Emily Datnow, a UCSF technician, prepares a PCR swab at a Unidos en Salud pop up test site. SAN FRANCISCO - Dec. 1, 2020 (Mike Kai Chen/Freelance).

When the pandemic began last year, local residents faced a cavalcade of challenges to test, isolate, and quarantine for Covid-19. In an unusual collaboration, scientists from the Chan Zuckerberg Biohub and the University of California, San Francisco began working with the Latino Task Force to figure out how best to get control of infections. Rapid tests were first tried and then scaled up across the city,  cutting down wait times for test results and connecting people to resources faster.

The success, notably so in a community of color, urged the city to rethink its Covid-19 response.

“The collaboration has been pretty extraordinary,” said Patrick Ayscue, a Chan Zuckerberg Biohub epidemiologist crediting his UCSF colleagues Joe DeRisi and Diane Havlir for integrating advanced science at a local community level. “You’re really meaningfully moving the needle at that point.”

Part of that was DeRisi running the tests faster than any other lab, but it also included genomic sequencing of every test specimen they received from the collaborative, known as Unidos en Salud/United in Health.

The sequencing data is crucial during outbreak response, as it helps front-line public health workers quickly understand dynamics of disease transmission and how to implement more targeted interventions to stop that spread effectively. Earlier this year, Ayscue, DeRisi, Havlir, and others published a study about how the L452R mutation, which appears in several covid variant lineages, operated in Mission households.

The pandemic underscored the value of genome sequencing, and, when the Chan Zuckerberg Initiative’s science program turned five last week, it announced an ambitious redoubling of its work including an extension of the nonprofit, independent Chan Zuckerberg Biohub research center through 2031. They will also launch a new Chan Zuckerberg Biohub Network to replicate their local community partnership model around the world. 

“It’s a general tenet of our work across Biohub and CZI that we tend to approach things from a bottom-up level … going to the frontline with those local groups,” said Ayscue.

Their renewed mission is bold, with the goal to “cure, prevent, and manage all disease by the end of the century.” Yes, that’s right: all disease. 

One way they’ll do this is through genomic sequencing, a public health game changer which contributes to the CZI endeavor to “observe, measure, and analyze any biological process throughout the human body — across spatial scales and in real time” by tracking changes in various pathogens’ genetic code.

Representatives of Unidos en Salud community partner organizations attended a press conference at the testing site on Nov. 22, including, from left: UCSF Chancellor Sam Hawgood, Dr. Joe DeRisi of the Chan Zuckerberg Biohub, Dr. Diane Havlir, the research lead from UCSF, and Salu Ribeiro, co-founder and CEO of Bay PLS. Photo by Anlan Cheney.

In addition to Unidos en Salud covid specimens, which they still sequence themselves, the Biohub opened up its sequencing capabilities to health departments across California at the start of the pandemic. As sequencing demand grew — “exponentially,” said Ayscue — they trained and supported departments to take on their own sequencing load.

The sequencing data is like breadcrumbs, said Ayscue, which help “track how people are getting infected and where.” Health departments may use these “breadcrumbs” over a period of time to “understand what’s circulating in their communities.” As a form of longitudinal surveillance, he said, they can then identify important trends and changes, such as variant mutations.

And, whereas traditional disease investigation requires trusting what Ayscue calls “circumstantial data” — an accepted degree of uncertainty in identifying transmission links — he said ”the genomic data really gives us concrete, tangible answers … [and] helps target where those limited public health resources are going.”

They’ve also begun to address the next challenge: making the data generated by sequencing accessible, approachable, and shareable.

“We have this tremendous volume of pathogen genomic data that we’ve never had for any pathogen previously,” said Ayscue. “So it’s really made it a challenge for people to actually be able to manage all of those data and then apply them to their analysis.”

During an emergency response like the covid pandemic, pointed out Ayscue, many health departments “haven’t been able to fully explore everything that [the genomic sequencing data] can do.”

That’s why the Biohub developed CZ Gen Epi, a free platform for analyzing genomic surveillance data that doesn’t require users to know how to write code. They’ve also created a “virtual workbench” capability for users to share and collaborate over this data, even across different health departments.

A key challenge remains, said Ayscue: “The genomic data are not very valuable sitting on their own.” 

To answer critical questions about covid variants and vaccine efficacy, disease severity, and infectiousness, for example, genomic data must be linked to demographic characteristics, clinical outcomes, epidemiologic investigations, and other helpful data points. Most of these are captured in separate surveillance systems that can’t “talk to each other.”

In the coming year, the Biohub plans to apply its sequencing expertise to respiratory pathogens and tuberculosis; California has, despite recent improvements, a higher burden of tuberculosis in the United States.

Ayscue said their public health partners have also expressed a desire to prioritize development of sequencing capabilities and systems for hospital acquired infections and sexually transmitted infections.

Editor’s note: The Chan Zuckerberg Initiative supports Mission Local

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"Annie" is originally from Nebraska, where she found her calling to journalism as editor of her high school newsletter. Before returning to the field, she studied peace and political science in the Balkans, taught elementary and middle school, and worked as an epidemiologist during the COVID-19 pandemic. Follow her on Twitter @anlancheney.

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