COVID-19 Immune Response Study Could Lead to More Effective Treatments

SEATTLE, Oct. 28, 2020 /PRNewswire/ -- A COVID-19 immune response study has revealed new findings that suggest that treatments aimed at arresting the infection at the stage of moderate severity may be most effective. The symptoms of COVID-19 vary widely, from very mild to severe conditions requiring ICU care. Researchers comprehensively studied a large number of patients during the week following a COVID-19 diagnosis, and found that mild COVID-19 is very distinct from the moderate or severe forms of disease, which appear surprisingly similar. 

For both moderate and severe COVID-19 cases, the team found that there is a sort of tug-of-war taking place, in which inflammation is promoting a stronger immune response, yet many of the key nutrients required for building that response are depleted. This leads to unusual and dysfunctional immune responses. 

A paper describing these findings has been accepted by Cell, and appeared online today. The study was led by the Institute for Systems Biology (ISB) and Swedish in Seattle, with help from Merck (known as MSD outside the United States and Canada), BARDA, and several other institutions and companies (listed below).

"These findings have practical implications for treatment of patients with COVID-19. Since patients with moderate illness have not yet developed end organ damage, our data suggest that early in the disease course would be the best time to intervene with various treatment options to prevent the immune, protein and metabolite derangements seen with more severe disease," said Dr. Jason Goldman of Swedish, who is the clinical lead for the study. "Our translational data align with data from randomized control trials, which have shown greater benefits from antiviral therapies given early. These data also provide intriguing hypotheses about the targeting of host-directed therapies, or even nutritional supplementation." 

The research team examined serial blood draws from 139 COVID-19 patients of all severities, from patients recovering at home to critically ill patients and in the ICU. From each blood sample, they measured thousands of proteins and metabolites to capture the environment of the circulating immune system. They also measured thousands of genes and proteins from individual immune cells. Finally, they utilized novel computational methods to merge all of these observations together to provide an integrated view of COVID-19 infection during the week following initial diagnosis. 

"This is what we mean by 'systems biology' -- thoroughly measure every component of the whole system, and then use computational methods to reassemble it back together again," said ISB President Dr. Jim Heath, who was the scientific lead of the study.

"The resources provided from this work could provide high value in developing new therapies that might target metabolite starvation, immune dysfunction, or blood clotting, each of which we see emerge at the level of moderate disease," said Dr. Yapeng Su, an ISB research scientist and lead author on the study. 

"This important and comprehensive study, in which Merck has been proud to participate, demonstrates the power of an integrated systems biology approach to dissect the complexity of molecular and cellular responses in patients suffering from COVID-19," said Dr. Roger M. Perlmutter, President, Merck Research Laboratories. "As we had hoped, the analysis defines a possible point of intervention in the progression of COVID-19 disease, which may in the near term permit the development of more effective, targeted therapeutics."

The COVID-19 Immune Response Study is made up by ISB, Swedish, Merck, Stanford University, Fred Hutchinson Cancer Research Center, Adaptive Biotechnologies, Bloodworks Northwest, Gilead, Isoplexis, Metabolon, Nanostring, Olink, Providence Molecular Genomics Laboratory, Scisco Genetics and 10x Genomics. 

Funding for this project comes from Merck and the Biomedical Advanced Research and Development Authority (BARDA), the Wilke Family Foundation, the MJ Murdock Charitable Trust, the Swedish Medical Center Foundation, the Parker Institute for Cancer Immunotherapy, Gilead, Novartis, Amazon Web Services, Omeros, the Washington State Andy Hill CARE Fund, the Department of Defense, and the National Institutes of Health.

About ISB
Institute for Systems Biology (ISB) is a collaborative and cross-disciplinary non-profit biomedical research organization based in Seattle. We focus on some of the most pressing issues in human health, including brain health, cancer, sepsis and aging, as well as many chronic and infectious diseases. Our science is translational, and we champion sound scientific research that results in real-world clinical impacts. ISB is an affiliate of Providence, one of the largest not-for-profit health care systems in the United States. Follow us online at www.isbscience.org, and on Facebook and Twitter.

About Swedish
Founded in 1910, Swedish is the largest nonprofit health provider in the Greater Seattle area. It is comprised of five hospital campuses (First Hill, Cherry Hill, Ballard, Edmonds and Issaquah); ambulatory care centers in Redmond and Mill Creek; and a network of more than 115 primary care and specialty-care clinics located throughout the Greater Puget Sound area. Swedish is known as a regional referral center, providing specialized treatment in areas such as cardiovascular care, cancer care, neuroscience, orthopedics, high-risk obstetrics, pediatric specialties, organ transplantation and clinical research. In 2019, Swedish provided $228 million in community benefit programs, including $22 million in free and discounted care in Western Washington.

Contact:
Joe Myxter
206.732.2157

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SOURCE Institute for Systems Biology