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Latest Fred Hutch research on COVID-19

How Hutch scientists have been tackling coronavirus in lab and clinic
photo of a woman looking through a microscope
Graduate research assistant Kate Crawford conducts research in the Bloom Lab at Fred Hutch, which pivoted to COVID-19 research since the pandemic swept into Washington state in early 2020. Photo by Robert Hood / Fred Hutch News Service

As COVID-19 became a pandemic, scientists at Fred Hutchinson Cancer Research Center have been on the forefront of research to understand the virus and save lives through prevention and treatment. About 20% of Fred Hutch researchers have active projects related to the disease and the SARS-CoV-2 virus that causes it.

Read more about these studies, and their most recent results, in the highlights below. We’ll update this page regularly as new research is published.

June 2022

Predicting effects of SARS-CoV-2 evolution

In a June 28 paper published under immediate release by the journal Science, Fred Hutch evolutionary biologist Dr. Jesse Bloom and colleagues describe how individual mutations in particular locations on the coronavirus spike protein may affect, for good or ill, the ability of other sites on the spike to bind to our cells. It is a phenomenon of combined effects called epistasis. The work, led by computational biologist Dr. Tyler Starr, tracks these effects in the original Wuhan isolate and in four other subsequent variants. It explores how these epistatic shifts add or detract to the ability of the spike to bind to ACE2, a receptor on cell surfaces that is the primary site used by the virus to infect humans. The research gives scientists a useful tool to predict more accurately the impact of rapid evolutionary changes occurring in current omicron variants of the virus.

April 2022

SARS-CoV-2 evolution and vaccine development

On April 6, Dr. Trevor Bedford presented his research on SARS-CoV-2 evolution to the Food and Drug Administration's advisory committee on vaccines and related biological products, which had convened to consider how the U.S. might approach updating the current coronvirus vaccines for future variants. 

According to a report on the meeting from the Associated Press, Bedford told the panel that the data shows that a major new strain of the coronavirus, like omicron, could emerge anywhere from every 1.5 to 10 years, and that uncertainty means that researchers need methods to quickly determine whether current vaccines work against emerging variants.

He shared his slides and a recording of his talk with the public via Twitter:

Tweet from Trevor Bedford (@trvrb) on April 6, 2022, that reads: Today, I presented to  @US_FDA  VRBPAC with an overview of SARS-CoV-2 evolution up to this point and a brief perspective for what to expect going forward. Slides are here: https://bedford.io/talks/sars-cov-2-continuing-evolution-vrbpac/ and my slot in the full recording is viewable here: https://youtu.be/x8rq247E80I?t=11572. 1/13
Click to view on Twitter

The committee's "focus on identifying a regulatory pathway to modifying vaccine strain composition is highly necessary, and has real urgency if we want to have as efficacious of a vaccine as we'd like," he wrote in that thread.

March 2022

An effective monoclonal antibody drug

Dr. Adrienne Shapiro is a senior author of a study published on March 15 in JAMA reporting results of a trial of the monoclonal antibody drug sotrovimab. Carried out at Fred Hutch and 56 other trials sites in the U.S. and overseas, it found that the drug reduced the risk of hospitalization or death by 79% among those who received the drug compared with those who were assigned to a placebo.

The study enrolled 1,057 patients who had recently tested positive for COVID-19 and were deemed at high risk of severe disease. Although enrollment in the trial was completed in March 2021, before the emergence of the more transmissible delta and omicron variants, Shapiro said subsequent lab testing has been evaluating the drug against all variants of concern through January 2022. 

Antibody responses to delta variant

In a non-peer-reviewed preprint manuscript posted March 14 on bioRxiv, researchers from the Bloom Lab at Fred Hutch showed that immune responses to a prior variant of SARS-CoV-2 (in this case, through mRNA vaccination) change the antibody response to the delta variant of the coronavirus. The team published the peer-reviewed work on June 30 in PLoS Pathogens.

The paper's first author, Bloom Lab postdoctoral research fellow Dr. Allie Greaney, explained the group's research in a thread on Twitter:

Tweet from Allie Greaney (@Allie Greaney) from 4:52 p.m. March 15 2022 that reads: (1/n) Excited to share our latest preprint on understanding the antigenic landscape of the #SARSCoV2 Delta variant. With  @jbloom_lab   @eguia_rachel   @tylernstarr  and great collaborators. Preprint link:
Click to view on Twitter

February 2022

Pandemic highlights longstanding inequities

Fred Hutch senior staff scientist Dr. Michele Andrasik is the lead author of an essay published online by Infectious Disease Clinics of North America that places in historical context the social inequities that led to disproportionate burdens of COVID-19 on Black, Indigenous and people of color, or BIPOC communities, throughout the world. As director of social and behavioral sciences and community engagement for the Hutch-based HIV Vaccine Trials Network, she took on a similar role for the COVID-19 Prevention Network that managed the clinical trials that led to authorization of SARS-CoV-2 vaccines. Because of their efforts, 47% of participants in the trials for the Moderna mRNA vaccine were from BIPOC communities.

Andrasik and her co-authors provide 15 recommendations for working with BIPOC communities to increase participation in preventive interventions like vaccines and participation in trials. Such interventions should foster trust, increase health literacy, and offer equitable partnerships with communities. Recommendations include calls to improve social safety nets, provide comprehensive training to medical personnel about bias and historic oppression, and to support community-based research.

Testing antibody as preventive in immunocompromised transplant patients

Dr. Jim Boonyaratanakornkit is one of the principal investigators on a Phase 1 Fred Hutch/Seattle Cancer Care Alliance trial testing the effectiveness of monoclonal antibody sotrovimab as a COVID-19 preventive in blood stem cell transplant patients. New treatments and preventive therapies are still sorely needed, he said, because the virus continues to mutate, rendering some treatments unusable.

Read more in Hutch News: Cancer, COVID-19 and proceeding with caution

Left to right: Drs. Jim Boonyaratanakornkit, Lue Ping Zhao and Jessica Hawley are three Fred Hutch faculty members involved in a range of research on COVID-19.
Drs. Jim Boonyaratanakornkit (left), Lue Ping Zhao (top right) and Jessica Hawley (bottom right) are three Fred Hutch faculty members involved in a range of research on COVID-19.

Photos: Fred Hutch file

Preparing for endemic SARS-CoV-2

Virus experts at Fred Hutch and the University of Washington are starting to explore new avenues of research focused on the anticipated transformation of COVID-19 from a fast-growing pandemic to a more stable, endemic disease. Over the next three years, the team members will work on finding innovative approaches to tracking, preventing and treating the disease as it settles in among a global population that, immunologically speaking, is becoming more accustomed to this unwanted viral newcomer.

Read more in Hutch News: Team of top researchers prepares for endemic COVID-19

SARS-related coronaviruses with theoretical spillover potential more widespread than previously thought

New work published Feb. 3 in the journal Nature suggests that to safeguard against other coronaviruses that could gain the ability to sneak into our cells, we need to think globally. The researchers found that the ability to bind ACE2 — a crucial trait in species-jumping coronaviruses — could be a more widespread possibility than previously thought. Instead of being a late evolutionary development, the ability to bind ACE2 is an ancient property of bat SARS-related coronaviruses — and found in coronaviruses outside of Asia.

Read more in Hutch News: Coronavirus’ distant past reveals ancient roots of trait that could help them jump species

January 2022 

Long COVID-19 research ongoing

Researchers worldwide are working to understand long COVID-19, the long-lasting effects of COVID-19 infection that can affect adults, teens and children. Fred Hutch and University of Washington investigators are building on deep expertise in immunology and infectious diseases like HIV to figure out what causes long COVID-19, who is at risk, and how to treat it. To do so, they’re tackling challenges that range from basic questions about how best to measure symptoms to uncovering the complex immunological interplay that may drive symptoms.

Read more in this Hutch News feature from Jan. 26: Tackling the unknowns of long-haul COVID-19

Coronavirus mutations linked to virulence

A team of researchers led by Dr. Lue Ping Zhao of Fred Hutch identified small mutations in genes of early COVID-19 viruses that appeared to have substantially increased the risk of severe disease in patients who contracted them. The researchers, who carried out extensive, whole-genome sequencing of the viruses taken from patients primarily in the first year of the pandemic, spotted in particular a group of four genetic mutations that were linked to a 5.46-fold increase in hospitalization. The study was published on Jan. 24 in the journal Scientific Reports.

Read more on Hutch News: Researchers link mutations in coronavirus' internal machinery to higher risk of severe disease

Are cancer patients with COVID-19 treated differently across the U.S.?

On Jan. 4, a team of researchers from the COVID-19 and Cancer Consortium (CCC19) published a study in JAMA Network Open on outcomes in cancer patients diagnosed with COVID-19 across the U.S. The researchers and lead author Dr. Jessica Hawley, an oncologist and clinical researcher with Fred Hutchinson Cancer Research Center, followed nearly 5,000 ethnically diverse cancer patients (just over half female) who were diagnosed with COVID-19 between March and November 2020, using data collected from cancer care delivery centers all across the U.S. After adjusting for patient characteristics, the team found the estimated 30-day mortality rate ranged from just over 5% to nearly 27% across the centers. Patients located in metropolitan areas under 250,000 people had lower odds of 30-day mortality than those in cities with at least a million people.

After analysis, the researchers found no significant differences in rates of mechanical ventilation, ICU admission or death among cancer patients with COVID-19 across U.S. census regions or divisions over time, although patients who were treated in more sparsely populated areas did have significantly improved outcomes than those treated in densely populated areas. And while there were no significant differences in COVID-19 outcomes across four different U.S. census divisions (Northeast, Midwest, South and West), there were substantial differences in COVID-19 outcomes across cancer care delivery centers, particularly between cancer centers that serve large metropolitan (over a million people) and those serving substantially less populated areas (under 250,000 people).

The authors concluded that standardized guidelines for the care of patients with cancer and COVID-19 could improve outcomes for the more vulnerable patients. They also recommended further exploration of the ongoing socioeconomic and health determinants that may be affecting COVID-19 and cancer patient outcomes.   

December 2021

mRNA COVID-19 vaccine efficacy study in people with HIV

On Dec. 13, the COVID-19 Prevention Network, whose operations center is based at Fred Hutch, announced a new clinical trial in eight sub-Saharan countries which will be the first to specifically evaluate the efficacy of a COVID-19 vaccine in people living with HIV, including those with poorly controlled infections. It also is the first study to evaluate the efficacy of vaccines — in this case, Moderna mRNA-1273 — against the omicron variant of SARS-CoV-2, the virus that causes COVID-19.  Read more about the new trial, called Ubuntu, in the CoVPN's press release.

Preliiminary data from this and another trial, released as a non-peer-reviewed preprint on Dec. 27, indicate a high rate of asymptomatic carriage associated with the omicron variant. Read more in the CoVPN's press release from Jan. 7.

Following omicron

Fred Hutch scientists have been tracking the omicron variant as soon as it was detected in November. Read more about what they're learning at Fred Hutch News as new data emerges: What Hutch coronavirus experts are saying about omicron.

Results of a remdesivir trial

On Dec. 22, an international team of researchers published in The New England Journal of Medicine the results of a Phase 3 clinical trial of the antiviral drug remdesivir in nonhospitalized patients with COVID-19. Hutch researcher Dr. Joshua Hill was among the principal investigators of the study, which showed remdesivir had an acceptable safety profile and lowered the risk of hospitalization or death by 87% compared to placebo. The trial was stopped early, not out of safety concerns, but due in part to the impracticality of requiring participants to make three visits to clinics to receive three IV infusions of the drug. One site for the trial was the Hutch's COVID-19 Clinical Research Center.

Read more about the trial and the CCRC in this Fred Hutch News story: Addressing a 'massive unmet need' in COVID-19 treatment.

COVID-19 outcomes after blood stem cell transplant

On Dec. 12, pediatric transplantation expert Dr. Neel Bhatt presents the latest data from his research on the outcomes of blood stem cell transplant recipients with COVID-19 at the annual meeting of the American Society of Hematology

Read more about Bhatt's study and related research at Fred Hutch News: Q&A: Returning to school, post-transplant

November 2021

Correlates of protection for Moderna vaccine

In the race to develop new and better vaccines and boosters to block COVID-19, scientists are eagerly seeking laboratory tests that can measure immune responses to quickly show how well these shots are working, instead of waiting months for results of clinical trials involving tens of thousands of people. In a paper published on Nov. 23 in Science, a group of scientists including Dr. Peter Gilbert of Fred Hutch report that they have defined such measurements — or correlates of protection — for the widely used Moderna mRNA vaccine.

Read more in Hutch News: Researchers pinpoint 'correlates of protection' for Moderna vaccine

Regulatory T cells show a distinct 'immune signature' in COVID-19 patients

On Nov. 10, researchers led by Dr. Jennifer Lund and Dr. Martin Prlic reported in Science Advances that hospitalized COVID-19 patients show a marked uptick in regulatory T cells, or "Tregs,” in their immune system’s response to SARS-CoV-2 infection. Tregs are a particular type of T cell that, in most viral infections, helps moderate the inflammatory response brought on by other T-cell varieties. The researchers describe it as a distinctive “immune signature” of severe COVID-19 infection.

Notably, with the exception of this higher proportion of Treg cells, the picture of our immune landscape against COVID-19 appears similar to that of severe cases of common respiratory infections such as influenza and respiratory syncytial virus. So, it’s unclear what this telltale COVID-19 signature means. Research is underway to find out whether this increase in regulatory T-cell levels is good or bad for patients, data that could inform development of COVID-19 therapies.

Read more in Hutch News: Sleuthing the immune system’s mysterious T-regs

Dr. Jennifer Lund (left) and Dr. Adrienne Shapiro
Dr. Jennifer Lund (top) and Dr. Adrienne Shapiro

Photos by Robert Hood / Fred Hutch News Service

October 2021

Efficacy of antibody treatment for reducing hospitalization

On Oct. 27, researchers published interim results in The New England Journal of Medicine from a Phase 3 study of the COVID-19 monoclonal antibody treatment sotrovimab, sponsored by Vir Biotechnology and GlaxoSmithKline. The study found that compared to the placebo group, COVID-19 patients who received sotrovimab had a significantly reduced risk of hospitalization or death and that the treatment, which was administered by intravenous infusion on an outpatient basis, was safe.

“As long as people are getting COVID-19, there is a need for effective treatment to prevent serious illness and death,” said Dr. Adrienne Shapiro of Fred Hutch and UW Medicine. “Based on these efficacy results, we are excited for the potential of sotrovimab — which now has emergency use authorization from the FDA — to reduce hospitalizations and thus relieve the burden of hospital crowding, another serious consequence of the COVID-19 pandemic.”

Read more in the Fred Hutch press release on these results from the COMET-ICE trial.

Modeling early worldwide spread of COVID-19

A new computer modeling paper in Nature gives more nuance to the early worldwide spread of COVID-19. Dr. Elizabeth Halloran is part of a team lead by Northeastern University researchers that uses transportation and population data to project where and when infectious diseases will spread. Their findings on early hidden spread complement genomic data showing where the coronavirus was in January and February 2020 and how it spread and suggest that this model could be used for surveillance and preparedness work for future outbreaks.

“I worked with the team to design our study and interpret its findings in the public health context,” said Halloran, who leads the Biostatistics, Bioinformatics and Epidemiology Program in the Vaccine and Infectious Disease Division at Fred Hutch. She’s among other experts to advise policymakers throughout the pandemic, and she was elected to the National Academy of Medicine in 2019 for her role in helping the world anticipate, manage and prevent infectious disease outbreaks. “In places that have limited testing, a model like ours could be used to find places that are most likely to see an outbreak based on transportation data and how people are moving around from international travel to people commuting.”

Read more about the role of Halloran and other Fred Hutch modelers in the COVID-19 response in Fred Hutch News.

Engagement with communities leads to equitable vaccine trials

A new study, published by a team from the COVID-19 Prevention Network in the journal PLOS ONE, discusses the need for engagement of Black, Indigenous and other communities of color in infectious disease research as a critical component in efforts to increase vaccine confidence, acceptability and uptake of future approved products.

Read more on Hutch News: Community engagement ensures equitable inclusion in vaccine trials

Revealing how different coronavirus variants shift antibody responses

In a new preprint on bioRxiv, researchers from the Bloom lab looked at how immune responses can change depending on which strain of coronavirus patients were infected with.

“We show that infection with a #SARSCoV2 variant elicits an antibody response with somewhat shifted specificity relative to early Wuhan-Hu-1-like viruses that were circulating early in the pandemic,” Dr. Jesse Bloom wrote in a Tweetorial about the study.

The team, led by graduate student Allison Greaney, found that antibodies raised against early 2020 strains of SARS-CoV-2 targeted slightly different regions of the spike protein’s receptor binding domain than antibodies generated by infection with the beta variant, which appeared in late 2020. In particular, they found that in lab-based studies of neutralization, or how well antibodies block infection by viruses, antibodies to the major region triggered by beta were less affected by mutations at a site of concern to vaccine developers. 

Infectious disease modeller Dr. Elizabeth Halloran has helped advise policymakers throughout the COVID-19 pandemic. Dr. Jesse Bloom studies evolution using viruses — including flu and SARS-CoV-2 — and viral proteins as models.
Infectious disease modeller Dr. Elizabeth Halloran has helped advise policymakers throughout the COVID-19 pandemic. Dr. Jesse Bloom studies evolution using viruses — including flu and SARS-CoV-2 — and viral proteins as models.

Photos by Robert Hood / Fred Hutch News Service

September 2021

Analyzing metabolic and immune changes in COVID-19 hyperinflammation

In new work published Sept. 6 in Nature Biotechnology, researchers from Fred Hutch and Seattle’s Institute for Systems Biology dove deep into the metabolic changes in patients suffering from COVID-19. The team combined metabolic measurements from blood samples with analysis of the genes and proteins being used by individual immune cells to define the metabolic changes and immune cell populations associated with COVID-19 hyperinflammation.

The team compared data from patients with COVID-19 who were not hospitalized to those who were hospitalized. They mapped out immune-cell metabolic signatures and found that certain immune cell populations increased in percentage and metabolic activity as disease severity intensified. The scientists also identified five blood metabolites that predicted poor outcomes in patients being hospitalized with COVID-19.

“We know that there are a range of immune responses to COVID-19, and the biological processes underlying those responses are not well understood,” said co-first author and Hutch M.D./Ph.D. student Jihoon Lee in a press release from the ISB. “The deeper understanding gained here may eventually lead to better therapies that can more precisely target the most problematic immune or metabolic changes.”

July 2021

Measuring COVID-19's impact on cancer clinical trials

A study published on July 29 in JAMA Network Open reports on enrollment during the COVID-19 pandemic to cancer clinical trials run by the SWOG Cancer Research Network, a cancer clinical trials group funded by the National Cancer Institute. Led by Dr. Joseph Unger, a SWOG health services researcher and biostatistician based at Fred Hutch, the researchers found that during the early weeks of the pandemic, from late February through mid-April 2020, registrations to cancer clinical trials dropped precipitously compared to previous years. This drop was followed by an initial recovery period lasting through the summer of 2020; in fact by the end of the summer, enrollment totals actually slightly exceeded what would have been expected without the pandemic. Enrollments again dropped during the wave of increasing COVID-19 virus infections in the winter of 2020/2021, but much more modestly compared to the initial wave of the pandemic.

"After the initial COVID-19 outbreak, we observed a dramatic drop-off in trial enrollments," Unger noted. "Now, a year later, we wanted to assess enrollment over an entire year of the pandemic, especially given the flexibilities that had been introduced into the system." 

Read more in a press release from SWOG about the study.

Charting ACE2 binding in SARS-related coronaviruses

Researchers in the Bloom Lab published a preprint on July 20 tracing the evolutionary history of ACE2 binding by SARS-related coronaviruses (also known as sarbecoviruses).

“ACE2 binding is only seen sporadically among the broader lineage of sarbecoviruses that cirvulate in bats,” said lead investigator Dr. Tyler Starr in a Tweetorial on the work.

He found that ACE2 binding has a spotty history in these viruses: though the earliest sarbecoviruses could bind ACE2, this capability was lost along some branches of the sarbecovirus evolutionary tree. Of those that retained ACE2 binding, it may take only as little as one change in the amino acid sequence of their receptor-binding domains to enable binding to ACE2 in a new species.

But single changes can have very different effects in different SARS-related viruses, the team found. One amino acid change seen in several SARS-CoV-2 variants of concern gives the COVID-19 virus a binding boost, but dampens ACE2 binding by SARS-CoV-1. 

Discovering antibodies that resist viral escape

In a study published in Nature on July 14, Dr. Tyler Starr of the Bloom Lab described the ability of 12 monoclonal antibodies to bind divergent receptor-binding domains, or RBDs, drawn from 45 divergent SARS-related coronaviruses, including some isolated from bats and pangolins. He and his colleagues in the lab of Hutch evolutionary biologist Dr. Jesse Bloom also mapped which mutations would allow the SARS-CoV-2 RBD to escape neutralization by the antibodies.

For the most part, Starr saw that antibodies traded potency for breadth: Those that neutralized SARS-CoV-2 RBD very effectively were less able to recognize RBD from more distantly related viruses. A few antibodies bucked this trend, including a standout dubbed S2H97 that binds a site deeply hidden within the closed RBD that only becomes accessible when it opens to contact ACE2. S2H97 bound RBDs separated by sometimes hundreds of years of evolution, including a divergent group of RBDs from bat coronavirus that have never spilled over into humans.

Though rarely recognized by our immune system, this epitope is incredibly similar across SARS-related coronaviruses, Starr said. If an antibody binds this site, it can block a wide range of those viruses.

Mapping antibody-escape mutations

Scientists in the Bloom Lab examined how mutations in the RBD may help SARS-CoV-2 escape antibodies that bind in different areas. Led by graduate student Allison Greaney, they examined  binding by both monoclonal antibodies — single antibodies that bind just one place on the virus — and polyclonal convalescent plasma, containing whatever mixture of antibodies were produced by a person infected with SARS-CoV-2. They tested mutations that aren’t yet found in prominent viral lineages, but could theoretically arise as the virus continues evolving.

Greaney and her colleagues found that how much an RBD mutation affected antibody binding varied among patients. Even so, a few spots on the RBD grabbed most of the immune system’s attention — including a rapidly changing location called E484. This result was “a bit worrying,” Greaney said, because changes here were most likely to affect how well polyclonal plasma bound RBD — and it had already mutated in the novel coronavirus’ beta and gamma variants. 

June 2021

Recovery of deleted deep sequencing data sheds more light on the early Wuhan SARS-CoV-2 epidemic

In a preprint published on bioRxiv, Fred Hutch's Dr. Jesse Bloom reported his discovery of SARS-CoV-2 sequences from early in the Wuhan outbreak that had been deleted from a National Institutes of Health database. In a complementary Twitter thread, he explained how he found and reconstructed 13 of these sequences and what he learned from his analysis of them.

He wrote that the sequences support other lines of evidence that SARS-CoV-2 was circulating in Wuhan before the December 2019 outbreak in a seafood market. They do not provide evidence either for or against either a natural animal origin for the virus or an accidental lab leak. More early sequences are probably out there, he wrote, and scientists should focus on identifying them and analyzing all available data to determine the origins of the pandemic. 

Read more in Fred Hutch News: Deleted SARS-CoV-2 sequences from early in Wuhan outbreak offer clues

Comparing vaccine and natural immunity

In work published in Science Translational Medicine on June 30, investigators in the Bloom lab compared the binding patterns of antibodies generated by the Moderna vaccine to those elicited by natural SAR-CoV-2 infection. Looking at where antibodies bind on the receptor-binding domain of the novel coronavirus' spike protein, they found that that vaccination appears to promote antibodies with a broader binding pattern than those generated by infection.

Expanded study in young adults

The Prevent COVID U study launched in late March to evaluate SARS-CoV-2 infection and transmission among university students vaccinated with the Moderna COVID-19 vaccine. On June 22, the study team announced that it has expanded beyond the university setting to enroll young adults ages 18 through 29, and that it will now also include people in this age group who choose not to receive a vaccine.

The expanded trial continues to test if, and to what degree, the Moderna COVID-19 vaccine can prevent infection with SARS-CoV-2, limit the amount of virus in the nose, and reduce transmission of the virus from vaccinated persons to their close contacts. It is being conducted through the federally funded COVID-19 Prevention Network, whose operational headquarters is at Fred Hutch.

"If our study demonstrates that a COVID-19 vaccine works to prevent infection and transmission of the virus, many more people may decide to get vaccinated, which has huge public health implications," the Hutch’s Dr. Larry Corey, principal investigator of the network's operations, told Reuters.

Math model shows tradeoffs in one- vs. two-dose vaccines

In a paper published June 8 in Nature Communications, Dr. Laura Matrajt and colleagues used a mathematical model and optimization algorithms to determine the optimal use of COVID-19 vaccines when supply is limited. This work, which Matrajt started last September before COVID-19 vaccines were available, remains important as worldwide vaccination efforts continue.

Matrajt and coauthors found that there is not a “one size fits all” for the best use of vaccine. The optimal vaccine allocation depends on how much transmission is occurring, vaccine supply, and the efficacy after one and two doses of vaccine. For instance, in the U.S. in February 2021 when transmission was high and vaccine supply was not yet high, it made the most sense to prioritize people who are at higher risk of dying of COVID-19. And, since there wasn't enough evidence about the efficacy and durability of a single dose, Matrajt said that the “less risky” approach was to give two doses to people at high risk.

Matrajt hopes that more data will become available on how well a single dose works: If a single-dose is proven to be durable and effective, one-dose vaccination strategies could be crucial to stretch supply and speed up worldwide vaccinations. In contrast, if a single-dose vaccine has low vaccine efficacy, one-dose strategies could result in a huge waste of precious resources.

May 2021

Charting viral escape routes from immunity

Investigators in Dr. Julie Overbaugh’s group examined the interaction between antibody binding and viral mutations in regions along the stem of the SARS-CoV-2 spike protein. In work published in Cell on May 27, Meghan Garrett, a graduate student in Overbaugh's lab, looked at the complex mixtures of antibodies produced in people naturall infected with the novel coronavirus. She found that most antibodiesmixtures homed in on just a couple of sites along the spike's stem, but individual immune responses still varied.

“Most people had responses to one site or the other, some had responses to both — but overall, the response was not uniform,” Overbaugh said.

Most people in Garrett’s study also had antibody targets sites that were unique to them as individuals, and not seen in other patients.

Garrett found less consistency among mutations that conferred antibody escape in this region of the spike. These areas are less changeable among viral variants, which means they may be attractive additions to future vaccines designed to provide people with broader protection against many different variants, Overbaugh said.

Call to investigate SARS-CoV-2 origins

In a letter published on May 13 in the journal Science, Dr. Jesse Bloom and colleagues argued that "greater clarity about the origins of this pandemic is necessary and feasible to achieve. We must take hypotheses about both natural and laboratory spillovers seriously until we have sufficient data." They wrote that such an investigation must be well managed to minimize the impacts of conflicts of interest, and be transparent, objective, data-driven, inclusive of broad expertise and have independent oversight.

“Most of the discussion you hear about SARS-CoV-2 origins at this point is coming from, I think, the relatively small number of people who feel very certain about their views,” Bloom told the New York Times, adding: “Anybody who’s making statements with a high level of certainty about this is just outstripping what’s possible to do with the available evidence.”

Detailed structure of a pan-coronavirus antibody

Whether they cause COVID-19, SARS or MERS — a camel disease that also can infect humans — all coronaviruses have a spike protein that acts like a lockpick to let the virus into our cells. As described in a paper published May 12 in Nature Structural & Molecular Biology, researchers at Fred Hutch and the University of Washington have identified a commonality could lead to the design of a future universal coronavirus vaccine. After immunizing mice against the spike protein of multiple coronaviruses, a team led by Dr. Andrew McGuire of Fred Hutch and Dr. David Veesler of UW identified and characterized one antibody that binds to a particular part of multiple coronavirus spikes that has been relatively unchanged over evolutionary history. This particular antibody can also block the spikes' lockpick action. The researchers hope that the detailed information they gained about this powerful antibody’s structure and function will help to inform the design of future vaccines that protect people against all types of coronaviruses, including those yet to jump to humans.

April 2021

Comparing immunity to SARS-CoV-2 generated by vaccination and infection

Though the novel coronavirus has taken a grim toll around the globe, worldwide vaccine efforts mean that eventually, most people will gain immunity against SARS-CoV-2 through vaccination. But the rise of viral variants has also raised the question of how much protection we'll retain as SARS-CoV-2 continues to evolve in ways that could help it escape the protective responses we’ve already mounted. Much of the immune protection in naturally infected or vaccinated people comes from specialized immune proteins called antibodies. By binding to proteins on the outside of viruses, neutralizing antibodies can block viruses from infecting their target cells.

In a recent preprint published on bioRxiv, researchers in Dr. Jesse Bloom’s lab at Fred Hutch compared neutralizing antibody responses from people who were infected with SARS-CoV-2 to the responses from people who received the Moderna RNA vaccine but were not exposed to the virus. RNA vaccines prompt vaccinated people’s cells to produce the spike protein that helps the novel coronavirus connect with its gateway to target cells, ACE2. Allison Greaney, a grad student in Bloom’s lab, found that over 90% of the neutralizing activity of antibodies produced after vaccination was focused on a specific region of the spike protein, called the receptor binding domain, or RBD. Immune responses to natural infection were more likely to include neutralizing antibodies that bound other regions of the spike protein, in addition to the RBD.

However, Greaney also found that vaccination generates antibodies that bind to more regions within the RBD than natural infection tends to. She found that this changed how easily single mutations in the RBD affected antibody neutralization (a lab-based proxy for measuring how a mutation may help the virus evade a protective immune response). Mutations in the RBD affected neutralization by vaccine-elicited antibodies less than neutralization by antibodies produced in response to natural infection. Her findings suggest that natural and vaccine-generated immunity to SARS-CoV-2 may respond differently to different viral variants.

Using machine learning to dampen the COVID-19 cytokine storm

An overactive immune response, or cytokine storm, is thought to underlie many of COVID-19’s worrying complications. In a preprint published on bioRxiv, Dr. Taran Gujral, with Drs. Julie McElrath and Eric Holland, used machine learning to identify key molecules that trigger this response when cells are exposed to a region of the novel coronavirus’ spike protein. This strategy also enabled the team to identify a drug that may hold potential to reduce immune overactivation to SARS-CoV2. They found several FDA-approved drugs, including one called ponatinib (trade name Iclusig), which block the activity of several molecules involved in the immune response to the virus. Treatment with these drugs inhibited the cytokine storm response when the researchers exposed cells in lab dishes to the spike protein from the novel coronavirus and its emerging variants.

Coronavirus evolution and immune escape

The team of Dr. Jesse Bloom and their colleagues sought to better understand SARS-CoV-2 by investigating the common-cold coronavirus 229E. A person who is infected with 229E develops an immune response against the signature coronavirus spike protein that protects them from reinfection with this virus, but only for a few years. Does reinfection then occur because the immune response wears off, or because 229E evolves to escape it? Their findings, published on April 8 in PLOS Pathogens, suggest the latter. Thus, it is possible that SARS-CoV-2 could undergo similar evolution, and that COVID-19 vaccines may require periodic updates to remain effective.

“It’s pretty clear that human coronaviruses undergo substantial antigenic evolution,” Bloom said about this study’s findings in a Bloomberg story about coronavirus evolution and COVID-19 vaccines.

Read the Bloom Lab’s Twitter thread on this research and a press release from PLOS Pathogens about the paper.

March 2021

Addressing vaccine hesitancy in BIPOC communities 

In a perspective published on March 31 in the New England Journal of Medicine, Dr. Michele Andrasik and colleagues discuss how to build trust, partnership and reciprocity between vaccine researchers and Black, Indigenous and people of color (or BIPOC) communities, with a special focus on the work of the COVID-19 Prevention Network.

Can coronavirus vaccines block asymptomatic transmission?

The new Prevent COVID U study, designed and managed by researchers at the Hutch-based COVID-19 Prevention Network, will enroll thousands of college students to answer one of the world’s most pressing questions about COVID-19 vaccines: Can these shots, which protect against serious symptoms, also prevent those who might still get infected from silently spreading the disease to others?   

“What we would like to see is that the vaccine recipients who become infected have lower levels of virus in the nose or a shorter duration of infection than participants who became infected and are not vaccinated,” Dr. Holly Janes told Fred Hutch News Service.

Fred Hutch researchers Dr. Michele Andrasik (left) and Dr. Holly Janes are involved in trials of new coronavirus vaccines.
Fred Hutch researchers Dr. Michele Andrasik (top) and Dr. Holly Janes are involved in trials of new coronavirus vaccines.

Photos by Robert Hood / Fred Hutch News Service

Analyzing ‘breakthrough’ infections in vaccine trials

On March 26, Dr. Peter Gilbert co-authored a paper in PLOS Pathogens describing a method for analyzing “breakthrough” SARS-CoV-2 infections in people who were vaccinated in a COVID-19 vaccine trial. Called genomic sieve analysis, the method is a critical tool to identify viral mutations associated with infection after vaccination — which can sometimes occur even with the highly effective COVID-19 vaccines now in distribution — and predict how vaccination impacts the virus’s evolution. 

“Think of the vaccine as a sieve and different variants as pebbles poured into the sieve: The vaccine will block some variants but allow others to pass through, and sieve analysis learns which variants make it through.” Gilbert said in a press release from the Military HIV Research Program.

Learn how a genomic sieve works in this animation.

Vaccine boosts natural protection to COVID-19 

In a paper posted online on March 25 by the journal Science, a Fred Hutch team led by Drs. Leo StamatatosJulie McElrath and Andrew McGuire report that a single shot of either the Moderna or Pfizer-BioNtech vaccine boosted participant immune responses against SARS-CoV-2 by as much as 1,000-fold. 

In a separate study posted on March 24 on the preprint server BioRxiv, Stamatatos and colleagues tested the neutralizing ability of 198 different antibodies found in blood samples donated by four different COVID-19 patients. They found several cross-neutralizing antibodies that could help inform the design of a “universal” human coronavirus vaccine. 

“I think it is encouraging that you can harness immune memory to SARS-CoV-2 and potentially neutralize forthcoming variants,” McGuire told Fred Hutch News Service

Super-spreader events and the variants 

In a non-peer-reviewed preprint posted on medRxiv on March 24, Dr. Josh Schiffer and colleagues find that super-spreader events will play a key role in the coronavirus variants’ ability to gain a foothold in a population, in addition to each variant’s natural infectiousness.  

“We will in all likelihood create new variants on top of those that have emerged,” Schiffer told the LA Times. “And the ones that will win are the ones that dodge the vaccine or transmit more easily.” 

“The public health message is more of the same. The really high-risk environments are crowded, indoor events. If we can avoid those and mask effectively, that is going to be key to prevent these variants from winning the race with the virus,” Schiffer told the Seattle Times

COVID-19 in cancer patients 

Dr. Petros Grivas and colleagues with the COVID-19 and Cancer Consortium published a study on March 18 in the Annals of Oncology that identified factors that were linked to more severe COVID-19 and death in patients with cancer who contract SARS-CoV-2.  

“This study provides an in-depth take on several timely and really pressing issues in health care — highlighting the effect of COVID-19 on mortality, need for hospitalization, ICU care and mechanical ventilation, while it also illustrated racial disparities in cancer care,” Grivas said in a press release from the Seattle Cancer Care Alliance

(l to r): Joel D. Meyers Endowed Chair holder Dr. Julie McElrath, Dr. Petros Grivas, and Dr. Neelendu Dey are among the Fred Hutch researchers contributing to coronavirus research.
(top to bottom): Joel D. Meyers Endowed Chair holder Dr. Julie McElrath, Dr. Petros Grivas, and Dr. Neelendu Dey are among the Fred Hutch researchers contributing to coronavirus research.

Photos by Robert Hood / Fred Hutch News Service

ACE2 and the microbiome 

To enter cells, the coronavirus binds to a protein called ACE2 on the cell surface. New research in mice by Dr. Neelendu Dey’s team found that the amount of the Ace2 gene turned on in cells in the digestive and respiratory tract is associated with the particular mix of microorganisms living in the gut, also known as the microbiome. The study, published in the journal PLOS ONE on March 16, suggests that modulating the microbiome could be one strategy to reduce the risk of COVID-19 infection or severity. 

Preliminary results from trial of pill for people with coronavirus 

On March 6 at the 2021 Conference on Retroviruses and Opportunistic Infections, a team of researchers reported preliminary results from a placebo-controlled, randomized trial of the experimental drug molnupiravir in people with symptomatic coronavirus infection. The team reported that molnupiravir reduced infectiousness by the last day of treatment (day five) with the antiviral.  

The trial is being conducted at multiple research centers, and its Fred Hutch site is led by Dr. Elizabeth Duke. 

“It won’t protect cells that are already infected, but it will prevent those infected cells from making new copies of the virus that might infect other cells,” Duke explained in a story on the Medium Coronavirus Blog

Read more in Medscape Medical News

Modeling single-dose vaccination 

In a non-peer-reviewed preprint paper posted on medRxiv on March 3, Drs. Laura Matrajt, Holly Janes and colleagues model the conditions under which a single-dose vaccination strategy could help contain the pandemic more quickly. They also demonstrate the important roles that physical distancing and rollout speed play in vaccination campaigns. 

“I hope people understand that it is really important to keep social distancing as much as possible while vaccination is happening,” Matrajt told the Seattle Met

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Last Modified, July 20, 2022