Seattle Flu Study pivots to SARS-CoV-2

From the University of Washington Medicine and the Fred Hutch Vaccine and Infectious Disease Division

Seasonal flu epidemics in the United states cause up to 45 million illnesses and 67,000 deaths annually, and emerging, hyper-virulent strains can result in increased infection and mortality. To monitor seasonal dynamics and to recognize and characterize emerging viruses, active surveillance of influenza is necessary. However, existing influenza surveillance systems rely on medically attended influenza cases, which may fail to capture many influenza infections in people who fail to present for care. Therefore, a community-wide testing program is necessary detect early cases of influenza and other respiratory viruses and to establish a pipeline for outbreak containment and pandemic response.

The Seattle Flu Study (SFS), a collaboration between the Brotman Baty Institute, Fred Hutch, University of Washington, and Seattle Children’s, was implemented during the 2018-2019 season to characterize how influenza enters and spreads within the community. This ongoing, multi-arm study enrolls participants with acute respiratory illness (ARI)-associated symptoms from various clinical and community sites in the Seattle area and collects and tests nasal samples for infection with influenza and other respiratory viruses. The results of these tests are linked to patient demographics and illness characteristics to further define influenza prevalence and transmission patterns, and influenza-positive samples are further sequenced to inform molecular epidemiology modeling of Seattle influenza outbreaks.  A recent publication in BMJ Open, led by Dr. Helen Y. Chu (University of Washington Medicine), along with collaborators from the Fred Hutch Vaccine and Infectious Disease Division, details the protocol for the SFS. This work demonstrates that an integrated surveillance system can more comprehensively estimate influenza prevalence from both clinical and community settings, and model transmission dynamics, presenting a paradigm for pandemic preparedness. Of course, having been first assembled more than two years ago, the authors could not have anticipated the timeliness of this study ahead of the Seattle SARS-CoV-2 outbreak, and later pandemic, of 2020.

As the SFS was already in place to detect early respiratory infections, the platform identified the first community transmission of SARS-CoV-2 in the United States in early 2020. Since then, the study has now been adapted to further characterize SARS-CoV-2 transmission dynamics in Seattle. “Following the start of the pandemic in the U.S., the Seattle Flu Study team quickly pivoted to providing at-home SARS-CoV-2 testing through the launch of the greater Seattle Coronavirus Assessment Network (SCAN). The study has since partnered with community-based organizations to expand testing to underserved and minority populations in the Seattle metropolitan area,” explained Jennifer Logue, the research coordinator for the Seattle Flu Study. Additionally, during the 2019-2020 season, the SFS “enrolled just over 300 households into a prospective longitudinal observational study, where participants submitted weekly symptom questionnaires and sent in self-collected nasal swabs in the event of an acute respiratory illness (ARI),” Logue said. “As part of year 2 of this study, we are testing swabs collected during ARI events for SARS-CoV-2 and studying transmission of COVID-19 within households,” she continued.

Laboratory pipeline for samples included in the Seattle Flu Study from time of collection through sequencing.
Laboratory pipeline for samples included in the Seattle Flu Study from time of collection through sequencing. Figure from publication.

“This work presents a replicable study design for the large-scale assessment of acute respiratory infections,” said Dr. Chu. “This framework can be implemented for pathogen surveillance across a major metropolitan area and allows for targeted public health interventions and the early detection of novel pathogens - which was demonstrated by the Seattle Flu Study’s detection of the first known community transmission of SARS-CoV-2 in the United States. Furthermore, the study design and infrastructure are scalable in a global pandemic setting and can provide early transmission mapping and wide-scale at-home community-based testing,” Dr. Chu explained.

Going forward, the researchers behind the SFS hope to test whether “this study design (can) be used to provide testing and public health interventions to underserved or rural populations,” said Dr. Chu. Pilot studies have been launched to survey respiratory virus prevalence in Seattle homeless shelters, and these studies “have continued into the 2020-2021 season and will help to inform the feasibility and effectiveness of surveying and mitigating the spread of respiratory pathogens within a high-risk population,” Dr. Chu explained. Additionally, the SFS has been adapted to collect samples from asymptomatic people to determine the role that asymptomatic transmission of respiratory pathogens plays in the community. 

This work was supported by Gates Ventures.

UW/Fred Hutch Cancer Consortium members Trevor Bedford, Michael Boeckh, Janet A. Englund, Deborah Nickerson, Lea Starita, and Jay Shendure contributed to this work.

Chu HY, Boeckh M, Englund JA, Famulare M, Lutz B, Nickerson DA, Rieder M, Starita LM, Adler A, Brandstetter E, Frazer CD, Han PD, Gulati RK, Hadfield J, Jackson M, Kiavand A, Kimball LE, Lacombe K, Newman K, Sibley TR, Logue JK, Lyon VR, Wolf CR, Suchsland MZ, Shendure J, Bedford T. The Seattle Flu Study: a multiarm community-based prospective study protocol for assessing influenza prevalence, transmission and genomic epidemiology. BMJ Open. 2020 Oct 7;10(10):e037295. doi: 10.1136/bmjopen-2020-037295.