When doctors assess a person with COVID-19, they normally measure viral load and antibodies. However, information on the combination of microclots and inflammation in lung tissue that creates life-threatening conditions would often be more important. Now researchers have identified several potential prognostic markers that can be assessed through a blood test to reliably predict the further COVID-19 trajectory. The new method may help in planning treatment in the current pandemic and future ones.
Why people react so differently to SARS-CoV-2 is still a mystery. Some people scarcely notice it, whereas others end up in intensive care with their life in the balance. To better understand what makes the difference and to focus on those at greatest risk, researchers examined blood serum samples taken from people hospitalised with COVID-19 to map their metabolome.
“We examined the serum of 120 people hospitalised with COVID-19 and found 20 metabolites that collectively indicated the disease trajectory and thus reliably predict severity. This means that a simple blood test can predict which people the healthcare system should be concerned about. Further, these metabolites provide insight into the mechanisms that contribute to exacerbating the disease,” explains co-author Douglas Kell, Professor and Research Chair in Systems Biology, Department of Biochemistry and Systems Biology, University of Liverpool, United Kingdom and Associated Scientific Director, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby.
Twenty most important metabolites
The COVID-19 pandemic has challenged healthcare systems worldwide with a sudden need to provide intensive care to an unprecedented number of people. In addition, healthcare professionals have been exposed to a disease with an unknown trajectory and many relatively mild symptoms: respiratory problems, fever, diarrhoea, cough and pneumonia. For one in 20 people, the symptoms developed suddenly and rapidly into failure of the lungs or other organs, with a need for oxygen and other intensive treatment.
“The reasons for great variation in how individuals respond to COVID-19 are still poorly understood. Interferons, the neurotransmitters released in viral infections, can clearly create a cytokine storm in COVID-19 that exerts pressure on the lungs, but other important mechanisms are also definitely involved. However, understanding these small changes among individuals who seem healthy and suddenly become seriously ill is a great challenge,” says Douglas Kell.
To try to understand these mechanisms and develop an indicator of the important ones to monitor, the researchers mapped which metabolites, such as amino acids, fatty acids, sugars and vitamins, are present in which concentrations in the blood of people with COVID-19 and their severity of disease. Who would have mild COVID-19, who would need intensive treatment and who would not survive?
“Instead of testing for the presence of metabolites we already suspected, we selected a completely untargeted metabolomic assessment of serum from 120 people hospitalised with COVID-19 using mass spectrometry to determine whether any important indicators emerged,” explains Douglas Kell.
Highest risk
The blood markers could identify people with a higher risk of severe illness or death when they were diagnosed and hospitalised. Thus, the researchers found 20 of the most indicative metabolites, 16 of which can be identified by mass spectrometry.
“Unsurprisingly, the biggest differences in the markers among the most severely affected people are related to the presence of SARS-CoV-2, meaning the metabolites that are used to excess in the cell when the virus is present and the metabolites produced through the inflammatory response of the tissue,” says Douglas Kell
Some have many fatty acids in the blood, which results from changes in energy metabolism among people with a high body mass index, who already have the highest risk of severe COVID-19.
“In addition, we found that the concentration of piperine, which usually results from eating black pepper, was significantly lower among people with severe COVID-19. However, this most likely reflects dietary changes among people experiencing severe symptoms!” explains Douglas Kell.
Predicting severity
Previous studies of people with COVID-19 who also have other diseases have focused more on whether the cells overexpress certain genes or proteins. However, the researchers think that the metabolome is a more direct and sensitive indicator, since it provides a snapshot of the cellular or biochemical status of organisms, which can determine more accurately the processes taking place during illness, how the body is reacting and perhaps even what treatments will work.
“Metabolomic analysis also has certain weaknesses, since the metabolites must be identified based on the peaks in the mass spectrum and then the metabolites that could correspond to those peaks determined. Of the 20 metabolites that seem to be most closely associated with severe illness, we therefore still need to identify at least four,” says Douglas Kell.
After the researchers found the 16 metabolites, they repeated the experiment on another 90 people and successfully predicted the disease severity and therefore think that this method may be very useful.
“We do not know whether this can affect the treatment of inpatients with COVID-19 before the pandemic is over. Nevertheless, we have shown the potential of the method, which in principle can be used for other diseases, including infections, metabolic diseases and cancer,” concludes Douglas Kell.
