demonstration of this backed by genomic data.

These findings help fill critical information gaps and highlighted the possible risk of spread among vaccinated people. In Provincetown, businesses started requiring indoor masking, which kept businesses open and gave tourists the confidence to visit safely. Linking data to action saves lives and livelihoods and is also great for business.

The Provincetown outbreak underscored how important it is to efficiently link viral genomic data with patient public health information–like vaccination status–to gain critical insights for a real-time, public health response. With the support of the Pandemic Prevention Institute, the Broad Institute team continues this collaborative work with public health colleagues in Massachusetts, intending to extend these lessons learned and new solutions to other groups in the Regional Accelerator Network and to other states across the U.S.