To wrap up this month’s theme of Olink Explore 1536, here is an example of Olink Explore in action: To better understand the pathology of severe COVID-19 and why SARS-Co-V2 elicits a severe response in some patients, but not in others.
Researchers at the Massachusetts General Hospital used Olink Explore 1536 to analyze plasma samples from 306 COVID-19 positive patients, as well as 78 controls presenting with respiratory distress. Patients were classified according to the WHO ordinal outcomes scale, and analysis took place over serial timepoints, day 0 (the day they were admitted to hospital), day 3, day 7 and day 28.
Overall, they found over 600 plasma proteins implicated in the immune response to SARS-Co-V2, many of which were involved in viral response and interferon pathways, as well as other pathways associated with vaccine response, innate immune activation, and T cell function.
Over 250 of the proteins identified were independently associated with COVID-19 severity and were already differentiated at day 0, serving as strong predictors of disease severity at later time points. IL6, IL1RL1, PTX3, and IL1RN were some of the strongest weighted proteins in the signature, as well as KRT19, which is associated with epithelial damage, and TRIAP1, an inhibitor of apoptosis.
When focusing specifically on patients who suffered acute respiratory distress syndrome (ARDS), the study found 24 proteins that were only elevated for severe COVID-19 patients. While these decreased at day 7 for survivors, for patients who died, they remained elevated. This suggests that a steady increase in pro-inflammatory signal, and a lack of anti-inflammatory response, were responsible for COVID-19 disease severity and mortality in these patients.
Lastly, the combined analysis by proteomics and single cell RNA-seq identified in which cells and tissues these proteins were primarily expressed. They found that SARS-Co-V2 directly infected lung epithelial cells, and that lung epithelial cell death was a key driver of the pathology of severe COVID-19. Importantly, this cell death can be measured at the protein level in plasma, a more clinically accessible sample type.
Using Olink Explore 1536, researchers were able to generate insightful data that set the stage for how the plasma proteome can be used to better understand the pathology of COVID-19. The study found that the plasma proteome could stratify patients according to disease severity, predict which patients would develop severe COVID-19, and contributed to the knowledge of how some patients are severely affected by SARS-Co-V2 compared to others.
With the launch of the Olink Explore as kits that can now be used in any lab, what scientific discoveries lie around the corner?
To find out more about this study, read further here:
Filbin et al. 2020, Plasma proteomics reveals tissue-specific cell death and mediators of cell-cell interactions in severe COVID-19 patients, BioRXV.