Proteins in saliva could aid in COVID-19 detection and predict severe illness

Reprinted with permission from the American Physiological Society.

Researchers have identified a family of proteins that is significantly elevated in the saliva of patients hospitalized with COVID-19. The proteins, known as ephrin ligands, could potentially serve as a biomarker to help doctors identify patients who are at risk for serious illness.

“Ephrins are detectable in saliva samples and could serve as adjunct markers to monitor COVID-19 disease progression,” said study author Erika Egal, DVM, PhD, a postdoctoral fellow in the laboratory of Patrice Mimche, PhD, in the Department of Pathology at University of Utah Health in Salt Lake City. “We can collect saliva without harm or discomfort for most patients, which can reveal patient responses to COVID-19 and potentially guide care.”

Egal presented the findings at the American Physiological Society annual meeting during the Experimental Biology (EB) 2022 meeting, held in Philadelphia April 2–5.

For the study, researchers analyzed saliva samples collected from patients admitted to the University of Utah Hospital emergency department with respiratory symptoms. Sixty-seven of the patients tested positive for COVID-19 while 64 patients did not. They found that the presence of ephrin ligands in saliva was strongly associated with the diagnosis of severe COVID-19.

Researchers said the study findings could help shed light on the biological processes involved in severe reactions to COVID-19 infection. Previous studies suggest ephrins play a role in injury and inflammation. The scientists say more research is needed to determine whether ephrin concentrations are linked with a higher likelihood of hospitalization, critical illness or death. In addition, as new viral variants emerge, it can be difficult to tell whether existing COVID-19 tests are able to accurately detect infections involving new variants. Looking for ephrins in saliva could offer a simple, non-invasive way to provide corroborating evidence when there is inconsistency between test results and the clinical picture, Egal said.

“Saliva is packed with information beyond detecting the COVID-19 infection itself,” said Mimche. “We demonstrate that immune cells, cytokines and soluble proteins can be reliably measured from saliva samples. Our findings provide a starting point for investigations looking into causal pathways between infection and bad medical outcomes.”

The research was overseen by Mimche in collaboration with Theodore Liou, MD and My N. Helms, PhD, from the Department of Internal Medicine at University of Utah Health, as part of a multidisciplinary project to better understand the biology of SARS-CoV-2 and how it causes serious COVID-19 infections.


About Experimental Biology 2022

Experimental Biology (EB) is the annual meeting of five scientific societies bringing together thousands of scientists and 25 guest societies in one interdisciplinary community. With a mission to share the newest research findings shaping clinical advances, EB offers an unparalleled opportunity to tap into the latest research in anatomy, biochemistry, molecular biology, investigative pathology, pharmacology and physiology. The Experimental Biology 2022 meeting will be held April 2–5 at the Pennsylvania Convention Center in Philadelphia. #expbio

About the American Physiological Society (APS)

Physiology is a broad area of scientific inquiry that focuses on how molecules, cells, tissues and organs function in health and disease. The American Physiological Society connects a global, multidisciplinary community of more than 10,000 biomedical scientists and educators as part of its mission to advance scientific discovery, understand life and improve health. The Society drives collaboration and spotlights scientific discoveries through its 16 scholarly journals and programming that support researchers and educators in their work.

Convalescent plasma could lower hospitalization risk for newly infected COVID-19 patients

Early treatment of newly diagnosed COVID-19 patients with plasma extracted from individuals who have recovered from the disease reduces the need for hospitalization by more than 50%, according to a new nationwide clinical trial.

The researchers, including scientists at University of Utah Health, say the study provides solid evidence that the use of plasma from convalescent patients—containing high levels of antibodies against SARS-CoV-2, the virus that causes COVID-19—should be part of the treatment arsenal for the disease and other emerging viral threats to global health.

The study, led by scientists at Johns Hopkins University School of Medicine in Baltimore, appears in the April 6, 2022 issue of the New England Journal of Medicine.

During the outpatient study, conducted between June 2020 and October 2021, the researchers randomly treated 1,181 patients with either plasma containing SARS-CoV-2 antibodies taken from individuals who had recovered from the disease or a placebo plasma that contained no SARS-CoV-2 antibodies. Patients were aged 18 or older and had tested positive for SARS-CoV-2 in the previous eight days.

Emily Spivak, associate professor of medicine in the Division of Infectious Diseases at U of U Health

Of the 592 patients who received convalescent plasma, only 17 (2.9%) required hospitalization within 28 days of transfusion. In contrast, 37 of 589 patients (6.3%) who were given the placebo plasma were hospitalized within a month. Overall, the findings translated into a 54% reduction in the relative risk of hospitalization for those who received convalescent plasma.

The researchers conclude that convalescent plasma is a viable early treatment for COVID-19 that has the advantages of being low-cost and widely available, particularly in countries with little or no access to vaccines and other treatments such as monoclonal antibodies. Since each person who recovers from a variant of COVID-19 produces antibodies that subdue that specific virus, convalescent plasma treatment can potentially keep new strains of SARS-CoV-2 in check.

“In theory, if you collect plasma from donors who have recovered from omicron or another new variant, they will likely have plenty of antibodies for that variant,” says Emily Spivak, a co-author of the study and an associate professor of medicine in the Division of Infectious Diseases at U of U Health. “As a result, convalescent plasma is theoretically more adaptable and may deal with new variants faster than other treatments currently available.”

The study, “Randomized Controlled Trial of Early Outpatient COVID-19 Treatment with High-Titer Convalescent Plasma,” appears in the April 6, 2022, issue of the New England Journal of Medicine. It was supported by the U.S. Department of Defense’s (DOD) Joint  Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO- CBRND), in collaboration with the Defense Health Agency (DHA). Additional support was provided by Bloomberg Philanthropies, State of Maryland, the National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases (NIAID), NIH National Center for Advancing Translational Sciences (NCATS), Division of Intramural Research NIAID NIH, Mental Wellness Foundation, Moriah Fund, Octapharma, HealthNetwork Foundation and the Shear Family Foundation.

University of Utah Health provides leading-edge and compassionate care for a referral area that encompasses 10% of the U.S., including Idaho, Wyoming, Montana and much of Nevada. A hub for health sciences research and education in the region, U of U Health touts a $428 million research enterprise and trains the majority of Utah’s physicians, including more than 1,460 health care providers each year at its Colleges of Health, Nursing and Pharmacy and Schools of Dentistry and Medicine. With more than 20,000 employees, the system includes 11 community clinics and five hospitals. For 11 straight years, U of U Health has ranked among the top 10 U.S. academic medical centers in the rigorous Vizient Quality and Accountability Study.

The miracle of mucus

Remember when it was nearly impossible to buy disinfectant wipes? In the early days of the COVID-19 pandemic, people desperately wiped down surfaces to prevent the spread because initial studies showed the virus could live on certain surfaces for weeks.

But later in 2020, newer studies showed touching a contaminated surface was not the real reason the infection was spreading. Most people were getting sick from virus-laden nasal droplets transmitted in the air.

Now, new research from University of Utah biomedical engineering assistant professor Jessica Kramer explains why the coronavirus is not really transmitted by touching surfaces. And it all has to do with our mucus, the slimy gunk that comes from our noses.

Kramer’s research was published in the newest issue of ACS Central Science. You can read a copy of it here.

Human mucus and saliva, when dry on a surface, may actually prevent the spread of coronaviruses, Kramer has learned. People produce different forms of mucus and salivary proteins, called mucins, depending on their unique genetics, diet, and environment. And certain forms of mucins form a barrier around the live virus which prevents the spread of infection.

In a laboratory, the research team tested two transmission modes: direct contact, such as touching, kissing, or a nearby sneeze, and infection from touching a contaminated surface. Researchers learned that without mucins to act as a barrier, the virus was able to spread well from surfaces or direct contact. But with the mucins in mucus and saliva, the rate of infection drops significantly when the mucus and the virus dry on the surface. That could happen in as little as just a few minutes, she says.

That’s because mucins are a special class of proteins that have sugars attached to them. The virus itself binds to the sugars instead of attaching to the surface of a human cell to replicate. The mucins act as a decoy to bind and trap the virus before it gets to the cells underneath.

Kramer’s team confirmed that without mucins, the coronavirus was viable and infected cells after recovery from a variety of common touch surfaces, including plastic, glass, steel, and surgical masks. Virus samples were infectious even after sitting dry on plastic for several days. However, when scientists recovered virus dried in simulated sneeze droplets with mucins, infection was essentially eliminated. This was true whether the virus had been dry for five minutes or three days.

Prior lab studies throughout the pandemic reported that coronaviruses are viable on surfaces for days or even weeks. However, these studies examined virus in water or a buffer rather than salivary fluid.

“This research explains how the mucins work, which we think is important,” Kramer says. “If we understand how they block the virus from infection, we can develop drugs that mimic that action.”

This new knowledge could help lead to new drugs that might be used by healthcare workers and first responders in high-risk environments. These drugs could for a short time prevent the virus from getting into their cells, as opposed to a vaccine that fights off the infection once it’s already in the cells.