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First Molecular Profiles of Severe COVID-19 Infections

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COVID-19 Severity Test
Credit: NIH

To ensure that people with coronavirus disease 2019 (COVID-19) get the care they need, it would help if a simple blood test could predict early on which patients are most likely to progress to severe and life-threatening illness—and which are more likely to recover without much need for medical intervention. Now, researchers have provided some of the first evidence that such a test might be possible.

This tantalizing possibility comes from a study reported recently in the journal Cell. In this study, researchers took blood samples from people with mild to severe COVID-19 and analyzed them for nearly 2,000 proteins and metabolites [1]. Their detailed analyses turned up hundreds of molecular changes in blood that differentiated milder COVID-19 symptoms from more severe illness. What’s more, they found that they could train a computer to use the most informative of the proteins and predict the disease severity with a high degree of accuracy.

The findings come from the lab of Tiannan Guo, Westlake University, Zhejiang Province, China. His team recognized that, while we’ve learned a lot about the clinical symptoms of COVID-19 and the spread of the illness around the world, much less is known about the condition’s underlying molecular features. It also remains mysterious what distinguishes the 80 percent of symptomatic infected people who recover with little to no need for medical care from the other 20 percent, who suffer from much more serious illness, including respiratory distress requiring oxygen or even more significant medical interventions.

In search of clues, Guo and colleagues analyzed hundreds of molecular changes in blood samples collected from 53 healthy people and 46 people with COVID-19, including 21 with severe disease involving respiratory distress and decreased blood-oxygen levels. Their studies turned up more than 470 proteins and metabolites that differed in people with COVID-19 compared to healthy people. Of those, levels of about 300 were associated with disease severity.

Further analysis revealed that the majority of proteins and metabolites on the list are associated with the suppression or dysregulation of one of three biological processes. Two processes are related to the immune system, including early immune responses and the function of particular scavenging immune cells called macrophages. The third relates to the function of platelets, which are sticky, disc-shaped cell fragments that play an essential role in blood clotting. Such biological insights might help pave the way for potentially effective new ways to treat COVID-19 down the road.

Next, the researchers turned to “machine learning” to explore the possibility that such molecular changes also might be used to predict mild versus severe COVID-19. Machine learning involves the use of computers to discern patterns, or molecular signatures, in large data sets that a human being couldn’t readily pick out. In this case, the question was whether the computer could “learn” to tell the difference between mild and severe COVID-19 based on molecular data alone.

Their analyses showed that a computer, once trained, could differentiate mild and severe COVID-19 based on just 22 proteins and 7 metabolites. Their model correctly classified all but one person in the original training set, for an accuracy of about 94 percent. And importantly, in further prospective validation tests, they confirmed that this model accurately identified mild versus severe COVID-19 in most cases.

While these findings are certainly encouraging, there’s much more work to do. It will be important to explore these molecular signatures in many more people. It also will be critical to find out how early in the course of the disease such telltale signatures arise. While we await those answers, I find encouragement in all that we’re learning—and will continue to learn—about COVID-19 each day.


[1] Proteomic and metabolomic characterization of COVID-19 patient sera. Shen B et al. Cell. 28 May 2020. [Epub ahead of publication]


Coronavirus (COVID-19) (NIH)

Blood Tests (National Heart, Lung, and Blood Institute/NIH)

Tiannan Guo Lab (Westlake University, Zhejiang Province, China)

Cool Videos: Battling Bad Biofilms

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Metabolomics of Bacterial BiofilmsPeriodically, I’ve posted some of the winners of the video competition to celebrate the Tenth Anniversary of the NIH Common Fund. After an intermission of several months, our scientific film fest is back to take another bow. This cool animation shows what some NIH-funded researchers are doing to address a serious health threat: hospital-acquired infections. Such infections can lead to hard-to-heal wounds, such as the foot sores that can trouble people with diabetes, and pressure ulcers in the elderly.

The stubbornness of such wounds owes, in part, to the infection-causing bacteria joining forces to improve their chances of survival within the injury. These microbes literally stick together to form microbial communities, called biofilms, that can resist antibiotics and evade our immune defenses. This strength in numbers has researchers pondering strategies that target the entire biofilm in innovative ways. One promising possibility involves exploiting metabolomics, which tracks the products produced by the bacterial troublemakers, and may provide new perspectives on how to battle this increasingly common healthcare problem.

The video was made by the laboratory of Mary Cloud Ammons at Montana State University in Bozeman. Ammons, who receives research support through the NIH Common Fund to study bacterial metabolomics, describes her work in this way: “The sixth leading cause of death in the United States is the result of hospital-acquired infections, which often result in nonhealing wounds colonized by communities of bacteria call biofilms. The research in our lab aims to uncover the mechanisms at the root of the deviation from the normal healing process that results in the development of chronic wounds. These metabolomic studies identify specific metabolite profiles that may be associated with pathogenicity in the chronic wound and could potentially be used in novel noninvasive diagnostics.”


Ammons Lab (Montana State University, Bozeman)

Ammons NIH Project Information (NIH RePORTER)

Common Fund (NIH)

Cool Videos: Metabolomics

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Metabolomics video screenshot

Today’s feature in my Cool Video series is a scientific film noir from the University of Florida in Gainesville. Channeling Humphrey Bogart’s hard-boiled approach to detective work, the protagonist of this video is tracking down metabolites—molecules involved in biological mysteries with more twists and turns than “The Maltese Falcon.”

If you’d like a few more details before or after watching the video, here’s how the scientists themselves describe their project: “Inside our cells, chemical heroes, victims, and villains leave behind clues about our health. Meet Dr. Art Edison, one of many metabolomics PIs who are on the case. Their quest? To tail and fingerprint small molecules, called metabolites, which result from the chemical processes that fuel and sustain life. Metabolites can shed light on the state of health, nutrition, or disease in a living thing—whether human, animal, or plant. Funded by National Institutes of Health grant U24DK097209, the University of Florida Southeast Center for Integrated Metabolomics is sleuthing through these cellular secrets.”

Metabolomics: Taking Aim at Diabetic Kidney Failure

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Patients with red tubes attached to their arms

Caption: Dialysis is often used to treat kidney failure related to diabetes.

My own research laboratory has worked on the genetics of diabetes for two decades. One of my colleagues from those early days, Andrzej Krolewski, a physician-scientist at the Joslin Diabetes Center in Boston, wondered why about one-third of people with type 2 diabetes eventually develop kidney damage that progresses to end-stage renal disease (ESRD), but others don’t. A stealthy condition that can take years for symptoms to appear, ESRD occurs when the kidneys fail, allowing toxic wastes to build up. The only treatments available are dialysis or kidney transplants.