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.
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.
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.
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.
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.
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.
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.
In a paper posted online on March 25 by the journal Science, a Fred Hutch team led by Drs. Leo Stamatatos, Julie 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.
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.
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.
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.
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.
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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