Infectious Disease Sciences (IDS) researchers are playing a key role in the development of new COVID-19 prevention and treatment strategies. Our researchers are heading up several population-based studies as well as leading the way in clinical response to the virus.
Content last updated 4/28/2021
Michael Boeckh and Alpana Waghmare are co-leading the COVID-19 Immune Protection Study: Investigating the role of pre-existing immunity to SARS-CoV-2 and the impact on infection outcomes. This may also help us understand which immune responses help to protect a person and need to be generated by a vaccine.
Michael Boeckh is part of a multi-organizational team collaborating on the Seattle Coronavirus Assessment Network (SCAN): By collecting nasal swabs from a representative sample of healthy and sick people across Seattle and King County, the study aims to develop a better understanding of the outbreak and help inform public health decisions.
Michael Boeckh is a co-investigator on a trial (PI: Shelly Karuna) that is being conducted at the Fred Hutch COVID-19 Clinical Research Center. The purpose of this trial is to evaluate treatment with IV-administered REGN-COV2, a combination therapy with two antibodies, in an outpatient setting for participants with confirmed SARS-CoV-2 infection, the virus that causes COVID-19, who are symptomatic and at risk for disease progression.
Larry Corey is head of the Fred Hutch-based operations center for the COVID-19 Prevention Network (CoVPN), which was formed by the National Institute of Allergy and Infectious Diseases (NIAID) at the United States (US) National Institutes of Health (NIH). CoVPN is developing and conducting studies to ensure rapid and thorough evaluation of US government-sponsored COVID-19 vaccines and antibodies for the prevention of COVID-19 disease. Please see the CoVPN website for more information on active trials, news releases summarizing trial results to date, or to volunteer for a COVID-19 prevention clinical study.
Elizabeth Duke is is the site PI of a trial of molnupiravir (MK4482) that is being conducted at the Fred Hutch COVID-19 Clinical Research Center. The purpose of this trial is to evaluate treatment with orally-administered molnupiravir in adults who live with someone with confirmed SARS-CoV-2 infection.
Manoj Menon is assessing the inflammatory cytokine profile in the treatment of COVID-19 among recipients of convalescent plasma or placebo for the Passive Immunity Trial for our Nation (PassItOn) study.
Content last updated 4/28/2021
Content last updated 4/28/21
Michael Boeckh and collaborators experimentally demonstrated that the spike protein of seasonal human coronavirus 229E evolves at a rate that, within one to two decades, allows it to escape neutralization by antibodies generated to provide immunity against the original strain.
Michael Boeckh and other Seattle Flu Study/SCAN investigators, including Amanda Casto, have demonstrated the feasibility of remote monitoring (using contactless methods of recruitment, enrollment and sample collection) for surveillance of influenza and other respiratory pathogens within households and in the community. The group has also applied these methods to investigate prevalence of SARS-CoV-2 in Seattle-area homeless shelters.
Amanda Casto contributed to a study that found that titers of neutralizing and binding antibodies targeting SARS-CoV-2 spike protein declined modestly within 4 months of COVID-19 symptom onset, consistent with other known viral infections.
Fabian Cardozo-Ojeda and Josh Schiffer developed an intra-host mathematical model of SARS CoV-2 kinetics that captures the timing and intensity of staged immune pressure against the virus, serves as a platform for clinical trial simulations, and identifies the relationship between viral shedding and immune responses. With Ashish Goyal. See manuscripts in Science Advances and Viruses.
Larry Corey is a co-author on two New England Journal of Medicine articles that describe safety and efficacy data from the Phase 3 trials of two SARS-CoV-2 vaccines. The first article demonstrated 94.1% efficacy of the Moderna mRNA-1273 SARS-CoV-2 vaccine at preventing symptomatic COVID-19 illness, with no safety concerns identified. The second article showed 66% efficacy of the single-dose Ad26.COV2.S vaccine from Johnson & Johnson in preventing moderate-to-severe COVID-19 illness, with an acceptable safety profile.
Larry Corey, Emily Ford, and Anton Sholukh published a sero-epidemiology study of SARS-CoV-2 in Blaine County, ID, with follow up analysis of humoral response to seasonal coronaviruses and functionality of SARS-CoV-2 antibodies (a collaboration with Ketchum FD, University of Washington [UW] Virology and Albany College of Pharmacy and Health Sciences).
Elizabeth Duke, Fabian Cardozo-Ojeda, and Josh Schiffer developed a mathematical model to explain why remdesivir has a greater antiviral effect on SARS CoV-2 in lung versus nasal passages in rhesus macaques. With Ashish Goyal.
Josh Hill and Manoj Menon conducted a retrospective observational study to assess whether use of the immunomodulatory therapy tocilizumab is associated with clinical improvement of patients hospitalized with COVID-19 and receiving supplemental oxygen.
Keith Jerome and Larry Corey conducted a population epidemiology study to characterize trends in PCR test positivity for SARS-CoV-2 in Washington (WA) State and the Seattle area before and after statewide physical distancing guidelines and stay-at-home orders.
Keith Jerome and Amanda Casto have completed a comparative assessment of the sensitivities and specificities of SARS-CoV-2 molecular assays using different primer sets and one commercial assay kit.
Keith Jerome and Pavitra Roychoudhury
Keith Jerome, Samuel Minot, and Pavitra Roychoudhury evaluated metagenomic approaches for unbiased detection of emerging pathogens including SARS-CoV-2.
Keith Jerome and Anna Wald contributed to a study which used B-cell epitope prediction methods, combined with comprehensive mining of sequence databases and structural data, to identify SARS-CoV-2 proteins suitable for diagnosis of SARS-CoV-2 in serum samples.
Catherine Liu, Chikara Ogimi, Steve Pergam, and Alpana Waghmare conducted a study on “Clinical and Virologic Characteristics and Outcomes of Coronavirus Disease 2019 at a Cancer Center.”
Chikara Ogimi, Alpana Waghmare, Keith Jerome and Michael Boeckh identified risk factors (including hyperglycemia) for lower respiratory tract infection caused by seasonal human coronaviruses, in a retrospective study of recipients of hematopoietic cell transplants.
Chikara Ogimi and Michael Boeckh conducted an ecological study to examine whether childhood vaccine status is associated with COVID-19 related outcomes on a country basis.
Chikara Ogimi has reviewed current knowledge and recent discoveries on the virology, epidemiology and disease associated with common, community-acquired human coronaviruses and coronaviruses responsible for past epidemics in pediatrics and immunocompromised hosts.
Steve Pergam contributed to a cross-sectional study of 230 US vaccine trials with 219,555 participants, which demonstrated that racial/ethnic minority groups and people 65 years and older are underrepresented in US vaccine trials.
Steve Pergam, Catherine Liu, and Keith Jerome investigated SARS-CoV-2 prevalence, clinical characteristics and outcomes in symptomatic Seattle-area healthcare workers.
Dan Reeves and Josh Schiffer developed a mathematical model, parameterized with demographic and contact data from King County, WA, to project SARS-CoV-2 transmission during and after various reopening scenarios, with the goal of understanding how adjunctive interventions and physical distancing may be used to help society return to “normalcy” including the safe reopening of schools, and to endure potential subsequent epidemic waves. Recently released COVID projections app. With Chloe Bracis (Grenoble), Eileen Burns, Dobromir Dimitrov, Mia Moore, and Dave Swan.
Dan Reeves, Fabian Cardozo-Ojeda, and Josh Schiffer developed a SARS CoV-2 transmission model that links observed viral shedding kinetics with key epidemiologic features of transmission, identifies viral loads necessary for SARS-CoV-2 transmission, and explains why super-spreader events are more common for SARS-CoV-2 than for influenza. They then used this model to demonstrate that widespread use of even modestly effective masks is predicted to severely limit epidemic spread, and to identify early super-spreader events as a likely determinant of SARS-CoV-2 variant predominance. With Ashish Goyal and Bryan Mayer. This work was featured directly in the New York Times and LA times and also cited in the Atlantic, the Washington Post, NPR and the Smithsonian.
Dan Reeves and Josh Schiffer identified rapid vaccination and early implementation of partial lockdown as critical variables to save lives in the context of emerging highly contagious SARS-CoV-2 variant, by simulating multiple scenarios using the above model. With Chloe Bracis (Grenoble), Dobromir Dimitrov, Mia Moore, and Dave Swan. This work was featured in Geekwire, and is also now featured on a user-friendly webpage intended to simulate possible trajectories for COVID-19 epidemiology in King County.
Dan Reeves used phylogenetically-informed models of viral evolution to determine that neutral evolution, rather than adaptive selection, can explain rare mutations seen across SARS-CoV-2 genomes, and that a single vaccine candidate should be efficacious against currently circulating lineages. In partnership with collaborators at Walter Reed Army Institute of Research.
Josh Schiffer determined that optimal COVID-19 vaccine allocation strategies depend critically on the degree of viral transmission and the single-dose efficacy of COVID-19 vaccines. The study used mathematical modeling combined with optimization algorithms to minimize five metrics of disease burden. With Laura Matrajt, Julia Eaton, Tiffany Leung, Dobromir Dimitrov, Dave Swan, and Holly Janes.
Josh Schiffer found that circulating immune signatures were similar in patients hospitalized with SARS-CoV-2, Flu, or respiratory syncytial virus (RSV) infection compared to healthy donors. However, regulatory T cells were elevated in the circulation of patients with the most critical COVID-19 disease, and showed phenotypic changes indicating increased suppressive capacity and tissue-migratory patterns. With Sarah Vick, Marie Frutoso, Florian Mair, Andrew J Konecny, Evan Greene, Caitlin Wolf, Jennifer Logue, Jim Boonyaratanakornkit, Raphael Gottardo, Helen Chu, Martin Prlic, and Jennifer Lund.
Josh Schiffer and Keith Jerome investigated the longitudinal dynamics of IgG and IgM antibodies to SARS-CoV-2 infection and demonstrated that antibody responses to SARS-CoV-2 do not appear to be the primary mechanism underlying viral clearance from the nasal passages. With Ashish Goyal, Shuyi Yang (summer student) and Alex Greninger.
Anton Sholukh, Emily Ford, Keith Jerome, and Larry Corey compared three platforms for SARS-CoV-2 neutralization and demonstrate high concordance between cell-based assays with live and pseudotyped virions.
Josh Schiffer and Dan Reeves used mathematical modelling to assess the potential impact of COVID-19 vaccines that prevent SARS-CoV-2 infection, versus those that only prevent symptomatic COVID-19 disease after infection, on the numbers of infections and deaths in King County, Washington. With Dobromir Dimitrov, Dave Swan, Chloe Bracis (Grenoble), Holly Janes, Mia Moore, Laura Matrajt, Elieen Burns, Deborah Donnell, and Myron Cohen.
Josh Schiffer, Fabian Cardozo-Ojeda, Dan Reeves and Larry Corey used this vaccine efficacy model to predict the extent to which a vaccine will need to reduce infectiousness in order to prevent or limit the extent of a fourth epidemic wave in spring 2021, the reduction in viral load needed for an adequate reduction in infectiousness, and the size of a study that is needed to determine how much a vaccine prevents infection. With Ashish Goyal, Dobromir Dimitrov, Dave Swan, Chloe Bracis (Grenoble), Mia Moore, Elizabeth Krantz, Elizabeth Brown, Fei Gao, Peter Gilbert, Myron Cohen (UNC), and Holly Janes. See coverage in Geekwire.
Alpana Waghmare, Josh Schiffer, Michael Boeckh, Keith Jerome, Elizabeth Duke, Dan Reeves, and Fabian Cardozo-Ojeda demonstrated that self-sampling with mid-nasal foam swabs is well-tolerated and provides quantitative viral output concordant with mid-turbinate flocked swabs, that nasal cytokine levels correlate and cluster according to immune cell of origin, and that periods of stable viral loads are followed by rapid elimination, which could be coupled with cytokine expansion and contraction using mathematical models. Studies are ongoing to determine the utility of the foam swab for SARS-CoV-2 testing at home. With Subhasish Baral.
Anna Wald contributed to a publication that describes comprehensive profiling of T cell and antibody functions related to targeting SARS-CoV-2 proteins. The study revealed a functionally diverse and coordinated response between T cells and antibodies targeting SARS-CoV-2, which is reduced in the presence of comorbid illnesses that are known risk factors for severe COVID-19.
Anna Wald, Elizabeth Duke and Amanda Casto, as study investigators in the ACTT-1 NIH randomized controlled trial of remdesivir for hospitalized patients, showed that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with COVID-19 and had evidence of lower respiratory tract infection.
Anna Wald and Keith Jerome, as part of the COVID-19 Post-exposure Prophylaxis (PEP) Trial, found that hydroxychloroquine did not demonstrate a clinically meaningful effect in preventing SARS-CoV-2 infection, among contacts of persons with SARS-CoV-2 infection.
Anna Wald, Keith Jerome, and Joshua Schiffer, as part of the COVID-19 Treatment Study: Hydroxychloroquine (HCQ) and Azithromycin (AZ), that neither HCQ nor HCQ/AZ shortened the clinical course of outpatients with COVID-19.
Danniel Zamora, Keith Jerome and Anna Wald assessed clinical, laboratory, and temporal predictors of neutralizing antibodies to SARS-CoV-2 among COVID-19 convalescent plasma donor candidates. With Jim Boonyaratanakornkit.
Content last updated 4/28/21
Fabian Cardozo-Ojeda and Josh Schiffer
Josh Hill was Interviewed for KIRO 7-TV’s evening newscast for a story on whether cancer patients should get the COVID-19 vaccines.
Catherine Liu was interviewed in “Lessons Learned About COVID and Cancer— Applying evidence, acknowledging uncertainty, adapting, moving forward with humility” for MedPage Today and quoted in “If I Have Cancer, Dementia or MS, Should I Get the Covid Vaccine?” for Kaiser Health News.
Manoj Menon was quoted in “Early Use of High-Titer Plasma May Prevent Severe COVID-19” for Medscape
Anton Sholukh was invited by the World Health Organization to present at a meeting of their Solidarity II workgroup, a global collaboration that promotes the implementation of serological studies of SARS-CoV-2.
Michael Boeckh’s CovidWatch study was recently featured on the front page of The Seattle Times, “Fred Hutch Study Targets Front-line Workers Most at Risk from the Coronavirus.”
Amanda Casto was interviewed by a writer for UW Medicine for an article on clinician recommendations for the upcoming influenza season in the context of the ongoing SARS-CoV-2 pandemic. Article to appear in UW Medicine patient publication Right as Rain.
Emily Ford and Danniel Zamora are part of a team of volunteers deployed to area nursing homes to provide SARS-CoV-2 testing to people in facilities with multiple confirmed COVID positive cases.
Fellow Olivia Kates was quoted by KING 5 News in “Experts concerned coronavirus cases could rise with Seattle protests.”
Catherine Liu and Steve Pergam
Steve Pergam has been very actively involved in keeping the public informed. Some engagements include talking to KUOW for “Coronavirus outbreak means tough decisions for cancer patients, physicians”, the Scientific American podcast “Coronavirus Hot Zone: Research and Responses in the U.S. Epicenter”, and KING 5 news for “The Do’s and Don’ts of Social Distancing.” He was featured in The Seattle Times article “The etiquette of social distancing in the time of coronavirus, from the 'Miss Manners' of germs” as well as GeekWire’s story “Infectious disease expert Steve Pergam shares his prescription for a safe weekend get-together.” Recently he was interviewed by NPR and Scripps National News about the importance and timing of flu vaccination in the context of the COVID-19 pandemic. Other media engagements include quotes and interviews with the Wall Street Journal, USAToday, NPR, Forbes, Scripps National News, ESPN, Healio, ACCC, MedPage Today, CURE Today and Cancer Health magazines, The Cancer Letter, Poz, The Washington Post, Bloomberg News, KOMO News, Q13 FOX News, Patient Worthy, Unravel Pediatric Cancer Podcast, CureTalks podcast, Uromigos podcast, MyNorthwest, Women’s Health Magazine, the SCCA blog and podcast, and Hutch News.
Danniel Zamora participated in the Northwest Hospital surge capacity response earlier this year by working in the medical ICU treating/caring for COVID-19 and non-COVID-19 patients, and volunteered covering the hospital-wide UW Medical Center clinical COVID-19 pager answering and advising clinical questions regarding COVID-19 treatment and testing.