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Researchers at the Australian National Phenome Center are developing a way to predict who is at risk of long COVID-19
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Can We Anticipate Who Is at Risk of Long COVID?

Researchers at the Australian National Phenome Center are developing a test to predict who is at risk of long COVID

We now know a lot more about how COVID-19 affects our body, from the contagious phase after the initial infection and symptom onset, through to either recovery or death. But as researchers are discovering, the road to recovery is complicated for a seemingly random subset of people. Known as “long haulers,” some sufferers report ongoing symptoms such as extreme fatigue, shortness of breath, chest pain and tightness, and cognitive problems, for weeks or even months after viral infection—a chronic condition dubbed “long COVID.” The serious impact of long COVID is becoming more apparent, with prolonged recovery causing considerable disability and leaving people unable to resume work long after the acute infection has subsided.

Researchers at the Australian National Phenome Center (ANPC) are leading groundbreaking studies to better understand why long COVID affects some people and not others, and whether there is anything we can do to predict who is at risk to provide those patients with earlier, more effective treatment.

The power of metabolic phenotyping

The metabolome provides a remarkable window through which we can peer into our body’s inner workings. Using metabolic phenotyping tools, we can analyze biological fluid to reveal how an individual’s genetics, environment, and lifestyle interact at the molecular level. The ANPC and its network of collaborators have recently identified metabolomic and lipidomic markers that could be used to map a patient’s risk of long COVID and associated systemic disease.

Using nuclear magnetic resonance (NMR) spectroscopy in combination with other analytical methods like mass spectrometry (MS), the researchers were able to identify a number of metabolic parameters whose dysregulation in COVID-19 patients is mirrored in a range of other illnesses, such as cardiovascular disease. This, together with advanced statistical analysis, allowed the group to develop risk maps for each parameter to build recovery profiles, both at the cohort and individual level.

NMR as a translational tool

NMR spectroscopy has far-reaching applications in scientific research, medicine, and industry, thanks to its ability to characterize the structure and dynamics of organic compounds, proteins, and other complex compounds, with atomic-level resolution. The ANPC has one of the largest collections of NMR instruments in the world for metabolic phenotyping that offers impressive reproducibility of generated data and a multitude of quantification parameters.

The success of the ANPC’s studies on long COVID relies on NMR’s robustness for longitudinal analysis. Large cohorts of patients were analyzed at various time points using NMR, which provided quantitative measurements of metabolite concentration and dynamics over time.

In their most recent study, the group found evidence that an individual’s lipoprotein and metabolic profile changed as their condition progressed, with many patients exhibiting elevated systemic inflammatory biomarkers and residual COVID-19 biomarker signatures after they had functionally recovered. The group observed a partial reversion of metabolites back to a phenotype resembling a healthy state for some but not all metabolic parameters, and there were significant differences between asymptomatic and symptomatic follow-up patients for multiple metabolites.

A step toward precision medicine?

These results help build a molecular picture of how long COVID alters patients’ metabolic phenotype from a healthy state to a diseased state), and back again. By developing this quantitative metabolic phenotyping approach, in the future, assessing an individual COVID-19 patient’s risk of long-term systemic disease could be possible.

Precision medicine is becoming tangible thanks to advances in analytical techniques like NMR and the expertise of researchers all over the globe. As a next step, the group at the ANPC is working to optimize its metabolite detection panels for use in a laboratory-developed test (LDT) to monitor long COVID recovery within its facility.

The work being carried out at the ANPC and by all other members of the network with standardized NMR brings hope of a harmonized and scalable approach to high-throughput phenotyping for global epidemiology studies, for long COVID, and possibly other complex systemic diseases or emerging zoonotic infections.

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